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Solitary fibrous tumor (SFT) is a distinct fibroblastic neoplasm of intermediate biological potential, prototypically presenting as a pleuraassociated tumor characterized by patternless proliferation of generally banal oval to spindle cells with hemangiopericytoma-like staghorn vessels in fibrocollagenous stroma. Over the past decades, the clinicopathological spectrum of SFT has been everexpanding with the incorporation of cases exhibiting myxoid, giant cell-containing, and fat-forming histology, as well as those from extrathoracic sites, including the meninx. Atypical, frankly malignant and even dedifferentiated variants have also been recognized in a subset of SFTs. Notably, the recent groundbreaking discovery of the disease-defining NAB2-STAT6 gene fusion, resulting from intrachromosomal inversion involving 12q13.3, has largely unified tumors with the aforementioned variations. The derived immunohistochemical detection of nuclear STAT6 expression has high diagnostic value in distinguishing SFTs from histologic mimics, although some relevant pitfalls have been proposed as a precaution. NAB2-STAT6 fusions yield numerous transcript subtypes associated with the clinicopathological variations. Despite mostly following a favorable course, SFT is notoriously difficult for prognostication because of the propensity for late relapse or even metastases in 10-40% of cases, which prompts several proposed schemes incorporating age, size, mitosis, and/or necrosis as factors for risk stratification. Mitotic figures >4/10 HPFs, TERT promoter and/or TP53 mutations have been considered as variables that are better correlated with aggressiveness. Although radiotherapy and chemotherapy provide unsatisfactory responses, a better understanding of SFT tumorigenesis may pave the way for new treatment modalities. In this review, we comprehensively discuss the recent advances of SFTs in diagnostic and molecular pathology.

SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc.

Myoepithelial (ME) tumors of soft tissue and bone display a heterogeneous histologic spectrum and in about half of the cases harbor EWSR1 gene rearrangements. Despite rare case reports, the prevalence of fused in sarcoma (FUS) gene abnormalities and its related fusion partners remains undetermined among ME tumors. Therefore, we screened 66 EWSR1-negative ME tumors for FUS abnormalities by fluorescence in situ hybridization (FISH). In an index FUS-rearranged case, 3'-rapid amplification of cDNA ends (RACE) was applied to identify the fusion partner. Results were further confirmed by reverse transcription-PCR, followed by FISH screening the entire cohort of FUS-rearranged and EWSR1-positive ME lesions lacking a known fusion partner. The correlation between genotype and clinicopathological features was also investigated. As a result, six (9%) FUS-rearranged cases were identified, spanning divergent age groups, tumor locations, and morphologic features. A novel FUS-KLF17 fusion was identified by 3'-RACE in an 11-year-old girl with a foot lesion associated with locoregional metastases. Three additional cases with FUS-KLF17 fusions were identified and one KLF17 rearrangement (6.3%) was found among the 16 EWSR1-positive cases tested. The KLF17-related ME tumors affected younger patients and often exhibited trabecular growth in a myxohyaline stroma, but this genotype did not correlate with a malignant phenotype. In conclusion, a small subset of ME tumors harbor FUS rearrangements, two thirds of them being associated with KLF17 fusion. FUS FISH analysis is recommended in EWSR1-negative lesions in which a ME diagnosis is suspected. KLF17 is also a rare gene fusion partner to EWSR1-rearranged ME tumors.