The many faces of solitary fibrous tumor; diversity of histological features, differential diagnosis and role of molecular studies and surrogate markers in avoiding misdiagnosis and predicting the behavior

Abstract

Background Solitary Fibrous Tumor (SFT) is a distinct soft tissue neoplasm associated with NAB2-STAT6 gene fusion. It can involve a number of anatomic sites and exhibits a wide spectrum of histological features. Main body Apart from diversity in morphological features seen even in conventional SFT, two histologic variants (fat-forming and giant cell-rich) are also recognized. In addition, a malignant form and dedifferentiation are well recognized. Owing to diverse histological features and involvement of diverse anatomic locations, SFT can mimic other soft tissue neoplasms of different lineages including schwannoma, spindle cell lipoma, dermatofibrosarcoma protuberans, liposarcoma, gastrointestinal stromal tumor (GIST), malignant peripheral nerve sheath tumor (MPNST), and synovial sarcoma. SFT is classified as an intermediate (rarely metastasizing) tumor according to World Health Organization Classification of Tumors of Soft tissue and Bone, 5th edition. The management and prognosis of SFT differs from its malignant mimics and correct diagnosis is therefore important. Although SFT expresses a distinct immunohistochemical (IHC) profile, the classic histomorphological and IHC profile is not seen in all cases and diagnosis can be challenging. NAB2-STAT6 gene fusion has recently emerged as a sensitive and specific molecular marker and its IHC surrogate marker signal transducer and activator of transcription 6 (STAT6) has also shown significant sensitivity and specificity. However, few recent studies have reported STAT6 expression in other soft tissue neoplasms. Conclusion This review will focus on describing the diversity of histological features of SFT, differential diagnoses and discussing the features helpful in distinguishing SFT from its histological mimics.

A Case Report of a Solitary Fibrous Tumor of the Maxillary Sinus

“…While these features are consistent with those previously reported in literature, it has to be said that none of them are pathognomonic of SFT [3]. Therefore, the differential diagnosis must include glomangiopericytoma, inverted papilloma, hemangioma, leiomyomas, schwannoma, squamous cell carcinoma, juvenile angiofibroma, angiomatous polyps, nerve sheets tumors, mesenchymal chondrosarcoma, and byphenotipic synovial sarcoma [7][8][9]. The former definition of hemangiopericytoma has been integrated under the SFT nomenclature in the 2013 WHO classification [6].…”

“…None of the benign tumors mentioned here show CD34 and STAT6 expression [8]. Tumors with neural differentiation, such as neurofibroma or schwannoma, can histologically mimic SFTs, but they differ by expressing S-100 protein and SOX10 while lacking STAT6 expression [8]. Histologically, synovial sarcomas appear to be made of spindle cells, with the possible presence of collagen bands and branching vessels, similarly to SFTs.…”

“…Nasopharingeal angiofibromas, on the other side, are usually positive for androgen receptor expression. None of the benign tumors mentioned here show CD34 and STAT6 expression [8]. Tumors with neural differentiation, such as neurofibroma or schwannoma, can histologically mimic SFTs, but they differ by expressing S-100 protein and SOX10 while lacking STAT6 expression [8].…”

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

“…Strong and diffuse nuclear immunoreactivity for Signal transducer and activator of transcription 6 (STAT6) is almost always diagnosed in SFTs, and CD34, Bcl-2 and CD99 immunoexpression is common . Aberrant epithelial, muscular or neuroendocrine marker expression has been described which may lead to confusion with other tumors that share a similar morphology [15][16][17][18][19][20][21][22][23][24][25]36]. The fusion gene NAB2/STAT6 and its variants confirm a diagnosis of SFT in those cases with unconvincing STAT6 immunoreactivity, and specific gene fusions have been related to prognosis and tumor location [6][7][8][9][10][11][12][13][14][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

“…Aberrant epithelial, muscular or neuroendocrine marker expression has been described which may lead to confusion with other tumors that share a similar morphology [15][16][17][18][19][20][21][22][23][24][25]36]. The fusion gene NAB2/STAT6 and its variants confirm a diagnosis of SFT in those cases with unconvincing STAT6 immunoreactivity, and specific gene fusions have been related to prognosis and tumor location [6][7][8][9][10][11][12][13][14][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. STAT6 nuclear expression is not exclusive to SFTs and has also been reported in dedifferentiated liposarcoma, glioma-associated oncogene homolog 1 (GLI1)-amplified tumor, Kaposi sarcoma and Hodgkin as well non-Hodgkin lymphomas [6,[12][13][14][15][16][17][18][19][20]…”