Liver failure due to metastatic melanoma: A case report

Abstract

BACKGROUND

Acute liver failure (ALF) due to diffuse hepatic infiltration by metastatic melanoma is extremely rare and often misdiagnosed. In the absence of prior malignancy, this presentation can mimic other hepatic emergencies such as Budd-Chiari syndrome. Early identification is crucial, especially in transplant candidates, to prevent inappropriate management.

CASE SUMMARY

A 61-year-old male presented with jaundice, abdominal distension, and encephalopathy. Liver imaging suggested acute Budd-Chiari syndrome, and liver transplantation was considered. However, biopsy revealed extensive hepatic infiltration by human melanoma black-positive melanoma cells. There was no known cancer history, although retrospective symptoms suggested uveal localization as a possible primary site. The patient rapidly deteriorated and died. A review of 12 similar cases revealed shared diagnostic challenges, frequent misdiagnoses, and poor outcomes.

CONCLUSION

Infiltrative melanoma should be considered in unexplained ALF, even without previously known malignancy.

Key Words: Acute liver failure; Melanoma; Budd-Chiari syndrome; Hepatic infiltration; Case report

Core Tip: Acute liver failure (ALF) due to diffuse hepatic infiltration by metastatic melanoma is an exceptionally rare and often misdiagnosed entity, especially in patients without a known history of malignancy. This case highlights the importance of considering infiltrative malignancy in unexplained ALF, even when initial imaging suggests vascular etiologies such as Budd-Chiari syndrome. Liver biopsy remains essential for accurate diagnosis and may alter transplant eligibility. Early recognition and histopathologic confirmation are critical for guiding appropriate clinical decisions in this rapidly fatal presentation.

INTRODUCTION

Acute liver failure (ALF) is a life-threatening condition characterized by sudden and severe impairment of hepatic function, coagulopathy, and hepatic encephalopathy in individuals without pre-existing liver disease[1]. While drug-induced liver injury, viral hepatitis, and autoimmune hepatitis are common causes, malignancy-associated ALF remains exceedingly rare[2]. Among these, metastatic melanoma represents an especially uncommon etiology, with only isolated cases reported in the literature.

Melanoma has a known predilection for hepatic metastasis; however, clinical manifestations of liver involvement are often silent or subtle until disease burden progresses. Infiltration of the hepatic parenchyma by melanoma cells can lead to rapid liver decompensation, and in rare cases, present as ALF.

Here, we present a case of a 61-year-old male who developed ALF secondary to diffuse hepatic infiltration by melanoma, initially suspected to be Budd-Chiari syndrome. In addition, we performed a systematic search of the PubMed database using the following search terms: ("melanoma"[Medical Subject Headings (MeSH) Terms] OR "melanoma"[Title/Abstract]) AND ("liver failure"[MeSH Terms] OR "hepatic failure"[Title/Abstract] OR "liver injury"[Title/Abstract] OR "hepatic injury"[Title/Abstract] OR "liver toxicity"[Title/Abstract] OR "hepatic toxicity"[Title/Abstract] OR "liver metastasis"[Title/Abstract] OR "hepatic metastasis"[Title/Abstract] OR "primary hepatic melanoma"[Title/Abstract]) AND (("case reports"[Publication Type]) OR "case series"[Title/Abstract]) AND (english[Language]). As of May 30, 2025, the search yielded a total of 173 studies, of which 13 were relevant to ALF due to melanoma infiltration. One study was excluded because the full text was not published in English, and one could not be retrieved in full text. The remaining 11 published cases over the past 40 years (1986 until 2025) were included in the manuscript, analyzed, and compared with our case aim to highlight common clinical patterns and diagnostic pitfalls in this rare yet lethal presentation. Characteristics of the analyzed case reports are shown in Table 1.

Table 1 Melanoma-associated acute liver failure cases.

Ref.	Clinical presentation	History of cancer	Diagnosis method of liver disease	Treatment	Outcome
Current case	Diffuse abdominal pain, jaundice, hepatic encephalopathy; progressive ALF with multi-organ dysfunction	No prior cancer history; possible uveal melanoma based on visual symptoms; no autopsy	Liver biopsy; HMB-45-positive melanoma	Supportive ICU care (intubation, dialysis, vasopressors); considered for transplant until result of biopsy	Death on day 7
O’Neill et al[3], 2024	RUQ pain, myalgia, nausea, subjective fevers; fulminant ALF	Previously excised cutaneous melanoma (in situ) on upper back, 1 year prior	Histopathological diagnosis via core biopsy of left axillary lymph node (MART1, SOX10, HMB45-positive)	Dual immunotherapy (nivolumab + ipilimumab), IV terlipressin, ICU support	Death on day 17 post-presentation due to refractory encephalopathy and hepatorenal syndrome
Lee et al[4], 2022	Nausea, vomiting, RUQ and LUQ pain, dyspepsia; fulminant ALF	No known history of melanoma; presumed first presentation, later verified suspicious skin lesions	Liver biopsy (S-100, HMB45, MART1-positive); stomach biopsy supportive	Supportive care; no specific antitumor therapy reported	Death shortly after liver biopsy; multiple organ failure before workup for primary site completed
Schlevogt et al[7], 2017	Right flank pain; rapid deterioration to ALF with renal failure and encephalopathy	Malignant melanoma of right flank (3 years prior), recurrent cutaneous metastases; colorectal carcinoma resected 6 months prior	Liver biopsy (S100-positive; HMB45/MART1-negative)	BRAF-inhibitor (Vemurafenib) + MEK-inhibitor (Cobimetinib)	Death after one week 7 days; autopsy confirmed diffuse hepatic infiltration
Escobar-Valdivia et al[5], 2017	RUQ pain, jaundice, weight loss, blindness in left eye; rapid ALF with encephalopathy	Undiagnosed uveal (choroidal) melanoma; visual impairment to blindness over 2 months, history revealed pigmented eye lesion 1 year prior	Post-mortem histopathology (liver and eye); coagulopathy precluded biopsy ante-mortem	Supportive care (FFP, vitamin K); no tumor-directed therapy	Death from multiorgan failure 4th in-hospital day; confirmed metastatic uveal melanoma on autopsy
Tanaka et al[11], 2015	Left hand necrotic ulcer, erythema on trunk, no encephalopathy; later developed ALF	No known history of melanoma; diagnosed post-mortem as melanoma of unknown primary origin	Post-mortem histopathology and immunohistochemistry (HMB-45, S100-positive)	Palliative care; patient not eligible for systemic therapy due to poor performance status	Death on day 47; diffuse hepatic and splenic infiltration by melanoma confirmed on autopsy
Mashayekhi et al[12], 2014	Jaundice, abdominal pain, oliguria; rapid ALF with multiorgan failure	Suspicious skin lesion (mole on back) noted 10 days before admission, not yet diagnosed or treated	Post-mortem histopathology; liver, heart, lung, kidney, bladder infiltrated with melanoma	Supportive care (antibiotics, fluids, inotropes); no tumor-directed therapy before death	Death on day 3; widespread multiorgan metastatic melanoma confirmed on autopsy
Bellolio et al[10], 2013	Abdominal pain, jaundice, acholic stools, dark urine; rapid progression to fulminant hepatic failure	History of breast cancer treated 5 years prior; no known melanoma	Post-mortem histopathology; liver, spleen, and lymph nodes infiltrated with melanoma; HMB-45 and S-100-positive	Supportive care; rapid deterioration precluded biopsy or targeted therapy	Death shortly after admission; melanoma of unknown primary confirmed at autopsy
Tanaka et al[13], 2004	Malaise, anorexia, abdominal distension, edema; ALF and encephalopathy, death within hours	No prior history; melanoma of unknown primary origin diagnosed post-mortem	Post-mortem histopathology; massive hepatic infiltration, melanoma cells in mesenteric lymph nodes	Supportive care only; rapid deterioration precluded therapeutic intervention	Death on hospital day 7; massive liver involvement, no primary site found on autopsy
Montero et al[8], 2002	Jaundice, nausea, vomiting, general malaise; ALF with encephalopathy and renal failure	Supraciliary melanoma treated 18 months prior (Clark II, < 1 mm depth, negative margins)	Transjugular liver biopsy; diffuse sinusoidal infiltration by melanoma, HMB-45-positive	Standard liver failure therapy; no antitumor intervention	Death on day 10; progressive hepatic encephalopathy and renal dysfunction
Te et al[6], 1999	Nausea, vomiting, RUQ pain, malaise; fulminant hepatic failure with encephalopathy and renal failure	Scalp lesion biopsied 2 months prior; initially non-diagnostic, later confirmed as melanoma	Percutaneous liver biopsy (HMB-45, S-100-positive); scalp mass re-biopsy-confirmed melanoma	Supportive therapy; chemotherapy deferred due to rapid deterioration	Death within 24 hours of encephalopathy onset; extensive sinusoidal infiltration confirmed histologically
Bouloux et al[9], 1986	Hypochondrial pain, nausea, vomiting, jaundice, encephalopathy; rapid onset ALF and hepatorenal syndrome	Previously treated nodular melanoma (Clark IV, 5 mm depth) of right scapula; in situ melanoma of sacrum	Post-mortem histopathology; liver almost entirely replaced by melanoma, confirmed microscopically	Supportive care (vitamin K, neomycin, lactulose); no tumor-specific therapy given	Death on day 10; diffuse liver infiltration confirmed on autopsy

ALF: Acute liver failure; FFP: Fresh frozen plasma; HMB-45: Human melanoma black; ICU: Intensive care unit; INR: International normalized ratio; IV: Intravenous; LUQ: Left upper quadrant; MART1: Melanoma antigen recognized by T cells 1; RUQ: Right upper quadrant; SOX10: SRY-box transcription factor 10.

CASE PRESENTATION

Chief complaints

A 61-year-old male was transferred to a tertiary transplant center due to clinical deterioration in terms of impaired consciousness, abdominal pain with marked distension, and jaundice.

History of present illness

Two weeks prior, the patient began experiencing symptoms of abdominal pain, progressive abdominal distension and jaundice for which he was admitted to a local hospital. Due to worsening liver injury and declining consciousness, the patient was referred to a tertiary transplant center.

History of past illness

The patient’s past medical history was significant for hypertension and dyslipidemia, which were both well-controlled with medication. He did not have a medical history of liver disease prior to hospitalization.

Personal and family history

The patient had no relevant family history.

Physical examination

The patient’s hemodynamic and respiratory status remained stable, but he exhibited somnolence (Glasgow Coma Scale 11, West Haven Grade 3), indicating a decreased level of consciousness. Physical examination revealed jaundice, tense, non-tender abdominal distension, and a palpably enlarged liver. The patient showed no cutaneous signs of chronic liver disease (e.g., spider angiomata, palmar erythema).

Laboratory examinations

Initial laboratory tests revealed hepatocellular liver injury (alanine transaminase [ALT] 500 IU/mL, aspartate transaminase [AST] 800 IU/mL, alkaline phosphatase 230 IU/mL, gamma-glutamyl transferase 350 IU/mL), elevated bilirubin (total 200 μmol/L, indirect 90 μmol/L, direct 110 μmol/L), and impaired liver synthetic function (international normalized ratio [INR] 1.72). Over the following days, there was a further rise in liver enzymes and bilirubin (ALT 700 IU/mL, AST 980 IU/mL, total bilirubin 279 μmol/L, direct bilirubin 156 μmol/L, indirect 123 μmol/L) with elevated serum ammonia levels (300 μmol/L). Diagnostic evaluation confirmed normal copper and iron metabolism, normal immunoelectrophoresis, and unremarkable tumor markers. Serological tests ruled out viral hepatitis (hepatitis A virus [HAV], hepatitis E virus [HEV], hepatitis B virus [HBV], and hepatitis C virus [HCV]).

Imaging examinations

Ultrasound examination showed hepatomegaly (liver size up to 28 cm in the midclavicular line) with a heterogeneous liver parenchyma, splenomegaly (longitudinal diameter 140 mm), and a small amount of free fluid. A multiphase contrast-enhanced multislice computed tomography (MSCT) revealed a markedly enlarged liver (32 cm × 25 cm × 31 cm) occupying almost the entire abdomen and displacing surrounding organs (Figure 1A and B). The liver parenchyma was described as very heterogeneous. Both the right and middle hepatic veins were completely compressed with absent blood flow, and thrombosis was observed in the left hepatic vein (Figure 1C). The inferior vena cava was obliterated in the intrahepatic portion up to the confluence of the renal veins. A small amount of ascites and splenomegaly was also noted.

Figure 1 Ultrasound examination. A: Marked hepatomegaly with multiple hypervascular lesions in the liver; B: Sagittal section showing hepatomegaly, thrombus in the left hepatic vein (arrow), with absence of the right and middle hepatic veins; C: Sagittal section showing hepatomegaly and thrombus in the left hepatic vein.

Pathohistological analysis

To rule out infiltrative liver disease, a percutaneous liver biopsy was performed under ultrasound guidance after preprocedural optimization. Initially, transjugular approach was considered but after consultation with an interventional radiologist, this approach was deemed technically unfeasible due to radiologically confirmed thrombosis and obliteration of the hepatic veins as well as the inferior vena cava. Histopathological examination revealed a sparse amount of normal liver parenchyma, with the remainder of the biopsy consisting of a necrotic tumor infiltrate composed of clusters and short strands of atypical, oval to spindle-shaped cells, with polymorphic nuclei and prominent nucleoli (Figure 2). Individual tumor cells and areas of necrosis were accompanied by scant yellow-brown pigment. Immunohistochemically, the tumor cells were diffusely positive for human melanoma black (HMB-45) and negative for cytokeratin AE1/AE3 and Discovered On Gastrointestinal Stromal Tumor 1, confirming the diagnosis of infiltrative melanoma (Figure 3).

Figure 2 Microscopic view shows a sparse amount of normal liver parenchyma, with the remainder of the biopsy consisting of a necrotic tumor infiltrate composed of clusters and short strands of atypical, oval to spindle-shaped cells, with polymorphic nuclei and prominent nucleoli. Arrows are pointing to the tumor cells.

Figure 3 Immunohistochemical analysis of liver biopsy. A: Human melanoma black; B: Cytokeratin AE1/AE3; C: Discovered On Gastrointestinal Stromal Tumor 1.

MULTIDISCIPLINARY EXPERT CONSULTATION

The patient was discussed by the multidisciplinary team for liver transplantation consisting of transplant hepatologists, infectious disease specialists, intensive care specialists, surgeons, radiologists, anesthesiologists, and pathologists. Given the patient's clinical deterioration and progressive liver failure, liver transplantation due to ALF was considered a potential treatment option; therefore, urgent pre-transplantation workup was initiated. Meanwhile, after confirming melanoma in the liver biopsy, the decision for liver transplant was contraindicated.

FINAL DIAGNOSIS

Based on clinical, laboratory, radiological and pathohistological findings, the patient was diagnosed with metastatic melanoma as the underlying cause of ALF.

TREATMENT

The patient's clinical condition worsened, with the development of sopor and oliguria (estimated glomerular filtration rate [eGFR] 30 mL/min/1.72 m²) and further elevation in liver enzymes (ALT 2110 IU/mL, AST 1900 IU/mL), with persistently high bilirubin (total bilirubin 279 μmol/L, direct bilirubin 156 μmol/L, indirect bilirubin 123 μmol/L), worsening of INR (3.5), and onset of hypoglycemia (2.3 mmol/L) and lactic acidosis (serum lactate 5 mmol/L, pH 7.20). Brain MSCT excluded acute cerebral pathology. While awaiting results of liver biopsy, the patient was transferred to the intensive care unit (ICU) intubated, mechanically ventilated, and started on vasoactive support and continuous hemodialysis.

OUTCOME AND FOLLOW-UP

The patient succumbed to ALF on the fourth day of hospital admission. Further discussion with the family revealed a history of visual disturbances in the left eye at 1 month prior, raising suspicion of a uveal melanoma as the primary site of the malignancy. Unfortunately, the patient’s family denied a medical request for autopsy, and the primary site remained undetermined.

DISCUSSION

Our patient presented with progressive abdominal pain, jaundice, and hepatic encephalopathy, manifestations consistent with fulminant hepatic failure as a result of metastatic melanoma of unknown primary origin. A 40-year literature review yielded 11 cases with similar presentations, often including initial non-specific symptoms such as nausea, malaise, right upper quadrant pain, and jaundice[3-6]. However, in several cases such as those by Escobar-Valdivia et al[5] and Te et al[6], ocular or dermatological signs (e.g., vision loss or skin lesions) preceded hepatic symptoms, potentially offering earlier diagnostic clues. These clinical presentations underline the deceptive onset of liver failure in patients with melanoma, which often lacks initial dermatologic or systemic warning signs, complicating timely diagnosis. The initial ambiguity of symptoms also contributes to misdiagnosis or delayed recognition. Our case initially presented as acute Budd-Chiari syndrome based on radiologic findings, further illustrating the clinical overlap with other hepatologic emergencies. This could lead to a diagnostic dilemma, necessitating a broader diagnostic approach, including a liver biopsy.

In our case, there was no documented prior history of malignancy, although post-mortem discussion revealed recent visual disturbances, raising suspicion of a uveal melanoma as the primary site. This contrasts with several other cases where patients had previously diagnosed melanomas, cutaneous or ocular, that were either excised or under surveillance[3,7-9]. Notably, some cases involved previously undetected or misdiagnosed lesions, such as in Lee et al[4], where suspicious skin changes were only noted retrospectively, and one case involved a patient with prior breast cancer, but without known melanoma[10]. The variable presence or absence of cancer history demonstrates the diagnostic challenge and the necessity of maintaining a high index of suspicion even in patients without known malignancy. This aspect is particularly relevant in the transplant setting, where identifying occult malignancy could alter management plans significantly. In our patient, the lack of prior oncological history initially supported transplant eligibility until liver biopsy results necessitated a change in course of treatment.

Our patient’s laboratory findings demonstrated profound liver dysfunction: Markedly elevated transaminases (ALT up to 2110 IU/L, AST up to 1900 IU/L), rising bilirubin (to 190 μmol/L), coagulopathy (INR 3.5), hypoglycemia, lactic acidosis and hyperammonemia. These values reflect severe hepatocellular injury and impaired synthetic function, features seen across many of the reported cases[4-6,11]. Importantly, a comprehensive laboratory workup aimed at excluding other potential causes of ALF was essential. In our case, viral hepatitis panels (HAV, HBV, HCV, HEV), metabolic markers (ceruloplasmin, ferritin, transferrin saturation), and tumor markers were all within normal limits or non-diagnostic. This exclusion of common etiologies reinforced the need for tissue diagnosis and justified the decision to proceed with liver biopsy.

Radiologic imaging in our case revealed an enlarged liver with heterogeneous enhancement, compression of the hepatic veins, and features suggestive of Budd-Chiari syndrome, without described focal liver lesion. These findings were initially misleading, highlighting the diagnostic overlap between vascular obstruction and infiltrative malignancies. Similar radiological patterns have been reported in other cases, including hepatomegaly, diffuse hypodensity, and lack of focal lesions despite extensive tumor infiltration[4,6,11]. The non-specific nature of these imaging findings often delays definitive diagnosis. While cross-sectional imaging such as contrast-enhanced CT or magnetic resonance imaging (MRI) is valuable in evaluating structural abnormalities and ruling out other causes, clinicians should be aware of potential disadvantages in detecting diffuse parenchymal infiltration without a mass-forming component. Therefore, imaging should be interpreted in the clinical context and followed promptly by biopsy when malignancy is suspected.

Diagnosis in our case was confirmed via percutaneous liver biopsy, revealing extensive infiltration by HMB-45-positive melanoma cells. This aligns with several other reports where liver biopsy, transjugular or percutaneous, was pivotal for diagnosis[3,6-7]. However, in multiple instances, diagnosis was made postmortem due to either clinical instability or rapid deterioration that precluded biopsy[5,9-13]. Immunohistochemistry remains essential, with markers such as HMB-45, S100, and melanoma antigen recognized by T cells aiding in confirming melanocytic origin. These findings underscore the critical role of timely liver biopsy in unexplained liver failure.

In patients with ALF and significant coagulopathy, transjugular liver biopsy is generally considered the safer diagnostic approach, as it minimizes the risk of intraperitoneal hemorrhage and allows simultaneous hemodynamic assessment of the hepatic circulation. By contrast, percutaneous biopsy can provide larger cores of parenchyma but carries a higher bleeding risk, particularly in the setting of hepatomegaly or ascites[14]. In our case, however, transjugular liver biopsy was technically impossible due to complete thrombosis and obliteration of the hepatic veins and intrahepatic inferior vena cava, precluding safe venous access, which is also a relative contraindication for performing transjugular liver biopsy[14]. Consequently, a percutaneous route was chosen after multidisciplinary discussion with interventional radiologist which ultimately yielded sufficient diagnostic material. This highlights that while transjugular liver biopsy is the procedure of choice in high-risk patients, percutaneous biopsy remains a valid alternative when transjugular access is not feasible.

Although MRI may provide additional diagnostic clues in cases of diffuse hepatic infiltration, in our patient, this modality was not feasible due to rapid clinical deterioration, impaired consciousness, and limited technical availability. After consultation with radiology colleagues, and considering the urgent need for histological confirmation to guide further management, the team decided to proceed directly with liver biopsy. This approach ensured timely diagnosis in a setting where delaying the procedure for further imaging was deemed unsafe.

Our patient received aggressive supportive therapy, including ICU care, mechanical ventilation, dialysis, and vasoactive support. Transplantation was initially considered but later withdrawn upon confirmation of metastatic melanoma. Most cases involved only supportive care without tumor-directed therapy due to rapid progression or delayed diagnosis. This highlights both the urgency and limitation in treatment options when metastatic melanoma presents with fulminant liver failure. Despite advancements in melanoma therapy, particularly with immunotherapy and B-Raf/MEK inhibitors, the rapid clinical decline in ALF settings rarely allows for timely initiation of such treatments. The prognosis in such cases is uniformly poor. In our case, death occurred on the seventh day. Similarly, in nearly all reported cases, patients passed away within days of encephalopathy onset or liver failure diagnosis.

CONCLUSION

This case highlights the rare but devastating presentation of ALF caused by diffuse hepatic infiltration of metastatic melanoma. The clinical onset was non-specific and initially mimicked vascular hepatic emergencies such as Budd-Chiari syndrome, illustrating the diagnostic challenge in distinguishing infiltrative malignancy from other acute hepatologic conditions. The absence of a known malignancy, along with misleading imaging and rapid clinical deterioration can often delay the correct recognition. Diagnosis was ultimately confirmed by liver biopsy, underscoring its critical role in unexplained ALF. Despite aggressive supportive management and initial consideration for liver transplantation, the discovery of metastatic melanoma rendered the patient ineligible. It reinforces the importance of maintaining a high index of suspicion for occult cancer in ALF, even in patients without documented oncologic history, and emphasizes the need for rapid diagnostic pathways to guide appropriate therapeutic decisions.