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Pathology of Cryptococcosis

 Dr Sampurna Roy MD





Cryptococcosis is a systemic mycosis caused by Cryptococcus neoformans. 

Organisms are yeast-like fungus with thick gelatinous, mucopolysaccharide capsule.

Epidemiology: Worldwide distribution and is usually present in soil, with main source in pigeon droppings.

Mode of infection:  Infection occurs by inhalation with initial lesion in lungs, followed by hematogenous spread, mainly to Central Nervous System, causing meningoencephalitis.


Lesions are most commonly seen in immunocompromised persons. Example: AIDS, leukemia, lymphoma, Hodgkins’ disease.

Lungs and meninges are usually involved.

Lesions differ in a person with normal immunity and in one with immune deficiency.

In immune deficient person following features are noted:

1. Progressive pulmonary lesions include miliary granulomas, small abscesses and large solid mucoid areas.

This is associated with cough, pleurisy, malaise and fever.

Free organisms are seen in mucopurulent exudate with little or no inflammatory infiltrate.

From lung, hematogenous dissemination occurs to Central Nervous System (brain and meninges), causing fulminating meningoencephalitis and death within a few days.

Some cases may show subacute or chronic course producing small cyst like spaces in the gray matter, so called "soap bubble" lesion. Cysts contain numerous fungi.

Disseminated lesions may be seen in skin, mucus membrane, prostate, bone, liver & other deep organs.

2. Skin lesions are papules or small abscesses.

3. Mucocutaneous lesions are usually granulomatous. Early lesions are mucinous & older lesions are granulomatous.


Microscopic features:   

Tuberculoid granuloma in the dermis and upper subcutis ; Organisms (5-15 micrometer in diameter); Dense chronic inflammatory infiltrate with multinucleated giant cells and numerous organisms with refractile walls ; occasionally neutrophils are present ; Overlying epidermis may show acanthosis ; Ulceration is present in some cases.

Capsule deficient (dry variant) elicit granulomatous reaction with organisms, mostly in giant cells. The lesion may mimic Histoplasma capsulatum.

In healthy persons with normal immunity-circumscribed nodules are seen in lung, with necrotic center containing organisms.

Nodules are surrounded by fibrous granulomatous reaction, but do not calcify.

In Hematoxylin and eosin stain lesions mimic H. capsulatum and Coccidioides immites but their capsule is not carminophilic and final confirmation is made by immunofluorescence stain.

Laboratory diagnosis:

1. Mucoid materials & tissue sections:

(i) Hematoxylin and eosin  stain shows lightly basophilic cell wall surrounded by a clear zone.


(ii) Cryptococcus neoformans will stain with Periodic acid–Schiff or silver methenamine.

(iii) Mucicarmine stains the capsule -  shows clear zone containing carminophilic material.

Alcian blue also stains the capsule.

(iv) A combined Periodic acid–Schiff - alcian blue stain contrasts the cell wall and capsule.

(v) Capsule-deficient variety is demonstrated by:

       (a) Immunofluorescent antibody.

       (b) Fontana-Masson silver staining

2. CSF-preparation-by India ink stain

3. Serum and CSF-Latex agglutination test (Antibody fixed to Latex is used to detect fungal antigen).




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)






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