A 38-year-old woman from rural Maharashtra presents with a 6-month history of progressive dyspnea, dry cough, and constitutional symptoms. On examination, she has bilateral hilar lymphadenopathy and erythema nodosum on the shins. Chest X-ray shows bilateral perihilar infiltrates. Serum calcium is elevated at 11.8 mg/dL. A transbronchial lung biopsy is performed. Histopathology reveals non-caseating granulomas with multinucleated giant cells. Acid-fast bacilli stain is negative. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Sarcoidosis ### Key Clinical Features **Key Point:** Sarcoidosis is a multisystem granulomatous disorder of unknown etiology characterized by non-caseating granulomas in multiple organs. This patient presents with the classic triad of sarcoidosis: 1. **Bilateral hilar lymphadenopathy** — hallmark radiological finding 2. **Erythema nodosum** — common cutaneous manifestation, especially in women 3. **Hypercalcemia** — due to extrarenal 1α-hydroxylase activity in granulomas producing calcitriol ### Histopathological Confirmation **High-Yield:** The **non-caseating granuloma** is the pathological hallmark of sarcoidosis. This distinguishes it from tuberculosis, which produces caseating (necrotizing) granulomas. | Feature | Sarcoidosis | Tuberculosis | |---------|-------------|---------------| | Granuloma type | Non-caseating | Caseating (necrotizing) | | AFB stain | Negative | Positive | | Hypercalcemia | Common (10–17%) | Rare | | Erythema nodosum | Frequent | Uncommon | | Löfgren syndrome | Yes (acute form) | No | ### Pathophysiology of Hypercalcemia **Clinical Pearl:** Activated macrophages in sarcoid granulomas express 1α-hydroxylase, converting 25-hydroxyvitamin D to the active form (1,25-dihydroxyvitamin D), leading to increased intestinal calcium absorption and hypercalcemia. ### Diagnostic Criteria **Mnemonic: SARCOID** — **S**ubcutaneous nodules, **A**cute presentation (Löfgren), **R**aised ACE levels, **C**aseating granulomas (absent), **O**rgan involvement (multisystem), **I**ncreased calcium, **D**iagnosis by exclusion. ### Why This Is the Best Answer The combination of non-caseating granulomas on biopsy, negative AFB stain, bilateral hilar lymphadenopathy, erythema nodosum, and hypercalcemia is pathognomonic for sarcoidosis. Tuberculosis is excluded by the absence of caseation and negative AFB stain.