Evan Kominsky, BA1, Andre E. Boyke, MS1, Daniel Madani, MD2, Ameet Kamat, MD3, Bradley A. Schiff, MD4, and Vijay Agarwal, MD4,5
Ear, Nose & Throat Journal2023, Vol. 102(6) 385–390© The Author(s) 2021Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/0145561321999196journals.sagepub.com/home/ear
AbstractObjectives: 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. Methods: 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 Two previously unpublished cases were included in the results.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. Results: 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%). Conclusions: 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.
Keywordsbiphenotypic sinonasal sarcoma, paranasal sinus, sarcoma, spindle cell tumor
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 2012.1 Patients typically present with vague, nonspecific symptoms related to tumor mass effect (eg, nasal obstruction, congestion, and sinonasal pain).2,3 Biphenotypic sinonasal sarcoma typically involves multiple subsites within the sinonasal tract, notably the ethmoid sinus and superior nasal cavity with extrasinonasal extension commonly to the orbit and cribriform plate.2 Due to the indolent nature of BSNS, surgical resection is performed routinely as the mainstay mode of treatment. In cases where the tumor sample reveals inconclusive or positive surgical margins, adjuvant chemotherapy or radiation therapy may be employed.2 Diagnosis is based on immunohistological findings consisting of spindle cell neoplasm with focal positivity for smooth muscle actin and S-100.4 Due to its rarity, limited literature is available in providing clinicians with a standardized treatment regimen. Reported cases often do not include treatment details, including surgical margin status, or have limited follow-up; only 1 prior case has included data from positron emission tomography.5 In this report, we review the literature and present 2 unpublished BSNS cases, including one with a positive surgical margin. We present relevant radiological, surgical, and pathological findings as well as treatment regimens.
A literature review was conducted in August 2019 employing the online electronic databases PubMed and Embase. Search terms included “biphenotypic sinonasal sarcoma” and “low-grade sinonasal sarcoma with neural and myogenic features.” Inclusion criteria included reported cases of (I) biphenotypic sinonasal sarcoma or low-grade sinonasal sarcoma with neural and myogenic features, with (II) confirmed histological diagnosis of BSNS. Two unpublished cases are also presented here as part of our comprehensive review of BSNS. Patient characteristics such as clinical presentation, epidemiologic data, radiologic evaluation, intraoperative report, histopathology, treatment modality, and postoperative follow-up information were included in this report.
A previously healthy 60-year-old male presents to clinic following a fall, on the background of bilateral nasal congestion, and blurry vision for the past 3 weeks. Computed tomography (Figure 1) and magnetic resonance (MR) imaging (Figure 2) performed as part of routine workup revealed a large infiltrative soft tissue mass localized to the left ethmoid sinus measuring 4.1 × 3.8 × 3 cm in dimension. The incidental mass extended into the right ethmoid air cells, superior nasal cavity, left orbital lamina, and left frontal sinus. Positron emission tomography (PET) demonstrated an avid fluorodeoxyglucose uptake of the mass, with SUV of 3.2 (Figure 3). An endoscopic transnasal approach was used for gross tumor resection. Intraoperatively, the mass was found to extend superiorly to involve the cribriform plate and was laterally adherent to the lamina papyracea. The cribriform plate and crista galli were resected, resulting in a small dural defect with a low flow cerebrospinal fluid (CSF) leak. This was repaired with a fascia lata graft, sealed with an acellular dermal matrix (Duragen) and oxidized cellulose (Surgicel) for hemostasis. Intraoperative margins returned negative. However, on final pathological diagnosis, multiple margins returned positive for tumor, including the dural margin. Histopathology of the tumor confirmed diagnosis of BSNS. The tumor exhibited focal staining with S-100 and smooth muscle actin (SMA) stain and was negative for epithelial membrane antigen and cytokeratin AE1/3 stain (Figure 4). Additionally, tumor cells were focally positive for desmin while negative for CD34, HMB-45, Mart-1, chromogranin, and synaptophysin. Fluorescence in situ hybridization testing for SS18 (SYT) rearrangement characteristic of synovial sarcoma was negative. The patient recovered well postoperatively. An informed discussion about the risks and benefits of adjuvant radiation therapy was had with the patient given the positive surgical margins. The patient elected to continue with clinical observation. Follow-up imaging at 1 year postoperatively revealed no gross evidence of disease recurrence.
A 70-year-old male with a history of chronic rhinosinusitis (CRS) presented to clinic with worsening nasal congestion, postnasal drip, and generalized facial pressure. Magnetic resonance imaging revealed an enhancing soft tissue mass in the left superior nasal cavity measuring approximately 1.6 × 1.2 × 1.2 cm, extending to the left frontal and anterior ethmoid sinuses and cribriform plate. An initial bilateral maxillary antrostomy and anterior ethmoidectomy were performed in treatment of the patient’s CRS and a tissue sample obtained for diagnosis. Intraoperatively, the mass was found to involve the left middle turbinate, which exhibited a large concha bullosa; the anterior frontal beak; and the left lamina papyracea, which was found to be dehiscent in multiple locations. Frozen pathology revealed a spindle cell neoplasm with indeterminate features, and the decision was made to end the initial procedure to await the final surgical pathology and to allow for appropriate treatment planning. The final pathological diagnosis revealed BSNS, and a second procedure was performed for complete tumor resection with negative surgical margins. The patient recovered well postoperatively, without evidence of a CSF leak. Follow-up imaging at 14 months revealed no evidence of tumor recurrence.
A total of 100 cases were identified in 12 previously published reports in addition to 2 novel cases presented here.1,4-12 Of all 102 cases, the mean age of presentation was 52.9 years old (range 24-87). The ratio of female:male patients was 1.8:1. The most common presenting symptoms included nasal obstruction, congestion, and epistaxis along with facial swelling, pain, and pressure. Ethmoid sinus and nasal cavity were frequently involved in this tumor series (64% and 60.9%, respectively). Extrasinonasal extension was observed in 27.4% of cases with cribriform plate and skull base representing the most common sites of tumor extension (50%). A total of 49 (49%) cases included treatment details and 58 (58%) included follow-up of any duration with median of 48 months (range: 2-336 months).
Of the reported cases, 9 included radiographic findings.5,7-10,13,14 Computed tomography scan demonstrated a homogeneous soft-tissue mass located in the paranasal sinuses and/or nasal canal. Additional findings included erosion through the lamina papyracea, hyperostotic bone formation, or thinning of the cribriform plate. One case demonstrated erosion of the anterior and posterior frontal plate with significant intracranial extension.9 Magnetic resonance imaging demonstrated a homogenously enhancing soft tissue mass with variable signal intensity (mild to strong). T1-weighted noncontrast images demonstrated low signal intensity that showed avid, homogenous enhancement in contrast sequences as well as heterogenous enhancement in postcontrast fat-saturated sequences. T2-weighted sequences showed homogeneous mild to moderate signal intensity. Magnetic resonance imaging was able to determine the extent of orbital involvement in one case.7 Intracranial extension with suspected dural involvement due to loss of CSF between the mass and brain parenchyma was seen in another case.13
Diagnosis of BSNS was based on both morphological and immunohistochemical characteristics. In all cases, the tumor cells demonstrated a spindle-shaped cell morphology as part of the diagnostic criteria. All cases showed either focal or patchy positivity for S100, and 92% showed focal or patchy positivity for SMA (81/88 cases). Positive b-catenin was observed in 19 (54%) cases. All cases tested were consistently negative to SOX10.
Of the 47 reported cases with treatment details, 29 (63%) underwent surgical excision alone; 11 (23.9%) underwent surgical excision and adjuvant radiation therapy; 3 (6.5%) underwent surgery and adjuvant chemotherapy; and 3 (6.5%) underwent surgery and chemoradiotherapy. One case was treated with chemoradiotherapy alone (Table 1). Of the cases with reported follow-up, recurrence occurred in 18 (31.0%) of 58 cases, with 2 cases reporting multiple recurrences. Average time to first recurrence was 34.5 months. Among patients treated with surgical excision alone, the recurrence rate was 33.3% (6/18) with median follow-up of 45 months. Median time to recurrence in this group was 24 months. Patients treated with surgical excision and adjuvant radiation therapy demonstrated a recurrence rate of 33.3% (3/9) with median follow-up of 47 months. Median time to recurrence in this group was 11 months.
The surgical excision treatment group demonstrated more frequent extrasinonasal extension (7 [24.1%] 29,) than the surgical excision with adjuvant radiation therapy group (1 [11.1%] 9,). The most frequent site of extension in the surgical group was the lamina papryacea, with the cribriform plate and anterior skull base being the next most common.
Biphenotypic sinonasal sarcoma is a rare entity only recently described in 2012.1 It was included in the most recent edition of the World Health Organization classification of head and neck tumors in 2017.15 The diagnosis of BSNS is based on its histological appearance of infiltrative spindle-shaped cells, focal immunohistochemical positivity for S-100 and SMA, and genetic translocations involving the PAX3 gene.3 Prior to its description, BSNS was most likely diagnosed as a fibrosarcoma or low-grade peripheral nerve sheath tumor owing to its similar morphology and immunohistochemical staining pattern.1 Given its biphenotypic expression, differential diagnoses for BSNS incorporated tumors with either neural or myogenic differentiation such as cellular schwannoma, peripheral nerve sheath tumors, glomangiopericytoma, and synovial sarcoma.16
Clinical symptoms of BSNS are typically due to mass effect as a consequence of its indolent growth course. There is only one reported case of a patient death as a direct result of tumor expansion.6 There have been no reported cases of metastatic disease. Twenty-nine cases were treated with surgical excision, with 17 (59%) having follow-up.5,7-11,13 Ten cases were treated with surgical excision and adjuvant radiation therapy, 9 of which had follow-up.10,11,14 Recurrence rates were equivalent between surgical excision alone and surgical excision with adjuvant radiation therapy (33.3%), suggesting little to no benefit for adjuvant radiation. Most cases with extrasinonasal extension were treated with surgical excision alone. The cases where adjuvant radiation was utilized do not describe whether negative surgical margins were achieved. Given the paucity of reported cases, it remains unknown if adjuvant radiation is indeed no better than surgical excision alone. Furthermore, it remains difficult to counsel patients with positive surgical margins as to the best treatment plan given the lack of long-term data on recurrence rates. Although cases are rare, postoperative outcome details are needed in order to achieve a greater understanding of the necessity and impact of various treatment regimens. Furthermore, the risks and consequences of chemotherapy or adjuvant radiotherapy should be given great consideration in patients with BSNS since the utility of these treatments are currently uncertain. Each case must be considered individually by an experienced group of multidisciplinary providers to determine the best treatment modality in conjunction with patient preference, with considerations given to feasibility of gross surgical resection, tolerability of chemotherapy and radiation toxicity, and patient goals of care.
Biphenotypic sinonasal sarcoma is a slow-growing tumor, with no known reports of metastatic disease, making it amenable to surgical resection. Recurrence rates are similar between surgical excision and surgical excision with adjuvant radiation therapy, but limited follow-up data in reported cases preclude a determination of treatment superiority, particularly in cases of positive surgical margins. As such, treatment planning by a multidisciplinary team is essential to achieve the best treatment outcome.
The authors wish to acknowledge Dr. Perry Cohen for his preparation and interpretation of the histological specimens presented herein.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Evan Kominsky https://orcid.org/0000-0001-8041-960X
Andre E. Boyke https://orcid.org/0000-0002-7485-0644
1 Albert Einstein College of Medicine, Bronx, NY, USA
2 University of Notre Dame, Sydney, Australia
3 Department of Otorhinolaryngology–Head and Neck Surgery, White Plains Hospital, NY, USA
4 Department of Otorhinolaryngology–Head and Neck Surgery, Montefiore Medical Center, Bronx, NY, USA
5 Department of Neurosurgery, Montefiore Medical Center, Bronx, NY, USA
Received: January 30, 2021; revised: January 30, 2021; accepted: February 9, 2021
Corresponding Author:Andre E. Boyke, MS, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.Email: andre.boyke@einsteinmed.org
