Human Brain Bank, NIMHANS, Bangalore 29

Fungal Infections

CASE 11: PNEUMOCYSTIS CARINII PNEUMONIA: (Slide 11A, B, C: H&E, PAS, GMS)

HIstology:Histology of the section from the lung shows distended alveoli and terminal bronchioles which are

filled with a foamy, honey combed, eosinophilic mesh-like material. Within this, small scattered pale basophillic oval bodies are seen. There is little cellular reaction within the alveoli. However, the alveolar septae are thickened and sparsely infiltrated by lymphomononuclear cells.

dIagnosIs: PNEUMOCYSTIS CARINII PNEUMONIA (Lung)

comment: Pneumocystosis is caused by a unicellular organism, Pneumocystis carinii, earlier regarded as

belonging to the Sporozoa family of protozoans. Others however consider the organism to be a fungus, but the controversy remains. The organism is acquired by the air borne route and exists saprophytically in the lungs, the activation and replication occurring with the development of immmunodeficient state. With the advent of AIDS, the incidence of Pneumocystis carinii pneumonia has risen dramatically.

Grossly, early involvement of the lung causes patchy consolidation but later on there is diffuse pinkish consolidation of the entire lung conferring a striking resemblance to lobar pneumonia interspersed with pale zones.

Within the lung, the organisms are found in the alveoli as cysts, each containing sporozoites. The latter have fine surface projections by which they anchor firmly to the alveolar wall which is probably the reason why they are infrequently detected in the sputum. In the alveolar space, the sporozoites liberated from the cyst mature into trophozoites which then have to pass through early, intermediate and late stages to become a mature cyst. They attach to the type I pneumocytes in the lung and appear to directly increase the permeability of the alveolar capillary membrane. This results in intra-alveolar edema and subsequent damage to type I pneumocytes which reduces oxygenation. Extrapulmonary spread (liver, spleen, lymph node, bone marrow, and kidney) is rare and is probably via the hematogenous route.

Definitive diagnosis relies on identifying the organism in tissue biopsies, bronchoalveolar lavage or in induced sputum. Grocott’s methenamine silver identifies the cysts while tissue Gram’s technique stains both the trophozoites and cysts. The organism has not been cultured so far.

Common Infections of the Nervous System

30 National Institute of Mental Health and Neuro Sciences

CASE 11 - PNEUMOCYSTIS CARINII PNEUMONIA

Fig A: Section through the lung from a HIV positive subject. The alveolar spaces are filled with foamy edematous material admixed with inflammatory cells suggesting patchy consolidation.

(H&E Obj X 10)Fig B: Close up view of the foamy material in the alveoli shows globular and black granular material,

colonies of Pneumocytis carinii. (PAS Obj X 20) Fig C: Higher magnification of the globular mass reveals multiple, oval to crescent shaped sporozoites of

Pneumocystis carinii. (GMS Obj X 40)

Human Brain Bank, NIMHANS, Bangalore 31

Fungal Infections

candIdIasIs: (Moniliasis, Candidiasis) (SLIDE NOT PROVIDED)

Common forms - Oral thrush, vaginal candidiasis - Rare in visceral organs - Saprophyte in GIT, genital, cutaneous floraSpread - Submucosal vessels, hematogenous dissemination - Intravenous spread following IV drugsAssociated with: - Long term antibiotics /steroid, IV hyper alimentation, Diabetes, burns, malignancy, neutropenia, GIT surgery, open heart surgery, head trauma, ventriculostomy, AIDSCandida - Yeast form, 2 – 3μm, round to oval elongated pseudohyphaeClinical - Low grade meningitisCSF - Mild rise in protein, Lymphocytosis/Neutrophilia. Organism can be seen phagocytosed in polymorphs and can be culturedPathology: Early hemorrhagic lesions – late abscesses - Vascular thrombosis by budding/pseudohyphae - Abscess with polymorphs; Granulomatous reaction – rare.CNS - Multiple micro abscesses. Common in ACA, MCA territories. Candida meningitis, encephalitis more common than recognized (Autopsy studies)Stains : PAS, Methenamine silverDrugs : Amphotericin B, 5-flurocytosine.Diagnosis : CSF examination may not be helpful. Culturing the organism in blood/CSF is essential to establish diagnosis. Rarely can be transmitted by transfusion, as it can remain dormant within macrophages and polymorphs.

Common Infections of the Nervous System

32 National Institute of Mental Health and Neuro Sciences

HIstoPlasmosIs: (SLIDE NOT PROVIDED)

Organism - CNS involvement is rare (less than 1% of cases of systemic disease) Cutaneous nodules and CNS involvement. Affect children and old people. - Histoplasma capsulatum – biphasic fungus, mycelia saprophyte in soil - Yeast like organisms in infected tissues - budding yeast 2 -5 μm3

Spread - Enter via lung – primary lesion in lung, mouth, stomachSkin - Calcified lesions. - Invades brain – hematogenously – immuno compromised host (insidious onset)Clinical : Splenomegaly, irregular fever, leucopoenia, anaemia, persistent cough, rapid loss of weight, irritability, lethargy, coma.Pathology : Bony lesions, paraspinal mass – rare. Diffuse/basal meningitis with thick exudates, mimics TBM with miliary tubercles along blood vessels, choroid plexus, ependyma Solitary brain granuloma – (Histoplasmoma) rare. Epithelioid cell granulomas with giant cells, with or without necrosis (resembles tuberculous/sarcoid granulomas) Arteritis with granulomas (resemble TBM) Histoplasma organisms in macrophages/epitheloid cellsStains : Methenamine silver demonstrates large number of packed, round organisms in histiocytes.Drugs : No effective treatment Amphotericin B, sulphonamides, Arsenical and Antimony compounds promising