Biphenotypic Sinonasal Sarcoma Research Articles

Biphenotypic Sinonasal Sarcoma With High-Grade Features: A Diagnostic Challenge.

Biphenotypic sinonasal sarcoma (BSNS) is a rare neoplasm of the sinonasal tract. These tumors show neural and myogenic differentiation and are characterized by PAX3 translocations. The immunophenotypic features reflect their dual differentiation. They are low-grade sarcomas that show monomorphic spindle cells in sheets, fascicles, and herringbone patterns and are positive for S100 and smooth muscle actin. These tumors are common in elderly female patients and have a locally aggressive course. High-grade presentation or transformation was not documented until recently. Total 3 BSNSs have now been documented in the literature and we report a fourth tumor with high-grade transformation 8 years after the initial presentation. We identify the morphologic and immunohistochemical features of the high-grade areas and we highlight the stark differences with the low-grade areas based on literature and our specimen. We also discuss the diagnostic challenges that may come up with such a presentation.

Challenging differential diagnoses in small biopsies from the sinonasal tract.

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 with Orbital and Skull Base Involvement Report of 3 Cases and Systematic Review of the Literature

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.

Detection of salivary gland and sinonasal fusions by a next-generation sequencing based, ligation-dependent, multiplex RT-PCR assay.

The discovery of tumour type-specific gene fusion oncogenes in benign and malignant salivary gland and sinonasal (SGSN) tumours has significantly increased our knowledge about their molecular pathology and classification. We developed a new targeted multiplexed next-generation sequencing (NGS)-based method that utilizes ligation dependent reverse-transcriptase polymerase chain reaction (LD-RT-PCR) to detect oncogenic fusion transcripts involving 116 genes, leading to 96 gene fusions known to be recurrently rearranged in these tumours. In all, 180 SGSN tumours (formalin-fixed, paraffin-embedded samples, 141 specimens and 39 core needle biopsies) from the REFCORpath (French network for rare head and neck cancers) with previously identified fusion genes by fluorescent in situ hybridisation (FISH), RT-PCR, or molecular immunohistochemistry were selected to test its specificity and sensitivity and validate its diagnostic use. Tested tumours encompassed 14 major tumours types, including secretory carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary gland intraductal carcinoma, clear cell carcinoma, pleomorphic adenoma, adamantinoma-like Ewing Sarcoma, EWSR1::COLCA2 sinonasal sarcoma, DEK::AFF2 sinonasal carcinoma, and biphenotypic sinonasal sarcoma. In-frame fusion transcripts were detected in 97.8% of cases (176/180). Gene fusion assay results correlated with conventional techniques (immunohistochemistry [IHC], FISH, and RT-PCR) in 176/180 tumours (97.8%). This targeted multiplexed NGS-based LD-RT-PCR method is a robust, highly sensitive method for the detection of recurrent gene fusions from routine clinical SGSN tumours. It can be easily customized to cover new fusions. These results are promising for implementing an integrated NGS system to rapidlydetect genetic aberrations, facilitating accurate, genomics-based diagnoses, and accelerate time to precision therapies in SGSN tumours.

Special mesenchymal neoplasms of the head and neck: Update from the 2022 WHO

Similar to the approach adopted in the classification of tumors in other organs, anew feature of the current Word Health Organization (WHO) classification of the head and neck tumors is the exclusion of soft tissue tumors from single organs and their inclusion in aseparate chapter devoted to them. This applies to tumors that are principally ubiquitous but show apredilection for the head and neck sites. The only exception to this rule represents those entities that are almost restricted to aspecific head and neck site/organ (such as nasopharyngeal angiofibroma, sinonasal glomangiopericytoma, and biphenotypic sinonasal sarcoma), which remain in their respective organ chapters. Included among soft tissue tumors are some old but still underrecognized entities, such as phosphaturic mesenchymal tumors, and newly defined entities, such as GLI1-altered tumors. The aim of including these entities is to enhance recognition of these uncommon but likely under-recognized entities to better characterize them in the future. This review summarizes the main features of these rare entities and discusses their differential diagnoses.

Sinonasal biphenotypic sarcoma of uvula: the first case report

Biphenotypic sinonasal sarcoma is a rare entity and it is a new term included in literature recently. It affects sinonasal tract exclusively but we report the first case of biphenotypic sinonasal sarcoma of uvula. The patient is a 56-year-old male who had a mass in the oropharynx hanging from the uvula exclusively. Contrast enhanced computed tomography of oral cavity reported homogenously enhancing benign mass arising from uvula probably pleomorphic adenoma. It was excised in toto and sent for histopathological examination. The detailed histopathological analysis concluded the diagnosis as sinonasal biphenotypic sarcoma of uvula. Sinonasal biphenotypic sarcoma is exclusively found in sinonasal tract. Occurrence of this entity in uvula is first of its kind and needs special attention.

Biphenotypic sinonasal sarcoma-A recently described entity with many mimics: A case report.

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.

Top 10 Significant Spindled Head and Neck Lesions to Scrutinze.

Spindled lesions are a challenging area in head and neck pathology. This is particularly true in the sinonasal tract, where several uncommon entities with both unique and overlapping morphologic, immunophenotypic, and/or molecular features can occur. Review. The clinicopathologic characteristics of biphenotypic sinonasal sarcoma and nine important differential diagnostic considerations with one or more overlapping feature are summarized to establish a practical framework for approaching spindled lesions of the sinonasal tract. Morphologic evaluation is central to the work up of sinonasal spindle cell lesions-in particular, cellular morphology, tumor architecture and growth pattern, and the presence of admixed epithelial elements - however, focused immunohistochemical analysis of neural, myogenic, rhabdomyoblastic, epithelial, and/or melanocytic marker expression and/or ancillary tests for tumor-specific molecular alterations may be necessary for definitive diagnosis.

Biphenotypic Sinonasal Sarcoma: A Genetically Confirmed Case Showing Bone Invasion Accompanying a Non-neoplastic Respiratory Epithelium.

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.

Biphenotypic sinonasal sarcoma – a case report on a newly described entity

Malignant spindle cell tumours comprise ∼1% of all head and neck malignancies.1 One such entity is biphenotypic sinonasal sarcoma. This is a new entity first introduced in the WHO head and neck tumours classification in 2017. This can be easily misdiagnosed due to its rarity, novelty and morphology that overlaps with other diagnoses, both benign and malignant in the sinonasal tract. Expressing both neural and myogenic immunophenotypes and its monomorphic appearance due to its origin from a genetic fusion is atypical but characteristic.

Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review

Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm. Retrospective review of patients affected by BSNS who were treated via an endoscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guidelines. A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively. BSNS is a locally aggressive tumour with a low recurrence rate and encouraging survival outcomes if properly treated with surgical resection and free margins followed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol.

Recurrent EWSR1::COLCA2 Fusions Define a Novel Sarcoma With Spindle/Round Cell Morphology and Strong Predilection for the Sinonasal Tract.

The last 2 decades have attended a dynamic evolution in the nosology of poorly differentiated sinonasal tract malignancies, with several new molecularly defined entities having been described in addition to delineation of the genetic driver/s of some established older entities. These discoveries, however, mostly concerned epithelial-derived neoplasms (carcinomas). Adamantinoma-like Ewing sarcoma and biphenotypic sinonasal sarcoma are the major representatives of the newly defined mesenchymal categories. The colorectal cancer associated 2 (COLCA2) has been discovered recently as a colorectal cancer risk gene locus, but fusions involving this gene have not been well characterized. We, herein, describe clinicopathologic and molecular features of a novel sinonasal sarcoma characterized by undifferentiated spindle/round cell morphology and defined by recurrent EWSR1::COLCA2 fusions. All patients (n=5) were adults (3 female and 2 male) with a median age of 46 years (range, 23 to 60y). The tumors originated in different subsites of the sinonasal tract with frequent multisite involvement. Original diagnoses were undifferentiated or unclassified round cell/spindle cell neoplasm/sarcoma (n=4) and neuroendocrine carcinoma (n=1). Surgery with or without adjuvant chemoradiation was the treatment in all cases. At the last follow-up, 1 patient developed multiple local recurrences over 21 years and another developed local recurrence and distant metastasis to bone 27 months after diagnosis. A third patient developed local recurrence 11 months later. Two patients were disease-free at 23, and 24 months. Histology showed nondescript highly cellular neoplasms with an admixture of spindled and round cells disposed into solid sheets and fascicles with brisk mitotic activity. Immunohistochemistry was negative for all lineage-specific markers with only limited focal membranous CD99 (4 of 5 cases) and weak pankeratin (1 of 5 cases) expression. Targeted RNA sequencing revealed an EWSR1::COLCA2 fusion, verified by EWSR1 fluorescence in situ hybridization, in all cases. This series identifies a novel member in the undifferentiated spindle/round cell sarcoma category with strong predilection for the sinonasal tract. None of >10,000 epithelial and mesenchymal neoplasms tested at the authors' centers during the same period showed this fusion, highlighting rarity of tumors carrying this gene fusion. Accordingly, molecular testing of unclassified sinonasal malignancies/sarcomas showing round and spindle cell morphology is recommended to enhance the identification and further characterization of this entity.

Small Biopsy Samples: Are They Representative for Biphenotypic Sinonasal Sarcoma?

(1) Background: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade neoplasm of the sinonasal tract. It is characterized by specific PAX3 gene rearrangements and both myogenic and neural differentiation. The purpose of the study was to describe the histologic, immunohistochemical and molecular features of BSNS and indicate important clues for small incisional biopsy diagnostics. (2) Methods: Archival samples from patients with nasal cavities or ethmoid sinuses tumors were searched for BSNS cases. Inclusion criteria were the presence of spindle cell morphology and low-grade appearance. Both biopsy and resection specimens were stained for identical IHC panels including, i.a., S100, SMA, SOX10 and PAX3. FISH for PAX3 and SS18 was performed on biopsy specimens. (3) Results: BSNS diagnosis was made in 6 cases included in the study and confirmed by PAX3 rearrangement by FISH in 5 specimens. The pattern of IHC expression was identical for paired biopsy and resection samples apart from one BSNS case. (4) Conclusions: Incisional biopsy seems to be a sufficient method to establish BSNS diagnosis in most cases. Characteristic morphological features together with S100, SOX10 and SMA as the screening markers are useful for confirming the diagnosis. In cases of divergent morphology and immunoprofile evaluation of PAX3 rearrangement is vital.

High-grade transformation of low-grade biphenotypic sinonasal sarcoma: Radiological, morphophenotypic variation and confirmatory molecular analysis

Biphenotypic sinonasal sarcoma (BSNS) is a recently described spindle cell sarcoma with neural and myogenic differentiation which arises exclusively in the sinonasal region.A man presented with swelling of left eyelid, and history of resection of a low-grade spindle cell mesenchymal tumor of left sinonasal cavity performed 15 years before. The original diagnosis was synovial sarcoma. Current MRI showed left supraorbital mass with intracranial extension. IR biopsy confirmed recurrence, and a left orbital craniotomy was done. NGS identified PAX3-MAML3 fusion in both, current and original tumor. The sarcoma was reclassified as BSNS, recurrent, with higher grade transformation. While the morphology, phenotype and molecular signature were in keeping with BSNS, the tumor showed biological progression towards a high-grade sarcoma.High-grade transformation of low-grade BSNS has not been described so far. High-grade transformation was not appreciated at the time of initial diagnosis, and it occurred in the local recurrence 15 years after.

A Case of Biphenotypic Sinonasal Sarcoma Found in a Young Woman’s Nasal Cavity

Biphenotypic sinonasal sarcoma (BSNS) is a newly recognized, very rare malignant tumor of nose and paranasal sinuses, which usually occurs in women. This tumor contains both neural and muscle tissue in the tumor tissue. It is an invasive disease occuring locally in the nasal cavity. However, if not found early, it can spread along the facial structure, for instance, the orbit, skull base, intracranium, and the oropharynx. This tumor is an uncommon disease that has not been reported in Korea to date. We report a case of a 35-year-old female recently diagnosed with BSNS with a review of the literature.

Low-Grade Biphenotypic Sinonasal Sarcoma: Case Report, Current Understanding, and Differential Diagnosis

Abstract Low-grade biphenotypic sinonasal sarcoma (BSS) is a rare, locally aggressive mesenchymal neoplasm of the sinonasal tract defined by dual expression of neural and myogenic antigens and recurrent PAX3 (paired box gene 3) gene rearrangements. We herein present the case of a 53-year-old woman with an incidentally identified lesion on surveillance magnetic resonance imaging for a pituitary microadenoma, ultimately leading to biopsy and resection of a low-grade BSS. Because of its relatively indolent behavior and extensive differential diagnosis, recognition and appropriate diagnostic workup of this entity are of utmost importance. The current understanding of low-grade BSS, its diagnosis, and differential diagnosis in the sinonasal tract are discussed.

Biphenotypic Sinonasal Sarcoma: A Case Report and Review of Literature.

Biphenotypic sinonasal sarcoma (BSNS), previously low-grade sinonasal sarcoma with neural and myogenic features, is a rare tumor of the sinonasal tract first described in 2012. Due to its rarity, limited literature is available in providing clinicians with a standardized treatment regimen, particularly in cases of positive surgical margins. This article aims to provide a clinical review of the currently available reported cases of BSNS, as well as presenting clinical, radiologic, and pathologic details of 2 novel cases. Online electronic databases include PubMed and Embase where queried for reports of biphenotypic sinonasal sarcoma or low-grade sinonasal sarcoma with neural and myogenic features. Two previously unpublished cases were included in the results. Data including clinical presentation, epidemiologic data, radiologic evaluation, intraoperative details, histopathology, treatment modality, and postoperative follow-up information were included. A total of 100 previously published cases were identified in 12 prior articles. Mean age at presentation was 52.9 years. Extrasinonasal extension was observed in 27.4% of cases with most common site of extension being cribriform plate. Forty-seven cases included treatment details with surgical excision being the most common modality. Recurrence rates were identical for both surgical excision alone and surgical excision with adjuvant radiotherapy (33.3%). Biphenotypic sinonasal sarcoma is a slow-growing tumor that is amenable to surgical resection. Recurrence rates are similar between surgical excision and surgical excision with adjuvant radiation therapy, but limited data in reported cases preclude a determination of treatment superiority.

Curating Archival Anatomic Pathology Material For Machine Learning Algorithm Development

Abstract Introduction/Objective Advances in whole slide imaging have enabled the application of machine learning algorithms to anatomic pathology. In the current state, the development of accurate algorithms requires robust training data with correctly assigned diagnostic and classification labels. Increasingly, institutions have looked to their archival slides as a source of “ground truth” for algorithm development. However, the curation and use of archival data poses several challenges. Here, we share lessons learned from reviewing head and neck pathology consult cases spanning a 10- year period at Mayo Clinic Rochester. Methods Archived surgical pathology slides from 2,590 consult cases were reviewed. Clinical and demographic information was recorded for each case, including surgical date, surgical procedure, anatomic site, age, gender and diagnosis. Cases were excluded from the curated archive if there was insufficient volume or quality of tissue to render a specific diagnosis (141 cases, 5.6%). Slides with a range of tissue size and quality, from numerable laboratories were included in the curated archive. Selected cases were collated by anatomic site: ear, gnathic, larynx, nasopharynx, neck, oral cavity, oropharynx, salivary gland and sinonasal tract. Results Common diagnostic reconciliations (115 cases, 4.4%) fell within the following categories: (1) novel entities (59 cases, 2.3%), including biphenotypic sinonasal sarcoma and clear cell carcinoma; (2) novel classifications (21 cases, 0.8%), as seen in HPV-related oropharyngeal squamous cell carcinoma and polymorphous adenocarcinoma; and (3) novel grading schema (35 cases, 1.4%), as seen in keratinizing dysplasia and oropharyngeal malignancies. Conclusion Several nuances emerged in the process of reviewing slides, highlighting the need for continual amendment of any machine learning dataset over time. Curating anatomic pathology cases for machine learning algorithm development requires the recognition of emerging entities, with re-classification and re-grading as needed.

BIPHENOTYPIC SINONASAL SARCOMA OF THE NASOPHARYNX: CASE REPORT

Biphenotypic sinonasal sarcoma is a rare and recently recognized entity. It is a low-grade sarcoma which exhibits both neural and myogenic differentiation. The objective of this study is to report a case of a 25-year-old male patient with nasal congestion and bleeding. Computed tomography showed a tumor mass in the nasopharynx. Microscopic analysis showed a cellular proliferation of spindle cells, forming mainly a herringbone-like fascicular growth pattern. Immunohistochemical analysis showed focal positivity for S100, alpha-smooth muscle actin, and calponin, and negativity for desmin, SOX 10, and FXIIIA. We present an uncommon case of biphenotypic sinonasal sarcoma of the nasopharynx and emphasize the importance of recognizing rare entities with impact on the health of these patients.

Clinical management of emerging sinonasal malignancies.

Several emerging sinonasal malignancies have recently been described in the pathology literature. Although not all distinctly classified by the World Health Organization, these rare tumors present a management challenge to surgeons and oncologists. While prior studies have summarized histologic details, a clinically focused review is currently lacking in the literature. This review describes the presentation, histopathology, imaging, treatment, and prognosis of newly described or recently evolving sinonasal malignancies while highlighting the distinguishing features of these entities. It includes teratocarcinosarcoma, human papillomavirus-related multiphenotypic carcinoma, biphenotypic sinonasal sarcoma, sinonasal renal cell-like adenocarcinoma, NUT-midline carcinoma, squamous cell carcinoma associated with inverted papilloma, sinonasal undifferentiated carcinoma, and INI-1-deficient sinonasal carcinoma. By describing the diagnosis, treatment, and prognosis of these recently defined entities, this clinical review aims to help guide oncologists in the clinical management of these patients.