Discussion
It has been appreciated in recent years that solitary fibrous tumour may occur at a wide variety of sites other than the pleura, including the peritoneum, mediastinum, retroperitoneum, upper respiratory tract, orbit, soft tissue, and in almost any organ-in fact, it seems likely that extrapleural lesions are more common than the pleural lesions. Extrapleural lesions, irrespective of site, almost invariably arise in adults of either sex aged 20-70 years,who present with a non-descript, slowly enlarging mass, most often located in deep soft tissue.
The clinical course in most cases seem to be benign; however, as in the pleura, up to 10% of those cases arising in soft tissue behave in a malignant fashion.
Solitary fibrous tumour in soft tissue tend often to be quite large, depending on location, and has a circumscribed, lobulated appearance. The cut surface generally is pale and firm.
Typical solitary fibrous tumours show a patternless architecture characterized by a combination of hypocellular and hypercellular areas separated by thick bands of hyalinized, sometimes keloidal, collagen and thin-walled branching haemangiopericytoma-like vessels. There may also be perivascular hyalinization. Tumour cells are ovoid to spindle-shaped with limited pale cytoplasm having indistinct borders and dispersed chromatin within vesicular nuclei. Rarely epithelioid or rhabdoid cells can be found focally. Myxoid change, areas of fibrosis and interstitial mast cells are commonly observed. Mitoses are generally scarce, rarely exceeding 3 mitoses per 10 high power field.
Some solitary fibrous tumours may contain giant multinucleate stromal cells and pseudo-vascular spaces, being formerly known as “giant cell angiofibroma”.
Malignant solitary fibrous tumours are usually hypercellular lesions, showing increased mitoses (>4 mitoses per 10 high power field), variable cytological atypia, tumour necrosis, and/or infiltrative margins, of which mitoses seem to be most prognostic. Rare cases show abrupt transition from conventional benign-appearing solitary fibrous tumours to high grade sarcoma, likely representing a form of dedifferentiation. Lesions may show cytological atypia in the absence of mitoses or necrosis.
The vast majority of solitary fibrous tumours, which behave aggressively show morphologic features of malignancy, but, rarely, benign-appearing solitary fibrous tumours give rise to metastases, hence the designation of this tumor type as “intermediate, rarely metastasizing” in the 2002 World Health Organization classification.
Tumour cells are characteristically immunoreactive for CD34, CD99, bcl-2 and STAT-6; but generally negative for S-100, actin, desmin and epithelial markers. 20-35% of cases are variably positive for EMA and SMA. Focal and limited reactivity for S-100 protein, keratins and/or desmin has also occasionally been reported. CD34 is a 110 kDa transmembrane glycoprotein present on human hematopoietic progenitor cells and vascular endothelial cells. Although originally described as a marker specific for vascular lesions, it is now clear that CD34 has a much broader reactivity in non-vascular mesenchymal tumors of diverse types.
The principal differential diagnoses of solitary fibrous tumor are monophasic fibrous synovial sarcomas, commonly bcl-2 positive and nerve sheath tumors, sometimes bcl-2 positive. Demonstration of S-100 positivity will help in differentiating between the nerve sheath tumor and solitary fibrous tumor. An immunohistochemical absence of CD34 in synovial sarcomas, serves to separate them from solitary fibrous tumor. In addition, demonstrating positivity of the spindle cells with cytokeratin and epithelial membrane antigen in synovial sarcoma and negative labeling with these antibodies in solitary fibrous tumor should be of aid in the diagnosis.
A variety of other entities, such as leiomyosarcoma, fibromatosis, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, fibrosarcoma and sarcomatoid mesothelioma, which are frequently considered in the differential diagnosis of solitary fibrous tumor, were uniformly bcl-2 negative, bcl-2 protein may play a role in rescuing of neoplastic cells from apoptotic cell death, leading to slower tumor growth.
Although most cases are benign, the behavior of solitary fibrous tumour can be unpredictable. About 10% behave aggressively, and local or distant recurrence can occur many years after primary resection. Although there is no strict correlation between morphology and behavior, malignant histology (especially high mitotic counts) remains the best indicator of poor outcome. Most (but not all) histologically benign solitary fibrous tumours prove to be non-recurring and non-metastasizing lesions, and most histologically malignant tumours behave aggressively. Lesions located in the mediastinum, abdomen, pelvis, retroperitoneum, and/or meninges also tend to behave more aggressively than those in the limbs. Tumour size >10cm and positive surgical margins also predict poorer prognosis. Metastases are most frequently observed in lungs, bone and liver. The behavior of solitary fibrous tumour with atypia alone is unpredictable.