S11C4-Fungus Diseases

Pheohyphomycotic Abscess

Fungus infections of the skin may be primary and localized, or they may be evidence of disseminated disease. The manifestations depend, in part, on the pathogenicity of the organisms and, in part, on the state of the host immune response. The category of primary cutaneous fungus infections includes examples that are superficial (confined by an epithelial surface) and those that are deep (deep to an epithelial surface). Many of the primary deep fungus infections of the skin are the result of local innoculations.

Pheohyphomycotic abcesses are caused by the dematiaceous fungi. The dematiaceous fungi are pigmented organisms which live in soil and decaying vegetable matter. These lesions mostly involve acral locations. They tend to be localized and often are diagnosed clinically as a cyst or tumor. Following excision, such lesions commonly are placed in formalin, without any attempt to submit material for culture. This is not a great problem since pigmentation of the organisms facilitates a histologic diagnosis on H&E stained sections. The pigment is a melanoid; it has an affinity for melanin stains, such as a Fontana-Masson stain.

The tissue response, in general, is granulomatous with a central area of necrosis or suppuration and with a peripheral zone of palisaded histiocytes. The organisms are variably pigmented but, if carefully searched for, even lightly pigmented forms usually can be identified on H&E stained sections. They are most readily identified in the zone of palisaded histiocytes. The organisms are pleomorphic. If the organisms are too lightly pigmented to be characterized as pigmented on H&E stained sections, pleomorphic qualities, if identified, will be an aid in diagnosis. The pleomorphism is demonstrated when both hyphal and yeast forms can be identified (S11C15P10-1-8).

Deep Fungal Infections

Blastomycosis:

In the category of deep fungal infections, blastomycosis is one of the more common examples. A cutaneous lesion of blastomycosis generally is evidence of disseminated disease.

The tissue response is both suppurative and granulomatous. In the skin, the lesions usually are associated with some degree of pseudoepitheliomatous hyperplasia. The organisms are fairly uniform in size; they are doubly contoured with a space separating the organism from its cell wall. Loosely distributed material in the body of the organism usually has a strong affinity for hematoxylin; this affinity may lead an observer to the mistaken notion that the organisms are representative of a peculiar, native cell, rather than a foreign, fungal organism. The organisms, in tissue, reproduce by budding; the buds are broad based (S11C16P11-1-3).

Chromomycosis

Chromomycosis is a form of infection by dematiaceous organisms. The organisms are pigmented and the tissue response is similar to that seen in lesions of blastomyosis. The lesions are both suppurative and granulomatous. They usually are associated with pseudoepitheliomatous hyperplasia. The pigmented organisms usuallly are easily identified on H&E stained sections. Occasionally, the disease may show lymphangitic spread or may disseminate.

The organisms of chromomycosis are somewhat smaller than those of blastomycosis. They are pigmented and reproduce by budding. Some reproduce by binary fission. Some of the organisms are septated; some are irregular in outline (sclerotic). The organisms often are found in clusters in the cytoplasm of multi-nucleated histiocytic giant cells. Hyphal forms, if represented, are said to exclude classic chromomycosis (S11C16P11-4-6).

Coccidioidomycosis

Cutaneous lesions of coccioidomycosis generally are evidence of disseminated disease.

The tissue response is both suppurative and granulomatous. The organisms are variable in size. Often, the organisms are larger in size than the organism of blastomycosis. This variability in size of organisms is an aid in making a distinctions between coccidiomycosis and blastomycosis; both organisms have a comparable affinity for hematoxylin. The organisms of coccidioidomycosis generally bud internally to form encysted forms. These small buds alter the pattern of the hematoxylinophilic material; the different internal patterns facilitate making a distinction between blastomycosis and coccidioidomycosis. The cysts eventually rupture. In the act, they release small endospores into the tissue. The walls of the empty cysts remain  as a marker for the process of endosporulation. Rarely, budding forms resembling those of blastomycosis are identified in tissue sections (S11C16P11-7 & 8, and S11C17P12-1-3).

Sporotrichosis

Sporotrichosis is another example of localized cutaneous disease that is secondary to innoculation. Local lymphangitic spread is common. Occasionally, the disease is disseminated.

The organisms of sporotrichosis are smaller than those of blastomycosis. They often are few in number in tissue sections. Rarely, they are numerous, in a pattern that might be mistaken for cryptococcosis, or histoplasmosis. The organisms, in size, are close to those of some examples of histoplasmosis, or some examples of cryptococcosis. Budding organisms tend to lend some degree of specificity to the histologic diagnosis; the buds tend to be thin, elongated, and have narrow bases; they are “cigar-shaped.” Another characteristic feature, which is not diagnostic, is the formation of radially projecting spicules of fibrinoid material about an organism; the spicules may be so sharply defined as to suggest crystalline material. These radial deposits are a variation of the Splendore-Hoeppli phenomena. This “asteroid form” is usually found in areas of suppuration (S11C17P12-4-8).

Cryptococcosis

Cryptococcosis of the skin is generally a feature of disseminated disease; it is a common infection in the setting of acquired immuno-deficiency. Cryptococcosis may present as a granulomatous disease of the lung and occasionally the disease presents as a meningitis.

In the skin, the infiltrates are diffuse and poorly organized. Organisms may be few or many; they may be found in giant cells, or individual histiocytes. If numerous, they also may be free in the tissue. The organism usually has a prominent mucoid capsule. In tissues section, the cell wall is separated from the surrounding tissue by a clear space. With a mucin stain, such as mucicarmine or alcian blue, the mucinous quality of the capsule can be demonstrated. The organism, as defined by it cell wall rather than the periphery of the capsule, is smaller than the organism of blastomycosis. In addition, the organism stains faintly and homogeneously with hematoxylin; the staining pattern lacks the chromatin-like qualities seen in the organism of blastomyocosis. Generally, the organism is larger than that of histoplasmosis. Buds along the surface of organisms have narrow bases (S11C18P13-1 & 2).

Histoplasmosis

In the skin, a lesion of histoplasmosis generally is a feature of disseminated disease. Histoplasmosis may present as a granulomatous disease of the lung and mediastinum. In disseminated disease, the infiltrates are prominently histiocytic, but the histocytes often do not form well-organized granulomas. Organisms mostly are numerous and intracellular. Cells of the reticulo-endothelial system of the liver and spleen may be heavily infected.

The organisms are small and buds have narrow bases. The organisms stain faintly, and diffusely, with hematoxylin. The organisms may pull away from the cell wall; they then appear to be outlined by a clear space (S11C18P13-3-6).

Cohen PR, et al: Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients. J Am Acad Dermatol 1990;23: 422-8.

Superficial Fungus Infections

The superficial fungus infections of the skin are characterized by the growth of organisms in the keratin layer of squamous epithelium. Superficial fungus infection is one of the categories to be considered when faced with a skin biopsy specimen showing both insignificant epithelial changes and minimal inflammatory infiltrates in the dermis. Superficial fungus infection should also be considered in lesions showing spongiotic and psoriasiform patterns.

The reaction to superficial fungus infections is variable; spongiotic and psoriasiform patterns are common. Spongioform, or subcorneal, pustular patterns may be a feature of some examples. Rarely, the reaction has the qualities of a leukocytoclastic vasculitis. Generally, it is not possible to relate tissue response to specific organisms (S11C19P14-1-4, 6 & 7, & S11C20P15-1 & 2). Tinea versicolor is an exception in that the tissue response generally is negligible; in addition, the morphologic features of the organism in tissue is an aid in diagnosis. Tinea nigra is distinguishied by pigmented organisms in the keratin layer; in addition, the anatomic site is an aid in diagnosis (S11C20P15-3 & 4). Generally, hyphal forms are a requisite for the diagnosis of superficial fungus infection; hyphae equate with the property of pathogenicity. Budding spores, that are common in the keratin layer, particularly in areas of parakeratosis and hyperkeratosis, usually are representative of pityrospora; rarely, pityrosporum is the causative agent of a folliculitis, particularly in association with immune deficiency, or immune suppression.

Fungi affecting follicles may present in endothrix (within the hair shaft), or ectothrix (in the keratin layer of the follicle) patterns (S11C19P14-5). Follicular variants may extend into the dermis beyond the confines of the affected follicle; in this variation, the organisms tend to produce suppurative and granulomatous inflammation in the affected tissue; the process becomes an invasive superficial fungus infection.

Dahl M: Dermatophytosis and the immune response. Am Acad Dermatol 1994;31:S34-S41.

MallorySB, Paller AS: Congenital immunodeficiency syndromes with cutaneous manifestations. J Am Acad Dermatol 1991;24 :107-11. 

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