A Large Cell Neuroendocrine Carcinoma of the Gall Bladder: Diagnosis with 18FDG-PET/CT-guided Biliary Cytology and Treatment with Combined Chemotherapy Achieved a Long-term Stable Condition

Abstract

Poorly differentiated neuroendocrine cell carcinomas of the gallbladder are rare and patients with such tumors have a poor prognosis. We describe a 64-year-old male with a large cell neuroendocrine carcinoma of the gallbladder and multiple lymph node metastases. Diagnostic excisional biopsy of the left axillary lymph nodes revealed atypical cells with predominantly large-sized round-to-oval nuclei, proliferating in a solid and focal nesting pattern. The tumor cells were positive for synaptophysin and chromogranin A, and strongly positive for Ki-67, leading to a diagnosis of poorly differentiated neuroendocrine cell carcinoma of the gallbladder, of large cell type. Using (18)F-fluorodeoxy glucose-positron emission tomography/computed tomography to determine the origin of these tumors, we observed the accumulation of (18)F-fluorodeoxy glucose in multiple large lymph nodes, a small part of the liver and the fundus of the gallbladder. Computed tomography-guided aspiration of the gallbladder showed the same pleomorphic tumor cells as the lymph nodes. The patient was diagnosed with a large cell neuroendocrine carcinoma of the gallbladder, only ∼25 mm in diameter. Combination chemotherapy with cisplatin and docetaxel, the regimen used for non-small cell lung carcinomas, and probably large cell lung carcinomas, resulted in the disappearance of the lymph node metastases and a marked improvement in the performance status for ∼22 months. The poor prognosis of patients with these aggressive tumors may be improved by the use of minimally invasive diagnostic procedures and combined systemic chemotherapy as soon as possible.

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

“…3,[6][7][8][9][10][11]23 It is not possible to preoperatively differentiate between gallbladder adenocarcinoma and gallbladder neuroendocrine carcinoma (NEC) with imaging techniques because other neoplasms (i.e., hepatocellular carcinoma, cholangiocarcinoma, hepatic metastasis involving the gallbladder, and gallbladder adenocarcinoma) may have similar patterns. 3,[6][7][8][9][10][11]23 Ultrasonography has low sensitivity (44%) for the identification of gallbladder cancer. 13 In our case, abdominal ultrasonography and radiologic findings revealed a 25-mm gallbladder tumor with suspected malignancy.…”

“…Okuyama et al 10 previously reported that 18FDG-PET/CT was useful for confirmation of the origin of lymph node metastases and the effective clinical diagnosis of patients with gallbladder LCNEC. 10 Nakagawa et al 14 suggested that cytologic screening had an advantage over histologic approaches based on hematoxylin and eosin (HE) staining with respect to qualitatively diagnosing gallbladder LCNEC. Conventional HE staining requires paraffin embedding of the tissue, which involves dehydration and deparaffinization during processing.…”

“…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. [16][17][18] Recent research has demonstrated that SSTR-2a is widely expressed in NETs; findings obtained using a scoring system indicated that this receptor could be a diagnostically and therapeutically valuable target.…”

“…The prognosis is very poor for patients with unresectable masses, although multimodal treatments, including chemotherapy and radiation ther-apy, have achieved good responses in some reports. 3,[6][7][8][9][10][11]23 Among our 9 reviewed case reports, 8 patients died of the disease, with a median survival time of 17.5 months. Four long-surviving patients had several similar characteristics, such as small tumor size and no liver invasion or metastasis; these patients underwent radical surgery.…”

“…5 Only a few studies involving pure LCNEC cases without other histologic components have been reported in the literature. 3,[5][6][7][8][9][10][11] Therefore, the biological behavior, appropriate treatment modalities, and overall patient prognosis remain largely unclear.…”