Ovarian microcystic stromal tumor: A novel extracolonic tumor in familial adenomatous polyposis

Abstract

Ovarian microcystic stromal tumor (MCST) is a very rare neoplasm; hence, its nomenclature was recently designated as "Distinctive morphologic and immunohistochemical features" in 2009. Its exact origin, etiological genetic alterations, and background are not yet clearly known. Familial adenomatous polyposis (FAP) is an autosomal dominant disease that leads to development of colorectal polyps via germ-line mutations of the APC gene on chromosome 5q21∼22. In this study, we report a 40-year-old female patient who had ovarian MCST and FAP. On sequencing the APC gene in ovarian MSCT, we detected a novel somatic mutation of the APC gene in exon 11, with a heterozygous deletion at nucleotide position c.1540delG (p.Ala514 Profs*9). Mutations of β-catenin (CTNNB1) and FOXL2 were not detected. Although one case demonstrating involvement of Wnt/β-catenin in ovarian MCST associated with FAP has been presented previously, no detailed information was provided. Thus, this is the ovarian MCST with a somatic mutation of APC in a patient with FAP.

Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli–Leydig cell tumour, microcystic stromal tumour and their mimics

“…A somatic mutation of CTNNB1 exon 3 has been reported in 73% (22/30) of MCSTs . The mutation was missense in all but one case, which was a deletion mutation .…”

“…Given the functional relationship between APC and the canonical Wnt–β‐catenin signalling pathway, and given the observation that there are rare examples of women with familial adenomatous polyposis (FAP) who also have MCST, investigators have examined whether APC mutations are present in MCST. Indeed, a few cases have been reported, suggesting that some MCSTs may form part of the FAP clinical phenotype . Although MCST is benign, the microscopic appearance may mimic a variety of malignancies, including JGCT, AGCT, yolk sac tumour, steroid cell tumour, and various ovarian metastases of non‐gynaecological carcinomas.…”

“…Sanger sequencing or targeted NGS of exon 3 (Figure C) is the mainstay of CTNNB1 mutation testing. In the specific setting of MCST, immunohistochemical testing for nuclear expression of β‐catenin appears to be a reasonable surrogate for mutation testing; the presence of nuclear staining in MCSTs is associated with CTNNB1 mutation in approximately three‐quarters of cases, and nearly all MCSTs with CTNNB1 mutation show β‐catenin nuclear staining …”

“…CTNNB1 encodes the protein b-catenin. Given the functional relationship between APC and the canonical Wnt-b-catenin signalling pathway, and given the observation that there are rare examples of women with familial adenomatous polyposis (FAP) who also have MCST, 53,54 investigators have examined whether APC mutations are present in MCST. Indeed, a few cases have been reported, suggesting that some MCSTs may form part of the FAP clinical phenotype.…”

“…Indeed, a few cases have been reported, suggesting that some MCSTs may form part of the FAP clinical phenotype. [53][54][55] Although MCST is benign, the microscopic appearance may mimic a variety of malignancies, including JGCT, AGCT, yolk sac tumour, steroid cell tumour, and various ovarian metastases of non-gynaecological carcinomas. Therefore, accurate diagnosis of MCST is important and warrants discussion of the potential roles for CTNNB1 and/or APC mutation testing and for b-catenin immunohistochemistry.…”