Extramedullary metastasis of the hilar bile duct in multiple myeloma: a case report and literature review
Case Report

Extramedullary metastasis of the hilar bile duct in multiple myeloma: a case report and literature review

Fei Liu1#, Wei Li1#, Wanfeng Wu1, Buwei Teng1, Wenlei Li1, Kai Li1, Xiangcheng Li2

1Department of Hepatobiliary Surgery, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang, China; 2Hepatobiliary Center, Key Laboratory of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, China

Contributions: (I) Conception and design: F Liu, Wei Li, X Li; (II) Administrative support: K Li; (III) Provision of study materials or patients: B Teng; (IV) Collection and assembly of data: W Wu, Wei Li; (V) Data analysis and interpretation: F Liu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Correspondence to: Kai Li, BA. Department of Hepatobiliary Surgery, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, No. 6 Zhenhua East Road, Lianyungang 222061, China. Email: lkgdwk03178@163.com; Xiangcheng Li, MD, PhD. Hepatobiliary Center, Key Laboratory of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, China. Email: drxcli@njmu.edu.cn.

Background: Extramedullary multiple myeloma (EMM) is defined by the infiltration of malignant plasma cells into non-osseous tissues. Its co-occurrence with hilar cholangiocarcinoma remains extraordinarily rare. This diagnostic overlap poses substantial clinical risks, as misclassification of EMM as biliary carcinoma may lead to inappropriate surgical interventions and delayed systemic therapy, ultimately compromising patient survival. Therefore, we report this case of misdiagnosis to help reduce the rate of misdiagnoses in the future.

Case Description: A 72-year-old male with λ multiple myeloma (MM) (type III, Group B) presented with painless jaundice and weight loss. Laboratory findings revealed obstructive jaundice [total bilirubin (TBIL) 312.3 mg/dL, direct bilirubin (DBIL) 161.5 mg/dL] and elevated carbohydrate antigen 19-9 (CA19-9) (130.5 U/mL). Contrast-enhanced computed tomography (CT) demonstrated a 3 cm hilar mass with peripheral ductal dilation, and magnetic resonance cholangiopancreatography (MRCP) showed abrupt biliary stricture. Despite radiographic features mimicking cholangiocarcinoma, considering the patient’s history of myeloma, our team selected CT-guided biopsy of the hilar bile duct tumor. Immunohistochemical analysis confirmed syndecan-1 (CD138)(3+)/cluster of differentiation 38 (CD38)(1+)/cluster of differentiation 3 (CD3)(+)/λ-restricted plasma cell infiltration. The patient was diagnosed with EMM complicated with hilar bile duct metastasis. Subsequently, the patient avoided unnecessary surgical procedures and received proper treatment in the hematology department.

Conclusions: This represents the first documented case of EMM metastasizing to the hilar bile duct, underscoring crucial diagnostic considerations. In patients presenting with hepatic hilar masses—particularly those with a history of MM—hematological malignancies must be included in the differential diagnosis. A multidisciplinary diagnostic approach integrating histopathological analysis, serum biomarkers, and advanced imaging modalities can effectively prevent unnecessary surgical interventions while optimizing therapeutic outcomes.

Keywords: Case report; multiple myeloma (MM); extramedullary multiple myeloma (EMM); hilar cholangiocarcinoma

Submitted Mar 03, 2025. Accepted for publication Jun 17, 2025. Published online Oct 30, 2025.

doi: 10.21037/jgo-2025-160

Highlight box

Key findings

• We report a case of multiple myeloma (MM) with hilar bile duct metastasis misdiagnosed as cholangiocarcinoma. The patient successfully avoided unnecessary surgery and received professional internal medicine treatment.

What is known and what is new?

• Extramedullary multiple myeloma (EMM) is a special subtype of MM, and the literature reports that EMM often involves soft tissues, the stomach, lymph nodes, and lungs. At present, there are no reports on MM complicated with hilar bile duct metastasis.

• This case report shows that myeloma can be accompanied by extramedullary metastasis to the hepatic hilar bile duct and is easily misdiagnosed as cholangiocarcinoma. Such misdiagnosis may result in patients undergoing unnecessary surgical procedures. This has certain reference value for guiding clinical diagnosis and reducing misdiagnosis of EMM.

What is the implication, and what should change now?

• For patients considering tumors in the bile duct or other areas, if there is a history of myeloma, surgical treatment should be performed with caution, and the pathological diagnosis should be actively clarified before intervention. For patients diagnosed with myeloma complicated with metastasis, chemotherapy treatment should be actively implemented instead of surgical treatment to maximize patient benefits.

Introduction

Multiple myeloma (MM) is a blood cancer caused by abnormal growth of plasma cells in the bone marrow, which can damage various organs, and there is no cure at present (1,2). A rare form called extramedullary multiple myeloma (EMM) occurs when cancer cells spread beyond the bone marrow (3,4). EMM presents with varied and complex symptoms, making both diagnosis and treatment challenging (5). This study describes a rare case of EMM involving hilar bile duct metastasis, outlining its clinical features and treatment plan, supported by a comprehensive literature review. Our goal is to help clinicians better recognize this condition, make more accurate diagnoses, and develop improved treatment approaches. By sharing this knowledge, we hope to reduce diagnostic mistakes and enhance patient survival and quality of life. We present this article in accordance with the CARE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-160/rc).

Case presentation

A 72-year-old male presented to The First People’s Hospital of Lianyungang with a one-month history of worsening jaundice (skin and eyes) and fatigue. His symptoms began with unexplained yellowing of the skin, dark urine, and occasional abdominal bloating and discomfort. He reported no fever, chills, digestive problems, or breathing difficulties. Over the month, his condition had gradually worsened, with noticeable declines in mental alertness, appetite, and sleep quality, along with an 8 kg weight loss. Despite these changes, his bowel movements remained normal. Importantly, he had not sought medical attention before attending The First People’s Hospital of Lianyungang on 28 June 2023.

The patient had been diagnosed with light chain λ-III group B MM in The First People’s Hospital of Lianyungang 28 months prior to this presentation and had begun to receive PCD treatment (pomalidomide, cyclophosphamide, and dexamethasone on days 1, 4, 8, and 11). However, due to the restrictions associated with coronavirus disease 2019 (COVID-19), this treatment was suspended. The treatment had resumed 14 months ago, comprising daratumumab and dexamethasone (day 1 and day 8). The patient showed yellowing of the eyes and skin, with no other notable physical findings.

Initial blood tests showed significant abnormalities: total bilirubin (TBIL; 312.3 µmol/L), direct bilirubin (DBIL; 161.5 µmol/L), and indirect bilirubin (IBIL; 150.8 µmol/L) were all elevated. Liver function tests revealed increased levels of alanine aminotransferase (ALT; 105 U/L), aspartate aminotransferase (AST; 74 U/L), gamma-glutamyl transferase (GGT; 228 U/L), alkaline phosphatase (ALP; 412 U/L), total bile acids (TBA; 152.0 µmol/L), and total protein (TP; 56.2 g/L). Notable tumor markers included elevated free light chain λ (337.5 mg/L; normal: 5.71–26.3 mg/L), urinary immunoglobulin light chain (371.00 mg/L; normal: <50 mg/L), and carbohydrate antigen 19-9 (CA19-9; 130.50 U/mL). Glutathione reductase activity was 89.8 U/L. Other test results were unremarkable. Computed tomography (CT) imaging of the upper abdomen, both with and without contrast, revealed a hilar bile duct lesion with intrahepatic bile duct dilation, suggesting possible cholangiocarcinoma.

The patient presented with significantly elevated CA19-9 levels and CT revealed an enhanced hilar bile duct mass. This lesion demonstrated characteristic delayed enhancement, strongly suggesting malignancy. Given the patient’s frail condition, the family refused additional invasive tests and opted for conservative care. To address the severe jaundice caused by high biliary obstruction, ultrasound-guided percutaneous transhepatic cholangial drainage (PTCD) was successfully performed on 30 June 2023. Bile drainage (amounting to a substantial volume) was maintained for 11 days (Figure 1A), and liver function also improved significantly (Figure 1B). Supportive therapies including hepatoprotective treatment, nutritional supplementation, and electrolyte correction were implemented. After achieving clinical stability, the patient was discharged on 11 July 2023.

Figure 1 Bile drainage volume and alterations in liver function. (A) The alteration in the volume of bile drainage through the PTCD catheter. (B) Changes in serum bilirubin (µmol/L) and transaminase (U/L) levels. PTCD, percutaneous transhepatic cholangial drainage.

The patient consented to surgical treatment and was readmitted on 31 August 2023. Initial laboratory tests revealed cholestatic patterns: TBIL 33.8 µmol/L (DBIL 14.8 µmol/L, IBIL 19.0 µmol/L) with elevated GGT (261 U/L). Hypoproteinemia (total protein 45.5 g/L) and abnormal coagulation (prothrombin time 142 mAU/mL) were observed. Notably, CA19-9 levels rose to 130.50 U/mL. Hepatic transaminases remained near-normal (ALT 41 U/L, AST 26 U/L). Other parameters showed no significant deviations.

The contrast-enhanced upper abdominal CT demonstrated the following: (I) intrahepatic biliary duct dilatation; (II) biliary stricture at the hepatic hilum; and (III) suspicious enhancing lesions exhibiting delayed-phase enhancement with encasement of the portal vein (Figure 2A). Complementary magnetic resonance cholangiopancreatography (MRCP) demonstrated clustered soft tissue abnormalities at the same site, displaying characteristic signal patterns: T1 hypointensity, T2 hyperintensity, and diffusion-weighted imaging (DWI) hyperintensity (Figure 2B,2C)—imaging features supporting a cholangiocarcinoma diagnosis.

Figure 2 Imaging and pathological features of hilar bile duct extramedullary metastasis. (A) Enhanced CT reveals a hilar bile duct mass, where the red arrow pointed. (B) Diffusion restriction (red arrow) in hilar bile duct mass on diffusion-weighted imaging. (C) MRCP showing hilar bile duct interruption with distal dilatation (red arrow). (D) Pathological examination (H&E staining) of the tumor shows small blue cells (red arrow, original magnification ×400). CT, computed tomography; H&E, hematoxylin-eosin; MRCP, magnetic resonance cholangiopancreatography.

Multidisciplinary team (MDT) discussions and literature review yielded no reported cases of myeloma with hilar bile duct metastasis. Elevated CA199 levels and imaging findings (CT and MRCP) supported a diagnosis of hilar cholangiocarcinoma. Given the patient’s myeloma history, a porta hepatis biopsy was performed to confirm the diagnosis and rule out metastasis.

Following family consent, CT-guided biopsy of the hilar bile duct mass was performed on 5 September 2023. Histopathological analysis integrating morphology, immunohistochemistry [syndecan-1 (CD138)(3+), cluster of differentiation 38 (CD38)(1+), multiple myeloma oncogene 1 (MUM1; 2+), antigen identified by monoclonal antibody Ki-67 (Ki-67; 40%+), with negative cluster of differentiation 56 (CD56)/cytokeratin 7 (CK7)/cytokeratin 19 (CK19)/cluster of differentiation 20 (CD20)], and clinical jaundice history confirmed a plasma cell neoplasm, indicating metastatic bone marrow tumor to the biliary system (Figure 2D). These findings established a final diagnosis of MM with hilar bile duct involvement, ruling out primary cholangiocarcinoma. The patient was subsequently transferred to the hematology department for specialized care on 13 September 2023.

During the follow-up period, the patient received treatment with daratumumab plus carfizomib/dexamethasone (Dara Kd). Partial mandibular resection and tooth extraction were performed at 6 months due to bone metastasis. The lung mass biopsy confirmed myeloma lung metastasis on 19 January 2024. The patient ultimately passed away on 14 September 2024. Figure 3 shows the timeline of patient treatment.

Figure 3 The timeline of patient treatment. PTCD, percutaneous transhepatic cholangial drainage.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report and accompanying images was waived from requiring patient consent according to The First People’s Hospital of Lianyungang Ethics Committee.

Discussion

This case report describes an MM patient with hepatic hilar duct metastasis initially misdiagnosed as cholangiocarcinoma. Accurate diagnosis prevented unnecessary surgery and offers management insights for extramedullary involvement. Histopathological examination was shown to be critical for avoiding misdiagnosis in this diagnostically challenging case. The findings reinforce the importance of tissue biopsy and multidisciplinary consultation when evaluating biliary lesions in myeloma patients.

Although therapeutic advances have improved MM management, extramedullary metastasis remains a key prognostic determinant (6). EMM refers to the spread of malignant plasma cells beyond the bone marrow microenvironment, establishing colonies in distant sites (7). EMM cells typically display immature plasmacytoid morphology, increased invasiveness, and distinct biological features compared to primary myeloma cells (8-10). EMM is rare in clinical practice, typically involving soft tissues, gastrointestinal organs, lymph nodes, lungs, and the central nervous system (CNS) (11,12). No prior cases of hilar bile duct metastasis have been reported. Current research suggests that EMM pathogenesis involves myelocytomatosis oncogene (Myc) mutations, long non-coding RNA (lncRNA) dysregulation, tumor microenvironment alterations, and genetic abnormalities (13-17).

Hilar bile duct metastasis in EMM involves malignant plasma cell infiltration of duct walls, causing stenosis or obstruction. Clinical manifestations include obstructive jaundice, right upper quadrant pain, anorexia, weight loss, and fatigue. EMM with hilar bile duct metastasis typically shows laboratory evidence of biliary obstruction and imaging findings of hilar mass with distal duct dilation on contrast-enhanced CT and MRCP. These features are radiologically identical to hilar cholangiocarcinoma, frequently leading to misdiagnosis. Accurate diagnosis of hilar bile duct EMM requires a multimodal approach combining imaging, laboratory tests, and histopathology. Biopsy remains the gold standard, with percutaneous or endoscopic approaches providing definitive diagnostic evidence. In this case, it was confirmed by histopathology.

No standardized treatment exists for hilar bile duct EMM, necessitating individualized therapy. Proteasome inhibitors form the treatment backbone: bortezomib and carfilzomib have shown significant progression-free survival (PFS) and overall survival (OS) benefits in EMM patients (18,19). Lenalidomide, a second-generation immunomodulator, reduces pro-inflammatory cytokines while increasing interferon gamma, enhancing dendritic cell antigen presentation and natural killer T cell activity (20). Pomalidomide, a newer agent in this class, inhibits cytokine production, suppresses MM cell proliferation, and induces apoptosis with improved safety (21).

Autologous hematopoietic stem cell transplantation (HSCT) improves survival in eligible MM patients, particularly as first-line therapy for those under 65 years of age, offering significant benefits for EMM (22). Radiotherapy (RT) effectively manages localized disease and bone pain, with studies showing partial remission in EMM patients receiving local RT (23). For patients with jaundice and hepatic dysfunction, routine interventions include biliary drainage [PTCD/endoscopic retrograde cholangiopancreatography (ERCP)], stenting, hepatoprotection, and nutritional support.

Following pathological confirmation, the patient received Dara Kd regimen chemotherapy with PTCD for jaundice management, hepatoprotection, and nutritional support. Subsequent pulmonary metastasis necessitated treatment modification to selenidazole-pomalidomide-dexamethasone. The patient ultimately died 16 months after initial presentation.

Conclusions

This report details a rare case of hilar bile duct extramedullary metastasis in myeloma, highlighting its clinical features and management challenges. Our findings, supported by literature review, emphasize the need for clinical vigilance in myeloma patients presenting with unexplained jaundice and liver dysfunction. Recognizing hilar bile duct metastasis’ potential is critical to avoid misdiagnosis and improve patient outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-160/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-160/prf

Funding: This study was supported by the 2023 Lianyungang Comprehensive Cancer Management and Technology Advancement Project (No. QN202302); 2022 Lianyungang First People’s Hospital Young Talent Development Initiative (No. QN2212); and Jiangsu Society of Research Hospital Translational Medicine Research Grant (No. 2024-GDZXKT-01-07).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-160/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report and accompanying images was waived from the requirement of patient consent according to The First People’s Hospital of Lianyungang Ethics Committee.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Jones)

Cite this article as: Liu F, Li W, Wu W, Teng B, Li W, Li K, Li X. Extramedullary metastasis of the hilar bile duct in multiple myeloma: a case report and literature review. J Gastrointest Oncol 2025;16(5):2492-2498. doi: 10.21037/jgo-2025-160

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