Non-Hodgkin’s lymphomas (NHLs) are a very heterogeneous group of cancers that develop in the lymph nodes present throughout the body.
There are over 25 subtypes of NHL, divided broadly into whether they originate from B-lymphocytes or T-lymphocytes. Most subtypes of NHL occur relatively infrequently, and the two most common (diffuse large B-cell and follicular B-cell lymphomas) account for over 50% of cases.
Hepatosplenic T-cell lymphoma is very uncommon. It was previously grouped with other peripheral T-cell NHLs but was identified as a distinct subtype in 1990. Since that time, less than 100 case reports have been described. Hepatosplenic T-cell lymphoma is considered an aggressive lymphoma and tends to occur more often in young adult and adolescent males, with an average age at diagnosis of 29 years.
The exact cause of hepatosplenic T-cell lymphoma is not known, although it has been described in patients who have undergone a solid organ transplant. It is thought that the immune suppressing drugs needed to prevent rejection of the transplanted organ enhance the risk of this subtype of NHL. Immune suppression is a risk factor for other subtypes of NHL as well.
Signs and Symptoms
As the name implies, hepatosplenic T-cell lymphoma involves the liver and spleen. The bone marrow is also involved in two-thirds of cases. Unlike most subtypes of NHL, hepatosplenic T-cell lymphoma rarely causes swollen lymph nodes. Not surprisingly, the most common presenting sign is hepatosplenomegaly, which is enlargement of the liver and/or spleen.
Patients often complain of abdominal fullness and pain. In addition, due to bone marrow involvement, low blood counts are commonly observed, especially low platelet and red blood cell counts. Systemic symptoms of hepatosplenic T-cell lymphoma include fatigue, fever, recurrent infections, and jaundice due to liver involvement. Abnormal liver function tests are also common.
Diagnosis and Staging
Diagnosis of hepatosplenic T-cell lymphoma can be complicated. Unlike most forms of NHL, there is not an easily accessible swollen lymph node to biopsy. In addition, there are many, more common causes of an enlarged liver and/or spleen and abnormal liver function tests; therefore, this diagnosis is often not suspected. The easiest way to diagnosis hepatosplenic T-cell lymphoma is to remove the spleen or perform a liver biopsy, with examination of the tissue by a pathologist experienced in the diagnosis of lymphoma.
Once the diagnosis of hepatosplenic T-cell lymphoma is established, patients should undergo tests to determine the extent of disease. This should include CT scans of the chest, abdomen, and pelvis, a bone marrow biopsy, a complete blood count, serum chemistries (including liver function tests, lactate dehydrogenase (LDH) and uric acid), and an HIV test. Hepatitis B testing is also recommended due to reports of hepatitis reactivation during chemotherapy.
Finally, a baseline echocardiogram or MUGA scan to evaluate heart function should be done prior to chemotherapy, as some drugs can damage the heart. Hepatosplenic T-cell lymphoma is not staged in the traditional sense, and is, by definition, advanced, stage IV disease.
Because of its rarity and aggressive course, hepatosplenic T-cell lymphoma has a very poor prognosis. The average survival time from diagnosis is only eight months.
Treatment of Hepatosplenic T-Cell Lymphoma
Unfortunately, an effective treatment for hepatosplenic T-cell lymphoma has not yet been found. Splenectomy (surgical removal of the spleen) has been reported to temporarily improve symptoms in a number of cases. This however is not a cure. Other treatments that have been tried with limited success include: corticosteroids such as prednisone, single-agent chemotherapy with agents such as chlorambucil, cyclophosphamide or fludarabine, and combination chemotherapy with the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone).
Complete responses have been reported in less than 15% of patients. Patients with hepatosplenic T-cell lymphoma would make very good candidates for clinical trials with new agents or new combinations of agents. Patients with a poor performance status may opt only for supportive care.
Hematopoietic stem cell transplant (so-called “bone marrow transplant”) is the standard of care in patients with a good performance status who have other subtypes of aggressive NHL. The most common procedure is an “autologous” transplant, in which the patient’s own blood stem cells are harvested, then re-infused following very-high-dose chemotherapy.
This is not a good option for patients with hepatosplenic T-cell lymphoma, as the patient’s bone marrow usually contains tumor cells. “Allogeneic” bone marrow transplant (blood stem cells from another person, usually a sibling) has been tried in several reports. Although complete responses were initially noted, all patients eventually relapsed with lymphoma.
Therefore, even this most aggressive treatment strategy is not curative in hepatosplenic T-cell lymphoma.
Supportive Care Issues
The focus of supportive care of the patient with hepatosplenic T-cell lymphoma is symptom management. Infections due to bone marrow involvement with lymphoma and/or chemotherapy immune suppression are common in patients with lymphoma. Prophylaxis with antibiotics may be appropriate in some, and patients should always contact their oncologist if they develop a fever.
Pain medications should be offered to patients with abdominal pain due to lymphoma, although care should be taken in initial dosing due to liver involvement and the potential for over-sedation. Patients with end-stage liver failure due to lymphoma may also need supportive medications such as lactulose for delirium and spironolactone for abdominal fluid retention.