Sporotrichosis: The Significance of Variations in Morphology of Spores in the Tissues HARRY I. LURIE Department of Pathology, Medical College of Virginia, Richmond Sporotrichosis was first discov­ even occasionally to the experi­ ered in the United States at the enced physician, primary sporo­ turn of the century (Schenck, 1898; trichotic lesions may present a Brayton, 1899; Hektoen and Per­ problem in diagnosis. It is well kins, 1900) and in France three known that they may resemble years later (de Beurmann and Ra­ lesions of syphilis or tuberculosis mond, 1903), and since then spo­ and some may simulate carcinoma. radic cases have been reported from In addition to the typical and almost every part of the globe. atypical primary lesions and the The disease appears to be endemic characteristic secondary lesions of in certain areas and minor epidem­ the lymphangitic type of sporotri­ ics have been reported, e.g., in chosis, occasional cases of dermal Mexico (Gonzalez Ochoa, personal sporotrichosis and disseminated communication) and the state of gummatous lesions may be en­ Florida (Gastineau et al., 1941), countered (Lurie, 1963a). The but the country in which the disease dermal lesions may simulate clinic­ is most prevalent is the Republic ally sarcoidosis or a reticulosis, and of South Africa. Since the disease the gummatous lesions may simu­ was first recognized there in 1927, late cold abscesses of tuberculosis 2,914 cases have been reported or syphilitic gummata. (Pijper and Pullinger, 1927; Gold­ These uncommon lesions are berg and Pijper, 1931; Dangerfield often biopsied or sometimes ex­ and Gear, 1941; Helm and Ber­ cised and submitted to the patholo­ man, 1947), and many more un­ gist for identification. In many well reported cases have been seen. known pathology text books the Presently about 60 cases per month statement is made that the histo­ are being diagnosed in the Wit­ logical features of sporotrichosis watersrand area alone. are not diagnostic. Generally speak­ There is ample evidence that the ing this is true unless the fungal Sporotrichum Schenckii lives as a spores are seen and recognized. saprophyte on certain types of vegetable matter such as sphagnum moss and barberry bushes. The rea­ Histopathology son for the high incidence in South Africa is the fact that the fungus The tissue reaction is, however, grows luxuriantly in the gold mines strongly suggestive of a fungal in­ on the timber in the hot, humid fection. A detailed description has atmosphere below ground (Brown already been published (Lurie, et al., 1947). 1963b). In the case of a primary The physician who has seen sporotrichotic "chancre" the reac­ many cases generally has no diffi­ tion consists of the following fea­ culty in making a clinical diagnosis, tures: hyperkeratosis, parakeratosis, and the usual procedure is to start some papillomatosis, and pseudo­ treatment immediately after having epitheliomatous hyperplasia of the taken a specimen for culture. How­ epithelium; in more advanced le­ ever, to the inexperienced and sions the centre is usually ulcer- MCV QUARTERLY 3(1): 13-19, 1967 13 SPOROTRICHOSIS ated, but occasionally one en­ counters a primary lesion in which there is marked papillomatosis without ulceration. In the down­ growths of epithelium intra-epider­ mal micro-abscesses are present (fig. 1), some of which rupture into the subjacent dermis. In the dermis there is a diffuse infiltra­ tion by lymphocytes, plasma cells, macrophages, multinucleated giant cells, and a variable number of eosinophiles. In some areas there may be small aggregations of neu­ trophiles. Embedded in the dermal infiltrate there are characteristic granulomata in all stages of de­ velopment. The earliest stage con­ sists of clusters of large histiocytes; later a few polymorphonuclear leu­ cocytes appear in the centre. The number of these latter cells in­ creases until a central micro-ab­ scess develops. The fully formed granuloma consists of three zones; a central area of polymorphonu­ clear leucocytes and necrotic de­ bris, a zone of large histiocytes, Fig. 1-P~im a ry lesion showi?g pseudo-epitheliomatous hyperplasia, intra-epi­ dermal micro-abscesses and diffuse dermal infiltrate (H&E 30). some of which in the outer layer are x multinucleated, and a peripheral zone of lymphocytes and plasma cells which merge imperceptibly with the diffuse dermal infiltrate (fig. 2) . The granuloma is easily differentiated from that of tuber­ culosis by the presence of the cen­ tral polymorphonuclear leucocytes; the histiocytes differ from epithe­ lioid cells by their abundant cyto­ plasm and round or oval vesicular nuclei; and the multinucleated cells are distinguishable from Langhan's giant cells as they have fewer nuclei which are irregularly distributed in the cell. At the periphery of the entire lesion there is a variable de­ gree of fibrosis and a perivascular lymphocytic infiltrate. The other types of sporotrichotic lesions mentioned, viz. the secon­ dary lymphangitic nodule and the gummatous type, show the same basic histological features apart from the fact that the epidermis shows no significant change. The early lesion consists of a deep­ Fig. 2-Early granuloma consisting of central zone of neutrophiles, middle zone of histiocytes and giant cells and peripheral zone of lymphocytes and seated infiltrate of lymphocytes, pl as ma cells (H&E x 190). 14 H. I. LURIE Fig. 3-Disintegration and confluence of granulomata (H&E X 200). plasma cells, and macrophages. cigar bodies in the tissue; later re­ Later typical granulomata appear, ports from France and elsewhere similar to those previously de­ mention the presence of round, scribed. These granulomata enlarge, oval or spindle-shaped spores; in disintegrate, and become confluent a few cases asteroid bodies were (fig. 3). Eventually the entire le­ seen. However, in most reported sion represents one large granu­ cases no fungal elements were de­ loma with a central abscess and a tected. In the South African series wall consisting of two zones, an Simson (1947) and Lurie (1963b) inner zone of histiocytes and multi­ consistently found asteroid bodies. nucleated cells and an outer zone The typical asteroid body consists of lymphocytes and plasma cells of a central round spore measuring (fig. 4). about 7 µ, in diameter surrounded by an amorphous mass of eosino­ philic material with radial projec­ Fungal Spores in Tissues tions (fig. 5a). It is of interest to This histological picture is not note that with the Gridley stain specific for sporotrichosis. Similar only the central spore is stained features may be seen in chromoblas­ purple-red while the asteroid ma­ t om y cos is, North American terial takes the color of the count­ blastomycosis, South American erstain (fig. 5c). With P.A.S. this blastomycosis, and sometimes in material is stained pale pink. coccidioidomycosis. For further In the primary lesions these as­ differentiation it is necessary to ob­ teroid bodies are almost invariably serve and identify the fungal spores. situated within the intra-epidermal It is on this point that opinions and microabscesses and in the central reports differ; the early French re­ polymorphonuclear zone of the ports described the presence of granulomata. Very occasionally 15 SPOROTRICHOSIS Fig. 4-Wall of fully developed secondary lesion, showing zone of histiocytes and giant cells (H&E X 240). Fig. 5-Various types of spores found in tissues. A and B: Typical asteroid bodies with central spore surrounded by radial eosinophilic material (H&E X 1500). C: Asteroid body showing failure of aster­ oid material to stain with Gridley stain (X 1300). D: "Asteroid body" with narrow zone of eosinophilic material without radial projections (H&E X 1880). E: "Asteroid body" with minimal amount of eosin­ ophilic material (H&E x 1880). F: Asteroid body showing budding of central spore (H&E x 1880). G: Cigar bodies in tissues, Gram's stain ( X 1500). 16 H. I. LURIE they are found elsewhere, usually in the vicinity of the aggregations of polymorphonuclear leucocytes in the dermal infiltrate. In the early secondary or gummatous lesions they are found in the granulomata; in the fully developed lesions they are distributed irregularly among the polymorphonuclear leucocytes and not in the wall. If numerous microabscesses and granulomata are present, the asteroid bodies can be found during the examination of a single section, but it is some­ times necessary to examine several sections; they are visible in H&E sections and do not require special stains. It should be noted, however, that the amount of the eosinophilic material around the spores may vary in different cases from the typical star-shaped rays to little or none (fig. 5d and e). In those cases where it is absent or minimal special stains such as P.A.S., Grid­ Fig. 6-Dry, hyperkeratotic, verrucous lesion of one year's duration. ley's or Gomori's fungal stains help in the search for the spores. It should be noted that the cigar bodies seen in most of the earlier French cases and the round, oval, or spindle-shaped spores reported from England, America, and South Africa (one case) are extremely difficult to recognize in H&E sec­ tions and require special stains. The round spores with minimal or no asteroid material are not dif­ ficult to differentiate from those of chromoblastomycosis, North or South American blastomycosis, and coccidioidomycosis. The first men­ tioned are dark brown, often occur in clusters, may be septate, and are often phagocytosed by giant cells. The blastomycosis and coc­ cidioidomycosis spores are gener­ ally larger, and are frequently phagocytosed by giant cells; the ' former show frequent budding, while the latter reproduce by endo­ spores. The sporotrichum spores are rarely seen to bud (fig. 5f); in only one case (possibly caused by a different species of sporotrichum) have they been seen within giant cells (Lurie, l 963b); and they never show endospores.