Endometrial neuroendocrine carcinoma frequently associated with mismatch repair deficiency

Abstract

Background: Endometrial neuroendocrine carcinoma (NEC) is a uncommon histologic subtype of endometrial cancer. It is currently unclear if the endometrial NEC has any particular relationship with mismatch repair (MMR) protein expression patterns. Here we report 3 endometrial NEC cases showing loss of MMR expression.Case presentation: The cancers had two components with one poorly differentiated or NEC component, accounting for 60–90% of the neoplasms and the other of well differentiated glandular component. The NEC cells mainly showed solid sheets and organoid patterns, whereas insular, trabecular and rosette/pseudorosette patterns were also found. The NEC component was composed of cells with large, polygonal, vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. In all cases, the NEC component was diffusely positive for p16 and at least 2 of the 3 neuroendocrine markers (CGA, SYN, CD56) reactive in > 10% of the cancer cells. Loss of MMR protein expression was found in all three cases with loss of MLH1 in cases 1 and 2 and loss of MSH2 and MSH 6 in case 3. No PMS2 loss was found. In addition, aberrant TP53 and SMARCB1 (INI1) expression was found in case 3 only. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, and two of them received postoperative chemotherapy and/or radiation therapy. The patients remained alive with no disease for 51, 17 and 6 months, respectively.Conclusion: Endometrial NEC is frequently associated with MMR deficiency, some of which may have a better prognosis than we expect.