ESSENTIAL FEATURES
• The diagnosis of non-Hodgkin lymphoma encompasses a wide spectrum of lymphoid-derived tumors
• More than 10 distinct tumor subtypes with variable biologic behavior
• Non-Hodgkin lymphoma may originate from B cells, T cells, or histiocytes
• In contrast to Hodgkin lymphoma, lymph node tumor involvement is more likely to spread in a noncontinous fashion in non-Hodgkin lymphoma
• Prognosis and treatment is more dependent on the grade and type of malignancy in contrast to the importance of clinical stage in Hodgkin lymphoma
• Functionally separated into low-grade and high-grade groups
• 33% of cases arise outside of the lymph nodes: oropharynx, paranasal sinuses, thyroid, GI tract, liver, testicles, skin, bone marrow, and CNS
• Most common extranodal site is the stomach, accounting for 50% of all GI lymphomas
• Most accepted classification system is the Revised European-American Lymphoma (REAL) classification
EPIDEMIOLOGY
• Risk factors for the development of lymphoma:
• Ataxia-telangiectasia
• Wiscott-Aldrich syndrome
• Celiac disease
• Prior chemotherapy
• History of radiation therapy
• Immunosuppressive therapy
• HIV
• Human T-cell lymphotropic virus type 1 infection
• Sjögren syndrome
• Extranodal lymphoma risk factors:
–Gastric lymphoma: Helicobacter pylori infection
–Thyroid lymphoma: Hashimoto thyroiditis
SYMPTOMS AND SIGNS
• Nontender enlargement of lymph nodes
• Constitutional symptoms:
–Fever
–Drenching night sweats
–Weight loss
• Gastric lymphoma symptoms and signs include epigastric pain, weight loss, and frequently a palpable epigastric mass
LABORATORY FINDINGS
• No distinctive basic laboratory findings present, although lymphomas tend to be associated with an elevated lactic dehydrogenase
IMAGING FINDINGS
• Imaging findings are specific to the location and type of lymphoma
• Chest film: May demonstrate mediastinal adenopathy
• CT scan: Main staging tool used to demonstrate areas of adenopathy
DIAGNOSTIC CONSIDERATIONS
• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• Reactive lymphadenopathy
–Infectious mononucleosis
–Cat-scratch disease
–HIV
–Drug reactions (eg, phenytoin)
• Tumor metastases
RULE OUT
• Reactive lymphadenopathy
• Metastatic disease to the lymph nodes
WORK-UP
• Detailed history of risk factors and presence of constitutional symptoms
• Thorough physical exam assessing all lymph node beds
• Routine laboratory testing
• Excisional biopsy of enlarged lymph node
• Bone marrow biopsy
• CT scans of the neck, chest, abdomen, and pelvis
• Gastric lymphoma work-up also includes esophagogastroduodenscopy with biopsy and brush cytology
WHEN TO admit
• Most patients with lymphadenopathy that is suspicious for lymphoma are worked-up urgently as an outpatient or admitted to expedite the process
WHEN TO refer
• Following histologic diagnosis, patients are referred to medical and radiation oncologists for definitive treatment
TREATMENT AND MANAGEMENT
• Treatment depends on grade and stage of the lymphoma:
–Low-grade localized: Radiation with or without adjuvant chemotherapy
–Low-grade systemic: “Watch and wait” approach; when more aggressive disease develops, single agent palliative chemotherapy is instituted
–High-grade localized: Radiation and adjuvant chemotherapy
–High-grade systemic: Chemotherapy with or without radiation (to areas of bulky disease)
• Gastric lymphoma: Systemic chemotherapy (vs surgical resection and radiation therapy, which are controversial)
• Thyroid lymphoma: Surgical resection followed by combined chemotherapy and neck irradiation
SURGERY
Indications
• Excisional lymph node biopsy to establish diagnosis
• Some centers perform gastric resections for gastric lymphoma to prevent chemotherapy-related perforation or hemorrhage although this practice is controversial and significantly delays beginning therapeutic chemotherapy
MEDICATIONS
• Chemotherapy: Classically, the CHOP regimen (cyclophosphamide, doxorubicin, oncovorin, and prednisone) for high-grade systemic disease and extranodal lymphomas
• Monoclonal antibodies to non-Hodgkin lymphoma tumor-specific antigens are being used in clinical trials
TREATMENT MONITORING
• Physical exam to evaluate for lymphadenopathy
• Radiographic evaluation as clinically indicated (eg, with the redevelopment of constitutional symptoms)
Complications omplications
• Localized radiation-induced complications
• Chemotherapy-induced pancytopenia with the resulting bleeding and infectious complications
Prognosis
• Although the course of low-grade lymphomas is typically indolent, they are difficult to cure and most patients eventually die; median survival times 6–12 years
• High-grade lymphomas are associated with an increased rate of early disease-related mortality but are often curable with aggressive chemotherapy regimens
RESOURCES
REFERENCES
• Ansell SM, Armitage JO: Non-Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc 2005;80:1087.
PRACTICE GUIDELINES
• The National Cancer Network web site
–http://www.nccn.org/
