• Clinical science

Non-Hodgkin lymphomas


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.


  • NHL is the most common hematopoietic neoplasm
  • Approx. 85% of lymphomas
  • Incidence of all NHL increases with age; peak incidence > 50 years
  • Subtype variance with age
    • High-grade lymphomas more common in children and young adults (20–40 years)


Epidemiological data refers to the US, unless otherwise specified.




B-cell lymphomas (85% of all NHL)

Lymphoma Features

Indolent (low-grade)

  • Waldenstrom's macroglobulinemia
  • Most common low-grade lymphoma in adults
  • Slowly progressive, painless lymphadenopathy of alternating size (“waxing and waning”) and splenomegaly
  • Translocation t(14,18): heavy-chain Ig (14) and Bcl-2 (18) are translocated, resulting in an overexpression of Bcl-2, which inhibits apoptosis
  • Nodular, small cells with cleaved nuclei

Aggressive (high-grade)

  • Precursor B-cell lymphoblastic lymphoma
  • More common in adolescents and young adults
  • More common in older men
  • Translocation t(11;14)
  • CD5+

T-cell lymphomas (15% of all NHL)

Lymphoma Features

Indolent (low-grade)

  • Cutaneous lymphoma
  • Atypical CD4+ cells
  • Heterogeneous skin lesions
  • May progress to Sézary syndrome
Aggressive (high-grade)
  • Precursor T-cell lymphoblastic lymphoma


Clinical features





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

Blood tests



  • X-ray and CT are required in all patients for staging
  • Brain MRI for patients with neurologic symptoms
  • Possibly PET-CT: initial evaluation for NHL staging, and post-treatment assessment

Further tests


Differential diagnoses

The 4 T's of a mediastinal mass: Thymoma, Teratoma (and other germ cell tumors), Thyroid neoplasm, and Terrible lymphoma!

The differential diagnoses listed here are not exhaustive.


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.

Grade Stage Therapeutic intention Therapy
Low-grade NHL Limited stage Curative
  • Radiation therapy
Advanced stage Palliative
  • Watch and wait
  • Polychemotherapy*
High-grade NHL All stages Curative
  • Polychemotherapy*



  • Low-grade lymphomas: median survival of 6–10 years
  • High-grade lymphomas: survival typically several months (years in less aggressive variants)
  • Indicators of poor prognosis: old age, number of involved nodal and extranodal sites, LDH, ↑ beta2 microglobulin