Hepatosplenic T-cell lymphoma (HSTCL) represents a rare and aggressive form of non-Hodgkin lymphoma, originating from malignant T-cells. This cancer is characterized by its distinct pattern of infiltrating the sinusoids within the liver, spleen, and bone marrow. It constitutes a very small percentage of all non-Hodgkin lymphomas, often less than one percent. The disease typically develops from cytotoxic T-cells, frequently those expressing a gamma-delta (γδ) T-cell receptor.
Associated Conditions and Risk Factors
Hepatosplenic T-cell lymphoma is often associated with long-term immunosuppressive therapy, particularly in individuals managing autoimmune conditions. HSTCL is linked to inflammatory bowel diseases like Crohn’s and ulcerative colitis. Thiopurines, such as azathioprine and 6-mercaptopurine, are a concern. Additionally, anti-tumor necrosis factor (TNF) agents, including infliximab and adalimumab, have been implicated, especially when used in combination with thiopurines.
The risk increases with the duration of immunosuppressive therapy, often after two or more years of treatment. Combination therapy involving both thiopurines and anti-TNF agents can further elevate this risk. Young males, particularly those under 35, are at higher risk when receiving these combined treatments for inflammatory bowel disease. Solid organ transplant recipients, who receive long-term immunosuppression, also have an increased association with HSTCL.
Symptoms and Clinical Presentation
Patients commonly experience enlargement of the spleen and liver (splenomegaly and hepatomegaly). This enlargement can lead to abdominal discomfort or a feeling of fullness. Systemic indicators, known as “B symptoms,” are also common. These include unexplained fevers, night sweats, and unintentional weight loss.
Malignant T-cell infiltration into the bone marrow leads to low blood cell counts (cytopenias). This can cause anemia, leading to fatigue and shortness of breath. Low platelet counts (thrombocytopenia) may result in easy bruising or bleeding. A decrease in white blood cells (neutropenia) can lead to frequent infections.
While less common, liver involvement can cause jaundice (yellowing of the skin or eyes). Unlike many other lymphomas, enlarged lymph nodes are absent in HSTCL.
The Diagnostic Process
Diagnosing hepatosplenic T-cell lymphoma requires examining tissue samples. A bone marrow biopsy and aspiration are required to identify malignant cells within the bone marrow. In some cases, a liver biopsy may also be performed to assess for direct involvement. These samples undergo specialized laboratory analyses.
Flow cytometry identifies the specific type of T-cells and their abnormal characteristics. Immunohistochemistry helps characterize the malignant cells, typically showing them to be positive for CD3, CD2, and CD7, while often being negative for CD4 and CD8, and frequently expressing CD56. A characteristic genetic abnormality often found in HSTCL is isochromosome 7q (i(7q)), and sometimes trisomy 8. The detection of these specific genetic changes provides strong evidence for the diagnosis.
Standard Treatment Protocols
Treating hepatosplenic T-cell lymphoma involves intensive multi-agent chemotherapy regimens due to its aggressive nature. However, HSTCL often demonstrates resistance to standard lymphoma treatments, such as CHOP. This resistance necessitates more specialized and aggressive therapeutic approaches. Regimens like ESHAP have shown some promise in certain cases.
The most promising approach for long-term control, and often the only potential curative option, is an allogeneic stem cell transplant. This procedure involves receiving healthy blood-forming stem cells from a compatible donor. The transplant is generally considered after initial chemotherapy has achieved remission. Pre-transplant conditioning regimens, which may include total body irradiation (TBI), are used to prepare the patient’s body for the new stem cells.
Prognosis and Disease Course
Hepatosplenic T-cell lymphoma generally carries a challenging outlook due to its aggressive biological characteristics and inherent resistance to many conventional treatments. Reported median survival times have varied, ranging from approximately 6 to 11 months, although some studies indicate a median overall survival of around 11.24 months or even up to 28.3 months in certain cohorts. Without a stem cell transplant, the five-year overall survival rate can be as low as 7%.
Several factors can influence the overall outcome, including the patient’s general health before treatment and how well they respond to the initial chemotherapy. The ability to undergo an allogeneic stem cell transplant is a significant factor associated with improved survival. Patients under 45 years of age and those who achieve complete remission prior to transplant may experience a more favorable prognosis. Conversely, elevated serum bilirubin levels, alpha-beta (αβ) T-cell receptor expression, and trisomy 8 are factors linked to shorter survival times.