Pathology · Lung Pathology (Obstructive, Restrictive, Tumors, Infections)

A 38-year-old immunocompetent woman from Ohio Valley develops progressive dyspnea, cough, bilateral pulmonary infiltrates, and mediastinal lymphadenopathy 3 weeks after excavating soil near a river. Biopsy shows a granulomatous pneumonitis with macrophages containing narrow-based budding yeast 2–4 µm in size within phagosomes. This organism's primary virulence mechanism involves:

  • A Yeast-phase survival and proliferation within macrophage phagolysosomes by blocking phagosome-lysosome fusion
  • B Capsule formation inhibiting phagocyte oxidative burst (Cryptococcus neoformans)
  • C Dimorphic conversion to hyphae within tissues causing destructive angioinvasion
  • D Endospore release (spherulin) causing rupture of host granulomas (Coccidioides)
Correct answer: A. Yeast-phase survival and proliferation within macrophage phagolysosomes by blocking phagosome-lysosome fusion

Explanation

Histoplasma capsulatum (the narrow-based budding, small intracellular yeast endemic in Ohio/Mississippi Valley) survives within macrophage phagolysosomes by blocking phagolysosomal acidification, scavenging iron through surface ferritin and siderophores, and modulating reactive oxygen species responses. Despite being ingested, the yeast resists killing and proliferates intracellularly. Immunity depends on Th1/IFN-gamma mediated macrophage activation to form granulomas. Cryptococcus evades via capsule and melanin; Coccidioides uses spherule-endospore biology; Aspergillus causes angioinvasion. The narrow-based bud and small size distinguish Histoplasma from Blastomyces (broad-based bud, larger).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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