The Journal of Dermatology Vol. 6: 47-57,1979

A LIGHT AND ELECTRON MICROSCOPIC STUDY OF A CASE OF RADIATION INDUCED MALIGNANT GIANT CELL TUMOR OF THE SOFT TISSUE SHUICHI INADA, SHOKO YANAI, REIKO YAMASAKI, TSUNEMI NUMATA, JOJI JIDOI, TAKUSO YAMURA* AND HIROMI EGAWA** ABSTRACT

A case of malignant giant cell tumor of the soft tissue in a 59-year-old female is presented. Total hysterectomy was performed for uterine carcinoma (histologically squamous cell carcinoma) in 1963, followed by radiation treatment for 6 months. Chronic radiodermatitis developed thereafter on the skin of the hip joint region, buttocks and lower abdominal region. A tumor developed in the lesion of chronic radiodermatitis of the left hip joint region in August 1976 and this was excised on February 23, 1977. Two recurrent tumors and a metastatic lesion in the inguinal lymph node developed, which were surgically removed. The main tumor, measuring 7.5cm in maximum diameter, was found chiefly in the subcutaneous adipose tissue. Histologically, it was composed of a mixture of fibroblastic spindle-shaped cells, histiocytic mononuclear cells, bizarre giant cells and osteoclast-like multinucleated giant cells. Occasionally osteoid tissues were seen. Electron microscopically, undifferentiated cells, fibroblastic cells, monohistiocytic cells, osteoclast like multinucleated giant cells and macrophages were observed, and these cells were considered to be divided into three cell lines, that is an undifferentiated cell line, fibroblastic cell line and histiocytic cell line. The histogenesis of malignant giant cell tumor in this case, is considered to have been from undifferentiated cells to both fibroblastic and histiocytic differentiation through the neoplastic stimulus of radiation.

Malignant giant cell tumor of the soft tissue (MGCTST) IS a rare malignant tumor developing in extraosseous tissue. Fewer than 100 cases of this tumor have been reported in the literature (1-9) and in Japan only one case (5) has been observed. MGCTST can be clinicopathologically divided into two groups (2, 7) and histologically resembles giant cell tumor of the bone (10). There are only two Received July 31, 1978; accepted for publication August 23, 1978. *Frorn the Department of Dermatology (Chief Director: Prof. Takuso Yamura), Hiroshima University School of Medicine. Kasumi, 1-2-3, Hiroshima, Japan. **From the Department of Pathology (Chief Director: Prof. Shoji Tokuoka), Hiroshima University School of Medicine, Kasumi, 1-2-3, Hiroshima,Japan.

reports describing the electron microscopic features of MGCST (8, 9) and, according to the electron microscopic study (9), MGCTST is considered to be a mesenchymal sarcoma with both monohistiocytic and fibroblastic differentiation. This paper describes the clinical, histologic and electron microscopic features of MGCTST developing in the lesion of chronic radiodermatitis of the hip joint region subsequent to radiation treatment for uterine carcinoma. The origin of MGCTST is discussed. CASE REPORT

The patient is a 59-year-old female who un-

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derwent total hysterectomy for uterine carcinoma (histologically, squamous cell carcinoma) in 1963, followed by radiation treatment for 6 months (cobalt-60 teletherapy with total dose of 15,900 R.). Several years later, chronic radiodermatitis developed on the skin of the hip joint region, buttocks and lower abdominal region. She noticed a skin tumor in the lesion of chronic radioderatitis of the left hip joint region in August, 1976, and this gradually increased in size. She visited the Hiroshima University Medical School Hospital on February 8 and was hospitalized on February 17, 1977. She had had a past history of pulmonary tuberculosis and diabetes mellitus. Her family history revealed that one son had died of a cerebral tumor. Physical examination: The patient was welldeveloped and well-nourished. The lesions of chronic radiodermatitis were present on the skin of the hip joint region, buttocks and lower abdominal region. The tumor, measuring 5X5X4cm in size, was seen in the lesion of chronic radiodermatitis of the left hip joint region (Fig. 1). The surface was red to dark red in color, ulcerative and nodular. It was elastically firm and fixed to the connective tissue below the tumor. Laboratory results at the time of admission: Examinations of the blood and urine revealed no evidence of any abnormality except for elevation of the erythrocyte sedimentation rate, anemia and

glycosuria. X-ray examination did not reveal the presence of any abnormal shadows in the femurs, pelvic bones or tumor lesion. Excision of the tumor was made on February 23, 1977, under the diagnosis of post-irradiation sarcoma. A recurrent tumor 1 cm in size and a lymph node of the left inguinal region 3 cm in size were observed, and these were excised on June 15,1977. Another recurrent tumor 1 cm in size was noticed subsequently and was excised on September 30, 1977. Grossfindings: Original tumor: It was a circumscribed, firm, ulcerative tumor reddish in color and measuring 7.5x5x4cm in size. When sectoned, it was reddish and partially greyish white in color and hemorrhagic. It was located mainly in the subcutaneous adipose tissue and extended up to the dermis and down to the fascial tissue (Fig. 2). Histologic, histochemical and electron microscopic observations were made. Recurrent tumors: These two tumors were morphologically similar in appearance to the original tumor. These were firm tumors dark red in color and 1 cm in size. On section, reddish lesions were present from the dermis to the muscular tissue. Lymph node of the left inguinal region; The lymph node in the subcutaneous adipose tissue was 2xlxl em in size and was encapsulated by fibrous connective tissue. On section, it was reddish in color and partially hemorrhagic.

Fig. L The tUfuor ~nd chronic radiodermatitis (_) in the left hip joint region.

Fig. 2. Grossfeatures of cut surface of excised tumor.

\lALlGNANT GIANT n.L1. TUMOR

The recurrent tumors and lymph node were prepared for histologic examination. Light microscopic examination: Original tumor: Paraffin block sections were prepared from seventeen tissue specimens obtained from the tumor and were stained with H-E, PAS, PAS with diastase digestion, alucian blue with and without pretreatment with bovine hyaluronidase, iron, Masson's trichrome stain and Gomori's method for silver stain. Frozen sections were prepared from other tissue specimens and were stained with oil red o and acid phosphatase stain using Gomori's

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method. With H-E staining, the neoplastic tissue was

revealed to be partially separated by dense collagenous tissue and arranged in a multinodular pattern. It was found to have proliferated from the dermis to the fascial tissue (Fig. 3). Cystic change (Fig. 4), hemorrhage, myxomatous change, diffuse necrosis (Fig. 5) and osteoid formation (Fig. 6) were frequently observed. It was chiefly composed of proliferations of three cell types; that is, osteoclastlike multinucleated giant cells, mononuclear cells and spindle-shaped cells. The osteoclast-like multinucleated giant cells had 10 to 30 nuclei and sometimes more than 100 nuclei with abandanr acidophilic cytoplasm. These cells had sometimes phagocytized erythrocytes. In these cells, nuclear

Fig. 3. The neoplastic tissue is located mainly in the subcutaneous adipose tissue and partially separated by dense collagenous tissue. H-E, xI.5

Fig. 5. The neoplastic tissue with necrosis and numerous osteoclast-like multinucleated giant cells. H-E, x20

Fig. 4. The neoplastic tissue with cystic changes and numerous osteoclast-like multinucleated giant cells.

Fig. 6. The osteoid tissue with a few osteoclast-like multinucleated giant cells. H·E, X80

H-E,x20

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atypism was slight and mitotic figures were not seen (Fig. 7, 8). The mononuclear cells which occupied most of the neoplastic tissue had a round to oval shaped nucleus with acidophilic fine granular cytoplasm. The nuclei of mononuclear cells varied in chromatin and size, and numerous mitotic figures were seen (Fig. 8). These cells also proliferated around the osteoclast-like multinucleated giant cells which were frequently seen around the cystic (Fig. 4), hemorrhagic and necrotic lesions (Fig. 5). The spindle shaped cells had a spindle to oval shaped nucleus of varying size with one or two prominent nucleoli and scanty cytoplasm. Mitotic figures were seen frequently. These cells partially proliferated in a bandlike pattern. In the proliferative regions of

Fig. 7. Many osteoclast-like multinucleated giant cells. One exhibits phagocytized erythrocytes (_). HE, x80

Fig. 8. Two osteoclast-like multinucleated giant cells and numerous mononuclear cells. H-E, x200

these cells bizarre giant cells with a large irregular nucleus and an abandant basophilic cytoplasm were also seen. Around the spinle shaped cells collagen fibers proliferated in a various degree (Fig. 9). These cells were also seen in lesions having myxomatous changes. In the osteoid tissue there were many osteoblast -Iike mononulear cells with a hyperchromatic nucleus and mitotic figure. A few osteoclast-like multinulceated giant cells were seen (Fig. 6,10). All of these neoplastic cells were mixed in varying ratios from section to section and from area to area of the same section. Vascularity was prominent where osteoclacr-like multinucleated giant cells and mononclear cells were predominant. At the peripheral areas of the neoplastic tissue,

Fig. 9. Numerous spindle-shaped cells and a bizarre giant cell. H-E, x200

Fig. 10. A osteoclast-like multinucleated giant cell and many osteoblast-like mononuclear cells with hyperchromatic nuclei and mitotic figures in the osteoid tissue. H-E, x80

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numerous foamy histiocytes and fibloblasts were present. In the dermis adjacent to the neoplastic tissue, a histologic feature of dense collagenous tissue and dilatation of blood vessels which resembled those of chronic radiodermatitis was observed. Sections stained by PAS and PAS with diastase digestion showed a small amount of glycogen in the neoplastic cells. Alucian blue stain demonstrated an abandance of intercellular acid mucopolysaccharide which was sensitive to bovine hyaluronidase. Iron stain demonstrated many phagocytized hemosiderin granules in a small number of osteoclast-like multinucleated giant cells and mononuclear cells. Masson's trichrome stain revealed that varying collagen fibers were produced around the spindle shaped cells. Gomori's silver stain revealed that silver positive fibers had enclosed the neoplastic cells. Oil red 0 stain of the frozen sections revealed the presence of numerous lipid droplets in osteoclast-like multinucleated giant cells and mononuclear cells. Acid phosphatase stain of Gomori's method revealed that many of the osteoclast-like multinucleated giant cells and a small number of the mononuclear cells had an abandance of positive reaction products (Fig. 11). Recurrent tumors lymph node: In H-E stained sections, the histologic features of the two recurrent tumors resembled those of the original tumor. Many osteoclast-like multinucleated giant cells and

mononuclear cells proliferated mainly in the dermis. On the other hand, osteoid tissue was absent and spindle shaped cells were few in number. H-E stained sections of the lymph node revealed a proliferation of bizarre giant cells, mononuclear cells and spindle shaped cells similar to the histologic features of the original tumor, but osteoclast-like multinucleated giant cells and osteoid tissue could not be seen (Fig. 12). Electron microscopic examination: Three specimens from the original tumor were cut into 1 mm cubes and fixed in 2.5% glutaraldehyde and 1% OsO.-phosphate buffer (pH 7.4) at 4°C and embedded in Epon 812. Ultra-thin sections were obtained and stained with uranyl. acetate and lead acetate. Five cell types were indentifiable; that is undifferentiated cells, fibroblastic cells monohistiocytic cells, osteoclast-like multinucleated giant cells and macrophages. The undifferentiated cells had a large oval nucleus with one or two nucleoli. The nuclear membrane was relatively smooth. The ratio of cytoplasm to nucleus was small. The cytoplasm contained a small number of mitochondria, polysomes and rough endoplasmic reticulum in which dilatation of cisterna with electron dense material was frequently seen (Fig. 13). The fibrobalstic cells had one or occasionally two large nuclei with two to three prominent nucleoli

Fig. 11. An abandance of positive reaction products of acid phosphatase stain in the osteoclast-like multinucleated giant cells and mononuclear cells. X200

Fig. 12. Many bizarre giant cells and mononuclear cells in the metastatic lesion of the lymph node. H-E, X200

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Fig. 13.

Two undifferentiated cells (U) with dilated cisterna of rough endoplasmic reticulum (r). E; erythrocyte, M; mitochondrion, xI2500

Fig. 14.

Fibroblastic cell (F). A; amorphous material, C; collagen fibers, G; Golgi complex, m; mitochondrion, r; rough endoplasmic reticulum. x12500

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MALIGNANT GIANT CELL TUMOR

Fig. 15.

A fibroblastic cell showing dilated cisterna of rough endoplasmic reticulum. A; amorphous material, C; collagen fibers, F; fibroblastic cell, M; macrophage, I; lysosome, m; mitochondrion, r ; rough endoplasmic reticulum, (-+); intercellular junction. x 10500

whose nuclear membrane showed irregular invagination. The cytoplasm contained many mitochondria, Golgi complexes, dense bodies, lipid vacuoles, polysomes and well developed rough endoplasmic reticulum with variously dilated cisterna containing electron dense material (Fig. 14-16) and sometimes with filamentous structures. Bundles of filaments were also frequently seen (Fig. 16). The plasma membrane was irregular and had frequently intercellular junctions with other fibroblastic cells. Many of these cells were in contact with collagen fibers and amorphous material (Fig. 14,15). The rnonohistiocytic cells had a large round, oval or sometimes irregular shaped nucleus whose nuclear chromatin appeared dense in the peripheral area. The cytoplasm contained many mitochondria, well developed Golgi complexes, rough endoplasmic reticulum, smooth endoplasmic reticulum and dense bodies suggestive of lysosomes. The plasma memebrane had many short pseudopodia (Fig. 17).

The osteoclast-like multinucleated giant cells had many oval or irregular shaped nuclei which were relatively regular in size and resembled those of monohitiocyric cells. The cytoplasm was abandant and contained numerous mitochondria. rough endoplasmic reticulum, Golgi complexes and lysosomes. The plasma membrane had many short pseudopodia (Fig. 18). The macrophage had an oval nucleus whose chromatin pattern resembled that of monohistiocytic cells and many well developed cell organelles and dense bodies suggestive of lysosomes. DISCUSSION

It has' been reported in clinicopathological studies that MGCTST is subdivided into superficial and deep group (2. 7). In the superficial group. tumors which occur in the subcutis and superficial fascia with a predilection for the leg showed a relatively low

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Fig. 16. The bundle of filaments (f) in the fibroblastic cell (F). E; erythrocyte, r; rough endoplasmic reticulum. X24000

Fig. 18.

Fig. 17. Monohistiocytic cell (M) F; fibroblastic cell,l; lysosome, m; mitochondrion, s; smooth endoplasmic reticulum. x7000

Osteoclast-like multinulceated giant cell. E; erythrocyte,l; lysosome, m; mitochondrion. x5000

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malignancy. The deep tumors which develop in the skeletal muscle, deep fascia and tendons with a predilection for the thigh showed a high malignancy. Histologically MGCTST was composed of proliferation of osteoclast-like multinucleated giant cells, mononuclear histiocytes, fibroblasts and plemorphic giant cells arranged in a multinodular pattern, and frequently showed malignant osteoid and bone formation. The histologic features of MGCTST resemble those of other soft tissue sarcomas, such as malignant fibrous histiocytoma, fibrosarcoma and extraskeletal osteosarcoma. The tumor in this case, which was considered to be histopathologically different from the above described sarcomas, was diagnosed as MGCTST and was considered to belong to the superficial group of MGCTST. Although the tumor of this case recurred twice after excision and metastasized to the regional lymph node, it has been reported that the superficial group of MGCT"ST recurred frequently, and that 2 of 12 cases of this group metastasized and terminated in death (2). Two electron microscopic studies of MGCTST have been reported (8, 9). Haelst (8) observed poorly differentiated mesenchymal cells, chondroblast- or osteoblast-like cells, histiocytes and multinucleated giant cells. As fibroblast, chondroblast and osteoblast showed similar electron microscopic features (11, 12) and were considered to belong to the fibroblast cell line (9), these cells observed by Haelst (8) may also be divided into three cell lines as reported by Alguacil-Garcia (9). On the other hand, Alguacil-Garcia (9) observed five cell types; clear, undifferentiated and poorly differentiated mesenchymal cells, dark monohistiocytic cells, large phagocytic cells, spindle cells, and osteoclastic and multinucleated giant cells. They divided these cells into three different cell lines; undifferentiated cells corresponding to some of

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the round to oval cells in light microscopy, a fibroblastic cell line corresponding to the spindle cells, and a monohistiocytic cell line corresponding to the round to oval cells and osteoclast-like multinucleated giant cells. In this case, these three different cell lines were also recognized by electron microscopic studies. As the rough endoplasmic reticulum with dilatated cisterna which contained electron dense material was frequently seen in the undifferentiated cells, at least some of these cells were considered to differentiate into the fibroblastic cell line. The cells belonging to the fibroblastic cell line contained well-developed rough endoplasmic reticulum with dilatated cisterna and Golgi complexes which were considered to be the characteristic features of cells capable of synthesis of collagen fibers as fibroblasts, chondroblasts and osteoblasts, and to produce or synthesize protein and acid mucopolysaccharide (12, 13). Additionally, these cells were in contact with the plasma membrane by means of collagen fibers and amorphous material considered to be acid mucopolysaccharide (14). It therefore appears that these cells acted as fibroblasts, chondroblasts or osteoblasts to produce acid mucopolysaccharide and collagen fibers and to form the osteoid tissues which were observed in light microscopic studies. The monohistiocytic cell line contained mono histiocytic cells, osteoclast -like multinucleated giant cells and macrophages. Electron microscopically, the osteoclast-like multinucleated giant cells had numerous nuclei similar in appearance to those of monohistiocytic cells and well-developed cell organelles. Histochemically they contained large amounts of acid phosphatase. From these morphological findings, osteoclast-like multinucleated giant cells of this case appeared to resemble those of giant cell tumor of the bone (15-17) and normal osteoclasts (18). They

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might be formed by fusion of monohistiocytic cells as observed in the study of the origin of osteoclast-like multinucleated giant cells in giant cell tumor of the bone (17). It has been reported that the osteoclast-like multinucleated giant cells show reactive proliferation in some tumors (19, 20). In this case the following findings suggest that osteoclast-like multinucleated giant cells might be not neoplastic but reactive. These cells showed no mitotic figures and were not present in the metastatic lesion. However, it has been observed in other cases of MGCTST that metastatic lesions contain multinucleated giant cells in accompany with histiocytic cells (2). It is therefore considered that the osteoclast-like multinucleated giant cell might be one of the mature cells of the monohistiocytic cell line and a neoplastic cell. Concerning the origin of MGCTST, Guccion (2) proposed a histiocytic origin because the histologic features of the neoplastic mononuclear cells and multinucleated giant cells demonstrated histiocytic characteristics. Recently Alguacil-Garcia (9) has suggested through electron microscopic studies that MGCTST is derived from undifferentiated mesenchymal cells with both monohistiocytic and fibroblastic-differentiation. On the other hand, MGCTST shows a similarity in cell type to benign and malignant fibrous histiocytomas which are composed of two cell types, fibroblast like cells and histiocyte like cells (4), and is considered to be a variant of malignant fibrous histiocytoma (9). The histogenesis of benign and malignant fibrous histiocytomas is yet unknown but several hypotheses have been proposed; culture of these tumors and electron microscopic examinations (21, 22) have suggested that the origin is tissue histiocytes which are capable of collagen synthesis as a "facultative fibroblast" . However, recent studies have suggested that the histiocyte

represents a morphologic state of a given mesenchymal cell (23) and the origin of malignant fibrous histiocytoma IS the undifferentiated mesenchymal cell which differentiates into both fibroblast like cells and histiocyte like cells (4). Furthermore, MGCTST resembles giant cell tumor of the bone histologically (2, 10) and electron microscopically (8, 9) and this tumor is considered to be derived from the bone marrow mesenchymal cells capable of differentiation into both fibroblastic and histiocytic directions (16). In contrast to the origin of these two tumors, the origin of MGCTST might be undifferentiated mesenchymal cells with both fibroblastic and histiocytic differentiation because, in the tumor of this case, there are various stages of cytodifferentiation in both the fibroblastic and histiocytic cell lines. On the other hand, the tumor of this case was considered to be induced by radiation treatment because it satisfied the following criteria for the diagnosis of radiation-induced sarcoma (24, 25); 1) The sarcoma was not present prior to radiation treatment. 2) The sarcoma appeared within the lesion of chronic radiodermatitis. 3) After radiation treatment there was a relatively long asymptomatic period of several years before the clinical manifestation of sarcoma. 4) The sarcoma was histologically demonstrated. It is therefore concluded that MGCTST in this case developed from undifferentiated cells with both fibroblastic and histiocytic differentiation through the neoplastic stimulus of radiation. REFERENCES 1) Salm, R. and Sissons, H.A.: Giant-cell tumours of soft tissues.]. Path., 107: 27-39,1972. 2) Guccion, J.G. and Enzinger, F.M.: Malignant giant cell tumor of soft parts, an analysis of 32 cases, Cancer, 29: 1518-1529, 1972. 3) Horacek, J. and Beranova, A.: Die bosartige Riesenzellgeschwulst der weichen Geweve, Mitteilung

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eines Falles, Derm. Mschr., 160: 126-131, 1974. 4) Fu, Y.S., Gabbiani, G., Kaye, G.1. and Lattes, R.: Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): general considerations and electron microscopic and tissue culture studies, Cancer, 35: 176-198, 1975. 5) Dochi, T. and Ogawa, S.: Case conference of bone and soft tissue tumors, din. Orthop. Surg. (Tokyo), 10:65-68,1975. 6) Yaghmai, I.: Malignant giant cell tumor of the soft tissue: angiographic manifestations, Radiology, 120: 329-331,1976. 7) Kondratiev, L.N. and Lavnikowa, G.A.: Malignant giant cell tumors of soft tissues, Arkh. Pathol., 38: 52-58, 1976. 8) Haelst, U.J.G.M. van and Dorsser, A.H.H., van: Giant cell tumor of soft parts, an ultrastructural study, virchows Arch. A Path. Anat. and Histol., 371: 199-217,1976. 9) Alguacil-Garcia, A., Unni , K.K. and Goellner, J.R.: Malignant giant cell tumor of soft parts, an ultrastructural study of four cases, Cancer, 40: 244-253,1977. 10) Ackerman, L.V. and Rosai, J.: Surgical pathology, 5th edition, the C.V. Mosby Company St. Louis, 1974, p. 1110. ll) Sandborn, E.B.: Cells and tissues by light and electron microscopy, vol. I, Academic Press, Inc. New York and London, 1970, p. 95. 12) Kajikawa, K.: Ultrastructure and degeneration of connective tissues, The cell (Tokyo) 3 (11): 2-11, 1971. 13) Ghadially, F.N.: Ultrastructural pathology of the cell; a text and atlas ofphysiological and pathological alterations in cell fine structure, Butterworths, London and Boston, 1975, p. 187-282. 14) Kahn, L.B.: Malignant giant cell tumor of the tendon sheath, ultrastructural study and review of the literature, Arch. Pathol., 95: 203-208, 1973.

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15) Pepler, W .J.: The histochemistry of giant -cell tumours (osteoclastoma and giant-cell epulis).]. Path. Bact., LXXVI: 505-511, 1958. 16) Horie, A.: An electron microscopic observation of giant cells and stromal cells in the benign giant cell tumor of the bone, Fukuoka Acta Med., 52: 817-828, 1961. 17) Hanaoka, H., Friedman, B. and Mack, R.P.: Ultrastructure and histogenesis of giant-cell tumor of bone, Cancer, 25: 1408-1423, 1970. 18) Gonzales, F. and Karnovsky, M.J.: Electron microxcopy of osteoclasts in healing fractures of rat bone.]. Biophys. Biochem. Cytol., 9: 299-316,1961. 19) Hallowes, R.C. and Chesterman, F.C.: Histochemistry of giant cells in tumours induced in golden hamsters by murine sarcoma virus-Harvey, Int. I Cancer, 7: 507-512,1971. 20) Hallowes, R.C. and Chesterman, LC.: Ultrastructure of giant cells in tumours induced in golden hamsters by murine sarcoma virus-Harvey. Int. I Cancer, 7: 513-525, 1971. 21) Ozzello, L, Stout, A.P. and Murray, M.R.: Cultural characteristics of malignant histiocytomas and fibrous xanthomas, Cancer 16: 331-344, 1963. 22) Merkow, L.P., Frich, J.C .. Slifkin, M., Kyreages, C.G. and Pardo, M.: Ultrastructure of a fibroxanthosarcoma (malignant fibroxanthorna), Cancer, 28: 372-383, 1971. 23) Taxy, J.B. and Battifora, H.: Malignant fibrous histiocytoma, an electron microscopic study, Cancer, 40:254-267,1977. 24) Cahan, W.G., Woodard, H.Q., Higinbotham, N.L., Stewart, F.W. and Coley, B.L.: Sarcoma arising in irradiated bone, report of eleven cases, Cancer, 1: 3-29, 1948. 25) Gonzalez-Vitale, J.C., Slavin, R.E. and McQeen, J.D.: Radiation-induced intracranial malignant fibrous histiocytoma, Cancer, 37: 2960-2963, 1976.

A light and electron microscopic study of a case of radiation induced malignant giant cell tumor of the soft tissue.

The Journal of Dermatology Vol. 6: 47-57,1979 A LIGHT AND ELECTRON MICROSCOPIC STUDY OF A CASE OF RADIATION INDUCED MALIGNANT GIANT CELL TUMOR OF THE...
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