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Hemangioendothelioma of Bone
Path. Res. Pract. 178, 297-300 (1984)
Hemangioendothelioma of Bone A Case Report with Massive Tissular Necrosis A. Vinuela, F. Fernandez-Raja and A. Gonzalez-Nunez Servicio de Anatomia Patologica, Residencia Sanitaria de la Seguridad Social, Leon, Spain
SUMMARY
Hemangioendothelioma or histiocytoid hemangioma of bone is a low grade tumor, which may be a quite indolent and controlable lesion, even in the rare case it develops distant metastasis. Our case presents features of such lesion by light microscopy and with a peroxidase-antiperoxidase technique for Factor VIII related antigen, but it exhibits an unusual extensive tissular necrosis. Necrosis does not seems to make worse the usual course, after six years and ten months of conservative surgical treatment and radiation therapy.
Introduction Among vascular tumors of bone, there is a type different from benign hemangioma and from fully anaplastic angiosarcoma, which has been variously named: hemangioendothelioma 6, !O, 13, angioblastoma lO , well-differentiated hemangioendothelial sarcoma 4 , histiocytoid hemangiomaS, and grade I and II hemangioendothelioma!. Ultrastructural studies have been made by Steinert and Dorfman (1972). The terms hemangioendothelioma and angiosarcoma have been used both as synonyms and to indicate separate pathologic entities 14 • According to Dorfman et al. (1971), a benign hemangioendothelioma has not been described, though Campanacci et al. (1980) have estimated the possibility of benign hemangioendothelioma as an entity distinct from capillary hemangioma. Schajowicz et al. (1972) have separated hemangioendothelioma as a group intermediate or indeterminate. Hemangioendothelioma of bone is a rare condition. Srinivasan et al. (1978) reviewed eighty-seven cases reported in the literature and added two new cases. In the Mayo Clinic experience, Dahlin (1978) refers twenty-five cases, less than 1 % of malignant tumors of bone. Multifocality occurs in approximately one third of cases, and multicentric tumors behaved in a somewhat more benign way. © 1984 by Gustav Fischer Verlag, Stuttgart
Its angiogenic capacity is evident. It exhibits architectural, cytologic, and ultrastructural features associated with endothelial cells elsewhere, but they are not entirely normal endothelial cells since, opposited to the latter, they do not stain for alkaline phosphatase, and are strongly positive for nonspecific esterase, acid phosphatase, dehydrogenase, 'glucosa-6-phosphate dehydrogenase, cytochrome oxidase, and NADH diaphorase 5,s. Rosai et al. (1979) designate them "histiocytoid endothelial cells", a term common for this bone lesion and for several previously described entities of skin, soft tissue, large vessels, and heart. Nevertheless, Wright et al. (1981) did not find in these cells such markers of histiocytes as are lysozyme and alpha!-antitrypsine. On the other hand, the inflammatory or reactive component of these lesions is thought to be variable and probably secondary. Case Report A 42-year-old white man had a pain in his left hip during four months, which became worse in bed at night. Radiographs showed an osteolytic defect in the left femoral neck (Fig. 1 a). ESR was 75/110 mm. Protei nogram, Ca, P, and alkaline phosphatase levels were normal. In March 1976 a curettage was made trough an indemne 0344-0338/84/0178-0297$3.50/0
298 . A. Vifmela, F. Fernandez-Rojo and A. Gonzalez-Nunez
Fig. 1. Left femoral neck: a) March 1976. b) December 1982.
cortical bone, and a bloody soft material was evacuated from a trabeculate cavity. With the diagnosis of low grade angiosarcoma, the lesion was treated with radiation therapy. The last radiographic control, in December 1982, showed no change in relation with previous years (Fig. 1 b). In January 1983 the patient was well, with a slight claudication and a functional limitation lesser than 20°. Material and Methods Multiple fragments of tissue (2.0 X 1.2 x 0.8 cm. all together) were fixed in 10% aqueous formalin, processed in paraffin, and stained with hematoxylin and eosin, silver (Gomori) for reticulin,
and P.A.S .. Other sections were stained with a peroxydase-antiperoxydase (PAP) technique for Factor VIII related antigen (Maciver et a!., 1979), with antiserum from Nordic Immunologic Reagents, at a titre of 1: 100 and 1: 200.
Results Many fragments of tissue are wholly or partly necrosed. The lesion consists of quite large cells and a variable cellular infiltrate of lymphocytes and eosinophils (Fig. 2). There are also hemorrhagies, thrombosis and siderophages. Large cells have abundant cytoplasm, large nuclei frequently cleaved, with much of chroma tine
Fig. 2. Clefts (vascular lumens) and cellular infiltrate (Hematoxylin and eosin, 45 x).
Hemangioendothelioma of Bone . 299
Fig. 3. Angiogenic vacuoles, precursors of vascular lumen (Hematoxylin and eosin, 515 x).
Fig. 4. Buds and tubules surrounded by reticulin. At the left botton corner, a well formed capillary vessel. (Gomori, 85 x).
attached to the inner aspect of the nuclear membrane (Fig. 3). One or more nucleoli are patent. Inside the cytoplasm there are vacuoles which, as they enlarge, become separated by thin septa, that finally are ruptured (Fig. 3). Clefts are thus formed, and cellular buds, solid at the beginning, become gradually vascular lumens, encircled by reticulin and sheathed on the inside by endothelium (Fig. 4), as in any angiogenic process. Mitotic figures are not seen. PAP technique for Factor VIII related antigen shows an elective coloration of solid or tubular elements and some isolated cells, opposited at the negative background (Fig. 5).
Discussion At an optical and immunochemical level we have been able to verify the well known angiogenic features of this specific morphologic variant of vascular tumors of bone, most of them quite benign or endowed with only a local degree of aggressiveness. But our case shows very extensive tissular necrosis, a point expressly mentioned as absent in other reports. First, we thought this could be a manifestation of increased aggressiveness, but after almost seven years of follow-up the patient is doing well and radiographically there is no change, so he is submited only to periodic vigilance.
300 . A. Vifmela, F. Fernandez-Rojo and A. Gonzalez-Nunez
Fig. 5. PAP technique for Factor VIII related antigen. Elective coloration of anomalous endothelial cells on a stainless background. (105 x).
Nevertheless, it must be kept in mind that six years can be a too short period for judging the final behavior of this lesion, sinceJa Craver and Brown' (1979) patient was alive twenty five years after the initial exeresis of the primitive bone tumor, having been resected two pulmonary metastasis at 15 and 20 years from the onset. Acknowledgement. We are grateful to Dr. L. Bacariza for permission to publish this case and for clinical data.
References 1 Campanacci M, Boriani S, Giunti A (1980) Hemangioendothelioma of bone. A Study of 29 cases. Cancer 46: 804-814 2 Craver WL, Brown BS (1979) Hemangioendothelioma of Bone with Pulmonary Metastases: A 25-year Course. Report of a Case. Cancer 43: 1917-1923 3 Dahlin DC (1978) Bone Tumors. General Aspects and Data on 6,221 cases. Third Edition, pp 344-355, Ch C Thomas, Springfield, Illinois 4 Dorfman HD, Steiner GC, Jaffe HL (1971) Vascular Tumors of Bone. Hum Path 2: 349-376 5 Eady RAJ, Wilson-Jones E (1977) Pseudo pyogenic Granuloma: Enzyme Histochemical and Ultrastructural Study. Hum Path 8: 653-668
6 Hartman WH, Stewart FW (1962) Hemangioendothelioma of Bone; Unusual Tumor Characterized by Indolent Course. Cancer 15: 846-854 7 MacIver AG, Giddingsan J, Mepham BL (1979) Demontration of Extracellular Immunoproteins in Formol-fixed Renal Biopsy Specimens. Kidney International 16: 632-636 8 Rosai J, Gold J, Landy R (1979) The Histiocytoid Hemangiomas: A Unifying Concept Embracing Several Previously Described Entities of Skin, Soft Tissue, Large Vessels, Bone and Heart. Hum Path 10: 707-730 9 Schajowicz F, Ackerman LV, Sissons HA (1972) Tipos histologicos de tumores oseos. pp 42-43 Geneve, WHO 10 Spjut HJ, Dorfman HD, Fechner RE, Ackerman LV (1970) Tumors of bone and cartilage. AFIP number 5, pp 334-340 11 Srinivasan CK, Patel MR, Pearlman HS, Silver JW (1978) Malignant hemangioendothelioma of bone. Review of the literature and report of two cases. J Bone and Joint Surg (Am) 60: 696-700 12 Steiner GC, Dorfman HD (1972) Ultrastructure of hemangioendothelial sarcoma of bone. Cancer 29: 122-135 13 Stout AP (1943) Hemangio-endothelioma: A tumor of blood vessels featuring vascular endothelial cells. Ann Surg 118: 445-464 14 Unni KK, Ivins JC, Beabout JW, Dahlin DC (1971) Hemangioma, hemangiopericytoma and hemangioendothelioma (anriosarcoma) of bone. Cancer 27: 1403-1414 1 Wright DH, Padley HR, Judd MA (1981) Angiolymphoid Hyperplasia with Eosinophilia simulating lymphadenopathy. Histopathology 5: 127-140
Received November 8, 1982 . Accepted February 10, 1983
Key words: Bone - Hemangioendothelioma - Angiosarcoma - Histiocytoid hemangioma - Necrosis Dr. A. Vinuela, Residencia Sanitaria S.S., Leon, Spain
Hemangioendothelioma of Bone A Case Report with Massive Tissular Necrosis A. Vinuela, F. Fernandez-Raja and A. Gonzalez-Nunez Servicio de Anatomia Patologica, Residencia Sanitaria de la Seguridad Social, Leon, Spain
SUMMARY
Hemangioendothelioma or histiocytoid hemangioma of bone is a low grade tumor, which may be a quite indolent and controlable lesion, even in the rare case it develops distant metastasis. Our case presents features of such lesion by light microscopy and with a peroxidase-antiperoxidase technique for Factor VIII related antigen, but it exhibits an unusual extensive tissular necrosis. Necrosis does not seems to make worse the usual course, after six years and ten months of conservative surgical treatment and radiation therapy.
Introduction Among vascular tumors of bone, there is a type different from benign hemangioma and from fully anaplastic angiosarcoma, which has been variously named: hemangioendothelioma 6, !O, 13, angioblastoma lO , well-differentiated hemangioendothelial sarcoma 4 , histiocytoid hemangiomaS, and grade I and II hemangioendothelioma!. Ultrastructural studies have been made by Steinert and Dorfman (1972). The terms hemangioendothelioma and angiosarcoma have been used both as synonyms and to indicate separate pathologic entities 14 • According to Dorfman et al. (1971), a benign hemangioendothelioma has not been described, though Campanacci et al. (1980) have estimated the possibility of benign hemangioendothelioma as an entity distinct from capillary hemangioma. Schajowicz et al. (1972) have separated hemangioendothelioma as a group intermediate or indeterminate. Hemangioendothelioma of bone is a rare condition. Srinivasan et al. (1978) reviewed eighty-seven cases reported in the literature and added two new cases. In the Mayo Clinic experience, Dahlin (1978) refers twenty-five cases, less than 1 % of malignant tumors of bone. Multifocality occurs in approximately one third of cases, and multicentric tumors behaved in a somewhat more benign way. © 1984 by Gustav Fischer Verlag, Stuttgart
Its angiogenic capacity is evident. It exhibits architectural, cytologic, and ultrastructural features associated with endothelial cells elsewhere, but they are not entirely normal endothelial cells since, opposited to the latter, they do not stain for alkaline phosphatase, and are strongly positive for nonspecific esterase, acid phosphatase, dehydrogenase, 'glucosa-6-phosphate dehydrogenase, cytochrome oxidase, and NADH diaphorase 5,s. Rosai et al. (1979) designate them "histiocytoid endothelial cells", a term common for this bone lesion and for several previously described entities of skin, soft tissue, large vessels, and heart. Nevertheless, Wright et al. (1981) did not find in these cells such markers of histiocytes as are lysozyme and alpha!-antitrypsine. On the other hand, the inflammatory or reactive component of these lesions is thought to be variable and probably secondary. Case Report A 42-year-old white man had a pain in his left hip during four months, which became worse in bed at night. Radiographs showed an osteolytic defect in the left femoral neck (Fig. 1 a). ESR was 75/110 mm. Protei nogram, Ca, P, and alkaline phosphatase levels were normal. In March 1976 a curettage was made trough an indemne 0344-0338/84/0178-0297$3.50/0
298 . A. Vifmela, F. Fernandez-Rojo and A. Gonzalez-Nunez
Fig. 1. Left femoral neck: a) March 1976. b) December 1982.
cortical bone, and a bloody soft material was evacuated from a trabeculate cavity. With the diagnosis of low grade angiosarcoma, the lesion was treated with radiation therapy. The last radiographic control, in December 1982, showed no change in relation with previous years (Fig. 1 b). In January 1983 the patient was well, with a slight claudication and a functional limitation lesser than 20°. Material and Methods Multiple fragments of tissue (2.0 X 1.2 x 0.8 cm. all together) were fixed in 10% aqueous formalin, processed in paraffin, and stained with hematoxylin and eosin, silver (Gomori) for reticulin,
and P.A.S .. Other sections were stained with a peroxydase-antiperoxydase (PAP) technique for Factor VIII related antigen (Maciver et a!., 1979), with antiserum from Nordic Immunologic Reagents, at a titre of 1: 100 and 1: 200.
Results Many fragments of tissue are wholly or partly necrosed. The lesion consists of quite large cells and a variable cellular infiltrate of lymphocytes and eosinophils (Fig. 2). There are also hemorrhagies, thrombosis and siderophages. Large cells have abundant cytoplasm, large nuclei frequently cleaved, with much of chroma tine
Fig. 2. Clefts (vascular lumens) and cellular infiltrate (Hematoxylin and eosin, 45 x).
Hemangioendothelioma of Bone . 299
Fig. 3. Angiogenic vacuoles, precursors of vascular lumen (Hematoxylin and eosin, 515 x).
Fig. 4. Buds and tubules surrounded by reticulin. At the left botton corner, a well formed capillary vessel. (Gomori, 85 x).
attached to the inner aspect of the nuclear membrane (Fig. 3). One or more nucleoli are patent. Inside the cytoplasm there are vacuoles which, as they enlarge, become separated by thin septa, that finally are ruptured (Fig. 3). Clefts are thus formed, and cellular buds, solid at the beginning, become gradually vascular lumens, encircled by reticulin and sheathed on the inside by endothelium (Fig. 4), as in any angiogenic process. Mitotic figures are not seen. PAP technique for Factor VIII related antigen shows an elective coloration of solid or tubular elements and some isolated cells, opposited at the negative background (Fig. 5).
Discussion At an optical and immunochemical level we have been able to verify the well known angiogenic features of this specific morphologic variant of vascular tumors of bone, most of them quite benign or endowed with only a local degree of aggressiveness. But our case shows very extensive tissular necrosis, a point expressly mentioned as absent in other reports. First, we thought this could be a manifestation of increased aggressiveness, but after almost seven years of follow-up the patient is doing well and radiographically there is no change, so he is submited only to periodic vigilance.
300 . A. Vifmela, F. Fernandez-Rojo and A. Gonzalez-Nunez
Fig. 5. PAP technique for Factor VIII related antigen. Elective coloration of anomalous endothelial cells on a stainless background. (105 x).
Nevertheless, it must be kept in mind that six years can be a too short period for judging the final behavior of this lesion, sinceJa Craver and Brown' (1979) patient was alive twenty five years after the initial exeresis of the primitive bone tumor, having been resected two pulmonary metastasis at 15 and 20 years from the onset. Acknowledgement. We are grateful to Dr. L. Bacariza for permission to publish this case and for clinical data.
References 1 Campanacci M, Boriani S, Giunti A (1980) Hemangioendothelioma of bone. A Study of 29 cases. Cancer 46: 804-814 2 Craver WL, Brown BS (1979) Hemangioendothelioma of Bone with Pulmonary Metastases: A 25-year Course. Report of a Case. Cancer 43: 1917-1923 3 Dahlin DC (1978) Bone Tumors. General Aspects and Data on 6,221 cases. Third Edition, pp 344-355, Ch C Thomas, Springfield, Illinois 4 Dorfman HD, Steiner GC, Jaffe HL (1971) Vascular Tumors of Bone. Hum Path 2: 349-376 5 Eady RAJ, Wilson-Jones E (1977) Pseudo pyogenic Granuloma: Enzyme Histochemical and Ultrastructural Study. Hum Path 8: 653-668
6 Hartman WH, Stewart FW (1962) Hemangioendothelioma of Bone; Unusual Tumor Characterized by Indolent Course. Cancer 15: 846-854 7 MacIver AG, Giddingsan J, Mepham BL (1979) Demontration of Extracellular Immunoproteins in Formol-fixed Renal Biopsy Specimens. Kidney International 16: 632-636 8 Rosai J, Gold J, Landy R (1979) The Histiocytoid Hemangiomas: A Unifying Concept Embracing Several Previously Described Entities of Skin, Soft Tissue, Large Vessels, Bone and Heart. Hum Path 10: 707-730 9 Schajowicz F, Ackerman LV, Sissons HA (1972) Tipos histologicos de tumores oseos. pp 42-43 Geneve, WHO 10 Spjut HJ, Dorfman HD, Fechner RE, Ackerman LV (1970) Tumors of bone and cartilage. AFIP number 5, pp 334-340 11 Srinivasan CK, Patel MR, Pearlman HS, Silver JW (1978) Malignant hemangioendothelioma of bone. Review of the literature and report of two cases. J Bone and Joint Surg (Am) 60: 696-700 12 Steiner GC, Dorfman HD (1972) Ultrastructure of hemangioendothelial sarcoma of bone. Cancer 29: 122-135 13 Stout AP (1943) Hemangio-endothelioma: A tumor of blood vessels featuring vascular endothelial cells. Ann Surg 118: 445-464 14 Unni KK, Ivins JC, Beabout JW, Dahlin DC (1971) Hemangioma, hemangiopericytoma and hemangioendothelioma (anriosarcoma) of bone. Cancer 27: 1403-1414 1 Wright DH, Padley HR, Judd MA (1981) Angiolymphoid Hyperplasia with Eosinophilia simulating lymphadenopathy. Histopathology 5: 127-140
Received November 8, 1982 . Accepted February 10, 1983
Key words: Bone - Hemangioendothelioma - Angiosarcoma - Histiocytoid hemangioma - Necrosis Dr. A. Vinuela, Residencia Sanitaria S.S., Leon, Spain