Atypical carcinoid of the uterine cervix accompanying adenocarcinoma in situ

Abstract

Clinical questionA 45-year-old woman presented with painless vaginal bleeding for 2 months. A biopsy was taken from the uterine cervix, and poorly differentiated adenocarcinoma was suspected. After three cycles of neoadjuvant chemotherapy treatment, the patient underwent radical hysterectomy with bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy.Review the high quality, interactive digital Aperio slide at http://virtualacp.com/JCPCases/jclinpath-2018-205081-1/ and consider your diagnosis.What is your diagnosis?Typical carcinoid.Poorly differentiated adenocarcinoma.Atypical carcinoid.Small cell neuroendocrine carcinoma.Sex cord-stromal tumours of the uterine cervix.­The correct answer is after the discussion.DiscussionNeuroendocrine tumours of the uterine cervix are a rare cancer of the female reproductive system, accounting for approximately 1% of all female cervical malignancies.1 2 In 1997, a consensus workshop suggested four types of neuroendocrine tumours of the uterine cervix: typical and atypical carcinoid tumours, small cell neuroendocrine carcinomas, and large cell carcinomas.1 Among all the categories, small cell neuroendocrine carcinomas are of the highest incidence. A PubMed search revealed that only 15 cases of atypical carcinoid tumours of the uterine cervix have been reported.3 4 Because of infrequency, the clinical and pathological features of atypical carcinoid tumours of the uterine cervix remain unknown.Atypical carcinoids are characterised by great cytological atypia, which means abundant or scanty cytoplasm and visible nucleoli with granular chromatin. Tumour cells lined up in insular, trabecular, columnar and nested organoid patterns; they are epithelioid in appearance, but can be spindled (figure 1A). Necrosis could be observed in some areas and mitotic activity is up to 10 mitotic figures/10 high-power field (figure 1B). On immunohistochemistry, atypical carcinoids are diffuse and positive for Syn, CgA and CD56 (figure 2). An electron microscopic test was done, and several neuroendocrine granules were distributed in the tumour cell plasma (figure 3).Figure 1(A) Insular, trabecular and columnar patterns of tumour cells were focally observed in the deep stroma of the cervix (H&E ×200). (B) Tumour cells showed small-sized, scanty cytoplasm, enlarged and deeply stained nuclei with condensed chromatin, obvious atypia, and increased mitotic activity (H&E ×400). (C) The cervical gland has shown atypical hyperplasia and adenocarcinoma in situ (H&E ×200).Figure 2Immunohistochemical study findings: (A–C) The neuroendocrine markers Syn, CgA and CD56 were diffuse with strong expression in the tumour cell plasma. (D–E) P63 and CK5/6 for the squamous cell carcinomas showed no expression. (F–G) P16 for atypical carcinoid and adenocarcinoma in situ, respectively, had strong diffuse expression. (H–I) Ki67 had low expression in both atypical carcinoid and adenocarcinoma in situ (×200).Figure 3Several neuroendocrine granules were distributed in the tumour cell plasma.Neuroendocrine tumours of the uterine cervix are sometimes combined with adenocarcinoma (figure 1C); their cytological and immunohistochemical features showed the neuroendocrine and adenomatous components shared the same origin.