S3080 Metastatic Merkel Cell Carcinoma Presenting as Silent Infiltrative Liver Disease: A Lesson Emphasizing the Utility of Liver Biopsy in the Exclusion of Immune Checkpoint Inhibitor-Mediated Hepatotoxicity

Abstract

Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor that arises on skin exposed to the sun and occurs in patients who are Caucasian, elderly, and immunocompromised. The mortality of MCC is about 33% and disseminated disease suggests poor prognosis. Metastasis to the liver is exceedingly rare, with only few reported cases presenting as infiltrative liver disease. We present a case of MCC with “silent” infiltration in the liver effectively differentiated from suspected immune checkpoint inhibitor-mediated hepatotoxicity (IMH) by liver biopsy Case Description/Methods: A 76-year-old man with a history of metastatic MCC of the left distal thigh status-post stem cell transplant presented to a cancer care center for evaluation of fatigue, nausea, and dyspnea. He reported consuming 10 alcoholic drinks a week for many years until 2 years ago. He was started on a treatment regimen of pembrolizumab and plinabulin (a phase I microtubule inhibitor) with radiation to the liver 2 months ago. On admission, serum transaminases were elevated from baseline as indicated in Table 1. After an initial period of observation, the patient was started on oral budesonide 9 mg/d and ursodiol 1000 mg/d for empiric treatment of IMH without subsequent improvement in liver enzymes. Liver imaging was unrevealing for liver lesions. A diagnostic parenchymal liver biopsy was performed to clarify the underlying diagnosis, including possible IMH, drug-induced liver injury from plinabulin toxicity, radiation-induced liver injury, or metastatic disease. Histology showed that the tumor cells were strongly positive for synaptophysin, chromogranin, and extensive metastatic MCC. The steroids were discontinued, and the worsening hepatitis was attributed to Merkel cell liver infiltration. The patient subsequently passed away 3 months later from cancer. (Figure) Discussion: Traditionally when there is high suspicion, IMH is clinically diagnosed without expectation for liver biopsy, and steroids are often prescribed upfront. One critique regarding the role of liver biopsy may be that histological features associated with IMH are nonspecific, with features of lobular to pan-lobular hepatitis. However, the absence of an alternative findings on the biopsy confers additional confidence towards the diagnosis of IMH. This case highlights the importance of the diagnostic liver biopsy prior to immunosuppressive treatment for suspected IMH to exclude other differentials and guide the decision for empiric steroids.Figure 1.: Solid nests and lobules of poorly differentiated neuroendocrine cells are seen in this liver biopsy A) Merkel cell chromogranin - Tumor cells are strongly and diffusely positive for chromogranin. B) Merkel cell CK20- Tumor cells show perinuclear dot-like reactivity to Cytokeratin20 C) Merkel cell synaptophysin- Tumor cells are strongly and diffusely positive for neuroendocrine marker Synaptophysin. Table 1. - Prior to initiating immunotherapy, serum transaminases rose slowly but remained within 3x upper limits of normal (ULN) Laboratory Value Prior to Admission On Immunotherapy Day 1 Of Admission After Initiating Steroids Aspartate Aminotransferase (AST) 41 U/L 269 U/L 281 U/L Alanine Aminotransferase (ALT) 46 U/L 315 U/L 240 U/L Alkaline Phosphatase (ALP) 87 U/L 226 U/L 227 U/L Total Bilirubin 0.3 mg/dL 0.7 mg/dL 1.1 mg/dL International Normalized Ratio (INR) 1.06 1.15 1.18 At the end of treatment, transaminases reached >5 times ULN. No improvement was seen in liver enzymes after initiating empiric steroid therapy for suspected IMH.