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Akbari A, Pors J, Lum A, Leung S, Cochrane D, Jamieson A, McAlpine J, Kommoss S, Huvila J, Huntsman D, Talhouk A, Singh N, Gilks CB, Hoang L. Papillary and ductal patterns of mesonephric-like adenocarcinomas are often overlooked: a retrospective revaluation of over 1000 endometrial carcinomas. Histopathology 2025; 86:862-877. [PMID: 39687985 PMCID: PMC11964581 DOI: 10.1111/his.15393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/23/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024]
Abstract
AIMS Mesonephric-like adenocarcinoma (MLA) of the endometrium is often a diagnostic challenge, due to its morphological resemblance to other more common Müllerian neoplasms. This study aimed to retrospectively identify overlooked MLA in a large endometrial carcinoma cohort, using a combination of immunohistochemistry (IHC), morphology and KRAS sequencing. METHODS AND RESULTS IHC was conducted on 1094 endometrial carcinomas, identifying 16 potential MLA cases based on GATA3+ and/or TTF1+ and ER- staining patterns, which subsequently underwent detailed histological review, KRAS sequencing and ProMisE molecular classification. Of the IHC screen-positive cases, one was positive for both GATA3 and TTF1, nine were positive for GATA3 only and six were positive for TTF1 only. All IHC screen-positive cases were POLE wild-type. All five tumours in the NSMP category showed morphological features of MLA, while the three MMRd and eight p53abn tumours did not show MLA morphology. The five cases diagnosed as MLA on review were all originally diagnosed as low-grade endometrioid adenocarcinoma probably because of rare morphological patterns, being predominantly papillary or ductal. Four of the five cases harboured a KRAS mutation. CONCLUSION This study highlights the importance of a comprehensive diagnostic approach for accurately identifying endometrial MLA and for pathologists to be aware of papillary and ductal patterns in endometrial carcinoma assessment. Further exploration into the molecular landscape of MLA is essential for refining diagnostic criteria and developing targeted therapies.
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Affiliation(s)
- Ardalan Akbari
- Pathology and Laboratory MedicineUniversity of British Columbia and Vancouver General HospitalVancouverBC
| | - Jennifer Pors
- Pathology and Laboratory MedicineUniversity of British Columbia and British Columbia Cancer AgencyVancouverBC
| | - Amy Lum
- Molecular OncologyBritish Columbia Cancer Research CentreVancouverBC
| | - Samuel Leung
- Molecular OncologyBritish Columbia Cancer Research CentreVancouverBC
| | - Dawn Cochrane
- Molecular OncologyBritish Columbia Cancer Research CentreVancouverBC
| | - Amy Jamieson
- Gynecologic OncologyUniversity of British ColumbiaVancouverBCCanada
| | - Jessica McAlpine
- Gynecologic OncologyUniversity of British ColumbiaVancouverBCCanada
| | - Stefan Kommoss
- Department of Women's HealthTübingen University HospitalTübingenGermany
| | - Jutta Huvila
- Department of Pathology, University of TurkuTurku University HospitalTurkuFinland
| | - David Huntsman
- Pathology and Laboratory MedicineUniversity of British Columbia and Vancouver General HospitalVancouverBC
- Molecular OncologyBritish Columbia Cancer Research CentreVancouverBC
- Imagia Canexia Health, Inc.VancouverBCCanada
| | - Aline Talhouk
- Gynecologic OncologyUniversity of British ColumbiaVancouverBCCanada
| | - Naveena Singh
- Pathology and Laboratory MedicineUniversity of British Columbia and Vancouver General HospitalVancouverBC
| | - C Blake Gilks
- Pathology and Laboratory MedicineUniversity of British Columbia and Vancouver General HospitalVancouverBC
- Genetic Pathology Evaluation Center (GPEC) and Molecular and Advanced Pathology Core, (MAPCore)University of British ColumbiaVancouverBCCanada
| | - Lynn Hoang
- Pathology and Laboratory MedicineUniversity of British Columbia and Vancouver General HospitalVancouverBC
- Genetic Pathology Evaluation Center (GPEC) and Molecular and Advanced Pathology Core, (MAPCore)University of British ColumbiaVancouverBCCanada
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Sim A, Stolnicu S, Chauleur C, Patrichi G, Péoc'h M, Karpathiou G. Ovarian mucinous tumors do not usually harbor a mesonephric-like component. Pathol Res Pract 2025; 268:155862. [PMID: 40020331 DOI: 10.1016/j.prp.2025.155862] [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: 10/07/2024] [Revised: 02/18/2025] [Accepted: 02/24/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND The origin of primary mucinous ovarian tumors remains uncertain. Recently, a number of published cases suggested a possible mesonephric origin. The aim of this study is to investigate the association between these two types of proliferation and to determine whether the theory regarding this origin of ovarian mucinous tumors could be further supported. MATERIAL AND METHODS In our retrospective study, we included 406 patients diagnosed with a primary ovarian mucinous tumor. Clinical parameters were extracted from the patients' files. The slides were reexamined to identify any potential mesonephric-like elements. Foci harboring characteristics suggestive of a mesonephric-like component were subjected to an immunohistochemical analysis with GATA3 (Eurobio, L50-823) and TTF-1 (Dako-Agilent, clone 8G7G3/1) antibodies. RESULTS The mean age at diagnosis was 47.4 years (range 6-94 years). The tumors (n = 417, 15 bilateral cases) were mucinous cystadenomas/cystadenofibromas (n = 305), borderline mucinous tumors (n = 84) and mucinous carcinomas (n = 28). Associated Brenner tumors were present in 16 cases and teratomas in 8 cases. Morphological analysis revealed 64 cases with a component that could be considered mesonephric-like. Two of these were TTF-1 positive and one of them expressed GATA3 weakly and very focally. However, these were interpreted as non-specific of mesonephric differentiation. CONCLUSION Our series of 417 ovarian mucinous tumors revealed no associated mesonephric-like components. To date, only eight mucinous tumors associated with mesonephric-like foci have been reported in the literature. Our results indicate that the association between these two types of tissue is probably too rare to imply a potential role in their histogenesis.
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Affiliation(s)
- Angela Sim
- Pathology Department, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Simona Stolnicu
- Pathology Department, University of Medicine, Pharmacy, Sciences and Technology "George E Palade" of Targu Mures, Targu Mures, Romania
| | - Celine Chauleur
- Gynecology and Obstetrics Department, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Gabriela Patrichi
- Pathology Department, University of Medicine, Pharmacy, Sciences and Technology "George E Palade" of Targu Mures, Targu Mures, Romania
| | - Michel Péoc'h
- Pathology Department, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Georgia Karpathiou
- Pathology Department, University Hospital of Saint-Etienne, Saint-Etienne, France.
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Chi C, Li G, Zheng Z, Wang X, Liu X. Malignant Wolffian adnexal tumor in the ovary: a case report and literature review. Front Oncol 2025; 15:1526030. [PMID: 40171260 PMCID: PMC11958227 DOI: 10.3389/fonc.2025.1526030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/25/2025] [Indexed: 04/03/2025] Open
Abstract
Background Wolffian adnexal tumor (WAT) is a rare neoplasm originating from the remnants of the Wolffian duct (mesonephric duct). Malignant WAT occurring in the ovary is exceptionally uncommon. This article presents a case of malignant WAT in the ovary, analyzing and discussing its histological features, diagnostic challenges, biological behavior, and treatment options in conjunction with relevant literature to enhance our understanding of this rare tumor. Case presentation A 64-year-old woman presented with an 8-month history of persistent abdominal pain and distension. An exploratory laparotomy revealed a small amount of pale-yellow ascites, a slightly atrophic uterus, and a left ovary without significant abnormalities. A solid mass measuring approximately 12 × 10 cm was observed between the left fallopian tube and ovary, displaying extensive dense adhesions to the posterior broad ligament and surrounding bowel. Frozen section pathology indicated a malignant tumor with necrotic areas suggestive of poorly differentiated carcinoma. The patient subsequently underwent a total hysterectomy, bilateral adnexectomy, omentectomy, pelvic lymphadenectomy, and pelvic adhesion release. Adjuvant chemotherapy with four cycles of paclitaxel and carboplatin (TC regimen) was administered, achieving normalization of tumor markers by the second cycle. Conclusions WAT is a rare entity within the spectrum of female reproductive system tumors, predominantly benign in nature. Due to its extremely low incidence, standardized treatment protocols remain elusive. Further research is warranted to establish effective management strategies and provide a reference for future cases.
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Affiliation(s)
- Cheng Chi
- Minjiang Road Community Health Service Center, Shinan District Medical Health Group, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Guoliang Li
- Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Zian Zheng
- Medical Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xiangyu Wang
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xiangyu Liu
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
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Praiss A, Park K, Makker S, Girshman J, Aghajanian C, Grisham RN. Controversies in the Management of Mesonephric and Mesonephric-Like Adenocarcinomas of the Female Genital Tract. Int J Gynecol Cancer 2025; 35:101638. [PMID: 39914268 DOI: 10.1016/j.ijgc.2025.101638] [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: 11/04/2024] [Accepted: 01/06/2025] [Indexed: 03/18/2025] Open
Abstract
Mesonephric and mesonephric-like adenocarcinomas of the gynecologic tract are a rare subset of gynecologic tumors that are frequently associated with the presence of somatic KRAS mutations. Owing to their rare nature and ability to arise in different gynecologic sites, pathologic diagnosis is often challenging and under-represented. Immunohistochemistry and routine use of next-generation sequencing has allowed these cases to be more readily identified; however, there is still a paucity of clinical outcomes data, and the efficacy of treatment paradigms remains largely unknown. Historically, mesonephric and mesonephric-like adenocarcinomas were considered to be less responsive to systemic treatment, but response rates to first-line platinum-doublet chemotherapy for metastatic disease may be higher than initially suspected. Recurrent disease is often distant and located in the lungs, suggesting an important role of surveillance chest imaging. Given that most of these tumors are associated with somatic mitogen-activated protein kinase pathway mutations, a currently open phase II trial is assessing the dual RAF/MEK clamp avutometinib in combination with the FAK inhibitor defactinib in patients with recurrent mesonephric and mesonephric-like adenocarcinomas. Continued multi-institutional prospective trials are necessary to elucidate additional treatment options for these rare tumors.
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Affiliation(s)
- Aaron Praiss
- Memorial Sloan Kettering Cancer Center, Department of Surgery, Gynecology Service, New York, NY, USA
| | - Kay Park
- Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory Medicine, New York, NY, USA
| | | | - Jeffrey Girshman
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY, USA
| | - Carol Aghajanian
- Memorial Sloan Kettering Cancer Center, Gynecologic Medical Oncology Service, New York, NY, USA; Weill Cornell Medical College, Department of Medicine, New York, NY, USA
| | - Rachel N Grisham
- Memorial Sloan Kettering Cancer Center, Gynecologic Medical Oncology Service, New York, NY, USA; Weill Cornell Medical College, Department of Medicine, New York, NY, USA.
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Maharjan D, Collins K, Hou T, Umphress B, Robertson SE, Segura S. Synchronous Bilateral Ovarian Carcinomas With Right Mesonephric-like Adenocarcinoma and Left High-grade Serous Carcinoma: A Case Report and Review of the Literature. Int J Gynecol Pathol 2025; 44:193-197. [PMID: 39254222 DOI: 10.1097/pgp.0000000000001070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
Mesonephric-like adenocarcinomas (MLAs) are rare neoplasms of the uterus corpus and ovary, while high-grade serous carcinoma (HGSC) is the most common and lethal epithelial ovarian malignancy. We report a case of a 56-yr-old woman who presented with bilateral solid and cystic ovarian masses. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, lymphadenectomy, omentectomy, and peritoneal biopsies. Histopathologic examination of the bilateral ovarian masses revealed 1 ovary with MLA, and the other ovary showed HGSC in association with serous tubal intraepithelial carcinoma. The morphology, immunophenotypes, and molecular profiling of the HGSC and the MLA were distinct and as expected for the different tumor types: HGSC was diffusely positive for WT-1, estrogen receptor, and p53 (mutant pattern), while negative for GATA-3 and TTF-1; MLA was positive for GATA-3 and TTF-1, while negative for WT1, estrogen receptor, and p53 (wild-type pattern); both tumors were diffusely positive for PAX-8. The HGSC revealed a TP53 c.659A>G (p.Y220C) mutation, and the MLA revealed a KRAS c.34G>T (p. G12C) mutation and a PIK3CA c.1034A>T (p.N345I) mutation. To the best of our knowledge, this is the first reported case of synchronous bilateral ovarian carcinomas with MLA and contralateral ovarian HGSC.
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Affiliation(s)
| | | | - Tieying Hou
- Departments of Pathology and Laboratory Medicine
| | | | - Sharon E Robertson
- Gynecologic Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Travaglino A, Arciuolo D, Santoro A, Fulgione C, Piermattei A, Martinelli M, Onori ME, Minucci A, Raffone A, Inzani F, Zannoni GF. Ovarian endometrioid carcinoma with a sex cord-like pattern: a morphological, immunohistochemical, and molecular analysis. Virchows Arch 2025; 486:355-363. [PMID: 38418687 PMCID: PMC11876222 DOI: 10.1007/s00428-024-03743-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 01/03/2024] [Accepted: 01/15/2024] [Indexed: 03/02/2024]
Abstract
Sex cord-like endometrioid carcinoma (SCLEC) is an uncommon entity which may constitute a diagnostic challenge. This study aimed to perform a clinicopathological, immunohistochemical, and molecular reappraisal of ovarian SCLEC. Consecutive ovarian SCLECs cases from a single institution were reviewed during a 13-year period. Twenty-three immunohistochemical markers were tested; 10 genes were analyzed by next-generation sequencing. Nine cases of ovarian SCLEC were identified. Mean patient age was 65.7 years; three cases showed extraovarian extension. Architectural pattern included sertoliform (n = 2), granulosa-like (n = 2), and mixed granulosa-like/sertoliform (n = 5). Eosinophilic changes accompanied by increased nuclear atypia were observed in four tumors. Endometrioid features (glands, squamous/morular differentiation) were observed in six cases. Most tumors were positive for cytokeratin-7 (8/9), EMA (9/9), estrogen and progesterone receptor (9/9), CD10 (7/9, including a luminal pattern reminiscent of mesonephric neoplasms), nuclear β-catenin (8/9), and CDX2 (8/9). A minority of cases showed block-type p16 pattern (2/9), PAX8-positivity (3/9), and non-diffuse positivity for WT1 (1/9), inhibin (1/9), chromogranin (1/9), and synaptophysin (2/9). All cases were negative for GATA3, TTF1, calretinin, and SF1. Ki67 range was 15-90%. Six cases showed CTNNB1 exon 3 mutation. Eight cases were of "no specific molecular profile" (NSMP) and one was p53-abnormal. In conclusion, SCLECs frequently exhibit a mixed sertoliform/granulosa-like architecture and express epithelial markers, hormone receptors, nuclear β-catenin, and CDX2, with luminal CD10 positivity and CTNNB1 mutations. PAX8 expression is often lost, while other mesonephric, sex cord, and neuroendocrine markers are negative.
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Affiliation(s)
- Antonio Travaglino
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
| | - Damiano Arciuolo
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Pathology Institute, Catholic University of Sacred Heart, Rome, Italy
| | - Angela Santoro
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Pathology Institute, Catholic University of Sacred Heart, Rome, Italy
| | - Caterina Fulgione
- Gynecology and Obstetrics Unit, Department of Neurociences, Reproductive Sciences and Dentistry, Federico II University of Naples, Naples, Italy
| | - Alessia Piermattei
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Manuela Martinelli
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maria Elisabetta Onori
- Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Angelo Minucci
- Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Raffone
- Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria Di Bologna, S. Orsola Hospital, University of Bologna, Bologna, Italy
| | - Frediano Inzani
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Gian Franco Zannoni
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
- Pathology Institute, Catholic University of Sacred Heart, Rome, Italy.
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Suzuki N, Chikazawa K, Kato F, Ando S, Okabe N, Imai K, Kuwata T. Diagnostic Imaging Characteristics of a Rare Primary Ovarian Mesonephric-Like Adenocarcinoma: A Case Report and Literature Review. Cureus 2025; 17:e79780. [PMID: 40161201 PMCID: PMC11954648 DOI: 10.7759/cureus.79780] [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: 02/26/2025] [Indexed: 04/02/2025] Open
Abstract
Ovarian mesonephric-like adenocarcinoma is rare and poorly understood, and preoperative diagnosis of this tumor with any diagnostic modality is challenging. Histological features can only be speculated through imaging. Herein, we present the case of a 64-year-old woman with primary ovarian mesonephric-like adenocarcinoma, characterized by a 13 cm pelvic mass detected via ultrasound. Further evaluation with magnetic resonance imaging showed low signal intensity in the solid component on T2-weighted images and high signal intensity on diffusion-weighted images, along with a smooth margin; these findings are consistent with those of previous reports. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. Postoperative pathology confirmed mesonephric-like adenocarcinoma with positive peritoneal cytology. Immunohistochemical analysis showed a positive result for GATA-3 and a negative result for thyroid transcription factor-1. The patient was diagnosed with stage IC3 mesonephric-like adenocarcinoma, and adjuvant chemotherapy with paclitaxel and carboplatin was initiated. Mesonephric-like adenocarcinoma can present with distinct imaging features, including low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging, with a smooth solid margin; these imaging features may aid in the preoperative differentiation from other ovarian malignancies, such as serous or clear cell carcinomas.
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Affiliation(s)
- Nanami Suzuki
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
| | - Kenro Chikazawa
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
| | - Fumi Kato
- Department of Radiology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
| | - Shiori Ando
- Department of Diagnostic Pathology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
| | - Naota Okabe
- Department of Diagnostic Pathology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
| | - Ken Imai
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
| | - Tomoyuki Kuwata
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, JPN
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Liu L, Storino M, Chen YS, Walker A, Da Costa D, Shukla S, Graul A. Mesonephric and Mesonephric-like Adenocarcinomas of the Gynecologic Tract: A Case Series and a Review of the Literature. Int J Gynecol Pathol 2025:00004347-990000000-00222. [PMID: 39869067 DOI: 10.1097/pgp.0000000000001097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
We sought to present and describe all cases of mesonephric adenocarcinoma (MNAC) and mesonephric-like adenocarcinomas (MLAs) at our institution. These cancers are rare, morphologically similar tumors of the female reproductive tract. In this case series, we present 13 new cases of MNAC/MLA that were identified at St. Luke's University Health Network from 2016 to 2024. Demographics, clinical characteristics, and pathologic findings were collected from chart review. There were 6 uterine, 5 ovarian, and 2 cervical MNAC/MLAs. At presentation, more than half of the patients presented at early stages with 7, 2, 3, and 1 diagnosed at stages I, II, III, and IV, respectively. All patients underwent upfront surgical resection and were recommended adjuvant therapy. One patient declined adjuvant treatment. At the time of writing, 9 of 13 patients have completed treatment and have no evidence of disease, 1 is alive with disease, 1 is currently undergoing treatment, and 2 died of disease. Median overall survival (OS) was 15 mo (95% CI: 2.2-27.8 mo). Current literature regarding MNACs/MLAs suggests an overall poor prognosis, with the majority presenting at advanced stages. This case series describes patients diagnosed with early-stage disease and reports on their histopathology, treatment regimens, and clinical outcomes. The majority of these patients are without recurrence after upfront treatment. Continued surveillance of these patients to determine long-term outcomes is necessary to further elucidate overall prognosis.
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Affiliation(s)
- Lisa Liu
- Temple University/St. Luke's School of Medicine, Philadelphia
| | - Morgan Storino
- Temple University/St. Luke's School of Medicine, Philadelphia
| | | | - Allison Walker
- Department of Obstetrics & Gynecology, Division of Gynecologic Oncology
| | - Deline Da Costa
- Department of Pathology, St. Luke's University Health Network, Bethlehem, Pennsylvania
| | - Shivani Shukla
- School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Ashley Graul
- Department of Obstetrics & Gynecology, Division of Gynecologic Oncology
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9
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Tahir M, Xing D, Ding Q, Wang Y, Singh K, Suarez AA, Parwani A, Li Z. Identifying mesonephric-like adenocarcinoma of the endometrium by combining SOX17 and PAX8 immunohistochemistry. Histopathology 2025; 86:268-277. [PMID: 39233315 PMCID: PMC11649513 DOI: 10.1111/his.15312] [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: 06/24/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/06/2024]
Abstract
AIMS Mesonephric-like adenocarcinoma (MLA) of the endometrium or ovary is a rare but distinct endometrial carcinoma which has a combination of characteristic morphological, immunohistochemical (IHC) and molecular features. SOX17 has been recently identified as a highly sensitive and specific marker for endometrial and ovarian carcinomas. In this study, we aimed to investigate SOX17 expression in MLA together with other IHCs to differentiate MLAs from other endometrial carcinomas. METHODS Seventeen previously diagnosed endometrial/ovarian MLAs were collected, and multiple IHCs were performed. Additionally, we performed SOX17, PAX8 and ER on tissue microarrays (TMAs) composed of 652 endometrial carcinomas from 2012 to 2015 when MLA diagnostic criteria were not established. RESULTS All 17 MLAs showed diffuse strong positive PAX8, negative ER and variable TTF1/GATA3 staining. Notably, all MLAs showed negative (n = 10) or focal weak/moderate (n = 7) staining for SOX17, which is more diffuse and stronger than PAX8 in other endometrial carcinoma subtypes. This finding prompted us to screen TMAs with 652 endometrial carcinomas diagnosed before MLA by an approach of combined SOX17 and PAX8 IHCs, and 14 cases with positive PAX8 but negative/focal weak SOX17 were identified. We further studied the 14 cases by examining morphology and performing additional IHCs (TTF1, GATA3, ER and CD10) and would classify seven (50%) of them as MLAs based on morphological features and positive CD10, TTF1 and/or GATA3 staining. CONCLUSION Our results suggest that a combination of SOX17 and PAX8 IHCs would aid in diagnosing MLA if the results show strong positive PAX8, but negative SOX17.
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Affiliation(s)
- Maryam Tahir
- Department of PathologyThe Ohio State UniversityColumbusOHUSA
| | - Deyin Xing
- Department of PathologyThe John Hopkins UniversityBaltimoreMDUSA
| | - Qingqing Ding
- Department of PathologyUniversity of Texas, MD Anderson Cancer CenterHoustonTXUSA
| | - Yihong Wang
- Department of PathologyBrown UniversityProvidenceRIUSA
| | | | - Adrian A Suarez
- Department of PathologyThe Ohio State UniversityColumbusOHUSA
| | - Anil Parwani
- Department of PathologyThe Ohio State UniversityColumbusOHUSA
| | - Zaibo Li
- Department of PathologyThe Ohio State UniversityColumbusOHUSA
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Daas M, Pappa C, Shibli D, Al-Ani A, Dhar S, Manek S, Sayasneh A, Alazzam M. The Clinical Characteristics and Treatment Outcomes of Mesonephric Tumours of the Uterine Cervix: A Systematic Review and Proposal of Embryologically-Oriented Surgical Resection. J Clin Med 2024; 14:117. [PMID: 39797200 PMCID: PMC11721025 DOI: 10.3390/jcm14010117] [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: 10/21/2024] [Revised: 11/21/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: Cervical mesonephric adenocarcinomas (MNACs) are among the rarest neoplasms of the female genital tract. Unlike the majority of cervical cancers, which are predominantly squamous in origin and strongly associated with HPV seropositivity, MNACs are distinct in both histology and pathophysiology. Despite their unique characteristics, MNACs have historically been managed in parallel with squamous cell carcinomas, resulting in a lack of optimised, evidence-based treatment protocols. In this systematic review, we aim to evaluate the current management strategies for MNACs and their associated clinical outcomes. Additionally, we critically appraise existing surgical and adjuvant therapies and propose embryologically oriented surgical techniques to achieve optimal tumour resection. Methods: We performed a systematic search across the MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov databases from 1960 to June 2024. The search strategy employed a combination of keywords and MeSH terms, including "Uterine Cervical Neoplasms" [MeSH], "mesonephric tumour", "mesonephric neoplasm", and "mesonephric cancer". All relevant publications, including case reports and case series, were considered. Results: A total of 49 publications were finally included in the analysis, involving a thorough description of 91 MNAC cases. Most patients had stage I disease (70.8%) (n = 51). Hysterectomy was performed in 77 patients. The median follow-up was 29 months (range 1-199 months). Disease recurrence was observed in 35.2% (n = 25) of the cases, with the median disease-free survival (DFS) being 24 months (range 1-199). At the follow-up, 64.8% (n = 46) of patients remained in remission irrespective of the treatment modality, while 27.4% (n = 20) died due to disease progression. Conclusions: Mesonephric neoplasms of the uterine cervix are rare and clinically aggressive cancers that signify poor prognosis. Accurate identification and effective management can be challenging due to their particular anatomic and immunohistochemical characteristics. Therefore, a more tailored embryological-based approach should be considered for an optimal oncologic outcome.
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Affiliation(s)
- Mohammad Daas
- Basildon and Thurrock University Hospital, Basildon SS16 5NL, UK;
| | - Christina Pappa
- Oxford University Hospitals, NHS Foundation Trust, Oxford OX3 9DU, UK; (S.D.); (S.M.); (M.A.)
| | - Dana Shibli
- Jordan University Hospital, Amman 11942, Jordan;
| | | | - Sunanda Dhar
- Oxford University Hospitals, NHS Foundation Trust, Oxford OX3 9DU, UK; (S.D.); (S.M.); (M.A.)
| | - Sanjiv Manek
- Oxford University Hospitals, NHS Foundation Trust, Oxford OX3 9DU, UK; (S.D.); (S.M.); (M.A.)
| | - Ahmad Sayasneh
- Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH, UK;
| | - Moiad Alazzam
- Oxford University Hospitals, NHS Foundation Trust, Oxford OX3 9DU, UK; (S.D.); (S.M.); (M.A.)
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11
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Fan Y, He Y, Sun L, Liu T, Shen Y. Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component. Oncol Lett 2024; 28:508. [PMID: 39233819 PMCID: PMC11369853 DOI: 10.3892/ol.2024.14641] [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: 05/17/2024] [Accepted: 08/07/2024] [Indexed: 09/06/2024] Open
Abstract
Mesonephric adenocarcinomas (MAs) with spindle cell components are rare malignant cervical tumours. In the present study, a retrospective analysis of these tumours was performed. Clinicopathological data were gathered from electronic surgical pathology records, and both immunohistochemistry and targeted next-generation sequencing (NGS) were performed. The present study included three postmenopausal female patients diagnosed with primary uterine cervical MA with prominent spindle cell components, aged 51-60 years. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. There were no recurrences or deaths after surgery. NGS analysis identified KRAS mutations in 2 cases and a PIK3-catalytic subunit α (PIK3CA) mutation in another. Spindle cell components may indicate MAs at an advanced stage. Spindle cell components in MAs are diagnostic pitfalls, and the use of immunohistochemical panels and molecular detection cases with overlapping morphological features is recommended. While KRAS mutations are the most common types of mutations in MAs with spindle cell components, the present study demonstrates that PIK3CA mutations can also occur independently in cases without KRAS mutations.
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Affiliation(s)
- Yingying Fan
- Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610011, P.R. China
| | - Ying He
- Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610011, P.R. China
| | - Liang Sun
- Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610011, P.R. China
| | - Tianmin Liu
- Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610011, P.R. China
| | - Yangmei Shen
- Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610011, P.R. China
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12
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Alafraidi M, Hoang L, Howitt BE, Longacre TA, McAlpine JN, Jamieson A, Singh N, Gilks CB, Pors J. The spectrum of oestrogen receptor expression in endometrial carcinomas of no specific molecular profile. Histopathology 2024; 85:660-670. [PMID: 38890776 DOI: 10.1111/his.15241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/24/2024] [Accepted: 05/25/2024] [Indexed: 06/20/2024]
Abstract
AIMS Decreased oestrogen receptor (ER) expression is a marker of poor prognosis in endometrial carcinomas (EC) of no specific molecular profile (NSMP), but the optimal cut-off to separate high-risk 'low ER' versus low-risk 'high ER' expression has not been defined. Here we characterised the distribution of ER staining in a cohort of ECs. METHODS AND RESULTS Biopsy specimens from 120 cases of NSMP EC were stained for ER and assigned an Allred score. In 66 additional cases ER staining of matched biopsy and hysterectomy were compared. Twelve of 120 tumours had an Allred score of 0-3, including three endometrioid carcinomas (EEA) (one G1, two G3), four clear cell carcinomas (CCC), two mesonephric-like adenocarcinoma (MLA) and one each of: gastric-type adenocarcinoma, carcinosarcoma and endometrial carcinoma NOS. Three had Allred scores of 4-5: two MLA and one high-grade carcinoma with yolk sac differentiation. Five had Allred scores of 6: four EEA (one G1, one G2, two G3) and one mixed clear cell and endometrioid carcinoma. The remaining 100 tumours with Allred scores ≥ 7 were all EEA (66 G1, 28 G2, five G3 and one grade unknown). Comparing the biopsy versus hysterectomy ER staining (n = 66), the results were within a single Allred score point, except two cases with strong diffuse expression in the biopsy (Allred 8) and moderate expression in the hysterectomy (Allred 5). CONCLUSIONS Most NSMP ECs (> 80%) show high ER expression (Allred score ≥ 7). All non-endometrioid carcinomas and a few endometrioid carcinomas had lower ER expression (Allred score ≤ 6) or were completely negative.
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Affiliation(s)
- Mona Alafraidi
- Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - Lynn Hoang
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - Brooke E Howitt
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Teri A Longacre
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Jessica N McAlpine
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
| | - Amy Jamieson
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
| | - Naveena Singh
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - C Blake Gilks
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - Jennifer Pors
- Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
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13
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Yasuda M. New clinicopathological concept of endometrial carcinoma with integration of histological features and molecular profiles. Pathol Int 2024; 74:557-573. [PMID: 39175262 PMCID: PMC11551833 DOI: 10.1111/pin.13471] [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: 05/30/2024] [Revised: 07/22/2024] [Accepted: 07/26/2024] [Indexed: 08/24/2024]
Abstract
The dual-stratified pathway of endometrial carcinomas (ECs) has long been dominant. However, in 2013, The Cancer Genome Atlas (TCGA) defined four EC subgroups with distinctive prognoses. Inspired by TCGA, in 2018, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) provided four pragmatic molecular classifiers to apply surrogate immunohistochemical markers to TCGA subgroup categorization. These trends prompted the revision of 2020 WHO Classification of Female Genital Tumors, 5th edition (2020 WHO classification), in which four molecular subtypes are recognized: POLE-ultramutated; mismatch repair-deficient; p53-mutant; and no specific molecular profile. In the 2020 WHO classification, the diagnostic algorithm is characterized by prioritizing POLEmut over other molecular abnormalities. Following the 2020 WHO classification, Federation of International Gynecology and Obstetrics (FIGO) proposed a new staging system in 2023. The updated system focuses on diagnostic parameters, such as histological type and grade, lymphovascular space invasion, and molecular alterations. These new histomolecular diagnostic concepts of ECs are being accordingly introduced into the routine pathology practice. For the first time, the 2020 WHO classification includes mesonephric-like adenocarcinoma (MLA) as a novel histological entity, mimicking the conventional mesonephric adenocarcinoma, but is considered of Müllerian ductal origin.
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Affiliation(s)
- Masanori Yasuda
- International Medical Center, Department of PathologySaitama Medical UniversitySaitamaJapan
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14
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Quddus MR, Mathews CA, Singh K. Ever Expanding Morphologic Patterns of Mesonephric-like Adenocarcinomas of the Uterine Corpus: A Report of Two Tumors and a Brief Review of the Literature. Int J Surg Pathol 2024; 32:1398-1403. [PMID: 38311895 DOI: 10.1177/10668969241228285] [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] [Indexed: 02/06/2024]
Abstract
Mesonephric-like adenocarcinoma (MLA) of the endometrium shows a variety of morphologic appearances, including small glands, tubules with eosinophilic materials in the lumen, prominent papillary patterns, spindled cells, solid formations, and corded and hyalinized patterns. Unique morphology, characteristic immunohistochemical staining patterns, molecular alterations, and awareness of the pathologists make it possible to identify this tumor accurately. This report of two additional morphologic patterns, intestinal goblet cells mimicking intestinal-type mucinous carcinoma and squamous differentiation with spindle and epithelioid cells mimicking carcinosarcoma of the endometrium will expand the literature on MLA.
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Affiliation(s)
- M Ruhul Quddus
- Departments of Pathology and Laboratory Medicine, Women & Infants Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Cara A Mathews
- Department of Women's Oncology, Women & Infants Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Kamaljeet Singh
- Departments of Pathology and Laboratory Medicine, Women & Infants Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA
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15
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Nagase S, Saeki H, Ura A, Terao Y, Matsumoto T, Yao T. Mixed Mesonephric-like Adenocarcinoma, Clear Cell Carcinoma, and Endometrioid Carcinoma Arising from an Endometriotic Cyst. Int J Surg Pathol 2024; 32:1140-1148. [PMID: 37994045 DOI: 10.1177/10668969231213390] [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] [Indexed: 11/24/2023]
Abstract
Mesonephric-like adenocarcinoma is a rare neoplasm of the uterine corpus and ovary. Unlike prototypical mesonephric adenocarcinoma of the uterine cervix, which is considered of Wolffian origin, recent evidence suggests that mesonephric-like adenocarcinoma is a Mullerian tumor associated with endometriosis. We report here on a 48-year-old woman with a mixed carcinoma of the ovary that consisted of mesonephric-like adenocarcinoma, clear cell carcinoma, and endometrioid carcinoma, arising from an endometriotic cyst. The mesonephric-like adenocarcinoma consisted of cuboidal cells with vesicular nuclei presenting with a tubular, ductal, papillary, and solid architecture forming nodules. Each component showed distinct immunophenotypes that were consistent with their morphology. The mesonephric-like adenocarcinoma showed diffuse positive staining for paired box 8 and GATA binding protein 3, and negative staining for estrogen and progesterone receptors. A p53 stain exhibited wild-type immunoreactivity. A complete loss of AT-rich interactive domain-containing protein 1A (ARID1A) expression was suggestive of an ARID1A mutation. Manual macrodissection and Sanger sequencing revealed identical KRAS and PIK3CA mutations in all three components. To the best of our knowledge, this is the first report of mesonephric-like adenocarcinoma combined with a clear cell carcinoma and endometrioid carcinoma, which supports the hypothesis that mesonephric-like adenocarcinoma is an endometriosis-associated neoplasm. The report also highlights a potential pitfall in diagnosing mesonephric-like adenocarcinoma combined with clear cell carcinoma.
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Affiliation(s)
- Shunsuke Nagase
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Harumi Saeki
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Ayako Ura
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yasuhisa Terao
- Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Toshiharu Matsumoto
- Department of Diagnostic Pathology, Juntendo Nerima Hospital Faculty of Medicine, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan
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16
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Ogawa A, Yoshida H, Kawano S, Kikkawa N, Kobayashi-Kato M, Tanase Y, Uno M, Ishikawa M. Ovarian Mesonephric-like Adenocarcinoma: Its Prevalence in a Japanese High-Volume Cancer Center and a Literature Review on Therapeutic Targets. Curr Oncol 2024; 31:5107-5120. [PMID: 39330006 PMCID: PMC11430596 DOI: 10.3390/curroncol31090378] [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: 08/10/2024] [Revised: 08/26/2024] [Accepted: 08/28/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. METHODS We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. RESULTS Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52-76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). CONCLUSION MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.
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Affiliation(s)
- Ayako Ogawa
- Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan (M.K.-K.); (Y.T.)
| | - Hiroshi Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Saria Kawano
- Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan (M.K.-K.); (Y.T.)
| | - Nao Kikkawa
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Mayumi Kobayashi-Kato
- Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan (M.K.-K.); (Y.T.)
| | - Yasuhito Tanase
- Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan (M.K.-K.); (Y.T.)
| | - Masaya Uno
- Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan (M.K.-K.); (Y.T.)
| | - Mitsuya Ishikawa
- Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan (M.K.-K.); (Y.T.)
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17
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Keyhanian K, Mack T, Forgo E, Tazelaar H, Longacre TA. Female Adnexal Tumor of Probable Wolffian Origin (Wolffian Tumor): A Potential Mimic of Peritoneal Mesothelioma. Am J Surg Pathol 2024; 48:1041-1051. [PMID: 38919071 DOI: 10.1097/pas.0000000000002237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2024]
Abstract
Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include endometrioid adenocarcinoma and sex cord stromal tumors. However, the morphologic and immunohistochemical features of these tumors exhibit considerable overlap with peritoneal mesothelioma. To fully characterize their immunophenotypic signature, we examined a total of 21 cases (18 Wolffian and 3 STK11 adnexal tumors) with standard markers used in the diagnosis of mesothelioma. Morphologic and immunohistochemical (IHC) features were reviewed and additional IHC performed for cases with available material. Patient age ranged from 25 to 73 (mean: 51) years. Sites included adnexa/broad ligament (6, 28%), paratubal (5, 24%), ovary/paraovarian (5, 24%), tubal (intraluminal) (2, 9.5%), pelvis (2, 9.5%), and liver (1, 5%). The mean tumor size was 9.3 cm (range: 0.2 to 22 cm). The histomorphology in most cases (14/21, 66%) consisted of tubular to solid sheets of neoplastic cells lined by columnar to cuboidal cells containing uniform round to oval nuclei. Compressed tubules with slit-like lumens and sieve-like pattern were also seen in at least 7 (33%) cases. Three cases demonstrated interanastomosing cords and trabeculae of epithelioid cells with cribriform and microacinar patterns growing within prominent myxoid stroma as described in STK11 adnexal tumors. In the cases with available IHC for 3 mesothelial markers (calretinin, WT1, D2-40), 55.5% (5 of 9) showed reactivity with all 3 markers. In cases with at least 2 available mesothelial markers, 69% (11/16) were positive for 2 markers (mostly calretinin and WT1). Claudin-4, MOC31, and BER-EP4 were negative in most cases tested (78% [7/9], 71.4% [5/7], and 100% [6/6], respectively). Given the resemblance to mesothelioma, there was initial strong consideration and/or actual misdiagnosis of mesothelioma in 3 cases (14%). In summary, the morphologic and immunohistochemical features of Wolffian tumor and its recently defined relative, STK11 adnexal tumor, can lead to misdiagnosis of mesothelioma, particularly when encountered in the disseminated or metastatic setting. Wolffian tumor and STK11 adnexal tumor should be considered in the differential diagnosis of all pelvic and peritoneal mesotheliomas.
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Affiliation(s)
- Kianoosh Keyhanian
- Department of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Tanner Mack
- Department of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Erna Forgo
- Department of Pathology, Cleveland Clinic, Cleveland, OH
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18
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Lee Y, Alam MR, Kim JH, Kim CJ, Lee SL, Yim K. Collision Tumor of the Ovary: Adult Granulosa Cell Tumor and Mesonephric-like Adenocarcinoma. Diagnostics (Basel) 2024; 14:1412. [PMID: 39001303 PMCID: PMC11241221 DOI: 10.3390/diagnostics14131412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/25/2024] [Accepted: 06/30/2024] [Indexed: 07/16/2024] Open
Abstract
Collision tumors of the ovaries are rare, with only a few reports in the literature. Adult granulosa cell tumors are a relatively common primary tumor component of previously reported collision tumors. The combination of serous and mucinous tumors with adult granulosa cell tumors has been reported in several cases. On the other hand, mesonephric-like adenocarcinomas are rare neoplasms that commonly arise in the uterine corpus and ovaries. In this report, we present the case of a collision tumor composed of an adult granulosa cell tumor and mesonephric-like adenocarcinoma of the ovary in a 63-year-old woman. The initial magnetic resonance imaging findings showed a cystic mass with an internal hemorrhage, which suggested an adult granulosa cell tumor, and a solid mass with different enhancements. Microscopically, the tumor had two distinct components: An adult granulosa cell tumor and a mesonephric-like adenocarcinoma. Recognizing collision tumors consisting of slow-growing and aggressive tumors may prove beneficial in future diagnostic and treatment strategies.
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Affiliation(s)
- Yujin Lee
- Department of Hospital Pathology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Mohammad Rizwan Alam
- Department of Hospital Pathology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Jin-Hwi Kim
- Department of Obstetrics and Gynecology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Chan Joo Kim
- Department of Obstetrics and Gynecology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Su Lim Lee
- Department of Radiology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Kwangil Yim
- Department of Hospital Pathology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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19
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Tan CY, Li TT, Xu N, Guo HH. Mesonephric adenocarcinoma of the cervix: An analysis for 3 cases and literature review. Asian J Surg 2024; 47:3233-3234. [PMID: 38521750 DOI: 10.1016/j.asjsur.2024.03.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 03/14/2024] [Indexed: 03/25/2024] Open
Affiliation(s)
- Chun-Yan Tan
- The First People's Hospital of Shuangliu District, Chengdu City, China; West China Airport Hospital of Sichuan University, China
| | - Ting-Ting Li
- West China Second Hospital, Sichuan University, Chengdu, China
| | - Ning Xu
- The First People's Hospital of Shuangliu District, Chengdu City, China; West China Airport Hospital of Sichuan University, China.
| | - Hui-Hui Guo
- West China Second Hospital, Sichuan University, Chengdu, China
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20
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Miyama Y, Ogasawara A, Hasegawa K, Yasuda M. Premature Classification of Early-stage Endometrioid Ovarian Carcinoma With Mesonephric-like Differentiation as Mesonephric-like Adenocarcinoma. Int J Gynecol Pathol 2024; 43:362-372. [PMID: 38870078 DOI: 10.1097/pgp.0000000000001002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.
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21
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Hiller GGR, Höhn AK, Krücken I, Monecke A, Reske D, Brambs CE, Horn LC. Mucinous cystadenoma and benign mesonephric-like proliferation in the ovary - Further evidence for clonal relationship. Pathol Res Pract 2024; 258:155336. [PMID: 38723326 DOI: 10.1016/j.prp.2024.155336] [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: 09/08/2023] [Revised: 04/25/2024] [Accepted: 04/27/2024] [Indexed: 05/29/2024]
Abstract
Mesonephric-like adenocarcinomas rarely occur in the uterus and the ovary. Benign mesonephric-like (ML) proliferations and hyperplasia have been described solely within the ovary. Pathogenetic data are very limited. We report a case with microscopic focus of benign ML-proliferation in association with mucinous cystadenoma in the ovary. The immunophenotype was distinct (mucinous tumor: focal weak nuclear positivity for PAX-8, CK 7, patchy cytoplasmic positivity for p16 and negativity for estrogen receptor, CD 10, TTF-1, p53 wildtype; mesonephric component: diffusely positive for PAX-8, CK 7, luminal CD 10, TTF-1, focal staining for estrogen receptor, patchy cytoplasmic for p16, p53 wildtype). On NGS-analysis there was clonal mutation of KRAS p.G12C. The data provide additional evidence for the concept of transdifferentiation (Müllerian tissue representing Wolffian/mesonephric features on histology and immunostaining) within the pathogenesis of mesonephric proliferation of the female genital tract and demonstrate the clonal relationship between these distinct morphologic components.
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Affiliation(s)
- Grit Gesine Ruth Hiller
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Germany.
| | - Anne Kathrin Höhn
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Germany
| | - Irene Krücken
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Germany
| | - Astrid Monecke
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Germany
| | - Dennis Reske
- Institute for Pathology and Cytology Niederrhein, Geldern, Germany
| | | | - Lars-Christian Horn
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Germany
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22
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Sugitani A, Ogawa A, Yoshida H, Kobayashi-Kato M, Kikkawa N, Tanase Y, Uno M, Ishikawa M, Kato T. Ovarian Mesonephric-Like Adenocarcinoma With Recurrent Liver Metastases: A Case Report with Analysis of Therapeutic Molecular Targets. Int J Surg Pathol 2024; 32:578-585. [PMID: 37345348 DOI: 10.1177/10668969231183631] [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] [Indexed: 06/23/2023]
Abstract
Ovarian mesonephric-like adenocarcinoma (MLA) is a rare cancer subtype. We describe a patient with ovarian MLA wherein liver metastases developed 1 month after surgery. A phenotypic analysis of the tumor was performed to identify molecular therapeutic targets. A 53-year-old woman, without any symptoms, underwent uterine cancer screening. Transvaginal ultrasonography revealed an ovarian mass, and subsequent pelvic magnetic resonance imaging showed a 13 × 10 cm multicystic ovarian lesion with a solid part. No extra ovarian lesions were observed and a staging laparotomy was performed. Pathological examination revealed an MLA of the left ovary (stage IC1). The tumor comprised tumor cells in a tubular pattern with intraluminal eosinophilic material, as well as mixed glandular and papillary, cord-like, and solid patterns. Endometriosis was also observed. Immunohistochemically, the tumor cells were positive for PAX8, GATA3 (focal), TTF1 (focal), and CD10 (luminal) and negative for the estrogen receptor, progesterone receptor, and WT1. One month after surgery, computed tomography revealed multiple liver metastases. Additional immunohistochemistry for therapeutic targets revealed that the tumor cells were weakly positive for human epidermal growth factor receptor 2 (focal; score 1+), pan-tropomyosin receptor kinase-negative, programmed death-ligand 1-negative, and PMS2 and MSH6 intact. The companion homologous recombination deficiency test (MyChoice®) showed homologous recombination repair proficiency. These findings suggest that poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors may not be effective treatment options. A literature review revealed that data on therapeutic targets in MLA are scarce. In summary, we report a patient with ovarian MLA showing an aggressive clinical course and the phenotypic analysis of the tumor may contribute to the identification of therapeutic targets for MLA.
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Affiliation(s)
- Ayumi Sugitani
- Department of Diagnostic Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Ayako Ogawa
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Hiroshi Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | | | - Nao Kikkawa
- Department of Diagnostic Radiology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Yasuhito Tanase
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Masaya Uno
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Mitsuya Ishikawa
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Tomoyasu Kato
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
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Lee Y, Choi S, Kim HS. Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma. Int J Gynecol Pathol 2024; 43:221-232. [PMID: 37566876 PMCID: PMC11022992 DOI: 10.1097/pgp.0000000000000976] [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] [Indexed: 08/13/2023]
Abstract
Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor (TTF1), GATA-binding protein 3 (GATA3), and cluster of differentiation 10 (CD10). Only a few studies have examined the expression levels of MLD markers in endometrial endometrioid carcinomas (EECs). This study aimed to analyze the frequency and pattern of MLD marker expression in low-grade EECs. We performed immunostaining for the detection of TTF1, GATA3, and CD10 expression in 50 low-grade EEC tissue samples and evaluated their staining proportion and intensity. Nine tumors (18.0%) expressed at least one MLD marker in varying proportions and intensities, and 2 of these tumors were positive for 2 MLD markers (TTF1/GATA3 and GATA3/CD10, respectively). Three (6.0%) tumors showed moderate-to-strong nuclear TTF1 immunoreactivity in ≤5% of the tumor cells. Five tumors (10.0%) had at least moderate nuclear GATA3 staining, and three of them displayed a staining proportion of ≥15%. Three tumors (6.0%) were focal (mean proportion, 15%) but strongly positive for CD10. Our findings indicate that a subset of EEC can express one or more MLD markers with varying staining proportions and intensities. Given that a diagnosis of uterine mesonephric-like adenocarcinoma should be established based on a combination of characteristic histologic features, unique immunophenotypes, and confirmed molecular findings, pathologists should not exclude EEC based only on the presence of focal immunoreactivity for MLD markers. Awareness of the atypical expression patterns of MLD markers in EEC helps pathologists avoid misdiagnosing EEC as a uterine mesonephric-like adenocarcinoma.
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24
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Li Z, Liu D, Wei W, Huang Z, Mo Y, Huang H. Identification of characteristics and construction of nomogram to predict the survival probability of mesonephric carcinoma patients: A population-based analysis and a case report. Cancer Rep (Hoboken) 2024; 7:e1940. [PMID: 38030392 PMCID: PMC10809193 DOI: 10.1002/cnr2.1940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 10/16/2023] [Accepted: 11/11/2023] [Indexed: 12/01/2023] Open
Abstract
BACKGROUND Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of published guidelines. OBJECTIVE To summarize the characteristics and construct an external-validated nomogram to predict the survival of MC patients. METHOD Sixty-four qualified patients derived from the Surveillance, Epidemiology, and End Results Plus database, and one patient from the Guangzhou Red Cross Hospital were enrolled. The entire cohort was randomly divided into a development (70%) and a validation cohort (30%). The Kaplan-Meier method and univariate and multivariate Cox regression analyses were applied. Two nomograms were established to predict the 3-to-8-year survival probability of MC patients, which were evaluated by C-index, ROC curves, DCA curves, and calibration plots. RESULTS The average survival time of MC patients was 84.22 ± 50.66 months. No significant difference was shown among different groups of race, primary site, tumor differentiated grade, and FIGO stages, while different SEER stages did distinguish patients' survival time, which indicated that the SEER stage standards might be a better staging system in the MC patients than FIGO stage (p = .0835). Additional survival analyses showed that MC patients benefited from shorter waiting times to begin treatment, accepting surgery, regional lymph node examination, radiotherapy, and chemotherapy. Two nomograms were established, both of which got satisfied scores in C-index, ROC curves, DCA curves, and calibration plots. CONCLUSION Sufficient regional lymph nodes examined, and applying radiotherapy in high-risk patients are recommended in MC patients. Nomograms established in the present study had good predicting and discriminating capabilities, which would be helpful in patients' individual risk estimation, management, counseling, and follow-up.
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Affiliation(s)
- Zhuoran Li
- Department of RadiotherapyGuangzhou Red Cross Hospital of Jinan UniversityGuangzhouGuangdongChina
- Department of RadiologyGuangzhou Red Cross Hospital of Jinan UniversityGuangzhouGuangdongChina
| | - Dongyu Liu
- Department of RadiotherapyGuangzhou Red Cross Hospital of Jinan UniversityGuangzhouGuangdongChina
| | - Wenlong Wei
- Department of Burns and Plastic SurgeryGuangzhou Red Cross Hospital of Jinan UniversityGuangzhouGuangdongChina
| | - Zhisheng Huang
- Department of RehabilitationGuangzhou Hospital of Integrated Traditional Chinese and Western MedicineGuangzhouGuangdongChina
| | - Yuzhen Mo
- Department of RadiotherapyGuangzhou Red Cross Hospital of Jinan UniversityGuangzhouGuangdongChina
| | - Haowei Huang
- Department of RadiotherapyGuangzhou Red Cross Hospital of Jinan UniversityGuangzhouGuangdongChina
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25
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Ise K, Tanei ZI, Oda Y, Tanikawa S, Sugino H, Ishida Y, Tsuda M, Gotoda Y, Nishiwaki K, Yanai H, Hasegawa T, Nagashima K, Tanaka S. A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features. Int J Gynecol Pathol 2024; 43:41-46. [PMID: 37406360 DOI: 10.1097/pgp.0000000000000949] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023]
Abstract
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3 , were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.
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26
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Turashvili G, Hanley K. Practical Updates and Diagnostic Challenges in Endometrial Carcinoma. Arch Pathol Lab Med 2024; 148:78-98. [PMID: 36943242 DOI: 10.5858/arpa.2022-0280-ra] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2022] [Indexed: 03/23/2023]
Abstract
CONTEXT.— Clinical management of endometrial carcinoma largely depends on the morphologic parameters ascertained based on the pathologic evaluation of surgical resection specimens. However, there are numerous controversial and nonstandardized aspects of both the macroscopic and microscopic assessment of surgical specimens, including grossing, adequate sampling, diagnosis, staging, reporting, and ancillary testing. OBJECTIVE.— To provide a comprehensive practical review of standardized grossing, key morphologic findings for reporting and staging, and diagnostic and prognostic use of ancillary testing in endometrial carcinomas. DATA SOURCES.— The existing literature, recommendations of the International Society of Gynecological Pathologists, and specialty consensus guidelines. CONCLUSIONS.— This review article summarizes important aspects of the grossing and sampling of surgical resection specimens for microscopic examination, key morphologic parameters that are required for reporting and staging, and morphologic features and immunoprofiles helpful in the differential diagnosis of low-grade and high-grade endometrial carcinomas, as well as the current status of the molecular classification of endometrial carcinoma and human epidermal growth factor receptor 2 testing in serous carcinoma. The information presented herein can be helpful in overcoming diagnostic challenges and issues related to the pathology reporting of endometrial carcinoma to practicing anatomic pathologists.
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Affiliation(s)
- Gulisa Turashvili
- From the Department of Pathology, Emory University Hospital, Atlanta, Georgia
| | - Krisztina Hanley
- From the Department of Pathology, Emory University Hospital, Atlanta, Georgia
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27
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Jenkins TM, Mehr CR. Updates in the Use of Immunohistochemical Stains in Breast and Gynecologic Pathology. Arch Pathol Lab Med 2024; 148:33-47. [PMID: 37406290 DOI: 10.5858/arpa.2022-0467-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2023] [Indexed: 07/07/2023]
Abstract
CONTEXT.— The use of immunohistochemical stains in breast and gynecologic pathology has become increasingly complex, with various diagnostic, prognostic, and predictive applications. OBJECTIVE.— To provide an update and review of immunohistochemical stains used in the practice of breast and gynecologic pathology. Established and new entities are reviewed, with descriptions of histomorphology and immunohistochemical staining patterns and discussion of interpretive pitfalls. DATA SOURCES.— Data were obtained from review of the English-language literature and firsthand experience of the authors in breast and gynecologic pathology. CONCLUSIONS.— Many entities in breast and gynecologic pathology benefit from evaluation with various immunohistochemical stains. These studies not only aid in the diagnosis and staging of tumors but also can provide prognostic and predictive information. Updated guidelines for recommended ancillary studies such as mismatch repair, p53, and human epidermal growth factor receptor 2 (HER2) studies in endometrium, as well as estrogen and progesterone receptors and HER2 in breast, are discussed. Finally, the use and interpretation of established and novel immunohistochemical stains are discussed in various breast and gynecologic malignancies.
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Affiliation(s)
- Taylor M Jenkins
- From the Department of Pathology, University of Virginia Health System, Charlottesville (Jenkins)
| | - Chelsea R Mehr
- Diagnostic Medicine Institute, Geisinger Health System, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania (Mehr)
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28
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Cai L, Yang C, Gu Y, Dong L, Feng W. Case Report: The first report of PPP2R1A mutations in mesonephric-like adenocarcinoma of endometrial carcinoma. Front Oncol 2023; 13:1212648. [PMID: 38111534 PMCID: PMC10725978 DOI: 10.3389/fonc.2023.1212648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 11/02/2023] [Indexed: 12/20/2023] Open
Abstract
We performed clinical treatment, histopathology, immunohistochemistry and molecular analyses. To compare with the published literature and have a reference overview. A 57-year-old woman and a 77-year-old woman presented with mesonephric-like adenocarcinoma of endometrium at an early clinical stage. The former had no deep myometrial infiltration and no regional lymph node involvement. The latter had deep myometrial infiltration, presence of LVSI and no regional lymph node involvement. Both of the tumor cells were positive for PAX8, GATA-3,CD-10,TTF-1,AE1/AEs,Ki67,P53 and P16 in immunohistochemical staining (IHC)Test. Primary tumors were examined for gene mutations by next generation sequencing. The former was identified KRAS mutation. The latter had KRAS,PIKCA and PPP2R1A mutations. To our knowledge, it is the first time that PPP2R1A(protein phosphatase 2,regulatory subunit A,α) mutation in MLA is reported in English literature.
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Affiliation(s)
- Lei Cai
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chenmin Yang
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yijin Gu
- Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Lei Dong
- Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Weiwei Feng
- Department of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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29
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Trecourt A, Boujida I, Devouassoux-Shisheboran M. [Mesonephric lesions of female genital tract: An overview from benign tumors to emerging malignancy]. Ann Pathol 2023; 43:431-442. [PMID: 37481413 DOI: 10.1016/j.annpat.2023.07.001] [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: 06/21/2023] [Accepted: 07/04/2023] [Indexed: 07/24/2023]
Abstract
Mesonephric lesions in the female genital tract are uncommon and heterogeneous. Those deriving from the upper tract differ from those developing in the lower tract, based on their morphology and immunohistochemical profile. Carcinomas of mullerian origine may display the morphology, the immunoprofile and even the molecular abnormalities of those deriving from mesonephric remnants and are designated mesonephric-like carcinomas. These are high-grade lesions despite their well-differentiated glandular morphology (wolf in sheep's clothing). New entities, such as STK11 adnexal tumors, have merged recently and should not be confused with adnexal tumors of wolffian origin (FATWO), which have a better prognostic and outcome. In this review, we provide an overview of these lesions and their mimickers, in order to help pathologists in the diagnostic approach of these complex and rare neoplasms.
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Affiliation(s)
- Alexis Trecourt
- Département de pathologie Sud, hospices civils de Lyon, centre hospitalier Lyon Sud, université Claude-Bernard Lyon I, 69310 Pierre-Bénite, France
| | - Ismail Boujida
- Département de pathologie Sud, hospices civils de Lyon, centre hospitalier Lyon Sud, université Claude-Bernard Lyon I, 69310 Pierre-Bénite, France
| | - Mojgan Devouassoux-Shisheboran
- Département de pathologie Sud, hospices civils de Lyon, centre hospitalier Lyon Sud, université Claude-Bernard Lyon I, 69310 Pierre-Bénite, France.
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30
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Brambs CE, Horn LC, Hiller R, Krücken I, Braun C, Christmann C, Monecke A, Höhn AK. Mesonephric-like adenocarcinoma of the female genital tract: possible role of KRAS-targeted treatment-detailed molecular analysis of a case series and review of the literature for targetable somatic KRAS-mutations. J Cancer Res Clin Oncol 2023; 149:15727-15736. [PMID: 37668797 PMCID: PMC10620254 DOI: 10.1007/s00432-023-05306-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 08/16/2023] [Indexed: 09/06/2023]
Abstract
PURPOSE Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and immunohistochemical findings commonly associated with a KRAS-mutation. Most cases display an aggressive clinical behavior, but knowledge about treatment approaches is limited, especially for targeting KRAS. METHODS We report a series of eight cases with a detailed molecular analysis for KRAS. These cases as well as the data of previously published cases with detailed information regarding KRAS-mutational events were reviewed for a potential targeted approach and its prognostic impact. RESULTS Both the uterine and ovarian MLA harbor a somatic KRAS-mutation in about 85% of the reported cases, affecting the hotspot codons 12 and 13. 15.7% of the endometrial and 15.6% of ovarian MLA are wild type for KRAS. A p.G12A-alteration was seen in 5.6% (5/89) of the endometrial and in 6.2% (2/32) of the ovarian tumors, for p.G12C in 7.9% and 6.2%, for p.G12D in 32.6% and 34.5% and for p.G12V in 36% and 37.5%, respectively. Very limited data are available regarding the prognostic impact of different mutational sites within the KRAS-gene without significant prognostic impact. CONCLUSION Because of a specific p.G12C-KRAS somatic mutation, only the minority of MLA (7.9% with uterine and 6.2% with ovarian primary) are potentially targetable by sotarasib in that rare but aggressive subtype of adenocarcinoma of the female genital tract. Until now, the different location of a somatic KRAS-mutation is of no prognostic impact.
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Affiliation(s)
- Christine E Brambs
- Department of Obstetrics and Gynecology, Lucerne Cantonal Hospital, Spitalstrasse, 6000, Lucerne, Switzerland.
| | - Lars-Christian Horn
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Ruth Hiller
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Irene Krücken
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Christian Braun
- Department of Obstetrics and Gynecology, Lucerne Cantonal Hospital, Spitalstrasse, 6000, Lucerne, Switzerland
| | - Corina Christmann
- Department of Obstetrics and Gynecology, Lucerne Cantonal Hospital, Spitalstrasse, 6000, Lucerne, Switzerland
| | - Astrid Monecke
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Anne Kathrin Höhn
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
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31
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Wang L, Li Y, Han L. Pulmonary metastasis of stage I, low-grade endometrioid carcinoma: two case reports and the literature review. Front Oncol 2023; 13:1266485. [PMID: 37901321 PMCID: PMC10602667 DOI: 10.3389/fonc.2023.1266485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/20/2023] [Indexed: 10/31/2023] Open
Abstract
Endometrial cancer (EC) is the most common malignant tumor of the female reproductive system, and the majority of ECs are low histological grade and confined to the uterus, resulting in a good prognosis. However, metastasis to the lung from a low-grade and early-stage endometrial endometrioid carcinoma (EEC) is extremely rare. Therefore, it is crucial to accurately differentiate between primary pulmonary malignancy and extra-thoracic malignancy presenting as metastatic disease, and flexible bronchoscopy with tissue acquisition plays a key role in this process. Despite its importance, there is limited literature available on the cytology of metastatic endometrial carcinoma in liquid-based cytology of bronchial brush (BB). In this article, we present two rare cases of lung metastasis from low-grade and early-stage EEC, along with a detailed analysis of the cytologic features observed in BB samples. These cases highlight the significance of cytological and histological pathology, complemented by immunohistochemistry (ICH) analysis, in the diagnosis and management of EEC patients. Pathologists should pay close attention to these aspects, while gynecologists need to be mindful of the follow-up and management of early-stage, low-grade EEC patients. By focusing on these areas, healthcare professionals can effectively contribute to the improved care and outcomes of patients with EEC.
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Affiliation(s)
- Li Wang
- Department of Gynecology & Obstetrics, Liaocheng People's Hospital, School of Medicine, Liaocheng University, Liaocheng, China
- Biomedical Laboratory, School of Medicine, Liaocheng University, Liaocheng, China
| | - Yingxue Li
- Department of Pathology, Liaocheng People's Hospital, Liaocheng, China
| | - Lin Han
- Department of Pathology, Liaocheng People's Hospital, Liaocheng, China
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32
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Parkash V, Aisagbonhi O, Riddle N, Siddon A, Panse G, Fadare O. Recent Advances in the Classification of Gynecological Tract Tumors: Updates From the 5th Edition of the World Health Organization "Blue Book". Arch Pathol Lab Med 2023; 147:1204-1216. [PMID: 36596270 DOI: 10.5858/arpa.2022-0166-ra] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2022] [Indexed: 01/04/2023]
Abstract
CONTEXT.— The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice. OBJECTIVE.— To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology. DATA SOURCES.— The 4th and 5th editions of the World Health Organization Classification of Tumours. CONCLUSIONS.— The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice.
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Affiliation(s)
- Vinita Parkash
- From the Department of Pathology (Parkash, Siddon, Panse), Yale University School of Medicine, New Haven, Connecticut
| | - Omonigho Aisagbonhi
- Department of Pathology, University of California at San Diego, La Jolla, California (Aisagbonhi, Fadare)
| | - Nicole Riddle
- The Department of Pathology and Cell Biology, Ruffolo, Hooper, and Associates, University of South Florida College of Medicine, Tampa, Florida (Riddle, Siddon)
| | - Alexa Siddon
- From the Department of Pathology (Parkash, Siddon, Panse), Yale University School of Medicine, New Haven, Connecticut
- Department of Laboratory Medicine (Siddon), Yale University School of Medicine, New Haven, Connecticut
- The Department of Pathology and Cell Biology, Ruffolo, Hooper, and Associates, University of South Florida College of Medicine, Tampa, Florida (Riddle, Siddon)
| | - Gauri Panse
- From the Department of Pathology (Parkash, Siddon, Panse), Yale University School of Medicine, New Haven, Connecticut
- The Department of Dermatology (Panse), Yale University School of Medicine, New Haven, Connecticut
| | - Oluwole Fadare
- Department of Pathology, University of California at San Diego, La Jolla, California (Aisagbonhi, Fadare)
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Shahi M, Palsgrove DN, Ronnett BM, Lin J, Murdock TA. Mesonephric Adenomyofibroma: A Biphasic Vaginal Mass of Mesonephric Type With Molecular Analysis: A Case Report of a Rare Entity. Int J Gynecol Pathol 2023; 42:523-528. [PMID: 36811844 PMCID: PMC11843574 DOI: 10.1097/pgp.0000000000000945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
Mesonephric neoplasms of the lower female genital tract are rare. To date, there are scarce reports of benign biphasic vaginal mesonephric lesions, and none have included immunohistochemical and/or molecular analysis. A biphasic neoplasm of mesonephric-type was incidentally identified in the vaginal submucosal tissue of a 55-yr-old woman who underwent a right salpingo-oophorectomy for an ovarian cyst. The well-circumscribed, 5 mm nodule exhibited white-tan, firm homogenous cut surfaces. Microscopic examination showed a lobular arrangement of glands with columnar to the cuboidal epithelium and intraluminal eosinophilic secretions, embedded within a myofibromatous stroma. Cytologic atypia and mitotic activity were absent. Immunohistochemical staining for PAX8 and GATA3 demonstrated diffuse expression in the glandular epithelium, CD10 exhibited a patchy luminal expression pattern, while TTF1, ER, PR, p16, and NKX3.1 were negative. Desmin highlighted a subset of the stromal cells, but myogenin was negative. Whole exome sequencing demonstrated variants of unknown significance in multiple genes including PIK3R1 and NFIA . The morphologic and immunohistochemical profiles are consistent with a benign mesonephric neoplasm. This is the first report describing the immunohistochemical and whole exome sequencing results for a benign biphasic vaginal mesonephric neoplasm. To the best of our knowledge, benign mesonephric adenomyofibroma has not been previously reported in this anatomic location.
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Zheng W. Molecular Classification of Endometrial Cancer and the 2023 FIGO Staging: Exploring the Challenges and Opportunities for Pathologists. Cancers (Basel) 2023; 15:4101. [PMID: 37627129 PMCID: PMC10452831 DOI: 10.3390/cancers15164101] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 08/13/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
This commentary explores the complexities of the FIGO 2023 staging system and the inclusion of The Cancer Genome Atlas's (TCGA) molecular classification in the management of endometrial cancer. It highlights the importance of histology as a prognostic tool, while scrutinizing the merits and demerits of its application to aggressive endometrial cancers. The commentary review sheds light on the recent introductions of lymphovascular space invasion (LVSI) and lymph node metastasis size in cancer staging. It outlines the difficulties in differentiating between synchronous and metastatic endometrial and ovarian cancers, underlining their implications on treatment strategies. Furthermore, the commentary discusses the integration of molecular classifications within the FIGO 2023 framework, emphasizing the pivotal yet challenging implementation of the pathogenic POLE mutation test. The commentary concludes by reaffirming the vital role of pathologists in executing the FIGO 2023 staging system.
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Affiliation(s)
- Wenxin Zheng
- Department of Pathology, Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Pors J, Hoang L, Singh N, Gilks CB. Commentary: novel observations and detailed molecular characterisation of mixed tumours and mesonephric-like carcinosarcomas by Mirkovic et al. (2023). Histopathology 2023; 82:974-977. [PMID: 37191121 DOI: 10.1111/his.14900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 02/25/2023] [Indexed: 05/17/2023]
Affiliation(s)
- Jennifer Pors
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada
| | - Lynn Hoang
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - Naveena Singh
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - C Blake Gilks
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada
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Euscher ED, Marques-Piubelli ML, Ramalingam P, Wistuba I, Lawson BC, Frumovitz M, Malpica A. Extrauterine Mesonephric-like Carcinoma: A Comprehensive Single Institution Study of 33 Cases. Am J Surg Pathol 2023; 47:635-648. [PMID: 37026792 DOI: 10.1097/pas.0000000000002039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma (EnMLC). Its rarity and histologic overlap with Mullerian carcinomas contribute to underrecognition of ExUMLC. Aggressive behavior of EnMLC is well-documented; behavior of ExUMLC is yet to be characterized. This study presents the clinicopathologic, IHC, and MOL features of 33 ExUMLC identified over a 20-year time period (2002-2022) and compares the behavior of this cohort to more common upper gynecologic Mullerian carcinomas (low-grade endometrioid, LGEC; clear cell, CCC; high-grade serous, HGSC) and EnMLC diagnosed over the same time period. ExUMLC patients ranged from 37 to 74 years old (median=59 y); 13 presented with advanced stage (FIGO III/IV) disease. Most ExUMLC had the characteristic mixture of architectural patterns and cytologic features, as previously described. Two ExUMLC had sarcomatous differentiation, 1 with heterologous rhabdomyosarcoma. Twenty-one ExUMLC (63%) had associated endometriosis, and 7 (21%) arose in a borderline tumor. In 14 (42%) cases, ExUMLC was part of a mixed carcinoma representing >50% of the tumor in 12. Twenty-six cases (79%) were incorrectly classified as follows: LGEC or HGEC (12); adenocarcinoma, not otherwise specified (3); HGSC (3); LGSC (2); mixed carcinoma (1); carcinosarcoma, Mullerian type (2); seromucinous carcinoma (1); transitional pattern of HGSC (1); and female adnexal tumor of probable Wolffian origin (1). Three patients had occult synchronous endometrial LGEC. IHC facilitated diagnosis in all cases with an expression of GATA-3 and/or TTF-1 in conjunction with decreased hormone receptor expression in most tumors. MOL testing (n=20) identified a variety of mutations, most frequently: KRAS (15); TP53 (4); SPOP (4); and PIK3CA (4). ExUMLC and CCC were more likely to be associated with endometriosis ( P <0.0001). ExUMLC and HGSC had more recurrences compared with CCC and LGEC ( P <0.0001). Histologic subtype was associated with longer disease-free survival for LGEC and CCC versus HGSC and ExUMLC ( P <0.001). ExUMLC trended towards a similar poor overall survival as HGSC compared with LGEC and CCC, and EnMLC trended to shorter survival compared with ExUMLC. Neither finding reached significance. No differences were seen between EnMLC and ExUMLC with respect to presenting stage or recurrence. Staging, histotype, and endometriosis were associated with disease-free survival, but on multivariate analysis, only stage remained as an independent predictor of outcome. The tendency of ExUMLC to present at an advanced stage and have distant recurrence points to more aggressive behavior compared with LGEC with which it is most frequently confused, underscoring the importance of an accurate diagnosis.
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Affiliation(s)
| | | | | | | | | | - Michael Frumovitz
- Gynecologic Oncology, The University of MD Anderson Cancer Center, Houston, TX
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Ishida K, Ashihara T, So M, Minamiguchi S, Matsumura N, Nonogaki T. Synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma: A case report. J Obstet Gynaecol Res 2023; 49:1052-1056. [PMID: 36597276 DOI: 10.1111/jog.15539] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 12/13/2022] [Indexed: 01/05/2023]
Abstract
Mesonephric-like carcinoma histologically resembles mesonephric adenocarcinoma (MA) of the cervix. MA arises from mesonephric duct remnants. However, the origin of mesonephric-like carcinoma is not extensively studied because of its rarity. Here, we present a case of synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma. A 69-year-old woman presented with an abdominal mass with no genital bleeding. She underwent simple total abdominal hysterectomy and bilateral adnexal resection. Histological and immunohistochemical analyses were consistent with mesonephric-like carcinoma involving both ovaries and the uterus. Endometrioid adenofibroma was present in both ovaries, while adenomyosis was observed in the uterus. The glandular duct of the endometrioid adenofibroma in the right ovary had areas suggestive of precursor lesions of mesonephric-like carcinoma. All tumors exhibited the KRAS G12D mutation. These findings suggest that the origin of the mesonephric-like carcinoma was the Müllerian duct, and that the ovarian and uterine tumors were monoclonal.
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Affiliation(s)
- Kentaro Ishida
- Department of Obstetrics and Gynecology, Osaka Red Cross Hospital, Osaka, Japan
| | - Takahito Ashihara
- Department of Obstetrics and Gynecology, Osaka Red Cross Hospital, Osaka, Japan
| | - Makiko So
- Department of Obstetrics and Gynecology, Kyoto Katsura Hospital, Kyoto, Japan
| | - Sachiko Minamiguchi
- Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Noriomi Matsumura
- Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takafumi Nonogaki
- Department of Obstetrics and Gynecology, Osaka Red Cross Hospital, Osaka, Japan
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38
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Chibbar R, Foerstner S, Suresh J, Chibbar R, Piche A, Kundapur D, Kanthan R, Kundapur V, Lee CH, Agrawal A, Lai R. Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma. Appl Immunohistochem Mol Morphol 2023; 31:181-188. [PMID: 36695555 PMCID: PMC9988232 DOI: 10.1097/pai.0000000000001102] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 12/28/2022] [Indexed: 01/26/2023]
Abstract
A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 ( CTNNB1 ) and Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.
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Affiliation(s)
- Rajni Chibbar
- Department of Laboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, SK
| | - Sabrina Foerstner
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB
| | - Janarathnee Suresh
- Department of Laboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, SK
| | | | - Alexandre Piche
- Department of Laboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, SK
| | | | - Rani Kanthan
- Department of Laboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, SK
| | | | - Cheng Han Lee
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB
| | - Anita Agrawal
- Department of Obstetrics and Gynecology, Queen’s University, Kingston, ON
| | - Raymond Lai
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB
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Seo Y, Park E, Kim HS. Cytological features of mesonephric-like adenocarcinoma of the uterine corpus. Diagn Cytopathol 2023; 51:294-306. [PMID: 36756667 DOI: 10.1002/dc.25111] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 01/17/2023] [Accepted: 01/23/2023] [Indexed: 02/10/2023]
Abstract
BACKGROUND Although several studies have documented the histological features of uterine mesonephric-like adenocarcinoma (MLA), its cytological features have been rarely reported. METHODS We searched for histologically confirmed uterine MLA cases in the pathology archives of three institutions between 2010 and 2021. All available cytology slides were examined to identify the cytological features of uterine MLA. RESULTS We included 16 patients with uterine MLA and reviewed the slides obtained from 21 cytology samples. Samples were obtained from the cervicovagina (9/21, 42.9%), peritoneal washing (8/21, 38.1%), pleural effusion (2/21, 9.5%), and transbronchial needle aspiration of mediastinal lymph node (2/21, 9.5%). Preparation methods included ThinPrep (11/21, 52.4%), SurePath (8/21, 38.1%), and conventional smear (2/21, 9.5%). Regardless of the sampling site and preparation method, cytology samples displayed tight three-dimensional cellular clusters showing monotonous, small-to-medium-sized, round, hyperchromatic nuclei, indistinct nucleoli, scant cytoplasm, and high nuclear-to-cytoplasmic ratio. Approximately half of the samples (10/21, 47.6%) showed hyaline-like globules. Mitotic figures (7/21, 33.3%) and apoptotic bodies (13/21, 61.9%) were also observed. No tumor diathesis or nuclear feathering was identified. CONCLUSIONS Irrespective of sampling site and preparation method, the majority of uterine MLA cases showed the following cytological features: tight three-dimensional cellular clusters showing small-to-medium-sized, round, hyperchromatic nuclei with indistinct nucleoli and high nuclear-to-cytoplasm ratio. In case a cytology sample suspicious of a glandular lesion displays these cytological features, which are distinct from those of endocervical adenocarcinoma, uterine MLA should be included in the differential diagnosis.
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Affiliation(s)
- Youjeong Seo
- Department of Pathology, Inha University Hospital, Incheon, South Korea
| | - Eunhyang Park
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyun-Soo Kim
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry. Br J Cancer 2023; 128:1360-1368. [PMID: 36690721 PMCID: PMC10050005 DOI: 10.1038/s41416-023-02141-0] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 12/20/2022] [Accepted: 01/04/2023] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement. METHODS Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan-Meier method, log-rank tests and Cox's proportional hazard models were used for survival analysis. RESULTS In total, 648 HR-EC were included. No independent prognostic value of ER, PR, L1CAM, and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15-0.75). CONCLUSIONS We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.
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Xing D, Liang SX, Gao FF, Epstein JI. Mesonephric Adenocarcinoma and Mesonephric-like Adenocarcinoma of the Urinary Tract. Mod Pathol 2023; 36:100031. [PMID: 36788068 DOI: 10.1016/j.modpat.2022.100031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/19/2022] [Accepted: 09/21/2022] [Indexed: 01/19/2023]
Abstract
Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other anatomical locations that harbor mesonephric remnants. In contrast, mesonephric-like adenocarcinoma (MLA) is thought to arise from Müllerian origin without an association with mesonephric remnants. The current case series characterizes 4 cases of MA arising in the urinary bladder (1 woman and 3 men), 1 case of MA in the perirenal region (woman), and 1 case of MLA in the ureter (woman). All cases displayed morphologic features similar to MA of the uterine cervix and MLA of the ovary and endometrium, characterized by predominant tubular and focal glandular/ductal architecture. Mesonephric remnants in the bladder wall were closely associated with adjacent MA in cases 1 and 4. MLA in case 6 was associated with mesonephric-like proliferations and endometriosis. All cases (6/6) were diffusely positive for Pax8, and all displayed a luminal pattern of CD10 staining, except case 4 for which CD10 immunostain was not available for review. Gata3 was either focally positive (cases 1, 2, and 6), negative (case 3), or diffusely positive (case 5). TTF-1 was diffusely expressed in cases 1 and 3 and negative in cases 2, 5, and 6. Although a KRAS G12C somatic mutation was detected in case 6, hotspot mutations in KRAS, NRAS, and PIK3CA were not present in other tested cases. Our study demonstrates that MAs and MLAs of the urinary tract share similar histopathogenesis, morphology, and immunophenotype to their counterparts in the female genital tract. We propose that, in the urinary tract, MA might be classified as a distinctive tumor that arises from mesonephric remnants or presumed Wolffian origin if they are not related to Müllerian-type precursors. The tumor displaying similar morphology and immunoprofile to MA but associated with Müllerian-type precursors should be classified as MLA.
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Affiliation(s)
- Deyin Xing
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Sharon X Liang
- Department of Pathology, Allegheny Health Network/West Penn Hospital, Pittsburgh, Pennsylvania
| | - Faye F Gao
- Department of Pathology, MedStar Washington Hospital Center, Washington, District of Columbia
| | - Jonathan I Epstein
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
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PARK SUJIN, PARK EUNHYANG, KIM HYUNSOO. Mesonephric-like Carcinosarcoma of the Uterine Corpus: Clinicopathological, Molecular and Prognostic Characteristics in Comparison With Uterine Mesonephric-like Adenocarcinoma and Conventional Endometrial Carcinosarcoma. Cancer Genomics Proteomics 2022; 19:747-760. [PMID: 36316041 PMCID: PMC9620445 DOI: 10.21873/cgp.20357] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND/AIM This study aimed to investigate the clinicopathological, prognostic and molecular characteristics of uterine mesonephric-like carcinosarcoma (MLCS). PATIENTS AND METHODS We collected clinical, pathological, and genetic information from 12 MLCS patients, and analyzed their differences from mesonephric-like adenocarcinoma (MLA) and conventional endometrial carcinosarcoma (CECS). RESULTS The epithelial component was exclusively MLA in all MLCS cases. Metastatic and recurrent tumors consisted predominantly or exclusively of MLA in the majority of MLCS cases. Patients with MLCS and MLA presented with more advanced-stage disease than those with CECS. They also exhibited post-treatment recurrence and lung metastases more frequently than CECS. Disease-free survival rates of MLCS and MLA were shorter than those of CECS. Tumor protein 53 gene mutations were detected in four MLCS cases. CONCLUSION The predominance or exclusive presence of MLA in metastatic and recurrent tumors highlights the possibility that MLA may determine the clinical outcomes of patients with MLCS. Further studies are required to provide direct molecular evidence of the monoclonal origin of uterine MLCS.
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Affiliation(s)
- SUJIN PARK
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - EUNHYANG PARK
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - HYUN-SOO KIM
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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43
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Arslanian E, Singh K, James Sung C, Quddus MR. Somatic mutation analysis of Mesonephric-Like adenocarcinoma and associated putative precursor Lesions: Insight into pathogenesis and potential molecular treatment targets. Gynecol Oncol Rep 2022; 42:101049. [PMID: 35880223 PMCID: PMC9307462 DOI: 10.1016/j.gore.2022.101049] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 07/16/2022] [Indexed: 11/29/2022] Open
Abstract
Mesonephric-like adenocarcinoma is a recently described malignancy of the Müllerian tract. It can behave aggressively. It can arise in association with Müllerian lesions that share its molecular alterations. We analyzed 3 tumors and concurrent Müllerian lesions. We detected a previously unreported potentially actionable H1047Q variant of PIK3CA. Aims Mesonephric-like adenocarcinoma (MLA) is a recently described histologic tumor subtype of the Müllerian tract. MLA can arise in association with Müllerian lesions that share common mutations. We report three MLAs and hypothesize that concurrent endometriosis and cystadenofibroma with focal borderline changes might also carry common mutations. Methods and results We searched “mesonephric” in our database from 2015 to mid-2021 to retrieve MLA cases. Somatic mutation analysis was performed on tumors and on associated benign proliferative lesions. All MLAs (2 ovarian and 1 uterine) harbored KRAS G12D or G12 V mutations. A PIK3CA alteration (H1047Q) was detected in one MLA and in the associated cystadenofibroma with focal borderline changes. The molecular profile of MLA-associated Müllerian lesions (endometriosis and seromucinous cystadenofibroma with focal borderline changes) was similar to concurrent adenocarcinoma. However, tumor contamination could not be excluded in the endometriotic lesion. Patients presented at various stages, with no evidence of post-operative recurrence after 15 months (FIGO IC) and 33 months (FIGO IIA2). One patient (FIGO IIIA1) died of disease 32 months after surgery. Conclusions KRAS mutations commonly characterize MLA. At least some MLA-associated Müllerian lesions show MLA-like genetic profiles, suggesting a precursor role. As far as we are aware, we describe for the first time in MLA the potentially actionable H1047Q variant of PIK3CA.
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Affiliation(s)
- Elizabeth Arslanian
- Brown University/Women & Infants Hospital Department of Pathology, Providence, Rhode Island, 101 Dudley Street, Providence, RI 02905, USA
| | - Kamaljeet Singh
- Brown University/Women & Infants Hospital Department of Pathology, Providence, Rhode Island, 101 Dudley Street, Providence, RI 02905, USA
| | - C. James Sung
- Brown University/Women & Infants Hospital Department of Pathology, Providence, Rhode Island, 101 Dudley Street, Providence, RI 02905, USA
| | - M. Ruhul Quddus
- Brown University/Women & Infants Hospital Department of Pathology, Providence, Rhode Island, 101 Dudley Street, Providence, RI 02905, USA
- Corresponding author at: Department of Pathology, Women & Infants Hospital, 101 Dudley Street, Providence, RI 02905, USA.
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44
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Ma T, Chai M, Shou H, Ru G, Zhao M. Mesonephric-Like Adenocarcinoma of Uterine Corpus: A Clinicopathological and Targeted Genomic Profiling Study in a Single Institution. Front Oncol 2022; 12:911695. [PMID: 35865471 PMCID: PMC9294373 DOI: 10.3389/fonc.2022.911695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 06/01/2022] [Indexed: 12/19/2022] Open
Abstract
Background Mesonephric-like adenocarcinoma (MLA) is a recently characterized, rare, and aggressive neoplasm that mostly arises in the uterine corpus and ovary. MLA shows characteristic pathological features similar to mesonephric adenocarcinoma of the cervix. The origin of MLA is still controversial and recognition of it remains challenging for pathologists. The aim of this study was to enrich the clinicopathological features of MLA in the uterine corpus and explore its molecular alterations by targeted next-generation sequencing (NGS). Methods Four cases of MLA were identified among a total of 398 endometrial carcinomas diagnosed in our institution between January 2014 and December 2021. Immunohistochemistry and targeted NGS spanning 437 cancer-relevant genes were performed. Results The most common symptom was abnormal vaginal bleeding, and the average age was 68 years. Histologically, the tumors showed a mixture of varied growth patterns including papillary, glandular, tubular, cribriform, solid, and slit-like architectures, which were lined by columnar to cuboidal cells with overlapping vesicular nuclei and sometimes nuclear grooves. Intraluminal eosinophilic colloid-like secretions were focally evident in three of the four cases. Immunohistochemically, the MLAs were positive for GATA3 (4/4), TTF-1 (3/3), luminal CD10 (3/3), calretinin (2/3), and patchy P16 (3/3) and were negative for ER (0/4) and PR (0/4). The expression of P53 was “wild type” (4/4). By targeted NGS, 3/4 (75%), 2/4 (50%), and 1/4 (25%) cases harbored PIK3CA, KRAS, and PTEN mutations, respectively. None of the tumors had mutations in DNA mismatch repair genes, ARID1A/B, POLE, CTNNB1, SMARCA4, or TP53. At the time of diagnosis, three were presented with FIGO IB stage and one with IIIC stage. Two patients received postoperative chemotherapy and radiotherapy and they were alive without evidence of disease at 8 and 56 months follow-up, respectively. One patient developed pulmonary metastasis 13 months after surgery and chemotherapy, and one was dead of the disease 24 months after the operation without adjuvant therapy. Conclusions MLA is a rare and aggressive malignancy, representing approximately 1% of all endometrial carcinomas. It exhibits mixed architectures associated with distinctive immunophenotype and recurrent KRAS and PIK3CA mutations, supporting classified as of Müllerian origin with mesonephric differentiation.
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Affiliation(s)
- Tianshi Ma
- Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Mengyu Chai
- Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
- Department of Pathology, Zhejiang Hospital, Hangzhou, China
| | - Huafeng Shou
- Cancer Center, Department of Gynecology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Guoqing Ru
- Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Ming Zhao
- Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, China
- *Correspondence: Ming Zhao,
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Mills AM, Jenkins TM, Howitt BE, Fan J, Ring KL, Cook I. Mesonephric-like Endometrial Carcinoma: Results From Immunohistochemical Screening of 300 Endometrial Carcinomas and Carcinosarcomas for This Often Overlooked and Potentially Aggressive Entity. Am J Surg Pathol 2022; 46:921-932. [PMID: 35195579 DOI: 10.1097/pas.0000000000001873] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Mesonephric-like endometrial carcinoma is a rare but frequently misclassified and aggressive malignancy. KRAS mutations, limited estrogen receptor (ER) expression, and TTF-1, GATA3, and luminal CD10 expression are described in these tumors, but an immunohistochemistry-based screening approach has not been studied. We assessed 300 endometrial carcinomas/carcinosarcomas to ascertain the specificity of TTF-1/GATA3/luminal CD10 expression with or without ER staining for this diagnosis. Next-generation sequencing and morphologic review were performed on screen-positive cases. In all, 3% (9/300) were TTF-1+; 2 coexpressed GATA3. No cases expressed luminal CD10 or GATA3 in isolation. Two TTF-1+/ER- cases, one of which was also GATA3+, were reclassified as mesonephric-like based on morphology and molecular results (KRAS mutations without mismatch repair deficiency, TP53 mutations, or PTEN mutations): these represented 0.7% of all cases (2/300). The reclassified cases were originally diagnosed as grade 1 and 2 endometrioid carcinoma, and the latter had pulmonary metastases and pelvic recurrences. Six TTF-1+ cases retained their original serous (3) and endometrioid (3) diagnoses; 1 was reclassified as dedifferentiated. All had negative or low ER. KRAS mutations were identified in 4 TTF-1+ non-mesonephric-like cases, including 1 serous and 1 grade 3 endometrioid with p53 abnormalities, 1 mismatch repair-deficient endometrioid with a complex molecular profile, and 1 endometrioid with mucinous differentiation. These findings suggest that TTF-1 and ER are good first-line screens for mesonephric-like carcinoma, but caution that a TTF-1+/ER- immunoprofile is not specific, even in the setting of KRAS mutations. A final diagnosis of mesonephric-like carcinoma requires integration of morphologic and immunohistochemical features, with molecular support when relevant.
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Affiliation(s)
| | | | - Brooke E Howitt
- Department of Pathology, Stanford University Hospitals & Clinics, Stanford, CA
| | - Jinbo Fan
- Department of Pathology, University of Virginia
| | - Kari L Ring
- Department of Obstetrics and Gynecologic, Division of Gynecologic Oncology, University of Virginia, Charlottesville, VA
| | - Ian Cook
- Department of Obstetrics and Gynecologic, Division of Gynecologic Oncology, University of Virginia, Charlottesville, VA
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McCluggage WG. Mesonephric-like Adenocarcinoma of the Female Genital Tract: From Morphologic Observations to a Well-characterized Carcinoma With Aggressive Clinical Behavior. Adv Anat Pathol 2022; 29:208-216. [PMID: 35384888 DOI: 10.1097/pap.0000000000000342] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Mesonephric-like adenocarcinoma (MLA) was introduced as a new tumor type in the endometrium and the ovary in the 2020 World Health Organization (WHO) Classification. This is a rare recently described (2016) and clinically aggressive carcinoma with a propensity for distant spread, especially to the lungs. MLA has a characteristic morphology and immunophenotype (hormone receptor negative; TTF1 and/or GATA3 positive). These neoplasms are commonly associated with KRAS and PIK3CA mutations and in the Cancer Genome Atlas (TCGA) molecular classification of endometrial carcinomas fall into the copy number low/no specific molecular profile category. Although they show significant morphological, immunophenotypic and molecular overlap with cervical mesonephric adenocarcinomas, there are other parameters which suggest a Mullerian origin and, as such, the term MLA seems apt. MLA can be added to the list of endometriosis-associated ovarian neoplasms. In this paper, I outline the series of events which lead to the first description of MLA and review the subsequent literature on this tumor type which has expanded on the morphologic features and immunophenotype, discovered the molecular underpinnings and elucidated the clinical behavior. The discovery of MLA represents an example of "new" entities still to this day being discovered through careful morphologic observations and referral of cases for specialist opinion.
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Affiliation(s)
- W Glenn McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK
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Abstract
This article presents features of uncommon high-grade endometrial carcinomas that often pose a significant diagnostic challenge. An update on undifferentiated and dedifferentiated endometrial carcinoma is first provided, followed by discussions on more recently defined entities such as mesonephric-like carcinoma of the endometrium and gastric-type endometrial carcinomas. Finally, endometrial carcinoma with germ cell or trophoblastic-like components is discussed.
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Affiliation(s)
- Jelena Mirkovic
- Division of Laboratory Medicine and Molecular Diagnostics, Anatomic Pathology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room E401, Toronto, Ontario M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
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Bennett JA, Oliva E. The complex and often confusing history, histology and histogenesis of mesonephric, STK11 adnexal tumour and mesonephric-like neoplasms of the upper female genital tract (including broad ligament). Histopathology 2022; 81:280-296. [PMID: 35395118 DOI: 10.1111/his.14662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/05/2022] [Accepted: 04/06/2022] [Indexed: 11/27/2022]
Abstract
Mesonephric lesions in the female genital tract are uncommon, with those arising from the upper tract being much less frequent than those developing in the lower tract (mesonephric hyperplasia and carcinoma). The most common upper tract lesions include rete cyst/cystadenoma and female adnexal tumour of Wolffian origin (FATWO). The integration of morphological, immunohistochemical and molecular studies on FATWOs has enabled recognition of a novel entity, the STK11 adnexal tumour, which is often associated with Peutz-Jeghers syndrome (~50%) and frequently has a salivary gland morphology but an unknown origin. Similarly, 'mesonephric-like' adenocarcinoma, an entity with striking similarities to mesonephric carcinoma but currently favoured to be of Müllerian derivation based on its association with other Müllerian tumours and molecular findings, has also been recently described, and may histologically mimic both FATWOs and STK11 adnexal tumours. In this review, we provide a historical overview of upper female genital tract mesonephric proliferations and discuss mesonephric lesions, STK11 adnexal tumour, mesonephric-like adenocarcinoma, and mimickers, the most common being endometrioid carcinoma.
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Affiliation(s)
- J A Bennett
- Department of Pathology, University of Chicago Medicine, Chicago, IL, USA
| | - E Oliva
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
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Al Nabhani S, Doyle A, Kennedy S, McVey R, Crown J, Gibbons D. Endometrial Mesonephric-like Adenocarcinoma Presenting as an Ocular Lesion: A Case Report. Int J Gynecol Pathol 2022; 41:161-167. [PMID: 33935158 DOI: 10.1097/pgp.0000000000000781] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Endometrial mesonephric-like carcinoma (ML-CA) is a recently recognized subtype of aggressive endometrial adenocarcinoma that is morphologically and immunophenotypically similar to mesonephric carcinoma but not typically associated with mesonephric remnants. Here, we report a case of 58-yr-old female who had a past medical history of fibroids and of irregular menstrual bleeding for ~20 yr who presented with visual disturbance. On further investigation, she was found to have a large choroidal peri-papillary tumor of the right eye. A presumptive diagnosis of choroidal melanoma was made. Right eye enucleation was performed, and microscopy revealed moderately differentiated metastatic adenocarcinoma. Further work up was advised. A uterine mass was identified on imaging followed by endometrial biopsy that showed a morphologically and immunohistochemically similar tumor to that in the eye. A hysterectomy was carried out and a malignant neoplasm with varying morphologic patterns including gland formation, solid sheets of tumor cells, cribriform, glomeruloid, spindled and papillary areas was seen. The immunohistochemical profile showed diffuse strong positivity for AE1/AE3, TTF1, P16, and vimentin. CD56, GATA3, Napsin A, and CD10 were focally positive. The neoplastic cells were negative for the following markers ER, PR, WT1, calretinin, and synaptophysin. PDL-1 was negative and mismatch repair protein was proficient. An identical KRAS mutation was detected in both the uterine corpus and ocular tumors. The findings are in keeping with a uterine mesonephric-like adenocarcinoma with an ocular metastasis. An Oncomine Focus-Mutation profile, Thermo-Fisher Scientific Inc., a 60 gene oncologic panel, performed on the ocular tumor, revealed no further mutations.
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Ovarian Mesonephric Adenocarcinoma. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2022. [DOI: 10.1007/s40944-022-00612-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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