Invasive fungal infections are life-threatening conditions caused by fungi that invade deep tissues, often in immunocompromised patients. Understanding their histopathology, clinical features, and treatment is essential for medical students, pathologists, and clinicians.

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Causes & Risk Factors:

• Immunosuppression – chemotherapy, corticosteroids, or transplant immunosuppressants.
• Diabetes mellitus (especially ketoacidosis) – predisposes to mucormycosis.
• Prolonged ICU stay – invasive devices, broad-spectrum antibiotics, and catheters increase risk of Candida infections.
• Environmental exposure – inhalation of spores from soil, bird droppings, and decaying matter (Histoplasma, Coccidioides).
• Disrupted normal flora – allows Candida overgrowth.

Symptoms:

• Pulmonary involvement – fever, persistent cough, hemoptysis, pleuritic chest pain.
• CNS involvement – headache, confusion, seizures (notable in cryptococcosis).
• Sinonasal mucormycosis – nasal obstruction, facial pain, black necrotic eschar.
• Disseminated candidiasis – persistent fever, skin lesions, multi-organ dysfunction.

Diagnosis:

Narrow-based budding:

• Very small organisms (2–6 µm).
• Appear as round yeast with narrow stalk-like budding.
• In Cryptococcus, a clear halo (capsule) is seen around the yeast in H&E stains.
• In Histoplasma – 2–6 μm, narrow-based budding, intracellular (within macrophages), halo appearance.
• Stains: H&E (shows halo), Silver stain (better contrast).

Broad-Based Budding Yeasts:

• Larger organisms (8–15 µm).
• Yeast cells are uniform in size.
• Daughter cell forms with a broad base of attachment (compared to narrow budding in cryptococcus).
• Thick, double-walled yeast.

Spherules with Endospores:

Coccidioides

• Large spherules (10–200 µm) containing smaller endospores (2–5 µm).
• No true budding.
• Seen in tissue biopsies of coccidioidomycosis.
• Important differentiator from budding yeasts.

Multiple Budding Yeast:

Paracoccidioides

• Variable size (4–60 µm).
• Characteristic “pilot wheel” or “mariner’s wheel” appearance.
• Multiple buds arise simultaneously from the mother yeast cell.
• Dimorphic fungus: mold at room temp, yeast at body temp.

Fungi with Hyphae and Pseudohyphae:

Candida

• Yeast + pseudohyphae seen.
• Pseudohyphae appear as elongated budding cells, not true hyphae
• Important in mucosal infections.

Aspergillus

• Thin septate hyphae with acute angle branching (45°).
• Fruiting bodies occasionally seen.
• Common cause of invasive pulmonary infections.

Rhizopus

• Broad, non-septate hyphae with right angle branching (90°).
• Seen in diabetic ketoacidosis and immunosuppressed patients.

Treatment:

• Candida – Echinocandins (first line), fluconazole if susceptible.
• Aspergillus – Voriconazole (drug of choice).
• Mucormycosis – Liposomal Amphotericin B + surgical debridement.
• Cryptococcus (meningitis) – Amphotericin B + Flucytosine, followed by fluconazole.
• Histoplasmosis / Coccidioidomycosis / Paracoccidioidomycosis – Itraconazole for mild-to-moderate disease, Amphotericin B for severe cases.
• Supportive measures: control diabetes, reduce immunosuppressants if possible, and remove infected catheters.

Prevention:

• High-risk patients may receive antifungal prophylaxis (e.g., posaconazole in transplant patients).
• Hospital infection control – HEPA filters, minimizing invasive devices.
• Lifestyle precautions – immunocompromised patients should avoid construction sites, soil, and bird droppings.
• Glycemic control – reduces mucormycosis risk.
• Judicious antibiotic use – prevents fungal overgrowth.

Mnemonics:

Fungus	Morphology	Histology Feature
Cryptococcus	Narrow budding	Halo, capsule
Blastomyces	Broad budding	Uniform yeast
Coccidioides	Spherules	Endospores inside
Paracoccidioides	Multiple budding	Pilot wheel
Aspergillus	Hyphae	45° branching
Rhizopus	Hyphae	90° branching

• ABC-P for budding fungi: Aspergillus (acute angle), Blastomyces (broad), Cryptococcus (capsule, narrow), Paracoccidioides (pilot wheel).

Multiple choice questions (MCQs):

Time to test what you have learnt

Identify this fungus?

Check answer

CORRECT ANSWER IS MUCOR

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Conclusion:

Invasive fungal infections remain a critical challenge in pathology, requiring accurate histopathological recognition for timely diagnosis. Early identification and treatment not only improve patient outcomes but also strengthen exam preparation for aspiring pathologists.

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