Case Presentation: A 77-year-old female was admitted with a 3-week history of pruritus and a 1-week history of jaundice and fatigue. Patient had not used any new medications, except for recently prescribed ACE inhibitors. There was no history of alcohol abuse or liver disease and no recent sick contacts. Other medical conditions are type 2 diabetes mellitus and hypertension. Physical exam was normal except for jaundice with no classic stigmata of liver disease such as angiomas, spider nevi or encephalopathy. On admission, laboratory findings were remarkable for AST/ALT 750/960, total bilirubin15, alkaline phosphatase 459, and INR 1.0. Further studies were unremarkable for IgG, IgA, IgM, IgE, SS-A Ab, SS-B Ab, SM Ab, RNP Ab, SMRNP Ab, ACHR binding Ab, Anna-1 and Anna-2. CT scan showed diffuse fatty liver. MRCP identified a partially visualized, 7.6 by 4.5 cm mediastinal mass and no biliary obstruction. Needle biopsy of the liver demonstrated a focus of lymphocyte aggregates suggestive of paraneoplastic cholestatic hepatitis. Needle biopsy of the mediastinal mass demonstrated thymoma (WHO type B1). Tumor was composed of small mature lymphocytes with single and admixed small clusters of epithelioid cells. Immunostaining showed a predominant population of CD3 positive T-cells, and a smaller population of CD68 positive macrophages. Rare CD20+, PAX5 positive B cells present. Contrast MRI showed lobulated lesions of the anterior mediastinum with a mass invasion of the left brachiocephalic vein near the aortic arch. MRI and mammogram showed a right breast mass and core biopsy showed histological findings of a cyst. Patient was treated with pulse steroids without liver function response. Chemotherapy options were limited due to the acute liver dysfunction.
Discussion: This clinical case presents diagnostic and therapeutic challenges. Acute liver dysfunction is a rare initial presentation of a paraneoplastic syndrome induced by thymomas. Liver core biopsy did not identify histological findings of an autoimmune hepatitis. Patient did not respond to a pulse of steroids, but to a modified dose of chemotherapy. The reduction size of the thymoma and improvement of the liver function test favored the clinical presentation as a paraneoplastic autoimmune disorder. The vast majority of paraneoplastic syndromes secondary to thymomas present as myasthenia gravis following by a diversity of autoimmune disorders. Less than a dozen cases of paraneoplastic autoimmune hepatitis have been described in the literature. The invasion of the tumor to the brachiocephalic vein and the aortic arch made the thymoma non-resectable. The severe acute liver damage limited the options for chemotherapy. Ultimately, the patient was treated with carboplatin and dose-reduced etoposide with interval decrease in size of thymoma and liver function tests.
Conclusions: The differential diagnosis of acute liver dysfunction and an anterior mediastinal mass should include a paraneoplastic syndrome induced by thymomas. The classic histological findings of autoimmune disorders are not always evident in autoimmune hepatitis, and the liver dysfunction response to therapeutic modalities should guide the diagnostic identity for autoimmune hepatitis. Due to the rarity of this paraneoplastic presentation, the correlation among type of thymoma, immune staining, therapeutic response and prognosis remains unknown.
