Sarcoid Lymphadenopathy



Sarcoid Lymphadenopathy


Sa A. Wang, MD





Key Facts


Terminology



  • Multisystemic chronic granulomatous disease


Etiology/Pathogenesis



  • Unknown


Clinical Issues



  • Multisystem involvement


  • Therapy may not be required if asymptomatic


  • Prognosis depends on involvement of critical organs


Image Findings



  • Bilateral hilar lymphadenopathy, many with lung nodules, PET active


Microscopic Pathology



  • “Hard” granulomas without acute inflammation or necrosis


  • No specific cause identified


  • Foci of fibrosis can be associated with granulomas


Ancillary Tests



  • Serum angiotensin converting enzyme (ACE)


  • Bronchoalveolar lavage fluid for CD4:CD8 ratio



    • CD4:CD8 > 4:1


  • Impaired pulmonary function


Top Differential Diagnoses



  • Tuberculosis


  • Atypical mycobacteria


  • Fungal lymphadenitis


Diagnostic Checklist



  • Compatible clinical and radiographic manifestations


  • Biopsy shows granulomatous lymphadenitis without identifiable causative agents







The lymph node parenchyma is substantially effaced by multiple granulomas.






Chest radiograph shows bilateral enlarged hilar lymph nodes. Fine linear and reticular opacities are present in the perihilar lung parenchyma.


TERMINOLOGY


Definitions



  • Multisystemic granulomatous disease of unknown etiology


  • Diagnosis of exclusion


ETIOLOGY/PATHOGENESIS


Exact Etiology and Pathogenesis Unknown



  • Occupational and environmental exposure



    • Inorganic particles, insecticides, and moldy environments


  • Probable role of genetics as shown by assessment of major histocompatibility complex



    • Positive association with HLA-A1, -B8, and -DR3


    • Negative association with HLA-B12 and -DR4


  • Possible role of infectious agents



    • Mycobacterium tuberculosis


    • Propionibacterium acnes


  • T-cell abnormalities



    • Increased CD4(+) T cells and CD4(+) and CD25(+) regulatory T- cells


    • Decreased CD1d-restricted natural killer cells


    • Oligoclonal TCR-αβ T-cell repertoire


  • Cytokines: Increased interferon-γ and interleukin-2


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 10-20 per 100,000 population


  • Age



    • All ages; peak 20-39 years


  • Gender



    • Female preponderance


  • Ethnicity



    • Lifetime risk in USA is 2.4% in African-Americans and 0.85% in Caucasians


    • More likely to be chronic and fatal in African-Americans


Presentation



  • Constitutional symptoms are common



    • Fatigue, malaise, fever, night sweats, and weight loss


  • Symptoms related to organ involvement



    • Lungs: Dyspnea and cough


    • Heart: Loss of ventricular function and sudden death


    • Eyes: Keratoconjunctivitis, uveitis, retinal vasculitis


    • Skin: Maculopapular eruptions, nodules, plaque-like lesions


    • Erythema nodosum



      • Painful, red, subcutaneous lesions on anterior surface of legs


      • Associated with sarcoidosis but not specific


    • Musculoskeletal: Arthritis


    • Kidneys and electrolytes: Abnormal calcium metabolism



      • Extrarenal production of calcitriol by activated macrophages


    • Nervous system: Central and peripheral nervous system can be affected



      • Hypothalamic hypopituitarism


      • Diabetes insipidus


      • Lymphocytic meningitis


    • Other organs: Symptoms directly related to organ involvement



      • Endocrine system, reproductive system, gastrointestinal tract


  • Lofgren syndrome: Occurs in subset of patients



    • Erythema nodosum, hilar lymphadenopathy, migratory polyarthralgias, and fever


  • In approximately 50% of cases, patients are asymptomatic when 1st diagnosed



    • Incidental detection by radiographic studies


    • Most children are asymptomatic



Laboratory Tests



  • Anemia, leukopenia, and thrombocytopenia



    • Uncommon but can be observed


  • Erythrocyte sedimentation rate is often increased


  • Hypercalciuria and hypercalcemia


  • Liver involvement results in increased serum alkaline phosphatase levels


  • Serum angiotensin converting enzyme (ACE) increased in 75% patients


  • D-dimer levels can be increased


  • Bronchoalveolar lavage



    • Flow cytometry immunophenotypic analysis



      • Increased lymphocyte percentage


      • Increased CD4:CD8 ratio


      • Decreased CD3(+), CD56(+) cytotoxic T cells


  • Kveim test, intradermal injection


Treatment



  • Indications for treatment



    • Most patients do not require therapy



      • Asymptomatic patients with low stage of disease have high rate of spontaneous remission


    • Indication for treatment of pulmonary sarcoidosis



      • Deteriorating lung function


      • Worsening symptoms


      • Progressive radiographic changes


    • Indications for treatment of extrapulmonary sarcoidosis



      • Ocular, neurologic, myocardial, or renal sarcoidosis or hypercalcemia need treatment to avoid consequences


      • Vision loss, impaired nervous system function, fatal arrhythmias, or renal damage


  • Treatment modalities



    • Oral or inhaled glucocorticoids


    • Other treatment modalities are largely experimental



      • Immunosuppressive and cytotoxic drugs: Methotrexate, cyclophosphamide, cyclosporin


      • TNF-α blockers: Infliximab, etanercept


      • Nonsteroidal anti-inflammatory agents


    • Heart and lung transplantation


Prognosis



  • Varies from patient to patient and depends on



    • Symptomatic vs. asymptomatic


    • Organ involvement and severity


    • Proper treatment received


IMAGE FINDINGS


Radiographic Findings

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Sarcoid Lymphadenopathy

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