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Bladder Leiomyoma with Synchronous Solitary Fibrous Tumor of the Pleura.

ABSTRACT: Bladder leiomyomas (BLs) are extremely rare benign tumors of mesenchymal origin. The exact pathophysiological mechanisms that lead to their appearance remain unclear including hormonal disorders, chromosomal abnormalities, and fetal remnants in the bladder. They usually remain asymptomatic for a long period of time. Solitary fibrous tumors (SFTs) are also rare neoplasms of mesenchymal origin with malignant potential usually affecting the pleura. The pathogenesis of SFTs remains unclear. We report the case of a 28-year-old male presenting with SFT of the pleura and synchronous BL. The patient presented with persistent cough as a sole symptom. Computed tomography (CT) of the thorax revealed a pleural mass, which was surgically removed and proved to be a SFT. At an early follow-up, abdominal CT scan revealed a bladder wall mass that proved to be a BL. This is the first report of BL with synchronous SFT of the pleura. Synchronous BLs and SFTs may be incidental, but the coexistence of two mesenchymal tumors at different sites, in a young patient, may raise the suspicion of a new clinical syndrome that warrants further investigation.

SUBMITTER: Mavridis C

PROVIDER: S-EPMC7061107 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Bladder Leiomyoma with Synchronous Solitary Fibrous Tumor of the Pleura.

Mavridis Charalampos C Georgiadis George G Lagoudaki Eleni D ED Skamagkas Iordanis I Heretis Ioannis I Koutsopoulos Anastasios V AV Mamoulakis Charalampos C

Case reports in urology 20200225

Bladder leiomyomas (BLs) are extremely rare benign tumors of mesenchymal origin. The exact pathophysiological mechanisms that lead to their appearance remain unclear including hormonal disorders, chromosomal abnormalities, and fetal remnants in the bladder. They usually remain asymptomatic for a long period of time. Solitary fibrous tumors (SFTs) are also rare neoplasms of mesenchymal origin with malignant potential usually affecting the pleura. The pathogenesis of SFTs remains unclear. We repor ...[more]

PMID: 32158588

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Project description:Solitary fibrous tumors (SFTs) are NAB2-STAT6 fusion-associated neoplasms. There are several subtypes of NAB2-STAT6 fusions, but their clinical significances are still unclear. Moreover, the mechanisms of malignant progression are also poorly understood. In this study, using 91 SFT cases, we examined whether fusion variants are associated with clinicopathological parameters and also investigated the molecular mechanism of malignant transformation using whole-exome sequencing. We detected variant 1b (NAB2ex4-STAT6ex2) in 51/91 (56%) cases and variants 2a/2b (NAB2ex6-STAT6ex16/17) in 17/91 (19%) cases. The NAB2-STAT6 fusion variant types were significantly associated with their primary site (P < 0.001). In addition, a TERT promoter mutation was detected in 7/73 (10%) cases, and it showed a significant association with malignant SFTs (P = 0.003). To identify molecular changes during malignant progression, we selected an index patient to obtain parallel tissue samples from the primary and metastatic tumors. In the metastatic tissue, 10 unique molecular alterations, including those in TP53 and APAF1, were detected. In vitro functional experiments showed that APAF1 depletion increased the tumor potency of cells expressing NAB2-STAT6 fusion protein under treatment with staurosporine. We found that TP53 immunopositivity (P = 0.006) and loss of APAF1 immunoreactivity (P < 0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of TP53 and APAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation. KEY MESSAGES: We firstly found that the TERT promoter mutation was strongly associated with malignant SFTs (P = 0.003) and the representative 1b (NAB2ex4-STAT6ex2) or 2a (NAB2ex6-STAT6ex16) fusion variants similarly contribute to tumorigenicity. We also found that TP53 immunopositivity (P = 0.006) and loss of APAF1 immunoreactivity (P < 0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of TP53 and APAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation.

Project description:Solitary fibrous tumor is a mesenchymal neoplasm exhibiting a broad spectrum of biological behavior and harboring the NAB2-STAT6 fusion. Clinicopathologic parameters are currently used in risk-prediction models for solitary fibrous tumor, but the molecular determinants of malignancy in solitary fibrous tumors remain unknown. We proposed that the activation of telomere maintenance pathways confers a perpetual malignant phenotype to these tumors. Therefore, we investigated telomerase reverse transcriptase (TERT) reactivation induced by promoter mutations as a potential molecular mechanism for aggressive clinical behavior in solitary fibrous tumor. The retrospective study included tumor samples from 94 patients with solitary fibrous tumor (31 thoracic and 63 extra-thoracic). Follow-up information was available for 68 patients (median, 46 months). TERT promoter mutation analysis was performed by PCR and Sanger sequencing, and TERT mRNA expression was assessed by real-time quantitative reverse transcription PCR. Patients were stratified into clinicopathologic subgroups (high-risk (n=20), moderate-risk (n=28), and low-risk (n=46)) according to the risk-stratification model proposed by Demicco et al. TERT promoter mutations were identified in 26 of 94 (28%) solitary fibrous tumors: -124C>T in 23 tumors (88%), -124C>A in 1 tumor (4%), and -146C>T in 2 tumors (8%). Real-time quantitative reverse transcription PCR revealed that TERT mRNA expression was higher in all solitary fibrous tumors with the mutant TERT promoter than those with the wild-type TERT promoter. TERT promoter mutations were strongly associated with high-risk clinicopathologic characteristics and outcome. An adverse event (relapse, death) occurred in 16 of 68 (24%) patients, 12 with solitary fibrous tumors with TERT promoter mutations and 4 with the wild-type TERT promoter. TERT promoter mutations were strongly associated with older age (P=0.006), larger tumor size (P=0.000002), higher risk classifications (P=2.9 × 10-9), and a worse event-free survival (P=0.0082). Thus, TERT promoter mutations in solitary fibrous tumor influence gene expression and are associated with adverse patient outcome. Integrating TERT promoter mutational status with existing multivariable risk-prediction models might improve risk prediction in patients with solitary fibrous tumor.

Dataset Information

Bladder Leiomyoma with Synchronous Solitary Fibrous Tumor of the Pleura.

Publications

Bladder Leiomyoma with Synchronous Solitary Fibrous Tumor of the Pleura.

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