Skeletal Radiol (1992) 21:538-541
Skeletal Radiology
Case report 759 Eamon Carmody, F.F.R.R.C.S.I. 1, Barbara Loftus, M.R.C. Path. 2, John Corrigan, F.R.C.S. 3, Tim O'Sullivan, F.R.C.S. 3, Mary Leader, M.R.C. Path. 2, and Frank Keeling, F.R.C.R. 1 Departments of 1 Radiology, z Pathology, and 3 Orthopaedics, Beaumont Hospital, Dublin, Ireland
Radiological studies
Fig. 1. Radiograph of lcft tibia and fibula demonstrating multiple, small, well-defined, lytic lesions involving the tibia, fibula, and talus
9 1992 International Skeletal Society
Fig. 2. Radiograph of the left tibia and fibula obtained 8 weeks later demonstrated an increase in size and number of lytic lesions affecting the tibia, fibula, and talus
Fig. 3. Radiograph of left femur demonstrates multiple, well-defined lytic lesions involving the neck and shaft of the femur
E. Carmody et al. : Case report 759 Clinical information
In September 1990, a 48-year-old white man presented to the orthopaedic clinic for assessment of a painful left ankle. One month prior to his presentation, he had twisted his ankle, but the pain had not settled. He had no relevant medical history and was otherwise well. Radiographs of the left ankle and left tibia and fibula were considered normal (Fig. 1), and conservative treatment with a support bandage was instituted. Eight weeks later the patient was again reviewed, complaining of pain Correspondence to: Dr. Eamon Carmody, Department of Radiology, Sunnybrook Health Science Centre, 2075 Bayview Avenue, North York, Ontario M4N 3M5, Canada
539 now extending to the left calf. Examination revealed mild swelling on the dorsum of the left foot and local tenderness along the medial malleolus and upper end of the tibia. On review of the previous radiographs from September, several small osteolytic lesions were seen in the tibia, fibula and talus. Myeloma or metastatic carcinoma was considered the most likely cause, and a skeletal survey was carried out; this revealed a dramatic increase in the number and size of the lytic lesions affecting the left tibia, fibula and left foot (Fig. 2). Additionally, the same process involved the left femur (Fig. 3) and the left ilium. The lytic lesions had welldefined margins but no bony expansion or periosteal reaction. The remainder of the skeleton was normal.
A technetium-99m methylene diphosphonate (99mTc-MDP) bone scan confirmed that the disorder was confined to the left lower limb and left ilium. A full blood count, serum urea and electrolytes, serum proteins, protein electrophoresis and bone marrow aspirate were all normal. The erythrocyte sedimentation rate (ESR) was mildly elevated at 35 mm/ h, and the serum alkaline phosphatase was also mildly elevated at 340 IU/1 (normal < 230). Human immunodeficiency virus (HIV) status was negative. Chest roentgengrams and ultrasound of the liver and abdomen were normal. An open biopsy of the left tibia was performed.
540
Diagnosis: Malignant epithelioid haemangioendotheliomaof bone Microscopically, the features were those of a malignant vascular tumour with vascular channels of varying sizes lined by plump, atypical endothelial cells (Fig. 4). Solid areas were also present. The tumour cells were large with rounded nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, conferring an "epithelioid" appearance. Cytoplasmic vacuolisation was also seen, with moderate pleomorphism and a mitotic count of 4 per l0 high power fields in the most cellular areas. Immunohistochemistry showed that the tumour cells were strongly positive for Factor VIII related antigen (Factor VIII RAg) and for vimentin. They were negative for cytokeratins. A diangosis of malignant epithelioid hemangioendothelioma was made.
E. Carmody et al. : Case report 759
Discussion Weiss and Enzinger [5] proposed the term epithelioid hemangioendothelioma (EH) to desribe an unusual, low-grade, malignant vascular tumor of soft tissue. Similar tumours have also been described in the lung [1], liver [2], and more recently in bone [3]. The tumours are characterised by the "epithelioid" endothelial cell which is Factor VIII RAg positive but, unlike normal endothelial cells, has a superabundance of vimentin intermediate filaments [6]. Intracytoplasmic vacuolisation is the second prominent feature and represents primitive vascular lumen formation. The vacuoles have been confused with the mucin vacuoles of metastatic adenocarcinoma, and indeed the cells may have a "signet-ring" appearance. However, mucin stains are consistently negative, as is immuno-
Pathological study
Fig. 4. Vascular channels of varying sizes lined by plump endothelial cells showing moderate pleomorphism (H&E, x 600)
staining for cytokeratins. Ultrastrucrurally, Wiebel-Palade bodies, a feature of normal endothelial cells, may be seen. Maruyama et al. [3] were the first to use the term EH in relation to an unusual tumour in bone. Tsuneyoshi et al. [4] described 14 such cases, and the histological features were similar to those described for soft tissue, lung and liver. The tumour is considered of low-grade malignancy [6]. The majority of patients affected are men, usually under the age of 30 years (range 7-76 years), with a second peak in the later decades [4]. Localized pain and pathological fracture are the usual modes of presentation. The chief sites of involvement are the skull, axial skeleton and lower extremities. Approximately 50% of the tumours show a polyostotic distribution, with a predilection for the lower limbs [4]. In addition, the bones involved are usually confined to one limb or are in continuity, as in this case. Characteristically, the affected bones show a multifocal involvement, emphasizing the need for a complete skeletal survey in these patients. Radiologically, this tumor presents as a solitary or multifocal and/or polyostotic process. A purely osteolytic appearance, with or without bony expansion, can occur. Local extension beyond the periosteum does occur occasionally. Some lytic lesions can produce a coarse trabeculated or honeycomb pattern suggestive of a vascular tumor [6]. Varying degrees of peripheral sclerosis may be seen around the margins of lytic lesions. A primary sclerotic lesion has not been described. The prognosis in the disease is not defined but appears to run a clinical course between that of a haemangioma and angiosarcoma of bone. The majority of the reported cases run an indolent course, particularly in a case of polyostotic disease; however, a minority of cases show aggressive behaviour, associated with cellular pleomorphism and increased mitotic activity [6]. The treatment of choice is complete local excision.
E. Carmody et al. : Case report 759
Clinical follow-up A hindquarter amputation was recommended but refused by the patient. In January 1991, a repeat skeletal and 99mTc-MDP bone scan revealed further bone destruction, again confined to the lower limb and left ilium. The patient was now experiencing widespread pain in his left leg and was mobile only with the aid of crutches. By May 1991, the turnout had spread to the sacrum. In summary, we present a patient with malignant epithelioid haemangioendothelioma of bone. Radiologically, this tumor demonstrates multifocal and polyostotic involvement, confined to the left lower limb and left ilium. This radiological pattern
541
is characteristic and should suggest the diagnosis. The earlier literature has suggestions that the multifocal, polyostotic form of this tumour follows an indolent course; however; our experience suggests that this form of presentation can be associated with rapid progression of the disease.
Acknowledgements. We wish to thank Dr. Andrew Huvos, Memorial Sloan Kettering Cancer Center, New York, and Dr. Denis Stoker, Royal National Orthopaedic Hospital, London, for reviewing the pathological and radiologicai features of this case.
References 1. Dail DH, Liebow AA (1975) Intravascular bronchio-alveolar tumour (abstract). Am J Pathol 78 : 6
2. Ishak KG, Sesterhenn LA, Goodman MZD, Rabin L, Stronmyer FW (1984) Epithelioid haemangioendothelioma of the liver, a clinicopathological and follow-up study of 32 cases. Hum Pathol 15:839 3. Maruyama N, Kmagai Y, Ishida Y, et al. (1985) Epithelioid haemangioendothelioma of the bone tissue. Virchows Arch (A) 407 : 159 4. Tsuneyoshi M, Dorfman t-ID, Bauer TW (1986) Epithelioid haemangioendothelioma of bone. Am J Surg Pathol 10:754 5. Weiss SW, Enzinger FM (1982) Epithelioid haemangioendothelioma. A vascular turnout often mistaken for a carcinoma. Cancer 50: 970 6. Weiss SW, Ishak GK, Dail DH, et al. (1986) Epithelioid haemangioendothelioma and related lesions. Semin Diagn Pathol 3 :259
Skeletal Radiology
Case report 759 Eamon Carmody, F.F.R.R.C.S.I. 1, Barbara Loftus, M.R.C. Path. 2, John Corrigan, F.R.C.S. 3, Tim O'Sullivan, F.R.C.S. 3, Mary Leader, M.R.C. Path. 2, and Frank Keeling, F.R.C.R. 1 Departments of 1 Radiology, z Pathology, and 3 Orthopaedics, Beaumont Hospital, Dublin, Ireland
Radiological studies
Fig. 1. Radiograph of lcft tibia and fibula demonstrating multiple, small, well-defined, lytic lesions involving the tibia, fibula, and talus
9 1992 International Skeletal Society
Fig. 2. Radiograph of the left tibia and fibula obtained 8 weeks later demonstrated an increase in size and number of lytic lesions affecting the tibia, fibula, and talus
Fig. 3. Radiograph of left femur demonstrates multiple, well-defined lytic lesions involving the neck and shaft of the femur
E. Carmody et al. : Case report 759 Clinical information
In September 1990, a 48-year-old white man presented to the orthopaedic clinic for assessment of a painful left ankle. One month prior to his presentation, he had twisted his ankle, but the pain had not settled. He had no relevant medical history and was otherwise well. Radiographs of the left ankle and left tibia and fibula were considered normal (Fig. 1), and conservative treatment with a support bandage was instituted. Eight weeks later the patient was again reviewed, complaining of pain Correspondence to: Dr. Eamon Carmody, Department of Radiology, Sunnybrook Health Science Centre, 2075 Bayview Avenue, North York, Ontario M4N 3M5, Canada
539 now extending to the left calf. Examination revealed mild swelling on the dorsum of the left foot and local tenderness along the medial malleolus and upper end of the tibia. On review of the previous radiographs from September, several small osteolytic lesions were seen in the tibia, fibula and talus. Myeloma or metastatic carcinoma was considered the most likely cause, and a skeletal survey was carried out; this revealed a dramatic increase in the number and size of the lytic lesions affecting the left tibia, fibula and left foot (Fig. 2). Additionally, the same process involved the left femur (Fig. 3) and the left ilium. The lytic lesions had welldefined margins but no bony expansion or periosteal reaction. The remainder of the skeleton was normal.
A technetium-99m methylene diphosphonate (99mTc-MDP) bone scan confirmed that the disorder was confined to the left lower limb and left ilium. A full blood count, serum urea and electrolytes, serum proteins, protein electrophoresis and bone marrow aspirate were all normal. The erythrocyte sedimentation rate (ESR) was mildly elevated at 35 mm/ h, and the serum alkaline phosphatase was also mildly elevated at 340 IU/1 (normal < 230). Human immunodeficiency virus (HIV) status was negative. Chest roentgengrams and ultrasound of the liver and abdomen were normal. An open biopsy of the left tibia was performed.
540
Diagnosis: Malignant epithelioid haemangioendotheliomaof bone Microscopically, the features were those of a malignant vascular tumour with vascular channels of varying sizes lined by plump, atypical endothelial cells (Fig. 4). Solid areas were also present. The tumour cells were large with rounded nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, conferring an "epithelioid" appearance. Cytoplasmic vacuolisation was also seen, with moderate pleomorphism and a mitotic count of 4 per l0 high power fields in the most cellular areas. Immunohistochemistry showed that the tumour cells were strongly positive for Factor VIII related antigen (Factor VIII RAg) and for vimentin. They were negative for cytokeratins. A diangosis of malignant epithelioid hemangioendothelioma was made.
E. Carmody et al. : Case report 759
Discussion Weiss and Enzinger [5] proposed the term epithelioid hemangioendothelioma (EH) to desribe an unusual, low-grade, malignant vascular tumor of soft tissue. Similar tumours have also been described in the lung [1], liver [2], and more recently in bone [3]. The tumours are characterised by the "epithelioid" endothelial cell which is Factor VIII RAg positive but, unlike normal endothelial cells, has a superabundance of vimentin intermediate filaments [6]. Intracytoplasmic vacuolisation is the second prominent feature and represents primitive vascular lumen formation. The vacuoles have been confused with the mucin vacuoles of metastatic adenocarcinoma, and indeed the cells may have a "signet-ring" appearance. However, mucin stains are consistently negative, as is immuno-
Pathological study
Fig. 4. Vascular channels of varying sizes lined by plump endothelial cells showing moderate pleomorphism (H&E, x 600)
staining for cytokeratins. Ultrastrucrurally, Wiebel-Palade bodies, a feature of normal endothelial cells, may be seen. Maruyama et al. [3] were the first to use the term EH in relation to an unusual tumour in bone. Tsuneyoshi et al. [4] described 14 such cases, and the histological features were similar to those described for soft tissue, lung and liver. The tumour is considered of low-grade malignancy [6]. The majority of patients affected are men, usually under the age of 30 years (range 7-76 years), with a second peak in the later decades [4]. Localized pain and pathological fracture are the usual modes of presentation. The chief sites of involvement are the skull, axial skeleton and lower extremities. Approximately 50% of the tumours show a polyostotic distribution, with a predilection for the lower limbs [4]. In addition, the bones involved are usually confined to one limb or are in continuity, as in this case. Characteristically, the affected bones show a multifocal involvement, emphasizing the need for a complete skeletal survey in these patients. Radiologically, this tumor presents as a solitary or multifocal and/or polyostotic process. A purely osteolytic appearance, with or without bony expansion, can occur. Local extension beyond the periosteum does occur occasionally. Some lytic lesions can produce a coarse trabeculated or honeycomb pattern suggestive of a vascular tumor [6]. Varying degrees of peripheral sclerosis may be seen around the margins of lytic lesions. A primary sclerotic lesion has not been described. The prognosis in the disease is not defined but appears to run a clinical course between that of a haemangioma and angiosarcoma of bone. The majority of the reported cases run an indolent course, particularly in a case of polyostotic disease; however, a minority of cases show aggressive behaviour, associated with cellular pleomorphism and increased mitotic activity [6]. The treatment of choice is complete local excision.
E. Carmody et al. : Case report 759
Clinical follow-up A hindquarter amputation was recommended but refused by the patient. In January 1991, a repeat skeletal and 99mTc-MDP bone scan revealed further bone destruction, again confined to the lower limb and left ilium. The patient was now experiencing widespread pain in his left leg and was mobile only with the aid of crutches. By May 1991, the turnout had spread to the sacrum. In summary, we present a patient with malignant epithelioid haemangioendothelioma of bone. Radiologically, this tumor demonstrates multifocal and polyostotic involvement, confined to the left lower limb and left ilium. This radiological pattern
541
is characteristic and should suggest the diagnosis. The earlier literature has suggestions that the multifocal, polyostotic form of this tumour follows an indolent course; however; our experience suggests that this form of presentation can be associated with rapid progression of the disease.
Acknowledgements. We wish to thank Dr. Andrew Huvos, Memorial Sloan Kettering Cancer Center, New York, and Dr. Denis Stoker, Royal National Orthopaedic Hospital, London, for reviewing the pathological and radiologicai features of this case.
References 1. Dail DH, Liebow AA (1975) Intravascular bronchio-alveolar tumour (abstract). Am J Pathol 78 : 6
2. Ishak KG, Sesterhenn LA, Goodman MZD, Rabin L, Stronmyer FW (1984) Epithelioid haemangioendothelioma of the liver, a clinicopathological and follow-up study of 32 cases. Hum Pathol 15:839 3. Maruyama N, Kmagai Y, Ishida Y, et al. (1985) Epithelioid haemangioendothelioma of the bone tissue. Virchows Arch (A) 407 : 159 4. Tsuneyoshi M, Dorfman t-ID, Bauer TW (1986) Epithelioid haemangioendothelioma of bone. Am J Surg Pathol 10:754 5. Weiss SW, Enzinger FM (1982) Epithelioid haemangioendothelioma. A vascular turnout often mistaken for a carcinoma. Cancer 50: 970 6. Weiss SW, Ishak GK, Dail DH, et al. (1986) Epithelioid haemangioendothelioma and related lesions. Semin Diagn Pathol 3 :259
