A fraction of the cells were immunoreactive for granzyme, perforin and TIA1 (Figure 3). Thus, monomorphic, phenotypically aberrant T lymphocytes, were already present in the
patient’s liver at the time of his initial diagnosis of cryptogenic cirrhosis. Together, these findings were consistent with a final diagnosis of primary hepatosplenic T-cell lymphoma (HSTCL) of the alpha/beta subtype. Figure 2 Liver biopsy demonstrating a monomorphic, mostly intrasinusoidal, lymphoid infiltrate composed of small to medium size cells with irregular Inhibitors,research,lifescience,medical hyperchromatic nuclei (H&E stain, 500×) Figure 3 Liver biopsy immunostained for CD3. Note the distribution of immunolabeled cells almost exclusively within hepatic sinusoids, (immunoperoxidase technique, 500×) Given bone marrow involvement, Inhibitors,research,lifescience,medical he was diagnosed with stage IV disease and treated with two cycles of EPOCH (etoposide, vincristine,
doxorubicin, cyclophosphamide and prednisone) followed by two cycles of alemtuzumab/cladribine and pentostatin. His clinical course involved multiple hospitalizations complicated by hyponatremia, neutropenic fevers and pulmonary emboli. Following his fourth cycle of chemotherapy, he developed worsening liver failure and expired approximately three months after diagnosis of HSTCL. Discussion HSTCL was first described in 1990 and is a rare malignancy Inhibitors,research,lifescience,medical and accounts for less than 1% of all non-Hodgkin’s lymphomas (1). HSTCL predominantly affects young males with Inhibitors,research,lifescience,medical median age at diagnosis of approximately 35 years (2). While the pathogenesis of HSTCL is largely unknown, there is an association with chronic immune suppression, particularly in patients who Inhibitors,research,lifescience,medical are on immunosuppressive agents for solid organ transplant, lymphoproliferative disorders, or inflammatory bowel disease. Anti-tumor necrosis factor LBH589 ic50 therapies have been implicated especially in patients with Crohn’s disease (3). However, up to 80% of cases of HSTCL occur in patients without chronic immune suppression. Associations with viral infections such as
hepatitis B virus and EBV have only been reported in several cases (4-6). While the clinical Ribonucleotide reductase presentation of HSTCL is variable, most patients initially present with prominent hepatosplenomegaly and thrombocytopenia in the absence of prominent lymphadenopathy (7). Abnormal liver-function tests as well as constitutional symptoms such as fevers and anorexia are also common. Histologically, HSTCL is characterized by sinusoidal infiltration of T-cells in the liver, spleen and bone marrow. In most cases, tumor cells express CD2 and surface CD3 while CD4, CD8 are absent. Cytogenetics frequently reveal isochromosome 7q or trisomy of chromosome 8 (8). Most tumors exhibit the gamma/delta TCR but few cases such as with our patient express the alpha/beta TCR instead.