A male patient presents with fever, cough, and hemoptysis. Bronchoalveolar lavage (BAL) fluid examination shows septate hyphae with acute angle (dichotomous) branching under microscopy. What is the most likely diagnosis?

Correct Answer: A. Aspergillosis

Aspergillosis is definitively identified by the septate hyphae with acute angle (45°) dichotomous branching seen on BAL fluid microscopy. This is the pathognomonic morphological feature that distinguishes Aspergillus from other fungal pathogens. The clinical presentation of fever, cough, and hemoptysis in the context of this specific fungal morphology is classic for pulmonary aspergillosis, which commonly occurs in immunocompromised patients (HIV/AIDS, post-transplant, prolonged corticosteroid use) and can also present as chronic pulmonary aspergillosis in patients with underlying lung disease like tuberculosis or COPD—a frequent scenario in Indian clinical practice. The BAL examination is the gold standard for diagnosis; direct visualization of septate hyphae with acute-angle branching is diagnostic. Aspergillus fumigatus is the most common species causing invasive disease in India. Culture on Sabouraud dextrose agar and histopathology showing angioinvasion with tissue necrosis further confirm the diagnosis. The hemoptysis reflects angioinvasive disease with vascular invasion and infarction, a hallmark of invasive aspergillosis.

Why the other options are wrong

B. Candidiasis — Candida species produce pseudohyphae and true hyphae, but WITHOUT septation (or with sparse septation) and show right-angle (90°) branching, not acute-angle branching. Additionally, candidiasis typically presents with oral thrush, esophagitis, or vaginal infection; pulmonary candidiasis with hemoptysis and BAL findings of septate hyphae is extremely rare. This is a common NBE trap pairing fungal infections without distinguishing morphology. C. Mucormycosis — Mucormycosis (Zygomycetes) shows broad, non-septate hyphae with right-angle (90°) branching—the opposite of Aspergillus morphology. While mucormycosis can cause hemoptysis and BAL findings in immunocompromised patients, the absence of septation and the characteristic right-angle branching pattern rule it out. Mucormycosis is more aggressive and angioinvasive but has distinct morphological features that differentiate it from the described septate acute-angle branching. D. Histoplasmosis — Histoplasma capsulatum is a dimorphic fungus that appears as small (2–4 μm) oval yeast cells within macrophages in tissue/BAL, not as hyphae. It does not produce septate hyphae with acute-angle branching. While histoplasmosis can present with fever, cough, and hemoptysis in disseminated disease, the BAL microscopy finding of septate hyphae with dichotomous branching is incompatible with Histoplasma morphology, making this diagnosis incorrect.

High-Yield Facts

Mnemonics

ASPERGILLUS = Acute-angle Septate Acute-angle (45°) branching + Septate hyphae = ASPERGILLUS. Remember: Aspergillus is 'acute' and 'sharp' (acute angle), while Mucor is 'right' (90° angle) and 'broad' (non-septate). Fungal Branching Angles Aspergillus = 45° (acute) + septate. Mucor = 90° (right) + non-septate. Candida = 90° (right) + pseudohyphae. Use angle to rule out in one glance.

NBE Trap

NBE commonly pairs fungal infections with hemoptysis and BAL findings, expecting students to confuse Aspergillus with Mucormycosis (both angioinvasive) or Candida (both can colonize airways). The discriminating feature—acute-angle septate branching—is the key to avoiding this trap; students who memorize only "fungal hemoptysis" without morphological details will guess incorrectly.

Clinical Pearl

In Indian clinical practice, post-TB patients with residual cavitary lung disease are at high risk for chronic pulmonary aspergillosis (CPA). A patient presenting with hemoptysis months to years after TB treatment completion should raise suspicion for aspergilloma or invasive aspergillosis—BAL with septate acute-angle hyphae confirms the diagnosis and guides antifungal therapy (voriconazole or liposomal amphotericin B).

_Reference: Jawetz, Melnick & Adelberg's Medical Microbiology (Ch. Aspergillus); Robbins Pathologic Basis of Disease (Ch. Infectious Diseases); Harrison's Principles of Internal Medicine (Ch. Fungal Infections)_