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.
Approximately 10% of all NHLs arise primarily from the gastrointestinal (GI) tract. Of these, enteropathy-type T-cell lymphoma (ETL) is one of the rarest subtypes, accounting for less than 5% of GI NHLs (less than 1% of NHLs overall). ETL was referred to as intestinal T-cell lymphoma in the medical literature prior to 1986. It tends to occur in older patients, with an average age at diagnosis of 60 years, but affects men and women with equal frequency.
The development of ETL appears to be linked to celiac disease, an association that was theorized over 30 years ago. Celiac disease is a disorder characterized by decreased nutrient absorption when wheat protein (gluten) is ingested. It can present in infancy or childhood, but it most often presents in patients in their thirties and forties.
Celiac disease is treated by advising patients to avoid gluten in their diet. This decreases the symptoms of malabsorption. Researchers have found that chronic stimulation of lymphocytes within the small intestine due to gluten in the diet may lead to the development of ETL, usually after at least several years. Patients who adhere to a gluten-free diet have a significantly decreased risk of lymphoma.
Signs and Symptoms
ETL originates most often in the jejunum, which is the middle segment of the small intestine. A single or multiple sites within the jejunum may be involved with lymphoma. The large intestine and stomach are affected much less frequently. In two-thirds of patients, lymphoma is confined to the gastrointestinal tract and surrounding lymph nodes. ETL rarely causes swollen peripheral lymph nodes that patients can feel.
Patients will complain of abdominal pain, diarrhea and vomiting. Weight loss is also commonly reported. This is due to decreased absorption of nutrients, especially protein, in the small intestine. Fatigue may also be present due to anemia. As many as 40% of patients will present with acute abdominal symptoms, including lymphoma-mediated intestinal obstruction or perforation.
This is a potentially life-threatening complication of ETL, requiring immediate surgery. Late in the course of ETL, the disease may spread to the liver, spleen and other organs.
Diagnosis and Staging
Diagnosis of ETL can be complicated, as many more common disorders can cause abdominal symptoms. Most patients will be diagnosed while undergoing exploratory abdominal surgery, with a biopsy of the affected lymph nodes.
Once the diagnosis of ETL is established, patients should undergo tests to determine the extent of disease. This should include CT scans of the chest, abdomen and pelvis, a complete blood count, serum chemistries (including liver function tests, lactate dehydrogenase (LDH) and serum albumin) and an HIV test. Hepatitis B testing is also recommended due to reports of hepatitis reactivation during chemotherapy.
A bone marrow biopsy is optional, as less than 10% of patients with ETL have involvement of this organ. Finally, a baseline echocardiogram or MUGA scan to evaluate heart function should be done prior to chemotherapy, as some drugs can damage the heart.
All of the above testing leads physicians to establish a stage of ETL for each patient. Stages for ETL include the following:
Stage I: One involved lymph node group
Stage II: Two or more involved lymph node groups on the same side of the diaphragm
Stage III: Multiple lymph node groups involved on both sides of the diaphragm
Stage IV: Disseminated involvement of other extra-nodal sites, such as the liver or spleen
Because of its rarity and aggressive course, ETL has a very poor prognosis. Only 20% of patients will survive five years from diagnosis, even with treatment. The majority of patients have recurrence of disease within six months of stopping treatment.
Part of this poor survival is due to late diagnosis: most patients are diagnosed with stage IV ETL. In addition, due to decreased absorption of nutrients from the diet, many patients with ETL have a poor performance status at the time of diagnosis and do not tolerate aggressive chemotherapy well.
Treatment of ETL
Unfortunately, an effective treatment for ETL has not yet been found. In patients with stage I disease, surgery alone may be attempted. Patients with more extensive stage ETL are usually offered combination chemotherapy with regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or VAMP (vincristine, doxorubicin, methotrexate, prednisone).
Complete responses have been reported in less than 50% of patients. Patients with ETL 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. Once a relapse occurs, there is no standard salvage treatment, and the roles of second-line chemotherapy and bone marrow transplant are not known.
Supportive Care Issues
The focus of supportive care of the patient with ETL is symptom management. Infections due to 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.
Patients may also develop abdominal infections (called peritonitis) due to the intestinal complications of ETL. Peritonitis in these patients is often fatal, especially if patients are immune suppressed from chemotherapy at the time.
Nutrition is a significant issue in patients with ETL. Many are already malnourished at the time of diagnosis. Half of patients beginning treatment with chemotherapy are unable to complete the planned courses due to malnutrition with poor performance status. If patients are or become malnourished, they may be offered nutrition by vein, so-called parenteral nutrition.
GI bleeding and/or GI perforation are potential complications of ETL during treatment with chemotherapy. Patients may receive acid-blocking drugs, such as famotidine or omeprazole, to decrease the risk of bleeding.
Patients should report any changes in abdominal symptoms to their oncologist promptly. Signs of GI bleeding, such as vomiting blood or passing dark, tarry stools, should be reported quickly as well.