Clinico-Pathologic Characteristics of Patients with Extra-Nodal Lymphoproliferative Disorders Diagnosed Using Liver Biopsy.
Authors: El-Sharkawi D. , Dooley J. , Cwynarski K. , Ramsey A. , McNamara C. 
Published: October 2019

Abstract
Autopsy studies of patients with lymphoma commonly demonstrate hepatic involvement but this is an infrequent mode of initial presentation. The utility of image-guided liver biopsies in this setting has not been reported previously. We describe the clinico-pathologic characteristics of a series of patients presenting to a single centre with extra-nodal lymphoproliferative disorders (LPD) in whom the diagnosis was made on a liver biopsy. There were 21 patients (11M, 10F) with a median age of 52 years (range 29–87). Nine of 21 patients were HIV-positive (median CD4 count at presentation of 97, range 6–212) and two patients had hepatitis C infection. One patient was receiving immunosuppressive therapy in the setting of a previous liver transplant. The most frequent mode of presentation was with B-symptoms which occurred in almost two-thirds (13/21) of patients. Abdominal pain occurred in less than one third (6/21). Six patients presented with jaundice. There was a mean delay of 7 weeks from the onset of symptoms to presentation and this was significantly longer in the group of patients who were HIV negative (9 weeks vs 3–4 weeks in HIV-positive patients). On examination, hepatomegaly was present in 16/21 patients. Cross-sectional imaging of the liver identified a solitary space-occupying lesion in 7 patients whilst 8 had multi-focal abnormalities. Six patients had either hepatomegaly or a normal sized liver and no focal abnormality on imaging studies. Eight patients had no demonstrable abnormality other than the hepatic lesion i.e. primary hepatic lymphoma. Twenty of 21 patients had abnormal liver enzymes with a mixed cholestatic/ hepatitic picture. Nineteen patients had an elevated lactate dehydrogenase (LDH); (median 934 U/L, range 245–20,000). Six of 21 patients had bone marrow involvement by lymphoma. Of these, 4 had abnormal blood counts including 3 with pancytopenia. Procedures to obtain a definitive diagnosis included an ultrasound-guided core biopsy of the liver in 12 patients, a trans-jugular biopsy in 7 and an ERCP-guided procedure in one case. All were successful at obtaining diagnostic material on the first attempt and there were no procedure related complications. The majority of patients had B-cell tumours: diffuse large B-cell lymphoma (DLBCL) 12 patients, Burkitt lymphoma 3 patients; 4 patients had Hodgkin lymphoma and only 1 patient had a T-cell neoplasm. The median IPI score was 4. All but one patient received chemotherapy for their disease but 50% had dose reductions in their treatment because of abnormal liver function. Complications were commonly seen and included neutropenic sepsis (15 patients) and coagulopathy (2 patients). Twelve of the 21 patients died; the median overall survival (OS) was 4 months (range 1–48). In summary, the OS of patients presenting with hepatic lymphoma is poor. Efforts to prevent delays in diagnosis might improve the prognosis. A bone marrow biopsy in patients with a hepatic mass, B symptoms and cytopenias is an important investigation as it could obviate the need for a liver biopsy. However, in patients without readily accessible tissue for diagnosis, an ultrasound-guided core biopsy (or transjugular liver biopsy) of hepatic lesions is a safe procedure with a high diagnostic yield. As well as late presentation, there are a number of other factors which may contribute to the worse prognosis in this group of patients including HIV coinfection, dose reductions in therapy due to poor liver function and frequent complications during therapy.