Unusual Presentation of Multiple Myeloma as a Liver Tumor at Initial Diagnosis: A Case Report

Introduction

Multiple myeloma (MM) is a hematological malignancy characterized by malignant plasma cell proliferation in the bone marrow, leading to the production of a monoclonal immunoglobulin. Common symptoms include bone pain, hypercalcemia, anemia, and renal insufficiency [1]. In some cases, the disease can progress to extramedullary myeloma (e-MM) [2], which can involve soft tissues or organs and is associated with a poor prognosis with conventional treatments [2,3]. At diagnosis, e-MM is usually found in skin and soft tissues, and at relapse, it is more likely to be found in the liver, kidneys, lymphatic system, central nervous system, breast, pleura, and pericardium [4,5]. In rare cases, patients present with liver involvement at diagnosis [4–7]. In the past, the incidence of e-MM ranged from 1.7% to 4.5%, with baseline staging using whole-body magnetic resonance imaging or positron emission tomography-computed tomography [7]. In recent decades, novel treatment agents and advancements in imaging technologies may have contributed to the increased incidence of e-MM, ranging from 7% to 18% during initial diagnosis [2,8]. In this case report, we present a rare case in which e-MM was initially diagnosed as a hypervascular liver lesion. With the increase in incidence of e-MM and limited information on the incidence and prognosis of this aggressive form of MM at initial diagnosis [6,8], this case report is aimed to increase awareness among clinicians.

Case Report

A 64-year-old woman with a history of moderate-severe aortic stenosis, transient ischemic attack, and gastroesophageal reflux disease presented with persistent epistaxis, melena, extreme fatigue, and shortness of breath. The patient did not have a history of liver disease, hepatitis B, or hepatitis C. Initial laboratory results revealed severe normocytic anemia (hemoglobin 4.6 g/dL), thrombocytopenia (platelets 97×109/L), elevated hepatic enzymes (gamma-glutamyl transferase 244 U/L), alanine transaminase (52 U/L), total bilirubin (30 umol/L), conjugated bilirubin (22 umol/L), alkaline phosphatase (148 U/L), and albumin (2.4 g/dL); hypercalcemia (calcium 2.62 mmol/L), with low parathyroid hormone (1.8 pmol/L); and mild kidney injury, with elevated creatinine (93 umol/L) and urea (9.1 mmol/L) and decreased estimated glomerular filtration rate (50 mL/min/1.73 m2). Using the Revised International Staging System (R-ISS), this case was stratified as R-ISS stage III.

Abdominal computed tomography (CT) revealed multiple arterial phase enhancing lesions in both liver lobes, suggestive of metastases (Figure 1). Several lesions were centrally necrotic, with the largest measuring approximately 2.57 cm. Right pleural effusion was noted. The liver size was abnormal, with hepatomegaly of 26.3 cm in diameter. At the initial stages, the patient had workup performed to rule out other cancers. Cancer markers showed elevated carcinoembryonic antigen (7.2 µg/L for a higher normal limit of 5 µg/L), cancer antigen (CA) 15-3 (155 U/mL), and CA 125 (70.9 U/mL for a higher limit of 35 U/mL), while alpha-fetoprotein (6.3 ng/mL) and CA 19-9 (11.3 U/mL) were normal. A biopsy was performed on the liver lesions (Figure 2A) identified on abdominal CT scan, and the results revealed sheets of plasma cells, which were diffusely positive for CD138, CD38, and CD56, and kappa light chain restriction. PanCK, CD117, estrogen, CK20, and CK7 were negative. Cytogenetic fluorescent in situ hybridization panel was performed to help understand the risk group and prognosis of the disease, showing 1p32.3 loss, 1q21.3 gain, and t(4;14), which indicated high-risk myeloma and poor prognosis.

Further MM workup confirmed the diagnosis, with immunofixation electrophoresis showing 2 abnormal monoclonal protein bands (1.84 g/dL and 2.72 g/dL), elevated IgA (56.08 g/L), and free light chain kappa (31.4 mg/L). Bone marrow biopsy (Figure 2B) revealed 60% plasma cells, hypercellular marrow (70%), and kappa clonal plasma cells. Skeletal survey showed no lytic, blastic, or metastatic bone lesions. A CT scan was performed for the chest-abdomen-pelvis area; however, it did not show other e-MM locations.

The patient was hospitalized for 112 days, during which she experienced recurrent pleural effusions and required a PleurX catheter drain. Plasma cells were found in the pleural effusion; however, we could not prove monoclonality. She also developed severe altered mental status, lethargy, jaundice, hypercalcemia, and hyperuricemia during her hospital stay. Magnetic resonance cholangiopancreatography identified choledocholithiasis and bile duct stricture; stones were removed, and a stent was placed via endoscopic retrograde cholangiopancreatography. Chemotherapy was initiated but paused due to febrile neutropenia. The patient later tested positive for COVID-19 and received treatment with Paxlovid and remdesivir. After 6 weeks, she was discharged and continued treatment as an outpatient. She received 7 cycles of daratumumab-dexamethasone-lenalidomide and was scheduled for autologous stem cell transplant. After 4 months of treatment, the patient had positive clinical outcomes. The IgA kappa band went down from 5.52 g/dL to 0.064 g/dL. The patient had improved hemoglobin (7.4 g/dL to 10.5 g/dL), WBC (8.19×109/L to 12.5×109/L, neutrophils (6.21×109/L to 9.15×109/L), and platelets (61×109/L to 452×109/L). The hepatic enzymes improved, with gamma-glutamyl transferase level of 185 U/L. Both monoclonal protein bands disappeared after 4 months of treatment. Additionally, the liver lesions had resolved, and the hepatomegaly decreased to 18.3 cm in diameter.

Discussion

Extramedullary MM is rare but increasing in incidence [8]. Hepatic involvement is one of the more common sites [4], often presenting with varied radiological features. Literature reviews and case reports show different patterns, including hypovascular and hypervascular lesions [9–11]. Our case initially suggested metastasis of primary adenocarcinoma, but biopsy confirmed e-MM (Figure 2). This case is notable for presenting directly as liver e-MM without preceding bone lesions.

The American Journal of Roentgenology published an article detailing the radiological characteristics of 15 different patients with e-MM. This article cited multiple autopsies revealing diffuse sinusoidal plasma cell infiltration and some with tumor nodules in the liver [11,12]. Among their 15 patients, 3 patients exhibited hypovascular liver lesions [11]. Other reports of myelomatous liver lesions have shown various radiological features. Most described hypodense lesions with low enhancement on CT scans and hypoechoic appearance on ultrasound. However, 2 case reports of e-MM highlighted hypervascular focal lesions in the liver, mirroring the findings demonstrated in our case.

Tan et al reported on a 68-year-old woman who experienced relapse with multiorgan involvement subsequent to treatment with external beam irradiation for a solitary sternal plasmacytoma [13]. In their case report, abdominal CT revealed 3 solid liver lesions exhibiting arterial enhancement. Another case report involved a 63-year-old man with chronic hepatitis B infection and a history of IgGk MM, which relapsed despite multiple pharmacological treatments, radiotherapy, and stem cell transplant [14]. Routine ultrasound imaging revealed multiple hypoechoic focal lesions, while multiphasic contrast-enhanced CT scan showed multiple focal lesions with mild contrast enhancement. Initially, these imaging features were suspected to be metastases of primary adenocarcinoma. However, upon liver biopsy, plasma cells with anaplastic features were identified, confirming the diagnosis of MM in the liver. In this case, the initial presentation was suspicious for metastasis of primary adenocarcinoma.

The 2 cases discussed previously involved patients with relapsed MM. However, in the present case, the patient had no prior history of MM and initially presented with liver lesions, which were subsequently confirmed as e-MM through biopsy. Supported by other case reports, this case represents a rare manifestation of MM, as the patient exhibited no bone lesions on skeletal surveys; instead, the disease manifested directly as e-MM in the liver [12]. As noted earlier, e-MM typically carries a poor prognosis and may not respond well to treatment [3]. However, in this instance, the patient achieved a complete response following treatment and was awaiting a stem cell transplant to achieve a better progression free survival.

Conclusions

This case represents a rare presentation of MM as liver metastasis with no bone lytic lesions. The patient achieved a complete response with treatment despite initially advanced disease and precarious status. When patients present with liver lesions, physicians should consider myeloma in their differential diagnosis. Early identification of liver involvement is crucial for accurate diagnosis and treatment planning. Future study is needed to understand the effect of early diagnosis and treatment on patients’ clinical outcomes and to provide valuable clinical guidance when clinicians are presented with atypical manifestations of multiple myeloma.