Updated: 12/27/2021

Non-Hodgkin Lymphoma

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  • 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
          • Burkitt lymphoma
          • diffuse large B-cell lymphoma
          • follicular lymphoma
          • mantle cell lymphoma
          • marginal zone lymphoma
          • primary CNS lymphoma
        • NHLs of T-cell origin
          • adult T-cell lymphoma
          • mycosis fungoides (cutaneous T-cell lymphoma)
      • may result from chromosomal translocations, infections, environmental factors, immunocompromised states, and chronic inflammation
    • Genetics
      • chromosomal translocations
      • Burkitt lymphoma
        • t(8;14)
          • translocation of c-myc and heavy-chain Ig
      • diffuse large B-cell lymphoma
        • ↑ expression of Bcl-2 and Bcl-6
          • ↑ levels of Bcl-2 inhibits apoptosis
      • follicular lymphoma
        • t(14;18)
          • translocation of heavy-chain Ig and BCL-2
      • mantle cell lymphoma
        • t(11;14)
          • translocation of cyclin D1 and heavy-chain Ig
      • marginal zone lymphoma
        • t(11;18)
          • translocation of API2 and MALT1
            • promotes the continuous activation of the transcription factor NF-κB
  • Presentation
    • Symptoms
      • low-grade NHLs
        • painless and slowly-progressive peripheral lymphadenopathy
          • enlarged lymph nodes may spontaneously regress
        • fatigue
        • weakness
      • intermediate and high-grade NHLs
        • lymphadenopathy
        • "B-symptoms"
          • fever
          • night sweats
          • weight loss
        • > 1/3 patients present with extranodal involvement
          • most common sites
            • GI tract
            • skin
            • bone marrow
            • sinuses
            • genitourinary tract
            • thyroid
            • CNS
    • 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
          • endoscopy is helpful in tumor localization and staging, detection of bleeding lesions, and the obtaining of biopsy specimens
    • 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
          • one of the most common combinations: CHOP
            • Cyclophosphamide, doxorubicin (or Hydroxydaunorubicin), vincristine (Oncovin) and Prednisone
      • 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

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