epithelioid hemangioendothelioma of the bone

Epithelioid hemagioendothelioma (EH) is a rare vascular tumor with an intermediate biological behavior between hemangioma and angiosarcoma.

Bone location is even more rare, and because the number of reported cases of EH is small and the follow-up periods short, the best surgical treatment, the role of radiotherapy and chemotherapy, as well as the definitive prognosis are still not established.

Epithelioid hemangioendothelioma (EH) is a rare vascular soft tissue tumor of intermediate malignancy. Although initially described as most common in the soft tissues of the extremities, other locations are possible, namely bone. Reported cases of spinal involvement are extremely rare and follow-up periods have been too short, so the best management and prognosis for these lesions is still not clear.

Vascular tumors account for less than 1% of all bone tumors. Malignant primary vascular tumors of bone are even more rare and include angiosarcoma and hemangioendothelioma.

EH was first described by Weiss and Enzinger in 1982 as a rare vascular lesion with an epithelioid appearance.

The tumor is composed of a discrete population of epithelioid endothelial cells arranged to resemble primitive capillaries with an intermediate biological behavior between hemangioma and angiosarcoma.

EH represents 1% of all vascular neoplasms and is locally aggressive.

Although initially described as being most common in the soft tissues of the extremities, other reported sites of occurrence include the liver, lung, breast, meninges, brain and long bones.

Osseous EH is an extremely rare lesion. Commonly affected bones include tibia (25%), femur (20%), metatarsals (15%), fibula (10%) and humerus
(10%). Vertebrae represent only 10% of all reported
cases.

Multiple lesions may be present either in the same bone (particularly the tibia and fibula), in adjacent bones in the same limb, in widely separated bones, or in nearby or distant soft tissues.

There seems to be no gender predilection, although some authors consider it to be more frequent in males. The highest incidence occurs in the third and fourth decades.

Recently a rare association with neurofibromatosis type I has been
reported.

Clinical features

Clinically, osseous EH presents with pain and swelling, especially if the affected bone is superficial, or as an enlarging mass (most are smaller than
5 cm.), and pathological fractures can occur in nearly 10% of the patients.

If the spine is involved, the lesion may cause radicular symptoms or
paraplegia, indicating urgent intervention.

Radiology

Radiographically, EH appears as an expansive, osteolytic lesion well demarcated if small (1-2 cm) or poorly demarcated if large. It has a distinctive soap-bubble matrix with a sclerotic margin like that found in benign vascular tumors, with no periostal reaction.

Lesions with ill-defined margins and loss of trabeculae are considered more aggressive.

Radiographic findings may be nonspecific and differential diagnosis should include osteomyelitis, aneurismal bone cyst, giant cell tumor, osteolytic sarcomas, lymphomas and metastasis.

On CT-scan these lesions enhance with contrast media, and though nondiagnostic, it may outline the extent of bone destruction and help distinguish EH from hemangioma, which has a characteristic CT appearance.

MRI findings are nonspecific. In T1-weighted contrast sequences, bone tumors of vascular origin show higher intensities than skeletal muscles
but lower intensities than fat; in pulse sequences emphasizing a T2 contrast, signal intensities of vascular bone tumors are considerably higher than intensities of muscle and fat.

Macroscopy

On gross pathology examination, EH present as reddish-brown lobulated masses, well demarcated with irregular scalloped borders and a bright
red hemorrhagic appearance.

Microscopy

Microscopically, the tumor is characterized by anastomosing cords, solid nests, or short strands of round to slightly spindled eosinophilic neoplastic endothelial cells embedded in a chondroid-like or hyalinized stroma.

Rarely large and distinct vascular channels are identified in the center of the tumor, as contrasted with the periphery of the lesion, and mitotic activity seldom is identified in these tumors.

In some instances, osteoclastic giant cells can be observed, and in others these tumors show atypical histological features such as marked nuclear atipia, higher mitotic activity, spindling of the neoplastic cells and necrosis,
which are associated with a more aggressive course.

Immunochemistry

Immunohistochemical analysis reveals that the tumor cells are positive for vimentin and endothelial markers such as factor VIII-related antigen, ulex
europaeus lectin, CD31 and CD349.

Differential diagnosis

Histological differential diagnosis mainly includes metastatic carcinoma in bone in which immunohistochemical demonstration of keratin and epithelial membrane antigen identifies the adenocarcinoma cells in the absence of reactivity for endothelial markers.

Grading

Campanacci et al. classified EH in 3 grades of malignancy, based on the morphology and differentiation of angioblasts, being treatment and
prognosis grade-dependent.

According to these criteria the present case could be classified as Grade
I EH.

Treatment

Treatment can vary from simple curettage for grade I lesions to vertebrectomy with preoperative embolization for grade III tumors.

En bloc resection, following oncologic surgical principles, significantly improves results and should be attempted whenever possible.

Radiation seems beneficial and safe for treating surgically inaccessible
tumors, and has also been proposed as adjuvant therapy after surgical excision.

Although there may be a place for chemotherapy in the management
of EH, precise indications and regimens have not yet been established.

The prognosis is often favorable, particularly for low-grade lesions where complete excision is performed.

However local recurrence or even metastasis are possible.

Since the number of reported cases of EH is small and the follow-up periods short, the best surgical treatment, the role of radiotherapy
and chemotherapy, as well as the definitive prognosis
are still not established.

Open references

 Epithelioid hemangioendothelioma presenting as a vertebral fracture. Neves N, Lima-Rodrigues F, Ribeiro-Silva M, Cacho-Rodrigues P, Eloy C, Paiva ME, Pinto R. Acta Reumatol Port. 2010 Jul-Sep;35(3):370-4. PMID: 20975643 [Free]

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