Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report

Nakamura, Kazuto; Nakayama, Kentaro; Minamoto, Toshiko; Ishibashi, Tatsuro; Ohnishi, Kaori; Yamashita, Hiroyuki; Ono, Ryo; Sasamori, Hiroki; Sultana, Rehena; Hossain, Mohammad Mahmud; Shanta, Kamrunnahar; Ishikawa, Masatoshi; Ishikawa, Noriyoshi; Kyo, Satoru

doi:10.3390/ijms19040979

Cited by 14 publications

(9 citation statements)

References 12 publications

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“…First, there was a somatic mutation in MLH1 in this case. Lynch syndrome‐related cCCC and POLE‐mutated cCCC have been previously documented, in which mismatch repair genes including MLH1 were commonly affected, leading to a mutator phenotype in these diseases. However, only a few mutations were identified in this cCCC case, suggesting that the MLH1 mutation might not be relevant in carcinogenesis or could exert protumorigenic effects by unknown mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…It is histologically characterized by clear cytoplasm of cancer cells, closely resembling the features of its ovarian counterpart . Due to the small number of cases, epidemiological, clinical, and pathological features of cCCC have remained largely unknown . Limited information thus far reported includes that patients with cCCC at an advanced stage had poor prognosis, and that in utero exposure to the antimiscarriage drug DES and HPV infection might be implicated in its pathogenesis .…”

Section: Introductionmentioning

confidence: 99%

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Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

et al. 2019

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Cervical clear cell carcinoma (cCCC) constitutes an extremely rare subtype of cervical cancer. Consequently, its pathogenesis remains largely unknown, with no cell lines established from primary tumors. Here, we report the first establishment of cCCC organoids, from biopsy samples of a 23‐year‐old patient diagnosed with cCCC. By applying a protocol that we recently optimized for gynecological tumors, we were able to propagate a patient‐derived cell line (PDC) for more than 6 months as organoids. This PDC tolerated cryopreservation and proliferated either as spheroids or adherent cells, and developed xenografts in immunodeficient mice, ensuring robust utility as a cell line. Intriguingly, the resected tumor focally contained serous carcinoma (SC) in a tiny protruding lesion. Both organoids and derivative xenografts resembled the CCC component of the original tumor in histology, immunostaining profile, and genome‐wide copy number changes, including focal gain of MET. Genomic analysis revealed that both organoids and the CCC component harbored only a few mutations, of which 2 mutations were shared in common. In contrast, the SC component showed a mutator‐phenotype and prominent genome instability along with biallelic inactivation of TP53, but none of them were found in organoids or the CCC component. The PDC proved sensitive to major chemotherapeutic agents and MET inhibitors. These observations clearly indicated that the PDC, designated as YMC7, can be used as a novel cCCC cell line and provide novel insights into the pathogenesis of mixed cervical adenocarcinoma. As a valuable resource for rare cancer, it will likely contribute to investigations in many fields.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

et al. 2019

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“…The one case report of cervical CCC in a Lynch patient is not convincing for a cervical origin, given that the tumour measured 4.2 cm and obliterated the entire cervix with involvement of the lower uterine segment. 31 Immunohistochemical staining patterns for cervical CCC are no different from that of CCC of the endometrium or ovary. Cervical CCC is usually (although not always) negative for oestrogen receptor (ER) and PR, and positive for PAX8, HNF1-beta and Napsin-A, with p16 and p53 ranging from negative to diffuse and strong.…”

Section: L E a R -C E L L C A R C I N O M Amentioning

confidence: 96%

“…Although it seems logical to consider DNA mismatch repair defect and the possible association of Lynch syndrome in cervical CCC, there has been no definitive evidence to support this. The one case report of cervical CCC in a Lynch patient is not convincing for a cervical origin, given that the tumour measured 4.2 cm and obliterated the entire cervix with involvement of the lower uterine segment …”

Section: Classification Of Endocervical Adenocarcinomamentioning

confidence: 99%

Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification

Park

2019

Histopathology

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Cervical adenocarcinoma is a heterogenous group of tumours with various aetiologies, molecular drivers, morphologies, response to treatment and prognosis. It has become evident that human papillomavirus (HPV) infection does not drive all adenocarcinomas, and appropriate classification is critical for patient management, especially in the era of the HPV vaccine and HPV‐only screening. Identified as one of the most important developments in gynaecological pathology during the past 50 years, the separation of cervical adenocarcinomas into HPV‐associated (HPVA) and HPV‐independent has resulted in a transformation of the classification system for cervical adenocarcinomas. HPVA has been traditionally subclassified by morphology, such as usual type (UEA), mucinous and villoglandular, etc. However, it has become evident that cell type‐based histomorphological classification is not clinically meaningful, and the newly proposed International Endocervical Adenocarcinoma Criteria and Classification (IECC) is a necessary and relevant break from this prior system. Non‐HPV‐associated adenocarcinomas can be divided by their distinct morphology and molecular genomics with very different responses to standard therapies and potential for future targeted therapies. These include gastric‐type, clear‐cell, mesonephric and endometrioid adenocarcinomas. So‐called ‘serous’ carcinomas of the cervix probably represent morphological variants of UEA or drop metastases from uterine or adnexal serous carcinomas, and the existence of true cervical serous carcinomas is in question. This review will discuss the advances since WHO 2014, and how HPV status, pattern of invasion as described by Silva and colleagues, histological features and molecular markers can be used to refine diagnosis and prognostication for patients with cervical adenocarcinoma.

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“…Family history 1 Hagen et al [20] 71 CRC ----N/A MSH2 wild type Mother: OvCa;son: CRC;Daughter: breast, CRC 2 Raymond et al [21] 75 CRC、OvCa -+ --MSI-H MSH6 wild type Father、brother: CRC 3 Rahner et al [22] N/A CRC -+ + -MSI-H MLH1 N/A N/A 4 Yokoyama et al [23] 49 EC -+ + -N/A MLH1 N/A First-degree relative: CRC; Second-degree relative:gastric cancer 5 Seiden et al [24] 46 CRC、EC、OvCa + --+ N/A MSH2 N/A Mother: EC、basal cell carcinoma; grandfather: CRC;grandmother: breast cancer 6 Hyun et al [25] 60 CRC、EC -+ N/A N/A N/A MSH6 N/A Sister: EC;brother:CRC 7 Chapel et al [26] 63 EC + --+ N/A N/A N/A N/A 8 Nakamura et al [27] 42 cervical cancer + --+ MSI-H MSH2/MSH6 N/A Not obvious IHC: immunohistochemistry colorectal cancer: CRC ovarian cancer: OvCa N/A: not available EC: endometrial cancer…”

Section: Braf Mutationmentioning

confidence: 99%

Lynch syndrome type II associated endometrial carcinoma: a case report and literature analysis

Lü

2021

Preprint

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Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report

Cited by 14 publications

References 12 publications

Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification

Lynch syndrome type II associated endometrial carcinoma: a case report and literature analysis

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