Pleuro-pulmonary Solitary Fibrous Tumors

Abstract

Pleuro-pulmonary solitary fibrous tumor (SFT) is a relatively uncommon mesenchymal neoplasm of uncertain histogenesis, unknown molecular features, and unpredictable clinical behavior. Although complete resection is universally accepted as the most important single prognostic factor, some clinicopathologic characteristics (gross appearance, tumor size, mitotic index, tumor necrosis, hypercellularity, and pleomorphism) are related to patient outcome, and a staging system based on these parameters with practical therapeutical implications has been recently proposed by de Perrot et al. Here, 88 pleuro-pulmonary SFTs were collected and clinicopathologic characteristics including de Perrot classification, patients' follow-up, p53 expression, and several "targetable" kinases [c-kit, v-raf murine sarcoma viral oncogene homolog B1, platelet-derived growth factor receptor (PDGFR)-alpha/beta, c-met, epidermal growth factor receptor (EGFR)] were retrospectively analyzed. Fifty-two cases (59%) had at least 1 clinicopathologic feature related to malignancy, whereas mortality and recurrences occurred in 10.2% and 18.2% of the cases, respectively. de Perrot staging and high p53 expression were significantly related to the conventional clinicopathologic prognostic features as well as to overall survival (OS) and disease-free survival (DFS) (P<0.001). At multivariate analysis, high p53 expression and tumor necrosis were the only parameters significantly associated with OS and DFS (P=0.017 and P=0.012, respectively). Immunohistochemical expression was frequently detected for PDGFR-alpha (97.7%), PDGFR-beta (86.5%), and hepatocyte growth factor receptor (96.6%), whereas missense mutations were only identified in 2 cases both involving PDGFR-beta (exons 18 and 20). We conclude that de Perrot stratification of SFT is a reliable prognostic indicator and merits consideration in view of its suggestions for the management of these tumors in daily practice. p53 expression may represent a valid and easy-to-test prognostic factor significantly related to OS and DFS. Although mutations of the corresponding genes are rare events in SFT, PDGFR-alpha/beta, and hepatocyte growth factor receptor tyrosine kinases should be further investigated given the availability of specific inhibitory molecules which might provide useful and novel therapeutical approaches for SFT patients.

Determinants of outcome of solitary fibrous tumors of the pleura: an observational cohort study

“…Histomorphologic characteristics apparently predicting aggressive behavior (including local recurrence, metastases or SFTP-related death) were first described by England et al [6] and included tumor size greater than 10 cm in diameter, atypical localization, sessile tumor, existence of necrosis or hemorrhage, more than four mitoses per 10 high-power fields (HPF), and nuclear pleomorphism. However, none of these factors seems to accurately predict an impaired outcome, as 59% of SFTP may display at least one of the above mentioned features, whereas mortality and recurrence have only been observed in 10% and 18% of all cases, respectively [11]. …”

“…In 2008, this modified staging system was evaluated by Schirosi et al [11] who were able to show a significant correlation with overall and disease-free survival. However, in the multivariate analysis of the latter study, the authors found that only tumor necrosis and high p53 expression were parameters significantly associated with overall and disease-free survival [11]. …”

“…To date, there is insufficient information to predict the biological behavior of these tumors which is partly related to very few data on immunohistochemical and molecular markers and limited long-term follow-up data in SFTP [11-13]. Hence, there is a need to define parameters that characterize the malignant variant based on clinico-pathological, immunohistochemical, or molecular findings.…”

Surgical therapy and next-generation sequencing-based genetic alteration analysis of malignant solitary fibrous tumor of the pleura

“…SFTPs are uncommon mesenchymal neoplasms with unpredictable clinical behavior and uncertain histogenesis 41. Because a single biopsy may be insufficient for identifying all gene mutations from a tumor,42 the sequencing results of this study were analyzed with reference to the COSMIC database to shed light on SFTP development and prognosis.…”

Efficacy and Safety of Pazopanib for Recurrent or Metastatic Solitary Fibrous Tumor

“…The most important biological feature of this tumor is its high expression of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) [9, 10]. Several molecular targeted drugs against the signaling pathways of these proteins have been reported to show efficacy in patients with SFT; these include bevacizumab, a recombinant monoclonal antibody that inhibits VEGF; sorafenib, which inhibits the tyrosine kinases B-Raf, c-kit, VEGFR, and PDGFR; and sunitinib, which inhibits the tyrosine kinases VEGFR, PDGFR, fms-like tyrosine kinase 3, kit, and rearranged during transfection [11-13].…”