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Journal of Cancer Research and Therapeutics, Vol. 7, No. 2, April-June, 2011, pp. 211-213 Case Report Large cell neuroendocrine carcinoma of the endometrium: An extremely uncommon diagnosis, but worth the efforts Kedar K Deodhar1, RA Kerkar2, Pallavi Suryawanshi1, Hari Menon3, Santosh Menon1 1 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra, India Code Number: cr11052 PMID: 21768718 Abstract Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors. They usually involve the cervix and ovary, and are seen very rarely in the endometrium. The overwhelming majority of endometrial NECs are of conventional small cell type (up to 60 cases). Only seven cases of large cell type NEC of the endometrium have been reported. We report a case of large-cell neuroendocrine carcinoma (LCNEC) of the endometrium in a 70-year-old female. The case is described for its rarity and shows that a high index of suspicion can help the pathologist to use immunohistochemistry and in turn help in selection of appropriate chemotherapy.Keywords: Endometrium, large-cell neuroendocrine carcinoma, neuroendocrine carcinoma Introduction Neuroendocrine carcinomas (NECs) of the female genital tract are aggressive and uncommon tumors. They usually involve the cervix and ovary, and are seen very rarely in the endometrium. [1] The overwhelming majority of the endometrial NECs are of the conventional small cell type (up to 60 cases). [2],[3],[4] In the majority of the cases, they are seen occurring concurrently with endometrioid type adenocarcinoma. [4],[5] Only seven cases of large-cell type neuroendocrine carcinoma of the endometrium are described. [5],[6],[7] Case Report A 70-year-old married woman presented with history of irregular post-menopausal bleeding and mild abdominal pain for two months. Clinical examination did not reveal any significant finding except for a mild vaginal discharge. Her hemoglobin was 11.1 gm% and all other laboratory investigations were within normal limits. Transvaginal sonography (TVS) and magnetic resonance imaging (MRI) showed a 3.5 × 3.1 cm mass in the endometrium. There was no lymphadenopathy. Bilateral adnexae were normal. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) with omentectomy. Grossly, the uterine cavity was dilated and showed a 3.5 cm polypoidal grey white tumor involving the fundic region. The tumor infiltrated the myometrium deeply. Paraffin blocks were received for review. Histology of the uterine mass showed a malignant tumor composed of large round to oval cells, arranged in trabeculae and nests. Nuclei were vesicular, at places hyperchromatic, and showed moderate pleomorphism with brisk mitotic activity [Figure - 1]a-d. Nucleoli were seen in few cells. Areas of geographic necrosis were present in the tumor. Immunohistochemistry revealed diffuse positivity for synaptophysin, chromogranin, CD56 (neuroendocrine markers) and epithelial membrane antigen (EMA). Immunonegativity for cytokeratin, CD10, MIC-2, vimentin and smooth muscle actin was seen [Figure - 2]a-f. The overall features were of high grade neuroendocrine carcinoma, large cell type. The tumor infiltrated more than half of the myometrial thickness. Sections from isthmus, cervix, both ovaries and fallopian tubes were unremarkable. Omentum was free of metastasis. The patient had an uneventful postoperative period. Computerized tomography (CT) scan of the abdomen and pelvis done after 3 months and subsequent whole body positron emission tomography (PET) scan revealed 1.7 cm-sized aortocaval lymph node (SUV max. of 13.6), multiple liver metastasis and few peritoneal nodules. Thereafter, the patient was offered adjuvant chemotherapy (etoposide and cisplatin) which she tolerated well. A repeat PET-CT scan after completion of six cycles of chemotherapy showed near total regression of the liver lesions and retroperitoneal lymphadenopathy. The patient is disease-free six months after completion of chemotherapy. Discussion Identifying diagnostic criteria for large-cell neuroendocrine carcinoma (LCNEC) of the endometrium is challenging, since these are extremely rare tumors. The diagnostic criteria applicable to LCNEC of lung are extrapolated to the endometrium; [8] They show features of neuroendocrine differentiation (nesting, trabeculae, rosettes and palisading) coupled with large cells with moderate to abundant cytoplasm, frequent nucleoli. Neuroendocrine differentiation is confirmed by using immunohistochemical stains for chromogranin, synaptophysin and CD56. Mulvany et al., [5] in their study of five cases of LCNEC describe nuclei to be either vesicular or hyperchromatic. Nuclei were small, but in any one tumor approximately 15% of well-preserved tumor cells possessed a single prominent nucleolus. Small cytoplasmic eosinophilic granules were seen. Our case showed moderate to large amount of cytoplasm in the majority of tumor cells, large nuclei, which were mainly vesicular but also hyperchromatic in some areas. Nucleoli were inconspicuous or small in most areas. Cytoplasmic eosinophilic granules are not seen. The differential diagnoses include undifferentiated carcinoma or endometrioid adenocarcinoma FIGO grade III, endometrial stromal sarcoma (ESS), PNET and epithelioid leiomyosarcoma. Use of neuroendocrine markers and other appropriate negative immunohistochemistry helped to exclude these diagnoses. To the best of our knowledge, only seven cases of primary endometrial large-cell neuroendocrine carcinoma have been reported in the literature [Table - 1]. [5],[6],[7] Interestingly, in all but one case described by Mulvany et al., [5] the tumor showed grossly a polypoid appearance; which was also the finding in our case. This appears to be the typical gross finding. Of these seven cases, four cases showed composite large-cell neuroendocrine carcinoma with endometrioid carcinoma, and one case showed LCNEC with sarcomatous stroma. Only two cases were of ′pure′ large-cell neuroendocrine carcinoma, [5],[6],[7] emphasizing the rarity of this case. We feel that the sampling in this case has been adequate and no other component was seen. LCNEC are aggressive tumors. Of the seven reported cases, two died of tumor. The maximum follow up is 16 months. Our patient is well at the last follow-up, six months after completion of treatment. Conclusion An LCNEC of endometrium is extremely rare and is usually mistaken for a poorly differentiated endometrioid adenocarcinoma. It can present as a polypoidal mass. Histopathology is important in making the diagnosis which can help in selecting the appropriate chemotherapy. References
Copyright 2011 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr11052fd2.jpg] [cr11052t1.jpg] [cr11052f1.jpg] |
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