Lymphadenopathy: Differential Diagnosis and Evaluation

A more recent article on lymphadenopathy is available.

ROBERT FERRER, M.D., Grand.P.H., University of Texas Health Sciences Center at San Antonio, San Antonio, Texas

Am Fam Physician. 1998 Oct 15;58(6):1313-1320.

Article Sections

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm'southward 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Terminal Comment
  • References

Although the finding of lymphadenopathy sometimes raises fears nearly serious illness, it is, in patients seen in primary care settings, usually a result of beneficial infectious causes. Most patients can exist diagnosed on the ground of a careful history and physical examination. Localized adenopathy should prompt a search for an next precipitating lesion and an exam of other nodal areas to rule out generalized lymphadenopathy. In full general, lymph nodes greater than 1 cm in diameter are considered to be abnormal. Supraclavicular nodes are the most worrisome for malignancy. A iii- to four-week period of observation is prudent in patients with localized nodes and a beneficial clinical picture. Generalized adenopathy should always prompt further clinical investigation. When a node biopsy is indicated, excisional biopsy of the almost abnormal node will best enable the pathologist to determine a diagnosis.

The cause of lymphadenopathy is oftentimes obvious: for example, the child who presents with a sore throat, tender cervical nodes and a positive rapid strep test, or the patient who presents with an infection of the manus and axillary lymphadenopathy. In other cases, the diagnosis is less clear. Lymphadenopathy may exist the only clinical finding or one of several nonspecific findings, and the discovery of swollen lymph nodes will often enhance the specter of serious disease such equally lymphoma, acquired immunodeficiency syndrome or metastatic cancer. The physician's task is to efficiently differentiate the few patients with serious illness from the many with self-express illness. This commodity reviews the evaluation of patients with a fundamental clinical finding of lymphadenopathy, emphasizing the identification of patients with serious illness.

Definition

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm's 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Final Comment
  • References

The body has approximately 600 lymph nodes, but but those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people.one Lymphadenopathy refers to nodes that are aberrant in either size, consistency or number. There are various classifications of lymphadenopathy, but a elementary and clinically useful organisation is to classify lymphadenopathy equally "generalized" if lymph nodes are enlarged in two or more than noncontiguous areas or "localized" if merely one expanse is involved. Distinguishing betwixt localized and generalized lymphadenopathy is important in formulating a differential diagnosis. In primary care patients with unexplained lymphadenopathy, approximately iii fourths of patients will present with localized lymphadenopathy and one fourth with generalized lymphadenopathy (Figure ane).2,three

FIGURE i.

Presentation of lymphadenopathy past anatomic site (in percentages).

Epidemiology

  • Abstruse
  • Definition
  • Epidemiology
  • Diagnostic Arroyo to Lymphadenopathy
  • Clinical Evaluation for Algorithm's 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Final Comment
  • References

Our understanding of the epidemiology of lymphadenopathy in family unit practice is express by the scarcity of relevant literature. Only one study4 provides reliable population-based estimates. Findings from this Dutch study revealed a 0.six per centum annual incidence of unexplained lymphadenopathy in the general population. Of 2,556 patients in the written report who presented with unexplained lymphadenopathy to their family physicians, 256 (10 percentage) were referred to a subspecialist and 82 (3.two percent) required a biopsy, just only 29 (i.1 pct) had a malignancy.

This low prevalence of malignancy is supported by the results of two instance series2,3 from family unit exercise departments in the United States, in which none of 80 patients and three of 238 patients with unexplained lymphadenopathy were diagnosed with malignancy. In contrast, the prevalence of malignancy in lymph node biopsies performed in referral centers is xl to threescore percent,five a statistic that has made its way into many textbooks (east.m., "In those more than than thirty years of age, nevertheless, lymphadenopathy is due to a benign process only twoscore percent of the time"6). Such assertions overestimate the probability of malignancy in patients with lymphadenopathy because they exclude the 97 percent of patients with lymphadenopathy who practice not undergo a biopsy. In primary intendance settings, patients 40 years of age and older with unexplained lymphadenopathy have about a 4 per centum risk of cancer versus a 0.iv percent risk in patients younger than age 40.4

Diagnostic Approach to Lymphadenopathy

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm's 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Terminal Comment
  • References

The algorithm in Figure ii provides a diagnostic framework for the evaluation of lymphadenopathy. The algorithm emphasizes that a careful history and physical examination are the core of the evaluation. In almost cases, a careful history and physical exam will identify a readily diagnosable cause of the lymphadenopathy, such as upper respiratory tract infection, pharyngitis, periodontal disease, conjunctivitis, lymphadenitis, tinea, insect bites, recent immunization, cat-scratch illness or dermatitis, and no further assessment is necessary (run across the "diagnostic" branch of the algorithm).

FIGURE 2.

Algorithm for the evaluation of a patient with lymphadenopathy. (HIV = human immunodeficiency virus; CBC = complete blood count; PPD = purified protein derivative; RPR = rapid plasma reagin; ANA = antinuclear antibiotic; HBsAg = hepatitis B surface antigen)

In other cases, a definitive diagnosis cannot be made on the ground of the history and physical exam solitary; even so, the clinical evaluation may strongly propose a particular crusade. Confirmatory testing should be performed in club to correctly place the patient's illness (see the "suggestive" branch of the algorithm).

A subset of patients will either have unexplained lymphadenopathy after the initial clinical evaluation or accept a presumptive diagnosis that is made in the "diagnostic" or "suggestive" branches of the algorithm and is not confirmed by test results or by the clinical form. In patients with unexplained localized lymphadenopathy and a reassuring clinical motion picture, a three- to four-week period of observation is appropriate before biopsy. Patients with localized lymphadenopathy and a worrisome clinical movie or patients with generalized lymphadenopathy will demand further diagnostic evaluation that often includes biopsy (run into the "unexplained" branch of the algorithm). Fine-needle aspiration is occasionally considered an culling to excisional biopsy simply often yields a high number of nondiagnostic results because of the small corporeality of tissue obtained and the inability to examine the architecture of the gland.7 In addition, there may be some risk of sinus tract formation, depending on the underlying pathology.viii

History

The doc should consider four key points when compiling a patient's history.i  First, are there localizing symptoms or signs to propose infection or neoplasm in a specific site? Second, are there constitutional symptoms such equally fever, weight loss, fatigue or dark sweats to propose disorders such every bit tuberculosis, lymphoma, collagen vascular diseases, unrecognized infection or malignancy? 3rd, are at that place epidemiologic clues (Table 1) such every bit occupational exposures, recent travel or loftier-risk behaviors that suggest specific disorders? Fourth, is the patient taking a medication that may cause lymphadenopathy? Some medications are known to specifically cause lymphadenopathy (e.grand., phenytoin [Dilantin]), while others, such equally cephalosporins, penicillins or sulfonamides, are more likely to crusade a serum sickness-like syndrome with fever, arthralgias and rash in addition to lymphadenopathy (Table 2).

Tabular array one

Epidemiologic Clues to the Diagnosis of Lymphadenopathy

Exposure Diagnosis

General

Cat

Cat-scratch affliction, toxoplasmosis

Undercooked meat

Toxoplasmosis

Tick bite

Lyme disease, tularemia

Tuberculosis

Tuberculous adenitis

Recent blood transfusion or transplant

Cytomegalovirus, HIV

High-risk sexual behavior

HIV, syphilis, canker simplex virus, cytomegalovirus, hepatitis B infection

Intravenous drug utilise

HIV, endocarditis, hepatitis B infection

Occupational

Hunters, trappers

Tularemia

Fishermen, fishmongers, abattoir workers

Erysipeloid

Travel-related

Arizona, southern California, New Mexico, western Texas

Coccidioidomycosis

Southwestern U.s.

Bubonic plague

Southeastern or central The states

Histoplasmosis

Southeast Asia, Republic of india, northern Australia

Scrub typhus

Cardinal or west Africa

African trypanosomiasis (sleeping sickness)

Central or South America

American trypanosomiasis (Chagas' affliction)

East Africa, Mediterranean, China, Latin America

Kala-azar (leishmaniasis)

United mexican states, Peru, Chile, India, Pakistan, Egypt, Indonesia

Typhoid fever

TABLE two

Medications That May Cause Lymphadenopathy

Allopurinol (Zyloprim)

Atenolol (Tenormin)

Captopril (Capozide)

Carbamazepine (Tegretol)

Cephalosporins

Gilded

Hydralazine (Apresoline)

Penicillin

Phenytoin (Dilantin)

Primidone (Mysoline)

Pyrimethamine (Daraprim)

Quinidine

Sulfonamides

Sulindac (Clinoril)

Physical Exam

When lymphadenopathy is localized, the clinician should examine the region drained by the nodes for evidence of infection, skin lesions or tumors (Table 3). Other nodal sites should also exist carefully examined to exclude the possibility of generalized rather than localized lymphadenopathy. This is an of import aspect of the examination, as a written report of primary care physicians plant that generalized lymphadenopathy was identified in only 17 per centum of the patients in whom it was present.9 Conscientious palpation of the submandibular, anterior and posterior cervical, supraclavicular, axillary and inguinal nodes can exist accomplished in a short time and volition identify patients with generalized lymphadenopathy.

Table iii

Lymph Node Groups: Location, Lymphatic Drainage and Selected Differential Diagnosis

Location Lymphatic drainage Causes

Submandibular

Natural language, submaxillary gland, lips and oral cavity, conjunctivae

Infections of head, neck, sinuses, ears, eyes, scalp, pharynx

Submental

Lower lip, floor of mouth, tip of tongue, skin of cheek

Mononucleosis syndromes, Epstein-Barr virus, cytomegalovirus, toxoplasmosiss

Jugular

Natural language, tonsil, pinna, parotid

Pharyngitis organisms, rubella

Posterior cervical

Scalp and cervix, skin of arms and pectorals, thorax, cervical and axillary nodes

Tuberculosis, lymphoma, caput and neck malignancy

Suboccipital

Scalp and head

Local infection

Postauricular

External auditory meatus, pinna, scalp

Local infection

Preauricular

Eyelids and conjunctivae, temporal region, pinna

External auditory canal

Correct supraclavicular node

Mediastinum, lungs, esophagus

Lung, retroperitoneal or gastrointestinal cancer

Left supraclavicular node

Thorax, belly via thoracic duct

Lymphoma, thoracic or retroperitoneal cancer, bacterial or fungal infection

Axillary

Arm, thoracic wall, chest

Infections, true cat-scratch disease, lymphoma, breast cancer, silicone implants, brucellosis, melanoma

Epitrochlear

Ulnar aspect of forearm and hand

Infections, lymphoma, sarcoidosis, tularemia, secondary syphilis

Inguinal

Penis, scrotum, vulva, vagina, perineum, gluteal region, lower intestinal wall, lower anal culvert

Infections of the leg or foot, STDs (e.g., herpes simplex virus, gonococcal infection, syphilis, chancroid, granuloma inguinale, lymphogranuloma venereum), lymphoma, pelvic malignancy, bubonic plague

If lymph nodes are detected, the following five characteristics should be noted and described:

Size. Nodes are by and large considered to exist normal if they are upwardly to i cm in diameter; however, some authors suggest that epitrochlear nodes larger than 0.v cm or inguinal nodes larger than i.five cm should be considered aberrant.7,8 Piddling data exists to suggest that a specific diagnosis can be based on node size. However, in one series10 of 213 adults with unexplained lymphadenopathy, no patient with a lymph node smaller than ane cm2 (i cm × 1 cm) had cancer, while cancer was nowadays in 8 percent of those with nodes from 1 cm2 to 2.25 cm2 (1 cm × ane cm to ane.5 cm × i.v cm) in size, and in 38 percent of those with nodes larger than ii.25 cm2 (1.v cm × 1.5 cm). In children, lymph nodes larger than ii cm in diameter (forth with an abnormal chest radiograph and the absence of ear, nose and pharynx symptoms) were predictive of granulomatous diseases (i.e., tuberculosis, true cat-scratch disease or sarcoidosis) or cancer (predominantly lymphomas).11 These studies were performed in referral centers, and conclusions may not apply in primary care settings.

Pain/Tenderness. When a lymph node rapidly increases in size, its capsule stretches and causes pain. Hurting is normally the outcome of an inflammatory procedure or suppuration, just hurting may also upshot from hemorrhage into the necrotic center of a cancerous node. The presence or absence of tenderness does non reliably differentiate benign from malignant nodes.4

Consistency. Stony-difficult nodes are typically a sign of cancer, unremarkably metastatic. Very firm, rubbery nodes propose lymphoma. Softer nodes are the effect of infections or inflammatory conditions. Suppurant nodes may exist fluctuant. The term "shotty" refers to small nodes that feel like buckshot under the skin, as found in the cervical nodes of children with viral illnesses.

Matting. A group of nodes that feels connected and seems to movement as a unit is said to be "matted." Nodes that are matted can be either benign (due east.chiliad., tuberculosis, sarcoidosis or lymphogranuloma venereum) or malignant (e.g., metastatic carcinoma or lymphomas).

Location. The anatomic location of localized adenopathy will sometimes exist helpful in narrowing the differential diagnosis. For instance, cat-scratch affliction typically causes cervical or axillary adenopathy, infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy (Table 4).

Supraclavicular lymphadenopathy has the highest risk of malignancy, estimated as 90 percentage in patients older than 40 years and 25 percent in those younger than age 40.four Having the patient perform a Valsalva's maneuver during palpation of the supraclavicular fossae increases the chance of detecting a node. Lymphadenopathy of the right supraclavicular node is associated with cancer in the mediastinum, lungs or esophagus. The left supraclavicular (Virchow'southward) node receives lymphatic flow from the thorax and abdomen, and may bespeak pathology in the testes, ovaries, kidneys, pancreas, prostate, stomach or gallbladder. Although rarely present, a paraumbilical (Sister Joseph'due south) node may be a sign of an abdominal or pelvic neoplasm.12

In patients with generalized lymphadenopathy, the physical examination should focus on searching for signs of systemic illness. The most helpful findings are rash, mucous membrane lesions, hepatomegaly, splenomegaly or arthritis (Tabular array 4). Splenomegaly and lymphadenopathy occur concurrently in many conditions, including mononucleosis-blazon syndromes, lymphocytic leukemia, lymphoma and sarcoidosis.

TABLE four

Evaluation of Suspected Causes of Lymphadenopathy

Disorder Associated findings Test

Mononucleosis-type syndromes

Fatigue, malaise, fever, singular lymphocytosis

Epstein-Barr virus*

Splenomegaly in 50% of patients

Monospot, IgM EA or VCA

Toxoplasmosis*

80 to 90% of patients are asymptomatic

IgM toxoplasma antibody

Cytomegalovirus*

Frequently mild symptoms; patients may have hepatitis

IgM CMV antibody, viral culture of urine or blood

Initial stages of HIV infection*

"Influenza-like" disease, rash

HIV antibody

Cat-scratch disease

Fever in one tertiary of patients; cervical or axillary nodes

Usually clinical criteria; biopsy if necessary

Pharyngitis due to group A streptococcus, gonococcus

Fever, pharyngeal exudates, cervical nodes

Throat culture on appropriate medium

Tuberculosis lymphadenitis*

Painless, matted cervical nodes

PPD, biopsy

Secondary syphilis*

Rash

RPR

Hepatitis B*

Fever, nausea, vomiting, icterus

Liver office tests, HBsAg

Lymphogranuloma venereum

Tender, disordered inguinal nodes

Serology

Chancroid

Painful ulcer, painful inguinal nodes

Clinical criteria, civilization

Lupus erythematosus*

Arthritis, rash, serositis, renal, neurologic, hematologic disorders

Clinical criteria, antinuclear antibodies, complement levels

Rheumatoid arthritis*

Arthritis

Clinical criteria, rheumatoid factor

Lymphoma*

Fever, night sweats, weight loss in 20 to 30% of patients

Biopsy

Leukemia*

Claret dyscrasias, bruising

Blood smear, bone marrow

Serum sickness*

Fever, malaise, arthralgia, urticaria; exposure to antisera or medications

Clinical criteria, complement assays

Sarcoidosis

Hilar nodes, skin lesions, dyspnea

Biopsy

Kawasaki affliction*

Fever, conjunctivitis, rash, mucous membrane lesions

Clinical criteria

Less common causes of lymphadenopathy

Lyme disease*

Rash, arthritis

IgM serology

Measles*

Fever, conjunctivitis, rash, coughing

Clinical criteria, serology

Rubella*

Rash

Clinical criteria, serology

Tularemia

Fever, ulcer at inoculation site

Blood culture, serology

Brucellosis*

Fever, sweats, malaise

Blood culture, serology

Plague

Febrile, acutely ill with cluster of tender nodes

Blood civilization, serology

Typhoid fever*

Fever, chills, headache, abdominal complaints

Claret civilisation, serology

Nonetheless's disease*

Fever, rash, arthritis

Clinical criteria, antinuclear antibody, rheumatoid cistron

Dermatomyositis*

Proximal weakness, pare changes

Musculus enzymes, EMG, muscle biopsy

Amyloidosis*

Fatigue, weight loss

Biopsy

Clinical Evaluation for Algorithm'due south 'Suggestive' Branch

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm'south 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Last Comment
  • References

Laboratory tests that may be useful in confirming the cause of lymphadenopathy are listed in Tabular array 4. The presence of certain characteristic clinical syndromes may assist the doc determine a suspected crusade of lymphadenopathy.

Mononucleosis-Type Syndromes

Patients with these syndromes present with lymphadenopathy, fatigue, malaise, fever and an increased singular lymphocyte count. Mononucleosis is most unremarkably due to Epstein-Barr virus infection. The presence of the typical syndrome and positive results on a heterophilic antibody exam (Monospot test) confirms the diagnosis. The most common cause of heterophil-negative mononucleosis is early Epstein-Barr virus infection. False-negative results on heterophilic antibody tests are especially common in patients younger than four years of age. Epstein-Barr virus infection may be confirmed by repeating the Monospot test in 7 to 10 days. Rarely is it necessary to confirm the diagnosis with IgM viral capsid antigen or early antigen antibody titers.

If Epstein-Barr virus antibodies are absent, other causes of the mononucleosis syndrome should exist considered. These include toxoplasmosis, cytomegalovirus infection, streptococcal pharyngitis, hepatitis B infection and astute human immunodeficiency virus (HIV) infection. Astute infections with cytomegalovirus and Toxoplasma may be identified with IgM serology for those organisms.

Ulceroglandular Syndrome

This syndrome is defined by the presence of a skin lesion with associated regional lymphadenopathy. The archetype crusade is tularemia, acquired by contact with an infected rabbit or tick; more common causes include streptococcal infection (due east.g., impetigo), cat-scratch disease and Lyme disease.

Oculoglandular Syndrome

This syndrome involves the combination of conjunctivitis and associated preauricular nodes. Mutual causes include viral kerato-conjunctivitis and cat-scratch affliction resulting from an ocular lesion.

HIV Infection

Enlargement of the lymph nodes that persists for at least three months in at least 2 extrainguinal sites is divers as persistent generalized lymphadenopathy and is common in patients in the early stages of HIV infection. Other causes of generalized lymphadenopathy in HIV-infected patients include Kaposi's sarcoma, cytomegalovirus infection, toxoplasmosis, tuberculosis, cryptococcosis, syphilis and lymphoma.

Unexplained Lymphadenopathy

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm's 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Final Annotate
  • References

When, later on the initial evaluation and later exploration of the "diagnostic" and "suggestive" branches of the algorithm ( Figure 2 ), a crusade for the lymphadenopathy remains unexplained, the medico must decide whether to pursue a specific diagnosis. The conclusion will depend primarily on the clinical setting as adamant by the patient'south historic period, the duration of the lymphadenopathy and the characteristics and location of the nodes.

Generalized Lymphadenopathy

Because generalized lymphadenopathy nearly ever indicates that a significant systemic disease is present, the clinician should consider the diseases listed in Table 4 and keep with specific testing as indicated. If a diagnosis cannot be fabricated, the clinician should obtain a biopsy of the node. The diagnostic yield of the biopsy can be maximized by obtaining an excisional biopsy of the largest and nigh aberrant node (which is non necessarily the near accessible node). If possible, the physician should not select inguinal and axillary nodes for biopsy, since they frequently bear witness only reactive hyperplasia.

Localized Lymphadenopathy

If the lymphadenopathy is localized, the decision almost when to biopsy is more difficult. Patients with a beneficial clinical history, an unremarkable physical exam and no ramble symptoms should exist reexamined in three to four weeks to see if the lymph nodes have regressed or disappeared. Patients with unexplained localized lymphadenopathy who take constitutional symptoms or signs, take a chance factors for malignancy or lymphadenopathy that persists for three to 4 weeks should undergo a biopsy. Biopsy should be avoided in patients with probable viral illness because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a fake-positive diagnosis of malignancy.

Initial Management

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm'southward 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Terminal Comment
  • References

Many patients worry about the cause of their abnormal lymph nodes. To fairly address their fears, the physician should ask the patient about his or her concerns and reply to questions about specific diagnoses. When biopsy is deferred, the physician should explain to the patient the rationale for waiting. Patients should exist cautioned to remain alarm for the reappearance of the nodes because lymphomatous nodes accept been known to temporarily backslide.

Concluding Annotate

  • Abstract
  • Definition
  • Epidemiology
  • Diagnostic Approach to Lymphadenopathy
  • Clinical Evaluation for Algorithm's 'Suggestive' Branch
  • Unexplained Lymphadenopathy
  • Initial Management
  • Final Comment
  • References

In most patients, lymphadenopathy has a readily diagnosable infectious cause. A diagnosis of less obvious causes can oftentimes exist made later because the patient'south age, the duration of the lymphadenopathy and whether localizing signs or symptoms, ramble signs or epidemiologic clues are present. When the cause of the lymphadenopathy remains unexplained, a three- to four-week observation period is appropriate when the clinical setting indicates a high probability of beneficial affliction.

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The Author

ROBERT FERRER, Yard.D., M.P.H., is an banana professor of family practice at the University of Texas Health Sciences Center at San Antonio. He received his medical caste from Hahnemann University School of Medicine in Philadelphia and completed a residency in family medicine at Duke University School of Medicine, Durham, North.C., and a fellowship in family medicine at the University of Washington School of Medicine, Seattle.

Address correspondence to Robert Ferrer, M.D., M.P.H., Department of Family unit Practise, University of Texas Health Sciences Middle at San Antonio, 7703 Floyd Curlicue Dr., San Antonio, TX 78284-7795; e-mail: ferrerr@uthscsa.edu. Reprints are not available from the author.

Figure 1 adjusted from Allhiser JN, McKnight TA, Shank JC. Lymphadenopathy in a family practice. J Fam Pract 1981;12:27–32, and Williamson HA Jr. Lymphadenopathy in a family practice: a descriptive study of 249 cases. J Fam Pract 1985;20:449–58.

REFERENCES

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1. Goroll AH, May LA, Mulley AG Jr. Primary care medicine: part evaluation and management of the adult patient. 2d ed. Philadelphia: Lippincott, 1987. ...

ii. Allhiser JN, McKnight TA, Shank JC. Lymphadenopathy in a family exercise. J Fam Pract. 1981;12:27–32.

3. Williamson HA Jr. Lymphadenopathy in a family unit practice: a descriptive study of 249 cases. J Fam Pract. 1985;xx:449–58.

4. Fijten GH, Blijham GH. Unexplained lymphadenopathy in family practice. An evaluation of the probability of malignant causes and the effectiveness of physicians' workup. J Fam Pract. 1988;27:373–6.

5. Lee Y, Terry R, Lukes RJ. Lymph node biopsy for diagnosis: a statistical study. J Surg Oncol. 1980;14:53–60.

vi. Bennett JC, Plum F, eds. Cecil textbook of medicine. 20th ed. Philadelphia: Saunders, 1996.

7. Libman H. Generalized lymphadenopathy. J Gen Intern Med. 1987;2:48–58.

8. Morland B. Lymphadenopathy. Curvation Dis Kid. 1995;73:476–9.

ix. Paauw DS, Wenrich MD, Curtis JR, Carline JD, Ramsey PG. Ability of primary intendance physicians to recognize physical findings associated with HIV infection. JAMA. 1995;274:1380–2.

10. Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol. 1993;20:570–82.

eleven. Slap GB, Brooks JS, Schwartz JS. When to perform biopsies of enlarged peripheral lymph nodes in young patients. JAMA. 1984;252:1321–6.

12. Sapira JD. The fine art and scientific discipline of bedside diagnosis. Baltimore: Urban & Schwarzenberg, 1990:139–44.

Each year members of a different family practice department develop manufactures for "Problem-Oriented Diagnosis." This serial is coordinated by the Section of Family Practice at the University of Texas Wellness Science Middle at San Antonio. Invitee editors of the series are David A. Katerndahl, M.D., and Clinton Colmenares.

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