Solitary Fibrous Tumor: Integration of Clinical, Morphologic, Immunohistochemical and Molecular Findings in Risk Stratification and Classification May Better Predict Patient outcome

Abstract

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On microscopic analysis, 38.1% of tumors revealed hypercellularity with a predominant patternless and/or hemangiopericytic growth pattern; 13.4% had ³4 mitoses/10HPF; 16.5% showed necrosis, and almost half the tumors showed at least focal myxoid areas. Dedifferentiation was observed in three tumors. Immunomarker expression in SFTs was as follows: CD34 92.9%, CD99 57.1%, Bcl2 67.9%, neuroendocrine markers (at least 1) 25.7%, Desmin 14.3%, CK(AE1/AE3) 3%, Apoptotic Protease Activating Factor (APAF-1) 87% and finally Ki-67 ≥ 10% in 14.4%. The NAB2/STAT6 gene fusion was detected in 50 tumors. After a median follow-up of 90 months, 9.3% recurred, 11.3% metastasized, 10.3% died of disease and 76.2% were free of disease. TERT mutations were detected in 40.6% of the SFTs; the TP53 mutation was detected in 17%, and only 9.3% showed both mutations. According to the Demicco RSS, 6.1%, 11.3% and 82.4% of the tumors were classified as high, intermediate or low-risk of metastasis, respectively. All high-risk tumors had ³4 mitoses/10HPF, necrosis, Ki-67 ≥ 10, HTER and/or TP53 mutation and poor evolution. The intermediate risk SFTs with worse evolution displayed the HTER mutation. Almost all low-risk tumors had a favorable evolution, although four showed at least one adverse factor (Ki-67 ≥ 10, ³4 mitoses/10HPF or high tumor size) and had a worse evolution. An integration of clinical, morphologic, immunohistochemical and molecular findings may improve risk stratification and classification and better predict patient outcome. The unfavorable course seems to be more frequent in high-risk SFTs, although it is not exceptional in low-risk SFTs either; hence, a long-term follow-up is required independently of the assigned risk stratification score. The inclusion of molecular findings in risk stratification systems could improve the precision in the classification of SFTs, especially those of intermediate risk. Future studies will be required to determine the most effective way to incorporate molecular analyses into RSS on SFTs. The coexistence of several adverse factors such as ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10%, mutations in HTER and/or p53 may suggest a closer clinical follow-up regardless of the histological appearance of the tumor.

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

“…Among them, the scoring system developed by Demicco and co-workers (mDemicco) [4] has been validated in other independent studies and is thus widely used in the clinical setting [5]. This model is based on age, tumor size, mitotic count, and necrosis to predict the risk of metastasis, but it is also accurate when considering different measures of patient outcome such as disease recurrence, which is the parameter used in other risk models [6,7]. Indeed, homogeneous criteria for adverse outcome measure need to be stablished in order to make the performance assessment of different risk systems possible.…”

The Third-Time Recurrence of a Thoracic Solitary Fibrous Tumor in a Patient Presenting With Paraneoplastic Hypoinsulinemic Hypoglycemia (Doege-Potter Syndrome)

“…Furthermore, as suggested by Machado et al [ 13 ], additional testing can be performed to further predict patient outcomes and guide management. In this particular study, genetic analysis with the search of NAB2/STAT6 gene fusion and TERT and TP53 mutations was done.…”

Retroperitoneal malignant solitary fibrous tumor with second recurrence and lymphatic metastases: A case report

“…SFTs consist of a histologically random arrangement characterized by a combination of hypercellular and hypocellular areas. Nuclear STAT6 protein expression and specific NGFI-A binding protein 2 (NAB2)-STAT6 gene fusion facilitates a definite diagnosis of SFT (4)(5)(6). Although most cases are benign, the features of malignant SFT may contain dense arrangements, evident atypia, increased mitotic figures, necrosis, peripheral infiltration, recurrence or metastasis (4,5).…”

“…Nuclear STAT6 protein expression and specific NGFI-A binding protein 2 (NAB2)-STAT6 gene fusion facilitates a definite diagnosis of SFT (4)(5)(6). Although most cases are benign, the features of malignant SFT may contain dense arrangements, evident atypia, increased mitotic figures, necrosis, peripheral infiltration, recurrence or metastasis (4,5). Recurrence occurs in 10-30% of SFTs, and metastasis to the lymph nodes is reported in <5% of malignant SFTs (7)(8)(9) .…”