Approach to Lymphadenopathy

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Approach to Lymphadenopathy

• Ashley Rosko, MD

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Case

• 41 yo male school teacher presents to your office
  with right sided cervical lymphadenopathy. His
  past medical history is significant for
  hypertension and dyslipidemia. His medications
  include hctz and simvastatin. NKDA. 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?
• Location and duration typical for viral etiology.
  Have your patient follow up for annual physical
  next year.
• Proceed to fine needle aspiration.
• Check a CXR and cbc.
• Have patient follow up in 3-4 weeks.

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Learning Objectives

• Provide an approach to the patient with
  peripheral lymphadenopathy
• Be able to differentiate between benign and
  serious illness
• Knowledgeable of nodal distribution and anatomic
  drainage
• Present a substantial differential diagnosis
• Indications for nodal biopsy

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Definition Lymphadenopathy

• Lymph nodes that are abnormal in size,
  consistency or number
• Generalized
• Localized

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Lymphatic System

• Network that filters antigens from the
  interstitial fluid
• Primary site of immune response from tissue
  antigens
• Lymphatic drainage in all organs of the body
  except brain, eyes, marrow and cartilage
• Flaccid thin walled channels?progressive caliber
• 600 lymph nodes in body
• Slow flow, low pressure system returns
  interstitial fluid to the blood system

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Secondary lymphoid tissue
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Lymph nodes

• Capsular shell
• Fibroblasts and reticulin fibers
• Macrophages
• Dendritic cells
• T cells
• B cells

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Peripheral lymphadenopathy

• Most cases benign, self limited illness
• Primary or secondary manifestation of 100
  illnesses
• The CHALLENGE is to decide if it is
  representative of a serious illness

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Parameters to help distinguish between benign and
serious illness

• Age
• Character
• Location

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Malignancy much more common in patients greater
50 yrs of age

• Not exactly

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Epidemiology

• Lee et al 1980 Referral centers 925 underwent a
  lymph node biopsy.
• Age lt30 79 benign 15 lymphomatous 6 carcinomas
• Age gt50 40 benign 16 lymphomatous 44
  carcinomas
• Age 30-50 indeterminate values

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Dutch study Fijten 1988

• 0.6 annual incidence of generalized
  lymphadenopathy
• 2,556 present with unexplained lymphadenopathy
• 10 referred to subspecialist?3.2 required bx
  and of that 1.1 had a malignancy
• 40 yrs 4 risk of cancer vs. 0.4 risk in pts
  younger than 40

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Lymph node character

• Size
• Site
• Consistency
• Pain with palpation

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Size

• Greater than one centimeter generally considered
  abnormal
• Exception inguinal area, lymph nodes commonly
  palpated (gt1.5 cm)
• Size does not indicate a specific disease process
• Obese and thin population

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Pain..

• Indication of rapid increase in size stretch of
  capsular shell
• NOT useful in determining benign vs malignant
  state
• Inflammation, suppuration, hemorrhage

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Consistency

• Stone hard typical of cancer usually metastatic
• Firm rubbery can suggest lymphoma
• Soft infection or inflammation
• Shotty buckshot under skin
• Suppurated nodes fluctuant
• Detect node from stroma
• Matting

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Location, location, location
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• Post cervical scalp, neck skin of arms thorax
  cervical and axillary nodes (lymphoma, head/neck
  ca)

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Supraclavicular Nodes

• Drain the mediastinum and abdomen
• Breast, GI, Lung Malignancies
• Hodgkins/NHL
• Chronic Fungal and mycobacterial

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Axillary Nodes

• Drain arm, breast, thorax and neck
• Hodgkin, NHL
• Melanoma (drains back of arm)
• Staph/strep
• Cat scratch
• Silicone prosthesis

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Inguinal lymphadenopathy

• Drain the lower extremity, genitalia, buttocks,
  abdominal wall
• Normal
• People who walk barefoot
• Squamous cell carcinoma of penis or vulva
• Venereal disease

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Epitrochlear

• Lymphoma/CLL
• Mono
• Historically associated with syphilis, rubella,
  leprosy
• Studies to indicate an association with early HIV
  disease in sub-Saharan Africa, areas with high
  prevalence of disease

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Hilar, mediastinal, abdominal

• gt1 cm considered pathological
• Pneumonia/inflammatory process can cause
  unilateral hilar disease
• Lymphadenopathy limited to abdomen likely
  malignant

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Highest rate of malignancy

• Right Supraclavicular
• Mediastinum
• Lungs
• Upper 2/3 esophagus

• Left Supraclavicular
• Virchow node
• Testes/ovaries
• Kidneys
• Pancreas
• Prostate
• Stomach
• Lower Esophagus

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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

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Presentation of lymphadenopathy

• Unexplained lymphadenopathy
• 3/4 presents with localized
• 1/4 present with generalized

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Algorithm to evaluate Lymphadenopathy

• Attention to history and physical exam
• Confirmatory testing
• Indication for biopsy

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History

• Localizing symptoms or signs to suggest a
  specific site
• Constitutional symptoms B symptoms
• (fever, night sweats, gt10body wt gt6months)
• Epidemiologic clues occupation, travel, high
  risk behavior
• Medications

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Creating a Differential

• CHICAGO

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ChicagoCancer

• Heme malignancies Hodgkins, NHL, acute and
  chronic leukemias, waldenstroms, multiple myeloma
  (plastmocytomas)
• Metastatic solid tumor breast, lung, renal, cell
  ovarian

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cHicagoHypersensitivity syndromes

• Serum sickness
• Serum sickness like illness

• Drugs
• Silicone
• Vaccination
• Graft vs Host

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Specific Medications

• Cephalosporins
• Atenolol
• Captopril

• Dilantin
• Sulfonamides
• Carbamazepine
• Primodine
• Gold
• Allupurinol

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ChicagoInfections

• Viral
• Bacterial
• Protozoan
• Mycotic
• Rickettsial (typhus)
• Helminthic (filariasis)

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VIRAL

• EBVmono spot test
• CMV.cmv titers, immunsuppresed, transplant
  recipient, recent blood transfusion
• HIVIV drug use, high risk sexual behavior
• Hepatitis.IV drug use
• Herpes Zoster.superficial cutaneous nodules

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Bacterial

• Staph/strep cutaneous source, lymphadenitis
• Cat scratch bartonella hensalae, two weeks after
  inoculation
• Mycobacterium TB and non-tb, host
  characteristics (HIV, foreign born, low
  socioeconomic status, homeless)

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Spirochete

• Syphilis Treponema pallidum Primary localized
  inguinal lymph nodes and secondary,
  non-treponemal, treponemal
• Lyme disease

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Protozoan

• Toxoplasmosis ELISA assay, intracellular
  protozoan toxoplasmosis gondii.bilateral,
  symmetrical, non-tender cervical adenopathy
• consider undercooked meat, reactivation in
  immuncompromised host

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chicagoConnective Tissue Disease

• Rheumatoid Arthritis
• SLE
• Dermatomyositis
• Mixed connective tissue disease
• Sjogren

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chicagoAtypical lymphoproliferative disorders

• Castlemans disease
• Wegeners
• Angioimmuonplastic lymphadenopathy with
  dysproteinemia

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chicaGoGranulomatous

• Histoplasmosis
• Mycobacterial infections
• Cryptococcus
• Silicosis coal, foundry, ceramics, glass
• Berylliosis metal, alloys
• Cat Scratch

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My cat Pigeon

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OTHER.chicago

• RARE
• Kikuchi
• Rosia Dorfman
• Kawasaki
• Transformation of germinal centers

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• Wait 3-4 weeks and reexamine
• No indication for empiric antibiotics or steroids
• Glucorticoids can be harmful and delay diagnosis
  can obscure diagnosis due to lympholytic affect

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Unexplained Generalized lymphadenopathy

• Always requires an evaluation
• Start with CXR and CBC
• Review Medications
• PPD, RPR, Hepatitis screen, ANA, HIV
• No yield on above test Biopsy most abnormal node

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BIOPSY

• Can be done by bedside, open surgery,
  mediastinocopy or by needle aspiration
• FNA not recommended cannot distinguish between
  lymphomas (nodal architecture needs to be intact)
• FNA reserved for established diagnosis and to
  demonstrate recurrence

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Diagnostic Yield

• Ideally axillary and inguinal nodes are avoided
  as often demonstrate reactive hyperplasia
• Preferred supraclavicular, cervical, axillary,
  epitrochlear, inguinal
• Complications include vascular and nerve injury

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Case

• 41 yo male school teacher presents to your office
  with right sided cervical lymphadenopathy. His
  past medical history is significant for
  hypertension and dyslipidemia. His medications
  include hctz and simvastatin. He has no known
  drug allergies. He believes he noticed the lump
  in his neck last week. He has not experienced any
  fevers, chills or weight loss. He denies a 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?
• Location and duration typical for viral etiology.
  Have your patient follow up for annual physical
  next year.
• Proceed to fine needle aspiration
• Check a CXR and cbc
• Have patient follow up in 3-4 weeks.

54
References

• Uptodate Fletcher 2008 Evaluation of Peripheral
  Lymphadenopathy
• Aster 2008 Castlemans
  Disease
• Glazer. G. Normal Mediastinal Nodes AJR
  144261-265 Feb 1985
• Ghirardelli, M. Diagnositc approach to lymph node
  enlargement. Haematologica 1999 84242-247
• Ferrer, R. Lymphadenopathy Differential
  Diagnosis and Evaluation 1998
• Haberman, T Lymphadenopathy Mayo Clinic Proc.
  2000 75723-732
• Lee,Y. Lymph Node Biopsy for Diagnosis A
  statistical study. Journal of Surgical Oncology
  1453-60 1980
• Skolnik, P Case 5-1999 37 yo male with fever and
  lymphadenopathy Volume 340 545-554
• Lichtman et al. (2006) Williams Hematology New
  York. McGraw-Hill
• Parslow et al. (2001) Medical Immunology new
  York. McGraw-Hill
• Malin, Ternouth (1994) Epitrochlear lymph nodes
  as a marker of HIV disease in Subsaharan Africa
  BMJ 1994 309 1550-1551
• Bazemore and Smucker Lymphadenopathy and
  Malignancy AAFP 2002

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Questions?