Epithelioid angiosarcoma of bone: report of a case with immunohistochemical study

Abstracts

Angiossarcoma primário do osso é muito raro, representando menos de 1% de todos os angiossarcomas(4). Neoplasias vasculares também são incomuns, ocorrendo em 14% dos tumores malignos primários do osso. Os autores relatam caso em coluna lombar que merece atenção porque inicialmente tratava-se de um hemangioendotelioma, um tumor de malignidade intermediária, definido pelos critérios estabelecidos por Stout(11). Foi tratado com embolização local e radioterapia. Após dez anos, recidivou, com maior grau de malignidade, fenômeno interpretado como progressão tumoral, com características de Angiossarcoma epitelióide. O estudo imuno-histoquímico revelou positividade para marcadores vasculares. (Fator VIII, CD31 e CD34). O paciente evoluiu com metástases pulmonares. Em revisão bibliográfica, não foi encontado nenhum relato de caso semelhante, tendo em vista a longa evolução e progressão tumoral após dez anos de seguimento e expressão do fenotipo epitelióide.

Angiossarcoma; Neoplasia vascular óssea

ARTIGO ORIGINAL

Epithelioid angiosarcoma of bone: report of a case with immunohistochemical study^*

Claudia Regina G.C.M. de Oliveira^I; Olavo Pires de Camargo^II; Tarcísio E.P. Barros Filho^III; Reginaldo P. Oliveira^IV; Alberto T. Croci^V; André Matias Baptista^VI

^IHead, Pathological Anatomy Department

^IIHead, Tumor Group

^IIIHead, Spinal Column Group

^IVHead, Cervical Group

^VAssistant Physician, Tumor Group

^VITrainee Physician, Tumor Group

SUMMARY

Primary angiosarcoma of bone is rare and accounts for less than 1% of all angiosarcomas⁽⁴⁾.

Vascular bone neoplasms represent 1,4% of primary malignant bone tumors. The authors describe an unusual case of bone angiosarcoma located in the spine.

The diagnosis was initially hemangioendothelioma, a borderline endothelial vascular tumor, as stated by Stout⁽¹¹⁾. The lesion was treated by local embolization and radiation therapy.

The tumor recurred locally ten years later as a high-grade

angiosarcoma, showing epithelioid features, which indicates tumor progression.

Immunohistochemical studies were positive for vascular markers such as factor VIII, CD31 and CD 34. The patient developed lung metastasis.

I was not observed in the literature any other case with ten-year follow-up and tumor progression with epithelioid features.

Keywords: Angiosarcoma. Vascular tumors.

INTRODUCTION

Angiosarcoma is a malignant neoplasia, composed by endothelial cells with vasoforming characteristics (4). Only 1.4% of the malignant primary tumors of bone are categorized as angiosarcomas (3). In 1943, Stout (11) has morphologically distinguished at least two types of malignant tumors in the blood vessels, the hemangioendothelioma and the hemangiopericytoma; the former was characterized by proliferation of endothelial cells and the latter of pericytic cells. Hemangioendothelioma and angiosarcoma were previously used as synonyms. Unni et al. (12), as Ackerman and Spjut (10), considered that the malignant endothelial vascular tumors of bone could be classified as a single entity.

They choose the term hemangioendothelioma since angiosarcoma denoted a higher degree of malignancy evident in a few cases. Actually, these tumors evolution was variable, predominantly progressive and lethal (7).

The hemangioendothelioma, according to the final criterion of Stout, is observed in all age groups, mainly in males, more frequently in the long bones, usually the femur proximal region (13). They appear as a single lesion, but they can be multicentric (4). In these cases, prognosis is apparently better (4).

Radiographically, they appear as lithic lesions which occur with little or none reactional bone neoformation.

The cortical can be sharpened or destructed, reaching the soft tissues. Arteriovenous shunts can occur and arteriography can be useful to distinguish vascular and non-vascular tumors and to determine the extension of the invasion in the soft tissues.

Radiographically, the differential diagnosis includes clear cell carcinoma, metastatic carcinoma, Ewing sarcoma, hemangiopericytoma, osteosarcoma, lymphoma, fibrous dysplasia and aneurismal bone cyst (6).

CASE REPORT

In 1989, a thirty-two year-old male patient was seen in the Orthopedics and Traumatology Institute, "Hospital das Clínicas", FMUSP, complaining of pain in the spinal column and five-month duration paraparesis.

The X-rays revealed a radiolucent lesion spreading to the soft tissues in L3, lumbar column, parallel and longitudinal trabeculation, cortical destruction, no sclerosis (Fig.-1).

The computerized tomography confirmed the cortical involvement and the magnetic ressonance evidenced the soft tissues extension. No other bones were involved. The biopsy evidenced hemangioendothelioma. Due to the localization, the lesion was unresectable thus local embolization was carried out and radiotherapy was instituted. The microscopic analysis evidenced a vascular neoplasia characterized by vessel anastomosis with atypical endothelial cells (Fig. 2) and intravascular papillary projections.

Rare mitoses and no necrosis were observed. The condition was diagnosed as hemangioendothelioma rather than angiosarcoma.

X-rays and computerized tomography showed that a lesion with destructive aspect had grown (Fig. 3) and spread to the soft tissues revealing more local aggressiveness. The patient also presented the cauda equina syndrome. Surgery with extensive and decompressive laminectomy was carried out and radiotherapy was instituted. The microscopical examination revealed solid clusters within the epithelioid cells that occasionally showed a greater degree of atypia, with eosinophilic cytoplasm sometimes with intense vascularization. Necrotic foci and a moderate number of mitoses were observed. The epithelioid characteristics of the tumor resemble metastatic carcinoma of bone (Fig. 4). The immunohistochemical analysis was carried out and the epithelioid cells were positive for Factor VIII, CD31 and CD34, vascular markers of the endothelial cells, characterizing vascular neoplasia. There was no expression of epithelial markers, as keratin and EMA, disproving the carcinoma hypothesis. The anatomopathological diagnosis was epithelioid angiosarcoma. The patient was staged, and multiple pulmonary lesions were found featuring pulmonary metastasis

DISCUSSION

Dorfman et al. (5) have shown that the bone seldom is the site of choice of blood and lymphatic vessels neoplasias, though they are highly vascularized. Vascular malignant tumors constitute less than 1% of the primary malignant neoplasias of bone, in the series reported by Dahlin (2).

We agree with other authors (13,6) that the malignant vascular tumors of bone are a distinct entity, with an unpredictable clinical evolution. In this case, the initial diagnosis was hemangioendothelioma, according to the morphological criteria of Stout (11) as follows:

1) Higher number of endothelial atypic cells outlining the vessels walls.

2) A tendency to form vascular lumen and anastomosis

It is difficult to determine the degree of malignancy in biopsies since there are several degrees in the same tumor. Unni et al. (12), reviewing 22 cases of hemangioendothelioma of bone, categorized these tumors in three different degrees, revealing that the best indicator for the prognosis was the degree of anaplasia. Hastman and Stewart (8) emphasized the possibility of a benign evolution with long survival after surgery, chemotherapy and radiotherapy. The prognosis for these tumors, however, is still poor, with 26% 5-year survival (7). The possibility of an indolent course with long survival was shown in some cases with eight- and fourteen-year follow-up. However, the disease seems to be aggressive and lethal, as Volpe and Mazabraud have shown (13), even after surgery, radiotherapy and chemotherapy. In this case, a modification in the histological pattern was observed ten years after the first presentation. Besides the higher degree of malignancy with the presence of mitosis, atypia and necrosis, an epithelioid phenotype was also identified showing acidophilic citoplasm due to the presence of numerous cytofilaments. The cytofilaments maintain the cytoskeleton of the vessels under high pressure meaning a "functional status" of the neoplastic cell.

Rosai et al.(9) called the attention to this epithelioid aspect of the cells, but only in 1982, Weiss and Enzinger proposed the terms hemangioendothelioma and epithelioid angiosarcoma. The immunohistochemistry is valuable in the differential diagnosis of these metastatic carcinomas. In some cases of hemangioendotheliomas, epithelial markers of low molecular weight may be present, but no vascular markers (as Factor VIII, CD31 and CD34) are observed in the carcinomas.

The malignant vascular tumors have unpredictable clinical evolution, and even a low grade tumor can form metastasis after several years evolution. The modification of the malignancy degree in our case may represent a tumoral progression phenomenon already described in other tumors as osteosarcomas, giant cell tumors, and chondrosarcomas (3), emphasizing another aspect of the unpredictable behavior of the malignant vascular tumors of bone.

These tumors treatment demands surgery, with extensive ressection of the lesion in the high degree cases; complementary radiotherapy can be used in difficult to reach lesions or when free surgical margins cannot be obtained.

In our case, as the tumor was firstly a low degree tumor (hemangioendothelioma), embolization of the lesion was carried out and radiotherapy was instituted with good initial response. After ten years we observed that the disease can be progressive, aggressive and lethal, and surgery and radiotherapy are the necessary approaches. Chemotherapy has not been considered as an adjuvant treatment.

REFERENCES

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*

This study was carried out in the Pathological Anatomy Department, Orthopedics and Traumatology Institute, “Hospital das Clínicas”, University of São Paulo College of Medicine (IOT-HC-FMUSP).

Publication Dates

• Publication in this collection
  27 June 2006
• Date of issue
  Mar 2001