OA: Colorectal Choriocarcinoma in a Patient with Probable Lynch Syndrome (PMS2)

 Choriocarcinoma is a fast-growing form of cancer that occurs in a woman's uterus (womb). The abnormal cells start in the tissue that would normally become the placenta. This is the organ that develops during pregnancy to feed the fetus. Choriocarcinoma is a type of gestational trophoblastic disease.
                   ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

open access: Frontiers | Colorectal Choriocarcinoma in a Patient with Probable Lynch Syndrome | Gastrointestinal Cancers

 MMR deficiency and MSI in colorectal choriocarcinoma have not been previously identified. Here, we report the comprehensive morphological, immunohistochemical, and molecular analysis of a colorectal choriocarcinoma in a patient with probable Lynch syndrome.

 Case Presentation

A 61-year-old Caucasian post-menopausal female with a history of stage I signet ring cell carcinoma of the stomach at age 36 was evaluated for a change in bowel habits and abdominal discomfort. There was a known family history of breast cancer in a second degree relative (aunt). Physical examination discovered a palpable resistance in the lower right quadrant. Colonoscopy identified a large stenosing mass in the cecum. An endoscopic biopsy was performed showing a poorly differentiated carcinoma with extensive necrosis. Computed tomography (CT) imaging confirmed the diagnosis of a 9.6-cm cecal mass (Figure 1A) and identified four hepatic metastases with a maximum diameter of 2.6 cm (Figure 1B). There was no evidence of a lesion involving the ovaries, the uterus, or a locoregional recurrence of gastric carcinoma. A right hemicolectomy with primary end-to-end anastomosis was performed. A diagnosis of primary colorectal choriocarcinoma in clinical stage IV was made. Pathological tumor stage according to the UICC TNM classification, 7th edition (2) was pT4a, pN0 (0/29), cM1 (HEPAR), L0, V1, Pn0, G3, and R0. Laboratory examinations showed significantly elevated serum β-HCG levels of 70.173 IU/ml (internal reference <2 IU/ml), a normal level of carcinoembryonic antigen (CEA; 1.9 μg/l; internal reference <5.0 μg/l), and CA19.9 (6.7 kU/l; internal reference <35 kU/l).......

 Fifteen months later, laboratory and radiographic evidence of intra-abdominal tumor progression with new peritoneal lesions was recorded. Third line therapy with five cycles of carboplatin and bleomycin was initiated, leading to stabilization of disease (Figure 1C). New peritoneal, splenic, uterine, ovarian, and rectal lesions were noted on follow-up studies 6 weeks later....

Immunohistochemical analysis of the MMR proteins MLH1, PMS2, MSH6, and MSH2, showed an isolated loss of PMS2 protein

 Remarkably, review of clinicopathological data shows that 9 of the 21 previously reported cases of colorectal choriocarcinoma have arisen in patients under 50 years of age (23, 24).