Endoscopic ultrasound‐guided fine‐needle aspiration diagnosis of large cell neuroendocrine carcinoma of the gallbladder and common bile duct: Report of a case

Abstract

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows a reliable and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report the cytopathologic findings of a case of large cell neuroendocrine carcinoma (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67-year-old woman who presented with progressive abdominal pain and jaundice. EUS-FNA of the mass involving the common bile duct and of a porta hepatis lymph node showed abundant cellularity with tumor cells arranged singly and occasionally in tight and loose clusters and rosette-like structures in a background showing extensive necrotic debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56, synaptophysin, and chromogranin and showed a very high proliferative fraction on Ki67 staining, supporting the diagnosis of a high-grade NEC. Due to the large size of the neoplastic cells, moderate amounts of cytoplasm and prominent nucleoli, a diagnosis of LCNEC was made on the EUS-FNA sample. Despite the prompt institution of chemotherapy, the patient died shortly thereafter and the diagnosis was confirmed at autopsy. This is to our knowledge the first case of LCNEC of the gallbladder and bile ducts diagnosed by EUS-FNA.

Neuroendocrine tumors of the gallbladder (Review)

“…Apart from the pathological immunohistochemical examinations, contrast-enhanced ultrasonography has differential clinical significance (38). Case reports using contrast-enhanced ultrasonography have revealed that biliary sludge is not enhanced (39) .In these case reports, the gallbladder polyp was enhanced with grape-like fine pedicles and the three-layer structure of gallbladder wall was clear (40) .For adenomyosis of the gallbladder, unenhanced vesiculoid echocardiography was observed and the inner and serous membranes of the gallbladder were intact (41). Gallbladder adenoma resulted in delayed enhancement that was identifiable by 'fast in and slow out' through the complete three-layer structure of the gallbladder wall (38).…”

Non-functioning neuroendocrine tumors of the common hepatic duct: a case report and literature review

“…In grade I (low) and grade II (intermediate), NET are considered well differentiated tumors, as for grade 3 (high), they are called poorly differentiated NEC. [6][7][8] But recently, the new European Neuroendocrine/WHO nomenclature and classification for neuroendocrine tumors has included in addition to the grading system, the mitotic count and the Ki-67 index.…”

“…Preoperative diagnosis was possible in few cases only. 6,7 The prognosis is based on the tumor grading on pathology. They are considered benign when dealing with well to moderately differentiated cells (Grades 1 and 2) and called NET.…”

“…However, when poorly differentiated cells (Grade 3) are found, they are identified as neuroendocrine carcinomas (NEC). 6,8,9 Specific data about extra pancreatic non GIT (ectopic pancreas) NET treatment is not available. But, surgery remains the only therapeutic option being a part of a multidisciplinary approach.…”

Large Cell Neuroendocrine Carcinoma of the Gallbladder: A Case Report and Literature Review

“…A previous report also described the advantages of cytologic examinations using endoscopic, ultrasound-guided, fine-needle aspiration samples for the early diagnosis of LCNEC in the biliary tract. 15 The histologic features of LCNEC are as follows: (1) positivity for neuroendocrine markers, among which chromogranin A and synaptophysin are the most commonly identified; (2) a mitotic count exceeding 20/10 high-power fields or a Ki67 index over 20%; and (3) a specific NET pattern of an organoid structure, rosette formation, and palisading and trabecular arrangement, as well as prominent nuclei that are more than 3-fold the diameter of a lymphocyte. 3,[5][6][7][8][9][10][11] Immunohistochemical examinations of chromogranin A, synaptophysin, CD56, and Ki67 were performed using enzyme-antibody and streptavidin-peroxidase techniques described in prior reports.…”