Giant cell-rich solitary fibrous tumour of the urinary bladder: case report of an unusual histological variant and literature review.

BACKGROUND: Giant cell-rich solitary fibrous tumour (GCR-SFT), previously referred to as giant cell angiofibroma, is an uncommon soft tissue tumour that classically occurs in the orbit but very rarely presents in deep organs. Here, we present a case of GCR-SFT occurring in the urinary bladder, which is one of the unusual histological subtypes of SFT. CASE PRESENTATION: A 56-year-old man was incidentally found to have a mass measuring 4.5 × 4.3 × 4.0 cm located in the left posterior wall of the bladder by computed tomography during a physical examination. The lesion was confirmed as GCR-SFT by pathological examination after laparoscopic radical surgery. Histopathologically, the tumour was a well-circumscribed, nonencapsulated lesion that was composed of bland spindle-ovoid tumour cells alternating with hypocellular and hypercellular areas, staghorn-like vasculatures and scattered large dark-stained multinucleate giant cells lining pseudovascular spaces. The spindle-ovoid cells and multinucleate giant cells showed strong and diffuse expression of CD34 and nuclear STAT6. In addition, the hallmark of the NAB2ex4-STAT6ex5 fusion gene was detected by RT‒PCR. The patient was classified as having a low risk of recurrence or metastasis according to the risk stratification criteria. The patient underwent regular follow-up for 34 months after surgery, and there was no evidence of local recurrence or metastasis. CONCLUSION: This is the first reported case of GCR-SFT occurring in the urinary bladder with underlying NAB2ex4-STAT6ex5 fusion. Complete surgical excision of the tumour and long-term follow-up are recommended to ensure no local recurrence or metastasis.

Trabectedin Is Active against Two Novel, Patient-Derived Solitary Fibrous Pleural Tumor Cell Lines and Synergizes with Ponatinib.

Solitary fibrous tumor of the pleura (SFT) is a rare disease. Besides surgery combined with radiotherapy in nondisseminated stages, curative options are currently absent. Out of fourteen primo-cell cultures, established from surgical SFT specimens, two showed stable in vitro growth. Both cell models harbored the characteristic NAB2-STAT6 fusion and were further investigated by different preclinical methods assessing cell viability, clone formation, and protein regulation upon single-drug treatment or in response to selected treatment combinations. Both fusion-positive cell models showed-in line with the clinical experience and the literature-a low to moderate response to most of the tested cytotoxic and targeted agents. However, the multi-tyrosine kinase inhibitors ponatinib and dasatinib, as well as the anti-sarcoma compound trabectedin, revealed promising activity against SFT growth. Furthermore, both cell models spontaneously presented strong FGFR downstream signaling targetable by ponatinib. Most interestingly, the combination of either ponatinib or dasatinib with trabectedin showed synergistic effects. In conclusion, this study identified novel trabectedin-based treatment combinations with clinically approved tyrosine kinase inhibitors, using two newly established NAB2-STAT6 fusion-positive cell models. These findings can be the basis for anti-SFT drug repurposing approaches in this rare and therapy-refractory disease.

[Fat-forming solitary fibrous tumor with NAB2/ STAT6 gene fusion. Case report of genial location and literature review]. / Tumor fibroso solitario variedad lipomatosa con fusión génica NAB2/STAT6. Estudio de un caso de localización geniana y revisión de la literatura.

The lipomatous variety solitary fibrous tumor is a soft tissue neoplasm composed of mature adipose tissue and hemangiopericytoma areas. A 53-year-old man consulted for facial asymmetry and maxillofacial magnetic resonance imaging showed a cystic lesion, 3 x 2 cm in size, in front of the anterior wall of the maxillary sinus. Histologically, there were dense spindle cells expressing CD34, CD99, Bcl-2, and STAT6, myxoid zones, hemangiopericytomatous blood vessels, and S100 positive adipocytes. NAB2/STAT6 gene fusion was revealed by RT-PCR. The main differential diagnosis was raised with the spindle cell lipoma and malignant variant of the lipomatous solitary fibrous tumor. STAT6 overexpression and NAB2/STAT6 gene fusion are specific for lipomatous solitary fibrous tumor and the presence of lipoblasts and atypical lipomatous tumor areas suggests malignancy. These tumors located in the head and neck region have a benign biological behavior.

Tumor fibroso solitario variedad lipomatosa con fusión génica NAB2/STAT6. Estudio de un caso de localización geniana y revisión de la literatura / Fat-forming solitary fibrous tumor with NAB2/ STAT6 gene fusion. Case report of genial location and literature review

El tumor fibroso solitario variedad lipomatosa es una neoplasia de partes blandas compuesta por tejido adiposo maduro y áreas de hemangiopericitoma. Un varón de 53 años se presentó clínicamente con asimetría facial. La resonancia magnética maxilofacial demostró una lesión quística, de 3 x 2 cm, por delante de la pared anterior del seno maxilar. Histológicamente, había áreas fusocelulares densas que expresaban CD34, CD99, Bcl-2 y STAT6, zonas mixoides, vasos sanguíneos hemangiopericitomatosos y adipocitos S100 positivos. La fusión génica NAB2/STAT6 fue revelada mediante RT-PCR. El principal diagnóstico diferencial se planteó con el lipoma de células fusiformes y la variante maligna del tumor fibroso solitario lipomatoso. La sobreexpresión de STAT6 y la fusión génica NAB2-STAT6 son específicas del tumor fibroso solitario lipomatoso y la presencia de lipoblastos y áreas de tumor lipomatoso atípico sugiere malignidad. Estos tumores en cabeza y cuello tienen un comportamiento biológico benigno.(AU)

The lipomatous variety solitary fibrous tumor is a soft tissue neoplasm composed of mature adipose tissue and hemangiopericytoma areas. A 53-year-old man consulted for facial asymmetry and maxillofacial magnetic resonance imaging showed a cystic lesion, 3 x 2 cm in size, in front of the anterior wall of the maxillary sinus. Histologically, there were dense spindle cells expressing CD34, CD99, Bcl-2, and STAT6, myxoid zones, hemangiopericytomatous blood vessels, and S100 positive adipocytes. NAB2/STAT6 gene fusion was revealed by RT-PCR. The main differential diagnosis was raised with the spindle cell lipoma and malignant variant of the lipomatous solitary fibrous tumor. STAT6 overexpression and NAB2/STAT6 gene fusion are specific for lipomatous solitary fibrous tumor and the presence of lipoblasts and atypical lipomatous tumor areas suggests malignancy. These tumors located in the head and neck region have a benign biological behavior.(AU)

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis.

BACKGROUND: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. METHODS: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. RESULTS: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. CONCLUSIONS: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis

BACKGROUND: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. METHODS: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. RESULTS: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. CONCLUSIONS: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.