Biphenotypic sinonasal sarcoma: demographics, clinicopathological characteristics, molecular features, and prognosis of a recently described entity

Abstract

Biphenotypic sinonasal sarcoma (BSNS) is a recently recognized type of sarcoma arising exclusively in the sinonasal tract displaying unique clinical course, histopathology, and genetics. Due to its rarity, only case series and case reports are available. In order to provide an overview of the current understanding of this disease, we present a comprehensive review of the literature and present three previously unreported cases of BSNS. A total of 55 genetically characterized and 41 cases without molecular data were identified in the literature. Two-thirds of patients were female and the peak incidence was in the fifth decade. Fatal outcome was rare (two cases with intracranial extension) and local recurrence occurred in 31.6%, all occurring within 5 years after initial treatment. Histologically, BSNS is highly cellular in the majority of cases and composed of fascicles of spindle cells, with entrapped hyperplastic surface epithelium being a frequent finding. The immunohistochemical profile is characteristic due to the biphasic nature of this lesion, with shared features of both myogenic and neural origin. Rhabdomyoblastic differentiation is apparent in a subset of cases. The most common genetic event is the PAX3-MAML3 fusion (58.6%) but isolated PAX3 rearrangement (19.2%), absence of rearrangements (9.1%), PAX3-FOXO1 (8.1%), PAX3-NCOA1 (4%), and isolated MAML3 rearrangement (2%) have also been reported. In conclusion, the recognition of BSNS is crucial due to its relatively indolent clinical course. A selected immunohistochemical panel and/or molecular confirmation can be used to aid in appropriate diagnosis and consequently in prognostication and to avoid overtreatment with chemotherapy regimens used in its mimics.

PRRX‐NCOA1/2 rearrangement characterizes a distinctive fibroblastic neoplasm

“…There is significant homology amongst members of the NCOA family; unsurprisingly, fusions involving other NCOA family members— NCOA1 and NCOA3 —have likewise been implicated in many of the same, or related, mesenchymal tumors. For example, rhabdomyosarcoma may have NCOA1 rearrangement, uterine adenosarcoma may have NCOA3 rearrangement, uterine tumor resembling ovarian sex cord tumor may also have NCOA3 or NCOA1 rearrangement (Dickson, unpublished), and biphenotypic sinonasal sarcoma may have NCOA1 rearrangement . The PRRX1 gene (paired related homeobox 1) encodes a DNA‐binding protein that acts as a transcription coactivator important for development, including skeletogenesis .…”

“…For example, rhabdomyosarcoma may have NCOA1 rearrangement, 30,37 uterine adenosarcoma may have NCOA3 rearrangement, 33,38 uterine tumor resembling ovarian sex cord tumor may also have NCOA3 34 or NCOA1 rearrangement (Dickson, unpublished), and biphenotypic sinonasal sarcoma may have NCOA1 rearrangement. [39][40][41] The PRRX1 gene (paired related homeobox 1) encodes a DNA-binding protein that acts as a transcription coactivator important for development, 42 including skeletogenesis. 43 Mutations have been linked to the agnathia-otocephaly complex, a rare condition associated with mandibular hypoplasia, auricular abnormalities, and microstomia.…”

Recurrence of a complex anterior skull base tumour managed with an uncommon surgical approach

“…Biphenotypic sinonasal carcinomas are a recently recognised low-grade sarcoma that exhibit both neural and myogenic differentiation and evolve exclusively in the sinonasal tract 2. Due to their rarity, only case reports and case series are available.…”

“…Sarcomas involving the head and neck are rare malignancies 1. Biphenotypic sarcomas represent a further rare histopathological classification of these which exhibits both neural and myogenic differentiation 2. This case of a frontoethmoidal tumour represents a challenge to treat due to the proximity of the sarcoma to the right orbit, its extension into the intracranial cavity and the involvement of the frontal sinus, cribiform plate and frontoethmoidal region.…”

An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome

“…As implied by its name, two cell populations emerge by immunohistochemistry, one of neural and one of myogenic lineage. Hence, the diagnosis is made by positive for S100 and at least one muscle marker, of which smooth muscle actin is most consistently positive, or by demonstration of the characteristic genetics of this lesion (; see below; Fig. C, D).…”