Neuroendocrine Carcinoma of Gall Bladder: A Series of 19 Cases with Review of Literature

Neuroendocrine neoplasms of the gall bladder (GB) are rare tumors classified as grade 1 and 2 neuroendocrine tumor (NET), neuroendocrine carcinoma (large cell or small cell type), and mixed adeno-neuroendocrine carcinoma (MANEC). Primary neuroendocrine carcinomas (NEC) of GB are rare with grave prognosis not withstanding radical surgical treatment. Chemotherapy forms the primary management due to the advanced stage at presentation, as complete surgical resection is generally not possible. The overall median survival is 4–6 months despite aggressive management. Only 73 cases of small cell carcinoma (SCC) and 10 cases of large cell neuroendocrine carcinoma (LCNEC) have been reported in English literature till now. We present a series of 19 cases of NEC of GB with their pathological and clinical features and response to treatment.

The objective of this study was to evaluate NECs of the GB for their clinical behavior, prognosis, and treatment outcome in terms of survival and to segregate NECs into further subcategories, that is 20–50 % and >50 %, based on MIB-1 index.

We retrospectively searched the clinical and pathological database over 2.5 years (January 2012 to June 2014) through existing electronic hospital medical records to collect cases of NEC arising in GB. A total of 447 cases of gall bladder pathologies were analyzed, of which 19 cases were diagnosed as NEC. All relevant investigations were documented and response to treatment/therapy was evaluated clinically and radiologically. Tumor specimen was obtained by fine-needle aspiration cytology and/or biopsy and classified using the latest World Health Organisation (WHO) classification (2010) via cytopathologic, histopathologic, and immunohistochemical visage.

Nineteen patients diagnosed as NEC of GB were evaluated in the study, with 16 having SCC, 2 having LCNEC, and 1 with MANEC. All patients presented in advanced clinical stage III or IV, along with distant metastasis and showed progressive disease during therapy. Ki67 index was between 20 and 50 % in 5 cases and >50 % in 8 cases. Follow-up was available in 14 cases with a median survival of 3 months, and 2 of these patients capitulated to their illness, before commencement of treatment. The remaining 5 cases were lost to follow-up. Out of these, 2 had deranged liver function test and no chemotherapy could be administered, and the other 3 refused treatment.

NECs are aggressive with generally poor prognosis, characterized by insidious onset and advanced clinical stage of presentation. A radical approach to treatment with chemotherapy is the best form of palliation. Role of radiotherapy remains undefined due to paucity of data.