Sporotrichosis: the Significance of Variations in Morphology of Spores in the Tissues

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.

17 SPOROTRICHOSIS

Significance of Variation in Spore Morphology This raises an interesting prob lem as to the reason for the varia tion in the morphology of the spores in human lesions in individ ual cases and in different parts of the world. Pinkus and Grekin ( 1950) noted that asteroid bodies were seen in two American cases which clinically appeared to be very mild and ran a protracted and bland course; Negroni and Prado (1951) are of the opinion that asteroid body formation is an ex pression of host resistance; the present author (Lurie, 1963b) is in agreement with this view and thinks that the eosinophilic mate rial of the asteroid body may rep resent an antigen-antibody reaction, and that the round central spore represents a chlamydospore which has formed from a cigar body. Support for the view that the pres ence of asteroid bodies is indicative of resistance or relative immunity to infection is provided by the fact that in South Africa where most of the cases examined histologically had asteroid bodies, only five cases out of a total of about 3,300 showed systemic involvement (Lu rie, 1963a). The experience of the author ap pears to confirm the findings of Pinkus and Grekin (1950) . The two asteroid bodies with abundant eosinophilic material (figs. 5a and b) are from mild cases which ran a Figs. 7 and 8- Garden worker with extensive involvement of hands and face. protracted and bland course. The He also had a bone lesion. first was found in the dry, ver-

18 H. I. LURIE rucous, hyperkeratotic lesion (fig. especially on the immunology of DANGERFIELD, L. F., AND J. GEAR. 6) which had been present for one sporotrichosis and the correlation Sporotrichosis among miners of year; the second was found in a of the clinical picture with both the Witwatersrand gold mines. S. Afri seven-month-old recurrent lesion in tissue reactions and the morphology can Med. J. 15: 128-131, 1941. a mine worker who had been in of the spores in the tissues. DE BEURMANN, L., AND L. RAMOND. adequately treated 10 years previ Abces sous-cutanes multiples d'ori ously. The asteroid body with a gine mycosique. Ann. Dermarol. Summary Syphilig. Paris 4: 678- 685, 1903. moderate amount of eosinophilic material shown in Fig. 5d is from 1. The histopathological diag GASTINEAU, F. M., L. W. SPOLYAR, a one-month-old lesion in a garden nosis of sporotrichosis is briefly AND E. HAYNES. Sporotrichosis: Six cases among florists. J. Am. Med. worker. Secondary nodules had ap reviewed. The primary lesion Assoc. 117: 1074-1077, 1941. peared after two weeks. The spore consists basically of pseudo-epi with the minimal amount of eosin theliomatous hyperplasia of the GOLDBERG, M., AND A. PIJPER. Spo ophilic material (Fig. 5e) is typical epidermis, intra-epidermal micro rotrichosis in white man. J. Med. Assoc. S. Africa. 5: 140, 1931. of those found in a secondary abscesses, a non-specific dermal HEKTOEN, L., AND C. F. PERKINS. Re nodule, one of many, of two weeks infiltrate and granulomata com fractory subcutaneous abscesses duration in a mine worker, in posed of a central micro-abscess caused by Sporothrix Schenckii: A whom no primary lesion could be surrounded by a zone of histiocytes new pathogenic fungus. J. Exp. found. The case shown in figures and multinucleated giant cells. Med. 5: 77-89, 1900. 7 and 8 was also a garden worker. Spores are found in the intra HELM, M. A. F., AND c. BERMAN. In addition to extensive lesions in epidermal abscesses and in the The clinical therapeutic and epi volving his hands, face, and neck, granulomata. These spores may be demiological features of the sporo he had an osteolytic lesion in his cigar-shaped, round or oval. The trichosis infection on the mines. In tibia. In sections of the cutaneous diagnostic spore is the asteroid Sporotrichosis Infection on Mines lesions there were no asteroid body which consists of a central of the Witwatersrand. Johannes bodies but cigar bodies were found round spore, about 7 µ, in diameter, burg, S. A.: The Transvaal Cham (fig. 5g). In another case pre surrounded by a variable amount ber of mines, 1947, pp. 59-72. viously described (Lurie, 1963a of eosinophilic material which fre LURIE, H. I. Five ususual cases of and b) in which there was wide quently has an asteroid shape. sporotrichosis from South Africa spread visceral involvement numer 2. The significance of the aster showing lesions in muscles, bones, ous cigar bodies were found in oid body is discussed. Evidence is and viscera. Brit. J. Surg. 50: 585- 591 , 1963a. smears prepared from a lesion in a presented to support the view that rib and an abscess of the orbit. the development of asteroid bodies LURIE, H. I. Histopathology of sporo trichosis. Arch. Pathol. 75: 421- and the amount of eosinophilic It is of interest to note that in 437, 1963b. experimental infections in rats gen material in these bodies is related NEGRONI, P., AND J. M. PRADO. Al erally only numerous cigar bodies to host resistance and that cigar bodies are found in those cases geria e inmunidad en la esporo and a few round or oval spores are tricosis experimental. Anales Soc. with little or no resistance and in seen. However, Simson (1947) Cienti. Arg. 151: 32, 1951. whom the disease disseminates found that in older lesions, six PIJPER, A., AND B. D. PuLLINGER. An rapidly and widely. weeks or more, a few asteroid outbreak of sporotrichosis among bodies appeared. He was able to 3. Avenues of research are sug South African native miners. Lan gested. trace the development of these cet. 2: 914-915, 1927. asteroid bodies from cigar bodies. PINKUS, H., AND J. N. GREKIN. Sporo In certain areas where the dis trichosis with asteroid tissue forms. Report of a case. Arch. Dermarol. ease is endemic, it has been shown References that many of the inhabitants have Syphilol. 61 : 813- 819, 1950. developed a degree of immunity as BRAYTON, A. W. On refractory sub SCHENCK, B. R. On refractory sub indicated by their positive reactions cutaneous abscesses caused by a cutaneous abscesses caused by a to intradermal sporotrichin. It is fungus possibly related to the fungus possibly related to the Spo highly likely that if such persons sporotricha. Indiana Med. J. 18: rotricha. Bull. Johns H opkins Hosp. were to become infected, many 272, 1899. 9: 286- 290, 1898. asteroid bodies would be found in BROWN, R., D. WEINTROUB, AND M. SIMSON, F. w. The pathology of their lesions. W. SIMPSON. Timber as a source of sporotrichosis in man and experi sporotrichosis infection. In Sporo mental animals. In Sporotrichosis To date this concept of the na trichosis Infection on Mines of the Infection on Mines of the Witwat ture and significance of the asteroid Witwatersrand. Johannesburg, S. ersrand. Johannesburg, S. A.: The body is not definitely proved. Much A.: The Transvaal Chamber of Transvaal Chamber of Mines, 1947, work still remains to be done, Mines, 1947, pp. 5- 33. pp. 34- 58.