Oncology Journal of India

: 2022  |  Volume : 6  |  Issue : 1  |  Page : 32--34

Primary small-cell neuroendocrine carcinoma of the gallbladder with bone metastasis: A rare presentation

Abhishek Anand1, Mohammad Ali1, Sumaira Qayoom2, Geeta Singh1,  
1 Department of Radiotherapy, King Georges' Medical University, Lucknow, Uttar Pradesh, India
2 Department of Pathology, King Georges' Medical University, Lucknow, Uttar Pradesh, India

Correspondence Address:
Abhishek Anand
S/O M. K. Srivastava, House No. 379, Unity City, Kursi Road, Post-Vikas Nagar, Lucknow - 226 022, Uttar Pradesh


Primary small-cell neuroendocrine carcinomas (NEC) of the gallbladder (GB) are rare with aggressive behavior. It has high malignancy potential with a low survival rate. In this case report, we present a case of primary small-cell NEC of GB in a 43-year-old female who presented with complaints of constipation, upper abdominal pain, and poor oral intake which was identified as a GB mass with liver nodularity on ultrasonography. It was subsequently diagnosed as a case of primary small-cell NEC of GB with liver and bone metastasis on contrast-enhanced computed tomography and core needle biopsy obtained from the left iliac bone. In view of severe jaundice, endoscopic retrograde cholangiopancreatography dilatation and stenting was done followed by palliative chemotherapy and radiotherapy. This case is unique in presenting with liver and bone metastases both instead of only liver metastasis as is commonly seen. Moreover, a sample for histopathological diagnosis was also obtained from a bony site rather than the liver as is the norm.

How to cite this article:
Anand A, Ali M, Qayoom S, Singh G. Primary small-cell neuroendocrine carcinoma of the gallbladder with bone metastasis: A rare presentation.Oncol J India 2022;6:32-34

How to cite this URL:
Anand A, Ali M, Qayoom S, Singh G. Primary small-cell neuroendocrine carcinoma of the gallbladder with bone metastasis: A rare presentation. Oncol J India [serial online] 2022 [cited 2022 Aug 19 ];6:32-34
Available from: https://www.ojionline.org/text.asp?2022/6/1/32/343577

Full Text


Neuroendocrine neoplasm (NEN) accounts for <1% of all malignant tumors.[1] It may occur anywhere in the body but most of the cases arise in the gastrointestinal tract (67%) followed by the bronchopulmonary tract (25%).[2] Neuroendocrine carcinomas (NEC), also known as poorly differentiated NEN is considered high-grade tumors and can be small cell, large cell, or mixed types.[3] Primary NEC of the gallbladder (GB) is a rare occurrence which constitutes 1.4% of all gastrointestinal endocrine tumors and 0.4%–4% of all malignant GB tumors.[1] They have a variable age of presentation and a female preponderance over male.[4] They frequently present with liver metastasis. It is rare to find bone metastasis at presentation which we are presenting in our case of GB NEC of small cell type (GB-NEC-SCT) in a 43-year-old woman.

 Case Report

A 43-year-old woman presented to the gastroenterology department on May 29, 2020, with complaints of constipation, upper abdominal pain, and poor oral intake for 4 months. Her WHO performance status was 1. On examination, icterus and pallor were noted. On per abdominal examination, the liver span was approximately 5 cm below the right subcostal margin at midclavicular line. Ultrasonography abdomen was performed which revealed GB mass with nodularity in liver. Thereafter computed tomography (CT) scan of the whole abdomen triple-phase was done, which revealed multiple peripherally enhancing irregular variable-sized hepatic space-occupying lesions in both lobes, largest measuring 4.7 cm × 4.2 cm in the left lobe. An enhancing mass of size 3.6 cm × 3.0 cm was noted in GB which was circumferentially involving GB neck and proximal body region. Fat planes with the adjacent common bile duct appeared lost pointing toward invasion, with proximal bilobar intrahepatic biliary radicle dilatation. Fat planes between the adjacent liver parenchyma (segment V) and GB mass were also lost. Spleen was mildly enlarged in size 12.2 cm with few subcentimetric celiac group of nodes noted. Multiple soft tissue lesions were also noted which involved dorsal lumbar vertebra as well as left iliac bone [Figure 1].{Figure 1}

Serum tumor markers revealed raised levels of CA19-9-79 u/ml.

Core needle biopsy was performed from soft tissue component of the expansile lytic left iliac bone region. On microscopy, a metastatic epithelial tumor with nesting pattern with areas of necrosis was seen [Figure 2]a and [Figure 2]b. Immunohistochemistry was done on tumor cells, which showed diffuse positivity for cytokeratin (weak) and synaptophysin, strong and diffuse positivity for p53, negative for P40, while ATRX showed retained expression. The proliferation marker Ki67 index was 50%–55% [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e.{Figure 2}{Figure 3}

A diagnosis of metastatic, high-grade NEC, favoring small-cell carcinoma of GB was made.

Further, whole-body PET-CT scan was done to assess the extent of metastasis. GB showed metabolically active lobulated circumferential wall thickening (SUV max 9.6), extending into the segments IV, V, and VI of the liver. The liver showed other metabolically active hypodense lesions of varying sizes in both lobes (segment II-5.0 cm × 4.7 cm, SUV max 7). Metabolically, active enlarged periportal and portocaval (3.8 cm × 3.2 cm, SUV max 9.5) lymph nodes were also noted. Both axial and appendicular systems were studded with metabolically active lytic lesions throughout and showed associated soft tissue components (left iliac bone-SUV max 6.3 and soft tissue component 5.6 cm × 4.2 cm) [Figure 4]. Following this, endoscopic retrograde cholangiopancreatography with biliary dilatation and stenting was done. Her case was subsequently put-up for discussion in tumor board and subsequently, palliative chemotherapy and radiotherapy were planned.{Figure 4}

Palliative radiotherapy was given followed by palliative chemotherapy. The patient received palliative radiotherapy for bone pain in the left iliac region in a dose of 30 Gy in 10 fractions. Total four cycles of chemotherapy were given. Cisplatin 40 mg (Day 1 and Day 2) and etoposide 100 mg (Day 1, Day 2, Day 3) 3 weekly and discharged after each cycle. Furthermore, three cycles of zoledronic acid 4 mg (Day 1) 28 days cycle were administered. The patient expired after 15 days of the last cycle of chemotherapy.


GB-NEC-SCT is an extremely rare entity with high malignancy potential. These patients are usually presented at a younger age in comparison to adenocarcinoma GB patients. Yun et al. in a retrospective review found that GB-adenocarcinoma patients were significantly older than GB-NEC-SCT patients (67.89 ± 11.15 vs. 55.75 ± 10.31 years; P = 0.029).[5]

The preoperative diagnosis of GB-NEC and to differentiate these patients from adenocarcinoma GB patients is difficult due to nonspecific symptoms and nonspecific imaging findings. Diffusion-weighted imaging in magnetic resonance imaging may be helpful for classifying these two types of cancer as NEC have a relatively low diffusion ability than adenocarcinoma due to its higher proliferation potential and a high-cell-density.[6],[7] Moreover, a combination of NEC with adenocarcinoma may be seen in the same patient.[4],[5]

GB-NEC is characterized by rapid development, early liver metastasis, lymph node metastasis, and metastasis to distant sites, and the prognosis is extremely poor.[1],[5],[8] According to Moskal et al., the common sites of metastasis in GB-NEC-SCT were nodes (88%), liver (88%), lung (23%), and peritoneum (19%).[4] Our case is initially detected with node, liver, and bone as the different sites of distant metastases in GB-NEC-SCT. Osseous metastasis in NEC of GB is extremely rare and such metastasis at initial diagnosis is rarer. Kamboj et al., in a retrospective review on NEC of GB find upfront bone metastasis in 2 of 19 NEC cases.[9] Tunio et al., in a report, found distal humerus as delayed site metastasis in a treated case of small-cell carcinoma of GB.[10]

The only curative therapeutic approach for GB-NEC-SCT is radical surgery. However, there is no rational surgical strategy due to the paucity of data and less understanding of the biology of the lesions.[1] The patients develop recurrent or metastatic disease even after complete surgical resection.[10] More than half of all patients have disseminated disease at diagnosis. The rational of radiotherapy and chemotherapy use is unclear. However, several case reports highlighted the useful of chemotherapeutic agents such as cisplatin, gemcitabine, and etoposide plus 5-fluorouracil.[11],[12] Instead of the poor prognosis of GB-NEC-SCT, aggressive multimodal treatment may improve survival.[1],[4]

GB-NEC-SCT has worse prognosis and low survival rate than GB-adenocarcinoma. A Surveillance, Epidemiology, and End Results database published in 2010 revealed 1-year and 5-year survival rates of 21% and 0% for small-cell NEC GB.[1] Our case is presented as advanced disease with liver and bone metastasis where definitive treatment had no role. In view of that palliative therapy with supportive care was planned to improve the quality of life.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

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