Snapshot A 72-year-old woman presents to the physician with concern that she has felt swollen lumps in her neck for the past 4 months. During this period, she has also had recurring fevers as high as 102°F (39°C) and sometimes wakes up in the middle of the night finding that she has soaked through her sheets. She notes that the nurse weighed her at the current visit and was surprised to discover that she has lost 15 pounds since her last check-up. An excisional lymph node biopsy is performed on her neck lymph nodes and is sent to pathology. Histology of the biopsy specimen is shown in the image. Introduction Overview non-Hodgkin lymphomas (NHLs) are tumors that originate from lymphoid tissues (i.e., lymph nodes) Epidemiology Incidence approximately 74,000 new cases/year in the US 5 times more common than Hodgkin lymphoma Demographics most commonly in people aged 65-74 median age at diagnosis is 67 years etiology Pathophysiology progressive clonal expansion of mature B-cells or T-cells arising from activated oncogenes or inactivated tumor suppressor genes 85% of NHLs are of B-cell origin NHLs of B-cell origin login to view 6 more bullets NHLs of T-cell origin login to view 2 more bullets may result from chromosomal translocations, infections, environmental factors, immunocompromised states, and chronic inflammation Genetics chromosomal translocations Burkitt lymphoma t(8;14) login to view 1 more bullet diffuse large B-cell lymphoma ↑ expression of Bcl-2 and Bcl-6 login to view 1 more bullet follicular lymphoma t(14;18) login to view 1 more bullet mantle cell lymphoma t(11;14) login to view 1 more bullet marginal zone lymphoma t(11;18) login to view 2 more bullets Presentation Symptoms low-grade NHLs painless and slowly-progressive peripheral lymphadenopathy login to view 1 more bullet fatigue weakness intermediate and high-grade NHLs lymphadenopathy "B-symptoms" login to view 3 more bullets > 1/3 patients present with extranodal involvement login to view 8 more bullets Physical exam peripheral lymphadenopathy splenomegaly hepatomegaly skin lesions in cutaneous T-cell lymphoma large abdominal mass in Burkitt lymphoma Imaging CT scan of neck, chest, abdomen, and pelvis indications for staging PET scanning indications for staging Upper GI series indications for patients with symptoms suggesting GI involvement login to view 1 more bullet MRI of brain and spinal cord indications for patients with suspected primary CNS lymphoma Studies CBC may show anemia, pancytopenia, lymphocytosis, and thrombocytosis LDH levels may be ↑ Serum β2-microglobulin may be ↑ Excisional lymph node biopsy histology Treatment Medical chemotherapy main treatment for most patients with NHL login to view 2 more bullets radiation therapy can be used as main treatment for some types of NHL if in stage I or II sometimes used along with chemotherapy for advanced and more aggressive lymphomas may palliate symptoms caused by lymphoma that has metastasized to internal organs bone marrow transplantation potential use in patients with relapsed NHL Surgical tumor resection rarely, may be used to treat lymphomas that start outside the lymphatic system (i.e., the spleen) Prognosis 5-year relative survival rate of patients with NHL is 71% Prognosis depends on several factors (i.e., tumor histology, tumor stage, and patient age) primarily dependent on histopathology secondarily influenced by clinical parameters, including age, presence of extranodal disease, and stage