Updated January 28, 2010

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A 53-year-old man presented with a large soft tissue mass in the chest wall. Tumor infiltration into the lung was demonstrated on CT scan. The resected tumor (16 x 14 x 8 cm) was received with a portion of lung. The cut surface showed a poorly demarcated tan-pink tumor with focal areas of necrosis and multifocal extension to surgical margins. Tumor cells were CD34(+), bcl-2(+), CD99(+) and focally smooth muscle actin(+) and were CD31(-), desmin(-), calretinin(-) and cytokeratin(-).

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2007, Case 2 and is a malignant solitary fibrous tumor.

Criteria for Diagnosis and Comments: The sections show a highly cellular tumor comprised of spindle cells arranged haphazardly without a distinct pattern (“patternless pattern”). In many areas the tumor shows moderate nuclear atypia, brisk mitoses (>5 per 10 high power fields) and small foci of necrosis. The cellular spindle cell component is interrupted by zones of hyalinized keloid-like collagen, a characteristic feature of this tumor. These morphologic and immunohistochemical features are typical of solitary fibrous tumor (SFT). The criteria of malignancy in SFT include increased cellularity with crowded, overlapping nuclei, cellular pleomorphism and mitoses >4 per 10 HPF. Based on these criteria, this tumor can be classified as malignant.

SFT typically occurs as a pedunculated mass in the thoracic cavity but can occur in almost any site of the body including other body cavities, soft tissues and visceral organs. Many SFTs show a branching “hemangiopericytomatous” vascular pattern, but this architecture is usually confined to a small portion of the tumor. Expression of vimentin, CD34 (90-95%) and CD99 (70%) is characteristic. Positive staining for bcl-2 is common. Barring anecdotal reports, SFTs are negative for desmin, S-100 and epithelial markers like keratin.

A vast majority of solitary fibrous tumors are benign, slow growing neoplasms with favorable prognoses. Recurrence and/or metastasis occur in ~10% of SFT (both thoracic and extrathoracic). Cytological features of malignancy correlate with aggressive outcome, but do not necessarily portend an unfavorable clinical course. Pleural tumors that are well circumscribed and completely resectable may behave in a benign fashion even if they have malignant histological features, while poorly circumscribed and infiltrative tumors are more uniformly malignant. Gross and microscopic features, however, are not reliable indicators of outcome as recurrences can occur in apparently benign tumors. Malignant SFT can occur either de novo or by transformation (“dedifferentiation”) within a pre-existing SFT. Loss of CD34 reactivity can occur in malignant SFT, while other markers like bcl-2 may be retained.

Hemangiopericytoma is an uncommon tumor of putative pericytic origin that most commonly occurs in soft tissue of lower extremity, pelvis, retroperitoneum, orbit, meninges, and rarely in visceral organs. It is composed of oval to plump spindle cells arranged around dilated variably-sized thin-caliber vascular channels. The branching pattern of these vessels creates a characteristic ‘staghorn’ or ‘hemangiopericytomatous’ pattern. The ramifying vascular pattern is not specific for hemangiopericytoma and can be seen in a variety of other soft tissue neoplasms like solitary fibrous tumor, synovial sarcoma, malignant fibrous histiocytoma and mesenchymal chondrosarcoma. However, in these tumors, this vascular pattern is often focal, as opposed to hemangiopericytoma where it is diffuse and prominent. The neoplastic cells typically express vimentin and CD34; smooth muscle actin can be focally positive. Positivity for CD99, bcl-2 and Factor XIIIa has been described. Size >5 cm, brisk mitoses (> 4 per 10 high power fields), high cellularity, cellular atypia, hemorrhage and necrosis correlate with overtly malignant behavior. The term ‘low malignant potential’ has been proposed for tumors with cellular atypia and high cellularity but lower (1-3 per 10 high power fields) mitotic activity.

The distinction between SFT and hemangiopericytoma can often be subtle. Some experts believe that hemangiopericytoma of soft tissue is very rare and a vast majority of these tumors represent cellular variants of solitary fibrous tumor. Since CD34 is positive in both tumors (more diffuse and intense in SFT), morphologic features like prominent areas of hyalinization and lack of or only focal branching vascular pattern are used to distinguish SFT from hemangiopericytoma. Rearrangements of 12q and homozygous deletion of p16 gene have been described in hemangiopericytomas, but not in SFT.

Monophasic (spindle cell) synovial sarcoma (SS) is characterized by spindle cells arranged in vague fascicles, often with prominent hemangiopericytoma-like areas. The tumor cells diffusely express vimentin and bcl-2. Expression of CD99 and S-100 can be seen in two-thirds and one-third of the cases respectively. Cytokeratin-expressing cells can be seen singly or in groups; these cells may be focal and difficult to demonstrate in some cases. Epithelial membrane antigen (EMA) is more diffusely expressed. Since, synovial sarcomas can be EMA (+) and cytokeratin (-), or vice versa, both markers should be included in the immunohistochemical panel. The t (X;18) translocation is the hallmark of SS and is observed in >90% of cases. This leads to fusion of SYT gene on chromosome 18 with SSX genes on the X chromosome. Absence of hyalinized zones of collagen as well as CD34-negative and keratin/EMA-positive phenotype distinguishes SS from SFT in most cases. Malignant SFT may lose CD34 reactivity and can be difficult to distinguish from monophasic synovial sarcoma. Demonstration of SYT-SSX gene fusion may be necessary for distinction in these cases.

The separation of spindle cell sarcomas, like fibrosarcoma, from malignant SFT can be challenging. The presence of broad zones of hyalinized collagen and the expression of bcl-2 and CD34 in SFT are the most useful features in this distinction.

The absence of hyalinized zones of collagen coupled with the immunohistochemical findings (cytokeratin and calretinin positive, CD34 negative) is helpful in arriving at the diagnosis of desmoplastic mesothelioma.