Short communications & case reports Myospherulosis of the jaws Charles L. Dunlap and Bruce F. Barker,
Kansas City, MO.
TWO cases of myospherulosis are reported. The history, histopathology, and nature of this condition are discussed. The placement of antibiotic ointment with a petrolatum base in oral wounds may be of significance. Petrolatum may provoke an inflammatory reaction and remain in tissue for years.
n 1969, McClatchie and associates’reported seven African patients with soft-tissue swellings of the arms, legs, gluteal region, and skin overlying the scapula. Microscopic examination of tissue from these patients revealed inflamed fibromuscular connective tissuecontaining cystic spaces. Some of the cysts were empty and appeared merely as spaces in the tissue; others contained particulate matter. The most striking material consisted of large “parent” bodies filled with smaller round “spherules” said to resemble “a bag of marbles. ” The authors suspectedthat they were dealing with a fungus becausethe structuresresembledRhinosporidium; however, fresh tissue known to contain the bodies injected into experimental animalsfailed to produce infection, even after immunosuppressionwith cortisone. After wide consultation, McClatchie and his colleagues concluded that they were dealing with a previously unreported diseaseof unknown etiology and chose the name myospherulosis. We herewith report two casesin which this condition occurred in the jaws. CASE REPORTS Case 1
A 25year-old woman was seen in August, 1978, for evaluationof a radiolucentlesionin the maxilla (Fig. 1). Six yearsearlier an impacted,permanentcuspidtooth had been surgicallyremovedfrom the site. The patienthad no symptoms. The clinical impressionwasthat the lesionwasa residualcyst. Two sectionsof soft tissuewere removed;the largest was 0.8 cm. in its greatest dimension.They were submittedfor microscopicstudy. 238
Fig. 1. Case1. Radiolucentareapresent6 yearsfollowing removalof uneruptedcuspidtooth. 0030-4220/80/090238+06$00.60/0
1980 The C. V. Mosby
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Fig. 2. Myosphemlosis, Case 1. Hyalinized connective tissue containing large and small spaces, some of which contain particulate matter. (Hematoxylin and eosin stain. Original magnification, x40.) Case 2 In April, 1979, a 34-year-old man had an unerupted lower third molar removed. Gelfoam coated with tetracyclinecortisone ointment* was placed in the wound. Because of persistent pain and slow repair, the patient consulted a second oral surgeon in August. A radiograph of the extraction site was interpreted as showing early osteomyelitis. A biopsy was performed to confirm that diagnosis and to rule out a tumor. Material submitted for microscopic study consisted of softtissue fragments measuring 2.0 cm. in aggregate.
Tissue from Case 2 was similar to that from Case 1. Parent bodies were present (Fig. 5). Many spherules floated freely unenclosed by a limiting membrane (Pig. 6). These spherules had a dense brown-black outer shell and a central area that ranged from light-tan to transparent. There were areas of intense acute and chronic inflammation which may have been related to the patient’s complaints, but the reaction was not centered around the cystic spaces containing the parent bodies and spherules .
Material from Case 1 consisted of hyalinized fibrous tissue which contained many spaces of varying size (Fig. 2). Some were empty, whereas others contained particulate matter. Parent bodies containing spherules or endobodies were present, as were brown-black round, dense bodies with no discernible internal structure (Figs. 3 and 4). A light lymphohistiocytic infiltrate was present. The inflammatory cells did not cluster around the particulate matter. Occasional foreign body giant cells were adjacent to the empty spaces.
was first recognized in the United described sixteen cases in the paranasal sinuses, nose, and middle ear. All patients had undergone previous surgical procedures in the involved areas, and in each case hemostatic packing which contained petrolatum-based ointment was used. The intervals between the first operation, when spherules were not present, and the second operation, when spherules were present, ranged from 38 days to 24 States in 1977 when Kyriako$
months *Terra-Cortril (Pfizer Laboratories,New York, N. Y.).
48 and 55
months, respectively, in the two remaining patients.
Oral Sure. September, 1980
Fig. 3. High-power view of a “cystic” space showing two well-formed “parent” spherules. (Hematoxylin and eosin stain. Original magnification, x400.)
In Kyriakos’ material the parent bodies ranged in size from 20 to 120 microns, with a mean diameter of 46 microns. They were round to oval, and somehad an irregular contour asif they had partially collapsed. The enclosed “endobodies” or spheruleswere found both within parent bodiesand scatteredfreely throughout the empty spaces.Their size ranged from 5 to 7 microns, slightly larger than adjacent erythrocytes. In sections stained with hematoxylin and eosin the spheruleswere brown to brownish black, but in areasof necrosisthey were eosinophilic, similar to the surrounding necrotic tissue. In addition, 9- to 40-micron “brown bodies” were seen, as well as other amorphous debris. A surrounding giant cell foreign body responsewas present, and phagocytized spherules, parent bodies and brown bodies were seen. Since pathologists, mycologists, and parasitologists were unable to identify the “organism,” Kyriakos also concluded that it may representa heretofore unrecognized pathogenic fungus. The petrolatum-base antibiotic packing was suspected of being the vehicle responsible for the transmission of the organism.
bodies which contain many
DeSchryver-Kecskemeti and Kyriakos3 were able to reproduce the condition experimentally by injecting antibiotic ointment into the abdominal cavities of rats. Despite strong circumstantial evidence that the ointment contained the organisms, attempts to recover them from the ointment failed. Further study of the ultrastructure of myospherulosis by DeSchryver-Kecskemeti and Kyriakos4 did not identify the structuresbut did rule out several possibilities. The absenceof chloroplasts ruled out vegetable matter, the lack of a triple wall eliminated pollen grains, and the absenceof cytoplasmic organellessuch as ribosomes militated against the known pathogenic fungi. Comments by consultants that the spherulesresembled erythrocytes led Rosai at the University of Minnesota to perform a simple experiment which finally revealed the nature of myospherulosis. Packed erythrocytes were added to test tubes whose walls had been coated with 3 percent tetracycline ointment. They were incubated at 37” C., and within 24 hours smearsof the preparation showed all the structures seenin the natu-
Fig. 4. Large parent body with partial rupture of wall. Numerous small, pale spherules can be seen within the parent body. Large, dark, brown-black amorphous bodies surround the parent body. (Hematoxylin and eosin stain. Original magnification, X400.) ^ rally occurring “disease. ” Parent bodies contained from 2 to 100 spherules, were eosinophilic to dark brown, and stained positively with Okajima’s stain for hemoglobin. The parent bodies and spherules were not fungi but were simple altered forms of erythrocytes. Special stains and electron microscopic study also supported the theory that the outer envelope is actually composed of rearranged erythrocytic membranes. More recently Rose and his co-workers,6 upon ultrastructural examination, have confirmed that the spherules do represent altered red blood cells but failed to support the theory that the outer envelope is altered erythrocyte membrane. Those authors offer the alternative hypothesis that the parent body is derived from cell membranes of histiocytes which have engulfed the erythrocytes. The nature and mechanism of how this envelope forms remain unclear. It is not known which ingredient (the antibiotic or the petrolatum base) is responsible for the erythrocyte alteration. The clear spaces present in the tissue are most likely due to the presence of the petrolatum, which is chemically similar to mineral oil. Clear spaces or voids
in conjunction with an inflammatory response, similar to those seen in our cases, are frequently encountered in tissues contaminated with mineral oil, paraffin, or exogenous lipids. Such a lesion has been called paraffinoma , lipogranuloma, liponecrosis , oleofibroma , and oil granuloma. One of the most recent articles on lipogranulomas is that of Stewart and co-workers,7 who discussed two cases in which vegetable oil and mineral oil were self-injected into the penile shaft. Grotesque disfiguration of the penis and histologic findings of lipogranulomas occurred in both cases. If the erythrocyte alteration (spherules) is due exclusively to changes induced by petrolatum-like materials, one would expect that these spherules would have been noticed in the many published cases of lipogranubma-like lesions. This has not been the case and suggests that the alteration is more likely due to a combination of the petrolatum and other substances, such as antibiotics. It is common practice of many dentists to place Gelfoam coated with Terra-Cortril into extraction sites following difficult extractions. We have direct knowledge that this combination was used in Case 2. The records
and Barker Septembe
Fig. 5. Myospherulosis, Case 2. A well-formed parent body and smaller spherules are present within space. (Hematoxylin and eosin stain. Original magnification, X 100.)
Fig. 6. High-power view of specimen shown in Fig. 5. Individual spherules surround a parent body which has the typical “bag of marbles” appearance. (Hematoxylin and eosin stain. Original magnification, X466.)
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of Case 1 did not specify what medication was placed in the wound, although the oral surgeon stated that he was using these agents almost exclusively at the time of surgery. Terra-Cortril is also one ingredient of the Sargenti technique of endodontic therapy.8 One would therefore expect to see similar histopathologic findings if this material is extruded into the periapical tissues. SUMMARY
Myospherulosis represents erythrocytes which have been altered by petrolatum-based ointments. The petrolatum may also be responsible for a foreign body reaction, a so-called lipogranuloma. It is not known at the present time whether the antibiotic, the petrolatum, or a combination of the drug and the petrolatum is responsible for the alteration of the erythrocytes. REFERENCES 1. McClatchie, M. D., Warambo, M. W., and Bremner, A. D.: Myospherulosis, a Previously Unreported Disease? Am. J. Clin. Pathol. 51: 699. 1969.
2. Kytiakos, M.: Myospherulosis of the Paranasal Sinuses. Nose and Middle Ear, a Possible Iatragenic Disease, Am. J. Clin. Pathol. 67: 118, 1977. 3. DeSchryver-Kecskemeti, K., and Kyriakos, M.: The Induction of Human Myospherulosis in Experimental Animals, Am. J Path01 87: 33, 1977. 4. DeSchryver-Kecskemeti, K., and Kyriakos, M.: Myospherulosis; an Electron-Microscopic Study of a Human Case, Am. J. Clin. Pathol. 67: 555, 1977. 5. Rosai, J.: The Nature of Myospherulosis of the Upper Respiratory Tract, Am. J. Clin. Pathol. 69: 475, 1978. 6. Rose,A.G.,Timme,A.H.,Price,S.K.,Emms,M.,andDale,J.: Myospherulosis: Further Ultrastructural Observations, Histopathology 3: 421-432, 1979. 7 Stewart, R. C., Beason, E. S., and Hayes, C. W.: Granulomas of the Penis From Self-Injections With Oils, Plast. Reconstr. Surg. 64: 108, 1979. 8. Sargenti, A.: Endodontics, Locamo, Switzerland. 1973, Endodontic Educational Service. Reprint
Dr. Charles Dunlap University of Missouri-Kansas City School of Dentistry 650 East 25th St. Kansas City, MO. 64108