A 32-year-old woman of African-American descent presents with a 6-week history of progressive dyspnea, bilateral ankle arthralgia, and a tender nodular rash on her shins. Chest X-ray shows bilateral hilar lymphadenopathy with right upper lobe infiltrates. Transbronchial biopsy of a mediastinal lymph node is performed. Histopathology reveals the lesion marked **A** in the diagram — compact collections of epithelioid histiocytes and multinucleated giant cells with a surrounding rim of lymphocytes, but WITHOUT central caseous necrosis. Which of the following diagnoses is MOST strongly supported by this histopathological finding?

Question

Accepted Answer

C. Sarcoidosis. ## Why Sarcoidosis is right

The hallmark pathological feature of sarcoidosis is the **non-caseating (non-necrotizing) granuloma** — a well-defined collection of epithelioid histiocytes and multinucleated giant cells surrounded by a rim of lymphocytes (predominantly CD4+ helper T cells), **WITHOUT central caseous necrosis**. This is precisely what the structure marked **A** depicts. The clinical presentation (young African-American woman, bilateral hilar lymphadenopathy, erythema nodosum, arthralgia, and absence of systemic symptoms suggesting infection) is classic for Löfgren syndrome, the acute, favorable-prognosis presentation of sarcoidosis. The absence of central necrosis is the critical discriminator that excludes tuberculosis and other granulomatous infections. Per the ATS/ERS/WASOG Sarcoidosis Guidelines 2020, the non-caseating granuloma is the hallmark pathology of sarcoidosis, and exclusion of caseating granulomas (TB, fungi) and other mimics is essential for diagnosis.

## Why each distractor is wrong

- **Tuberculosis**: TB granulomas are **caseating granulomas** with central caseous (cheese-like) necrosis, corresponding to structure **B** in the diagram, not **A**. The presence of necrosis is the key distinguishing feature.
- **Fungal infection (histoplasmosis)**: Fungal granulomas are typically **caseating** and may show suppurative features with neutrophilic infiltration. The absence of central necrosis in structure **A** argues against fungal etiology.
- **Berylliosis**: Chronic beryllium disease produces non-caseating granulomas histologically identical to sarcoidosis, but the clinical context (no occupational beryllium exposure history mentioned) and the classic Löfgren presentation (erythema nodosum + arthralgia) point to sarcoidosis. Berylliosis is a diagnosis of exclusion when occupational exposure is documented.

**High-Yield:** Non-caseating granulomas = sarcoidosis (or berylliosis); caseating granulomas = TB or fungi — the presence or absence of central necrosis is the single most important histological discriminator.

[cite: ATS/ERS/WASOG Sarcoidosis Guidelines 2020]

Answer

A. Berylliosis

Answer

B. Fungal infection (histoplasmosis)

Answer

D. Tuberculosis

Explanation

Why Sarcoidosis is right

Why each distractor is wrong

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