Lymphadenopathy

Introduction:    

          Infrequently, patients will note enlarged lymph nodes and present with the chief complaint of having a nodule, a swollen gland, a "knot," or enlarged lymph nodes. More commonly, patients do not recognize that they have significantly enlarged lymph nodes, and the physician discovers the lymphadenopathy. Since lymphadenopathy can be associated with a wide range of disorders spanning relatively benign medical problems such as streptococcal pharyngitis to life-threatening malignancies, the discovery of enlarged nodes represents an important physical finding that demands a systematic evaluation.

          In searching for lymph nodes, one must be gentle; otherwise, lymph nodes that are only minimally enlarged or embedded in tissue may not be apparent. Particular attention should be directed to the size, shape, and consistency of enlarged nodes. Lymph nodes that are smooth and relatively soft, but slightly enlarged, may be normal and reveal only hyperplasia when biopsied. Enlarged lymph nodes that have an irregular shape and a rubbery, hard consistency may be infiltrated by malignant cells. Tender nodes are suggestive of an inflammatory process. Matted nodes or nodes fixed to underlying structures should raise the question of malignancy or infection; freely movable nodes are more likely to occur in benign conditions.

          The enlargement of lymph nodes, either localized or generalized, can be the consequence of several different pathologic mechanisms. Lymphadenopathy may represent an increase in the number and size of lymphoid follicles with proliferation of lymphocytes as a response to a new antigen. There can be enlargement of lymph nodes with infiltration of the node by cells normally not present, such as metastatic tumor or leukemic cells. Lymphadenopathy can occur secondary to unknown stimuli that cause normal cells to become transformed to lymphoma cells and to proliferate autonomously. Lymph nodes can be infiltrated by polymorphonuclear cells, a condition called lymphadenitis, or lymph nodes can be infiltrated by macrophages laden with metabolites, as in lipid storage diseases.

Possible causes of lymphadenopathy

I.                  Generalized lymphadenopathy

Generalized lymphadenopathy is defined as enlargement of more than 2 noncontiguous lymph node groups.

A.   Infections

1.     Viral

§  Common upper respiratory infections

§  Infectious mononucleosis

§  Cytomegalovirus (CMV) infection.

§  Human immunodeficiency virus (HIV).

§  Rubella

§  Varicella

§  Measles

2.     Bacterial

§  Septicemia

§  Typhoid fever

§  Tuberculosis

§  Syphilis

§  Plague

3.     Protozoal as Toxoplasmosis.

4.     Fungal as Coccidioidomycosis.

B.   Autoimmune disorders and hypersensitivity states

1.     Juvenile rheumatoid arthritis

2.     Systemic lupus erythematosus

3.     Drug reactions (eg, phenytoin, allopurinol and INH)

4.     Serum sickness

C.   Storage Diseases

1.     Gaucher disease

2.     Niemann-Pick disease.

D.   Neoplastic and proliferative disorders

1.     Acute leukemias (ALL, AML)

2.     Lymphomas (Hodgkin, non-Hodgkin)

3.     Neuroblastoma

4.     Histiocytoses.

II. Regional lymphadenopathy

A.   Cervical

                                                                                     i.      Viral upper respiratory infection

                                                                                   ii.      Infectious mononucleosis

                                                                                iii.      Rubella ……

                                                                                iv.      Catscratch disease

                                                                                   v.      Streptococcal pharyngitis

                                                                                vi.      Acute bacterial lymphadenitis

                                                                              vii.      Toxoplasmosis

                                                                           viii.      Tuberculosis/atypical mycobacterial infection

                                                                                ix.      Acute leukemia

                                                                                   x.      Lymphoma

                                                                                xi.      Neuroblastoma

                                                                              xii.      Rhabdomyosarcoma

                                                                           xiii.      Kawasaki disease.

                                                                           xiv.      Oral and dental infections

                                                                              xv.      Acute lymphadenitis

B.   Occipital

                                                                                     i.      Pediculosis capitis

                                                                                   ii.      Tinea capitis

                                                                                iii.      Secondary to local skin infection

                                                                                iv.      Rubella

C.   Preauricular

                                                                                     i.      Local skin infection

                                                                                   ii.      Chronic ophthalmic infection

                                                                                iii.      Catscratch disease

D.   Mediastinal

                                                                                     i.      Acute lymphoblastic leukemia

                                                                                   ii.      Lymphoma

                                                                                iii.      Sarcoidosis

                                                                                iv.      Cystic fibrosis

                                                                                   v.      Tuberculosis

                                                                                vi.      Histoplasmosis

                                                                              vii.      Coccidioidomycosis

E.   Supraclavicular

                                                                                     i.      Lymphoma

                                                                                   ii.      Tuberculosis

                                                                                iii.      Histoplasmosis

                                                                                iv.      Coccidioidomycosis

F.    Axillary

                                                                                     i.      Local infection

                                                                                   ii.      Catscratch disease

                                                                                iii.      Brucellosis

                                                                                iv.      Reactions to immunizations

                                                                                   v.      Lymphoma

                                                                                vi.      Juvenile rheumatoid arthritis

G.  Abdominal

                                                                                     i.      Acute mesenteric adenitis

                                                                                   ii.      Lymphoma

H.  Inguinal bacterial infections 

                                                                                     i.      Local infection    Diaper dermatitis

                                                                                   ii.      Insect bites

                                                                                iii.      Syphilis                Lymphogranuloma venereum

          In most patients with lymphadenopathy, a diagnosis can be made after a careful history, physical examination, and appropriate testing including hematologic parameters, serologic tests, skin tests, and routine x-rays. If a specific diagnosis cannot be established after appropriate evaluation, but infection is suspected, cautious observation after appropriate cultures have been obtained may be warranted. On the other hand, if the diagnosis cannot be established and a malignancy is a major concern, biopsy of a lymph node is appropriate.

          Although the differential diagnosis of lymphadenopathy may be broad and sometimes initially confusing, the careful gathering of data from the history, physical examination, and appropriate laboratory tests will resolve the differential in the vast majority of patients.