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Mixed adenoendocrine carcinoma in the extrahepatic biliary tract: A case report and literature review

Neuroendocrine neoplasm (NEN) comprises a group of tumors that exhibit neuroendocrine phenotypes. NEN is subclassified into neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC), based on histopathological parameters. NEN in the extrahepatic biliary tract (EHBT) is uncommon. Little is known about its clinicopathological features and prognostic indicators. The present study presented a case of MANEC in the distal common bile duct (CBD) and reviewed…

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. 2019 Aug;18(2):1585-1596.

doi: 10.3892/ol.2019.10502. Epub 2019 Jun 20.

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Liang Zhang et al. Oncol Lett. .

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Abstract

Neuroendocrine neoplasm (NEN) comprises a group of tumors that exhibit neuroendocrine phenotypes. NEN is subclassified into neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC), based on histopathological parameters. NEN in the extrahepatic biliary tract (EHBT) is uncommon. Little is known about its clinicopathological features and prognostic indicators. The present study presented a case of MANEC in the distal common bile duct (CBD) and reviewed previous cases of NENs in the EHBT to characterize the clinical settings of this disease entity and to identify influencing factors of survival outcomes. A 64-year-old Chinese woman presented with abdominal pain and jaundice. Imaging studies demonstrated malignant stenosis in the distal CBD. Bile duct brush cytology revealed small clusters of atypical cells. Following an initial diagnosis of distal cholangiocarcinoma (CCA), the patient underwent pancreaticoduodenectomy. Histological analysis combined with immunohistochemical investigation of the resected specimen revealed a collision tumor that was composed of poorly differentiated adenocarcinoma and NEC. Each histological component accounted for >30% of the tumor. The definitive diagnosis was a MANEC in the distal CBD. Multiple intrahepatic and pulmonary metastases were observed postoperatively over 8 months. The patient succumbed to the disease 12 months after surgery. In conclusion, NEN occurs infrequently in the EHBT, with NET being the predominant type. NEN in the EHBT is extremely challenging to diagnose preoperatively due to its tendency to mimic CCA. Patients with NEN in the EHBT exhibited extremely distinct oncology outcomes according to pathological types. Additionally, old age (>60 years) and the presence of tumor recurrence were associated with decreased survival of patients with NEN.

Keywords: extrahepatic biliary tract; management; mixed adenoendocrine carcinoma; neuroendocrine neoplasm; prognosis.

Figures

Figure 1.

Figure 1.

(A) Magnetic resonance cholangiopancreatography and (B) endoscopic retrograde cholangiopancreatography. The images show severe stenosis at the distal common bile duct (white arrows). Marked dilations of the proximal biliary tract and main pancreatic duct were observed.

Figure 2.

Figure 2.

Pathological analysis of the surgical specimen. (A) Tumor was composed of adenocarcinoma and neuroendocrine components, with each occupying >30% of the lesion. The two components were arranged in a clearly separated pattern (H&E; magnification, ×100). (B) Neuroendocrine component was formed by small tumor cells with scant cytoplasm and hyperchromatic nuclei (H&E; magnification, ×200). (C) Mucin pool and signet ring-like cell clusters were noted in the adenocarcinoma component (H&E; magnification, ×200). (D) Metastatic lesions in the lymph nodes were predominantly neuroendocrine carcinoma (H&E; magnification, ×40). Immunohistochemical staining revealed that the neuroendocrine component was strongly positive for (E) chromogranin A (magnification, ×200), (F) cluster of differentiation 56 (magnification, ×200) and (G) synaptophysin (magnification, ×200), with a (H) Ki-67 labeling index >50% (magnification, ×200). H&E, hematoxylin and eosin.

Figure 3.

Figure 3.

Kaplan-Meier survival curves of patients with neuroendocrine neoplasm in the extrahepatic biliary tract. (A) NEC was associated with the worst prognosis, followed by MANEC and NET (P0.001). (B) Patients aged >60 years exhibited a worse survival rate compared with those who were ≤60 years old (P=0.033). (C) Tumor recurrence was associated with a decreased survival rate (P0.001). MANEC, mixed adenoendocrine carcinoma; NEC, neuroendocrine carcinoma; NET, neuroendocrine tumor.

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References

    1. Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72. doi: 10.1016/S1470-2045(07)70410-2. – DOI PubMed
    1. Uccella S, La Rosa S, Volante M, Papotti M. Immunohistochemical biomarkers of gastrointestinal, pancreatic, pulmonary, and thymic neuroendocrine neoplasms. Endocr Pathol. 2018;29:150–168. doi: 10.1007/s12022-018-9522-y. – DOI PubMed
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