Signs and symptoms
Fever, weight loss, and night sweats, referred to as systemic B symptoms, as well as fatigue and weakness, are more common in advanced or aggressive NHL but may be present in all stages and histologic subtypes.
Painless, slowly progressive peripheral adenopathy is the most common clinical presentation in patients with low-grade lymphomas. Patients sometimes report a history of waxing and waning adenopathy before seeking medical attention. Spontaneous regression of enlarged lymph nodes can occur and can cause a low-grade lymphoma to be confused with an infectious condition.
Primary extranodal involvement and B symptoms are uncommon at presentation; however, both are more common in advanced or end-stage disease. Bone marrow is frequently involved, sometimes in association with cytopenias. Splenomegaly is seen in about 40% of patients, but the spleen is rarely the only involved site at presentation.
The clinical presentation of aggressive-histology lymphomas is more varied. Although the majority of patients present with adenopathy, more than one-third present with extranodal involvement, the most common sites being the GI tract (including Waldeyer's ring), skin, bone marrow, sinuses, bone, and CNS. B symptoms are more common, occurring in about 30% to 40% of patients.
Lymphoblastic lymphoma often typically presents with an anterior superior mediastinal mass with possible superior vena cava syndrome, and leptomeningeal disease with possible cranial nerve palsies.
American patients with Burkitt lymphoma often present with a large abdominal mass and symptoms of bowel obstruction.
No effective methods are available for screening or identifying populations at high risk of developing NHL. A definitive diagnosis can be made only by biopsy of pathologic lymph nodes or tumor tissue. It is critical to perform an excisional lymph node biopsy (fine-needle aspiration [FNA] is insufficient for diagnostic purposes) to avoid false-negative results and inaccurate histologic classification. One study showed that when FNAs and biopsy results for the diagnosis of NHL and Hodgkin lymphoma were compared, only 12% of FNAs correlated with subsequent excisional biopsy results. When clinical circumstances make surgical biopsy of involved lymph nodes or extranodal sites prohibitive, a core biopsy obtained under CT or ultrasonographic guidance may suffice but often requires the integration of histologic examination for diagnosis. A formal review by an expert hematopathologist is mandatory. Additional studies, such as immunophenotyping and genotyping, are often necessary.
Initial diagnostic evaluation
Initial diagnostic evaluation of patients with lymphoproliferative malignancy should include the following:
• Careful history (night sweats, weight loss, fever; neurologic, musculoskeletal, or GI symptoms)
• Physical examination (lymph nodes, including submental, infraclavicular, epitrochlear, iliac, femoral, and popliteal nodes; pericardial rub, pleural effusion, distended neck and/or upper extremity veins in superior vena cava syndrome; breast masses; hepatosplenomegaly, bowel obstruction, renal mass, and testicular or ovarian mass; focal neurologic signs, such as plexopathy, spinal cord compression, nerve root infiltration, and meningeal involvement; skin lesions) [dropped copy here and below]
• Biopsy of peripheral lymphadenopathy (excisional biopsy)
• CT scan of the neck (cervical lymph nodes, Waldeyer's ring) and chest (mediastinal, hilar, or parenchymal pulmonary disease)
• CT scan of the abdomen and pelvis (enlarged lymph nodes, splenomegaly, filling defects in the liver and spleen)
• Bilateral bone marrow biopsy and aspirate
• FDG-PET scans (selected cases: aggressive histologies) for staging at diagnosis, response, assessment, and relapse; off of a clinical trial, "early" repeat PET scans (eg, following 2 cycles) are not advocated, in part due to the frequent disparate interpretation of PET scans.
• Complete blood count (CBC) with differential and platelet count (peripheral blood lymphocytosis with circulating malignant cells is common in low-grade lymphoma and MCL). Bone marrow and peripheral blood involvement may be present, and the distinction between leukemia and lymphoma is difficult to make in some cases.
• General chemistry panel (including lactate dehydrogenase [LDH] level determination) is mandatory.
• Hepatitis B virus (HBV) and HCV panels should be considered, especially in patients anticipated to receive monoclonal antibody therapy and/or chemotherapy (HBV: HBV surface antigen and HBV core antibody; HCV: HCV antibody).
• HIV serology in at-risk patients with DLBCL and other aggressive and Burkitt histologies; HTLV-1 serology in select patients with cutaneous T-cell lymphoma, especially if they have hypercalcemia.
• Cytogenetic and molecular analyses of lymph node, bone marrow, and peripheral blood (selected cases).
• Immunophenotyping can be of particular benefit in distinguishing B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) from other lymphomas (Table 2). Immunophenotyping and histochemical markers may also be of benefit in distinguishing T-cell lymphomas/leukemias (Table 3).
• Examination of cerebrospinal fluid (CSF) and consideration of intrathecal chemotherapy prophylaxis in patients with (1) diffuse aggressive NHL with bone marrow, epidural, testicular, paranasal sinus, breast, or multiple extranodal sites; (2) high-grade lymphoblastic lymphoma and Burkitt lymphoma and its variants; (3) primary CNS lymphoma if no evidence of increased intracranial pressure.
• Upper GI endoscopy in patients with head and neck involvement (tonsil, base of tongue, nasopharynx) and those with a GI primary NHL; MCL is associated with a high incidence of occult GI involvement.
• Ultrasonography of opposite testis in patients with a testicular primary.
• Spinal MRI scan for epidural disease when clinically indicated (critical in the evaluation of suspected spinal cord involvement).