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Luchini C. Diagnostic Pearls and Pitfalls in the Evaluation of Biopsies of the Pancreas. Arch Pathol Lab Med 2025; 149:e54-e62. [PMID: 38387616 DOI: 10.5858/arpa.2023-0426-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2023] [Indexed: 02/24/2024]
Abstract
CONTEXT.— The examination of small pancreatic biopsies is a difficult task for pathologists. This is due to the scant and fragmented material often obtained from diagnostic procedures as well as the significant overlap between different neoplastic and nonneoplastic entities. In the upcoming neoadjuvant era, biopsies could become even more important, representing the only possibility to look at the real histomorphology of tumors before chemotherapy-induced modifications. OBJECTIVES.— To summarize and discuss the state-of-the-art diagnostic workflow for small pancreatic biopsies, including the most important morphologic and immunohistochemical features and molecular alterations. The main diagnostic pearls and pitfalls of this challenging scenario are also discussed. The most important topics of this review are represented by: (1) pancreatic ductal adenocarcinoma, along with its main differential diagnoses, including autoimmune pancreatitis; (2) solid hypercellular neoplasms, including neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasms; and (3) cystic lesions. Real-world considerations will also be presented and discussed. DATA SOURCES.— Sources included a literature review of published studies and the author's own work. CONCLUSIONS.— The correct diagnosis of pancreatic lesions is a crucial step in the therapeutic journey of patients. It should be based on robust, standardized, and reliable hallmarks. As presented and discussed here, the integration of morphology with immunohistochemistry, and, in selected cases, with molecular analysis, represents a decisive step in this complex scenario.
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Affiliation(s)
- Claudio Luchini
- From the Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy; and the ARC-Net Research Center, University of Verona, Verona, Italy
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Bisharah S, Mahmoud A. Evaluation of the Value of Fine Needle Aspiration Cytology and Cell Morphology in Determining the Histogenesis of Pancreatic Lesions With Review of Literature, Overview and Cytological Experience of 25 Years: Original Research. Health Sci Rep 2025; 8:e70347. [PMID: 39807486 PMCID: PMC11725609 DOI: 10.1002/hsr2.70347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 09/09/2024] [Accepted: 12/27/2024] [Indexed: 01/16/2025] Open
Abstract
Background and Aims Benign lesions, inflammation, cysts and pseudocysts, as well as neoplasms of the exocrine and endocrine parts of the pancreas can be easily identified using cytological methods. The sensitivity and specificity can be increased with the help of additional examination methods. The sensitivity of intraoperative rapid cytology reaches about 99%. In the literature, the sensitivity reaches an average of about 85% for biopsies. The method is easy to use, has very low complication rates (1%-2%) and is safe for the patient. Methods 1290 cytological samples from pancreatic lesions were processed in the institute of pathology at Hannover Medical School (MHH), as cytological smears and stained with Giemsa and PAS stains as conventional methods. They were compared with the histological specimens that were processed at the same institute. Immunocytochemistry and molecularpathology have been processed only in selected cases. In general, it is routine in the university that the patients give their written consent to participate in clinical studies. The local ethics committee has stated that there is no need for approval due to the retrospective nature of the study. Results In this work, we detected 20.077% malignant lesions, 63.333% benign findings and inflammation, 7.441% pseudocysts and cysts. About 9.147% samples were unrepresentative due to insufficient number of cells. Conclusion This work will highlight the importance of fine aspiration cytology (FNAC) of suspicious pancreatic lesions, its possibilities and limitations in routine diagnostics with discussing the differential diagnoses, pointing to its great value and safety for patients. FNAC is the gold standard, its power is strongly associated with high specificity and sensitivity in the diagnosis of pancreatic lesions, and is very useful in the differential diagnosis between malignant and inflammatory lesions in pancreas.
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Affiliation(s)
- Soudah Bisharah
- Institute of PathologyHannover Medical School (MHH)HannoverGermany
| | - Abbas Mahmoud
- Gerhard‐Domagk Institute of PathologyUniversity Hospital Muenster (UKM)MuensterGermany
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Suster D, Mejbel HA, Mackinnon AC, Suster S. Large-cell Basaloid Adenocarcinoma of the Lung: A Clinicopathologic Study of 12 Cases of a Distinctive Form of Lung Cancer Often Mistaken for Large-cell Neuroendocrine Carcinoma. Am J Surg Pathol 2025; 49:83-93. [PMID: 39450943 DOI: 10.1097/pas.0000000000002318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
A distinctive form of lung adenocarcinoma that closely mimics large-cell neuroendocrine carcinoma is described. The tumors arose in 6 women and 6 men aged 46-86 years (mean=58.4). They presented as peripheral subpleural masses measuring 2-12 cm (mean=6.5 cm). Histologically they were characterized by islands or anastomosing and serpiginous strands of large, atypical cells showing striking peripheral palisading of nuclei, with high mitotic activity and prominent comedo-like areas of necrosis. Because of the striking resemblance to neuroendocrine tumors, some of the cases were initially diagnosed as large-cell neuroendocrine carcinoma despite the absence of neuroendocrine markers. Immunohistochemistry showed positivity of the tumor cells for TTF1 and napsin-A, and negative staining for p40. The tumors were also uniformly negative for multiple neuroendocrine markers, including chromogranin, synaptophysin, CD56, and INSM1. Electron microscopy performed in 2 cases was negative for membrane-bound dense core neurosecretory granules. Pathogenic alterations were detected in 5 of 8 tumors tested by next-generation sequencing. Point mutations in KRAS and TP53 were identified in 5 patients. Low-level amplification of GNAS , KIT , and FGFR1 was present in 2 patients. No RB1 mutations were identified. Clinical follow-up in 10 cases showed that 2 patients died of their tumors, 2 experienced distant metastases, and 6 were alive and well from 1 to 13 years after diagnosis (median=7.1 y). Large-cell basaloid adenocarcinoma is an unusual variant of lung cancer that is easily confused with large-cell neuroendocrine carcinoma. Awareness of this unusual variant of lung adenocarcinoma is important for treatment and prognosis and for avoiding misdiagnosis.
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MESH Headings
- Humans
- Middle Aged
- Male
- Lung Neoplasms/pathology
- Lung Neoplasms/genetics
- Lung Neoplasms/chemistry
- Female
- Aged
- Carcinoma, Neuroendocrine/pathology
- Carcinoma, Neuroendocrine/genetics
- Carcinoma, Neuroendocrine/chemistry
- Carcinoma, Neuroendocrine/diagnosis
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/genetics
- Aged, 80 and over
- Adenocarcinoma of Lung/pathology
- Adenocarcinoma of Lung/genetics
- Adenocarcinoma of Lung/chemistry
- Diagnosis, Differential
- Carcinoma, Large Cell/pathology
- Carcinoma, Large Cell/chemistry
- Carcinoma, Large Cell/genetics
- Carcinoma, Large Cell/diagnosis
- Immunohistochemistry
- Predictive Value of Tests
- Diagnostic Errors
- Adenocarcinoma/pathology
- Adenocarcinoma/chemistry
- Adenocarcinoma/genetics
- Adenocarcinoma/diagnosis
- Mutation
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Affiliation(s)
- David Suster
- Department of Pathology, Rutgers New Jersey Medical School, Newark, NJ
| | - Haider A Mejbel
- Department of Pathology, Emory University School of Medicine, Atlanta, GA
| | | | - Saul Suster
- Department of Pathology, The Medical College of Wisconsin, Milwaukee, WI
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Balachandran Pillai A, Yousef M, Yousef A, Alfaro-Munoz KD, Smaglo BG, Willis J, Wolff RA, Pant S, Hurd MW, Maitra A, Wang H, Katz MHG, Prakash LR, Tzeng CWD, Snyder R, Castelnovo LF, Chen A, Kravets A, Kudriavtseva K, Tarasov A, Kryukov K, Ying H, Shen JP, Zhao D. Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series. Cancers (Basel) 2024; 16:3421. [PMID: 39410042 PMCID: PMC11475689 DOI: 10.3390/cancers16193421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/18/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023-2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.
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Affiliation(s)
| | - Mahmoud Yousef
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Abdelrahman Yousef
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Kristin D. Alfaro-Munoz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Brandon G. Smaglo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Jason Willis
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Robert A. Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Shubham Pant
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Mark W. Hurd
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
- Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Anirban Maitra
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (A.M.); (H.W.)
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Huamin Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (A.M.); (H.W.)
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Matthew Harold G. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (C.-W.D.T.); (R.S.)
| | - Laura R. Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (C.-W.D.T.); (R.S.)
| | - Ching-Wei D. Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (C.-W.D.T.); (R.S.)
| | - Rebecca Snyder
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (C.-W.D.T.); (R.S.)
| | - Luca F. Castelnovo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Anthony Chen
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Andrey Kravets
- BostonGene Corporation, 100 Beaver St, Waltham, MA 02453, USA; (A.K.); (K.K.); (A.T.); (K.K.)
| | - Kseniia Kudriavtseva
- BostonGene Corporation, 100 Beaver St, Waltham, MA 02453, USA; (A.K.); (K.K.); (A.T.); (K.K.)
| | - Artem Tarasov
- BostonGene Corporation, 100 Beaver St, Waltham, MA 02453, USA; (A.K.); (K.K.); (A.T.); (K.K.)
| | - Kirill Kryukov
- BostonGene Corporation, 100 Beaver St, Waltham, MA 02453, USA; (A.K.); (K.K.); (A.T.); (K.K.)
| | - Haoqiang Ying
- Department of Molecular and Cellular Oncology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - John Paul Shen
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
| | - Dan Zhao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (A.Y.); (K.D.A.-M.); (B.G.S.); (J.W.); (R.A.W.); (S.P.); (M.W.H.); (L.F.C.); (A.C.); (J.P.S.)
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Teramatsu K, Fujimori N, Murakami M, Yasumori S, Matsumoto K, Nakata K, Nakamura M, Koga Y, Oda Y, Ogawa Y. Pathological complete response with FOLFIRINOX therapy for recurrence of pancreatic acinar cell carcinoma. Clin J Gastroenterol 2024; 17:776-781. [PMID: 38761340 DOI: 10.1007/s12328-024-01983-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/06/2024] [Indexed: 05/20/2024]
Abstract
Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.
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Affiliation(s)
- Katsuhito Teramatsu
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Nao Fujimori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Masatoshi Murakami
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Sho Yasumori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kazuhide Matsumoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kohei Nakata
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yutaka Koga
- Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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de Jesus VHF, Donadio MDS, de Brito ÂBC, Gentilli AC. A narrative review on rare types of pancreatic cancer: should they be treated as pancreatic ductal adenocarcinomas? Ther Adv Med Oncol 2024; 16:17588359241265213. [PMID: 39072242 PMCID: PMC11282540 DOI: 10.1177/17588359241265213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 06/13/2024] [Indexed: 07/30/2024] Open
Abstract
Pancreatic cancer is one of the deadliest malignancies in humans and it is expected to play a bigger part in cancer burden in the years to come. Pancreatic ductal adenocarcinoma (PDAC) represents 85% of all primary pancreatic malignancies. Recently, much attention has been given to PDAC, with significant advances in the understanding of the mechanisms underpinning disease initiation and progression, along with noticeable improvements in overall survival in both localized and metastatic settings. However, given their rarity, rare histological subtypes of pancreatic cancer have been underappreciated and are frequently treated as PDAC, even though they might present non-overlapping molecular alterations and clinical behavior. While some of these rare histological subtypes are true variants of PDAC that should be treated likewise, others represent separate clinicopathological entities, warranting a different therapeutic approach. In this review, we highlight clinical, pathological, and molecular aspects of rare histological types of pancreatic cancer, along with the currently available data to guide treatment decisions.
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Affiliation(s)
- Victor Hugo Fonseca de Jesus
- Oncoclínicas, Department of Gastrointestinal Medical Oncology, Santos Dumont St. 182, 4 floor, Florianópolis, Santa Catarina 88015-020, Brazil
- Department of Medical Oncology, Centro de Pesquisas Oncológicas, Florianópolis, Santa Catarina, Brazil
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Merz V, Maines F, Marcucci S, Sartori C, Frisinghelli M, Trentin C, Kadrija D, Carbone FG, Michielan A, Gabbrielli A, Melisi D, Barbareschi M, Brolese A, Caffo O. Complete pathological response to pembrolizumab in pretreated pancreatic acinar cell carcinoma. J Cancer Res Clin Oncol 2024; 150:347. [PMID: 38990367 PMCID: PMC11239721 DOI: 10.1007/s00432-024-05841-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 06/06/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC). CASE PRESENTATION We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response. CONCLUSIONS Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis.
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Affiliation(s)
- Valeria Merz
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy.
- Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, Verona, Italy.
| | - Francesca Maines
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | - Stefano Marcucci
- Department of General Surgery and HPB Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Chiara Sartori
- Department of Laboratory Medicine - Pathology Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Michela Frisinghelli
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | - Dzenete Kadrija
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | | | - Andrea Michielan
- Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, APSS, Trento, Italy
- Center for Medical Sciences (CISMed), University of Trento, Trento, Italy
| | - Davide Melisi
- Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, Verona, Italy
| | - Mattia Barbareschi
- Department of Laboratory Medicine - Pathology Unit, Santa Chiara Hospital, APSS, Trento, Italy
- Center for Medical Sciences (CISMed), University of Trento, Trento, Italy
| | - Alberto Brolese
- Department of General Surgery and HPB Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Orazio Caffo
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
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Yamane K, Tsukano K, Umino Y, Nagami T, Tarumoto K, Hattori K, Maemoto R, Iwasaki J, Kanazawa A. Successful curative treatment for a ruptured pancreatic acinar cell carcinoma by radical resection following modified FOLFIRINOX: a case report and literature review. Int Cancer Conf J 2024; 13:281-288. [PMID: 38962046 PMCID: PMC11217244 DOI: 10.1007/s13691-024-00679-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 03/28/2024] [Indexed: 07/05/2024] Open
Abstract
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor type, and ruptured pancreatic tumors are rarer. Computed tomography (CT) in a 48-year-old man incidentally revealed a raptured pancreatic tail tumor. The patient was treated conservatively because he was asymptomatic, and his general condition was stable. After a detailed examination, the pancreatic tumor was diagnosed as raptured PACC. Considering the potential infiltration of tumor cells into the hematoma within the omental sac, our decision is to initiate chemotherapy as the primary course of action. A liquid biopsy was performed, and comprehensive genomic profiling of circulating tumor DNA showed a tumor BRCA2 mutation. Chemotherapy with modified FOLFIRINOX (mFFX) was selected as the first treatment. After seven courses of mFFX, the primary tumor diminished remarkably. At this time, the radical resection was performed via distal pancreatectomy with simultaneous resection of the gastric wall and colon, which had adhered strongly to the tumor. Histopathological examination revealed that the tumor had shrunk to less than 5% of its original size due to chemotherapy (Grade 3 of Evans Classification). Devising treatment strategies for ruptured pancreatic malignant tumors is challenging due to the worsening general condition caused by severe abdominal symptoms and intra-abdominal bleeding. In this context, this case-report documents a rare instance of raptured PACC with a tumor BRCA2 mutation that underwent radical resection following mFFX treatment.
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Affiliation(s)
- Kei Yamane
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Kosuke Tsukano
- Department of Gastroenterology, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Yosuke Umino
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Tadashi Nagami
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Koji Tarumoto
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Kuniaki Hattori
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Ryo Maemoto
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Junji Iwasaki
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
| | - Akiyoshi Kanazawa
- Department of Surgery, Shimane Prefectural Central Hospital, Izumo-Shi, Shimane, 693-8555 Japan
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Ikezawa K, Urabe M, Kai Y, Takada R, Akita H, Nagata S, Ohkawa K. Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment. Jpn J Clin Oncol 2024; 54:271-281. [PMID: 38109477 PMCID: PMC10925851 DOI: 10.1093/jjco/hyad176] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 11/29/2023] [Indexed: 12/20/2023] Open
Abstract
Pancreatic acinar cell carcinoma is a rare form (0.2-4.3%) of pancreatic neoplasm with unique clinical and molecular characteristics, which largely differ from pancreatic ductal adenocarcinoma. Pancreatic acinar cell carcinoma occurs more frequently in males and can occur in children. Serum lipase is elevated in 24-58% of patients with pancreatic acinar cell carcinoma. Pancreatic acinar cell carcinomas tend to be large at diagnosis (median tumour size: ~5 cm) and are frequently located in the pancreas head. Radiologically, pancreatic acinar cell carcinoma generally exhibits a solid appearance; however, necrosis, cystic changes and intratumoral haemorrhage can occur in larger lesions. Immunostaining is essential for the definitive diagnosis of pancreatic acinar cell carcinoma. Compared with pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma has a more favourable prognosis. Although radical surgery is recommended for patients with pancreatic acinar cell carcinoma who do not have distant metastases, the recurrence rate is high. The effectiveness of adjuvant therapy for pancreatic acinar cell carcinoma is unclear. The response to FOLFIRINOX is generally favourable, and some patients achieve a complete response. Pancreatic acinar cell carcinoma has a different genomic profile compared with pancreatic ductal adenocarcinoma. Although genomic analyses have shown that pancreatic acinar cell carcinoma rarely has KRAS, TP53 and CDKN2A mutations, it has a higher prevalence of homologous recombination-related genes, including BRCA1/2 and ATM, than pancreatic ductal adenocarcinoma, suggesting high sensitivity to platinum-containing regimens and PARP inhibitors. Targeted therapies for genomic alternations are beneficial. Therefore, genetic testing is important for patients with pancreatic acinar cell carcinoma to choose the optimal therapeutic strategy.
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Affiliation(s)
- Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Makiko Urabe
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yugo Kai
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Shigenori Nagata
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
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10
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Karamitopoulou-Diamantis E. [Exocrine meets neuroendocrine: mimickers of pancreatic neuroendocrine neoplasms]. PATHOLOGIE (HEIDELBERG, GERMANY) 2024; 45:42-49. [PMID: 38091082 DOI: 10.1007/s00292-023-01286-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/07/2023] [Indexed: 01/31/2024]
Abstract
Neuroendocrine neoplasms (NENs) originate from various epithelial or neuroectodermal tissues, can occur in any organ, including the pancreas, and are characterized by the expression of the neuroendocrine markers synaptophysin and chromogranin A. Pancreatic neuroendocrine tumors (PanNETs) are well-differentiated epithelial neoplasms with morphological and immunohistochemical features of neuroendocrine differentiation of low, intermediate, or high grade. Pancreatic neuroendocrine carcinomas (PanNECs) are clinically aggressive, high-grade (poorly differentiated) carcinomas with morphologic features suggesting neuroendocrine differentiation, a high proliferative rate (> 20 mitoses per 2 mm2 and Ki67 index > 20%), and immunohistochemical labeling for neuroendocrine markers. They include the small cell neuroendocrine carcinoma and the large cell neuroendocrine carcinoma categories.Neuroendocrine-like morphology coupled with immunohistochemical markers of neuroendocrine differentiation are highly specific. However, neuroendocrine markers may also be expressed in non-neuroendocrine neoplasms, which can therefore be confused with NENs. Mimickers of pancreatic NENs comprise a number of important pitfall tumors, including epithelial and non-epithelial neoplasms, such as acinar cell carcinomas, solid pseudopapillary neoplasms (SPNs), or even non-neoplastic lesions. All of these lesions have the expression of neuroendocrine markers in common, such as synaptophysin and chromogranin A, and although they are comparatively rare, they can cause considerable diagnostic problems. This review article deals with some of the most important mimickers of pancreatic neuroendocrine neoplasms and even non-neoplastic lesions, such as islet aggregation. The similarities and differences between these entities and pancreatic neuroendocrine neoplasms are highlighted, and key findings that facilitate the correct diagnosis are discussed.
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Affiliation(s)
- Eva Karamitopoulou-Diamantis
- Institut für Gewebemedizin und Pathologie, Universität Bern, Bern, Schweiz.
- PATHOLOGIE INSTITUT ENGE, Hardturmstr. 133, 8005, Zürich, Schweiz.
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11
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Bellotti R, Paiella S, Primavesi F, Jäger C, Demir IE, Casciani F, Kornprat P, Wagner D, Rösch CS, Butturini G, Giardino A, Goretzky PE, Mogl M, Fahlbusch T, Kaiser J, Strobel O, Nießen A, Luu AM, Salvia R, Maglione M. Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients. HPB (Oxford) 2023; 25:1411-1419. [PMID: 37563033 DOI: 10.1016/j.hpb.2023.07.897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 07/04/2023] [Accepted: 07/20/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. METHODS This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. RESULTS 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. DISCUSSION Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.
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Affiliation(s)
- Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Florian Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; Department of General, Visceral and Vascular Surgery, Salzkammergut Hospital, 4840 Vöcklabruck, Austria
| | - Carsten Jäger
- Department of Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Ihsan E Demir
- Department of Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Fabio Casciani
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Peter Kornprat
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | | | | | | | - Peter E Goretzky
- Department of Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 13353, Germany
| | - Martina Mogl
- Department of Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 13353, Germany
| | - Tim Fahlbusch
- St. Josef Hospital, Department of General and Visceral Surgery, Ruhr-University Bochum, Germany
| | - Jörg Kaiser
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Anna Nießen
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Andreas M Luu
- St. Josef Hospital, Department of General and Visceral Surgery, Ruhr-University Bochum, Germany; Klinikum für Allgemein, Viszeral- und Minimalinvasive Chirurgie, HELIOS Klinikum, Krefeld, Germany
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
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12
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Ciardiello D, Urbano F, Zamboni G, Palladino N, Bazzocchi F, Parente P. Left abdominal mass with carcinosis: Unusual presentation of pancreatic acinar cell carcinoma. Hepatobiliary Pancreat Dis Int 2023; 22:412-414. [PMID: 36307307 DOI: 10.1016/j.hbpd.2022.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 09/29/2022] [Indexed: 11/04/2022]
Affiliation(s)
- Davide Ciardiello
- Oncology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo 71013, Italy
| | - Filomena Urbano
- Radiology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo 71013, Italy
| | - Giuseppe Zamboni
- Pathology Unit, Ospedale Sacro Cuore Don Calabria, vai Sempreboni, Negrar and University of Verona, Negrar 37024, VR, Italy
| | - Nicola Palladino
- Radiology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo 71013, Italy
| | - Francesca Bazzocchi
- Abdominal Surgical Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo 71013, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo 71013, Italy.
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13
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Uhlig R, Bröker N, Weidemann S, Gorbokon N, Menz A, Büscheck F, Luebke AM, Putri D, Kluth M, Hube-Magg C, Hinsch A, Lennartz M, Reiswich V, Höflmayer D, Fraune C, Möller K, Bernreuther C, Lebok P, Sauter G, Minner S, Steurer S, Burandt E, Krech R, Dum D, Marx A, Simon R, Krech T, Clauditz TS, Jacobsen F. CELA3B immunostaining is a highly specific marker for acinar cell carcinoma of the pancreas. PLoS One 2023; 18:e0287528. [PMID: 37379306 DOI: 10.1371/journal.pone.0287528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 06/07/2023] [Indexed: 06/30/2023] Open
Abstract
Chymotrypsin-like elastase family member 3B (CELA3B, elastase-3B) is a pancreatic enzyme with digestive function in the intestine. Since RNA analyses of normal tissues suggest that CELA3B expression is limited to the pancreas, the potential diagnostic utility of CELA3B immunohistochemistry for the distinction of pancreatic from extrapancreatic cancers and in the distinction of acinar cell carcinoma from ductal adenocarcinoma was assessed. CELA3B expression was successfully analyzed in 13,223 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types by immunohistochemistry in a tissue microarray format (TMA). In normal tissues, CELA3B immunostaining was only seen in acinar cells and in a fraction of ductal cells of the pancreas as well as on some apical membranes of surface epithelial cells of the intestine. Among tumors, CELA3B immunostaining was seen in 12 of 16 (75%) acinar cell carcinoma of the pancreas including 6 cases with strong staining (37.5%) as well as in 5 of 13,207 other tumors (0.04%). These included 1.2% of 91 adenoid cystic carcinomas, 1.2% of 246 mucoepidermoid carcinomas and 0.8% of 127 acinic cell carcinomas of salivary glands. Our data show a good sensitivity (75%) and a high specificity (99.9%) of CELA3B immunohistochemistry for diagnosing acinar cell carcinoma of the pancreas.
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Affiliation(s)
- Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nina Bröker
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sören Weidemann
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Natalia Gorbokon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas M Luebke
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Devita Putri
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Viktor Reiswich
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rainer Krech
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Till S Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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14
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Uruga H, Tamura T, Miura Y, Itonaga J, Koyama R, Imamura T, Takazawa Y. Pancreatic acinar cell carcinoma with pleomorphic and spindle cells: An autopsy-proven case. Pathol Int 2023. [PMID: 37133201 DOI: 10.1111/pin.13326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 04/12/2023] [Indexed: 05/04/2023]
Abstract
Pancreatic acinar cell carcinomas are glandular and have amphophilic/eosinophilic cytoplasm, presenting acinar, solid, and trabecular structures. Unusual histological features of acinar cell carcinoma are known, such as oncocytic, pleomorphic, spindle, and clear cell variants, but their clinical significance has not been well described. A man in his 70s was referred to our hospital because of elevated serum pancreatic enzymes. Contrast-enhanced abdominal computed tomography revealed slight swelling of the pancreatic head and suspension of the main pancreatic duct in the pancreatic body. He died only 14 days after admission. Gross findings at autopsy showed an ill-defined tumor located in the pancreatic head, involving the gastric and duodenal walls. Peritoneal dissemination, liver metastases, and lymph node metastases were also observed. Microscopically, tumor cells had moderate-to-severe nuclear atypia and amphophilic cytoplasm showing pleomorphism, and diffusely proliferated in solid pattern without lumina, were admixed with spindle cells. Immunohistochemically, tumor cells including pleomorphic and spindle cells were positive for B-cell lymphoma/leukemia 10 and trypsin. Consequently, the diagnosis was pancreatic acinar cell carcinoma with pleomorphic and spindle cells. We encountered a rare variant of pancreatic acinar cell carcinoma with pleomorphic and spindle cells. Clinically, our case showed rapid progression.
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Affiliation(s)
- Hironori Uruga
- Department of Diagnostic Pathology, Toranomon Hospital, Tokyo, Japan
- Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Tetsuo Tamura
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Yasuro Miura
- Department of Diagnostic Pathology, Toranomon Hospital, Tokyo, Japan
| | - Jumpei Itonaga
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Rikako Koyama
- Okinaka Memorial Institute for Medical Research, Tokyo, Japan
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Tsunao Imamura
- Okinaka Memorial Institute for Medical Research, Tokyo, Japan
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Yutaka Takazawa
- Department of Diagnostic Pathology, Toranomon Hospital, Tokyo, Japan
- Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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15
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Ishimoto-Namiki U, Ino Y, Esaki M, Shimada K, Saruta M, Hiraoka N. Novel Insights Into Immunohistochemical Analysis For Acinar Cell Neoplasm of The Pancreas: Carboxypeptidase A2, Carboxypeptidase A1, and Glycoprotein 2. Am J Surg Pathol 2023; 47:525-534. [PMID: 36815573 DOI: 10.1097/pas.0000000000002024] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
Acinar cell carcinoma (ACC) is a rare and highly malignant pancreatic tumor. Owing to histologic similarity, ACC is often difficult to distinguish from other solid medullary pancreatic tumors, particularly neuroendocrine neoplasm (NEN) and intraductal tubulopapillary neoplasm (ITPN). We aimed to identify new immunohistochemical markers commonly expressed in tumor cells with acinar cell differentiation and useful for both surgical and small biopsy specimens. Candidate molecules exclusively expressed in neoplastic or non-neoplastic acinar cells in pancreatic tissues with specific and available antibodies suitable for immunohistochemistry were selected. We selected carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and glycoprotein 2 (GP2), which were expressed in 100%, 100%, and 96% of cases, respectively, in ACC (n=27) or neoplasia with acinar cell differentiation, including mixed acinar-neuroendocrine carcinoma (n=9), mixed acinar-ductal carcinoma (n=3), pancreatoblastoma (n=4), and acinar cystic transformation (n=2), in the cytoplasm of tumor cells with a granular pattern. Both CPA2 and CPA1 were not expressed in any other tumors without acinar cell differentiation, including NEN (n=44), pancreatic ductal adenocarcinoma (n=44), and ITPN (n=4). GP2 was not expressed in these tumors except in rare cases, including 14% of NEN, 15% of intraductal papillary-mucinous neoplasm, 25% of intraductal oncocytic papillary neoplasm, 25% of ITPN, and 7% of pancreatic ductal adenocarcinoma, wherein a small proportion of tumor cells expressed GP2 in their apical cell membrane. NEN cases also showed cytoplasmic GP2 expression. Therefore, CPA2, CPA1, and potentially GP2 may act as ACC markers.
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Affiliation(s)
- Utako Ishimoto-Namiki
- Division of Molecular Pathology
- Department of Analytical Pathology, National Cancer Center Research Institute
- Department of Molecular Oncology
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University Graduate School of Medicine
| | - Yoshinori Ino
- Division of Molecular Pathology
- Department of Analytical Pathology, National Cancer Center Research Institute
| | - Minoru Esaki
- Hepatobiliary Pancreatic Surgery Division, National Cancer Center Hospital
| | - Kazuaki Shimada
- Hepatobiliary Pancreatic Surgery Division, National Cancer Center Hospital
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University Graduate School of Medicine
| | - Nobuyoshi Hiraoka
- Division of Molecular Pathology
- Department of Analytical Pathology, National Cancer Center Research Institute
- Department of Molecular Oncology
- Division of Innovative Pathology and Laboratory Medicine, National Cancer Center EPOC, Tokyo, Japan
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16
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Mormul A, Włoszek E, Nowoszewska J, Fudalej M, Budzik M, Badowska-Kozakiewicz A, Deptała A. Rare Non-Neuroendocrine Pancreatic Tumours. Cancers (Basel) 2023; 15:cancers15082216. [PMID: 37190144 DOI: 10.3390/cancers15082216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/30/2023] [Accepted: 04/07/2023] [Indexed: 05/17/2023] Open
Abstract
The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms.
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Affiliation(s)
- Agata Mormul
- Students' Scientific Organization of Cancer Cell Biology, Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Emilia Włoszek
- Students' Scientific Organization of Cancer Cell Biology, Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Julia Nowoszewska
- Students' Scientific Organization of Cancer Cell Biology, Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Marta Fudalej
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Michał Budzik
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | | | - Andrzej Deptała
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
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17
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Goto H, Koga Y, Kohashi K, Ono H, Takemoto J, Matsuura T, Tajiri T, Ihara K, Oda Y, Ohga S. Pancreatoblastoma with a novel fusion gene of IQSEC1-RAF1. Pediatr Blood Cancer 2023; 70:e30155. [PMID: 36519595 DOI: 10.1002/pbc.30155] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 10/05/2022] [Accepted: 10/17/2022] [Indexed: 12/23/2022]
Affiliation(s)
- Hironori Goto
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan
| | - Yuhki Koga
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Pediatric and Perinatal Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Kohashi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroaki Ono
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Junkichi Takemoto
- Department of Pediatric Surgery, Reproductive and Developmental Medicine Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Reproductive and Developmental Medicine Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tatsuro Tajiri
- Department of Pediatric Surgery, Reproductive and Developmental Medicine Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenji Ihara
- Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shouichi Ohga
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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18
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Mendoza D, Giorgadze T, Evans J, Miller JA. Touch preparation from a pancreatic core biopsy. Cytojournal 2023; 20:6. [PMID: 37026153 PMCID: PMC10070336 DOI: 10.25259/cytojournal_66_2019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 07/07/2022] [Indexed: 03/08/2023] Open
Affiliation(s)
- David Mendoza
- Department of Pathology, Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, United States,
| | - Tamara Giorgadze
- Department of Pathology, Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, United States,
| | - John Evans
- Department of Pathology, Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, United States,
| | - James A. Miller
- Department of Pathology, Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, United States,
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19
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Hoshi D, Kita E, Maru Y, Kogashi H, Nakamura Y, Tatsumi Y, Shimozato O, Nakamura K, Sudo K, Tsujimoto A, Yokoyama R, Kato A, Ushiku T, Fukayama M, Itami M, Yamaguchi T, Hippo Y. Derivation of pancreatic acinar cell carcinoma cell line HS-1 as a patient-derived tumor organoid. Cancer Sci 2023; 114:1165-1179. [PMID: 36382538 PMCID: PMC9986095 DOI: 10.1111/cas.15656] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 10/31/2022] [Accepted: 11/09/2022] [Indexed: 11/17/2022] Open
Abstract
Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long-term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy-derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS-1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS-1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.
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Affiliation(s)
- Daisuke Hoshi
- Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan.,Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Emiri Kita
- Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan.,Department of Gastroenterology, Chiba Cancer Center, Chiba, Japan
| | - Yoshiaki Maru
- Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Hiroyuki Kogashi
- Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Yuki Nakamura
- Division of Oncogenomics, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Yasutoshi Tatsumi
- Division of Oncogenomics, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Osamu Shimozato
- Division of Oncogenomics, Chiba Cancer Center Research Institute, Chiba, Japan
| | | | - Kentaro Sudo
- Department of Gastroenterology, Chiba Cancer Center, Chiba, Japan
| | - Akiko Tsujimoto
- Department of Gastroenterology, Chiba Cancer Center, Chiba, Japan
| | - Ryo Yokoyama
- Division of Pathological Diagnosis, Matsudo City General Hospital, Chiba, Japan
| | - Atsushi Kato
- Department of Hepatobiliary-Pancreatic Surgery, Chiba Cancer Center, Chiba, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masashi Fukayama
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Pathology, Asahi General Hospital, Chiba, Japan
| | - Makiko Itami
- Division of Surgical Pathology, Chiba Cancer Center, Chiba, Japan
| | - Taketo Yamaguchi
- Department of Gastroenterology, Chiba Cancer Center, Chiba, Japan.,Department of Internal Medicine, Funabashi Central Hospital, Chiba, Japan
| | - Yoshitaka Hippo
- Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Japan
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20
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Machado I, López-Guerrero JA, Fernandez A, López R, García Casado Z, Ferrandez A, Llombart-Bosch A, Charville GW. Adult Pancreatoblastoma: Report of 3 new Cases With Genetic Diversity and Autopsy Findings. Int J Surg Pathol 2022:10668969221133351. [PMID: 36573045 DOI: 10.1177/10668969221133351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
We report the histopathological, immunohistochemical (IHC), and molecular findings in 3 patients with adult pancreatoblastoma, including 2 with autopsy features. The tumors were located in the tail and body of the pancreas, and the 2 autopsy examinations revealed liver and lung metastases. Histopathologically the neoplasms were composed of solid epithelial elements with nested or trabecular growth patterns, fibrous stroma, and squamoid clusters. Keratin 19 was positive mainly in squamoid corpuscles, and trypsin or chymotrypsin was positive in the acinar component. Neuroendocrine differentiation was observed in all tumors, and nuclear β-catenin expression in 2 tumors. Despite nuclear β-catenin expression, CTNNB1 mutation was found only in tumor 2. APC mutation was detected in tumor 1, and SMAD4 as well as MEN1 mutations in tumor 3. This last tumor also revealed chromosomal instability with many chromosomal losses and gains. The follow-up showed regional or distant metastases in all patients. Two patients died of disease after 3 and 26 months of follow-up and 1 patient is alive with no evidence of disease 6 years and 2 months after surgery. Adult pancreatoblastoma can display genetic heterogeneity, diverse histological appearance, and overlapping IHC findings. As a result, the differential diagnosis with other adult pancreatic tumors, such as acinar cell carcinoma, neuroendocrine neoplasm, solid pseudopapillary neoplasm, and mixed tumors may be challenging, especially when dealing with limited tumor tissue. The identification of squamoid corpuscles is essential for diagnosis. Although molecular findings might provide useful information, the integration of clinical, radiological, and histopathological findings is essential in pancreatoblastoma diagnosis.
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Affiliation(s)
- Isidro Machado
- Department of Pathology, Instituto Valenciano de Oncología, Valencia, Spain
- Patologika Laboratory, Hospital QuirónSalud, Valencia, Spain
- Department of Pathology, University of Valencia, Valencia, Spain
| | | | | | - Raquel López
- Department of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain
| | - Zaida García Casado
- Department of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain
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21
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Calimano-Ramirez LF, Daoud T, Gopireddy DR, Morani AC, Waters R, Gumus K, Klekers AR, Bhosale PR, Virarkar MK. Pancreatic acinar cell carcinoma: A comprehensive review. World J Gastroenterol 2022; 28:5827-5844. [PMID: 36353206 PMCID: PMC9639656 DOI: 10.3748/wjg.v28.i40.5827] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/14/2022] [Accepted: 10/14/2022] [Indexed: 02/06/2023] Open
Abstract
Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients. As there are no significant patient series about ACCs, our understanding of this illness is mainly based on case reports and limited patient series. Surgical resection is the treatment of choice for patients with the disease restricted to one organ; however, with recent breakthroughs in precision medicine, medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon. There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible. As a result of shared genetic alterations, ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas. The role of neoadjuvant or adjuvant chemoradiotherapy has not been established. This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.
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Affiliation(s)
| | - Taher Daoud
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Dheeraj Reddy Gopireddy
- Department of Diagnostic Radiology, University of Florida College of Medicine Jacksonville, Jacksonville, FL 32209, United States
| | - Ajaykumar C Morani
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Rebecca Waters
- Department of Pathology and Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Kazim Gumus
- Department of Research and Diagnostic Radiology, University of Florida College of Medicine Jacksonville, Jacksonville, FL 32209, United States
| | - Albert Russell Klekers
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Priya R Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Mayur K Virarkar
- Department of Diagnostic Radiology, University of Florida College of Medicine Jacksonville, Jacksonville, FL 32209, United States
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22
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Abstract
Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare neoplasms, composed of at least two components. The neuroendocrine part is always present. Histology is the most important tool for the diagnosis, but in the case of MiNEN, it is also important for the use of immunohistochemistry, which should include neuroendocrine but also ductal and acinar markers. Each component should be specifically described in the final pathology report, including the percentage on the entire tumor mass. The prognosis of MiNEN is very heterogeneous and depends on the different tumor components.
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Affiliation(s)
- Vassilena Tsvetkova
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy.
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23
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Ghosh T, Greipp PT, Knutson D, Kloft-Nelson S, Jenkins S, Mounajjed T, Said S, La Rosa S, Vanoli A, Sessa F, Naini BV, Bellizzi A, Zhang L, Kerr SE, Graham RP. BRAF Rearrangements and BRAF V600E Mutations Are Seen in a Subset of Pancreatic Carcinomas With Acinar Differentiation. Arch Pathol Lab Med 2022; 146:840-845. [PMID: 34614142 DOI: 10.5858/arpa.2020-0739-oa] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2021] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Comprehensive genomic profiling has demonstrated that approximately 20% of pancreatic carcinomas with acinar differentiation harbor potentially targetable BRAF fusions that activate the MAPK pathway. OBJECTIVES.— To validate the above finding by BRAF break-apart fluorescence in situ hybridization (FISH) in a large series of pure acinar cell carcinomas (ACCs), evaluate tumors for the presence of BRAF V600E mutations, and compare clinicopathologic features of tumors with BRAF rearrangements with those without. DESIGN.— Thirty cases of pure ACC and 6 cases of mixed acinar-neuroendocrine carcinoma (ACC-NEC) were retrieved. A break-apart FISH probe was used to detect BRAF rearrangements. Immunohistochemistry for BRAF V600E was performed. RESULTS.— BRAF rearrangements by FISH were found in 6 of 36 cases (17%), 5 of which were pure ACC and 1 was a mixed ACC-NEC. Follow-up was available in 29 of 36 cases (81%). The median survival was 22 months for BRAF-rearranged cases and 16 months for BRAF-intact cases; the 2-year overall survival was 50% for BRAF-rearranged cases and 35% for BRAF-intact cases. No significant clinicopathologic differences were identified in cases with BRAF rearrangement compared with those without BRAF rearrangement. BRAF V600E mutation was identified in 2 of 34 cases (6%), both of which were pure ACC and were BRAF-intact by FISH. CONCLUSIONS.— This study supports the finding that BRAF rearrangements are present in approximately 20% of cases and identified BRAF V600E mutations in approximately 5% of cases. These cases may benefit from targeted therapy.
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Affiliation(s)
- Toshi Ghosh
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Patricia T Greipp
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Darlene Knutson
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Sara Kloft-Nelson
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Sarah Jenkins
- From the Department of Health Sciences Research (Jenkins), Mayo Clinic, Rochester, Minnesota
| | - Taofic Mounajjed
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Samar Said
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Stefano La Rosa
- From the Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (La Rosa)
| | - Alessandro Vanoli
- From the Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, and IRCCS San Matteo Hospital, Pavia, Italy (Vanoli)
| | - Fausto Sessa
- From the Anatomic Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy (Sessa)
| | - Bita V Naini
- From the Department of Pathology, University of California, Los Angeles (Naini)
| | - Andrew Bellizzi
- From the Department of Pathology, University of Iowa, Iowa City (Bellizzi)
| | - Lizhi Zhang
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Sarah E Kerr
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
| | - Rondell P Graham
- From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, Minnesota
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24
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Takayama Y, Shimizu K, Tokushige K, Egawa H, Yamamoto M. A case of pathologically complete response after preoperative chemotherapy in a pancreatic acinar cell carcinoma patient with portal vein tumor thrombosis. Clin J Gastroenterol 2022; 15:642-648. [PMID: 35013933 DOI: 10.1007/s12328-021-01571-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 12/02/2021] [Indexed: 10/19/2022]
Abstract
Preoperative treatment is being proposed as a standard treatment for pancreatic ductal adenocarcinoma though few cases show a pathologically complete response. On the other hand, there is no consensus regarding preoperative chemotherapy for pancreatic acinar cell carcinoma (ACC). The present study described a rare case of ACC in the pancreatic head with portal vein tumor thrombosis (PVTT) treated with preoperative chemotherapy using modified FOLFIRINOX, which achieved a pathologically complete response. A 65-year-old man was referred for consideration of treatment strategy. Contrast-enhanced abdominal computed tomography revealed a pancreatic tumor and PVTT. The pancreatic tumor was diagnosed as ACC by an endoscopic ultrasound-guided fine-needle aspiration biopsy. Initially, the tumor was assessed as unresectable due to the presence of PVTT, and therefore, a chemotherapy using modified FOLFIRINOX was administered. After 14 courses of the chemotherapy, imaging studies revealed that the tumor and PVTT showed marked reduction in size; thus, the patient underwent pancreaticoduodenectomy with combined resection of the portal vein (PV). A pathological examination uncovered a complete degeneration of the primary tumor and the PV embolus without any residue of carcinoma. The patient did not receive adjuvant chemotherapy and survived with no evidence of recurrence for 33 months after surgery. The chemotherapy using modified FOLFIRINOX could give a complete response in patients with pancreatic ACC with PVTT.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai, 980-8575, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Yukiko Takayama
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Kyoko Shimizu
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Katsutoshi Tokushige
- Department of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
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25
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Holmager P, Langer SW, Kjaer A, Ringholm L, Garbyal RS, Pommergaard HC, Hansen CP, Federspiel B, Andreassen M, Knigge U. Surgery in Patients with Gastro-Entero-Pancreatic Neuroendocrine Carcinomas, Neuroendocrine Tumors G3 and High Grade Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms. Curr Treat Options Oncol 2022; 23:806-817. [PMID: 35362798 DOI: 10.1007/s11864-022-00969-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2022] [Indexed: 12/19/2022]
Abstract
OPINION STATEMENT In the 2019 WHO guidelines, the classification of gastro-entero-pancreatic neuroendocrine neoplasms (GEP NEN) has changed from one being based on Ki-67 proliferation index alone to one that also includes tumor differentiation. Consequently, GEP NENs are now classified as well-differentiated neuroendocrine tumor (NET), NET G1 (Ki-67 <3%), NET G2 (Ki-67 3-20%) and NET G3 (Ki-67 >20%), and poorly differentiated neuroendocrine carcinoma (NEC) (Ki-67 >20%). It has been suggested that NET G3 should be treated as NET G2 with respect to surgery, while surgical management of NEC should be expanded from local disease to also include patients with advanced disease where curative surgery is possible. High grade mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have a neuroendocrine and a non-neuroendocrine component mostly with a poor prognosis. All studies evaluating the effect of surgery in NEC and MiNEN are observational and hold a risk of selection bias, which may overestimate the beneficial effect of surgery. Further, only a few studies on the effect of surgery in MiNEN exist. This review aims to summarize the data on the outcome of surgery in patients with GEP NET G3, GEP NEC and high grade MiNEN. The current evidence suggests that patients with NEN G3 and localized disease and NEN G3 patients with metastatic disease where curative surgery can be achieved may benefit from surgery. In patients with MiNEN, it is currently not possible to evaluate on the potential beneficial effect of surgery due to the low number of studies.
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Affiliation(s)
- Pernille Holmager
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. .,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark.
| | - Seppo W Langer
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Oncology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lene Ringholm
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark
| | - Rajendra Singh Garbyal
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Pathology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Hans-Christian Pommergaard
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Surgery and Transplantation, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Carsten Palnæs Hansen
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Surgery and Transplantation, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Birgitte Federspiel
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mikkel Andreassen
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark.,Department of Surgery and Transplantation, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
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26
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Couvelard A, Cros J. An update on the development of concepts, diagnostic criteria, and challenging issues for neuroendocrine neoplasms across different digestive organs. Virchows Arch 2022; 480:1129-1148. [PMID: 35278097 DOI: 10.1007/s00428-022-03306-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 02/11/2022] [Accepted: 02/27/2022] [Indexed: 12/16/2022]
Abstract
Digestive neuroendocrine neoplasms (NENs) are a group of heterogeneous neoplasms found throughout the digestive tract, with different behaviour and genetic background. In the last few years, nomenclature and WHO/UICC classifications of digestive NENs have changed, and molecular classifications have emerged, especially in pancreatic locations. Increasing patho-molecular details are needed to diagnose the different categories of NEN, including the use of helpful immunohistochemical markers. In this review, we address these topics in three successive chapters. We first briefly review recent updates in classifications, discuss important grading and proliferating issues and advances in the molecular understanding of NEN. Then, we provide an update on diagnosis, including the most important differential diagnoses of NEN, with a focus on high-grade neoplasms and mixed tumours. Finally, we highlight a variety of currently used and next-generation predictive and prognostic biomarkers as well as biomarkers of tumour origin and describe some site specificities of gastrointestinal NEN. We specifically focus on biomarkers available to pathologists with the potential to change the way patients with NEN are diagnosed and treated.
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Affiliation(s)
- Anne Couvelard
- Department of Pathology of Bichat and Beaujon AP-HP Hospitals, ENETS Centre of Excellence, Université Paris Cité, 46 Rue Henri Huchard, 75018, Paris, France.
| | - Jérôme Cros
- Department of Pathology of Bichat and Beaujon AP-HP Hospitals, ENETS Centre of Excellence, Université Paris Cité, 46 Rue Henri Huchard, 75018, Paris, France
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27
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Yachida S, Totoki Y, Noë M, Nakatani Y, Horie M, Kawasaki K, Nakamura H, Saito-Adachi M, Suzuki M, Takai E, Hama N, Higuchi R, Hirono S, Shiba S, Kato M, Furukawa E, Arai Y, Rokutan H, Hashimoto T, Mitsunaga S, Kanda M, Tanaka H, Takata S, Shimomura A, Oshima M, Hackeng WM, Okumura T, Okano K, Yamamoto M, Yamaue H, Morizane C, Arihiro K, Furukawa T, Sato T, Kiyono T, Brosens LA, Wood LD, Hruban RH, Shibata T. Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System. Cancer Discov 2022; 12:692-711. [PMID: 34880079 PMCID: PMC9394397 DOI: 10.1158/2159-8290.cd-21-0669] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 08/23/2021] [Accepted: 10/14/2021] [Indexed: 01/07/2023]
Abstract
The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. SIGNIFICANCE GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587.
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Affiliation(s)
- Shinichi Yachida
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.,Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.,Division of Genomic Medicine, National Cancer Center Research Institute, Tokyo, Japan.,Corresponding Author: Shinichi Yachida, Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81(6)6879-3360; Fax: 81(6)6879-3369; E-mail:
| | - Yasushi Totoki
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Michaël Noë
- Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.,Sol Goldman Pancreatic Cancer Research Center, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Yoichiro Nakatani
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Masafumi Horie
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Kenta Kawasaki
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hiromi Nakamura
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Mihoko Saito-Adachi
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Masami Suzuki
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Erina Takai
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Natsuko Hama
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Seiko Hirono
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Satoshi Shiba
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Mamoru Kato
- Department of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan
| | - Eisaku Furukawa
- Department of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan
| | - Yasuhito Arai
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Hirofumi Rokutan
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Taiki Hashimoto
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Shuichi Mitsunaga
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Hidenori Tanaka
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - So Takata
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Ayaka Shimomura
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Minoru Oshima
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Wenzel M. Hackeng
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Tomoyuki Okumura
- Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Toshiro Sato
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tohru Kiyono
- Project for Prevention of HPV-Related Cancer, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Lodewijk A.A. Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Laura D. Wood
- Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.,Sol Goldman Pancreatic Cancer Research Center, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Ralph H. Hruban
- Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.,Sol Goldman Pancreatic Cancer Research Center, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Tatsuhiro Shibata
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.,Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Ozcan K, Klimstra DS. A Review of Mucinous Cystic and Intraductal Neoplasms of the Pancreatobiliary Tract. Arch Pathol Lab Med 2022; 146:298-311. [PMID: 35192699 DOI: 10.5858/arpa.2021-0399-ra] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2021] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically silent, thanks to the increased use of sensitive imaging techniques. Cystic and intraductal neoplasms of the pancreas are often resectable and curable and constitute about 5% of all pancreatic neoplasms. Owing to their preinvasive nature and different biology, recognition of these entities remains a major priority. Mucinous cystic neoplasms are histologically and clinically distinct from other cystic pancreatic neoplasms. Pancreatic intraductal neoplasms encompass 3 major entities: intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Intraductal papillary neoplasms of bile ducts are also preinvasive mass-forming neoplasms with both similarities and differences with their pancreatic counterparts. All of these pancreatobiliary neoplasms have diverse and distinctive clinicopathologic, genetic, and prognostic variations. OBJECTIVE.— To review the clinical, pathologic, and molecular features of mucinous cystic and intraductal neoplasms of the pancreatobiliary tract. DATA SOURCES.— Literature review, diagnostic manuals, and guidelines. CONCLUSIONS.— This review will briefly describe well-known clinical and pathologic features and will focus on selected recently described aspects of morphology, grading, classification, and genomic alterations of cystic and intraductal neoplasms of the pancreatobiliary tract.
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Affiliation(s)
- Kerem Ozcan
- From the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - David S Klimstra
- From the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
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29
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Xu JY, Guan WL, Lu SX, Wei XL, Shi WJ, Ren C, Li YH, Li SP, Qiu MZ, Wang FH. Optimizing Chemotherapy of Pancreatic Acinar Cell Carcinoma: Our Experiences and Pooled Analysis of Literature. CLINICAL MEDICINE INSIGHTS: ONCOLOGY 2022; 16:11795549221090186. [PMID: 35509769 PMCID: PMC9058357 DOI: 10.1177/11795549221090186] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 03/09/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Pancreatic acinar cell carcinoma (PACC) is rare, and its appropriate treatment remains unknown. We aim to explore the characteristics and optimal treatment of it. Methods: The data on clinicopathologic characteristics, molecular alteration, treatment, and survival of patients diagnosed with PACC at the Sun Yat-sen University Cancer Center from 2005 to 2020 were collected. The optimal treatment was explored by co-analyzing our results and published literatures. Results: Twenty-two PACC patients were enrolled. Eight of 17 non-metastatic patients received adjuvant chemotherapy. The patients receiving fluoropyrimidine-based regimen (n = 3) had a better median disease-free survival (mDFS) than those with gemcitabine-based regimen (n = 5) (unreached vs 27 months). Eight metastatic patients received first-line chemotherapy. Four patients received second-line chemotherapy. The objective response rate (ORR) of the fluoropyrimidine-based regimen was 85.7% (6/7), much better than that of the gemcitabine-based regimen (0/5). One patient who had responded to the first-line FOLFIRINOX (5-fluorouracil + oxaliplatin + leucovorin + irinotecan) regimen received olaparib as maintenance treatment for 5 months with good tolerance. Thirty-one published literatures, with a total of 86 cases, were included in the co-analysis. The ORR of the first-line fluoropyrimidine-based regimen (n = 47) was higher than that of gemcitabine-based regimen (n = 39) (59.6% vs 15.3%, P < .001). Eight of 11 patients treated with the FOLFIRINOX regimen achieved partial response (PR). Conclusions: For patients with metastasis, a fluorouracil-based regimen such as FOLFIRINOX may be preferred, and maintenance treatment of poly ADP-ribose polymerase (PARP) inhibitors after effective platinum-containing treatment for breast cancer susceptibility gene (BRCA) mutation patients must be assessed.
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Affiliation(s)
- Jian-Ying Xu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Long Guan
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shi-Xun Lu
- Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Li Wei
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Jie Shi
- University Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany
| | - Chao Ren
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yu-Hong Li
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Sheng-Ping Li
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Miao-Zhen Qiu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Feng-Hua Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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30
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Uhlig R, Contreras H, Weidemann S, Gorbokon N, Menz A, Büscheck F, Luebke AM, Kluth M, Hube-Magg C, Hinsch A, Höflmayer D, Fraune C, Möller K, Bernreuther C, Lebok P, Sauter G, Wilczak W, Izbicki J, Perez D, Schrader J, Steurer S, Burandt E, Krech R, Dum D, Krech T, Marx A, Simon R, Minner S, Jacobsen F, Clauditz TS. Carboxypeptidase A1 (CPA1) Immunohistochemistry Is Highly Sensitive and Specific for Acinar Cell Carcinoma (ACC) of the Pancreas. Am J Surg Pathol 2022; 46:97-104. [PMID: 34889867 PMCID: PMC8860221 DOI: 10.1097/pas.0000000000001817] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Carboxypeptidase A1 (CPA1) is a zinc metalloprotease that is produced in pancreatic acinar cells and plays a role in cleaving C-terminal branched-chain and aromatic amino acids from dietary proteins. This study assessed the utility of immunohistochemical CPA1 staining for diagnosing pancreatic acinar cell carcinoma (ACC). A total of 12,274 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types were interpretable by immunohistochemistry in a tissue microarray format. CPA1 was strongly expressed in acinar cells of all normal pancreas samples but not in any other normal tissues. CPA1 immunostaining was detected in 100% of 11 pancreatic ACCs and 1 mixed acinar endocrine carcinoma, but absent in 449 pancreatic ductal adenocarcinomas, 75 adenocarcinomas of the ampulla Vateri, and 11,739 other evaluable cancers from 128 different tumor entities. A weak to moderate diffuse staining of epithelial and stromal cells of cancer tissues immediately adjacent to non-neoplastic pancreatic acinar cells often occurred and was considered to be caused by the diffusion of the highly abundant CPA1 from normal acinar cells that may have suffered some autolytic cell damage. In conclusion, our data show that CPA1 is a highly sensitive and largely specific marker for normal and neoplastic pancreatic acinar cells. CPA1 immunohistochemistry greatly facilitates the otherwise often difficult diagnosis of pancreatic ACC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Jakob Izbicki
- General, Visceral and Thoracic Surgery Department and Clinic
| | - Daniel Perez
- General, Visceral and Thoracic Surgery Department and Clinic
| | - Jörg Schrader
- General, Visceral and Thoracic Surgery Department and Clinic
- I. Medical Department—Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg
| | | | | | - Rainer Krech
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck
| | | | - Till Krech
- Institute of Pathology
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck
| | - Andreas Marx
- Institute of Pathology
- Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
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31
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Manfrin E, Parisi A, Stefanizzi L, D'Onofrio M, Bernardoni L, Crino SF, Pelosi G, Pancione M, Giordano G, Sina S, Remo A. Bcl-10, trypsin and synaptophysin helps recognize acinar cell and mixed acinar neuroendocrine cell carcinoma of the pancreas on both preoperative cytological samples and needle biopsy specimens. Pathol Res Pract 2021; 226:153593. [PMID: 34481211 DOI: 10.1016/j.prp.2021.153593] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/18/2021] [Accepted: 08/20/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Acinar cell carcinoma (ACC) of the pancreas are known to be rare and difficult to be recognize because they mimic other unrelated tumors (neuroendocrine, solid pseudopapillary) with different clinical behavior. Especially in the setting of inoperable patients, fine needle aspiration cytology (FNAC), core needle biopsy (FNAB) and immunocyto/histochemistry (ICC/IHC) play a crucial role in the differential diagnosis. The biological material available for ICC tests obtained by minimal invasive procedures is usually limited. Aim of the current study was to evaluate diagnostic panel based on a limited number of ICC markers for typing preoperatively ACC of the pancreas. METHODS Of 1820 needle sampling procedures performed and related to pancreatic lesions, 21 cases were extracted with a confirmed diagnosis of ACC on histology. Of them,12 were pure ACC and 9 mixed acinar-neuroendocrine carcinoma (MANEC). Smears of ACC, MANEC and a control group composed of 34neuroendocrine, 7solid pseudopapillary, 50ductal and 4 adenosquamous carcinoma were assessed with an ICC panel made up of BCL10, trypsin, synaptophysin, chromograninA, β-catenin. RESULTS On cytology, BCL10 sensitivity and specificity for ACC was 100%. Trypsin correctly recognized 90% of the cases. Synaptophysin was helpful to correctly identify all the cases with a mixed neuroendocrine component. No significant cross-reaction was observed between BCL10 and trypsin in any of the control group case. CONCLUSIONS BCL10 is a determinant marker for the diagnosis of acinar cell carcinoma and mixed acinar neuroendocrine cell carcinoma of the pancreas in a pre-operative citologic/histologic setting.
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Affiliation(s)
- Erminia Manfrin
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, L.A. Scuro Square, 10, 37134 Verona, Italy.
| | - Alice Parisi
- Department of Pathology and Diagnosis, Section of Pathology, University of Verona Hospital Trust, L.A. Scuro Square, 10, 37134 Verona, Italy
| | - Lavinia Stefanizzi
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, L.A. Scuro Square, 10, 37134 Verona, Italy
| | - Mirko D'Onofrio
- Department of Diagnostics and Public Health, Section of Radiology, University of Verona, L.A. Scuro Square, 10, 37134 Verona, Italy
| | - Laura Bernardoni
- Department of Medicine, Unit of Digestive Endoscopy, Pancreas Institute, University of Verona Hospital Trust, L.A. Scuro Square, 10, 37134 Verona, Italy
| | - Stefano Francesco Crino
- Department of Medicine, Unit of Digestive Endoscopy, Pancreas Institute, University of Verona Hospital Trust, L.A. Scuro Square, 10, 37134 Verona, Italy
| | - Giuseppe Pelosi
- Department of Oncology and Hemato-Oncology, University of Milan School of Medicine, via Festa del Perdono, 7, 20122 Milan, Italy
| | - Massimo Pancione
- Department of Science and Technologies, University of Sannio, Port'Arsa 11, 82100 Benevento, Italy
| | - Guido Giordano
- U.O.C. Oncologia Medica, Ospedali Riuniti Azienda Ospedaliera Universitaria, 71122 Foggia, Italy
| | - Sokol Sina
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, L.A. Scuro Square, 10, 37134 Verona, Italy
| | - Andrea Remo
- Department of Pathology, ULSS9 "Scaligera", Via Valverde 42, 37100 Verona, Italy.
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32
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Ikeda M, Miura S, Hamada S, Sano T, Matsumoto R, Tanaka Y, Hongo S, Yoshida N, Takikawa T, Kikuta K, Kume K, Hata T, Unno M, Omori Y, Furukawa T, Masamune A. Acinar Cell Carcinoma with Morphological Change in One Month. Intern Med 2021; 60:2799-2806. [PMID: 33746172 PMCID: PMC8479223 DOI: 10.2169/internalmedicine.7121-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 64-year-old man was admitted to our hospital to undergo examination of a pancreatic tumor accompanied by sudden epigastric pain. The tumor had a well-defined oval shape that was mostly less enhanced, with the exception of part of the tumor on the pancreatic head side, on contrast enhanced (CE)-CT. However, CE-CT performed one-month later revealed that the viable part of the tumor grew toward the pancreatic tail with the reduction of necrotic tissue. We performed distal pancreatectomy and the tumor was diagnosed as acinar cell carcinoma (ACC). One important characteristic of ACC is that it may develop morphological changes within a short period of time.
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Affiliation(s)
- Mio Ikeda
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Shin Miura
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Shin Hamada
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Takanori Sano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Ryotaro Matsumoto
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Yu Tanaka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Seiji Hongo
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Naoki Yoshida
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Tetsuya Takikawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Kazuhiro Kikuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Kiyoshi Kume
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Tatsuo Hata
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Yuko Omori
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
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33
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Hämmerle M, Bergmann F. [Rare pancreatic tumors]. DER PATHOLOGE 2021; 42:484-490. [PMID: 34402979 DOI: 10.1007/s00292-021-00967-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/06/2021] [Indexed: 10/20/2022]
Abstract
Beyond pancreatic ductal adenocarcinoma, which is by far the most frequent pancreatic neoplasm, a great variety of tumors occur in the pancreas. They include solid and cystic masses and epithelial and nonepithelial neoplasms, and they show a great diversity in their biological behavior, ranging from benign tumors to highly aggressive neoplasms. As examples of rare pancreatic tumors, clinical, morphological, and molecular aspects of acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary neoplasm, and serous cystic neoplasms are presented and discussed.
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Affiliation(s)
- M Hämmerle
- Institut für Pathologie, Universitätsklinikum Halle, Halle, Deutschland
| | - F Bergmann
- MVZ für Klinische Pathologie, Klinikum Darmstadt, Grafenstraße 9, 64283, Darmstadt, Deutschland. .,Institut für Pathologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland.
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34
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Liu Y, Raimondo M, Wallace MB, Mody K, Stauffer JA, Zhang L, Ji B, Bi Y. Exome Sequencing of Pancreatic Acinar Carcinoma Identified Distinctive Mutation Patterns. Pancreas 2021; 50:1007-1013. [PMID: 34629449 PMCID: PMC8516064 DOI: 10.1097/mpa.0000000000001870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism. METHODS Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package. RESULTS A median of 34 somatic mutations were detected (range, 19-60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon. CONCLUSIONS Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.
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Affiliation(s)
- Yuanhang Liu
- From the Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | | | | | - Kabir Mody
- Division of Hematology and Medical Oncology
| | | | - Lizhi Zhang
- Department of Pathology, Mayo Clinic, Rochester, MN
| | - Baoan Ji
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL
| | - Yan Bi
- Division of Gastroenterology and Hepatology
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35
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Omiyale AO. Adult pancreatoblastoma: Current concepts in pathology. World J Gastroenterol 2021; 27:4172-4181. [PMID: 34326617 PMCID: PMC8311526 DOI: 10.3748/wjg.v27.i26.4172] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/23/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Adult pancreatoblastoma is an exceptionally rare malignant tumour of the pancreas that mimics other solid cellular neoplasms of the pancreas, which may pose diagnostic difficulties. Because of its rarity, little is known about its clinical and pathologic features. This article reviews the clinical and pathologic features of pancreatoblastoma in adults including differential diagnosis, treatment, and follow-up. Although pancreatoblastoma commonly occurs in childhood, there have now been more than 70 adult pancreatoblastomas described in the literature. There is a slight male predominance. There are no symptoms unique to pancreatoblastomas and adult patients are frequently symptomatic. The most common presenting symptom is abdominal pain. Grossly, the tumours are often large and well-circumscribed. Microscopically, pancreatoblastomas are composed of neoplastic cells with predominantly acinar differentiation and characteristic squamoid nests. These tumours are positive for trypsin, chymotrypsin, lipase, and BCL10. Loss of heterozygosity on chromosome 11p is the most common molecular alteration in pancreatoblastomas. Adult pancreatoblastomas are aggressive tumours with frequent local invasion, recurrence, and distant metastasis. Treatment consists of surgical resection. Chemotherapy and radiotherapy may have a role in the treatment of recurrent, residual, unresectable, and metastatic disease. It is important to distinguish pancreatoblastomas from morphological mimics such as acinar cell carcinomas, solid pseudopapillary neoplasms, and pancreatic neuroendocrine neoplasms.
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Affiliation(s)
- Ayo O Omiyale
- Department of Cellular Pathology, Imperial College Healthcare NHS Trust, London W6 8RF, United Kingdom
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36
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Menz A, Bauer R, Kluth M, Marie von Bargen C, Gorbokon N, Viehweger F, Lennartz M, Völkl C, Fraune C, Uhlig R, Hube-Magg C, De Wispelaere N, Minner S, Sauter G, Kind S, Simon R, Burandt E, Clauditz T, Lebok P, Jacobsen F, Steurer S, Wilczak W, Krech T, Marx AH, Bernreuther C. Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors. Hum Pathol 2021; 115:19-36. [PMID: 34102222 DOI: 10.1016/j.humpath.2021.05.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 05/27/2021] [Indexed: 12/13/2022]
Abstract
To evaluate cytokeratin 19 (CK19) expression in normal and cancerous tissues, 15,977 samples from 122 tumor types and 608 samples of 76 normal tissue types were analyzed by immunohistochemistry (IHC). In normal tissues, CK19 expression occurred in epithelial cells of most glandular organs but was strictly limited to the basal cell layer of nonkeratinizing squamous epithelium and absent in the skin. CK19 expression in ≥90% of cases was seen in 34% of the tumor entities including the adenocarcinomas of the pancreas (99.4%), colorectum (99.8%), esophagus (98.7%), and stomach (97.7%), as well as breast cancer (90.0%-100%), high-grade serous (99.1%) or endometrioid (97.8%) ovarian cancer, and urothelial carcinoma (92.6%-100%). A low CK19 positivity rate (0.1-10%) was seen in 5 of 122 tumor entities including hepatocellular carcinoma and seminoma. A comparison of tumor versus normal tissue findings demonstrated that upregulation and downregulation of CK19 can occur in cancer and that both alterations can be linked to unfavorable phenotypes. CK19 downregulation was linked to high grade (p = 0.0017) and loss of estrogen receptor- and progesterone receptor-expression (p < 0.0001 each) in invasive breast carcinoma of no special type. CK19 upregulation was linked to nodal metastases in neuroendocrine tumors and papillary thyroid carcinomas (p < 0.05 each) and to poor grade in clear cell renal cell carcinoma (p < 0.05). CK19 upregulation was particularly common in squamous cell carcinomas. We concluded that CK19 IHC might separate primary liver cell carcinoma from liver metastases, seminoma from other testicular tumors, and helps in the detection of early neoplastic transformation in squamous epithelium.
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Affiliation(s)
- Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Rifka Bauer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Clara Marie von Bargen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Natalia Gorbokon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Florian Viehweger
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Cosima Völkl
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Noémi De Wispelaere
- Department and Clinic of Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Simon Kind
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Till Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Till Krech
- Institute of Pathology, Clinical Center Osnabrueck, 49076 Osnabrueck, Germany
| | - Andreas H Marx
- Department of Pathology, Academic Hospital Fuerth, 90766 Fuerth Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Kanber Y, Pusztaszeri M, Auger M. Immunocytochemistry for diagnostic cytopathology-A practical guide. Cytopathology 2021; 32:562-587. [PMID: 34033162 DOI: 10.1111/cyt.12993] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/18/2021] [Accepted: 04/19/2021] [Indexed: 11/29/2022]
Abstract
Cytological specimens, which are obtained by minimally invasive methods, are an excellent source of diagnostic material. Sometimes they are the only material available for diagnosis as well as for prognostic/predictive markers. When cytomorphology is not straightforward, ancillary tests may be required for a definitive diagnosis to guide clinical management. Immunocytochemistry (ICC) is the most common and practical ancillary tool used to reach a diagnosis when cytomorphology is equivocal, to differentiate entities with overlapping morphological features, and to determine the cell lineage and the site of origin of a metastatic neoplasm. Numerous immunomarkers are available, and some are expressed in multiple neoplasms. To rule out entities within a differential diagnosis, the use of more than one marker, sometimes panels, is necessary. ICC panels for diagnostic purposes should be customised based on the clinical context and cytomorphology, and the markers should be used judiciously to preserve material for additional tests for targeted therapies in the appropriate setting. This review offers a practical guide for the use of ICC for diagnostic cytopathology, covering the most commonly encountered non-hematolymphoid diagnostic scenarios in various body sites.
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Affiliation(s)
- Yonca Kanber
- Department of Pathology, McGill University Health Center, McGill University, Montreal, QC, Canada
| | - Marc Pusztaszeri
- Department of Pathology, Jewish General Hospital, McGill University, Montréal, QC, Canada
| | - Manon Auger
- Department of Pathology, McGill University Health Center, McGill University, Montreal, QC, Canada
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Thompson ED, Wood LD. Pancreatic Neoplasms With Acinar Differentiation: A Review of Pathologic and Molecular Features. Arch Pathol Lab Med 2021; 144:808-815. [PMID: 31869246 DOI: 10.5858/arpa.2019-0472-ra] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2019] [Indexed: 12/11/2022]
Abstract
CONTEXT.— Pancreatic acinar lesions encompass a broad spectrum of malignant tumors and benign reactive processes affecting both adults and children, with clinical, pathologic, and molecular features that are distinct from more common ductal neoplasms. Accurate morphologic diagnosis and molecular assessment of these uncommon neoplasms is critical for effective patient care. OBJECTIVE.— To review the clinical, pathologic, and molecular features of pancreatic neoplasms with acinar differentiation, the most common of which is acinar cell carcinoma but which also includes mixed carcinomas with acinar components, cystic acinar lesions, and pancreatoblastoma. DATA SOURCES.— We assessed the current primary literature, as well as recently updated diagnostic manuals. CONCLUSIONS.— Pancreatic acinar neoplasms are a morphologically and molecularly heterogeneous group of diseases that are characterized by acinar differentiation of at least a subset of the neoplastic cells, defined either morphologically (granular cytoplasm, single prominent nucleoli) or immunohistochemically. Squamoid nests are a key morphologic feature of pancreatoblastoma. Alterations in WNT signaling and chromosomal 11p loss are common molecular features of both acinar cell carcinoma and pancreatoblastoma. Targetable molecular alterations in acinar carcinoma include BRAF rearrangements and DNA repair defects, including mismatch repair deficiency and BRCA pathway defects. For practicing pathologists, morphologic recognition of such acinar neoplasms is critical, and in the future, molecular diagnostics to identify lesions susceptible to targeted therapy will likely form an important component of patient care.
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Affiliation(s)
- Elizabeth D Thompson
- From the Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Laura D Wood
- From the Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Sridharan V, Mino-Kenudson M, Cleary JM, Rahma OE, Perez K, Clark JW, Clancy TE, Rubinson DA, Goyal L, Bazerbachi F, Visrodia KH, Qadan M, Parikh A, Ferrone CR, Casey BW, Fernandez-Del Castillo C, Ryan DP, Lillemoe KD, Warshaw AL, Krishnan K, Hernandez-Barco YG. Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes. Pancreatology 2021; 21:S1424-3903(21)00162-9. [PMID: 34023183 DOI: 10.1016/j.pan.2021.05.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/03/2021] [Accepted: 05/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. METHODS This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. RESULTS Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). CONCLUSION Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.
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Affiliation(s)
- Vishwajith Sridharan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Mari Mino-Kenudson
- Division of Pathology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - James M Cleary
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Osama E Rahma
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Kimberly Perez
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Jeffrey W Clark
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Thomas E Clancy
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Douglas A Rubinson
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Lipika Goyal
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Kavel H Visrodia
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Motaz Qadan
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Aparna Parikh
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Cristina R Ferrone
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Brenna W Casey
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | | | - David Patrick Ryan
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Keith D Lillemoe
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Andrew L Warshaw
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Kumar Krishnan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Yasmin G Hernandez-Barco
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA.
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Shaib WL, Zakka K, Huang W, Chen Z, Alese OB, Wu C, Akce M, El-Rayes BF. Survival Outcomes of Acinar Cell Pancreatic Cancer: A National Cancer Database Analysis. Pancreas 2021; 50:529-536. [PMID: 33939665 DOI: 10.1097/mpa.0000000000001788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Acinar cell pancreatic carcinomas (ACPCs) are rare neoplasms accounting for 1% to 2% of pancreatic tumors in adults. The objective of this study is to evaluate the benefit of chemotherapy in the adjuvant setting in resected ACPC and in the palliative setting for metastatic ACPC. METHODS Data were obtained from all US hospitals that contributed to the National Cancer Database between 2004 and 2014. Cases were identified using the histology code 8550. RESULTS A total of 593 patients with ACPC were identified. The mean age was 64.4 years (range, 18-90 years), with a male preponderance (72.8%, n = 432). Localized stage disease comprised 52.3% (n = 310) of patients. Among localized ACPC patients, 88.0% (n = 191) underwent surgery and 50.6% (n = 91) received adjuvant chemotherapy. The 5-year overall survival in those who received adjuvant treatment was slightly higher than those who did not receive adjuvant treatment (46.7% vs 44.8%, P = 0.3271). Among advanced-stage ACPC patients, 67.6% received chemotherapy, which translated into improved 5-year overall survival compared with no chemotherapy (8.1% vs 0%, P < 0.0001). CONCLUSIONS Chemotherapy in the palliative setting for advanced-stage ACPC patients was associated with improved survival. Adjuvant therapy did not translate into significant survival benefit.
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Affiliation(s)
- Walid L Shaib
- From the Department of Hematology and Oncology, Winship Cancer Institute
| | - Katerina Zakka
- From the Department of Hematology and Oncology, Winship Cancer Institute
| | - Weixing Huang
- Winship Research Informatics, Biostatistics, Emory University, Atlanta, GA
| | - Zhengjia Chen
- Winship Research Informatics, Biostatistics, Emory University, Atlanta, GA
| | - Olatunji B Alese
- From the Department of Hematology and Oncology, Winship Cancer Institute
| | - Christina Wu
- From the Department of Hematology and Oncology, Winship Cancer Institute
| | - Mehmet Akce
- From the Department of Hematology and Oncology, Winship Cancer Institute
| | - Bassel F El-Rayes
- From the Department of Hematology and Oncology, Winship Cancer Institute
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Ooe Y, Watanabe K, Hashimoto I, Takenaka S, Ojima T, Yamamoto S, Fujii H. Title: pancreatic-type mixed acinar neuroendocrine carcinoma of the stomach: a case report and review of the literature. Diagn Pathol 2021; 16:11. [PMID: 33531019 PMCID: PMC7852210 DOI: 10.1186/s13000-021-01070-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 01/21/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The majority of gastrointestinal tumors are adenocarcinomas. Rarely, there are other types of tumors, such as acinar cell carcinoma, and these are often called pancreatic-type acinar cell carcinomas. Among these tumors, some are differentiated into neuroendocrine components. A few of them are MiNENs. CASE PRESENTATION The patient was an 80-year-old male who was referred to our hospital for treatment of a pedunculated gastric tumor. It was 5 cm in diameter and detected in the upper gastric body with upper GI endoscopy conducted to investigate anemia. In the biopsy, although hyperplasia of gastric gland cells was noted, no tumor cells were found. Retrospectively, the diagnosis was misdiagnosed. An operation was arranged because bleeding from the tumor was suspected as a cause of anemia and because surgical resection was considered to be desirable for accurate diagnosis. Hence, laparoscopic and endoscopic cooperative surgery was performed. In the pathological examination, several types of epithelial cells that proliferated in the area between the mucosa and deep inside the submucosa were observed. These consisted of acinar-glandular/trabecular patterns and solid. A diagnosis of pancreatic-type acinar cell carcinoma of the stomach with NET G2 and G3 was made based on characteristic cellular findings and the results of immunostaining tests. Each of them consisted of more than 30% of the lesion; a diagnosis of pancreatic-type mixed acinar neuroendocrine carcinoma (pancreatic-type MiNEN) of the stomach or a type of gastric MiNEN was obtained. Anemia was resolved after the operation, and the patient was discharged from the hospital without perioperative complications. CONCLUSIONS Pancreatic-type ACC of the stomach that is differentiated into neuroendocrine tumors is very rare. Hence, we report this case along with a literature review.
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Affiliation(s)
- Yuka Ooe
- Department of Surgery, Toyama Nishi General Hospital, 1019 Shimokutsuwada, Fuchumachi, Toyama, Toyama, 939-2716, Japan.
| | - Kishichiro Watanabe
- Watanabe's Consultancy for Pathological Diagnosis, 1007 Surpass Sakurada-cho Ichibankan 3-30-1 Sakurada-cho, Kanazawa, Ishikawa, 920-0057, Japan
| | - Isaya Hashimoto
- Department of Surgery, Toyama Nishi General Hospital, 1019 Shimokutsuwada, Fuchumachi, Toyama, Toyama, 939-2716, Japan
| | - Satoshi Takenaka
- Department of Surgery, Suzu General Hospital, 1-1 Nonoemachi, Suzu, Ishikawa, 927-1213, Japan
| | - Toshihiko Ojima
- Department of Surgery, Toyama Nishi General Hospital, 1019 Shimokutsuwada, Fuchumachi, Toyama, Toyama, 939-2716, Japan
| | - Seiichi Yamamoto
- Department of Surgery, Toyama Nishi General Hospital, 1019 Shimokutsuwada, Fuchumachi, Toyama, Toyama, 939-2716, Japan
| | - Hisatake Fujii
- Department of Surgery, Toyama Nishi General Hospital, 1019 Shimokutsuwada, Fuchumachi, Toyama, Toyama, 939-2716, Japan
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Presentation and outcome of mixed neuroendocrine non-neuroendocrine neoplasms of the pancreas. Pancreatology 2021; 21:224-235. [PMID: 33309225 DOI: 10.1016/j.pan.2020.11.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 11/25/2020] [Accepted: 11/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) of the pancreas and periampullary region are extremely rare and heterogeneous malignancies. Literature is sparse, clinical management is not standardized and little is known about survival outcomes. The aim of this study was to identify pathological and radiological features of MiNEN and assess the outcome of surgical management. METHODS Patients undergoing surgery for pancreatic and periampullary MiNEN between 2001 and 2019 were retrospectively analysed based on a prospective database. Histological, radiological and clinical features were assessed. Survival was analysed in a nested case-control study and matched-pair analyses with pure neuroendocrine neoplasms (pNEN) and ductal adeno- or acinar cell carcinomas of the pancreas. A literature review with focus on survival after surgical resection was additionally performed. RESULTS Of 13 patients with MiNEN, 5 had acinar-MiNEN and 8 adeno-MiNEN. Two of 5 (40%) acinar-MiNEN and one adeno-MiNEN patients had liver metastases. All but one adeno-MiNEN (88%) showed preoperative radiological features of pancreatic adenocarcinoma, 3 of 5 (60%) acinar-MiNEN exhibited mainly neuroendocrine features. No surgical mortality was observed. The 5-year overall survival rate in all MiNEN was 40%. Five-year survival rate was 58% in adeno-MiNEN and comparable to that of matched ductal adenocarcinomas (36%) and pNEN (48%). Five-year overall survival rate was 20% in acinar-MiNEN, compared to 39% in acinar carcinoma patients and 59% in matched pNEN patients. CONCLUSIONS MiNEN are rare and difficult to distinguish from pure adenocarcinoma or neuroendocrine neoplasm preoperatively. Surgical resection would therefore be the treatment of choice in localized tumors.
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Yassin-Kassab A, Gainor D, Sufyan AS. Atypical Presentation of Mammary Analogue Secretory Carcinoma of the Lip. EAR, NOSE & THROAT JOURNAL 2020; 101:NP212-NP217. [PMID: 32951456 DOI: 10.1177/0145561320957756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Mammary analogue secretory carcinoma (MASC) of the salivary gland is a rare tumor that was first described by Skalova et al in 2010, and since then, only a few hundred cases have been reported in the literature. Prior to Skalova's report, MASC was histologically misclassified as acinic cell carcinoma (ACC), pleomorphic adenoma, mucoepidermoid carcinoma, or adenocarcinoma, not otherwise specified. Mammary analogue secretory carcinoma has a low incidence rate overall, accounting for less than 0.3% of all salivary gland tumors. Histopathologic and cytogenic analysis of MASC is identical to secretory carcinoma of the breast, leading to the proposed name by Skalova. The purpose of this case presentation is to describe an atypical presentation of MASC, to compare this case with the classic description of MASC, and to contrast the various features of MASC to ACC in order to improve the accuracy of future diagnoses and help guide treatment.
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Uccella S, La Rosa S. Looking into digestive mixed neuroendocrine - nonneuroendocrine neoplasms: subtypes, prognosis, and predictive factors. Histopathology 2020; 77:700-717. [PMID: 32538468 DOI: 10.1111/his.14178] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Mixed neuroendocrine - nonneuroendocrine neoplasms (MiNENs) of the digestive system represent a challenge for both pathologists and clinicians. Their nomenclature has changed several times, and their diagnostic criteria, classification and clinical behaviour have been matter of debate over the years. Although several attempts have been made to elucidate the pathogenesis and biology of MiNENs, some issues remain open. This review will provide: a historical background that helps in understanding the evolution of the concept and nomenclature of mixed neoplasms; a revision of the knowledge on this topic, including molecular aspects, to give the reader a comprehensive and practical overview on this challenging field of pathology; a focus on the diagnostic criteria and on the determination of prognostic and predictive factors; and a description of the different tumour types in the different sites of origin.
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Affiliation(s)
- Silvia Uccella
- Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Stefano La Rosa
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
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Kimura T, Tabata S, Togawa T, Onchi H, Iida A, Sato Y, Goi T. Pancreatic acinar cell carcinoma with a ductal adenocarcinoma component: a case report and analysis of the histogenesis of the tumor. World J Surg Oncol 2020; 18:238. [PMID: 32891173 PMCID: PMC7487580 DOI: 10.1186/s12957-020-02014-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 08/25/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Pancreatic cancer composed of acinar cell carcinoma (ACC) and ductal adenocarcinoma (DAC) is rare, and the clinicopathological characteristics of ACC with DAC have yet to be elucidated. Herein, we report a case of ACC with a DAC component of the pancreas and examined the histogenesis of this tumor. CASE PRESENTATION A 69-year-old man was admitted to our hospital complaining of appetite loss, constipation, epigastric dull pain, and jaundice. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a pancreatic head tumor with dilatation of the bile duct and the distal main pancreatic duct. Under the diagnosis of pancreatic head cancer, a pancreatoduodenectomy was performed. The histology of the resected tumor consisted of mainly ACC with a focus of DAC, which was confirmed by mucin staining and immunohistochemistry for antigens such as BCL10, trypsin, Smad4, p16, p53, and MUC1. There was histological transition between the components of ACC and DAC, and immunostaining of the transitional zone showed equivocal results for the antigens. KRAS was wild-type in both ACC and DAC. The patient was treated with adjuvant chemotherapy with S-1 for 1 year. No evidence of recurrence or metastasis was observed after 9 years of follow-up. CONCLUSIONS A rare case of pancreatic ACC with a DAC component in a patient with long-term survival after surgery was reported. Immunohistochemical and molecular analysis indicated that DAC might have arisen from ACC through transdifferentiation in this case.
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Affiliation(s)
- Toshihisa Kimura
- Department of Surgery, National Hospital Organization Tsuruga Medical Center, 33-1 Sakuragaoka-cho, Tsuruga, 914-0195, Japan.
| | - Shinsuke Tabata
- Department of Surgery, Jouhoku Hospital, 20-3 Kyomachi, Kanazawa, 920-8616, Japan
| | - Tamotsu Togawa
- Department of Surgery, National Hospital Organization Tsuruga Medical Center, 33-1 Sakuragaoka-cho, Tsuruga, 914-0195, Japan
| | - Hidetoshi Onchi
- Department of Surgery, Fukui General Hospital, 58-16-1, Egamimachi, Fukui, 910-8561, Japan
| | - Atsushi Iida
- Department of Surgery, National Hospital Organization Tsuruga Medical Center, 33-1 Sakuragaoka-cho, Tsuruga, 914-0195, Japan
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1, Takara-machi, Kanazawa, 920-8640, Japan
| | - Takanori Goi
- First Department of Surgery, Faculty of Medicine, University of Fukui, 23-3, Matsuoka, Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
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Luchini C, Grillo F, Fassan M, Vanoli A, Capelli P, Paolino G, Ingravallo G, Renzulli G, Doglioni C, D’Amuri A, Mattiolo P, Pecori S, Parente P, Florena AM, Zamboni G, Scarpa A. Malignant epithelial/exocrine tumors of the pancreas. Pathologica 2020; 112:210-226. [PMID: 33179623 PMCID: PMC7931574 DOI: 10.32074/1591-951x-167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 07/07/2020] [Indexed: 02/07/2023] Open
Abstract
Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumscribed neoplasms, include acinar cell carcinoma (pure and mixed), pancreatoblastoma, and solid pseudopapillary neoplasms. The most important macroscopic, histologic, immunohistochemical and molecular hallmarks of all these tumors, highlighting their key diagnostic/pathological features are presented. Lastly, standardized indications regarding gross sampling and how to compile a formal pathology report for pancreatic malignant exocrine tumors will be provided.
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Affiliation(s)
- Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Federica Grillo
- Anatomic Pathology, San Martino IRCCS Hospital, Genova, Italy
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, and IRCCS San Matteo Hospital, Italy
| | - Paola Capelli
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Gaetano Paolino
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Giuseppe Ingravallo
- Department of Emergency and Organ Transplantation, Section of Pathological Anatomy, University of Bari Aldo Moro, Bari, Italy
| | - Giuseppina Renzulli
- Department of Emergency and Organ Transplantation, Section of Pathological Anatomy, University of Bari Aldo Moro, Bari, Italy
| | - Claudio Doglioni
- Vita e Salute University, Milan, Italy
- Pathology Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Sara Pecori
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Ada M. Florena
- Department of Sciences for Promotion of Health and Mother and Child Care, Anatomic Pathology, University of Palermo, Italy
| | - Giuseppe Zamboni
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
- IRCSS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
- ARC-NET Research Centre, University of Verona, Verona, Italy
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Said S, Kurtin PJ, Nasr SH, Graham RP, Dasari S, Vrana JA, Yasir S, Torbenson MS, Zhang L, Mounajjed T, Eric Chen ZM, Lee HE, Wu TT. Carboxypeptidase A1 and regenerating islet-derived 1α as new markers for pancreatic acinar cell carcinoma. Hum Pathol 2020; 103:120-126. [PMID: 32702400 DOI: 10.1016/j.humpath.2020.07.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 02/08/2023]
Abstract
Acinar cell carcinoma (ACC) is a rare tumor that differentiates toward pancreatic acinar cells and shows evidence of pancreatic enzyme production. Mixed acinar-neuroendocrine carcinoma (MANC) is defined as having more than 30% of both acinar and neuroendocrine cell types as per immunohistochemistry analysis. Trypsin is currently the most commonly used stain for acinar differentiation. In this study, we investigate the utility of two novel markers, carboxypeptidase A1 (CPA1) and regenerating islet-derived 1α (REG1a), in diagnosing ACC/MANC. Immunohistochemical staining for CPA1 and REG1a was performed on 14 cases of ACC and 5 cases of MANC as well as on 80 other pancreatic tumors including 20 cases each of ductal adenocarcinoma, well-differentiated neuroendocrine tumor, mucinous cystic neoplasm, and solid pseudopapillary tumor. All ACCs and MANCs were positive for CPA1 (all diffuse) and REG1a (12 diffuse, 4 patchy, and 3 focal). A diffuse or patchy staining pattern was significantly more common in ACC/MANC cases (100% diffuse/patchy for CPA1 and 84% for REG1a) than in other pancreatic tumors (5% diffuse/patchy for CPA1 and 7.5% for REG1a), with a P-value of <0.0001 for both CPA1 and REG1a. The sensitivity and specificity of diffuse/patchy staining for CPA1 and REG1a in diagnosing pancreatic ACC/MANC were 100% and 95% for CPA1 and 84% and 93% for REG1a, respectively. In conclusion, CPA1 and REG1a are sensitive markers for ACC that can be used as additional acinar cell differentiation markers to help in the diagnosis of pancreatic ACC and MANC. A negative result for CPA1 virtually excludes ACC/MANC.
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Affiliation(s)
- Samar Said
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States.
| | - Paul J Kurtin
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Samih H Nasr
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Surendra Dasari
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, United States
| | - Julie A Vrana
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Saba Yasir
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Michael S Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Lizhi Zhang
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Taofic Mounajjed
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Zong-Ming Eric Chen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Hee Eun Lee
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
| | - Tsung-Teh Wu
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, United States
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Abstract
Neuroendocrine neoplasms (NENs) of the gastrointestinal (GI) tract and pancreas are a rare and heterogeneous group of neoplasms characterized by common cellular features as well as unique site-specific traits. GI and pancreatic NENs are much rarer than the more common adenocarcinomas arising at these sites. However, the incidences of GI and pancreatic NENs have increased significantly, particularly in the stomach and common site, followed by rectum, appendix, colon, and stomach. Pancreatic NENs are also uncommon, with fewer than 1 per 100,000, accounting for 1% to 2% of all pancreatic neoplasms.
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BAP1 is a haploinsufficient tumor suppressor linking chronic pancreatitis to pancreatic cancer in mice. Nat Commun 2020; 11:3018. [PMID: 32541668 PMCID: PMC7295806 DOI: 10.1038/s41467-020-16589-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 05/07/2020] [Indexed: 02/08/2023] Open
Abstract
Chronic pancreatitis represents a risk factor for the development of pancreatic cancer. We find that heterozygous loss of histone H2A lysine 119 deubiquitinase BAP1 (BRCA1 Associated Protein-1) associates with a history of chronic pancreatitis and occurs in 25% of pancreatic ductal adenocarcinomas and 40% of acinar cell carcinomas. Deletion or heterozygous loss of Bap1 in murine pancreata causes genomic instability, tissue damage, and pancreatitis with full penetrance. Concomitant expression of KrasG12D leads to predominantly intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, while pancreatic intraepithelial neoplasias are rarely detected. These lesions progress to metastatic pancreatic cancer with high frequency. Lesions with histological features mimicking Acinar Cell Carcinomas are also observed in some tumors. Heterozygous mice also develop pancreatic cancer suggesting a haploinsufficient tumor suppressor role for BAP1. Mechanistically, BAP1 regulates genomic stability, in a catalytic independent manner, and its loss confers sensitivity to irradiation and platinum-based chemotherapy in pancreatic cancer.
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Taskin OC, Clarke CN, Erkan M, Tsai S, Evans DB, Adsay V. Pancreatic neuroendocrine neoplasms: current state and ongoing controversies on terminology, classification and prognostication. J Gastrointest Oncol 2020; 11:548-558. [PMID: 32655934 DOI: 10.21037/jgo.2020.03.07] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Significant improvements have taken place in our understanding of classification neuroendocrine neoplasms of the pancreas in the past decade. These are now regarded in three entirely separate categories: (I) neuroendocrine tumors (PanNETs) are by definition well differentiated, the pancreatic counterpart of carcinoids; (II) neuroendocrine carcinomas, which are poorly differentiated (PDNEC), the pancreatic examples of small cell carcinomas or large cell neuroendocrine carcinomas; (III) other neoplasms that have neuroendocrine differentiation or a distinct neuroendocrine component. PanNETs are by far the most common. They are now regarded as malignancies (albeit often curable when low grade and low stage) with the exception of minute incidental proliferations (tumorlets, or dysplastic-like changes) seen in the setting of some syndromes like MEN. PanNETs are staged based on their size, and for small T1 tumors, watchful waiting is now being considered, although these tumors are also known to show about 10% metastatic rate and/or progression, creating concerns about this approach. PanNETs are graded into 3, based on the proliferative activity, mostly based on the Ki-67 index, and also partly mitotic activity, although the latter seldom if ever is the determinant of the final grade. Neuroendocrine neoplasms with well differentiated morphology but Ki-67 >20% are now regarded as PanNET Grade 3 (G3); they have been shown to have a prognosis significantly worse than lesser grade PanNETs but still incomparably better than frank PDNECs, the latter typically has Ki-67 >50% (often much higher) and require platinum-based chemotherapy. There are also cases that are ambiguous between PanNET-G3 and PDNEC, and very rarely transformation of the former to the latter appears to occur. For low grade (G1/G2) PanNETs, more refined criteria to further prognosticate this group are needed. Morphologic variants being recognized may bring new perspectives to this group.
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Affiliation(s)
- Orhun Cig Taskin
- Department of Pathology, Koç University Hospital, Istanbul, Turkey
| | - Callisia N Clarke
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mert Erkan
- Department of Surgery, Koç University Hospital, Istanbul, Turkey.,Koç University, Research Center for Translational Medicine, Istanbul, Turkey
| | - Susan Tsai
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Douglas B Evans
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital, Istanbul, Turkey
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