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Non-Hodgkin lymphomas

Last updated: November 29, 2020

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Lymphomas are a type of cancer that arises from lymphocytes. These malignancies are classified into Hodgkin lymphomas, which are characterized by the presence of Reed-Sternberg cells, and non-Hodgkin lymphomas (NHLs), which comprise all other types of lymphoma. NHLs are further classified according to the cell type, i.e., B cells, T cells, and natural killer (NK) cells, and tumor grade. Low-grade tumors originate from mature cells that have a slow growth rate and an indolent clinical course. The most common low-grade B-cell lymphoma is follicular lymphoma, while the most common low-grade T-cell lymphomas are the cutaneous T-cell lymphomas such as mycosis fungoides. High-grade tumors, on the other hand, have a rapid growth rate and an aggressive clinical course. Certain subtypes of NHL are more common in children and young adults, such as Burkitt lymphoma. There is a variety of treatment options, depending on the type of lymphoma. Generally, treatment involves a combination of chemotherapy and radiation therapy. Limited disease low-grade tumors and high-grade NHL are treated with a curative approach. Advanced, low-grade tumors are treated with a palliative approach in symptomatic patients.

Epidemiological data refers to the US, unless otherwise specified.

B-cell lymphomas (85% of all NHL)

B-cell lymphomas
Grade Lymphoma Features

Indolent (low-grade)

  • Follicular lymphoma
  • Most common low-grade lymphoma in adults
  • Slowly progressive and painless course with an alternating (waxing and waning) pattern of lymphadenopathy and splenomegaly
  • Translocation t(14,18), which involves the heavy-chain Ig (chromosome 14) and Bcl-2 gene (chromosome 18) overexpression of Bcl-2 → dysregulation of apoptosis (normally inhibited by Bcl-2)
  • Nodular, small cells with cleaved nuclei
  • Hairy cell leukemia
  • Small lymphocytic lymphoma (SLL) [3]

Aggressive (high-grade)

  • Diffuse large B-cell lymphoma (DLBCL)
  • More common in adult men
  • Translocation t(11;14), involving cyclin D1 (chromosome 11) and heavy-chain Ig (chromosome 14) increased levels of cyclin D1 → promotes S phase transition of cells
  • CD5+
  • Spreads rapidly; most patients are diagnosed with advanced disease (stage IV)
  • Burkitt lymphoma [7]
    • Sporadic: typically located in the abdomen or pelvis
    • Endemic: EBV-associated (most prevalent in equatorial Africa and South America) and typically located in the maxillary and mandibular bones
    • AIDS-related

T-cell lymphomas (15% of all NHL)

T-cell lymphomas
Grade Lymphoma Features

Indolent (low-grade)

Aggressive (high-grade)
  • Aggressive NK-cell leukemia [10]
  • Angioimmunoblastic T-cell lymphoma [11]

Think of an aggressive man to remember that the occurrence of mantle cell lymphoma is greater in men and that the disease has an aggressive course.

Hair can get TRAPped in the hairdryer: hairy cell leukemia, TRAP stain, dry tap.

See ”Differential diagnosis of B symptoms”, “Enlarged lymph nodes”, and “Differential diagnosis of granulomatous disease for more information.

Extranodal masses

The 4 T's of anterior mediastinal masses: Thymoma, Teratoma (and other germ cell tumors), Thyroid neoplasm, and Terrible lymphoma.

Necrotizing lymphadenitis (Kikuchi-Fujimoto disease) [12]

  • Etiology: unknown
  • Epidemiology
    • Rare; most commonly reported in Asian population
    • Sex: >
    • Mean age: 30 years
  • Clinical features: painful cervical lymphadenopathy and fever
  • Diagnostics: Lymph node biopsy shows single or multiple necrotic foci, histiocytic cellular infiltration, without granulocytic involvement.
  • Treatment: typically resolves spontaneously within 1–4 months of onset without treatment

The differential diagnoses listed here are not exhaustive.

Diagnosis of NHL is primarily based on medical history and clinical features and is confirmed with lymph node biopsy.

Blood tests

Histology [13]

Imaging [13]

  • X-ray and CT: required in all patients for staging
  • Brain MRI: for patients with neurologic symptoms
  • Endoscopy: for tumor localization and staging, obtaining of biopsy specimens
  • Possibly PET-CT: initial evaluation for NHL staging, and post-treatment assessment of response to treatment

Further tests

  • Staging: similar to the one used for Hodgkin lymphoma (see “Cotswold modification of Ann Arbor staging system”), but without B symptoms
  • Classification [14][15]
    • Limited disease (stage I + II): lymph node involvement confined to one side of the diaphragm
    • Advanced disease (stage III + IV): lymph node and/or extranodal involvement on both sides of the diaphragm

There is a variety of treatment options, depending on the type of lymphoma. The choice of treatment is primarily based on the tumor grade, rather than the disease stage.

Treatment of non-Hodgkin lymphomas [16]
Grade Stage Therapeutic intention Therapy
Low-grade NHL
  • Limited stage
  • Curative
  • Advanced stage
  • Palliative
High-grade NHL
  • All stages
  • Curative
  • Polychemotherapy*
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  2. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J Clin Oncol. 2014 . doi: 10.1200/JCO.2013.54.8800 . | Open in Read by QxMD
  3. Report of the Committee on Hodgkin's Disease Staging Classification. http://cancerres.aacrjournals.org/content/canres/31/11/1860.full.pdf. Updated: November 1, 1971. Accessed: February 8, 2017.
  4. Tests for Non-Hodgkin Lymphoma. https://www.cancer.org/cancer/non-hodgkin-lymphoma/detection-diagnosis-staging/how-diagnosed.html. Updated: August 1, 2018. Accessed: October 16, 2020.
  5. Mahajan T, Merriman RC, Stone MJ. Kikuchi-Fujimoto Disease (Histiocytic Necrotizing Lymphadenitis): Report of a Case with Other Autoimmune Manifestations. Baylor University Medical Center Proceedings. 2007; 20 (2): p.149-151. doi: 10.1080/08998280.2007.11928275 . | Open in Read by QxMD
  6. Batchelor T. Treatment and prognosis of primary central nervous system lymphoma. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-and-prognosis-of-primary-central-nervous-system-lymphoma?source=search_result&search=primary%20CNS%20lymphoma&selectedTitle=1~66.Last updated: October 10, 2016. Accessed: February 8, 2017.
  7. Hairy Cell Leukemia Treatment. https://www.cancer.gov/types/leukemia/hp/hairy-cell-treatment-pdq. Updated: March 23, 2018. Accessed: October 17, 2020.
  8. Key Statistics for Non-Hodgkin Lymphoma. https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html. Updated: January 8, 2020. Accessed: October 17, 2020.
  9. Survival Rates and Factors That Affect Prognosis (Outlook) for Non-Hodgkin Lymphoma. https://www.cancer.org/cancer/non-hodgkin-lymphoma/detection-diagnosis-staging/factors-prognosis.html. Updated: January 8, 2020. Accessed: October 16, 2020.
  10. Gayer G, Luboshitz J, Hertz M, et al. Congenital Anomalies of the Inferior Vena Cava Revealed on CT in Patients with Deep Vein Thrombosis. American Journal of Roentgenology. 2003; 180 (3): p.729-732. doi: 10.2214/ajr.180.3.1800729 . | Open in Read by QxMD
  11. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300147. Updated: December 1, 2016. Accessed: February 8, 2017.
  12. Pasqualucci L. The genetic basis of diffuse large B-cell lymphoma.. Curr Opin Hematol. 2013; 20 (4): p.336-44. doi: 10.1097/MOH.0b013e3283623d7f . | Open in Read by QxMD
  13. Cerami E. AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discovery. 2017; 7 (8): p.818-831. doi: 10.1158/2159-8290.cd-17-0151 . | Open in Read by QxMD
  14. Mantle Cell Lymphoma. https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/. Updated: January 1, 2005. Accessed: October 18, 2020.
  15. Freedman AS, Aster JC. Epidemiology, clinical manifestations, pathologic features, and diagnosis of Burkitt lymphoma. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-clinical-manifestations-pathologic-features-and-diagnosis-of-burkitt-lymphoma?source=search_result&search=burkitt%20lymphoma&selectedTitle=1~76.Last updated: September 14, 2016. Accessed: February 8, 2017.
  16. Rook AH, Olsen EA, Kuzel TM, Zic JA, Rosmarin AG. Clinical Presentation, Pathologic Features, and Diagnosis of Sézary Syndrome. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-presentation-pathologic-features-and-diagnosis-of-sezary-syndrome.Last updated: July 14, 2016. Accessed: February 8, 2017.
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  18. Ishida F. Aggressive NK-Cell Leukemia. Frontiers in Pediatrics. 2018; 6 . doi: 10.3389/fped.2018.00292 . | Open in Read by QxMD
  19. Angioimmunoblastic T-Cell Lymphoma. https://rarediseases.org/rare-diseases/angioimmunoblastic-t-cell-lymphoma/. Updated: July 18, 2017. Accessed: October 16, 2020.
  20. Freedman AS, Friedberg DW. Evaluation, staging, and response assessment of non-Hodgkin lymphoma. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/evaluation-staging-and-response-assessment-of-non-hodgkin-lymphoma.Last updated: February 2, 2017. Accessed: February 8, 2017.