• 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.


  • Incidence: NHL is the most common hematopoietic neoplasm. [1]
  • Age
    • Incidence of all NHL increases with age; peak incidence > 50 years
    • High-grade lymphomas are 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)

B-cell lymphomas
Grade Lymphoma Features

Indolent (low-grade)

  • 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

Aggressive (high-grade)

  • Mantle cell lymphoma [6]
  • 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
  • Precursor B-cell lymphoblastic lymphoma
  • More common in adolescents and young adults

T-cell lymphomas (15% of all NHL)

T-cell lymphomas
Grade Lymphoma Features

Indolent (low-grade)

Aggressive (high-grade)
  • Precursor T-cell lymphoblastic lymphoma

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 trap.

Clinical features



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

Blood tests

Histology [14]

Imaging [14]

  • 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

Differential diagnoses

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) [15]

  • 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.


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
  • Watch and wait
  • Polychemotherapy*
High-grade NHL
  • All stages
  • Curative
  • Polychemotherapy*


  • Prognosis of Non-Hodgkin lymphoma is worse than that of Hodgkin lymphoma. [18]
    • 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 [19]