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Case Report
Diagnostic Radiology
2023
:13;
30
doi:
10.25259/JCIS_53_2023

Small-cell cancer of the perihilar bile duct with bleeding esophageal varices: A report of a rare case

Department of Medical Imaging, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam
Department of Internal Medicine, Hanoi Medical University Hospital, Ha Noi, Vietnam
Department of Pathology, Hanoi Medical University, Ha Noi, Vietnam
Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
Corresponding author: Nguyen Minh Duc, Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam. bsnguyenminhduc@pnt.edu.vn
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Xuan Tuan H, Quang Lieu D, Luan D, Minh Duc N. Small-cell cancer of the perihilar bile duct with bleeding esophageal varices: A report of a rare case. J Clin Imaging Sci 2023;13:30.

Abstract

Small-cell cancer is an uncommon histological subtype of neuroendocrine carcinoma. It frequently has a poor prognosis because of distant metastasis. It is diagnosed using histopathological and immunohistochemical tests. We report the case of a 29-year-old female with small-cell cancer in the perihilar bile duct who presented with bleeding esophageal varices. This case report aims to improve physicians’ understanding of small-cell cancer, thereby helping to reduce the frequency of missed clinical diagnoses.

Keywords

Bleeding esophageal varices
Small-cell cancer
Perihilar tumor

INTRODUCTION

Extrapulmonary small-cell cancer (EPSCC), often referred to as high-grade neuroendocrine tumors (NETs), is a malignancy that develops from cells in the amine precursor uptake and decarboxylation pathway. Small-cell lung cancer (SCLC), which is most frequently caused by these cells and originates in the lungs, can occur anywhere in the body.[1] Duguid and Kennedy described for the 1st time EPSCC in a mediastinal lymph node.[2] Since then, cases have been reported of small-cell carcinoma in numerous locations, including the esophagus, stomach, small intestine, colon, rectum, anal canal, appendix, pancreas, gallbladder, and biliary tree[3] and salivary glands, oral cavity, tongue, nasal cavity, and paranasal sinuses[4] as well as the head and neck.[3,4] There are reports of small-cell carcinoma in both the gallbladder[5] and the pancreas.[6] A few studies have reported small-cell cancer of the ampulla of Vater.[7] However, reports of small-cell carcinoma of the liver or common bile duct are extremely rare.

We report the case of a 29-year-old female with small-cell cancer of the perihilar bile duct, presenting as bleeding esophageal varices, and review the relevant literature on this condition.

CASE REPORT

An otherwise healthy 29-year-old woman with no relevant family or medical history of liver diseases presented at our hospital with a sudden onset of hematemesis. The patient was conscious and had vague epigastric pain. All results of cardiopulmonary examinations were negative. There was no yellowing of the skin or sclera, no spider nevus, no edema in both lower limbs, and no vascular murmur. The liver and spleen were not palpable under the ribs and there was no percussion pain in the liver and spleen. Murphy’s sign and shifting dullness were negative. All neurological investigations were also normal.

Routine blood tests showed a significant decrease in hemoglobin concentration (79 g/L) and red blood cell count (3.04 T/L). Laboratory investigations showed normal prothrombin time, increased blood urea nitrogen (14.9 mmol/L), normal liver and renal function, normal electrolytes, and negative hepatitis serology. An upper gastrointestinal endoscopic examination showed evidence of ruptured esophageal varices. Endoscopic variceal ligation with one rubber band was performed successfully on the 1st day of the patient’s admission [Figure 1].

Figure 1:
A 29-year-old woman with small-cell cancer of the perihilar bile duct who presented bleeding esophageal varices. (a) Upper gastrointestinal endoscopy showed the esophageal varices (white arrow), (b) gastric retroflexion experienced the blood in fundus, (c) esophageal endoscopic imaging showed the position of bleeding esophageal varices (white arrow), and (d) endoscopic variceal ligation with one rubber band (white arrow) was done.

Abdominal ultrasound revealed multiple hyperechoic masses in the liver and a large heterogeneous mass in the perihilar bile duct [Figure 2]. Enhanced computed tomography (CT) of the whole abdomen showed multiple calcified intra-abdominal lymph nodes, with a larger mass located in the hepatic hilar region and thrombosis of the main portal vein. No lesion was found on chest CT [Figure 3].

Figure 2:
A 29-year-old woman with small-cell cancer of the perihilar bile duct who presented bleeding esophageal varices. (a) Abdominal ultrasonography revealed a 9 × 12 cm sized heterogeneous mass located in the perihilar bile duct (white arrow), (b) multiple hyperechoic mass were experienced in ultrasound imaging of the liver (white arrow).
Figure 3:
A 29-year-old woman with small-cell cancer of the perihilar bile duct who presented bleeding esophageal varices, (a) abdominal computed tomography (CT) scan revealed the low-density perihilar bile duct mass (white arrow), (b) the tumor gradually improved the density in the arterial (white arrow), (c) the tumor invaded portal vein (white arrow), and caused liver collateral circulation to enlarge (black arrow), and (d) The tumor invaded the duodenum and pancreas (white arrow), (e and f) the chest CT was normal.

A percutaneous needle biopsy of the tumor was performed. Histological examination showed a malignant tumor with small round to oval cells with minimal cytoplasm, fine chromatin, and no distinct nucleoli; necrosis predominated. The tumor cells were positive for synaptophysin and Ki-67: 85% and negative for chromogranin A and CD56. The tumor was then classified as small-cell cancer based on histological and immunohistochemical findings [Figure 4].

Figure 4:
A 29-year-old woman with small-cell cancer of the perihilar bile duct who presented bleeding esophageal varices. A low-density perihilar bile duct mass was detected on an abdominal computed tomography scan. The tumor underwent a percutaneous needle biopsy. Histologic findings of the liver biopsy in the described patient with small-cell cancer. (a and b) Images illustrate hematoxylin and eosin staining, ×10 and ×40, respectively, the tumor consists of round, oval small cells with minimal cytoplasm, fine chromatin, and no distinct nucleoli; necrosis is predominant. Immunohistochemistry for positive synaptophysin (c), Ki67: 85% (e); negative for chromogranin A (d) and CD 56 (f).

These findings led us to diagnose small-cell carcinoma. The tumor was unresectable; therefore, palliative chemotherapy was considered to be the best treatment option. However, the patient died 8 weeks after the diagnosis was confirmed because of a recurrence of bleeding esophageal varices.

DISCUSSION

A case of EPSCC, which was called oat cell carcinoma of the mediastinal glands, was first described as a distinct clinicopathologic disease entity in 1930, which was 34 years after the first of small-cell carcinoma of the lung.[2] Since that time, it has come to be recognized more often. Although 20–25% of bronchogenic carcinomas are small-cell carcinomas, primary locations outside the lung are substantially less common.[8] EPSCC accounts for 2.5–5% of all small-cell carcinomas in the United States.[9] The median age of EPSCC patients in the biggest study was 70 years.[10] The male-to-female sex ratio in this study was also slightly out of balance (1.3:1); nonetheless, the previous studies demonstrated that males are more likely to get cancer than women.[10,11]

To the best of our knowledge, no case of portal hypertension brought on by small-cell carcinoma of the perihilar bile duct has been documented in the literature. Obstructive jaundice has been reported in certain cases; however, there have not been any cases of portal hypertension leading to gastrointestinal bleeding from tumors in the liver and perihilar bile duct. However, this case’s therapy of gastrointestinal bleeding is the same as that given to patients who have cirrhosis-related gastrointestinal bleeding. The tumor’s existence, however, makes the prognosis worse.

Immunohistochemistry is used in conjunction with morphological diagnostics to confirm EPSCC. The neural cell adhesion molecule is also known as CD56, which is the most sensitive neuroendocrine marker. The neurosecretory granule protein chromogranin A, with <50% reactivity, is the least sensitive and most specific marker for neuroendocrine differentiation in EPSCC. The neuron-specific enolase and synaptophysin are two additional sensitive neuroendocrine markers.[1] NETs are separated into well-differentiated (lowto-intermediate grade) NETs and poorly-differentiated (high-grade) neuroendocrine carcinomas (NECs) based on morphological characteristics and proliferation rate (Ki-67 proliferation index).[12] Those that have a Ki-67 proliferation index of more than 55% are considered small-cell carcinomas.[13] The diagnostic criteria for EPSCC need small-cell carcinoma histological hallmarks to be present in the tumor in the absence of clinical symptoms of SCLC, which imaging investigations rule out.[14] Our patient’s sputum cytology test findings for malignancy were negative, and a chest CT indicated no indications of lung cancer; thus, there was no need for a bronchoscopy. Chromogranin A and CD56 were negative in our patient, but synaptophysin was positive, supporting our conclusion. Over 80% of the Ki-67 cells were in mitosis, and 5 mitotic cells/10 HPF were found. Our investigation enabled us to identify small-cell cancer. We classified the carcinoma as a grade 3 (G3) NEC (small-cell type) according to the World Health Organization’s 2010 classification of NETs/NECs.

It is generally agreed on that adjuvant chemotherapy followed by a sufficient surgical resection is the best line of action for EPSCC. Surgery does not increase survival in either EPSCC or SCLC, according to Levenson. This could be the case since the most important prognostic factor for EPSCC patients is the severity of the disease on diagnosis, when the majority of them already have concealed metastases.[8] A poor prognosis for small-cell carcinoma is caused by the frequent presence of distant metastases. The long-term survival rate of EPSCC patients is hence frequently poor.

CONCLUSION

Extrapulmonary small-cell carcinoma is an uncommon type of cancer. Due to the lack of disease specificity in clinicomorphological findings and serological and radiological investigations, diagnosis can only be made through pathology and immunohistochemistry studies. Small-cell carcinoma frequently shows distant metastasis and, consequently, has a poor prognosis. Therefore, the long-term survival of patients with EPSCC is generally poor.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest

There are no conflicts of interest

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Financial support and sponsorship

Nil.

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