Clinical Chameleon: To Be or Not To Be Metastasis

Abstract

Question: A 65-year-old woman with a prior history of renal cell carcinoma, status post left nephrectomy, presented with vague right upper quadrant abdominal pain. Physical examination revealed no jaundice and a negative Murphy sign. Alanine and aspartate aminotransferases were elevated at 102 and 124 U/L, respectively, prompting subsequent imaging. Right upper quadrant ultrasonography demonstrated multiple hepatic masses with peripheral hypoechoic halo (Figure A). Computed tomography (CT) and magnetic resonance imaging (MRI; Figure B) showed innumerable hepatic masses with central T2 hyperintensity and incomplete peripheral enhancement on arterial and portal venous phase imaging. There was no evidence of extrahepatic disease. CT-guided biopsy of one of these lesions showed replacement of liver parenchyma by a proliferation of large cells with intracytoplasmic lumina, some containing red blood cells (Figure C, high-magnification photomicrograph; stain, hematoxylin and eosin), which were strongly reactive for CD31 immunostain (Figure D, high-magnification photomicrograph). Immunostains for renal cell carcinoma were nonreactive. The patient complained of mild right upper quadrant pain and was otherwise unremarkable. What is the diagnosis? Look on page 978 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin described in 1982,1Weiss S.W. Enzinger F.M. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma.Cancer. 1982; 50: 970-981Crossref PubMed Scopus (1107) Google Scholar which can present in the liver as well as soft tissues, bone, and brain, arising from a medium sized or large vein. It has low incidence in the general population <0.1 per 100,0002Hertl M. Cosimi A.B. Liver transplantation for malignancy.Oncologist. 2005; 10: 269-281Crossref PubMed Scopus (107) Google Scholar and is more common in females (61%).3Lau K. Massad M. Pollak C. et al.Clinical patterns and outcome in epithelioid hemangioendothelioma with or without pulmonary involvement: insights from an internet registry in the study of a rare cancer.Chest. 2011; 140: 1312-1318Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar Hepatic EHE usually presents as multiple tumors (EHE nodular type) ranging in size from 0.2 to 14 cm that, in late-stage disease, may coalesce to form a large infiltrative mass present in the periphery (EHE diffuse type).1Weiss S.W. Enzinger F.M. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma.Cancer. 1982; 50: 970-981Crossref PubMed Scopus (1107) Google Scholar The radiologic appearance of multiple hepatic lesions is often nonspecific and suggestive of metastatic disease or infectious etiology. However, the “targetoid” appearance of EHE lesions on MRI suggests this diagnosis. Histologically, the EHE is composed of multiple, atypical, “epithelioid” endothelial cells with prominent cytoplasmic vacuolization, suggestive of primitive lumen formation embedded within a fibrous–myxoid stroma and replacing the hepatic parenchyma (Figure C). The tumor cells are strongly reactive for vascular markers (CD31 and CD34). A disease-defining genetic alteration was identified as a chromosomal translocation in the t(1;3)(p36;q25), which was present in virtually all cases tested and is a useful diagnostic tool in evaluation of this diagnostically challenging neoplasm. Hepatic EHE is classified as tumor of “borderline” biologic potential and clinical outcome is unpredictable. Metastatic disease at the time of diagnosis does not necessarily correspond with reduced survival; some cases show long-term survival of up to 73% at 5 years,3Lau K. Massad M. Pollak C. et al.Clinical patterns and outcome in epithelioid hemangioendothelioma with or without pulmonary involvement: insights from an internet registry in the study of a rare cancer.Chest. 2011; 140: 1312-1318Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar despite extensive disease presence. Treatment is challenging owing to the rarity of the disease, which precludes large-scale trials. Surgical resection and chemotherapeutic agents are offered in some cases and disease recurrence after orthotopic liver transplantation has been reported. In our case, chemotherapy was unsuccessful and the patient refused transplantation. She is alive with disease.