Dr  Sampurna Roy  MD

July  2009

PUB MED: ARTICLES RELATED TO CRYTOCCOCCUS  NEOFORMANS

Image Links: (Dr Tsutsumi)

Myxoid Tumours of Soft Tissue

Cryptococcosis is a systemic mycosis caused by C. neoformans. Organisms are yeast-like fungus with thick gelatinous, mucopolysaccharide capsule.

Epidemiology: Worldwide distribution & 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 CNS, causing meningoencephalitis.

Pathology:

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

Lungs & meninges are usually involved.

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

In immune deficient person:

1. Progressive pulmonary lesions include miliary granulomas, small abscesses & large solid mucoid areas. This is associated with cough, pleurisy, malaise & fever.

Microscope:   Image1 ; Image2

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

From lung, hematogenous dissemination occurs to CNS (brain & 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.

Image Link: Cutaneous Cryptoccosis(Dr Reed)

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

Laboratory diagnosis:

1.Mucoid materials & tissue sections:

i) H & E stain shows lightly basophilic cell wall surrounded by a clear zone.

ii) C. neoformans will stain with PAS or silver methenamine

 iii) Mucicarmine stains the capsule -  shows clear zone containing carminophilic material. Alcian blue also stains the capsule

 iv) A combined PAS-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 & CSF-Latex agglutination test (Antibody fixed to Latex is used to detect fungal antigen).

Grading of soft tissue tumours