|
1
|
Xu Z, Theisen BK, Chang Q, Schultz D, Ahsan BU. Survival outcomes of poorly differentiated colorectal carcinoma variants: Insights from a single teaching institute. Hum Pathol 2024; 154:105710. [PMID: 39716575 DOI: 10.1016/j.humpath.2024.105710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 11/16/2024] [Accepted: 12/18/2024] [Indexed: 12/25/2024]
Abstract
The morphologic diagnosis of colorectal carcinoma (CRC) is typically straight forward. However, there are certain subtypes of CRC that pose diagnostic challenges for daily practice due to sometimes overlapping morphologic and immunohistochemical features. These subtypes include poorly differentiated adenocarcinoma NOS, in the absence of conventional morphology (PDA-NOS), large cell neuroendocrine carcinoma (LCNEC), medullary carcinoma (MC), undifferentiated carcinoma (UC) and lymphoepithelioma-like carcinoma (LELC). This study aims to see if there is a survival difference between poorly differentiated variants of CRC, as well as other clinicopathological features that may affect prognosis. Additionally, we analyzed interobserver agreement among gastrointestinal pathologists (GP) at our institution in subclassifying poorly differentiated CRC. All consecutive patients with the diagnoses of PDA-NOS, MC, LCNEC, UC and LELC between July 2018 and July 2023 were included. Cox proportional regression test was used for multivariate analysis, while log-rank and Kaplan-Meier tests were used for univariate and survival analyses. Out of the same cohort of patients, 58 samples identified and reviewed by 3 GI-subspecialty-trained pathologists who were asked to assign the cases as PDA-NOS, LCNEC, MC, UC and LELC. Interobserver agreement was analyzed using Fleiss Kappa. Of the total 77 patients, 63 were PDA-NOS, 3 were LCNEC, 6 were MC, 4 were UC and 1 was LELC patients. Multivariate analysis using Cox proportional regression showed that tumor size (p = 0.001, HR = 1.22, 95% CI 1.08-1.38), patient age (p = 0.001, HR 1.73, 95% CI 1.24-2.40), and M stage (p = 0.02, HR 2.22, 95% CI 1.14-4.32) were significantly associated with worse OS. For the 58 cases analyzed, 3 GP agreed on 42 (72%) cases. The most common diagnosis was PDA-NOS and for 33 (57%) agreement was unanimous. There was moderate agreement (k 0.41-0.60) between all 3 GP. Our study evaluated the challenges associated with histological evaluation of colon cancers with poorly differentiated morphologies. Among the diagnoses considered in the study, MC and LCNEC had different prognostic implications compared to PDA-NOS and UC. Additionally, our GP showed moderate interobserver agreement, indicating that some level of variability in diagnosing poorly differentiated CRC subtypes may be inevitable.
Collapse
Affiliation(s)
| | - Brian K Theisen
- Henry Ford Health, Detroit, MI, USA; Michigan State University College of Human Medicine, East Lansing, MI, USA
| | | | | | - Beena U Ahsan
- Henry Ford Health, Detroit, MI, USA; Michigan State University College of Human Medicine, East Lansing, MI, USA.
| |
Collapse
|
|
2
|
Rong Y, Kato I, Okubo N, Tsuyuki S, Katsuta E, Kobayashi N, Nakagawa K, Ozawa M, Watanabe J, Ishibe A, Yamanaka S, Fujii S, Endo I, Ichikawa Y. Potential neuroendocrine differentiation in poorly differentiated colorectal adenocarcinoma: A hidden trait? Mol Clin Oncol 2024; 21:91. [PMID: 39421232 PMCID: PMC11484215 DOI: 10.3892/mco.2024.2789] [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: 08/01/2024] [Accepted: 09/09/2024] [Indexed: 10/19/2024] Open
Abstract
Neuroendocrine carcinoma (NEC) of the colon and rectum is a rare malignancy with a poor prognosis that is characterized by distinct clinical and histopathological features that differ significantly from those of more prevalent adenocarcinomas. Poorly differentiated colorectal adenocarcinoma (PDC) is also rare and carries a poor prognosis. Considering the morphological similarities between these two rare, poorly differentiated cancers of the colon and rectum, it is plausible that certain cases of colorectal cancer (CRC) diagnosed as PDC may contain NEC as well. In the present study, cases of CRC that were diagnosed as PDC at our institution were investigated, searching for patients who exhibited NEC characteristics based on the expression of neuroendocrine markers (NEMs), including chromogranin A, synaptophysin and insulinoma-associated 1 (INSM1), and the loss of retinoblastoma 1 (Rb). Of 816 total CRC cases, 74 cases (9.1%) were identified as PDC. These were further divided into 13 (17.5%) cases that were positive for NEMs and others. Of these 13 cases, the expression rates for chromogranin A and synaptophysin were 69.2% each, while that of INSM1 was 100%. Upon re-examination of the 13 PDC cases, two cases were morphologically identified as NEC, including one large- and one small-cell NEC. A total of two cases showed loss of Rb in their PDC lesions. NEM positivity was considered an independent prognostic factor in the 74 PDC cases. Among these cases, some may exhibit characteristics of NEC. Unraveling the molecular mechanisms using CRC that harbors both PDC and NEC will be a task for future research.
Collapse
Affiliation(s)
- Yuhan Rong
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Ikuma Kato
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Naoki Okubo
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Sho Tsuyuki
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Eriko Katsuta
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Noritoshi Kobayashi
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Kazuya Nakagawa
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Mayumi Ozawa
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Jun Watanabe
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Atsushi Ishibe
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Shoji Yamanaka
- Department of Pathology, Yokohama City University Hospital, Yokohama, Kanagawa 236-0004, Japan
| | - Satoshi Fujii
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| | - Yasushi Ichikawa
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
| |
Collapse
|
|
3
|
Saegusa Y, Akabane S, Shimomura M, Okuda H, Yano T, Mochizuki T, Inoue W, Yamaguchi M, Yamaguchi S, Sentani K, Yamauchi M, Tokumo K, Ohdan H. Successful outcome achieved with adjuvant chemotherapy with irinotecan plus cisplatin in rectal neuroendocrine carcinoma: a case report. Surg Case Rep 2024; 10:220. [PMID: 39294428 PMCID: PMC11411022 DOI: 10.1186/s40792-024-02010-9] [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: 07/24/2024] [Accepted: 08/26/2024] [Indexed: 09/20/2024] Open
Abstract
BACKGROUND Rectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin. CASE PRESENTATION A 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence. CONCLUSION This case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.
Collapse
Affiliation(s)
- Yoshitaka Saegusa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shintaro Akabane
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
| | - Manabu Shimomura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Okuda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tetsuya Mochizuki
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Wako Inoue
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Mizuki Yamaguchi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinji Yamaguchi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Kentaro Tokumo
- Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
4
|
Emile SH, Horesh N, Garoufalia Z, Gefen R, Wignakumar A, Wexner SD. Predictors of lymph node metastasis and survival in radically resected rectal neuroendocrine tumors: A Surveillance, Epidemiology, and End Results (SEER) database analysis. Surgery 2024; 176:668-675. [PMID: 38918107 DOI: 10.1016/j.surg.2024.05.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/16/2024] [Accepted: 05/19/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND Rectal neuroendocrine tumors are uncommon tumor types. Lymph node metastases may occur in up to 40%, potentially impacting decision-making. We aimed to assess risk factors for lymph node metastases of rectal neuroendocrine tumors and their association with overall and cancer-specific survival. METHODS This retrospective case-control study involved patients with stage I to III rectal neuroendocrine tumors who underwent radical resection. Data were derived from the Surveillance, Epidemiology, and End Results database (2000-2020). Patients with pathologic evidence of lymph node metastases were compared to those without lymph node metastases for baseline patient and tumor characteristics. The main outcomes were lymph node metastases, overall survival, and cancer-specific survival. RESULTS In total, 580 patients (50.9% male; mean age: 58.9 years) were included. The lymph node metastases rate was 37.1%. Independent predictors of lymph node metastases were Grade 2 neuroendocrine tumors (odds ratio: 8.06; P = .001), neuroendocrine carcinoma (odds ratio: 2.59, P = .006), large-cell neuroendocrine carcinoma (odds ratio: 4.89; P = .017), T2 tumors (odds ratio: 6.44; P < .001), T3 tumors (odds ratio: 27.5; P < .001), and T4 tumors (odds ratio: 17.3; P < .001). Lymph node metastases were associated with shorter restricted mean overall survival (40.8 vs 52.7 months; P < .001) and cancer-specific survival (41.3 vs 54.8 months; P < .001). When adjusted for other confounders, the nodal status of rectal neuroendocrine tumors was not independently associated with overall (hazard ratio = 1.56; P = .165) or cancer-specific survival (hazard ratio = 1.69; P = .158). Significant factors associated with worse overall survival and cancer-specific survival were age, tumor size, neuroendocrine carcinomas, large-cell neuroendocrine carcinomas, and the number of positive lymph nodes. CONCLUSIONS Lymph node metastases of rectal neuroendocrine tumors were more likely associated with high-grade, large-sized, and T2 to T4 tumors. The number of involved lymph nodes was an independent predictor of overall and cancer-specific survival. Other independent survival predictors were tumor grade, size, and T stage.
Collapse
Affiliation(s)
- Sameh Hany Emile
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL; Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Egypt. https://twitter.com/dr_samehhany81
| | - Nir Horesh
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL; Department of Surgery and Transplantation, Sheba Medical Center, Ramat-Gan, Israel. https://twitter.com/nirhoresh
| | - Zoe Garoufalia
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL. https://twitter.com/ZGaroufalia
| | - Rachel Gefen
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL; Department of General Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. https://twitter.com/Rachellgefen
| | - Anjelli Wignakumar
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL
| | - Steven D Wexner
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL.
| |
Collapse
|
|
5
|
Ben Thayer M, Helal I, Khanchel F, Khdhiri N, Ben Brahim E, Jouini R, Chadli-Debbiche A. Large cell neuroendocrine carcinoma of the colon: An unexpected diagnosis: A case report. Int J Surg Case Rep 2024; 121:109929. [PMID: 38917703 PMCID: PMC11254182 DOI: 10.1016/j.ijscr.2024.109929] [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: 05/22/2024] [Revised: 06/14/2024] [Accepted: 06/19/2024] [Indexed: 06/27/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE Large cell neuroendocrine carcinomas of the colon (LCNECC) are exceptionally rare, comprising only 0.2 % of all colonic carcinomas. Their diagnosis poses a significant challenge due to their propensity to mimic colonic adenocarcinomas. Typically diagnosed at advanced stages, LCNECCs carry a grim prognosis. Herein, we present a rare case of LCNECC and aim to elucidate its clinico-pathological characteristics. CASE PRESENTATION A 56-year-old female patient presented with complaints of constipation, abdominal pain, and weight loss. On physical examination, a sizable mass was palpable in the right flank. Colonoscopy revealed a polyp in the descending colon and a friable multinodular stenosing mass in the ascending colon. Microscopic examination of the biopsy from the ascending colon mass exhibited a poorly differentiated large cell carcinomatous proliferation with positivity for synaptophysin and CD56, along with a Ki-67 proliferation index of 50 %. The polyp in the descending colon was consistent with a low-grade dysplastic tubular adenoma. A diagnosis of LCNECC with synchronous low-grade dysplastic tubular adenoma was established. A right hemicoloctomy was performed. Final pathological examination confirmed LCNECC invading the muscularis propria, with lymph node metastases. The tumor was classified as pT2N1M0 (Stage III). CLINICAL DISCUSSION LCNECCs often mimic adenocarcinomas clinically, endoscopically, and radiologically. Pathological examination is the key for diagnosis. An immunohistochemical study using neuroendocrine markers is imperative to prevent overlooking the diagnosis of LCNECC. CONCLUSION LCNECCs represent rare aggressive carcinomas. Their diagnosis might be challenging. A better knowledge of this rare entities would enable early diagnosis.
Collapse
Affiliation(s)
- Maissa Ben Thayer
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of Pathology, Tunis, Tunisia.
| | - Imen Helal
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of Pathology, Tunis, Tunisia
| | - Fatma Khanchel
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of Pathology, Tunis, Tunisia
| | - Nizar Khdhiri
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of General Surgery, Tunis, Tunisia
| | - Ehsen Ben Brahim
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of Pathology, Tunis, Tunisia
| | - Raja Jouini
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of Pathology, Tunis, Tunisia
| | - Aschraf Chadli-Debbiche
- Tunis El Manar University, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia; Habib Thameur Hospital, Department of Pathology, Tunis, Tunisia.
| |
Collapse
|
|
6
|
Owaki S, Mori Y, Nakai S, Maeda H, Imazu M, Tomita Y, Kanaiwa H, Yamaguchi A, Kitagawa M, Hirano A, Kimura Y, Tsuchida K, Kataoka H. BRAF V600E-mutated Colorectal Neuroendocrine Carcinoma Effectively Treated with a Chemotherapy Protocol for BRAF-mutated Metastatic Colorectal Cancer. Intern Med 2024; 63:1995-1999. [PMID: 37981300 PMCID: PMC11309870 DOI: 10.2169/internalmedicine.2870-23] [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: 09/03/2023] [Accepted: 10/05/2023] [Indexed: 11/21/2023] Open
Abstract
Metastatic colorectal neuroendocrine carcinoma (NEC) is often treated using a chemotherapy protocol for small-cell lung cancer; however, the prognosis is extremely poor. A 55-year-old woman with BRAF V600E-mutated transverse colon NEC and liver metastases underwent colectomy followed by FOLFOXIRI plus bevacizumab. Consequently, the liver metastases markedly shrank. Owing to later worsening of the liver metastases, she received encorafenib and binimetinib plus cetuximab. Despite discontinuing binimetinib due to myalgia, she had a long-term response with a progression-free survival of 14 months and an overall survival of more than 27 months. A chemotherapy protocol for BRAF-mutated metastatic colorectal cancer may be a treatment option for BRAF V600E-mutated colorectal NEC.
Collapse
Affiliation(s)
- Seira Owaki
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
- Department of Medical Oncology, National Hospital Organization Nagoya Medical Center, Japan
| | - Yoshinori Mori
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Shunsuke Nakai
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Hideki Maeda
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Mitsuki Imazu
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Yusaku Tomita
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Hiroki Kanaiwa
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Ayana Yamaguchi
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Mika Kitagawa
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Atsuyuki Hirano
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Yoshihide Kimura
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Kenji Tsuchida
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| |
Collapse
|
|
7
|
Ono Y, Yilmaz O. Emerging and under-recognised patterns of colorectal carcinoma morphologies: a comprehensive review. J Clin Pathol 2024; 77:439-451. [PMID: 38448211 DOI: 10.1136/jcp-2023-208816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 02/22/2024] [Indexed: 03/08/2024]
Abstract
While the overwhelming majority of colorectal carcinomas (CRC) are diagnosed as adenocarcinoma not otherwise specified, there are numerous under-recognised morphologic patterns of CRC. These patterns are recognised by the WHO, appear in reporting manuals for the American Joint Committee of Cancer, and/or are listed on synoptic reports, while many other variants have either fallen out of favour or are emerging as future bona fide patterns. Herein, we discuss 13 variants: serrated adenocarcinoma, micropapillary adenocarcinoma, medullary carcinoma, neuroendocrine carcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, adenosquamous carcinoma, adenoma-like adenocarcinoma, lymphoglandular complex-like CRC, carcinoma with sarcomatoid components, cribriform-comedo-type adenocarcinoma, undifferentiated carcinoma and low-grade tubuloglandular adenocarcinoma. The purpose of this review is to scrutinise these variants by assessing their clinical characteristics, morphologic cues, as well as pitfalls, and address their prognostic significance. Our analysis aims to bring clarity and updated understanding to these variants, offering valuable insights for pathologists. This contributes to more nuanced CRC diagnosis and treatment strategies, highlighting the importance of recognising a broad spectrum of morphologic patterns in CRC.
Collapse
Affiliation(s)
- Yuho Ono
- Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Osman Yilmaz
- Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| |
Collapse
|
|
8
|
Suraju MO, Freischlag K, McKeen A, Nayyar A, Thompson D, Gordon DM, Mishra A, Sherman SK, Goffredo P, Hassan I. Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma. J Surg Oncol 2024; 129:1449-1455. [PMID: 38685721 DOI: 10.1002/jso.27645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 03/18/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. METHODS Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. RESULTS There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CONCLUSION CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.
Collapse
Affiliation(s)
- Mohammed O Suraju
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Kyle Freischlag
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Andrew McKeen
- Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Apoorve Nayyar
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Dakota Thompson
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Darren M Gordon
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Aditi Mishra
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Scott K Sherman
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Paolo Goffredo
- Division of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Imran Hassan
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Department of Surgery, Mercy Hospital, Cedar Rapids, Iowa, USA
| |
Collapse
|
|
9
|
Ho YH, Hsu CY, Yau Li AF, Liang WY. Colorectal neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasm: Prognostic factors and PD-L1 expression. Hum Pathol 2024; 145:80-85. [PMID: 38423221 DOI: 10.1016/j.humpath.2024.02.012] [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: 11/27/2023] [Revised: 02/15/2024] [Accepted: 02/26/2024] [Indexed: 03/02/2024]
Abstract
Colorectal neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare malignancies with unclear boundaries and poor prognoses. Our study aimed to conduct a comparative analysis of these diseases, identify prognostic factors, and explore potential therapeutic targets. We collected and analyzed clinicopathological data of NEC and MiNEN in our hospital from 2011 to 2020. Immunohistochemical staining for PD-L1, BRAF V600E, and mismatch repair proteins was performed. We identified 14 NEC and 7 MiNEN cases. Demographic data, including median overall survival (17.1 months for NEC and 18.5 months for MiNEN), did not significantly differ. NEC showed a higher tendency to occur in the rectum and sigmoid colon (p = 0.025) and had fewer cases with metastatic adenocarcinoma components in lymph nodes (p = 0.009) compared to MiNEN. Adverse prognostic factors were age ≥70 years (p = 0.012), N2 nodal status (p = 0.032), and stage IV disease (p = 0.013) based on multivariate Cox regression analysis. We identified five PD-L1 positive cases, two BRAF V600E mutated cases, and one Lynch syndrome case with MSH2 and MSH6 loss. Patients with colorectal NEC or MiNEN exhibited poor survival rates. Adverse prognostic factors included older age, N2 nodal status, and distant metastasis. Potential therapeutic avenues such as immune checkpoint and BRAF inhibitors were suggested for patients with these carcinomas.
Collapse
Affiliation(s)
- Yi Hsuan Ho
- Department of Pathology, Tao-Yuan General Hospital, Ministry of Health and Welfare, Tao-Yuan, Taiwan
| | - Chih Yi Hsu
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Anna Fen Yau Li
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen Yih Liang
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| |
Collapse
|
|
10
|
Miccio JA, Tian Z, Mahase SS, Lin C, Choi S, Zacharia BE, Sheehan JP, Brown PD, Trifiletti DM, Palmer JD, Wang M, Zaorsky NG. Estimating the risk of brain metastasis for patients newly diagnosed with cancer. COMMUNICATIONS MEDICINE 2024; 4:27. [PMID: 38388667 PMCID: PMC10883934 DOI: 10.1038/s43856-024-00445-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND Brain metastases (BM) affect clinical management and prognosis but limited resources exist to estimate BM risk in newly diagnosed cancer patients. Additionally, guidelines for brain MRI screening are limited. We aimed to develop and validate models to predict risk of BM at diagnosis for the most common cancer types that spread to the brain. METHODS Breast cancer, melanoma, kidney cancer, colorectal cancer (CRC), small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC) data were extracted from the National Cancer Database to evaluate for the variables associated with the presence of BM at diagnosis. Multivariable logistic regression (LR) models were developed and performance was evaluated with Area Under the Receiver Operating Characteristic Curve (AUC) and random-split training and testing datasets. Nomograms and a Webtool were created for each cancer type. RESULTS We identify 4,828,305 patients from 2010-2018 (2,095,339 breast cancer, 472,611 melanoma, 407,627 kidney cancer, 627,090 CRC, 164,864 SCLC, and 1,060,774 NSCLC). The proportion of patients with BM at diagnosis is 0.3%, 1.5%, 1.3%, 0.3%, 16.0%, and 10.3% for breast cancer, melanoma, kidney cancer, CRC, SCLC, and NSCLC, respectively. The average AUC over 100 random splitting for the LR models is 0.9534 for breast cancer, 0.9420 for melanoma, 0.8785 for CRC, 0.9054 for kidney cancer, 0.7759 for NSCLC, and 0.6180 for SCLC. CONCLUSIONS We develop accurate models that predict the BM risk at diagnosis for multiple cancer types. The nomograms and Webtool may aid clinicians in considering brain MRI at the time of initial cancer diagnosis.
Collapse
Affiliation(s)
- Joseph A Miccio
- Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA
| | - Zizhong Tian
- Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA
| | - Sean S Mahase
- Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA
| | - Christine Lin
- Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, OH, USA
| | - Serah Choi
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, OH, USA
| | - Brad E Zacharia
- Department of Neurosurgery, Penn State Cancer Institute, Hershey, PA, USA
| | - Jason P Sheehan
- Department of Neurosurgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Paul D Brown
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
| | | | - Joshua D Palmer
- Department of Radiation Oncology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH, USA
| | - Ming Wang
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Nicholas G Zaorsky
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, OH, USA.
| |
Collapse
|
|
11
|
Zhuang Y, Yu H, Chen CJ, Jian JL, Wu XY. Establishment and validation of a prognostic nomogram for patients with colorectal neuroendocrine carcinoma. Asian J Surg 2024; 47:433-442. [PMID: 37778975 DOI: 10.1016/j.asjsur.2023.09.099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 09/15/2023] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND Colorectal neuroendocrine carcinoma is a relatively rare tumor, for which a prognosis prediction model is lacking. Based on the data from Surveillance, Epidemiology, and End Results (SEER) database and Fujian Cancer Hospital, the study constructed and validated a prognostic nomogram to assess overall survival of patients with colorectal neuroendocrine carcinoma(CRNEC). METHODS We extracted data of patients diagnosed with CRNEC from the SEER database. These patients were randomly divided into a training cohort(N = 1425) and an internal validation cohort(N = 612). Data of patients diagnosed with CRNEC in Fujian Cancer Hospital was collected as an external validation cohort(N = 54). A prognostic nomogram was established. The performance of the nomogram was assessed with ROC curve, C-index and calibration curve. Decision curve analysis(DCA) and ROC curve were used to compare the prediction efficacy of nomogram with the seventh edition of the TNM classification of the American Joint Commission of Cancer. RESULTS Nine variables were identified as independent predictors. Nomogram were established by the nine variables. AUC of the nomogram in predicting 1-, 3- and 5-year OS were 0.900, 0.912 and 0.915 in training cohort, 0.900, 0.925 and 0.919 in internal validation cohort, 0.900, 0.903 and 0.928 in external validation cohort. C-index were 0.845, 0.854 and 0.837. Calibration curves overlapped well with reference lines. Compared with the AJCC TNM staging system, the nomogram performed more effectively. Patients classified into low-risk and high-risk groups by the nomogram scores and performed well in stratification. CONCLUSION The prognostic nomogram established and validated in our study can accurately and effectively predict the prognosis of patients with CRNEC.
Collapse
Affiliation(s)
- Yong Zhuang
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
| | - Hui Yu
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Chang-Jiang Chen
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Jin-Liang Jian
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Xian-Yi Wu
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
| |
Collapse
|
|
12
|
Agboola JO, Attia H, Zhonghua L, Pittman M. Large Cell Neuroendocrine Carcinoma Presenting as Adult Intussusception. Cureus 2024; 16:e51546. [PMID: 38313961 PMCID: PMC10834885 DOI: 10.7759/cureus.51546] [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] [Accepted: 01/02/2024] [Indexed: 02/06/2024] Open
Abstract
Large cell neuroendocrine carcinoma (LCNEC) is an extremely rare malignant tumor of the colon, presenting with more severe clinical outcomes in comparison to colonic adenocarcinoma. There are very few reported cases in the literature. We hereby add our voice to the incidence of this disease by presenting the first report of a patient with ileocolic intussusception secondary to a large cell neuroendocrine cancer of the cecum. The patient was a 48-year-old woman who presented with acute onset of generalized abdominal pain and leukocytosis. CT scan revealed an ileocecal intussusception and multiple liver metastases suggestive of a malignant bowel lesion. She underwent emergency surgery, and an extended right hemicolectomy with ileo-transverse anastomosis was performed. Histology of the resected lesion revealed large cell neuroendocrine carcinoma of the cecum with invasion through the muscularis propria into peri colorectal tissues. The tumor retained mismatch repair (MMR) proteins with low potential for microsatellite instability (MSI). With a clinical diagnosis of stage IV LCNEC, the patient began platinum doublet chemotherapy with carboplatin and etoposide; however, her disease progressed, and the patient expired within a few months after her diagnosis. Clinical diagnosis of adult intussusception should prompt clinicians to rule out malignant etiology. This patient had a large cell neuroendocrine carcinoma of the colon, a rare and extremely aggressive malignancy. Patients with LCNEC will benefit from a multidisciplinary approach to treatment.
Collapse
Affiliation(s)
- John O Agboola
- Pathology Anatomic & Clinical, State University of New York (SUNY) Downstate Health Science University, Brooklyn, USA
- Pathology, Kings County Hospital Center, Brooklyn, USA
| | - Hagar Attia
- Pathology Anatomic & Clinical, State University of New York (SUNY) Downstate Health Science University, Brooklyn, USA
| | - Li Zhonghua
- Pathology, Kings County Hospital Center, New York, USA
| | - Meredith Pittman
- Department of Pathology, Maimonides Medical Center, Brooklyn, USA
| |
Collapse
|
|
13
|
Le ZHM, Khoo WSK, Kumar K. A Rare Case of Rectosigmoid Small Cell Carcinoma. Cureus 2023; 15:e41339. [PMID: 37546029 PMCID: PMC10397522 DOI: 10.7759/cureus.41339] [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] [Accepted: 07/03/2023] [Indexed: 08/08/2023] Open
Abstract
Colorectal small cell carcinomas are very rare neuroendocrine malignancies of the colon or rectum. They have poor prognosis due to the aggressive and highly recurrent nature of the disease. It is a malignancy that is also poorly understood with limited literature, and thus there is no consensus in management. This case report presents the clinical features and radiological images of an otherwise healthy 74-year-old gentleman with a rare and aggressive 112-mm rectosigmoid small cell carcinoma with evidence of metastatic disease. This report will also discuss the most current and pertinent diagnostic and therapeutic recommendations from the literature.
Collapse
Affiliation(s)
- Zhuang Hui Mark Le
- Department of General Surgery, Logan Hospital, Brisbane, AUS
- Department of General Surgery, Redland Hospital, Brisbane, AUS
| | | | - Kaushik Kumar
- Department of General Surgery, Queen Elizabeth II Hospital, Brisbane, AUS
- Department of General Surgery, Redland Hospital, Brisbane, AUS
| |
Collapse
|
|
14
|
Chen Y, Liang Y, Cao L, Dong X, Sun D. Neuroendocrine differentiation: a risk fellow in colorectal cancer. World J Surg Oncol 2023; 21:89. [PMID: 36899368 PMCID: PMC9999536 DOI: 10.1186/s12957-023-02952-8] [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: 10/14/2022] [Accepted: 02/14/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Neuroendocrine differentiation (NED) is often found in colorectal cancer (CRC) and may have unique biological behavior, which has not been previously delineated. Here, we explore the relationship between CRC, NED, and clinicopathological factors. We also offer a preliminary explanation of the mechanism underlying the malignant biological behavior of NED in CRC. METHODS Between 2013 and 2015, 394 CRC patients who underwent radical operations were selected for analysis. The relationship between NED and clinicopathological factors was analyzed. To further clarify the pivotal role of NED in CRC, we performed bioinformatic analyses and identified genes that may be involved in NED, which were obtained from in silico data from The Cancer Genome Atlas (TCGA) database. Then, we conducted functional enrichment analyses and confirmed the critical pathways for intensive study. Moreover, we detected the expression of key proteins by immunohistochemistry and analyzed the correlation of their expression with NED. RESULTS The statistical analysis showed that CRC with NED was positively correlated with lymph node metastasis. Through bioinformatic analysis, we found that chromogranin A (CgA) was positively correlated with invasion and lymph node metastasis. ErbB2 and PIK3R1, which are key proteins in the PI3K-Akt signaling pathway, were closely related to NED. Furthermore, we determined that the PI3K-Akt signaling pathway likely plays a critical role in the NED of CRC. CONCLUSIONS CRC with NED is associated with lymph node metastasis. The PI3K-Akt signaling pathway, which is closely related to CRC, may be the mechanism promoting the malignant biological behavior of CRC with NED.
Collapse
Affiliation(s)
- Yue Chen
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Yu Liang
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Lianqun Cao
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Xinxin Dong
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Deyu Sun
- Department of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China.
| |
Collapse
|
|
15
|
Ding X, Yang X, Hao Q, Xu F, Yu X, Rao L, Yuan C, Tian S. Risk prediction of second primary malignancies in primary colorectal neuroendocrine neoplasms patients: a population-based study. J Endocrinol Invest 2023:10.1007/s40618-023-02047-x. [PMID: 36870016 DOI: 10.1007/s40618-023-02047-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 02/19/2023] [Indexed: 03/05/2023]
Abstract
PURPOSE In this study, we aimed to identify risk factors for developing second primary malignancies (SPMs) in colorectal neuroendocrine neoplasms (NENs) patients and develop a competing-risk nomogram to predict SPMs' probabilities quantitatively. METHODS Patients with colorectal NENs were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2013. Potential risk factors for SPMs' occurrence in colorectal NENs' patients were identified by the Fine and Gray's proportional sub-distribution hazards model. Then, a competing-risk nomogram was constructed to quantify SPMs' probabilities. The discriminative abilities and calibrations of this competing-risk nomogram were assessed by the area under the receiver-operating characteristic (ROC) curves (AUC) and calibration curves. RESULTS We identified 11,017 colorectal NENs' patients, and randomly divided them into training (n = 7711 patients) and validation (n = 3306 patients) cohorts. In the whole cohort, 12.4% patients (n = 1369) had developed SPMs during the maximum follow-up of approximately 19 years (median 8.9 years). Sex, age, race, primary tumor location, and chemotherapy were identified as risk factors for SPMs' occurrence in colorectal NENs' patients. Such factors were selected to develop a competing-risk nomogram and showed excellent predictive ability for SPMs' occurrence (the 3-, 5-, and 10-year AUC values were 0.631, 0.632, and 0.629 in the training cohort and 0.665, 0.639, 0.624 in the validation cohort, respectively). CONCLUSIONS This research identified risk factors for SPMs' occurrence in colorectal NENs' patients. Competing-risk nomogram was constructed and proved to have good performance.
Collapse
Affiliation(s)
- X Ding
- Department of Clinical Laboratory, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, People's Republic of China
| | - X Yang
- Department of Clinical Laboratory, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, People's Republic of China
| | - Q Hao
- Department of Nursing, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, People's Republic of China
| | - F Xu
- Department of Pharmacy, The People's Hospital of China Three Gorges University, Yichang, 443000, People's Republic of China
| | - X Yu
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, People's Republic of China
| | - L Rao
- Department of Clinical Laboratory, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, People's Republic of China
| | - C Yuan
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, People's Republic of China.
| | - S Tian
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
| |
Collapse
|
|
16
|
Kobayashi N, Yoshida H, Kawaguchi S, Shiraso S, Nemoto N, Fujikawa N, Haji Y, Kono E, Kokubo S, Tsukuda K, Asano S, Shinya F. A case of strongly suspected Lynch syndrome with colorectal neuroendocrine carcinoma. Surg Case Rep 2022; 8:114. [PMID: 35713748 PMCID: PMC9206053 DOI: 10.1186/s40792-022-01471-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 06/13/2022] [Indexed: 11/10/2022] Open
Abstract
Background Neuroendocrine cell carcinomas (NEC) of the colon and rectum are uncommon, representing ~ 0.1% of all colorectal carcinomas. They are associated with a much worse prognosis compared to adenocarcinoma of the colon and rectum, as death occurs in approximately half of all patients within 1 year. Lynch syndrome (LS) is the most common cause of inherited colorectal cancer, accounting for 2–4% of newly diagnosed colorectal cancer cases. This case is extremely rare which was strongly suspected LS as the background, and NEC as the histological type of colorectal cancer. Case presentation The patient was a 44-year-old man presenting with vomiting as the main complaint. He had undergone ileocecal resection for cecal cancer at age 29. The diagnosis was obstructive descending colorectal cancer, and colonoscopy revealed tumors in the rectum and sigmoid colon in addition. Due to multiple occurrences of colorectal cancer and its prevalence in the patient’s family, LS was suspected. The operation which was a subtotal proctocolectomy was performed. Pathological analysis revealed complete curative resection and the descending colon cancer of the obstructed portion was at the most advanced pathological Stage IIIC in UICC TNM classification, and the tissue type was a NEC. The Ki-67 index was 70%. The results of the microsatellite instability (MSI) test showed high-frequency MSI. The BRAF V600E variant was negative. The immunoexpression of MLH1 was positive, MSH2 was negative, PMS2 was positive, and MSH6 was negative. Conclusions Extended surgery is recommended for incipient colorectal cancer in LS cases in order to reliably reduce the risk of developing metachronous colorectal cancer. The survival outcome of surgery alone on digestive tract NECs, even locoregional lesions that are completely resection, is extremely poor. It is currently unclear if digestive tract NECs develop more readily in patients with LS. The accumulation of additional cases is necessary.
Collapse
|
|
17
|
Bloemen H, Kneepkens K, Deraedt K, Ivanova A, Sergeant G, Mebis J, Van der Speeten K. Evaluation of quality of clinical management of neuroendocrine tumors. CANCER INNOVATION 2022; 1:305-315. [PMID: 38089084 PMCID: PMC10686178 DOI: 10.1002/cai2.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/10/2022] [Accepted: 11/18/2022] [Indexed: 10/15/2024]
Abstract
Background Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms predominantly found in the gastrointestinal and bronchopulmonary tractus. Despite a rising incidence, implementation of evidence-based standardized care for this heterogenous group remains challenging. The European Neuroendocrine Tumor Society regularly reviews guidelines regarding diagnostic and treatment strategies for NETs. The aim of this study is to shed light on the care of patients with a NET in Belgian Limburg, to provide data as a basis for future studies and to check whether data and results are according to consensus guidelines and outcomes described in literature. Methods Our study concerned a detailed observational data collection of two large Belgian hospitals (Jessa Hospital Hasselt and Hospital Oost-Limburg Genk) with special interest in patient profile, quality of pathology reports, use of diagnostic imaging, and overall survival. Data on 188 patients were assembled between January 2010 and December 2014 with follow-up until June 2016 (median follow-up: 33.6 months). Results Fifty percent of patients were male. NETs were located mainly in the digestive tract (63.8%) and lung (20.2%). Appendiceal NETs were diagnosed at a significantly younger age than other tumors (41.3 vs. 64.0 years). Overall, a mean pathology report quality score of 3.0/5 was observed with the highest scores for small bowel NETs. Diagnostic and nuclear imaging was performed in 74.5% and 29.8% of cases, respectively. Seventy-four percent of the population survived until the end of the observation period with highest survival rates for appendiceal and small bowel NETs. Conclusion Overall, epidemiological results were comparable with findings in the literature. Gastrointestinal NETs met most of the requirements of qualitative pathology reporting and diagnostic imaging as listed in the European Neuroendocrine Tumor Society consensus guidelines. However, consensus with regard to bronchopulmonary NETs is still scarce and remains an objective for future research. Moreover, discussing treatment strategies in specialized multidisciplinary tumor boards would facilitate regional care.
Collapse
Affiliation(s)
- Hannah Bloemen
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
| | - Kristien Kneepkens
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
| | - Karen Deraedt
- Department of Pathology and Department Future HealthZiekenhuis Oost‐LimburgGenkBelgium
| | - Anna Ivanova
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
| | - Gregory Sergeant
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
- Department of Abdominal Surgery and Department Jessa & ScienceJessa HospitalHasseltBelgium
| | - Jeroen Mebis
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
- Department of Medical Oncology and Department Jessa & ScienceJessa HospitalHasseltBelgium
| | - Kurt Van der Speeten
- Department of Medicine, Faculty of Medicine and Life Sciences (LCRC)Hasselt UniversityDiepenbeekBelgium
- Department of Surgical Oncology and Department Future HealthZiekenhuis Oost‐LimburgGenkBelgium
| |
Collapse
|
|
18
|
Baek HS, Kim SW, Lee ST, Park HS, Seo SY. Silent advanced large cell neuroendocrine carcinoma with synchronous adenocarcinoma of the colon: A case report. World J Gastrointest Oncol 2022; 14:2266-2272. [PMID: 36438698 PMCID: PMC9694276 DOI: 10.4251/wjgo.v14.i11.2266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/31/2022] [Accepted: 10/12/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Large cell neuroendocrine carcinoma (LCNEC) accounts for about 0.25% of colorectal cancer patients. Furthermore, synchronous LCNEC and adenocarcinoma coexistence in the colon is very rare. LCNEC are usually aggressive and have a poor prognosis. Usually, colorectal LCNEC patients complain of abdominal symptoms such as pain, diarrhea or hematochezia because it is often diagnosed as an advanced disease that accompanies metastatic lesions.
CASE SUMMARY We describe a case of relatively asymptomatic synchronous LCNEC and colon adenocarcinoma. A 62-year-old male patient visited our hospital due to anemia detected by a local health check-up. He did not complain of melena, hematochezia or abdominal pain. Physical examination was unremarkable and his abdomen was soft, nontender and nondistended with no palpable mass. Laboratory tests revealed anemia with hemoglobin 5.1 g/dL. Colonoscopy revealed an ulcerofungating lesion in the ascending colon and about a 1.5 cm-sized large sessile polyp in the sigmoid colon. Endoscopic biopsy of the ascending colon lesion revealed the ulcerofungating mass that was LCNEC and endoscopic mucosal resection at the sigmoid colon lesion showed a large polypoid lesion that was adenocarcinoma. Multiple liver, lung, bone and lymph nodes metastasis was found on chest/abdominal computed tomography and positron emission tomography. The patient was diagnosed with advanced colorectal LCNEC with liver, lung, bone and lymph node metastasis (stage IV) and synchronous colonic adenocarcinoma metastasis. In this case, no specific symptom except anemia was observed despite the multiple metastases. The patient refused systemic chemotherapy and was discharged after transfusion.
CONCLUSION We report a case of silent LCNEC of the colon despite the advanced state and synchronous adenocarcinoma.
Collapse
Affiliation(s)
- Hyeon Seok Baek
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju-si 56445, Jeollabuk-do, South Korea
| | - Sang Wook Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju-si 56445, Jeollabuk-do, South Korea
| | - Soo Teik Lee
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju-si 56445, Jeollabuk-do, South Korea
| | - Ho Sung Park
- Department of Pathology, Jeonbuk National University Medical School, Jeonju-si 56445, Jeollabuk-do, South Korea
| | - Seung Young Seo
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju-si 56445, Jeollabuk-do, South Korea
| |
Collapse
|
|
19
|
Bancheno WM, Adidam SR, Melaku MA. Metastatic rectal neuroendocrine carcinoma presenting with treatment-refractory immune thrombocytopenia: A case report and literature review. Medicine (Baltimore) 2022; 101:e29616. [PMID: 35866784 PMCID: PMC9302362 DOI: 10.1097/md.0000000000029616] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Colorectal neuroendocrine cancer (CRNEC) accounts for < 1% of all colorectal cancers. It presents in advanced stages and carries a risk of poor survival. CRNEC may be diagnosed incidentally on imaging or routine endoscopy. When symptomatic, it may mimic colorectal adenocarcinoma. Syncope and immune thrombocytopenic purpura (ITP) have not previously been reported as clinical presentations. PATIENT CONCERNS A 57-year-old man with human immunodeficiency virus infection on treatment, seizure and stroke without residue presented for the evaluation of fall and syncope. DIAGNOSIS Physical examination revealed tachycardia, swelling, and ecchymosis of his proximal left lower extremity. Laboratory tests showed a new isolated thrombocytopenia of 26,000/mm3. Computed tomography for a trauma survey showed an incidental left posterior rectal wall mass. After hospital admission, his platelet count dropped to 14,000/mm3. A peripheral blood smear revealed low platelet count, no schistocytes or immature cells. ITP at a high risk for bleeding was diagnosed and treated with standard medical therapy but remained refractory. Bone marrow biopsy showed metastatic neuroendocrine carcinoma, likely from the rectum. INTERVENTIONS Patient received courses of high-dose dexamethasone and intravenous immunoglobulin. He also receive eleven units of platelet transfusion. A course of rituximab was administered. The platelet count response was suboptimal or short lived with drop to a nadir of 4000/mm3. However, after initiation of Eltrombopag, the thrombocytopenia resolved. Patient was started on etoposide, carboplatin, Atezolizumab. His hospital stay was complicated by neutropenia and sepsis, which was successfully treated. OUTCOMES He was discharged to subacute rehab in stable condition. About 4 months later, he was readmitted for severe thrombocytopenia, septic shock, and acute respiratory failure. Despite appropriate treatment, the patient deteriorated and expired. CONCLUSION CRNEC is a rare aggressive disease with dismal outcome that lacks standardized treatment. Metastasis to the bone marrow is uncommon and concomitant ITP has not been reported. We report a rare case of rectal neuroendocrine carcinoma metastatic to bone marrow associated with refractory ITP and review the relevant literature.
Collapse
Affiliation(s)
- Wouhabe Marai Bancheno
- Internal Medicine, Howard University Hospital, Washington, DC
- * Correspondence: Wouhabe Marai Bancheno, MD, MSc, Internal Medicine, Howard University Hospital, 2041 GA Ave NW, Washington, DC 20060 (e-mail: )
| | | | | |
Collapse
|
|
20
|
Khanna V, Reddy T, Nagar T, Tegeltija V. Metastatic Large Cell Neuroendocrine Carcinoma of the Colon: A Case Report. Cureus 2022; 14:e26075. [PMID: 35747103 PMCID: PMC9209407 DOI: 10.7759/cureus.26075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2022] [Indexed: 11/05/2022] Open
|
|
21
|
Manhal K, Christophe R, Radu B, Daniel L, Jeremy S, Alex K. Case report of multiple rectal neuroendocrine tumors in a context of ulcerative colitis. Int J Surg Case Rep 2022; 91:106760. [PMID: 35091352 PMCID: PMC8803596 DOI: 10.1016/j.ijscr.2022.106760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/06/2022] [Accepted: 01/06/2022] [Indexed: 12/23/2022] Open
Affiliation(s)
- Kalaji Manhal
- Colorectal Surgery Unit (Saint-Luc Hospital - Brussels), Belgium
| | - Remue Christophe
- Colorectal Surgery Unit (Saint-Luc Hospital - Brussels), Belgium
| | - Bachmann Radu
- Colorectal Surgery Unit (Saint-Luc Hospital - Brussels), Belgium
| | - Leonard Daniel
- Colorectal Surgery Unit (Saint-Luc Hospital - Brussels), Belgium
| | - Schoelinck Jeremy
- Department of Anatomopathology (Saint-Luc Hospital - Brussels), Belgium
| | - Kartheuser Alex
- Colorectal Surgery Unit (Saint-Luc Hospital - Brussels), Belgium.
| |
Collapse
|
|
22
|
Felux K, McCarty B, Turner D, Gray TK, Patel V. Poorly Differentiated Large Cell Neuroendocrine Carcinoma of the Colon: A Case Report. Cureus 2022; 14:e20949. [PMID: 35154929 PMCID: PMC8815286 DOI: 10.7759/cureus.20949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2022] [Indexed: 11/05/2022] Open
Abstract
Colon cancer is one of the most common diagnoses of cancer and a leading cause of death in America. Large cell neuroendocrine tumors are a very uncommon type of colon cancer that tends to have a poor prognosis. Usually, these tumors are only found at the time of metastasis making them even more difficult to treat. A 65-year-old female presented with worsened generalized abdominal pain associated with abdominal distention. She had not had a bowel movement in over a week and did not have any flatulence. She had a colonoscopy four years prior that was normal. Physical examination was significant for abdominal distention and a large right-sided palpable mass in her abdomen with generalized tenderness. A CT scan showed a large irregular mass at least 9.8 x 10.5 cm at the mid to distal ascending colon resulting in significant colonic narrowing significant for a large bowel obstruction. The CT also demonstrated suspicious nodules in the lung, lesions in the liver, and lymphadenopathy. She had an exploratory laparotomy with an extended hemicolectomy to remove the mass. Pathology revealed the mass was neuroendocrine carcinoma, a large cell subtype, that was poorly differentiated with involvement of at least 32 of 34 lymph nodes. This tumor was positive for AE1/AE3, CEA, CK20, and synaptophysin. Ki-67 showed 70% positivity. TTF1 was negative and ruled out a primary lung tumor. Microsatellite immunostains were positive for MLH-1, MSH-2, MSH-6, and PMS2. The patient was started on Carboplatin AUC6 and Etoposide 100mg/m2 in three-week intervals. Pegfilgrastim was also added to her treatment plan every 21 days. This is a review of a female who presented with colonic obstruction that was found to be poorly differentiated large cell neuroendocrine carcinoma after a previous negative colonoscopy.
Collapse
|
|
23
|
Zheng X, Wu M, Er L, Deng H, Wang G, Jin L, Li S. Risk factors for lymph node metastasis and prognosis in colorectal neuroendocrine tumours. Int J Colorectal Dis 2022; 37:421-428. [PMID: 34997303 PMCID: PMC8803742 DOI: 10.1007/s00384-021-04082-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/08/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs. METHODS The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up. RESULTS A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses. CONCLUSIONS When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.
Collapse
Affiliation(s)
- Xiuli Zheng
- grid.452582.cDepartment of Endoscopy, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| | - Mingli Wu
- grid.452582.cDepartment of Endoscopy, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| | - Limian Er
- grid.452582.cDepartment of Endoscopy, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| | - Huiyan Deng
- grid.452582.cDepartment of Pathology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| | - Gongning Wang
- grid.452582.cDepartment of Endoscopy, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| | - Lingyao Jin
- grid.452582.cDepartment of Endoscopy, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| | - Shengmian Li
- grid.452582.cDepartment of Gastroenterology, the Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang’an District, Shijiazhuang, 050000 Hebei China
| |
Collapse
|
|
24
|
GILL I, SHAMS C, QUIROZ E, KRISHNAN SM, GAIKAZIAN S. Large cell neuroendocrine tumor of the gastrointestinal tract with concurrent tubular adenomas. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2021. [DOI: 10.23736/s0393-3660.20.04399-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
|
|
25
|
Basendowah MH, Ashour MA, Hassan AY, Alshaynawi S, Alyazidi LK. Multiple Small Intestinal Neuroendocrine Tumors With Findings of Intestinal Obstruction. Cureus 2021; 13:e17629. [PMID: 34646678 PMCID: PMC8485364 DOI: 10.7759/cureus.17629] [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] [Accepted: 09/01/2021] [Indexed: 12/04/2022] Open
Abstract
Carcinoid tumors are one of the most common types of small intestinal neuroendocrine tumors (SI-NETs). However, SI-NETs that manifest as subacute intestinal obstruction are extremely rare. The annual occurrence rate of jejuno-ileal NETs is 0.28-0.8 per 100,000 people. In this report, we describe a case of subacute intestinal obstruction due to a mid-ileal stricture. The patient underwent laparotomy after evaluation and investigation. Mid-ileal growth was noted, and small bowel resection was performed with primary end-to-end anastomosis. Postoperative histopathology revealed the growth to be a well-differentiated NET.
Collapse
Affiliation(s)
| | - Mohammed A Ashour
- Medicine, College of Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| | - Ammar Y Hassan
- Medical Physics, College of Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| | - Shahad Alshaynawi
- Surgery, College of Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| | - Lujain K Alyazidi
- Medicine, College of Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| |
Collapse
|
|
26
|
Chen I, Zhang D, Velez M, Kovar S, Liao X. Poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract: A single-institute study of 43 cases. Pathol Res Pract 2021; 226:153614. [PMID: 34555651 DOI: 10.1016/j.prp.2021.153614] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/05/2021] [Accepted: 09/08/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVES To characterize the clinicopathologic and immunohistochemical features of poorly differentiated neuroendocrine carcinomas (NEC) in the gastrointestinal tract. DESIGN A total of 43 cases were identified and reassessed based on modern classification. RESULTS The cohort (27M, 16F; median age: 66 years) included 16 (37%) large cell NEC, 12 (28%) small cell NEC, 5 (12%) NEC not otherwise specified, and 10 (23%) mixed adenoneuroendocrine carcinomas. Tumor predominantly involved the colon (n = 14, 33%), rectum (n = 13, 30%), and esophagus (n = 9, 21%). Immunohistochemically, INSM1 was the most sensitive marker for neuroendocrine differentiation (28/28, 100%), followed by synaptophysin (40/43, 93%), CD56 (22/35, 63%), and chromogranin (18/40, 45%). SATB2, CDX2, CK20, CK7, abnormal p53, and PD-L1 was positive in 21/26 (81%), 26/37 (70%), 11/35 (31%), 10/35 (29%), 19/24 (79%), and 12/23 (52%) cases, respectively. Three of 25 (11%) were mismatch repair protein deficient. Of 21 resected tumors, 19 (90%) were ≥ pT3 and 13 (62%) had nodal metastasis. Twenty-eight (65%) had distant metastasis. The 5-year survival rate was 21%. The prognosis was stage dependent (p < 0.05), but not associated with tumor type, location, or specific immunomarkers. CONCLUSION Gastrointestinal NECs are aggressive neoplasms. INSM1, synaptophysin, and SATB2 are sensitive markers, although not site or tumor type specific.
Collapse
Affiliation(s)
- Irene Chen
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Dongwei Zhang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Moises Velez
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Sierra Kovar
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Xiaoyan Liao
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
| |
Collapse
|
|
27
|
Khan S, Haider G, Abid Z, Bukhari N, Khan SZ, Abid M. Adequacy of Surgical Pathology Reports of Colorectal Carcinoma and Its Significance. Cureus 2021; 13:e16965. [PMID: 34540379 PMCID: PMC8423118 DOI: 10.7759/cureus.16965] [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] [Accepted: 08/06/2021] [Indexed: 11/05/2022] Open
Abstract
Introduction Colorectal cancer is the fifth most common cancer in the world. For loco-regionally confined disease surgery is the definitive treatment. An adequate surgical pathology report is mandatory for the selection of adjuvant therapy. The objective of this study is to analyze whether adequate information is provided or not in the surgical pathology reports of colorectal carcinoma as according to College of American Pathologists (CAP) guidelines. Method This is a cross-sectional study carried out in the Department of Clinical Oncology, Jinnah Postgraduate Medical Center (JPMC) Karachi, tertiary care hospital in Pakistan. The duration of the study was from February 2020 to January 2021. A total of 153 surgical pathology reports issued by 11 different hospital-based laboratories after definitive surgery was assessed to look at its concordance rate with the checklist adapted from the CAP guidelines. Results Out of 153 surgical pathology reports, clinical information was provided in 72.5% of reports. Details of tumor extension were present in 88.2%, tumor margin in 75%, surgical procedure in 79%, and tumor deposits in 39.2% of reports. Macroscopic details including tumor perforation and evaluation of mesorectum were documented in 51.6% and 53.5% of the reports respectively. Details regarding perineural invasion along with lymphovascular invasion were present in 81.6% and 93% of the reports, respectively. The treatment effect was documented in only 25% of reports and regional lymph node status has been described in 85% of reports. Parameters described in all surgical pathology reports were: tumor site, tumor type, histologic type, and histologic grade. The pathological stage of the disease was documented in 91.5% of the reports. Conclusion This study concluded that surgical pathology reports of the majority of pathology laboratories were not fully adhered to the checklist provided by the CAP guidelines. This will affect post-operative management along with the prediction of disease prognosis.
Collapse
Affiliation(s)
- Salahuddin Khan
- Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Ghulam Haider
- Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Zain Abid
- Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Neelma Bukhari
- Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Shah Zeb Khan
- Clinical Oncology, Bannu Institute of Nuclear Medicine Oncology and Radiotherapy, Bannu, PAK
| | - Masooma Abid
- Medicine, Jinnah Medical and Dental College, Karachi, PAK
| |
Collapse
|
|
28
|
Risk and prognostic nomograms for colorectal neuroendocrine neoplasm with liver metastasis: a population-based study. Int J Colorectal Dis 2021; 36:1915-1927. [PMID: 34061225 DOI: 10.1007/s00384-021-03920-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/30/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Liver metastasis (LM) significantly shortens the survival time of colorectal neuroendocrine neoplasms (NENs) patients. This research aimed to explore risk and prognostic factors in colorectal NENs patients with LM and develop nomograms for predicting the risk of LM and survival probability quantitatively. METHODS A total of 9926 colorectal NENs patients registered in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017 were included. Risk factors for LM in colorectal NENs patients were identified by multivariate logistic regression analysis. Potential prognostic factors for colorectal NENs patients with LM were identified by multivariable Cox regression analysis. Nomograms were constructed for quantifying the probability of LM occurrence and survival. RESULTS At diagnosis, 8.7% of colorectal NENs patients suffered LM, with 1-, 3-, and 5-year cancer-specific survival (CSS) rates of 44.3%, 26.5%, and 18.0%, respectively. Factors associated with LM occurrence included gender, age at diagnosis, primary tumor location, carcinoembryonic antigen (CEA), histological differentiation, T stage, and N stage. Age at diagnosis, race, histological differentiation, N stage, tumor size, primary tumor location, primary site surgery, and extraliver metastasis were prognostic factors of cancer-specific mortality. The area under the receiver operating characteristics (ROC) curve of the nomogram for predicting LM was 0.888 (95% CI: 0.877-0.898), and the C-index of the nomogram for estimating CSS probability was 0.705 (95% CI: 0.682-0.729). CONCLUSIONS This research identified the risk and prognostic factors in colorectal NENs patients with LM. The nomograms constructed by this study can be convenient tools for facilitating clinical decision-making.
Collapse
|
|
29
|
Lessons learned about appendiceal neuroendocrine neoplasms from data analysis of the Belgian Cancer Registry 2010-2015. Acta Gastroenterol Belg 2021; 84:458-466. [PMID: 34599571 DOI: 10.51821/84.3.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND AND STUDY AIMS Appendiceal neuroendocrine neo-plasms (aNENs) are a diverse group of malignant neoplasms of varying biological behavior for which information about manage-ment and outcome is sparse, with the majority of available studies being retrospective, including only a limited number of patients, and therefore not necessarily reflecting the reality in the community. In the present study clinical, epidemiological and pathological data of appendiceal neuroendocrine neoplasms in Belgium is provided and compared with current literature. METHODS A population-based study was conducted by linking data of the Belgian Cancer Registry with medical procedures in the Belgian Health Insurance database for patients diagnosed with aNEN between 2010 and 2015. RESULTS We found an aNEN incidence of 0.97/100.000 person years in Belgium. Neuroendocrine carcinoma of the appendix are rare. Most appendiceal neuroendocrine tumors (aNETs) are small G1 tumors. Positive lymph nodes are often found in tumors larger than 2cm, especially aNET G2. CONCLUSION A rapid uptake of changing classifications was seen in the community. However, systematic reporting of risk factors for small aNEN can still be improved and should be stimulated. In 9% of cases, reclassifications had to be made, pointing out that in a retrospective analysis, original pathological reports should be checked for specific parameters, before reliable conclusions can be drawn.
Collapse
|
|
30
|
Della Torre S, de Nucci G, Lombardi PM, Grandi S, Manes G, Bollina R. Long-term complete response in metastatic poorly-differentiated neuroendocrine rectal carcinoma with a multimodal approach: A case report. World J Clin Oncol 2021; 12:500-506. [PMID: 34189072 PMCID: PMC8223717 DOI: 10.5306/wjco.v12.i6.500] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/24/2020] [Accepted: 03/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine gastrointestinal tumors (NETs) are rare and have different natural behaviors. Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective. Poorly differentiated neuroendocrine carcinomas (NECs) represent only 5%-10% of digestive NETS. Due to aggressive growth and rapid metastatic diffusion, early diagnosis and a multidisciplinary approach are mandatory. The role of surgery and radiotherapy in this setting is still debated, and chemotherapy remains the treatment of choice.
CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3 (Ki67 index > 90%) on May 2015 and initially treated with 3 cycles of first-line chemotherapy, but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection. In September 2015, the first post-surgery total-body computed tomography (CT) scan showed an early pelvic disease relapse. Therefore, systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response. This was followed by pelvic radiotherapy (50 Gy). On April 2016, a CT scan and 18F-fluorodeoxyglucose positron emission tomography imaging showed a complete response (CR) of the pelvic lesion, but pathological abdominal inter-aortocaval lymph nodes were observed. Due to disease progression of abdominal malignant nodes, the patient received radiotherapy at 45 Gy, and finally obtained a CR. As of January 2021, the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.
CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.
Collapse
Affiliation(s)
| | - Germana de Nucci
- Department of Gastroenterology, Garbagnate Milanese Hospital, ASST Rhodense, Garbagnate Milanese 20024, Italy
| | | | - Samuele Grandi
- Robotic and Emergency Surgery, General Surgery Division, Manzoni Hospital, Lecco 23900, Italy
| | - Gianpiero Manes
- Gastroenterology Unit, ASST Rhodense-Garbagnate Milanese, Garbagnate Milanese 20054, Italy
| | | |
Collapse
|
|
31
|
Wahab A, Rafae A, Mushtaq K, Venkata K, Sarmad R. Lurbinectedin-Induced Tumor Lysis Syndrome in Small Cell Neuroendocrine Cancer of the Cecum: A First-Ever Case Report. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e932081. [PMID: 34125741 PMCID: PMC8212840 DOI: 10.12659/ajcr.932081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Patient: Female, 38-year-old Final Diagnosis: Tumor lysis syndrome Symptoms: Abdominal pain Medication:— Clinical Procedure: — Specialty: Hematology • Oncology
Collapse
Affiliation(s)
- Ahsan Wahab
- Department of Hospital Medicine/Internal Medicine, Baptist Medical Center South, Montgomery, AL, USA
| | - Abdul Rafae
- Department of Internal Medicine, McLaren Regional Medical Center, Flint, MI, USA
| | - Kamran Mushtaq
- Department of Hospital Medicine, Northeast Internal Medicine Associates, LaGrange, IN, USA
| | - Krishna Venkata
- UAB Montgomery Internal Medicine Residency, Baptist Medical Center South, Montgomery, AL, USA
| | - Rehan Sarmad
- Department of Hematology-Oncology, Alabama Oncology Hematology Associates, Montgomery, AL, USA
| |
Collapse
|
|
32
|
Sato H, Shiota M, Urano M, Tsukamoto T, Honda K, Toyama K, Uyama I. Mixed neuroendocrine-non-neuroendocrine neoplasm with squamous cell carcinoma covered by tubulovillous adenoma in the rectum. Clin J Gastroenterol 2021; 14:1136-1141. [PMID: 33905093 DOI: 10.1007/s12328-021-01420-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 04/15/2021] [Indexed: 12/19/2022]
Abstract
A variety of histologies is often mixed in neuroendocrine carcinoma (NEC) called mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). However, tumors consisting of both large-cell NEC and squamous cell carcinoma (SCC) are rare. NEC of the large intestine is aggressive; however, an ideal treatment strategy has not been established. In this study, we have reported a case of rectal MiNEN containing large-cell NEC and SCC that was covered by tubulovillous adenoma. A 73-year-old man was referred to our hospital for the treatment of an upper rectal tumor. The results of preoperative biopsy indicated tubulovillous adenoma, whereas computed tomography revealed multiple liver tumors and swollen lymph nodes around the rectum. Laparotomy was performed because of severe dyschezia caused by rectal stenosis. Hartmann's operation was performed because of peritoneal metastases. Histopathological examination of the rectal tumor revealed MiNEN containing large-cell NEC, SCC, well-differentiated adenocarcinoma, and tubulovillous adenoma covering the surface of the tumor. The patient died 73 days after surgery due to liver metastases. It is important to consider NEC in the differential diagnosis and tissue sampling should be performed to ensure appropriate management when pathological findings and clinical diagnosis do not match. More research is required to determine the ideal treatment for these rare and aggressive tumors.
Collapse
Affiliation(s)
- Harunobu Sato
- Department of Surgery, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
| | - Miho Shiota
- Department of Surgery, Kaisei Hospital, Sakaide, Japan
| | - Makoto Urano
- Department of Pathology, School of Medicine, Fujita Health University, Toyoake, Japan
| | - Tetsuya Tsukamoto
- Department of Pathology, School of Medicine, Fujita Health University, Toyoake, Japan
| | | | | | - Ichiro Uyama
- Department of Surgery, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan
| |
Collapse
|
|
33
|
Gopalakrishnan G, Srinivas BH, Pottakkat B, Gnanasekaran S, Kalayarasan R. Perforated High-Grade Mixed Neuroendocrine Nonneuroendocrine Neoplasm of Cecum: Unusual Presentation of Rare Disease. Gastrointest Tumors 2021; 8:128-133. [PMID: 34307311 DOI: 10.1159/000512237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 09/21/2020] [Indexed: 11/19/2022] Open
Abstract
Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) are rare neoplasms of the gastrointestinal tract, where the neuroendocrine as well as the nonneuroendocrine components each comprise at least 30% of the tumor. Of all cases of colorectal malignancies, MiNENs constitute around 3-9.6%, with only a few cases reported to be arising in the cecum. Since majority present with nonspecific clinical and radiological findings, its diagnosis preoperatively is almost impossible and these are usually diagnosed after histopathological examination of the resected specimen. Owing to the rarity of these tumors as well as lack of complete molecular characterization, optimal treatment remains unestablished. We, here, report a rare case of MiNENs of the cecum infiltrating the right psoas muscle and presenting with perforation for which right hemicolectomy and en bloc excision of the involved psoas muscle was done followed by adjuvant chemotherapy.
Collapse
Affiliation(s)
- Gunasekaran Gopalakrishnan
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | | | - Biju Pottakkat
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Senthil Gnanasekaran
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Raja Kalayarasan
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| |
Collapse
|
|
34
|
Targeted Cancer Therapy: What's New in the Field of Neuroendocrine Neoplasms? Cancers (Basel) 2021; 13:cancers13071701. [PMID: 33916707 PMCID: PMC8038369 DOI: 10.3390/cancers13071701] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/29/2021] [Accepted: 03/31/2021] [Indexed: 12/18/2022] Open
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms of increasing incidence and high prevalence due to their relatively indolent nature. Their wide anatomic distribution and their characteristic ability to secrete hormonally active substances pose unique challenges for clinical management. They are also characterized by the common expression of somatostatin receptors, a target that has been extremely useful for diagnosis and treatment (i.e., somatostatin analogues (SSAs) and peptide-receptor radionuclide therapy (PRRT)). Chemotherapy is of limited use for NETs of non-pancreatic origin, and the only approved targeted agents for advanced progressive NETs are sunitinib for those of pancreatic origin, and everolimus for lung, gastrointestinal and pancreatic primaries. Despite recent therapeutic achievements, thus, systemic treatment options remain limited. In this review we will discuss the state-of-the-art targeted therapies in the field of NETs, and also future perspectives of novel therapeutic drugs or strategies in clinical development, including recently presented results from randomized trials of yet unapproved antiangiogenic agents (i.e., pazopanib, surufatinib and axitinib), PRRT including both approved radiopharmaceuticals (177Lu-Oxodotreotide) and others in development (177Lu-Edotreotide, 177Lu-Satoreotide Tetraxetan), immunotherapy and other innovative targeted strategies (antibody-drug conjugates, bites,…) that shall soon improve the landscape of personalized treatment options in NET patients.
Collapse
|
|
35
|
Chen Y, Tu J, Zhou S, Fu J, Wang Q. Poorer prognosis for neuroendocrine carcinoma than signet ring cell cancer of the colon and rectum (CRC-NEC): a propensity score matching analysis of patients from the Surveillance, Epidemiology, and End Results (SEER) database. Int J Colorectal Dis 2021; 36:745-756. [PMID: 33415449 DOI: 10.1007/s00384-020-03809-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/23/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Colorectal neuroendocrine carcinomas (CRC-NECs) are rare, comprising < 1% of colorectal cancers. This study aimed to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes of CRC-NEC. METHODS We analysed the Surveillance, Epidemiology, and End Results (SEER) database to identify patients from 20 to 74 years old diagnosed with CRC-NEC or common CRC (non-NEC) during 2004-2013. Log-rank testing was conducted to assess survival differences. A competing-risks regression model was used to adjust for covariate effects in the propensity score-matched (PSM) cohort, and adjusted hazard ratios (HRs) were calculated for the raw and PSM cohorts. RESULTS We identified 67,484 patients (344 CRC-NEC and 67,140 non-NEC). Lymph node metastasis (LNM) was more common in CRC-NEC (75.29%, n = 259) than in non-NEC (51.53%, n = 34,600) (P < 0.001); 56.40% (n = 194) of CRC-NECs were located on the right side, while 18.31% (n = 63) were located on the left side, with a statistically significant difference in distribution (P < 0.001) compared to that in non-NEC CRC. Multivariate analysis indicated that a left-side location was an independent adverse prognostic factor for CRC-NEC (P = 0.043). CRC-NEC had the poorest cancer-specific survival (median CSS, 9.0 months) among assessed cancers, even poorer than that of signet ring cell cancer (median CSS, 24.0 months). However, both radical operation (P = 0.007) and chemotherapy (P = 0.008) were beneficial for CSS. CONCLUSION NEC is a rare and extremely aggressive tumour with a poor prognosis. Right-side NEC has a better prognosis than left-side NEC. Early diagnosis, radical surgery, and chemotherapy are imperative for improving survival.
Collapse
Affiliation(s)
- Youwei Chen
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China
| | - Jiangfeng Tu
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China
| | - Shishi Zhou
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, China
| | - Jianfei Fu
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, China.
| | - Qinghua Wang
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, China.
| |
Collapse
|
|
36
|
Lee SM, Sung CO. Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas. Sci Rep 2021; 11:6203. [PMID: 33737597 PMCID: PMC7973429 DOI: 10.1038/s41598-021-85593-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 03/02/2021] [Indexed: 12/28/2022] Open
Abstract
Poorly differentiated neuroendocrine carcinoma (NEC) is a rare subtype of colorectal cancer (CRC). This study aimed to investigate clinicopathologic characteristics of colorectal NECs and elucidate genomic differences and similarities between colorectal NECs and colorectal adenocarcinomas (ACs). A total of 30 colorectal NECs were screened for frequently identified CRC oncogenic driver genes by targeted next-generation sequencing of 382 genes. The median age of the patients was 67 years (range, 44 to 88 years). NECs occurred predominantly in the rectum (47%) and exhibited multiple adverse prognostic pathologic factors, including frequent lymphatic and vascular invasions, high rates of lymph node metastasis and distant metastasis and advanced TNM stage. The 1-, 3-, and 5-year overall survival rates of NEC patients were 46.7%, 36.4%, and 32.7%, respectively, with a median overall survival period of 11.5 months. In a molecular analysis, NECs showed high rates of BRAF mutation (23%), predominantly p.V600E (71%), and alterations in RB1 (47%), particularly deletion (57%). The frequencies and distributions of other genes, such as KRAS, APC, SMAD4, and PIK3CA, and microsatellite instability status were similar to those of ACs. These findings provide beneficial information for selecting therapeutic options, including targeted therapy, and a better understanding of the histogenesis of this tumour.
Collapse
Affiliation(s)
- Sun Mi Lee
- Department of Pathology, Jeju National University Hospital, 15 Aran 13-gil, Jeju-si, 63241, Jeju-do, South Korea.
| | - Chang Ohk Sung
- Department of Pathology and Molecular Diagnostic Laboratory, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| |
Collapse
|
|
37
|
Gerosa M, Incarbone N, Di Fratta E, Mari GM, Guttadauro A, Cioffi U, Maggioni D. Incarcerated sigmoid large-cell neuroendocrine carcinoma in an inguinal hernia. J Surg Case Rep 2021; 2021:rjaa585. [PMID: 33604019 PMCID: PMC7880701 DOI: 10.1093/jscr/rjaa585] [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: 11/25/2020] [Accepted: 01/22/2021] [Indexed: 11/13/2022] Open
Abstract
Large-cell neuroendocrine carcinomas (NECs) of the colon are extremely rare aggressive tumors. A 79-year-old man presented at our hospital for muco-hematic diarrhea, weight loss and incarcerated hernia in his left groin. Colonoscopy revealed sigmoid stenosis. Computed tomography confirmed an incarcerated hernia containing sigmoid mass and massive abdominal adenopathy. In absence of colonic obstruction, the patient underwent elective palliative sigmoid resection and colostomy by laparoscopic approach, and direct hernia repair through inguinal access. Histopathological examination revealed a large cells sigmoid NEC. We report the first case of large-cell neuroendocrine colon cancer incarcerated in an inguinal hernia. Due to the advanced stage, we have performed a palliative laparoscopic resection in order to reduce surgical trauma, confirm pre-operative results and minimize post-operative complications, and direct hernia repair through inguinal access.
Collapse
Affiliation(s)
- Martino Gerosa
- Laparoscopic and Oncological General Surgery Department, ASST Monza, Desio Hospital, Via Mazzini 1, Desio, Italy
| | - Niccolò Incarbone
- Laparoscopic and Oncological General Surgery Department, ASST Monza, Desio Hospital, Via Mazzini 1, Desio, Italy
| | - Emanuele Di Fratta
- Laparoscopic and Oncological General Surgery Department, ASST Monza, Desio Hospital, Via Mazzini 1, Desio, Italy
| | - Giulio Maria Mari
- Laparoscopic and Oncological General Surgery Department, ASST Monza, Desio Hospital, Via Mazzini 1, Desio, Italy
| | - Angelo Guttadauro
- Department of Surgery, University of Milan Bicocca, Istituti Clinici Zucchi, Via Zucchi 24, Monza, Italy
| | - Ugo Cioffi
- Department of Surgery, University of Milan, Via F. Sforza 35, Milan, Italy
| | - Dario Maggioni
- Laparoscopic and Oncological General Surgery Department, ASST Monza, Desio Hospital, Via Mazzini 1, Desio, Italy
| |
Collapse
|
|
38
|
Ueberroth BE, Liu AJ, Starr JS, Hobday TJ, Ashman JB, Mishra N, Bekaii-Saab TS, Halfdanarson TR, Sonbol MB. Neuroendocrine Carcinoma of the Anus and Rectum: Patient Characteristics and Treatment Options. Clin Colorectal Cancer 2020; 20:e139-e149. [PMID: 33551318 DOI: 10.1016/j.clcc.2020.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/01/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Anorectal neuroendocrine carcinomas (NECs) are uncommon malignancies with poor prognosis. Consensus guidelines exist for treating extrapulmonary NEC. However, limited data is available to guide treatment for anorectal NEC. In this study, we sought to review the clinical characteristics and outcomes of patients with NEC of the rectum and/or anus at Mayo Clinic. PATIENTS AND METHODS This is a retrospective study of all patients with the diagnosis of NEC of the anus and/or rectum treated across Mayo Clinic sites since 2000. Baseline patient characteristics, tumor pathology, imaging profiles, treatment strategies utilized, and survival outcomes were analyzed. Kaplan-Meier analysis was used with a significance level of P < .05. RESULTS The study included a total of 38 patients with primary NEC of the anus and/or rectum. The median age at diagnosis was 55.5 years. The median follow-up was 18.8 months. Fifteen patients had locoregional disease (LRD) at diagnosis. The remaining 23 had metastatic disease. Overall survival was significantly shorter in patients with LRD compared with those with metastatic disease at diagnosis (18.1 vs. 13.8 months; P = .039). The majority (n = 11) of patients with LRD were treated with concurrent chemoradiation therapy, and 10 underwent surgical resection of the primary tumor. The majority (13/15) of patients with LRD progressed, with the majority (11/15) of progressions being distant. The median progression-free survival for patients with LRD was 5.7 months (1-year progression-free survival, 26.7%). CONCLUSION Anorectal NEC is an aggressive malignancy with poor prognosis requiring multidisciplinary discussion. In addition, the systemic nature of anorectal NEC with distant recurrences in LRD and poor outcomes in metastatic disease emphasizes the need to further develop better systemic treatment options that can potentially improve outcomes in NEC.
Collapse
Affiliation(s)
| | - Alex J Liu
- Department of Internal Medicine, Mayo Clinic, Phoenix, AZ
| | - Jason S Starr
- Department of Oncology, Mayo Clinic, Jacksonville, FL
| | | | | | - Nitin Mishra
- Department of Colon and Rectal Surgery, Mayo Clinic, Phoenix, AZ
| | | | | | | |
Collapse
|
|
39
|
Suga K, Ogawa H, Sohda M, Katayama C, Ozawa N, Osone K, Okada T, Shiraishi T, Katoh R, Sano A, Sakai M, Yokobori T, Shirabe K, Saeki H. A case of colorectal large cell neuroendocrine carcinoma accompanied by disseminated peritoneal leiomyomatosis. Surg Case Rep 2020; 6:316. [PMID: 33296060 PMCID: PMC7726067 DOI: 10.1186/s40792-020-01069-4] [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: 09/02/2020] [Accepted: 11/05/2020] [Indexed: 11/23/2022] Open
Abstract
Background Neuroendocrine carcinomas (NECs) of the colon are among the rarest types of colorectal cancers. Among these, large cell type neuroendocrine carcinoma (LCNEC) is particularly rare. Colorectal NEC is an aggressive disease, and there are few reports of long-term survivors. Here, we report a case of LCNEC accompanied by disseminated peritoneal leiomyomatosis that was difficult to diagnose. Case presentation The case involves a 62-year-old female found to be positive for fecal occult blood by medical examination. An endoscopy revealed a tumor in the ascending colon, and the biopsy revealed poorly differentiated cancer. Abnormal FDG accumulation with peritoneal thickening was visible on 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) and suspected to be peritoneal dissemination. Laparoscopic ileocecal resection was performed for the tumor of the ascending colon with abdominal wall invasion. At that time, numerous intra-abdominal nodules were observed, indicating peritoneal dissemination. The pathological diagnosis of the primary lesion was LCNEC, and the patient requested to undergo total peritoneal resection. After one course of chemotherapy with irinotecan plus cisplatin, she underwent total peritoneal resection, uterine annex resection, left inguinal lymph node resection, and intra-abdominal hyperthermic intraperitoneal chemotherapy with mitomycin C. Because a postoperative pathological examination revealed that the intra-abdominal nodules were leiomyomas, we diagnosed the patient with disseminated peritoneal leiomyomatosis. The left inguinal lymph node was diagnosed with a metastatic tumor. In summary, the final diagnosis was LCNEC in the ascending colon with inguinal lymph node metastasis. Postoperative chemotherapy has been administered to date. She is currently 18 months post-primary surgery and 15 months post-peritonectomy without apparent recurrence or metastatic findings. Conclusion We experienced a case of Stage IVa colorectal LCNEC accompanied by disseminated peritoneal leiomyomatosis. Although the prognosis is generally poor, multidisciplinary treatment for advanced colorectal LCNEC may result in a favorable outcome for some patients. If peritoneal dissemination is suspected during operation, sampling of the nodule to confirm the pathological diagnosis is advisable.
Collapse
Affiliation(s)
- Kunihiko Suga
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Hiroomi Ogawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Makoto Sohda
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan.
| | - Chika Katayama
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Naoya Ozawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Katsuya Osone
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Takuhisa Okada
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Takuya Shiraishi
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Ryuji Katoh
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Takehiko Yokobori
- Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), 3-39-22 Showa-machi, Maebashi, Gunma, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, 371-8511, Japan
| |
Collapse
|
|
40
|
Xiao C, Song B, Yi P, Xie Y, Li B, Lian P, Ding S, Lu Y. Deaths of colon neuroendocrine tumors are associated with increasing metastatic lymph nodes and lymph node ratio. J Gastrointest Oncol 2020; 11:1146-1154. [PMID: 33456989 PMCID: PMC7807263 DOI: 10.21037/jgo-20-444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 11/25/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Colon neuroendocrine tumors (NETs) are uncommon. Currently, the impact of the number of metastatic lymph nodes (LNs) and lymph node ratio (LNR) on survival has been well investigated in other colon malignancies, but both remain nebulous for patients with colon NETs. METHODS Surgically resected patients with histologically proven nonmetastatic colon NETs were queried from the Surveillance, Epidemiology, and End Results database between 1988 and 2011. Patients with lymph nodes involved were investigated and categorized into four LNs-based classifications (≤4, >4-10, >10-13, and >13) or three LNR-based subgroups (≤0.51, >0.51-0.71, and >0.71) according to the threshold, determined by Harrell's C statistic. Univariate and multivariate survival analyses were performed by log-rank test and Cox stepwise regression analysis, respectively. RESULTS Eight hundred fifty-one patients met the inclusion criteria. Among them, higher LNR and LNs classification are associated with a worse prognosis. The 10-year NETs-specific survival rate was 78.3% (74.2-82.6%), 61.3% (52.4-71.7%), 40.8% (20.7-80.7%) for patients in the ≤4, >4-10, and 10-13 LNs groups, respectively. When patients were classified with LNR, the observed 10-year NETs-specific survival rate was 79.9% (74.8-85.5%) for ≤0.51, 57.4% (43.8-75.2%) for >0.51-0.71, and 40.0% (31.0-51.5%) for >0.71. In stratified analysis, higher LNs and LNR groups have worse prognosis only in patients with advanced T stage (T3-T4). Regarding stage migration, the LNR-based system did not show superiority to LNs-based classification. CONCLUSIONS Current TNM staging classification could be improved by considering the count of metastatic nodes and LNR instead of a simple record of lymph node status (N1 or N0) for colon NETs.
Collapse
Affiliation(s)
- Changchun Xiao
- Department of General Surgery, Shanghai Electric Power Hospital, Shanghai, China
| | - Baorong Song
- Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Peipei Yi
- Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, China
| | - Yangyang Xie
- Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Biqing Li
- Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Peng Lian
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shaoqing Ding
- Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Yuanming Lu
- Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, China
| |
Collapse
|
|
41
|
Prognostic relevance of neuroendocrine differentiation in colorectal cancer: a population-based, propensity score matching study. Int J Colorectal Dis 2020; 35:2185-2195. [PMID: 32720185 DOI: 10.1007/s00384-020-03708-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/23/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Neuroendocrine differentiation (NED) may serve as a prognostic factor in colorectal cancer; however, the prognostic relevance of NED remains controversial. The aim of the present study was to determine whether NED influenced the survival of patients in colorectal cancer while exploring its potential interactions with other clinicopathological features. METHODS Patients with primary stage I to IV colorectal adenocarcinoma ranging between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier technique, Cox proportional hazards model, propensity score matching, and stratification analyses were employed in this study. RESULTS A total of 94,291 patients (including 101 patients with NED and 94,190 patients without NED) were included. In the univariable analyses, NED was found to be correlated with a significantly poorer overall survival (hazard ratio (HR) of death = 3.09, 95% CI 2.42-3.95, P < 0.001) and cancer-specific survival (HR of death = 3.77, 95% CI 2.94-4.83, P < 0.001). Moreover, NED remained independently correlated with overall survival (HR of death = 1.84, 95% CI 1.34-2.51, P < 0.001) and cancer-specific survival (HR of death = 2.01, 95% CI 1.45-2.79, P < 0.001) after adjusting in multivariable and propensity score analyses. Furthermore, further stratification analyses indicated that the influence of NED on survival was not affected by tumor location, differentiation, T stage, and distant metastasis status; however, it was found to be associated with lymph node metastasis. CONCLUSIONS NED is associated with poor survival outcomes among colorectal cancer patients, especially in those with positive lymph nodes.
Collapse
|
|
42
|
Woischke C, Jung P, Jung A, Kumbrink J, Eisenlohr S, Auernhammer CJ, Vieth M, Kirchner T, Neumann J. Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity. JOURNAL OF PATHOLOGY CLINICAL RESEARCH 2020; 7:75-85. [PMID: 33197299 PMCID: PMC7737761 DOI: 10.1002/cjp2.183] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 09/12/2020] [Accepted: 09/19/2020] [Indexed: 12/16/2022]
Abstract
We present two rare cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon. A literature search revealed only three published cases with similar histology but none of these reports provided profound molecular and mutational analyses. Our two cases exhibited a distinct, colon-like immunophenotype with strong nuclear CDX2 and β-catenin expression in more than 90% of the tumour cells of both components. We analysed the two carcinomas regarding microsatellite stability, RAS, BRAF and PD-L1 status. In addition, next-generation panel sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 was performed. This approach revealed mutations in FBXW7, CTNNB1 and PIK3CA in the first case and FBXW7 and RB1 mutations in the second case. We looked for similar mutational patterns in three publicly available colorectal adenocarcinoma data sets, as well as in collections of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) and colorectal neuroendocrine carcinomas. This approach indicated that the FBXW7 point mutation, without being accompanied by classical adenoma-carcinoma sequence mutations, such as APC, KRAS and TP53, likely occurs at a relatively high frequency in mixed neuroendocrine and squamous cell carcinoma and therefore may be characteristic for this rare tumour type. FBXW7 codifies the substrate recognition element of an ubiquitin ligase, and inactivating FBXW7 mutations lead to an exceptional accumulation of its target β-catenin which results in overactivation of the Wnt-signalling pathway. In line with previously described hypotheses of de-differentiation of colon cells by enhanced Wnt-signalling, our data indicate a crucial role for mutant FBXW7 in the unusual morphological switch that determines these rare neoplasms. Therefore, mixed large cell neuroendocrine and a squamous cell carcinoma can be considered as a distinct carcinoma entity in the colon, defined by morphology, immunophenotype and distinct molecular genetic alteration(s).
Collapse
Affiliation(s)
- Christine Woischke
- Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Peter Jung
- Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.,German Cancer Consortium (DKTK), partner site, Munich, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Andreas Jung
- Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.,German Cancer Consortium (DKTK), partner site, Munich, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jörg Kumbrink
- Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.,German Cancer Consortium (DKTK), partner site, Munich, Germany
| | | | - Christoph Josef Auernhammer
- Medizinische Klinik und Poliklinik 4, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.,Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Thomas Kirchner
- Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.,German Cancer Consortium (DKTK), partner site, Munich, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jens Neumann
- Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.,German Cancer Consortium (DKTK), partner site, Munich, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| |
Collapse
|
|
43
|
Large cell neuroendocrine carcinoma of the colon with brain metastasis: A case report. Int J Surg Case Rep 2020; 76:421-424. [PMID: 33099246 PMCID: PMC7585040 DOI: 10.1016/j.ijscr.2020.10.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 10/05/2020] [Indexed: 01/20/2023] Open
Abstract
Large cell neuroendocrine carcinoma of the colon is rare and aggressive, and its prognosis is very poor. Effective treatment of large cell neuroendocrine carcinoma of the colon has not been established. If local Large cell neuroendocrine carcinoma is completely resected, the 5-year survival rate has been reported to be 61%. Most patients are metastatic and not candidates for curative resection. The efficacy of systemic chemotherapy is highest in patients with poorly differentiated neuroendocrine tumors with a combination of cisplatin and etoposide. Background Large cell neuroendocrine carcinoma of the colon is rare, and its prognosis is very poor especially when diagnosed at a metastatic stage. Early diagnosis can allow early curative surgery that can increase the survival for more than 5 years. Case report We report a 62-year-old man who presented for neurologic signs and symptoms followed by constipation. He was diagnosed with large cell neuroendocrine carcinoma of the colon with brain metastasis. Patient was treated with right hemi colectomy due to obstructive gastro-intestinal symptoms, followed by chemotherapy (cisplatin and etoposide). Discussion Because of its rarity, effective treatment of large cell neuroendocrine carcinoma of the colon has not been established. If local large cell neuroendocrine carcinoma is completely resected, the prognosis can be largely influenced, and patients can benefit from a 5-year survival rate of 61% compared to 0% in patients without curative surgery. However, most patients are metastatic and not candidates for curative resection. The efficacy of systemic chemotherapy is highest in patients with poorly differentiated neuroendocrine tumors with a combination of cisplatin and etoposide. Conclusion Patient with metastatic large cell neuroendocrine tumor have very poor prognosis with a 1 year survival rate of 10% without curative surgery. Increasing awareness of these types of cancer and their prognosis, may allow better comprehension of the importance of screening to allow early diagnosis and better outcomes. In case of late presentation, palliative surgery is always a must in patients with obstruction, bleeding or perforation.
Collapse
|
|
44
|
Crown A, Simianu VV, Kennecke H, Lopez-Aguiar AG, Dillhoff M, Beal EW, Poultsides GA, Makris E, Idrees K, Smith PM, Nathan H, Beems M, Abbott D, Barrett J, Fields RC, Davidson J, Maithel SK, Rocha FG. Appendiceal Neuroendocrine Tumors: Does Colon Resection Improve Outcomes? J Gastrointest Surg 2020; 24:2121-2126. [PMID: 31749094 DOI: 10.1007/s11605-019-04431-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 10/16/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Appendiceal neuroendocrine tumors (A-NETs) are rare neoplasms of the GI tract. They are typically managed according to tumor size; however, the impact of surgical strategy on the short- and long-term outcomes is unknown. METHODS All patients who underwent resection of A-NET at 8 institutions from 2000 to 2016 were analyzed retrospectively. Patient clinicopathologic features and outcomes were stratified according to resection type. RESULTS Of 61 patients identified with A-NET, mean age of presentation was 44.7 ± 16.0 years and patients were predominantly Caucasian (77%) and female (56%). Mean tumor size was 1.2 ± 1.3 cm with a median of 0.8 cm. Thirty-one patients (51%) underwent appendectomy and 30 (49%) underwent colonic resection. The appendectomy group had more T1 tumors (87% vs 42%, p < 0.01) than the colon resection group. Of patients in the colon resection group, 27% had positive lymph nodes and 3% had M1 disease. R0 resections were achieved in 90% of appendectomy patients and 97% of colon resection patients. Complications occurred with a higher frequency in the colon resection group (30%) compared with those in the appendectomy group (6%, p = 0.02). The colon resection group also had a longer length of stay, higher average blood loss, and longer average OR time. Median RFS and OS were similar between groups. CONCLUSION A-NET RFS and OS are equivalent regardless of surgical strategy. Formal colon resection is associated with increased length of stay, OR time, higher blood loss, and more complications. Further study is warranted to identify patients that are likely to benefit from more aggressive surgery.
Collapse
Affiliation(s)
- Angelena Crown
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
- Section of General, Thoracic and Vascular Surgery, Virginia Mason Medical Center, 1100 Ninth Av, Seattle, WA, 98101, USA
| | - Vlad V Simianu
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
- Section of General, Thoracic and Vascular Surgery, Virginia Mason Medical Center, 1100 Ninth Av, Seattle, WA, 98101, USA
| | - Hagen Kennecke
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mary Dillhoff
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Eliza W Beal
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Eleftherios Makris
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Paula Marincola Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Hari Nathan
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Daniel Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - James Barrett
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Jesse Davidson
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Flavio G Rocha
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA.
- Section of General, Thoracic and Vascular Surgery, Virginia Mason Medical Center, 1100 Ninth Av, Seattle, WA, 98101, USA.
| |
Collapse
|
|
45
|
Metildi C, McLemore EC, Tran T, Chang D, Cosman B, Ramamoorthy SL, Saltzstein SL, Sadler GR. Incidence and Survival Patterns of Rare Anal Canal Neoplasms Using the Surveillance Epidemiology and End Results Registry. Am Surg 2020. [DOI: 10.1177/000313481307901023] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Small cell, neuroendocrine tumors, and melanoma of the anus are rare. Limited data exist on the incidence and management for these rare tumors. A large, prospective, population-based database was used to determine incidence and survival patterns of rare anal neoplasms. The Surveillance, Epidemiology and End Results registry was queried to identify patients diagnosed with anal canal neoplasms. Incidence and survival patterns were evaluated with respect to age, sex, race, histology, stage, and therapy. We identified 7078 cases of anal canal neoplasms: melanoma (n = 149), neuroendocrine (n = 61), and small cell neuroendocrine (n = 26). Squamous cell carcinoma (SCC) (n = 6842) served as the comparison group. Anal melanoma (AM) demonstrated the lowest survival rate at 2.5 per cent. Neuroendocrine tumors (NETs) demonstrated similar survival as SCC (10-year survival for regional disease of 25 and 22.3%, respectively). Ten-year survival of small cell NETs resembled AM (5.3 vs 2.5%). Age 60 years or older, sex, black race, stage, and surgery were independent predictors of survival. This study presents the largest patient series of rare anal neoplasms. NETs of the anal canal demonstrate similar survival patterns to SCC, whereas small cell NETs more closely resemble AM. Accurate histologic diagnosis is vital to determine treatment and surgical management because survival patterns can differ among rare anal neoplasms.
Collapse
Affiliation(s)
- Cristina Metildi
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
| | - Elisabeth C. McLemore
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
- Moores UCSD Cancer Center, University of California San Diego, San Diego, California
| | - Thuy Tran
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
| | - David Chang
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
| | - Bard Cosman
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
| | - Sonia L. Ramamoorthy
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
- Moores UCSD Cancer Center, University of California San Diego, San Diego, California
| | - Sidney L. Saltzstein
- Department of Family Medicine and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
- Moores UCSD Cancer Center, University of California San Diego, San Diego, California
| | - Georgia Robins Sadler
- From the Departments of Surgery and Preventive Medicine, Department of Pathology, University of California, San Diego, San Diego, California
- Moores UCSD Cancer Center, University of California San Diego, San Diego, California
| |
Collapse
|
|
46
|
Chen Y, Ohki R. p53-PHLDA3-Akt Network: The Key Regulators of Neuroendocrine Tumorigenesis. Int J Mol Sci 2020; 21:ijms21114098. [PMID: 32521808 PMCID: PMC7312810 DOI: 10.3390/ijms21114098] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/02/2020] [Accepted: 06/06/2020] [Indexed: 01/10/2023] Open
Abstract
p53 is a well-known tumor suppressor gene and one of the most extensively studied genes in cancer research. p53 functions largely as a transcription factor and can trigger a variety of antiproliferative programs via induction of its target genes. We identified PHLDA3 as a p53 target gene and found that its protein product is a suppressor of pancreatic neuroendocrine tumors (PanNETs) and a repressor of Akt function. PHLDA3 is frequently inactivated by loss of heterozygosity (LOH) and methylation in human PanNETs, and LOH at the PHLDA3 gene locus correlates with PanNET progression and poor prognosis. In addition, in PHLDA3-deficient mice, pancreatic islet cells proliferate abnormally and acquire resistance to apoptosis. In this article, we briefly review the roles of p53 and Akt in human neuroendocrine tumors (NETs) and describe the relationship between the p53-PHLDA3 and Akt pathways. We also discuss the role of PHLDA3 as a tumor suppressor in various NETs and speculate on the possibility that loss of PHLDA3 function may be a useful prognostic marker for NET patients indicating particular drug therapies. These results suggest that targeting the downstream PHLDA3-Akt pathway might provide new therapies to treat NETs.
Collapse
|
|
47
|
Nam S, Kim D, Jung K, Choi YJ, Kang JG. Analysis of the Incidence and Clinical Features of Colorectal Nonadenocarcinoma in Korea: A National Cancer Registry-Based Study. Ann Coloproctol 2020; 36:390-397. [PMID: 33486908 PMCID: PMC7837402 DOI: 10.3393/ac.2020.05.03.2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 05/03/2020] [Indexed: 02/07/2023] Open
Abstract
Purpose Although most colorectal malignancies are adenocarcinomas from mucosa, various types of malignant and benign tumors can develop. Due to extremely low incidence, little research has been conducted. The purpose was to assess incidence and compare it according to demographic factors. Methods Data from the Korea National Cancer Registry from 2007 to 2016 were used. The crude incidence, age-standard incidence rate (ASR) of colorectal nonadenocarcinomas were calculated. Results Over 11 years, there were 267,142 patients with colorectal malignancies. The patients of 14,495 (5.43%) were diagnosed with nonadenocarcinoma. The ASR was 2.52 per 100,000 in men and 1.56 in women. Lesions were classified according to histologic categories; neuroendocrine tumor (NET) was the most common malignancy (10,919 [75.33%]). Nonadenocarcinoma was the most common in 40s and 50s (40 to 49 years, 3,530 [24.35%]; 50 to 59 years, 3,991 [27.53%]). Lymphoma was high (54.46%) in patients in teenagers. Proportion of NET decreased with age and that of carcinoma increased with age. Carcinoma, sarcoma, and lymphoma were more common among men and melanoma was more common among women. The most common site was the rectum (11,066 [76.34%]). Lymphoma occurred more frequently in proximal colon. Melanoma, gastrointestinal stromal tumor, and NET occurred mostly in rectum. A total of 10,155 patients (70.06%) were classified as having localized disease. Conclusion This study is meaningful as it is the first study to examine incidence of colorectal nonadenocarcinoma. Differences in incidence of different lesions based on demographic factors were identified. This study will play a role in cancer prevention and diagnosis projects.
Collapse
Affiliation(s)
- Soomin Nam
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Dongwook Kim
- Big Data Department, National Health Insurance Service, Wonju, Korea
| | - Kyuwon Jung
- Divsion of Cancer Registration and Surveillance, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Yoon Jung Choi
- Department of Pathology, National Health Insurance Service Ilsan Hospital, Goyang, Korea.,Department of Pathology, Yonsei University Yongin Severance Hospital, Yongin, Korea
| | - Jung Gu Kang
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea.,Department of Surgery, Ilsan Cha Medical Center, Cha Medical University, Goyang, Korea
| |
Collapse
|
|
48
|
Successful Treatment of a Mixed Neuroendocrine-Nonneuroendocrine Neoplasm of the Colon with Metastases to the Thyroid Gland and Liver. Case Rep Otolaryngol 2020; 2020:5927610. [PMID: 32099708 PMCID: PMC7040413 DOI: 10.1155/2020/5927610] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 01/30/2020] [Indexed: 12/12/2022] Open
Abstract
Patients with mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the colon have poor prognosis. Herein, we report a patient with MiNEN of the colon with metastases to the liver and the thyroid gland, with long-term survival. A 45-year-old man presented with anterior neck swelling. Histopathological examination of the thyroid tumor revealed neuroendocrine carcinoma (NEC), suggesting that a primary NEC in another organ had metastasized to the thyroid gland. Computed tomography to identify a primary NEC revealed two tumors: one in the liver and one in the transverse colon. A biopsy revealed that the histopathology of the liver and colon tumors was NEC and adenocarcinoma, respectively. Thereafter, the patient underwent surgical resection of the colon tumor and was finally diagnosed as colon MiNEN with metastases to the thyroid and liver. The surgical resection of the metastatic liver tumor was performed after several courses of systemic chemotherapy, and the patient survives presently without any recurrence for approximately seven years after the diagnosis. Surgical resection of each metastatic lesion combined with systematic chemotherapy apparently improved the prognosis of MiNEN of the colon with distant metastases.
Collapse
|
|
49
|
Taggart MW, Foo WC, Lee SM. Tumors of the Gastrointestinal System Including the Pancreas. ONCOLOGICAL SURGICAL PATHOLOGY 2020:691-870. [DOI: 10.1007/978-3-319-96681-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
50
|
Ghanadan A, Jahanzad I, Abbasi A. Immunohistochemistry of Cancers. CANCER IMMUNOLOGY 2020:645-709. [DOI: 10.1007/978-3-030-30845-2_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|