This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

Lymphadenopathy A Systematic Approach Abdulaziz F. Al Mana Medical Student

Case 35 yo male taxi driver presents to your office with right sided cervical lymphadenopathy. His past medical history is unremarkable. His not taking any medications. He noticed the lump in his neck last week. He has not experienced any fevers, chills or weight loss. He denies any sore throat, ear pain or dental problems. His vital signs are stable. On physical exam he has a 2cm anterior cervical lymph node which is firm, non-tender and mobile. His HEENT exam is unremarkable. No skin lesions are evident. No other lymphadenopathy is found. How should you proceed with this patient? A. Location and duration typical for viral etiology. Have your patient follow up for annual physical next year. B. Proceed to fine needle aspiration. C. Check a CXR and cbc. D. Have patient follow up in 3-4 weeks.

Definition: Lymphadenopathy One or more lymph nodes that are abnormal in size, consistency, or number. Benign/self limiting or serious underlyng disease. Generalized Localized

Evaluation: History & Examination Key Points: AGE LOCATION NUMBER (local or generalized “ 2 or more”) +/- SYSTEMIC SIGNS/SYMPTOMS +/- SPLENOMEGALY SIZE, CONSISTENCY, TENDERNESS, FIXATION and OVERLYING SKIN DRUG Hx Hx of EXPOSURES

AGE Very IMP Helps predict the likelihood of a benign vs. malignant process Patients < 30 yrs (benign 80% of the time) Patients > 50 yrs (malignant 60 % of the time)

LOCATION 3 major regions: H&N(including oral cavity), Axilla and Inguinal regions. Other: Epitrochlear, Popliteal, Para-aortic and supraclavicular regions.

ASSOCIATED SIGNS/SYMPTOMS Constitutional: Fever, chills, night sweats and weight loss (>10%body wt >6month) “ B symptoms” Anemic symptoms (weakness, tiredness, breathlessness,..) Bone pain Bleeding tendency(epistaxis, bruising,..) Local disease (ear, throat, skin, teeth,..) +/- Splenomegaly and/or hepatomegaly (IMP) Rash, arthralgia, arthritis, mucous membrane lesions

CHARACTER Size : Large > 1 cm (abnormal) Exceptions: * inguinal region (> 1.5 cm) * Obese and thin indivi duals Consistancy: Stone hard: typical of cancer usually metastatic. Firm rubbery: can suggest lymphoma Soft: infection or inflammation Fixation: fixed, non mobile nodes are more likely to be infiltrated by carcinoma than mobile nodes. Matting: A group of nodes that feels connected and seems to move as a unit. Nodes that are matted can be either benign (e.g., tuberculosis, sarcoidosis or lymphogranuloma venereum) or malignant (e.g., metastatic carcinoma or lymphomas).

cont. CHARACTER Tenderness: Indication of rapid increase in size: stretch of capsular shell NOT useful in determining benign vs malignant state Inflammation, suppuration, hemorrhage Overlying skin: Inflamed skin: warm, erythematous suggests infection Tethered skin: suggests carcinoma Other: sinus, ulceration,..

History of Exposures Cats: cat scratch disease, Toxoplasmosis Unpasteurized milk: Brucellosis Uncooked meat: Toxoplasmosis Ticks: Lyme disease Blood transfusion/ transplants: CMV, HIV High risk sexual behavior: STD IVDU: HIV, Endocarditis, HBV Travel Hx : Many possibilities

Drug History Specific medications: eg: Antibiotics: Sulphonamides, Penicillins, Cephalosporins Anticonvulsants: Phenytoin, Carbamazepine Antihypertensive: Captopril, Hydralazine, methyldopa Allopurinol Gold Sulphas

Evaluation: Differential diagnosis A) By LOCATION:

Famous nodes Virchows Left supraclavicular (abdominal or thoracic ca) Sister Joseph Para-umbilical (gastric adenoca) Delphian node Prelaryngeal (thyroid or laryngeal ca) Node of Cloquet (Rosenmuller node) Deep inguinal near femoral canal

B) By Cause: “CHICAGO” Cancer Hypersensitivity Infectons Connective tissue disease Atypical lymphoproleferative disorders Granulomatous Other

CANCER Hematologic: lymphoma (Hodgkins, NHL), leukemia, waldenstroms, multiple myeloma (plastmocytomas). Solid tumors(metastatic): H&N cancers  Cervical Thoracic and abdominal ca  Supraclavicular Breast ca, melanoma  Axillary Squamous cell ca, melanoma  Inguinal

Hypersensitivity syndromes Also known as serum sickness syndromes Causes: Drug reaction Vaccinations Exposure to animal serum Graft vs host

Infection Viral: EBV, CMV, HIV, HSV, Herpes zoster, HBV Bacterial: Staph/strep(cellulitis, Pharyngitis, abcess, lymphadenitis), salmonellosis, cat scratch( B.henslae 2 w after inoculation), mycobacterial (TB or non TB), Spirochete (Syphilis, Lyme disease) Fungal: Histo, Cryptococossis Parasitic: Toxoplasmosis,leshmaniasis Filariasis

Connective Tissue Disease Rheumatoid Arthritis SLE Dermatomyositis Mixed connective tissue disease Sjogren

Atypical lymphoproliferative disorders Castleman’s disease Angioimmunoblastic lymphadenopathy with dysproteinemia

Granulomatous Histoplasmosis Mycobacterial infections Cryptococcus Sarcoidosis Silicosis: coal, foundry, ceramics, glass Berylliosis: metal, alloys Cat Scratch

Other RARE Kikuchi Rosia Dorfman Kawasaki Transformation of germinal cente

Evaluation: Investigations Directed toward the most likely cause. Includes: CBC ESR Renal and liver function LDH Serology and confirmatory tests CXR CT FNA Biopsy ( BEST but not always )

When to biopsy? Lymphadenopathy from an infectous etiology can be diagnosed without biopsy. Biopsy is indicated when malignancy is suspected. FNA for cytology is usually sufficient to evaluate for metastatic malignancies ( NOT the case if lymphoma is suspected  Excisional biopsy)

cont. When to biopsy? In case of localized lymphadenopathy (Benign clinical history, unremarkable physical examination and no constitutional symptoms): reexamine in three to four weeks to see if the lymph nodes have regressed or disappeared. In case of unexplained localized lymphadenopathy & constitutional symptoms or signs, if persists for three to four weeks or high risk for malignancy or serious illness should undergo a biopsy. Note: Patients with probable viral illness biopsy should be avoided because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a false-positive diagnosis of malignancy.

Unexplained Generalized lymphadenopathy Always requires an evaluation Start with CXR and CBC Review Medications PPD, RPR, Hepatitis screen, ANA, HIV No yield on above tests: Biopsy most abnormal node

Conclusion Key factors to consider when evaluating a patient with lymphadenopathy includes: Age, location, and associated symptoms. Most cases are due to infections, malignancy, and immunologic disorders. Lymphadenopathy is most likely due to a benign self-limited infectious process in younger individuals or may be a sign of a serious underlying disease such a malignancy in older individuals.

Case 35 yo male taxi driver presents to your office with right sided cervical lymphadenopathy. His past medical history is unremarkable. His not taking any medications. He noticed the lump in his neck last week. He has not experienced any fevers, chills or weight loss. He denies any sore throat, ear pain or dental problems. His vital signs are stable. On physical exam he has a 2cm anterior cervical lymph node which is firm, non-tender and mobile. His HEENT exam is unremarkable. No skin lesions are evident. No other lymphadenopathy is found. How should you proceed with this patient? A. Location and duration typical for viral etiology. Have your patient follow up for annual physical next year. B. Proceed to fine needle aspiration. C. Check a CXR and cbc. D. Have patient follow up in 3-4 weeks.