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Human Brain Bank, NIMHANS, Bangalore 23
Fungal Infections
CASE 9: ZYGOMYCOSIS (MUCORMYCOSIS): Slide 9A, B: H&E, GMS)
HIstology:The section though the cerebral cortex shows extreme degree of cerebral edema with spongy
parenchyma and breakdown. The subarachnoid space is widened, with dense acute and chronic inflammatory infiltrate, entrapping the vessels. Pools of fibrin are observed enclosing both necrosed and thrombosed arteries and veins. These vessels have dense polymorph and lymphocytic inflammatory infiltrate around, invading the vessel wall and extending into the cerebral cortex. In the white matter many venous channels are seen with fibrinoid necrosis of the wall, thrombosis of the lumen and dense inflammatory infiltrate around. In the cortex, many areas of fresh hemorrhage are found, following transudation from the damaged vessels. In H&E stain, fungal bodies are not distinct. But GMS stain has highlighted many broad, non septate fungi of Rhizopus species. They are seen invading the arteries, penetrating the medial muscle coat. The ones in the white matter are encrusted with a layer of fibrin and polymorphs.
The histological features are characteristic of Rhizopus (Mucor mycosis) species fungal invasion of cerebral cortex with angio invasion, thrombosis of vessels, parenchymal hemorrhage and severe cerebral edema.
dIagnosIs: ZYGOMYCOSIS
(Courtesy: Prof.C.Sundaram, Professor of Pathology, Nizam Institute of Medical Sciences, Hyderabad)
comment: mucor mycosIs (ZygomycosIs): - Fungi genera – Rhizopus, Mucor, Absidia - Opportunistic fungus (can involve previously healthy individual)Source - Soil, manure, decaying vegetable material, air borne.Spread - Hematogenous spread or direct invasion Rhino-sino-orbital, pulmonary, GIT, skin Infection of skin, rhino orbital, mucosa of nose / nasopharynx , arterial spread with thrombosis, brain invasion Sinonasal infection , bone invasion, venous spread , basifrontal cerebral infection
Haematogenous sPread assocIated wItH
- Diabetic ketoacidosis, IV Drug use, Diarrhea/Dehydration in children, old age, Organ transplantation, Immunosuppressive therapy, Long term steroid/antibiotic/cytotoxic therapy & AIDS
clInIcal Features
Rhino orbital form - unilateral opthalmoplegia, proptosis, oedema of eye lids, corneal ulcers and blindness, meningeal signsCerebral invasion - seizures, aphasia, hemiplegia, lethargy, coma – acute fulminant course – death in 4-6 days
Common Infections of the Nervous System
24 National Institute of Mental Health and Neuro Sciences
Diagnosis : Predisposing factors arouse suspicion Biopsy of nasal mass / antral scraping/hemorrhagic scarPathology : Necrotic, hemorrhagic lesion – Base of frontal lobes, basal ganglia and thalamus.Fungi : Angiotropic Broad, aseptate, obtuse angle branching fungi in the walls of arteries (occasionally large veins) Acute inflammatory response in tissue – resembling acute abscess, fresh infarct. Granulomatous reaction – rare.Stains : PAS, Methenamine silverDrugs : Amphotericin B, Trimethoprim, sulphamethoxazole.
The causative fungi belong to the order Mucorales in the class Zygomycetes. The family Mucormyceae in the order Mucorales includes the genera Absidia, Mucor, Rhizopus, and Rhizomucor. The Rhizopus is the most commonly isolated organism causing the human disease Mucormycosis. The fungi are broad, 10-20µm in diameter, with non-septate hyphae that branch at right angles. They are ubiquitous saprophytes and cause disease in debilitated, diabetic with keto acidosis or immunocompromised patients. Germination of the inhaled spores is a requirement for infection and this occurs when the alveolar macrophages are unable to ingest the spores and prevent germination. This may explain the development of Mucormycosis in diabetic ketoacidosis and following steroid therapy. The importance of neutrophils in the prevention of this infection may explain the relative infrequency of this infection in patients with AIDS.
The most common types of Mucormycosis are:
1) Pulmonary 2) Rhino-orbito-cerebral 3) Cutaneous 4) Gastrointestinal 5) CNS
In the rhino-orbito-cerebral Mucormycosis, the primary focus is often from an infection of the skin of the face, nasal/paranasal mucosa or hard palate. The fungi have a special affinity for blood vessels and grow through the blood vessel walls producing thrombosis, hemorrhage and ischemic necrosis. Apart from hemorrhagic infarcts, other manifestations include abscesses, meningitis, mycotic aneurysms and cavernous sinus thrombosis.
Microscopically there is severe vasculitis involving arteries and veins, cerebritis, hemorrhage, infarction and tissue necrosis. Fungal hyphae invading the vessel wall and entering vascular lumen are seen with thrombosis.
Human Brain Bank, NIMHANS, Bangalore 25
Fungal Infections
CASE 9 - ZYGOMYCOSIS – BRAIN
Fig A: Broad, non-septate hyphal forms of Zygomycosis in the midst of acute inflammatory exudates in edematous cerebral cortex. (H&E Obj X 10)
Fig B: Higher magnification shows Zygomycotic, non-septate, branching hyphae forms in the midst of inflammatory exudates. (H&E Obj X 20)
Fig C: Zygomycosis hyphae forms stained with Silver Methenanine, arranged along the border of central necrotic zone. (GMS Obj X 10)
Fig D: Invasion of the vessel wall by the hyphae of Zygomycosis. (GMS Obj X 20)Fig E: Higher magnification shows broad, aseptate, branching hyphae of Zygomycosis in the inflammatory
exudates. (GMS Obj X 40)