Clinicopathological findings in a case series of extrathoracic solitary fibrous tumors of soft tissues

Solitary fibrous tumors (SFT) – previously known as benign fibrous mesotheliomas – were considered being of serosal origin and being exclusively located in the thoracic cavity as pleural fibrous tumors. More recently, however, SFT have been reported in many extrapleural locations such as the head and neck region; in particular, the meninges, the orbita, the nasal and oral cavity, the salivary glands, and the visceral organs, the retroperitoneum, and the pelvic space. Extrapleural solitary fibrous tumors (ESFT), especially those at the extremities, still represent a rare entity of soft tissue tumors. In a previous study extrapleural solitary fibrous tumors (ESFT) counted for 0.6% of all soft tissue tumors, sent in for analysis [1]. In fact, by taking into account the bias caused by the fact that rare tumor specimens accumulate at specialised institutions, the general proportion might be much smaller. Usually the tumor is of benign behaviour (showing no local recurrence or metastasis), but malignant variants have also been described and local recurrence as well as metastasis may occur depending on the initial tumor size and the histological status of the surgical resection margins [1‐18]. We report 9 cases of ESFT including 4 tumors localized at the extremities with clinicopathological, immunohistochemical and follow-up data.

From January 1999 to May 2005, nine patients were diagnosed with extrapleural SFT at our institutions. Data were obtained from patients records and phone calls to the patients and their general practitioners.

The patients included 6 women and 3 men. Their age at time of diagnosis ranged from 32 to 92 years and averaged 62.2 years. Tumors were painless or became symptomatic by their mass effect, causing localized pain, or as in one patient, hypaesthesia. There were no other (especially no generalized) symptoms. The tumors existed 5 months to 5 years before being diagnosed. All tumors were located in deep soft tissues, 3 of them epifascial, 2 subfascial, 4 intramuscular. Four tumors were located at the extremities (thigh, fossa poplitea (Fig. 1), 2× lower arm (Fig. 2)) and one each in the flank, the neck, at the shoulder, in the deep groin, and in the gluteal region. The diameters of the tumors ranged from 4.5 to 10 cm (mean: 7 cm). In 7 patients, primary resection could be performed with free surgical margins; four of them were primarily incisional biopsied. In one patient, treated externally, the resection had to be considered a R1-resection due to an intraoperative tumor incision with possible contamination of the situs. Whether or not this will influence the long term outcome cannot yet be determined because of a follow-up time of 1 month. Another patient with unfavourable clinical course (Patient 5) presented at our institution after pre-treatment at another institution 2 years before consisting of incomplete primary resection and secondary resection then with free margins, followed by 60 Gy of radiation. This patient showed extensive local recurrence and an amputation at upper arm level had to be performed. Five months later, the patient presented again with two new metastases: one in the right axilla and another one epifascial at the right subscapular region which were resected with free surgical margins. At the time of this study all other patients had no evidence (NED) of disease. The detailed clinical findings are summarized in table 2.

SFT represents a distinct entity within the wide range of soft tissue tumors. Its cellular origin is believed to be fibroblastic in type. Most cases of formerly diagnosed "hemangiopericytomas" seemingly share essential features with SFT and may indeed represent true SFT. According to overlapping histological criteria between SFT and hemangiopericytoma, SFT represents a wider range of neoplasias (probably in fact including the former "favourite" diagnosis of hemangiopericytoma) which should best be regarded as a "waste basket" and be considered a mere diagnosis of exclusion. The lipomatous variant of SFT ("lipomatous hemangiopericytoma") includes a mature fat component intermingling with typical areas of SFT. Rare myxoid SFT may cause considerable problems in differential diagnosis to more aggressive soft tissue neoplasms or soft tissue tumors of another differentiation. Branching and ectatic blood vessels typical for SFT known as hemangiopericytoma-like vessels may be a feature of several other predominantly malignant soft tissue tumors (e.g. synovial sarcomas or malignant peripheral nerve sheath tumors), implicating that a wider range of other soft tissue neoplasias has to be considered in the histopathological differential diagnosis of SFT. The so-called "patternless pattern" or the combination of different histological patterns such as storiform, fascicular, neuraltype, diffuse sclerosing, and heringbone growth pattern may lead to a wrong diagnosis [19]. Therefore, it is evident that an experienced soft tissue pathologist should evaluate the specimens. For differential diagnosis, so-called hemangiopericytoma, synovial sarcoma, dermatofibrosarcoma protuberans, leiomyosarcoma, malignant peripheral nerve sheath tumor, and liposarcoma, should be taken into consideration. Positron emission tomography (PET) may be helpful to distinguish between a malignant and a benign variant of the tumor [20‐22], but the gold standard for diagnosis remains incisional biopsy.

Extrathoracic solitary fibrous tumors (ESFT) by now have been reported at almost every anatomic location, but reports of tumors at the extremities or intramuscular tumors as well as tumors with malignant clinical behaviour or atypical histologic features are rare [1‐18].

Other series of ESFT's showed almost equal distribution of the incidence for male and female, with patients' ages ranging from the third to the eighth or ninth decade with a maximum in the sixth decade concurring with our data [3, 7, 8].

Some studies suggested a very low rate of recurrence and metastasis [8, 11, 23], whereas other authors indicated a possibly increased relapse rate with extended follow-up periods. In their studies Vallat-Decouveleare et al. and Gold et al. [3] in their studies found local recurrence in 4.3% and 6.7% and metastasis in 5.4% and 5.3%, respectively. Tumor relapse occurred after up to 168 months, but most of the metastasis or local recurrences were diagnosed within the first two years after initial treatment. Sites of distant metastasis were lung, liver, bones, mesentery, omentum, mediastinum and retroperitoneum with preference for lung and liver [1, 3].

Vallat-Decouveleare suggested atypical histologic features, such as nuclear atypia, areas of increased cellularity, necrosis and 4 or more mitoses per 10 HPF as being predictive for clinical malignant behaviour of the tumor and found local or distant relapse in those cases in 80%, but also reported a case of clinically malignant behaviour of a histological benign appearing case. Recurrent tumor specimens showed a higher grade of atypia than the primary tumor but usually retained their immunohistochemical profile. Gold's data proposed to add the size of the primary tumor as well as the resection status to the predictive factors of clinical behaviour. Positive surgical resection margins and primary tumor sizes of more than 10 cm were positively correlated with unfavourable clinical outcome.

In our series, the only patient with recurrent disease and metastasis was primarily resected incompletely, underlining this suggestion. In the recurrent tumor specimen increased atypia was seen, but if this atypia had already been present in the primary tumor and therefore could be considered as of predictive value cannot be determined. The recurrence occurred 2 years and the metastasis 2 ½ years after primary resection and following radiation. Detailed histopathological information about the primary tumor could not be obtained.

Complete surgical resection is commonly accepted as treatment of choice for ESFT. Due to improved techniques in reconstructive surgery, even large lesions can usually be completely resected, preserving the limbs. Amputations should be limited to extended or recurrent tumors. Befitting the rareness of this entity reports of radiation therapy and chemotherapy of ESFT are anecdotal and so far, no significant benefit of adjuvant treatment has been reported. In some cases, especially malignant variants or incomplete resections with no further surgical option, it may although be used [1, 3]. This concurs with the findings for intrathoracic SFT [24, 25].

According to the late recurrence or metastasis, long follow-up periods (at least 15 years) should be maintained with closer follow-up during the first two years. In cooperative patients a life long follow-up may be recommended. Follow-up should include clinical examination as well as abdominal ultrasound and chest x-ray.

Soft Tissue sarcoma specimens should be evaluated by experienced soft tissue pathologists for correct diagnosis of SFT and detection of atypia. SFT with atypical histologic features, such as nuclear atypia, areas of increased cellularity, necrosis and 4 or more mitoses per 10 HPF, tumor sizes of more than 10 cm and incomplete resection are positively correlated with local recurrence and metastatic disease. Therefore complete resection at an early stage should be the main purpose of surgical treatment. Follow-up should be maintained for 10 years.