Targeted Sequencing of Mixed Neuroendocrine- Non-neuroendocrine Neoplasm of the Gallbladder Suggests a Monoclonal Origin: A Case Report

Flora Mae Sta. Ines, Anna Louise Anceno, Rachelle Arah Salamat, Narciso Navarro Jr., Glenda Lyn Pua, Jose Jasper Andal, Daphne Ang

Abstract

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the gallbladder is a rare tumor that is defined in the World Health Organization (WHO) 2019 digestive system tumor classification as the presence of a neuroendocrine neoplasm admixed with a non-neuroendocrine carcinoma, each component constituting at least 30% of the neoplasm. The exact pathogenesis of MiNENs remains unclear. We present a case of a 74-year-old Filipino woman who presented with nonspecific clinical and radiologic findings and subsequently underwent cholecystectomy. Histopathologic and immunohistochemical evaluation of the gallbladder confirmed the diagnosis of a mixed well-differentiated adenocarcinoma (30%) and large cell neuroendocrine carcinoma (70%). The adenocarcinoma and neuroendocrine carcinoma components were separately microdissected and submitted for targeted 15-gene sequencing using the Illumina Trusight Tumor 15 (TST15) panel. NGS identified a TP53 missense mutation leading to a stop codon in both components. The finding of similar molecular signatures in the two morphologically distinct components supports the hypothesis that MiNEN arises from a common precursor stem cell capable of divergent phenotypic differentiation.

Keywords

gallbladder, MiNEN, molecular analysis

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References

Liu W, Wang L, He XD, Feng C, Chang XY, Lu ZH. Mixed large cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder: a case report and brief review of the literature. World J Surg Oncol. 2015;13:114. PMID: 25890047. PMCID: PMC4365805. https://doi.org/10.1186/s12957-015-0533-6.

Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. WHO classification of tumour of the digestive system, 5th edition. Lyon: IARC Press, 2019.

Miyamoto R, Kikuchi K, Uchida A, et al. Large cell neuroendocrine carcinoma of the gallbladder: a case report and literature review. Int Surg. 2016;101:458-64. https://doi.org/10.9738/10.9738/INTSURG-D-16-00122.1.

Acosta AM, Wiley EL. Primary biliary mixed adenoneuroendocrine carcinoma (MANEC): a short review. Arch Pathol Lab Med. 2016;140(10):1157-62. PMID: 27684986. https://doi.org/10.5858/arpa.2015-0102-RS.

Jung J, Chae YS, Kim CH, et al. Combined adenosquamous and large cell neuroendocrine carcinoma of the gallbladder. J Pathol Transl Med. 2018;(52):121-5. PMID: 28994275. PMCID: PMC5859238. https://doi.org/10.4132/jptm.2017.08.20.

Chen XS, Xie XF, Zhou JJ. Mixed large cell neuroendocrine carcinoma and adenosquamous carcinoma of gallbladder: a case report. Int J Clin Exp Pathol 2017;10(2):1882-5. http://www.ijcep.com/files/ijcep0042195.pdf.

Skalický A, Vištejnová L, Dubová M, Malkus T, Skalický T, Troup O. Mixed neuroendocrine-non-neuroendocrine carcinoma of gallbladder: case report. World J Surg Oncol. 2019;17. https://doi.org/10.1186/s12957-019-1598-4.

De Mestier L, Cros J. Digestive system mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN). Ann Endocrinol (Paris). 2019;80(3):172–3. PMID: 31064662. https://doi.org/10.1016/j.ando.2019.04.006.

Goldblum JR, Odze RD. Odze and Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. Philadelphia, PA: Elsevier Saunders, 2015.

Eltawil KM, Gustafsson BI, Kidd M, Modlin IM. Neuroendocrine tumors of the gallbladder: an evaluation and reassessment of management strategy. J Clin Gastroenterol. 2010;44(10):687-95. PMID: 20375728. https://doi.org/10.1097/MCG.0b013e3181d7a6d4.

Mills SE. Histology for Pathologists. Fourth ed. Philadelphia, PA: Wolters Kluwer, 2012.

Buscemi S, Orlando E, Damiano G, et al. "Pure" large cell neuroendocrine carcinoma of the gallbladder: report of a case and review of the literature. Int J Surg. 2016; 28(Suppl 1): S128-32. PMID: 26708705. https://doi.org/10.1016/j.ijsu.2015.12.045.

Paniz Mondolfi AE, Slova D, Fan W, et al. Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: a possible stem cell tumor? Pathol Int. 2011;61(10):608-14. PMID: 21951672. https://doi.org/10.1111/j.1440-1827.2011.02709.x.

Diamantis I. Karamitopoulou E, Perentes E, Zimmermann A. p53 protein immunoreactivity in extrahepatic bile duct and gallbladder cancer: correlation with tumor grade and survival. Hepatology. 1995;22(3):774-9. PMID: 7657282.

Sato K, Imai T, Shirota Y, Ueda Y, Katsuda S. Combined large cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder. Pathology Res Pract. 2010;206(6):397-400. PMID: 19945229. https://doi.org/10.1016/j.prp.2009.10.008.

Javle M, Rashid A, Churi C, et al. Molecular characterization of gallbladder cancer using somatic mutation profiling. Hum Pathol. 2014;45(4):701-8. PMID: 24508317. PMCID: PMC4428571. https://doi.org/10.1016/j.humpath.2013.11.001.

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