Ovarian MCST is a rare variant of the pure stromal tumor that was first described by Irving and Young in 2009 . Additional studies have been published since then, and demonstrated the unique histologic and immunohistochemical features of MCST, including the involvement of the Wnt/β-catenin pathway in the pathogenesis. Nevertheless, to date, less than 40 cases of MCST have been reported worldwide, all of which are described as having benign biological behavior, but one patient experienced recurrence [1,2,3,4,5,6,7,8,9,10,11,12,13,14].
The tumor of the present case includes all classical histologic features of MCST, such as microcysts, solid cellular regions, and hyalinized fibrous stroma. The markers of sex cord tumors (calretinin and inhibin-α) and germ cell tumors (SALL4 and OCT3/4) are negative, while CD10 and β-catenin (nuclear and cytoplasmic) are characteristically positive. Other positive markers reported in previous literature, such as WT-1, SF-1, cyclin D1, AR, ER, PR, vimentin, and CD99 (perinuclear dot-like), are also expressed in our case. The expression profiles of relative markers from references listed in present article are summarized in Table 1. Both morphology and immunoprofile exclude other microcystic tumors of the ovary but MCST. Tumors in the omentum share the same histologic features and β-catenin immunoexpression as those in the left ovary, which is highly indicative of omentum metastasis. Mitosis is rare, and the Ki-67 index is low, indicating a low proliferation rate of the tumor . However, tumorlet metastasis in the omentum suggests undetermined biological behavior.
Concerning the molecular mechanism of MCST,Maeda first reported a point mutation in exon 3 of CTNNB1 in two cases . Given the rarity of this tumor and the limited investigation of genomic and immunohistochemical profile, we compared our results with others reported and summarized their similarities. The Genetic characteristics of 38 cases of ovarian MCST have been summarized (Table 2). According to our retrospective study, in 26 of 38 cases in which CTNNB1 mutations were detected in the original study and all cases but one exhibited nuclear and cytoplasmic β-catenin immunoreactivity [1,2,3,4,5,6,7,8,9,10,11,12,13,14],which indicates the important role of Wnt/β-catenin in the MCST. In addition, APC mutations were identified in 5 women with MCST, 4 of whom showed clinical features of FAP [2, 4, 13, 14], which explained the strong nuclear immunostaining for β-catenin, although in the absence of β-catenin mutations, further indicating that the Wnt/β-catenin/APC pathway mediated the occurrence and development of MCST. In the present study, however, an oncogenic missense mutation (c.98C > G) in CTNNB1 was detected. Unfortunately, APC mutational status was not checked. The patient denied a family history of FAP, and no polyps were found on gastrointestinal endoscopy. Hence, we speculate that APC gene mutations are unlikely to be present. In 2018, McCluggage et al. clarified that ovarian MCST may be an extracolonic manifestation of FAP and that APC mutations occur in a minority of MCSTs and are mutually exclusive to CTNNB1 mutations . Accordingly, it is also possible that alterations in the other genes involved in the Wnt/β-catenin pathway are involved in its tumorigenesis. It is unclear whether there is a common morphology of MCST in different genetic backgrounds . Therefore, it is beneficial for all females with MCST to be evaluated for FAP, including an assessment of different genes involved in the Wnt/β-catenin signaling pathway.
The behavior of MCST is not well known because of limited case reports and follow-ups, but the available information suggests that MCST is likely benign. The most unique aspect of the present case revealed a 2-mm-diameter tumorlet in the omentum. Both morphology and immunophenotype are identical to the primary ovarian MCST, which indicated that MCST is not a purely benign ovarian tumor, as previously believed. Previous studies have elucidated the crucial role of Wnt/β-catenin in the MCST. β-Catenin-mediated migration and adhesion is linked on the one hand to stimulating the expression of protooncogenes due to its nuclear accumulation and on the other to E-cadherin stabilization . The E-cadherin/β-catenin complex affects cell adhesion and may regulate cancer invasion and seeding metastasis. In the current case, mutation of β-catenin may affect cell adhesion, which results in the detachment of tumor cells and causes omental deposits. On the basis of these pathological findings and molecular alterations, we assume that MCST more likely belongs to an underrecognized tumor of undetermined potential.
Not much is known regarding the biophysical behavior of MCST because of its rarity. Here, we present a rare case of ovarian MCST with omental metastasis, which alerts us to the undetermined potential, and even the malignant biological behavior, of MCST. More cases and molecular studies will be necessary to further warrant this speculation.