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Diagnostic Considerations for Lymphadenopathy



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Am Fam Physician. 2001 Jan 1;63(1):138-140.

Lymphadenopathy is a common condition affecting all ages; however, its lengthy differential diagnosis can be quite challenging. Habermann and Steensma discuss essential diagnostic considerations that can help in the evaluation of a patient with lymphadenopathy.

TABLE 1

Causes of Lymphadenopathy: CHICAGO

Cancers

Hematologic malignancies: Hodgkin's disease, non-Hodgkin's lymphoma, acute and chronic leukemia, Waldenström macroglobulinemia, multiple myeloma (uncommon), systemic mastocytosis

Metastatic “solid” tumors: breast, lung, renal cell, prostate, other

Hypersensitivity syndromes

Serum sickness

Drug sensitivity: diphenylhydantoin, carbamazepine, primidone, gold, allopurinol, indomethacin, sulfonamides, others

Silicone reaction

Vaccination related

Graft-vs-host disease

Infections

Viral: infectious mononucleosis (Epstein-Barr virus), cytomegalovirus, infectious hepatitis, postvaccinial lymphadenitis, adenovirus, herpes zoster, HIV/AIDS, human T-lymphotropic virus 1

Bacterial: cutaneous infections (staphylococcus, streptococcus), cat-scratch fever, chancroid, melioidosis, tuberculosis, atypical mycobacteria, primary and secondary syphilis

Chlamydial: lymphogranuloma venereum

Protozoan: toxoplasmosis

Mycotic: histoplasmosis, coccidioidomycosis

Rickettsial: scrub typhus

Helminthic: filariasis

Connective tissue diseases

Rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease, Sjögren's syndrome

Atypical lymphoproliferative disorders

Angiofollicular (giant) lymph node hyperplasia (Castleman disease), angioimmunoblastic lymphadenopathy with dysproteinemia, angiocentric immunoproliferative disorders, lymphomatoid granulomatosis, Wegener's granulomatosis

Granulomatous disorders

Tuberculosis, histoplasmosis, mycobacterial infections, cryptococcus, silicosis, berylliosis, cat-scratch fever

Other unusual causes of lymphadenopathy

Inflammatory pseudotumor of lymph nodes, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), vascular transformation of sinuses, progressive transformation of germinal centers


HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome.

Adapted with permission from Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc 2000;75:726.

TABLE 1   Causes of Lymphadenopathy: CHICAGO

View Table

TABLE 1

Causes of Lymphadenopathy: CHICAGO

Cancers

Hematologic malignancies: Hodgkin's disease, non-Hodgkin's lymphoma, acute and chronic leukemia, Waldenström macroglobulinemia, multiple myeloma (uncommon), systemic mastocytosis

Metastatic “solid” tumors: breast, lung, renal cell, prostate, other

Hypersensitivity syndromes

Serum sickness

Drug sensitivity: diphenylhydantoin, carbamazepine, primidone, gold, allopurinol, indomethacin, sulfonamides, others

Silicone reaction

Vaccination related

Graft-vs-host disease

Infections

Viral: infectious mononucleosis (Epstein-Barr virus), cytomegalovirus, infectious hepatitis, postvaccinial lymphadenitis, adenovirus, herpes zoster, HIV/AIDS, human T-lymphotropic virus 1

Bacterial: cutaneous infections (staphylococcus, streptococcus), cat-scratch fever, chancroid, melioidosis, tuberculosis, atypical mycobacteria, primary and secondary syphilis

Chlamydial: lymphogranuloma venereum

Protozoan: toxoplasmosis

Mycotic: histoplasmosis, coccidioidomycosis

Rickettsial: scrub typhus

Helminthic: filariasis

Connective tissue diseases

Rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease, Sjögren's syndrome

Atypical lymphoproliferative disorders

Angiofollicular (giant) lymph node hyperplasia (Castleman disease), angioimmunoblastic lymphadenopathy with dysproteinemia, angiocentric immunoproliferative disorders, lymphomatoid granulomatosis, Wegener's granulomatosis

Granulomatous disorders

Tuberculosis, histoplasmosis, mycobacterial infections, cryptococcus, silicosis, berylliosis, cat-scratch fever

Other unusual causes of lymphadenopathy

Inflammatory pseudotumor of lymph nodes, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), vascular transformation of sinuses, progressive transformation of germinal centers


HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome.

Adapted with permission from Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc 2000;75:726.

The authors provide an acronym, “CHICAGO” (cancers, hypersensitivity syndromes, infections, connective tissue disease, atypical lymphoproliferative disorders, granulomatous lesions, other unusual causes of lymphadenopathy) that includes common causes of lymphadenopathy (see Table 1). The essential considerations in lymphadenopathy follow another acronym, “ALL AGES” (age, location, length of time present, associated signs and symptoms, generalized lymphadenopathy, extranodal associations, splenomegaly and fever). The critical task is to decide which nodes are associated with benign disease rather than malignancy, thus determining treatment. The authors state that age is the most important factor predicting benign or malignant disease, and they cite a study of 925 patients in which carcinoma was found to be more common in patients older than 50 years. Lymphoproliferative disorders, however, were not found to have an age predilection.

Although some patients are asymptomatic, others have a temperature higher than 38°C (100.4°F), drenching night sweats and unexplained weight loss. The physician should be aware that symptomatic and asymptomatic patients may have pathologic lymphadenopathy, and that qualitative characteristics like node consistency may not be helpful in distinguishing benign versus malignant lesions. For example, metastatic disease, Hodgkin's disease and tuberculosis can be associated with rock-hard nodes, but they can also present with soft nodes. Two helpful tips the authors present are that lymphangitic streaking is often consistent with cutaneous infection, and that splenomegaly is rare in metastatic cancer. Splenomegaly is more commonly associated with infectious mononucleosis, Hodgkin's disease, non-Hodgkin's lymphoma, chronic lymphocytic leukemia and acute leukemia. Adenopathy in the presence of fever points toward a broad differential, mainly consisting of infection or lymphoma.

The size, length of time present and location can help determine when a biopsy is needed. If lymphoma is suspected, a surgical biopsy is preferred over needle aspiration to ensure adequate sampling. The least helpful biopsies are in the inguinal region, unless the most abnormal or accessible node is located there. The authors recommend that lymph nodes that have been present outside the inguinal region for longer than one month and measure 1 cm or larger in diameter without an obvious diagnosis should be considered for biopsy. When multiple sites are involved, the initial biopsy site should be in the largest peripheral node outside of the inguinal region. When nodes are the same size, the following order should be used: supraclavicular, cervical, axillary, epitrochlear, inguinal. Table 2 lists the various regions of lymphadenopathy and associated etiologies.

TABLE 2

Regional Differential Diagnosis of Lymphadenopathy

Cervical

Infections: pharyngitis, dental abscess, otitis media and otitis externa, infectious mononucleosis, toxoplasmosis, cytomegalovirus, hepatitis, adenovirus, rubella

Malignancies: Hodgkin's disease, non-Hodgkin's lymphoma, squamous cell carcinoma of the head and neck

Kikuchi disease

Supraclavicular and prelaryngeal

Virchow node: abdominal and thoracic neoplasm

Delphian node: thyroid and laryngeal disease

Infections: mycobacterial (e.g., scrofula), fungal

Axillary

Infections: staphylococcal and streptococcal arm infections, cat-scratch fever, tularemia, sporotrichosis

Malignancies: breast carcinoma, Hodgkin's disease, non-Hodgkin's lymphoma, melanoma

Epitrochlear

Lymphoproliferative disorders

Connective tissue diseases and sarcoidosis

Dermatologic diseases

“Historical” associations: syphilis, leprosy, leishmaniasis, rubella

Inguinal

Benign reactive (especially in shoeless walkers)

Malignancies: Hodgkin's disease, non-Hodgkin's lymphoma, melanoma, squamous cell carcinoma of the penis and vulva, anal cancer

Infections: cellulitis, venereal disease

Hilar

Unilateral

Infections: bacterial pneumonia, mycobacterial diseases, fungal infections, tularemia, psittacosis, pertussis

Other granulomatous diseases

Malignancies: bronchogenic carcinoma, metastatic breast cancer and gastrointestinal cancers, non-Hodgkin lymphoma, Hodgkin disease

Bilateral

Granulomatous diseases: sarcoidosis, berylliosis, etc.

Bilateral infections

Malignancies: non-Hodgkin's lymphoma, Hodgkin's disease, metastatic carcinoma

Calcified: tuberculosis, histoplasmosis, silicosis

Mediastinal

Exclude other causes of mediastinal widening

Differential diagnosis is similar to that for hilar lymphadenopathy

Abdominal

Malignancies: metastatic adenocarcinoma (including gastric), non-Hodgkin lymphoma, transitional cell carcinoma of the urinary collecting system, chronic lymphocytic leukemia, hairy cell leukemia, Hodgkin disease (rarely mesenteric)

Tuberculosis

Generalized

Hematologic malignancies: non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, acute lymphocytic leukemia

Infections: infectious mononucleosis, cytomegalovirus, human immunodeficiency virus, tuberculosis, toxoplasmosis, histoplasmosis, coccidioidomycosis, brucellosis

Rheumatoid arthritis, systemic lupus erythematous

Sarcoidosis

Angioimmunoblastic lymphadenopathy


Adapted with permission from Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc 2000;75:728.

TABLE 2   Regional Differential Diagnosis of Lymphadenopathy

View Table

TABLE 2

Regional Differential Diagnosis of Lymphadenopathy

Cervical

Infections: pharyngitis, dental abscess, otitis media and otitis externa, infectious mononucleosis, toxoplasmosis, cytomegalovirus, hepatitis, adenovirus, rubella

Malignancies: Hodgkin's disease, non-Hodgkin's lymphoma, squamous cell carcinoma of the head and neck

Kikuchi disease

Supraclavicular and prelaryngeal

Virchow node: abdominal and thoracic neoplasm

Delphian node: thyroid and laryngeal disease

Infections: mycobacterial (e.g., scrofula), fungal

Axillary

Infections: staphylococcal and streptococcal arm infections, cat-scratch fever, tularemia, sporotrichosis

Malignancies: breast carcinoma, Hodgkin's disease, non-Hodgkin's lymphoma, melanoma

Epitrochlear

Lymphoproliferative disorders

Connective tissue diseases and sarcoidosis

Dermatologic diseases

“Historical” associations: syphilis, leprosy, leishmaniasis, rubella

Inguinal

Benign reactive (especially in shoeless walkers)

Malignancies: Hodgkin's disease, non-Hodgkin's lymphoma, melanoma, squamous cell carcinoma of the penis and vulva, anal cancer

Infections: cellulitis, venereal disease

Hilar

Unilateral

Infections: bacterial pneumonia, mycobacterial diseases, fungal infections, tularemia, psittacosis, pertussis

Other granulomatous diseases

Malignancies: bronchogenic carcinoma, metastatic breast cancer and gastrointestinal cancers, non-Hodgkin lymphoma, Hodgkin disease

Bilateral

Granulomatous diseases: sarcoidosis, berylliosis, etc.

Bilateral infections

Malignancies: non-Hodgkin's lymphoma, Hodgkin's disease, metastatic carcinoma

Calcified: tuberculosis, histoplasmosis, silicosis

Mediastinal

Exclude other causes of mediastinal widening

Differential diagnosis is similar to that for hilar lymphadenopathy

Abdominal

Malignancies: metastatic adenocarcinoma (including gastric), non-Hodgkin lymphoma, transitional cell carcinoma of the urinary collecting system, chronic lymphocytic leukemia, hairy cell leukemia, Hodgkin disease (rarely mesenteric)

Tuberculosis

Generalized

Hematologic malignancies: non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, acute lymphocytic leukemia

Infections: infectious mononucleosis, cytomegalovirus, human immunodeficiency virus, tuberculosis, toxoplasmosis, histoplasmosis, coccidioidomycosis, brucellosis

Rheumatoid arthritis, systemic lupus erythematous

Sarcoidosis

Angioimmunoblastic lymphadenopathy


Adapted with permission from Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc 2000;75:728.

Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc July. 2000;75:723–32.


Copyright © 2001 by the American Academy of Family Physicians.
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