History and exam

Key diagnostic factors

uncommon

B symptoms (fever, night sweats, weight loss)

Signs and symptoms of NHL are often vague, but the presence of B symptoms (unexplained fever, drenching night sweats, and weight loss >10% of body weight within 6 months) is important as it may indicate aggressive (high-grade) NHL or advanced-stage disease.[3][4][5][6]

fatigue/malaise

May be from anaemia.[3][4]

Other diagnostic factors

common

lymphadenopathy

May present with peripheral lymphadenopathy.[3]

splenomegaly

Due to infiltration of the spleen by lymphoma cells.[72]

Can be massive in splenic marginal zone lymphoma.[72] May cause splenic infarction.[100]

uncommon

hepatomegaly

Due to infiltration of the liver by lymphoma cells.[99]

shortness of breath

May be from anemia, pulmonary or pleural involvement, or pleural/pericardial effusion.[7][8]

cough

May be from pulmonary, mediastinal, or lymph node involvement.[5][7]

abdominal discomfort or pain

May be from gastrointestinal, liver, spleen, or lymph node involvement.[9]

headache

May be from central nervous system involvement.[10]

change in mental status

May be from central nervous system involvement.[10]

focal neurological deficits

For example ataxia, cognitive changes, and focal weakness. Possible central nervous system involvement.[10]

chest pain

May be from cardiac ischaemia secondary to severe anaemia, or from pleural, pericardial, pulmonary, or mediastinal involvement.[7][101]

bone pain

May be from bone involvement.[11]

back pain

May be from spinal bone or epidural involvement.[11][12]

jaundice

Due to liver infiltration, or intrahepatic or extrahepatic biliary obstruction.[102][103][104]

pallor

Due to anaemia.[3]

purpura

Due to thrombocytopenia, coagulation abnormalities secondary to liver involvement, or disseminated intravascular coagulation.

skin lesions

Cutaneous NHL presents primarily with skin lesions; other types of NHL may involve the skin.[73]

Lesions may be patches or raised plaques. Some may ulcerate. Itching is common.

See Cutaneous T-cell lymphoma topic.

neurological abnormalities on examination

May result from central nervous system involvement.[10]

Examination findings depend on the site and type of involvement.

visual abnormalities

May result from vitreoretinal involvement (e.g., blurring, decreased acuity, floaters).[10]

breast pain

May occur in patients with breast implant involvement (breast implant-associated anaplastic large cell lymphoma).[13]

swelling or mass in the breast

May occur in patients with breast implant involvement (breast implant-associated anaplastic large cell lymphoma [BIA-ALCL]).[13]​​​

Swelling around breast implants (seroma) occurring >1 year after implantation is the most common presentation in patients with BIA-ALCL.[13][105][106][107]

metabolic abnormalities (acute renal injury, tumour lysis syndrome, hypercalcaemia)

May occur in patients with aggressive (high-grade) NHL (e.g., Burkitt's lymphoma) or those with advanced-stage disease.[14][15]

Risk factors

strong

age >60 years

Non-Hodgkin's lymphoma incidence increases with age; median age at diagnosis in the US is 68 years.[17]

male sex

In the US, non-Hodgkin's lymphoma (NHL) incidence is higher among men than women (22.4 vs. 15.7 new cases per 100,000, respectively [2018-2022 data]).[17] 

Incidence among men and women may vary depending on NHL subtype.

Epstein-Barr virus (EBV)

EBV is associated with certain types of B-cell lymphoma (e.g., diffuse large B-cell lymphoma, primary central nervous system lymphoma, Burkitt's lymphoma) and T-cell lymphoma (e.g., peripheral T-cell lymphoma, extranodal NK/T-cell lymphoma).[29][30]

human T-lymphocytotrophic virus-1 (HTLV-1)

HTLV-1 is the causative agent for adult T-cell leukaemia/lymphoma.[34]​​

Kaposi sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV8)

KSHV/HHV8 is the causative agent for primary effusion lymphoma (in patients with HIV).[35]

KSHV/HHV8 is also associated with diffuse large B-cell lymphoma and germinotropic lymphoproliferative disorder.[35]

coeliac disease

There is an association between autoimmune disorders and non-Hodgkin's lymphoma (e.g., coeliac disease with aggressive enteropathy-associated T-cell lymphoma/intestinal T-cell lymphoma).[38][63][64]

HIV

HIV is associated with certain types of B-cell lymphoma (e.g., Burkitt's lymphoma, diffuse large B-cell lymphoma, primary central nervous system lymphoma).[25][26][27][65]

Aetiology is likely associated with EBV coinfection and ineffective immunoregulation of this oncovirus.[25][66]

hepatitis C virus (HCV)

HCV has been linked to splenic marginal zone lymphoma and to diffuse large B-cell lymphoma.[31]​​​[32][33]​​

Sjogren syndrome

There is an association between autoimmune disorders and non-Hodgkin's lymphoma (e.g., Sjogren syndrome with marginal zone lymphoma and diffuse large B-cell lymphoma).[38][39]​​​​​

Wiskott-Aldrich syndrome

There is an association between inherited immunodeficiency disorders and non-Hodgkin's lymphoma (e.g., Wiskott-Aldrich syndrome with diffuse large B-cell lymphoma).[40]

ataxia-telangiectasia

An inherited immunodeficiency disorder associated with diffuse large B-cell lymphoma.[40]

use of immunomodulatory drugs

Use of immunomodulatory drugs, such as tumour necrosis factor (TNF)-alpha antagonists (e.g., infliximab, adalimumab), is associated with an increased risk for non-Hodgkin's lymphoma.[47]

weak

organ transplant

Immunosuppression following organ transplantation is associated with non-Hodgkin's lymphoma.[67]​​

Coxiella burnetii

Coxiella burnetii is associated with B-cell lymphoma.[36]

rheumatoid arthritis

Patients with rheumatoid arthritis are at increased risk for diffuse large B-cell lymphoma compared with the general population.[37][38][39]​​​​

systemic lupus erythematosus (SLE)

SLE increases risk for haematological malignancies including diffuse large B-cell lymphoma and marginal zone lymphoma.[37][38][39]​​​​

haemolytic anaemia

Various non-Hodgkin's lymphomas can coexist with autoimmune haemolytic anaemia.​[38][68]

common variable immunodeficiency

Common variable immunodeficiency is associated with an increased risk for non-Hodgkin's lymphoma.[40][69]

Klinefelter syndrome

Patients with Klinefelter syndrome (47, XXY karyotype) appear to be at increased risk for non-Hodgkin's lymphoma.[42][43]

pesticides

Occupational exposure to certain pesticides has been associated with non-Hodgkin's lymphoma (e.g., phenoxy herbicides with diffuse large B-cell lymphoma).​​[44][45][46]

breast implants

Breast implants are associated with an increased risk of anaplastic large cell lymphoma (ALCL).​[21][24][48]​​​​​​​​​[49][50]

As of June 2024, the US Food and Drug Administration identified 1380 cases of breast implant-associated ALCL (BIA-ALCL) worldwide, with 64 related deaths.[22]

As of May 2025, the American Society of Plastic Surgeons recognises approximately 1618 cases of BIA-ALCL worldwide.[23]

Most cases of BIA-ALCL have occurred with textured implants, but there have been reports of BIA-ALCL with smooth-surface implants.[22]​​​​ Median time from implant to diagnosis of BIA-ALCL is 8 years.​[22]

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