Mixed large and small cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium with high microsatellite instability: A case report and literature review

Abstract

A 65-year-old, gravida 3, para 2 Japanese woman was referred to our hospital for symptomatic thickening of the endometrial lining. Endocervical and endometrial cytology revealed an adenocarcinoma. The endometrial biopsy specimen was mixed, with a glandular part diagnosed as endometrioid carcinoma and a solid part diagnosed as high-grade mixed large and small cell neuroendocrine carcinoma (L/SCNEC). She underwent extra-fascial hysterectomy with bilateral salpingo-oophorectomy, complete pelvic and para-aortic lymphadenectomy, and omentectomy (FIGO IIIB, pT3b pN0 M0). She currently has no deleterious germline mutation, but high tumor mutation burden and high microsatellite instability (MSI) were identified. She underwent six cycles of platinum-based frontline chemotherapy and achieved complete remission. Immune checkpoint blockade therapy is a promising second-line therapy for MSI-high solid tumors. However, the MSI or mismatch repair (MMR) status of endometrial L/SCNEC remains unclear in the literature. Universal screening for MSI/MMR status is needed, particularly for a rare and aggressive disease.

Keywords: DNA mismatch repair; Endometrial cancer; microsatellite instability; neuroendocrine carcinoma.

Figure 1.

(a) Contrast-enhanced magnetic resonance imaging demonstrating a 24 mm lesion protruding from the endometrium and invading less than half of the myometrium. (b) Gross examination showing a 55 mm tumor that is mainly developing from the mid and posterior endometrium. (c) An endometrial gland-like architecture composed of severe atypical cells can be seen accompanied by approximately 30% of solid growth (hematoxylin and eosin stain). (d) A nested or diffuse architecture composed of ovoid cells with condensed chromatin and scant cytoplasm can be seen, accompanied by increased mitotic figures. These atypical cells morphologically resemble a lung small cell carcinoma and are morphologically divided into large (left) and small (right) cell components. (e) Small cell component displays a stronger immunoreactivity for CD56 than does large cell component. (f) Immunoreactivity for synaptophysin is positive only in small cell neuroendocrine carcinoma. (g) Representative image of large cell neuroendocrine carcinoma. (h) Representative image of small cell neuroendocrine carcinoma.

Figure 2.

Scattered or clustered atypical cells with a small shape and a high nucleocytoplasmic ratio are seen on endocervical (a) and endometrial (b) cytology (Papanicolaou stain).