Primary Neuroendocrine Carcinoma of Gallbladder Revisited: An Evaluation and Reassessment of Management Strategy

Abstract

Background: Primary neuroendocrine carcinoma of the gall bladder (GB) is an unusual entity. It accounts for 0.2% of all neuroendocrine tumors. It is usually characterized by late diagnosis and poor prognosis.

Materials and Methods: On retrospective analysis of patient record of GBC patients treated in our institute, we identified seven cases of primary gall bladder neuroendocrine tumor over last 5 years (August 2010 to October 2014). It represents 2.6% of all primary gall bladder carcinoma patients (630 patients). Data regarding clinical features, radiological findings, treatment aspects and their disease outcome was recorded and analyzed.

Results: All seven patients were female (mean age of 46.8 years) presented with locally advanced (n=4) and  metastatic disease (n=3)[ one in stage IIIA, two in stage III B, one patient in stage IIIA and three patients in stage IVB]. Pain abdomen was the most common presenting symptom. Three patients underwent definitive surgery, while four patients with palliative chemotherapy in view of distant disease/ locally advanced disease (inoperable). Final diagnosis of NEC was made on histopathological and immunohistochemical examination (IHC) of the resection specimen (N=3) or image guided biopsy tissue (N=4). Immunohistochemistry (IHC) studies revealed positivity of tumor cells for chromogranin (100%), synaptophysin (85.7%), NSE (85.7%) and Cytokeratin in all patients (100%). Five patients were in WHO grade 3 (poorly differentiated) and two in intermediate grade (moderately differentiated). Patients had a mean follow up of 11months (range: 8- 20 months). A correlation was seen with the poor differentiation of the tumor and high Ki-67 proliferative index with poor patient survival. Patients treated with definitive surgery had a mean survival duration of 12.6 months (range: 8 - 14 months), with local recurrence in one patient. Patients with metastasis treated with palliative chemotherapy had a mean disease control rate of 9.1 months (range 8 -12 months).

Conclusion: We present this case series to highlight the rarity of this entity, discuss the disease outcome and utility of immunohistochemical analysis in its identification. Ki-67 index and poor differentiation may be a predictive/prognostic marker of progressive disease. Surgery is the mainstay of treatment with ill-defined role of chemo radiotherapy with poor disease outcome.