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Lymphadenopathy Soheir Adam, MD, MSc, MRCPath. The Lymphatic System The body has approximately 600 lymph nodes, but only those in the submandibular, axillary.

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Presentation on theme: "Lymphadenopathy Soheir Adam, MD, MSc, MRCPath. The Lymphatic System The body has approximately 600 lymph nodes, but only those in the submandibular, axillary."— Presentation transcript:

1 Lymphadenopathy Soheir Adam, MD, MSc, MRCPath

2 The Lymphatic System The body has approximately 600 lymph nodes, but only those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people.1 Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. There are various classifications of lymphadenopathy, but a simple and clinically useful system is to classify lymphadenopathy as "generalized" if lymph nodes are enlarged in two or more noncontiguous areas or "localized" if only one area is involved.

3 Distinguishing between localized and generalized lymphadenopathy is important in formulating a differential diagnosis. In primary care patients with unexplained lymphadenopathy, approximately 3/4 of patients will present with localized lymphadenopathy and 1/4 with generalized lymphadenopathy.


5 Lympahdenopathy Findings from a Dutch study revealed a 0.6% annual incidence of unexplained lymphadenopathy in the general population. Of 2,556 patients in the study who presented with unexplained lymphadenopathy to their family physicians, 256 (10 %) were referred to a subspecialist and 82 (3.2 %) required a biopsy, but only 29 (1.1 %) had a malignancy.


7 Lymphadenopathy

8 History First, are there localizing symptoms or signs to suggest infection or neoplasm in a specific site? Second, are there constitutional symptoms such as fever, weight loss, fatigue or night sweats to suggest disorders such as tuberculosis, lymphoma, collagen vascular diseases, unrecognized infection or malignancy?

9 History Third, are there epidemiologic clues such as occupational exposures, recent travel or high-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.g., phenytoin ), while others, such as cephalosporins, penicillins or sulfonamides, are more likely to cause a serum sickness-like syndrome with fever, arthralgias and rash in addition to lymphadenopathy.

10 Medications That May Cause Lymphadenopathy Allopurinol (Zyloprim) Atenolol (Tenormin) Captopril (Capozide) Carbamazepine (Tegretol) Cephalosporins Gold Hydralazine (Apresoline) Penicillin Phenytoin (Dilantin) Primidone (Mysoline) Pyrimethamine (Daraprim) Quinidine Sulfonamides Sulindac (Clinoril) Adapted with permission from Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol 1993; 20:570-82.

11 Physical Examination Size. Pain/Tenderness :The presence or absence of tenderness does not reliably differentiate benign from malignant nodes. Consistency: Stony-hard nodes are typically a sign of cancer, usually metastatic. Very firm, rubbery nodes suggest lymphoma. Softer nodes are the result of infections or inflammatory conditions. Suppurant nodes may be 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.

12 Physical Examination Matting : can be either benign (e.g., tuberculosis, sarcoidosis) or malignant (e.g., metastatic carcinoma or lymphomas Location : infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy

13 Physical Examination Supraclavicular lymphadenopathy has the highest risk of malignancy, estimated as 90 percent in patients older than 40 years and 25 percent in those younger than age. Lymphadenopathy of the right supraclavicular node is associated with cancer in the mediastinum, lungs or esophagus. The left supraclavicular (Virchow's) node receives lymphatic flow from the thorax and abdomen, and may signal pathology in the testes, ovaries, kidneys, pancreas, prostate, stomach or gallbladder. Although rarely present

14 DisorderAssociated findingsTest Evaluation of Suggestive S & S Associated with Lymphadenopathy Mononucleosis-type syndromes Fatigue, malaise, fever, atypical lymphocytosis Epstein-Barr virus*Splenomegaly in 50% of patientsMonospot, IgM EA or VCA Toxoplasmosis*80 to 90% of patients are asymptomatic IgM toxoplasma antibody Cytomegalovirus*Often mild symptoms; patients may have hepatitis IgM CMV antibody, viral culture of urine or blood Initial stages of HIV infection* "Flu-like" illness, rashHIV antibody Cat-scratch diseaseFever in one third 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 nodesPPD, biopsy Secondary syphilis*RashRPR Hepatitis B*Fever, nausea, vomiting, icterusLiver function tests, HBsAg

15 Lymphogranuloma venereumTender, matted inguinal nodesSerology ChancroidPainful ulcer, painful inguinal nodesClinical criteria, culture Lupus erythematosus*Arthritis, rash, serositis, renal, neurologic, hematologic disorders Clinical criteria, antinuclear antibodies, complement levels Rheumatoid arthritis*ArthritisClinical criteria, rheumatoid factor Lymphoma*Fever, night sweats, weight loss in 20 to 30% of patientsBiopsy Leukemia*Blood dyscrasias, bruisingBlood smear, bone marrow Serum sickness*Fever, malaise, arthralgia, urticaria; exposure to antisera or medications Clinical criteria, complement assays SarcoidosisHilar nodes, skin lesions, dyspneaBiopsy Kawasaki disease*Fever, conjunctivitis, rash, mucous membrane lesionsClinical criteria

16 Less common causes of lymphadenopathy Lyme disease* Rash, arthritisIgM serology Measles* Fever, conjunctivitis, rash, coughClinical criteria, serology Rubella* RashClinical criteria, serology Tularemiala* Fever, ulcer at inoculation siteBlood culture, serology Brucellosis* Fever, sweats, malaiseBlood culture, serology Plague Febrile, acutely ill with cluster of tender nodesBlood culture, serology Typhoid fever* Fever, chills, headache, abdominal complaintsBlood culture, serology Still's disease* Fever, rash, arthritisClinical criteria, antinuclear antibody, rheumatoid factor Dermatomyositis* Proximal weakness, skin changesMuscle enzymes, EMG, muscle biopsy Amyloidosis* Fatigue, weight lossBiopsy *--Causes of generalized lymphadenopathy. EA=early antibody; VCA=viral capsid antigen; CMV=cytomegalovirus; HIV=human immunodeficiency virus; PPD=purified protein derivative; RPR=rapid plasma reagin; HBsAg=hepatitis B surface antigen; EMG=electromyelography.

17 Unexplained Lymphadenopathy Generalized Lymphadenopathy almost always indicates a systemic disease is present, proceed with specific testing as indicated. If a diagnosis cannot be made, 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 most abnormal node The physician should not select inguinal and axillary nodes for biopsy, since they frequently show only reactive hyperplasia

18 Unexplained Lymphadenopathy Localized Lymphadenopathy  The decision about when to biopsy is more difficult.  Patients with a benign clinical history, an unremarkable physical examination and no constitutional symptoms should be reexamined in three to four weeks to see if the lymph nodes have regressed or disappeared.  Patients with unexplained localized lymphadenopathy who have constitutional symptoms or signs, risk factors for malignancy or lymphadenopathy that persists for three to four weeks should undergo a biopsy.

19 Unexplained Lymphadenopathy Localized Lymphadenopathy  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 false-positive diagnosis of malignancy.

20 Lymphoma

21 Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation

22 A practical way to think of lymphoma CategorySurvival of untreated patients CurabilityTo treat or not to treat Non- Hodgkin lymphoma IndolentYearsGenerally not curable Generally defer Rx if asymptomatic AggressiveMonthsCurable in some Treat Very aggressive WeeksCurable in some Treat Hodgkin lymphoma All typesVariable – months to years Curable in most Treat

23 Diagnosis requires an adequate biopsy Diagnosis should be biopsy-proven before treatment is initiated Need enough tissue to assess cells and architecture – open bx vs core needle bx vs FNA

24 Stage IStage IIStage IIIStage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss

25 Case: M.S. 25 year old woman persistent dry cough fever, NS, weight loss x 3 months left cervical lymphadenopathy (2 cm) left supraclavicular node (2 cm) no splenomegaly

26 M.S. at presentation


28 Case: M.S. differential diagnosis lymphoma – Hodgkin – non-Hodgkin lung cancer other neoplasms: thyroid, germ cell non-neoplastic causes less likely – sarcoid, TB,...

29 What next? Needle aspirate of LN: a few necrotic cells Needle biopsy of LN: admixture of B- and T- lymphocytes. A few atypical cells.

30 Case: M.S. lymph node biopsy


32 Case: M.S. staging investigations CT chest / abdo / pelvis bone marrow gallium scan Blood work: normal

33 Staging Investigations bone marrow normal CT scan: L supraclavicular adenopathy; large mediastinal mass; R hilum; no disease below diaphragm gallium avid

34 What is her diagnosis and stage? nodular sclerosis HD stage IIB with bulky mediastinal mass

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