The diagnosis of sarcoidosis is one of exclusion. The disease is established when clinical and radiographic findings are supported by a tissue biopsy specimen showing noncaseating granuloma (NCG), although NCG inflammation may be seen in biopsies from fungal infection, foreign body inclusions, and other noninfectious granulomatous diseases such as Langerhans cell histiocytosis (also referred to as eosinophilic granulomatosis or pulmonary histiocytosis X) and Wegen-er's granulomatosis. Tissue biopsy can usually be obtained from the lung, a palpable lymph node, a skin lesion, or the eye (conjunctiva or lacrimal gland). Percutaneous fine-needle aspiration specimen is less frequently obtained from the liver or from retroperitoneal or abdominal nodes by CT guidance. Biopsy from a CNS or cardiac location requires specialty consultation.

Along with clinical symptoms and biopsy, chest x-ray findings are added to support the diagnosis of sarcoidosis. The Scadding staging system classifies chest radiographs into stage 0 (normal), stage 1 (bilateral hilar adenopathy), stage 2 (adenopathy and infiltrates), stage 3 (infiltrates alone), and stage 4 (fibrosis and retractions). A chest film showing bilateral hilar adenopathy in HIV-negative patients with negative skin test and cultures for TB is suggestive, but lymphoma and other causes must be ruled out. HRCT can confirm the size and location of adenopathy as well as granulomas and early pulmonary fibrosis.

Transbronchial biopsy can document pathology and endo-bronchial involvement of the respiratory mucosa. Fine-needle aspiration of endobronchial lymph nodes is being used increasingly. Endobronchial ultrasound to localize more peripheral adenopathy enhances accuracy. Analysis of BAL fluid showing a C4/C8 lymphocyte ratio greater than 3.5 has high specificity for sarcoidosis. Open-lung biopsy is usually not needed but can be diagnostic. Several biomarkers and cytokine profiles that may be helpful in the diagnosis and disease activity in sarcoidosis are under investigation (Barga-gli et al., 2008). The serum angiotensin-converting enzyme (ACE) level has historically been used and is often elevated in initial cases, but it is not fully reliable as the disease progresses. A sarcoidosis assessment instrument has been developed to help clinicians better characterize organ involvement in patients with sarcoidosis (Judson et al., 1999).

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