Biphenotypic sinonasal sarcoma (BSNS), previously known as low-grade sinonasal sarcoma, is a rare tumour of the sinonasal tract, first described in 2012. It involves both myogenic and neural differentiation and is characterized by PAX3 rearrangement. MAML3 is the most frequent fusion partner of PAX3; however, its partner remains unidentified in a subset of cases. These tumours have significant local recurrence rates but lack metastatic potential. Here, we report a case of BSNS with PAX3/FOXO1 fusion and discuss its clinicopathological features and differential diagnosis.

This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches.
Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.

Spindle cell neoplasms arising in the head and neck may be challenging to recognize due to their relative rarity. While underlying molecular alterations are increasingly elucidated, testing for these features may not be readily available. In most cases, combinations of key morphologic features and diagnostic immunohistochemical markers can be used to replace molecular diagnostics. Conversely, some molecular alterations and expression of their surrogate biomarkers are not specific for any one entity, and it is important to recognize these to avoid diagnostic pitfalls. In this review, we discuss both old and new spindle cell tumors of the sinonasal tract, with an emphasis on histologic features and clinically relevant immunohistochemical markers serving as surrogate markers for underlying genomic alterations.

Biphenotypic sinonasal sarcoma (BSNS) is a rare malignant tumour of the upper nasal cavity and ethmoid sinuses that presents predominantly in middle aged female patients and show a characteristic infiltrative and hypercellular proliferation of spindle cells that demonstrate a specific immunoreactivity. We present three cases with BSNS that had different presenting complaints, either sinonasal or orbital problems, underwent endoscopic surgical treatment and/or radiotherapy and have been disease free on long follow up. A systematic review of all published cases was performed to identify all BSNS cases known at present. BSNS requires prompt and correct diagnosis with accurate surgical resection as well as consideration of radiotherapy. Our three cases confirm the findings of the literature and support that BSNS is an aggressive but treatable malignant disease of the sinonasal tract.

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Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade malignancy occurring in the sinonasal tract that is characterized by dual neural and myogenic differentiation. Rearrangements involving the PAX3 gene, usually with MAML3, are a hallmark of this tumor type and their identification are useful for diagnosis. Rarely, a MAML3 rearrangement without associated PAX3 rearrangement has been described. Other gene fusions have not been previously reported. Herein, we report a 22 year-old woman with a BSNS harboring a novel gene fusion involving the PAX7 gene (specifically PAX7::PPARGC1A), which is a paralogue of PAX3. The histologic features of the tumor were typical with two exceptions: a lack of entrapment of surface respiratory mucosa and no hemangiopericytoma-like vasculature. Immunophenotypically, the tumor was notably negative for smooth muscle actin, which is usually positive in BSNS. However, the classic S100 protein-positive, SOX10-negative staining pattern was present. In addition, the tumor was positive for desmin and MyoD1 but negative for myogenin, a pattern that is common among BSNS with variant fusions. Awareness of the possibility of PAX7 gene fusions in BSNS is important as it may aid in the diagnosis of PAX3 fusion negative tumors.

Sinonasal biopsy specimens are a challenging area in anatomic pathology. The small, often fragmented or crushed nature of these biopsies can hinder morphologic assessment. Additionally, many of the tumors in this area are rare and share morphologic, and sometime immunophenotypic similarities. In many cases, immunohistochemistry is helpful if not necessary to reach a specific diagnosis. In other cases, a specific diagnosis is not possible and a differential diagnosis must be given on a biopsy specimen despite access to a well-equipped immunohistochemistry laboratory. This review article groups some of the more challenging entities in the sinonasal region based on morphologic patterns. These include low grade squamoid lesions such as sinonasal (Schneiderian) papilloma and DEK::AFF2 rearranged carcinoma, glandular neoplasms such as intestinal and non-intestinal type sinonasal adenocarcinoma, high-grade carcinomas such as HPV-related multiphenotypic sinonasal carcinoma, NUT carcinoma and SWI/SNF deficient carcinomas, small round blue cell tumors such as teratocarcinosarcoma, neuroendocrine carcinoma and olfactory neuroblastoma, and finally, low grade spindle cell neoplasms such as glomangiopericytoma, biphenotypic sinonasal sarcoma and solitary fibrous tumor.

Biphenotypic sinonasal sarcoma (BSNS) is a recently described, low-grade, slow-growing sarcoma with neural and myogenic features with exclusive location in sinonasal track and characteristic PAX3- MAML3 gene fusion. Differentiating this tumor from its commoner mimics needs knowledge of this entity to avoid over treatment. This tumor has unique morphology, clinical course, and genetics. We report this in a 47-year-old female who was diagnosed with such a rare, solitary fibrous tumor-hemangiopericytoma (HPC-SFT) on limited initial biopsy. On subsequent excision, typical morphology and immunohistochemistry helped to clinch the diagnosis.

BACKGROUND: Biphenotypic sinonasal sarcoma (BSNS) is a rare spindle cell sarcoma distinctly arising in the sinonasal area, with dual myogenic and neural differentiation, and characterised by the presence of PAX3 gene fusion, typically with MAML3. Although the majority may be indolent, up to 25% of cases reported in the literature are locally aggressive, with invasion of adjacent critical structures in the head and neck region.
METHODS: We report 3 cases of BSNS reviewed at our institution between 2016-2020 in addition to the current literature. Patient 1 underwent surgery followed by adjuvant radiotherapy but relapsed 24 months later and was not fit for systemic anticancer therapy and managed with palliative care. Due to comorbidities, patient 2 was recommended for active surveillance, with a view to intervening with radiotherapy should there be evidence of clinical progression. At 60 months, the nasal cavity mass remained stable on serial imaging. Patient 3 underwent primary surgical R0 resection and was offered adjuvant post operative radiotherapy 60 Gy/30 fractions/6 weeks but opted for active surveillance and has no clinical or radiological evidence of recurrence 22 months after surgery.
CONCLUSIONS: The primary management for BSNS is surgical resection. We recommend discussing the role of postoperative adjuvant radiotherapy 60 Gy/30 fractions/6 weeks in patients who are fit for treatment. In clinical practice, dose levels will be constrained by surrounding normal tissues. At present, the role of systemic anticancer therapy is undefined. A prospective registry of ultra-rare cases may provide an evidence base with which to select optimal treatment strategies for BSNS in the future.

Biphenotypic sinonasal sarcoma is a newly established tumor entity that is associated with distinct clinicopathological findings. Biphenotypic sinonasal sarcoma is a rare, low-grade spindle cell sarcoma that arises in middle-aged females, exclusively in the sinonasal tract. A fusion gene involving PAX3 is detected in most biphenotypic sinonasal sarcomas, which aids in its diagnosis. Here, we report a case of biphenotypic sinonasal sarcoma with its cytological findings. The patient was a 73-year-old woman who presented with purulent nasal discharge and dull pain in the left cheek area. Computed tomography showed a mass extending from the left nasal cavity to the left ethmoid sinus, the left frontal sinus, and the frontal skull base. She underwent a combined transcranial and endoscopic approach for en bloc resection with a safety margin. Histologically, spindle-shaped tumor cells have been thought to proliferate mainly in the subepithelial stroma. Here, nasal mucosal epithelial hyperplasia was noted, and the tumor had invaded the bone tissue accompanying the epithelial cells. Fluorescence in situ hybridization (FISH) analysis showed a PAX3 rearrangement, and next-generation sequencing identified a PAX3::MAML3 fusion. Based on FISH, split signals were observed not in respiratory cells but in stromal cells. This indicated that respiratory cells were non-neoplastic. In the diagnosis of biphenotypic sinonasal sarcoma, the inverted growth of the respiratory epithelium can be a diagnostic pitfall. FISH analysis using a PAX3 break-apart probe is helpful not only for an accurate diagnosis but also for detecting the true neoplastic cells.