Hepatic granulomas: histological and molecular pathological approach to differential diagnosis - a study of 442 cases

Background/Aims: The incidence of hepatic granulomas is reported in 2-15% of liver biopsies. This study was carried out to evaluate the incidence and aetiology of hepatic granulomas in a German Institute of Pathology with specialization in liver diseases. Methods: A retrospective case review was performed on 12 161 liver biopsies of the Institute of Pathology (University of Cologne) between 1996 and 2004. Aetiology was determined according to histomorphological changes, clinicopathological data and liver tissue polymerase chain reaction (PCR) for detection of diverse putative pathogens in the liver tissue. Results: Four hundred and forty-two liver biopsies revealed granulomatous lesions (3.63%). Two hundred and fifteen cases (1.77% of all biopsies and 48.64% of granulomatous lesions) were diagnosed as primary biliary cirrhosis. In 37 cases (0.3% of all biopsies and 8.37% of granulomatous lesions), the diagnosis of sarcoidosis was established. A positive PCR result for an infectious pathogen was obtained in 15 samples (3.39%) [Bartonella henselae (n = 2), Listeria (n = 3), Mycobacterium tuberculosis (n = 3), Yersinia pseudotuberculosis (n = 1), cytomegalovirus (n = 2), Epstein-Barr virus (n = 4)]. In six cases, a putative diagnosis was established according to the report of clinical conditions. In 11 cases (2.48%), drugs were the putative causative agent. In 158 cases (36%) a definite diagnosis could not be established. Conclusions: Hepatic granulomas have a broad range of underlying aetiologies. With a combined histological, clinical, serological, and molecular approach, we were able to clarify the cause in 64% of the cases. Owing to the diverse prognosis and therapeutic implications, a detailed interdisciplinary workup of all liver biopsies with granulomatous lesions is mandatory.