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J Gastrointest Cancer. 2019 Feb 20. doi: 10.1007/s12029-019-00213-0. [Epub ahead of print]

Dilemmas in Diagnosis and Management of Gastroenteropancreatic Mixed Neuroendocrine Non-neuroendocrine Neoplasms: First Single-Centre Report from India.

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Department of Gastrointestinal Surgery, Lilavati Hospital and Research Center, Mumbai, Maharashtra, 400050, India.
, Navi Mumbai, India.
Department of Gastrointestinal Surgery, Lilavati Hospital and Research Center, Mumbai, Maharashtra, 400050, India.
Department of Surgical Oncology, Lilavati Hospital and Research Centre, Mumbai, Maharashtra, 400050, India.



Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neoplasm comprising of exocrine and neuroendocrine elements, each representing ≥ 30% lesion. It is commonly misdiagnosed as adenocarcinoma or grade-3 neuroendocrine neoplasm (NEN). Management is not well-defined.


Retrospective analysis of prospectively entered data at our centre from January 2011 to January 2018 revealed 16 MiNENs off 130 neuroendocrine neoplasms (NENs). These were analysed for demographics, clinicopathological characteristics, management strategies and prognosis.


Four out of 16 patients, metastatic at presentation, were started on chemotherapy. Eleven of remaining 12 patients had pre-operative biopsy. Only two were diagnosed MiNEN. Four patients (33.34%) received 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy and underwent curative surgery with adjuvant cisplatin+etoposide (Cis-Eto). Out of these, two patients (16.6%) developed metastasis and were shifted to capecitabine+temozolomide (Cap-Tem). Six patients (50%) with neuroendocrine-dominant MiNEN received adjuvant Cis-Eto after surgery. Two (16.6%) developed metastases for which Cap-Tem was started. One of them developed locoregional and liver metastasis. Three patients (25%) have succumbed to progressive disease, three (25%) are on treatment, and six (50%) are disease-free at 4-30 months.


Preoperative diagnosis of MiNEN is challenging, and it needs quality histopathological examination and immunohistochemistry. The 30% criteria is therapeutically insignificant, and treatment based on most aggressive component is prognostically more relevant. Neoadjuvant 5-FU-based regimens may downstage adenocarcinoma-dominant tumours. There are no guidelines on adjuvant Cis-Eto. Cap-Tem can be considered second-line chemotherapy. Poor survival is reported irrespective of site of origin and adjuvant therapy.


Capecitabine–temozolomide; Cisplatin–etoposide; MANET; MiNEN; Neuroendocrine neoplasms


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