Solitary Fibrous Tumor

Solitary fibrous tumor (SFT) was first described in 1870 by Wagner and further established in 1931 by Klemperer and Rabin as a pleural neoplasm. The term hemangiopericytoma (HPC) was first used by Stout and Murray in 1942 to describe a distinct neoplasm of pericytic origin. However, over time, the staghorn-branching vascular pattern representative of HPC was found to be present at least focally in 15% of all soft-tissue tumors and was more of a characteristic histopathologic pattern than a specific clinicopathologic entity.[1]

Today, the diagnosis of HPC is primarily reserved to neuropathologists. The term SFT is favored by soft-tissue pathologists to describe a rare, heterogeneous group of benign and malignant neoplasms along a morphologic continuum.[2, 3]

Three classical clinical forms of SFT are recognized, as follows[2] :

• Pleural SFT
• Soft-tissue SFT - This variety occurs across a histopathologic spectrum; on one end, a fibrous form is characterized by hyalinized, thick-walled vessels with opened lumina and strong CD34 reactivity, and on the other, a cellular form, representing conventional HPC, has branching, thin-walled vessels and focal or absent CD34 reactivity ^[1]
• Meningeal HPC

Lesions formerly known as HPC have been partitioned into three main groups, as follows:

• The first group includes so-called true HPCs; these lesions show clear evidence of myoid and pericytic differentiation and include a subset of sinonasal HPC, subcutaneous infantile myofibromatosis or infantile HPC, and glomangiopericytoma or myopericytoma ^[1]  
• The second group includes various lesions with HPC-like features, which are sometimes miscategorized; most notably, the monophasic spindle cell or fibroblastic synovial sarcoma variant can be confused with HPC ^[4]
• The third group includes conventional SFT, a fat-forming SFT or lipomatous HPC, and a giant cell–rich variant of SFT or giant cell angiofibroma ^[1]  

This article focuses on the cellular variant of conventional SFT, or what was previously termed conventional HPC.

SFTs are tumors of mesenchymal origin that occur in the extremities. The 2013 classification of soft-tissue tumors published by the World Health Organization[5]  defined malignant forms of SFT as hypercellular, mitotically active (>4 mitoses/10 high-power fields) lesions characterized by cytologic atypia, tumor necrosis, or infiltrative margins. A single-center study by DeVito et al found that malignant SFT, as compared with benign SFT, was associated with larger tumors, elevated mitotic counts, the presence of metastases at diagnosis, and more extensive use of chemotherapy and radiation therapy.[6]

This tumor typically spreads via hematogenous dissemination, primarily to the lungs, but rarely spreads via the lymphatics. Metastatic disease is usually the cause of death. Metastasis appears to be more likely with SFT of extrathoracic origin than with thoracic SFT.[7]  The 2020 WHO classification of soft-tissue tumors listed SFT as an intermediate (rarely metastasizing) tumor.[3]

The etiology is unknown.

Most SFTs occur in adults, with a median age of 45-50 years. SFT is less common in infants and children. Soft-tissue SFTs represent only about 1-2% of all soft-tissue tumors.[2]

Conventional HPCs and SFTs have a better prognosis than some older studies may suggest, in that these studies may have inadvertently included sarcomas with HPC-like features. For patients with a primary tumor who undergo complete resection, 5-year survival is 89-100%. For patients with SFTs of an extremity, the local recurrence rate is 0-6%, and the distant metastasis rate is 0-19%.[4, 8, 9]

Most patients with SFT or HPC have a benign clinical course, but because of the lesion's malignant potential, wide resection and careful long-term follow-up are necessary. Favorable long-term outcomes have been reported in cases of intracranial SFT that required repeat radiosurgery.[10]

Various risk models have been proposed in an effort to predict outcome in patients with SFT.[3]  Demicco et al, in a study comparing five such models designed for soft-tissue and/or pleural SFT—(1) modified Demicco, (2) Pasquali, (3) Salas overall survival (OS), (4) Salas metastasis, and (5) Salas local recurrence (LR)—in 303 patients with extrameningeal SFT found that models (1), (3), and (4) models predicted metastasis and recurrence-free survival and that model (2) correlated best with overall survival.[11]

A solitary fibrous tumor (SFT) typically presents as a deep, painless enlarging mass in the thigh, axilla, or pelvis. Males and females are equally affected; the median age is 45 years.[2, 4] Patients may exhibit symptoms associated with a local compressive effect on viscera or neurovascular structures. Paraneoplastic syndromes such as hypoglycemia have been described.[12]

In addition to a complete physical examination, all patients should undergo local imaging (including intravenous contrast-enhanced magnetic resonance imaging [MRI] and plain radiography), as well as chest radiography or computed tomography (CT).[13] A solitary fibrous tumor (SFT)  demonstrates a heterogeneous appearance on MRI, with high signal on T2-weighted series and intermediate to moderately high signal on T1-weighted images.[14] (See the images below.) Cellular SFTs also show rapid initial enhancement on dynamic contrast-enhanced MRI.[15]

MRI of solitary fibrous tumor demonstrates a deep soft-tissue mass in the anteromedial aspect of the thigh with heterogenous high signal intensity on coronal STIR imaging.

Similar signal intensity as skeletal muscle on precontrast axial T1-weighted fat-suppressed turbo-spin echocardiography.

Intense uptake on postcontrast comparison images.

SFTs are generally well-circumscribed. Small satellite nodules separate from the main lesion are not uncommon, and 12% of patients may present with metastasis or locally recurrent tumors.[4] No distinctive radiologic criteria for malignancy are recognized, other than distant metastasis.

Biopsy should be performed by a musculoskeletal oncologist. If the mass is palpable and accessible, a core needle biopsy may be an alternative to open incisional biopsy. The fibrous nature, potential low cellularity, and usually deep location of the mass may not allow fine-needle aspiration biopsy (FNAB). The biopsy should be placed in line with the incision for definitive tumor resection to allow en-bloc resection of the biopsy tract. Adequate tissue should be acquired to allow for histologic analysis, molecular genetics,[16] and immunohistochemistry (IHC).[17]

SFTs must be carefully distinguished from other entities, such as synovial sarcoma and angiosarcoma, which have a worse prognosis and a different treatment course.

The cell of origin for SFTs is controversial.[2] Fibroblasts are elongated, spindle-shaped cells with long processes; on electron microscopy, they are devoid of a basement membrane and demonstrate a prominent rough endoplasmic reticulum. Pericytes also have elongated cell processes and are spindle-shaped. They are contractile and surround capillaries and postcapillary venules. However, few tumors formerly labeled as hemangiopericytomas (HPCs) had actual pericytic differentiation, and most had nonspecific ultrastructural features.[1]

On histology, one can appreciate a staghorn-type branching of vessels, a bland cell morphology, and positive staining for CD34. (See the images below.)

Histology of solitary fibrous tumor demonstrates a bland cell morphology and staghorn-type branching of vessels on low magnification of hematoxylin and eosin stained slides. Image courtesy of Paul E. Wakely, Jr, MD.

Histology of solitary fibrous tumor demonstrates a bland cell morphology and staghorn-type branching of vessels on high magnification of hematoxylin and eosin stained slides. Image courtesy of Paul E. Wakely, Jr, MD.

Positive staining for CD34. Image courtesy of Paul E. Wakely, Jr, MD.

Before the use of IHC, HPC and SFT were commonly confused with synovial sarcoma, particularly monophasic variants. Epithelioid differentiation can help distinguish biphasic synovial sarcomas. Approximately 90% of synovial sarcomas demonstrate the chromosomal translocation t(X;18)(p11.2;q11.2) and the fusion gene SYT-SSX1 or SYT-SSX2, detectable with cytogenetics and reverse transcription polymerase chain reaction (RT-PCR).[16] Nuclear STAT6 immunoreactivity can be helpful in cases where the diagnosis is uncertain.[17, 18]

SFTs are generally regarded as benign but can demonstrate aggressive behavior even if they appear morphologically benign. Histologic criteria for malignancy include the following[2, 8, 6] :

• Cellular pleomorphism
• Tumor necrosis
• Hemorrhage
• Infiltrative margins with surrounding tissues
• Hypocellularity
• Moderate-to-severe nuclear atypia
• Sharply demarcated anaplastic or poorly differentiated foci
• High mitotic count (>4 mitoses/10 hpf)

Because even benign-appearing solitary fibrous tumors (SFTs) can be locally recurrent and metastatic, wide resection is recommended for both benign and malignant SFTs. Preoperative vascular studies and arterial embolization should be considered because of the known bleeding risk with resection.[2, 14] Careful exclusion of other diagnoses (eg, synovial sarcoma) is important. Because of the favorable outcome with SFTs, it may be possible to avoid limb-threatening and deforming operations.[4]

No evidence suggests that adjuvant chemotherapy is beneficial. If the SFT appears malignant histologically, adjuvant radiation therapy may be considered. Long-term follow-up is recommended because local and distant relapse is possible, even with benign-appearing tumors.