DOI: 10.1148/rg.261055017
RadioGraphics 2006;26:265-270
© RSNA, 2006
Best Cases from the AFIP
Epithelioid Hemangioendothelioma of Bone1
Olivier Larochelle, MD,
Martine Périgny, MD,
Réal Lagacé, MD, FRCPC,
Norbert Dion, MD, FRCSC and
Caroline Giguère, MD, FRCPC
1 From the Departments of Radiology (O.L., C.G.), Pathology (M.P., R.L.), and Orthopedic Surgery (N.D.), Centre Hospitalier Universitaire de Québec, L’Hôtel-Dieu de Québec, Laval University, 11 côte du Palais, Québec City, Québec, Canada G1R 2J6. Received January 31, 2005; revision requested March 2 and received April 18; accepted April 22. All authors have no financial relationships to disclose.
Address correspondence to O.L. (e-mail: olivier.larochelle.2{at}ulaval.ca).
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History
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A 57-year-old man complained of right ankle pain that had increased gradually over several months. The patient stated that walking increased the pain. There were no significant findings (eg, history of smoking or neoplasia) at review of systems. At physical examination, edema associated with pain was noted around the ankle, which demonstrated limited movement.
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Imaging Findings
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Radiography of the right ankle demonstrated multiple lytic lesions with ill-defined borders involving the distal tibial metaphysis and the talus. Cortical destruction without periosteal reaction was also noted (Fig 1).
Bone scintigraphy showed increased radionuclide uptake in the distal tibia and talus (Fig 2). There were also foci of increased uptake in several right ribs, findings that were compatible with acute fractures sustained in a recent fall.
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Figure 2. Bone scintigram demonstrates increased radionuclide uptake in the distal tibia and talus. The focal areas of increased uptake in several right lower ribs represent fractures sustained in a recent fall.
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Nonenhanced computed tomography (CT) demonstrated multifocal eccentric lytic lesions in the tibia and talus involving both the medullar cavity and the cortex (Fig 3). The largest lesion was localized in the distal talus with cortical disruption.
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Figure 3. Axial nonenhanced CT scan of the distal tibia shows multiple osteolytic lesions (arrows) with cortical disruption. No periosteal reaction or mineralized matrix is seen, nor is there any evidence of a soft-tissue mass.
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Magnetic resonance (MR) imaging of the right ankle showed multiple nodular masses with low signal intensity on T1-weighted images (Fig 4) and high signal intensity on T2-weighted images. The lesions were characterized by homogeneous enhancement after the injection of gadolinium-based contrast material (Fig 5). The largest lesion measured 8 x 3x 3 cm and originated at the anteromedial portion of the talus, with a joint extension superior to the anterior part of the distal tibial epiphysis (Fig 6). There was also a lesion on the posterior distal tibia that measured 3 x 2.5 cm; this lesion was in close relation to the articular surface with a thin residual line of cortex (Fig 6). Other lesions were in close contact with the cortex without transgression (Fig 7). There was mild soft-tissue edema with minimal joint effusion. Edematous bone reaction surrounding the lesions was also seen. CT of the chest and ultrasonography of the abdomen showed no sign of other lesions. Initially, the patient was thought to have metastasis, infection, and myeloma.
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Figure 4. Axial nonenhanced T1-weighted MR image (repetition time msec/echo time msec = 400/23) shows the same osteolytic lesions (arrows) of the distal tibia. The lesions are homogeneously hypointense and have destroyed the adjacent cortex.
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Figure 5. On an axial gadolinium-enhanced fat-suppressed T1-weighted MR image (416/19), the lesions demonstrate marked homogeneous enhancement. Note also the bone marrow edema (arrows).
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Figure 6. Sagittal gadolinium-enhanced fat-suppressed T1-weighted MR image (450/17) shows enhanced lesions involving the anterior distal tibia with a joint extension (arrow). Arrowheads indicate edema in the bone and surrounding soft tissue. A second lesion is seen at the base of the talus neck and protruding into the talus sinus, with a third lesion on the posterosuperior part of the talus.
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Figure 7. Coronal fast relaxation fast spin-echo T2-weighted MR image (2400/23) shows two homogeneously hyperintense lesions (arrows) in the distal tibia with bone marrow edema (arrowhead).
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Pathologic Evaluation
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Following the diagnosis of epithelioid hemangioendothelioma (EH) on the basis of findings at open biopsy, the patient decided, after discussion with his orthopedic surgeon, to undergo a right below-knee amputation. The specimen was submitted for pathologic evaluation. Three separate red, gelatinous lesions with irregular borders were present in the distal tibia (Fig 8). The largest lesion (3.8 cm) was localized on the anteromedial side and protruded into the articular surface, with destruction of the cortex. The other two lesions measured 2 and 1.2 cm and were located on the posterior and anterolateral aspects of the distal tibia, respectively. There were also two lesions in the talus (Fig 9), one measuring 3.5 cm and localized on the posterior and anterior side with intra-articular involvement, and the other measuring 1 cm and situated on the anterior side.
At conventional light microscopy, the tumor showed solid nests and anastomosing cords of epithelioid cells with abundant eosinophilic cytoplasm (Fig 10). Cells were polygonal or spindle shaped and sometimes contained intracytoplasmic vacuoles, creating a signet ring–like appearance. There were few mitoses as well as mild pleomorphism. Distinct vascular channels lying in a fibromyxoid stroma and neoplastic extension to the cortex and soft tissues could also be seen. Tumor cells were immunoreactive for vascular and stromal markers (vimentin, CD34, factor VIII) but were negative for epithelial cytokeratin markers (CAM 5.2, AE1–AE3). The overall morphologic features were diagnostic for an EH.
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Figure 10. Photomicrograph (original magnification, x250; hematoxylin-eosin stain) of a characteristic area of the tumor shows tumor cells (arrows) with intracytoplasmic vacuolization having a signet ring–like appearance.
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Discussion
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EH is a rare endothelial vascular neoplasm that was first identified and described in soft tissues in 1982 by Weiss and Enzinger (1). This initial study has since been followed by case reports on other locations such as liver, lung, and bone. EH is defined as an intermediate-grade malignant vascular neoplasm whose clinical course is between those of epithelioid hemangioma and angiosarcoma. It can occur at almost any age (1), most frequently during the 2nd and 3rd decades of life, with a male predilection of approximately 2:1 (2,3). Generally, patients complain of pain and swelling in the affected area. Hemolytic anemia and consumption coagulopathy have been reported but are rare. Pathologic fractures may also occur. EH most commonly involves the calvarium, axial skeleton, and lower limbs. The most frequently affected long bones are the tibia (23% of cases), femur (18%), and humerus (13%) (3), either proximally or distally. In over 50% of cases, multifocal disease is seen, with either multiple lesions in a single bone or multiple bone involvement. EH has a tendency to involve bones of the same region, most frequently the foot. Visceral involvement (lung, liver, or spleen) is less common. The location can be metaphyseal, diaphyseal, or, less commonly, epiphyseal.
At gross examination, EH is a well-circumscribed tumor with irregular borders and a soft, bright red hemorrhagic appearance (4,5). The tumor consists of solid nests and anastomosing cords of round, polygonal, or spindle-shaped cells with eosinophilic cytoplasm. Intracytoplasmic vacuolization, indicating primitive vascular channels, is characteristic. There are few mitoses and only mild pleomorphism.
Radiography and CT typically reveal a lytic lesion without matrix mineralization, and osseous expansile remodeling may be seen. These lesions can be localized in the cortical or medullary bone. Calcification is rare, and periosteal reaction is rare in the absence of pathologic fracture. Cortical disruption and extension into soft tissues can be present. Joint invasion is a common feature. Homogeneous enhancement is present at contrast material–enhanced CT.
There is no specific pattern of signal intensity at MR imaging. Most frequently, EH has low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with homogeneous enhancement after the injection of gadolinium-based contrast material. Interestingly, serpentine vascular structures are not typically seen at MR imaging of EH of bone, findings that would suggest the diagnosis (3). This phenomenon is likely related to the small size of the vascular channels and the hyper-cellularity seen at pathologic analysis.
The differential diagnosis for EH of bone should include angiomatosis, Langerhans cell histiocytosis (LCH), angiosarcoma, infection, myeloma, metastasis, and lymphoma.
Skeletal angiomatosis, also known as cystic angiomatosis, is a rare, multicentric benign vascular tumor characterized by multiple cystic lesions throughout the entire skeleton. Visceral involvement is also often seen, especially in the spleen. Although radiologic features are nonspecific, calcified phleboliths can sometimes be seen in soft tissues.
LCH is a benign tumor characterized by histiocytic infiltration. It is most often seen in children during the first 2 decades of life. LCH normally has a monostotic appearance, although a polyostotic pattern can be seen in up to 20% of cases (6). LCH may appear aggressive, with a permeative pattern and a soft-tissue mass. The calvarium, femur, and axial skeleton are the most frequently affected bones.
Angiosarcoma, a high-grade malignant vascular tumor, is very rare and is difficult to differentiate histologically from the less aggressive hemangioendothelioma. It occurs during the 4th and 5th decades of life. Osseous angiosarcoma is characterized by an aggressive permeative appearance without mineralization. Polyostotic lesions are seen in 38% of angiosarcomas and have a regional pattern (6). The metaphyses of the femur, tibia, and humerus are the most common locations.
Osteomyelitis can also manifest as multiple aggressive lytic lesions. A serpiginous lytic pattern is more specific for infection. In addition, sequestrum and involucrum are often seen in osteomyelitis. A soft-tissue abscess with a sinus tract and extensive inflammatory changes is also seen. The enhancement surrounding the abscess will be regular, in contrast with the nodular enhancing pattern seen in tumor necrosis.
Multiple myeloma is a neoplastic proliferation of plasma cells in patients over 40 years of age. Many "punched-out" lytic lesions can be seen in the skull, vertebral bodies, ribs, and pelvis. Diffuse osteopenia may be present without focal lytic lesions.
Metastatic disease of bone is more common than any primary bone tumor. Metastatic lytic lesions almost always arise from primary tumors of the lung, breast, kidney, thyroid gland, and gastrointestinal tract. The pattern of these lesions is more diffuse than regional. The presence of lytic lesions in a patient with a positive history for neoplasm is highly suggestive of metastatic disease.
Primary lymphoma of the bone is very rare. It is most commonly seen in patients between 30 and 60 years of age. Lymphoma typically manifests as permeative, aggressive lytic lesions, usually involving the diaphysis of the long bones, pelvis, and scapula. The lesion can grow rapidly, with a disproportion between the very large soft-tissue mass and the cortical destruction. Because of the rapid growth of the tumor and the lack of blood supply, sequestrum can be seen, as in osteomyelitis.
Despite all of these specific radiologic findings, however, the definitive diagnosis of EH is often difficult to make on the basis of radiologic findings alone. Therefore, the final diagnosis of EH requires histopathologic analysis.
EH of bone is a locally destructive tumor with a variable course. Its behavior cannot be predicted on the basis of histologic features alone. Some studies have reported a better prognosis with a multifocal tumor (2,7), although the number of cases studied is limited. However, visceral involvement seems to be the most important criterion in predicting a poor prognosis (8). Because of the potential for multifocal bone or visceral involvement, patients should be thoroughly evaluated with CT of the chest and abdomen, bone scintigraphy, and a skeletal survey. In one series, 13% of EHs of soft tissue developed local recurrence, and 31% developed regional or distant metastasis (9); however, there are only a few data for EH of bone. The clinical course is variable; consequently, the choice of treatment is not well established. Although most studies recommend wide surgical resection (3,8,10), limited surgery (curettage) is also an option (7,11). Successful radiofrequency ablation with a multimodal approach was reported for the treatment of two lesions in a patient with multiple areas of bone involvement (12). Radiation therapy can be used, either alone or in conjunction with and after surgery, particularly for unresectable lesions or meta-static disease. The role of chemotherapy is not yet clear. At present, treatment plans should be tailored to the individual patient in correlation with the extension and location of the disease. In our case, the patient continues to do well 8 months after undergoing amputation, with no evidence of recurrence or metastasis.
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Footnotes
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Abbreviations: EH = epithelioid hemangioendothelioma, LCH = Langerhans cell histiocytosis
Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer 1982;50:970–981.[CrossRef][Medline]
- Tsuneyoshi M, Dorfman HD, Bauer TW. Epithelioid hemangioendothelioma of bone: a clinicopathologic, ultrastructural, and immunohistochemical study. Am J Surg Pathol 1986;10:754–764.[Medline]
- Ignacio EA, Palmer KM, Mathur SC, Schwartz AM, Olan WJ. Residents’ teaching files: epithelioid hemangioendothelioma of the lower extremity. RadioGraphics 1999;19:531–537.[Free Full Text]
- Dorfman HD, Czerniak B. Vascular lesions. In: Dorfman HD, Czerniak B, eds. Bone tumors. St Louis, Mo: Mosby, 1998; 769–795.
- Forest M. Vascular tumors. In: Forest M, Tomeno B, Vanel D, eds. Orthopedic surgical pathology. Edinburgh, Scotland: Churchill Livingstone, 1998; 345–362.
- Manaster BJ. Vascular tumors. In: Thrall JH, ed. Musculoskeletal imaging: the requisites. 2nd ed. St Louis, Mo: Mosby, 2002; 65–68.
- Roessner A, Boehling T. Vascular tumors. In: Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization classification of tumors, pathology and genetics, tumors of soft tissue and bone. Lyon, France: IARC, 2002; 319–323.
- Kleer CG, Unni KK, McLeod RA. Epithelioid hemangioendothelioma of bone. Am J Surg Pathol 1996;20:1301–1311.[CrossRef][Medline]
- Enzinger FM, Weiss SW. Soft tissue tumor. 4th ed. St Louis, Mo: Mosby, 2001; 891–914.
- Gosheger G, Hardes J, Ozaki T, Horst E, Burger H, Winkelmann W. The multicentric epithelioid hemangioendothelioma of bone: a case example and review of the literature. J Cancer Res Clin Oncol 2002;128:11–18.[CrossRef][Medline]
- Fechner RE, Mills SE. Vascular lesions. In: Rosai J, ed. Atlas of tumor pathology: tumors of the bones and joints, fasc 8, ser 3. Washington, DC: Armed Forces Institute of Pathology, 1993; 129–144.
- Rosenthal DI, Treat ME, Mankin HJ, Rosenberg AE, Jennings CL. Treatment of epithelioid hemangioendothelioma of bone using a novel combined approach. Skeletal Radiol 2001;30:219–222.[CrossRef][Medline]
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History
Imaging Findings
