• The term mixed adenoneuroendocrine carcinoma (MANEC) was introduced by the WHO in 2010 referring to a neoplasm with dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumor.• MANECs are more commonly diagnosed in the appendix, colon, and stomach. • Gall bladder MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are rarely identified in the normal biliary tract.(GIST).

MIXED ADENONEUROENDOCRINE CARCINOMAOF THE GALLBLADDER: A CASE REPORT

References

Dr. Suhail Saleem1, Dr. Nita Mary John2, Dr. Deepak Varma3

1,2 Department of Pathology and Lab Medicine, 3 Center of Excellence in GastroenterologyAster Medcity, Kochi, India

Take home message

Introduction

Case Report

Histopathology

Immunohistochemistry

Gross

• MANEC cases can be easily misdiagnosed as cholangiocarcinoma. The acquisition of a surgical specimen and thorough investigations by the pathologist are crucial to make the correct diagnosis in order to determine the best treatment and estimate the prognosis.

• 46 year old female presenting with abdominal pain and weight loss for 6 months.• Radiological images showed focal gall bladder wall thickening with multiple portal, peripancreatic and paraaortic lymph nodes (Figure1).• An EUS-FNAC revealed poorly differentiated adenocarcinoma (Figure 2).• EUS guided biopsy was reported as suggestive of Neuroendocrine tumour( Figure 3).• Radical cholecystectomy was performed.

Figure 1

Figure 2-small clusters of cells with highnucleocytoplasmic ratio, hyperchromatic nuclei with coarse chromatin.

Figure 3-Clusters of cells with moderateamount of eosinophilic cytoplasm andround to ovoid hyperchromatic nucleus.

Gall bladder showsthickened wall witha grey-white growthmeasuring4.5 x 2.5 x 2.5 cmprojecting into thelumen and involvingthe entire circumferenceof the gallbladder.

Neoplasm having complex adenomatousmorphology intermingled with areasshowing a neuroendocrine component

1. Acosta AM1, Wiley EL. Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review. Arch Pathol Lab Med. 2016 Oct;140(10):1157-62.2. Azad S,Shukla D, Garg A, Negi SS, Malhotra V.Mixed denoneuroendocrine carcinoma of thegallbladder, histopathological features. Indian J Pathol Microbiol 2015;58:543-5.3. Gurzu S, Kadar Z, Bara T, Bara TJ, Tamasi A, Azamfirei L, Jung I. Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: Report of two cases. World J Gastroenterol 2015; 21(4): 1329-13334. Lee S. W., Lee I. S., Cho Y. K., et al. A case of mixed adenoneuroendocrine carcinoma of the common bile duct: initially diagnosed as cholangiocarcinoma. Korean Journal of Pathology. 2014;48(6):445–448.

Discussion• MANEC’s are mixed exocrine-endocrine tumours in which each component forms atleast 30% of the tumour.• MANEC’s pose a diagnostic challenge as the neuroendocrine component can have varied morphology, and morphological evaluation and immunohistochemistry is essential for precise diagnosis.• The prognosis of these tumors will depend on the degree of differentiation of each component.• The treatment algorithm of MANEC is not well established. • Surgery may be the mainstay of the treatment and adjunctive therapy with chemotherapy, radiotherapy and somatostatin analogues can be considered according to the NEC type.

Final Impression

MIXED ADENONEUROENDOCRINECARCINOMA OF THE GALL BLADDER

Synaptophysin - positive Chromogranin - positive Ki 67- 70 %

Adenomatous component

Neuroendocrine component