Cutaneous Cryptococcus Workup
- Author: David G Moskowitz, MD; Chief Editor: Dirk M Elston, MD more...
The latex agglutination test is a sensitive and specific method for testing serum, cerebrospinal fluid, and urine. Lesional skin scrapings have also reportedly been used for testing. The test may yield false-positive results in the presence of rheumatoid factor. Decreasing titers indicate regression of the disease. Patients who do not have AIDS but have single, localized skin lesions are often antigen negative.
Enzyme-linked immunosorbent assay is sensitive and specific for testing blood or cerebrospinal fluid. It is capable of detecting the presence of antigen earlier and at a lower concentration than other tests.
Direct preparations are performed on a drop of serum or exudate placed on a slide. The cells seen are large (5-15 µm), budding cells with capsules. Stain with periodic acid-Schiff, mucicarmine, or India ink (for capsule).
The diagnosis can be confirmed by tissue culture of a skin biopsy specimen. The colony appears moist, shiny, and white on Sabouraud dextrose agar, but it may darken with aging. Results are urease positive. It can pigment on Guizotia seed medium.
Chest radiography may demonstrate local or diffuse infiltrates, nodules, hilar lymphadenopathy, cavitation, or pleural effusions. The diffuse interstitial infiltrates may be difficult to distinguish from Pneumocystis carinii pneumonia.
Head CT scanning shows normal results in approximately half the patients with CNS infection. No signs are pathognomonic for Cryptococcus infection, but studies may show hydrocephalus, gyral enhancement, and single or multiple nodules that may or may not be enhancing.
MRI is thought to be a more sensitive study than CT scanning.
Because cutaneous disease should be presumed to be disseminated, an appropriate workup for systemic involvement is essential. This includes a thorough history and physical examination, chest radiography or CT scanning to evaluate pulmonary involvement, lumbar puncture and imaging of the CNS, and other studies as indicated.
Lumbar puncture may reveal an increased opening pressure (associated with a poor prognosis), low glucose level, increased protein level, and an elevated white blood cell count, with lymphocytes predominating.
Typically, the organism can be visualized on histologic sections as an oval, thick-walled spherule surrounded by a polysaccharide capsule. Special staining with methylene blue, Alcian blue, or mucicarmine may be performed to demonstrate the capsule.
Two patterns of involvement can be seen. The first is the gelatinous type, which shows numerous budding yeasts in a foamy stroma with little or no inflammation. The second is the granulomatous type, which shows fewer, smaller organisms and a granulomatous inflammatory infiltrate.
Sing and Ramdial described 5 solitary cryptococcal inflammatory pseudotumors in 2 men and 3 women ranging in age from 19-43 years. All were HIV positive and had been treated for disseminated cutaneous and/or meningeal cryptococcosis with antifungal therapy 6-12 months earlier. The cryptococcal inflammatory pseudotumors were located in the soft tissues of the anterior chest wall, thigh, and arm. They showed the following:
A storiform arrangement of plump spindle cells
Spindle and polygonal cells arranged in a haphazard manner
Background lymphocytes, plasma cells, and fibrosis
Scattered giant cells and focal necrosis
C neoformans yeasts on high-power examination, which were within and between vacuolated spindle and polygonal cells after routine and special staining
Cryptococcal inflammatory pseudotumors are part of a heterogeneous spectrum of reactive, infective, and neoplastic entities characterized by a clinical mass composed of a histologic proliferation of spindle cells in a background of inflammatory cells and collagen fibers.
An interesting report from the Cleveland Clinic in 2013 noted disease mimicking cryptococcus manifesting mostly neutrophil dermal infiltrate mixed with abundant acellular bodies encircled by capsulelike vacuolated spaces, which looked like cryptococcus histologically in 2 patients with hematological malignancies and 1 with immune dysregulation. It seemed to the observers that the diagnosis, even using electron microscopy, was that of autolysing human cells. All the patients expired despite immunosuppressive treatment.
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