Lymphadenopathy and Splenomegaly

LYMPHADENOPATHY

Exposure to antigen through a break in the skin or mucosa results in antigen

being taken up by an antigen-presenting cell and carried via lymphatic channels

to the nearest lymph node. Lymph channels course throughout the body except

for the brain and the bones. Lymph enters the node through the afferent vessel

and leaves through an efferent vessel. As antigen-presenting cells pass through

lymph nodes,they present antigen to lymphocytes residing there. Lymphocytes

in a node are constantly being replaced by antigen-naive lymphocytes from the

blood. They are retained in the node via special homing receptors. B cells populate

the lymphoid follicles in the cortex; T cells populate the paracortical

regions. When a B cell encounters an antigen to which its surface immunoglobulin

can bind,it stays in the follicle for a few days and forms a germinal

center where the immunoglobulin gene is mutated in an effort to make an antibody

with higher affinity for the antigen. The B cell then migrates to the

medullary region,differentiates into a plasma cell, and secretes immunoglobulin

into the efferent lymph.

When a T cell in the node encounters an antigen it recognizes,it proliferates

and joins the efferent lymph. The efferent lymph laden with antibodies and T cells specific for the inciting antigen passes through several nodes on its way

to the thoracic duct,which drains lymph from most of the body. From the

thoracic duct,lymph enters the bloodstream at the left subclavian vein. Lymph

from the head and neck and the right arm drain into the right subclavian vein.

From the bloodstream,the antibody and T cells localize to the site of infection.

Lymphadenopathy may be caused by infections,immunologic diseases, malignancies, lipid storage diseases, or a number of disorders of uncertain etiology

(e.g.,sarcoidosis, Castleman’s disease; Table 58-1). The two major mechanisms

of lymphadenopathy are hyperplasia,in response to immunologic or infectious

stimuli,and infiltration,by cancer cells or lipid- or glycoprotein-laden macrophages.

Approach to the Patient

History Age, occupation,animal exposures,sexual orientation, substance

abuse history,medication history, and concomitant symptoms influence diagnostic

workup. Adenopathy is more commonly malignant in origin in those over

age 40. Farmers have an increased incidence of brucellosis and lymphoma. Male

homosexuals may have AIDS-associated adenopathy. Alcohol and tobacco

abuse increase risk of malignancy. Phenytoin may induce adenopathy. The concomitant

presence of cervical adenopathy with sore throat or with fever,night

sweats,and weight loss suggests particular diagnoses (mononucleosis in the

former instance,Hodgkin’s disease in the latter).

Physical Examination Location of adenopathy,size, node texture, and

the presence of tenderness are important in differential diagnosis. Generalized

adenopathy (three or more anatomic regions) implies systemic infection or lymphoma. Subclavian or scalene adenopathy is always abnormal and should be

biopsied. Nodes _ 4 cm should be biopsied immediately. Rock hard nodes fixed

to surrounding soft tissue are usually a sign of metastatic carcinoma. Tender

nodes are most often benign.

Laboratory Tests Usually lab tests are not required in the setting of localized

adenopathy. If generalized adenopathy is noted,an excisional node biopsy

should be performed for diagnosis,rather than a panoply of laboratory

tests.

TREATMENT

Pts over age 40,those with scalene or supraclavicular adenopathy, those with

lymph nodes _ 4 cm in diameter,and those with hard nontender nodes should

undergo immediate excisional biopsy. In younger patients with smaller nodes

that are rubbery in consistency or tender,a period of observation for 7–14

days is reasonable. Empirical antibiotics are not indicated. If the nodes shrink,

no further evaluation is necessary. If they enlarge,excisional biopsy is indicated.

SPLENOMEGALY

Just as the lymph nodes are specialized to fight pathogens in the tissues,the

spleen is the lymphoid organ specialized to fight bloodborne pathogens. It has

no afferent lymphatics. The spleen has specialized areas like the lymph node

for making antibodies (follicles) and amplifying antigen-specific T cells (periarteriolar lymphatic sheath,or PALS). In addition, it has a well-developed

reticuloendothelial system for removing particles and antibody-coated bacteria.

The flow of blood through the spleen permits it to filter pathogens from the

blood and to maintain quality control over erythrocytes (RBCs)—those that are old and nondeformable are destroyed,and intracellular inclusions (sometimes

including pathogens such as babesia and malaria) are culled from the cells in a

process called pitting. Under certain conditions,the spleen can generate hematopoietic cells in place of the marrow.

The normal spleen is about 12 cm in length and 7 cm in width and is not

normally palpable. Dullness from the spleen can be percussed between the ninth

and eleventh ribs with the pt lying on the right side. Palpation is best performed

with the pt supine with knees flexed. The spleen may be felt as it descends when

the pt inspires. Physical diagnosis is not sensitive. CT or ultrasound are superior

tests.

Spleen enlargement occurs by three basic mechanisms: (1) hyperplasia or

hypertrophy due to an increase in demand for splenic function (e.g.,hereditary

spherocytosis where demand for removal of defective RBCs is high or immune

hyperplasia in response to systemic infection or immune diseases); (2) passive

vascular congestion due to portal hypertension; and (3) infiltration with malignant

cells,lipid- or glycoprotein-laden macrophages, or amyloid (Table 58-2).

Massive enlargement,with spleen palpable _8 cm below the left costal margin,

usually signifies a lymphoproliferative or myeloproliferative disorder.

Peripheral blood RBC count,WBC count, and platelet count may be normal,

decreased,or increased depending on the underlying disorder. Decreases in one

or more cell lineages could indicate hypersplenism,increased destruction. In

cases with hypersplenism,the spleen is removed and the cytopenia is generally

reversed. In the absence of hypersplenism,most causes of splenomegaly are diagnosed on the basis of signs and symptoms and laboratory abnormalities

associated with the underlying disorder. Splenectomy is rarely performed for

diagnostic purposes.

Individuals who have had splenectomy are at increased risk of sepsis from

a variety of organisms including the pneumococcus and Haemophilus influenzae.

Vaccines for these agents should be given before splenectomy is performed.

Splenectomy compromises the immune response to these T-independent antigens.

Diseases Associated with Lymphadenopathy

1. Infectious diseases

a. Viral—infectious mononucleosis syndromes (EBV,CMV), infectious

hepatitis,herpes simplex, herpesvirus-6, varicella-zoster virus, rubella,

measles,adenovirus, HIV, epidemic keratoconjunctivitis, vaccinia, herpesvirus-

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b. Bacterial—streptococci,staphylococci,cat-scratch disease, brucellosis,

tularemia, plague, chancroid,melioidosis,glanders, tuberculosis, atypical

mycobacterial infection,primary and secondary syphilis, diphtheria, leprosy

c. Fungal—histoplasmosis,coccidioidomycosis,paracoccidioidomycosis

d. Chlamydial—lymphogranuloma venereum,trachoma

e. Parasitic—toxoplasmosis, leishmaniasis,trypanosomiasis,filariasis

f. Rickettsial—scrub typhus,rickettsialpox

2. Immunologic diseases

a. Rheumatoid arthritis

b. Juvenile rheumatoid arthritis

c. Mixed connective tissue disease

d. Systemic lupus erythematosus

e. Dermatomyositis

f. Sjo¨gren’s syndrome

g. Serum sickness

h. Drug hypersensitivity—diphenylhydantoin,hydralazine, allopurinol,

primidone,gold, carbamazepine, etc.

i. Angioimmunoblastic lymphadenopathy

j. Primary biliary cirrhosis

k. Graft-vs.-host disease

l. Silicone-associated

3. Malignant diseases

a. Hematologic—Hodgkin’s disease,non-Hodgkin’s lymphomas,acute or

chronic lymphocytic leukemia,hairy cell leukemia, malignant histiocytosis,

amyloidosis

b. Metastatic—from numerous primary sites

4. Lipid storage diseases—Gaucher’s,Niemann-Pick, Fabry, Tangier

5. Endocrine diseases—hyperthyroidism

6. Other disorders

a. Castleman’s disease (giant lymph node hyperplasia)

b. Sarcoidosis

c. Dermatopathic lymphadenitis

d. Lymphomatoid granulomatosis

e. Histiocytic necrotizing lymphadenitis (Kikuchi’s disease)

f. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

g. Mucocutaneous lymph node syndrome (Kawasaki’s disease)

h. Histiocytosis X

i. Familial mediterranean fever

j. Severe hypertriglyceridemia

k. Vascular transformation of sinuses

l. Inflammatory pseudotumor of lymph node

Diseases Associated with Splenomegaly Grouped by

Pathogenic Mechanism

INFILTRATION OF THE SPLEEN

Intracellular or extracellular depositions

Amyloidosis

Gaucher’s disease

Niemann-Pick disease

Tangier disease

Hurler’s syndrome and other mucopolysaccharidoses

Hyperlipidemias

Benign and malignant cellular infiltrations

Leukemias (acute,chronic,lymphoid, myeloid, monocytic)

Lymphomas

Hodgkin’s disease

Myeloproliferative syndromes (e.g.,polycythemia vera)

Angiosarcomas

Metastatic tumors (melanoma is most common)

Eosinophilic granuloma

Histiocytosis X

Hamartomas

Hemangiomas,fibromas,lymphangiomas

Splenic cysts

UNKNOWN ETIOLOGY

Idiopathic splenomegaly

Berylliosis

Iron-deficiency anemia