Dr. Connors has written an excellent review of the management of five unusual sites of lymphomatous involvement. Several basic principles are illustrated in his discussion of rare entities:
- Low-grade lymphomas are best managed with radiation therapy when a single region is symptomatic.
- Doxorubicin(Drug information on doxorubicin)-based combination chemotherapy, with or without adjuvant irradiation, is always indicated for intermediate-grade lymphomas.
- Sanctuary sites, such as the testis and central nervous system (CNS), must be separately addressed, since systemic therapy alone is inadequate.
Gastric MALT Lymphoma
The classification of mucosa-associated lymphoid tissue (MALT) lymphomas has made it possible to identify radiosensitive diseases that are frequently present in isolated extranodal sites. As Dr. Connors points out, radiation therapy is often a good choice for local control. However, he does not include the stomach as such an extranodal site, and on this point there certainly is disagreement. The prior successful use of resection followed by adjuvant irradiation of gastric MALT is now being supplanted by primary irradiation—thus preserving the stomach with minimal side effects.[1]
The question of critical importance is whether gastric MALT is curable with the antibiotics prescribed for Helicobater pylori, or whether this systemic approach simply results in a cosmetic improvement of the gastric mucosa, allowing further growth of MALT in submucosal locations or distant sites. In the future, endoscopic ultrasound and directed deep biopsy may aid in making this evaluation.[2] A prospective collaborative study of antibiotic therapy and primary gastric irradiation is now underway to address this important question.
Intermediate-Grade Lymphomas
Extranodal intermediate-grade lymphomas are a frequent presentation of HIV-associated lymphoma, in particular, in ocular and CNS sites. When HIV-negative, these sites should be managed aggressively, with attention to both parenchymal and cerebrospinal fluid (CSF) involvement. Initial results of this strategy have been promising,[3] and it is now being studied in a larger patient cohort. Moreover, as emphasized by Dr. Connors, CNS prophylaxis is an important component of potentially curative therapy for both sinus and testicular large cell lymphomas.
Role of Autologous Stem-Cell Transplantation
This review does not address the role of autologous stem cell transplantation. However, what should be kept in mind is that incomplete response of large cell lymphoma to doxorubicin-based therapy is unlikely to be salvaged with radiation therapy alone, even when isolated to an extranodal site, such as the sinus. Moreover, patients who present with advanced disease and extranodal involvement may meet International Prognostic Index[4] criteria for high risk or high-intermediate risk and may thus be eligible for transplantation as primary treatment.
Summary
Dr. Connors’ review of unusual sites of lymphoma presentation provides the framework for standard management. Future questions must address improving remission durability with such strategies as primary irradiation of gastric MALT, intensive combined-modality therapy of ocular and CNS large cell lymphoma, and stem-cell transplantation of poor-risk, intermediate-grade lymphomas presenting with extranodal site involvement.
A 48-year-old female presents with complaints of irregular vaginal bleeding and postcoital bleeding. Images from a PET/CT and pelvis MRI reveal characteristic findings. What is your diagnosis?
