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CASE REPORT Table of Contents  
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Biphenotypic sinonasal sarcoma—a recently described entity with many mimics: A case report


1 Department of Pathology, Yashoda Hospital, Hyderabad, Telangana, India
2 Department of ENT Surgery, Yashoda Hospital, Hyderabad, Telangana, India
3 Department of Neuro Surgery, Yashoda Hospital, Hyderabad, Telangana, India

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Date of Submission24-Feb-2021
Date of Acceptance06-Jan-2022
Date of Web Publication06-Jun-2022
 

   Abstract 


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.

Keywords: Biphenotypic sinonasal sarcoma, BSNS, low-grade sinonasal sarcoma with neural and myogenic features, PAX3 gene, sinonasal sarcoma


How to cite this URL:
Ingle A, Mahendra N, Gopal Reddy G V. Biphenotypic sinonasal sarcoma—a recently described entity with many mimics: A case report. Indian J Pathol Microbiol [Epub ahead of print] [cited 2022 Aug 8]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=346689





   Introduction Top


Biphenotypic sinonasal sarcoma (BSNS) is a recently described, rare sarcoma comprising around 1% of all sinonasal sarcomas which in turn comprise < 1% of all head and neck malignancies.[1] It has characteristic histological, immunohistochemical, and molecular features—most frequently characteristic recurrent PAX3- MAML3 gene fusion and typical location of sinonasal track.[2] Still, due to its morphological overlap with other tumors, diagnosis on biopsy can be challenging. This tumor is included in the recent fourth edition of WHO classification of head and neck tumors. We report a case of this rare entity to highlight its morphological and clinical features and importance of differentiating this tumor from its mimics.


   Case History Top


We report a case of 47-year-old lady presenting with swelling of her right lower eyelid with progressive protrusion of right eyeball for 2 months. On examination, she had mild proptosis of right eye with swelling of right lower eyelid. There was no chemosis. She did not give any history of nasal bleed, frequent attacks of cold, headache, ear or throat complaints. Eye movements were normal and there were no visual disturbances. She was non-hypertensive and non-diabetic. Anterior rhinoscopy showed a fleshy growth at anterior end of middle turbinate [Figure 1]a, frontal recess, and anterior ethmoids [Figure 1]c. There was no evidence of fungal mucus. Examination of ear and throat was unremarkable. There was no lymphadenopathy. Systemic examination was unremarkable.
Figure 1: Anterior rhinoscopy showing a fleshy growth (arrows) at anterior end of middle turbinate (a), frontal recess to anterior ethmoids (b). CT scan showing a lobulated, heterogeneously enhancing mass lesion at right osteomeatal complex, infiltrating the right maxillary sinus, the middle turbinate, frontal/ethmoid sinus, right orbit, and displacing the globe laterally (c and d)

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Computed tomography (CT) scan and magnetic resonance imaging (MRI) showed a lobulated, heterogeneously enhancing mass lesion centering at right osteomeatal complex, infiltrating the right maxillary sinus, the middle turbinate, frontal/ethmoid sinuses, right orbit and was displacing the globe laterally [Figure 1]b and [Figure 1]d.

Biopsy from the mass (1.5 × 0.5 cm) was done by functional endoscopic sinonasal surgery (FESS). On histopathological examination, it was reported as spindle cell lesion with hemangiopericytomatous pattern favoring solitary fibrous tumor (SFT). Features of malignancy were not seen in this biopsy. Later, the mass was excised through extended frontonasal craniotomy along with endonasal endoscopic approach (5 × 2.5 × 2.0 cm). On histopathological examination, multiple biopsy bits, some lined by pseudostratified, columnar ciliated epithelium and at places lined by metaplastic stratified squamous epithelium were seen. Underlying stroma was variably cellular with spindly cells in fascicles and herring bone pattern. The cells had relatively monomorphic, spindly nuclei with fine chromatin. Mitoses or necrosis were not seen. Amidst this were small cystic spaces lined by tall columnar, pseudostratified, ciliated and at places by stratified squamous and oncocytic epithelium. Some of these cystic spaces were filled with eosinophilic secretions. Also noted were conspicuous thin-walled branching blood vessels in hemangiopericytoma pattern. Tumor was seen infiltrating the bone [Figure 2]. On immunohistochemistry, the tumor cells expressed Bcl2 and focally expressed SMA and S100. They were negative for CD34, HMB45/MelanA, and CD99. CD34 highlighted the hemangiopericytomatous vasculature [Figure 3]. Hence, the diagnosis of biphenotypic sinonasal sarcoma was rendered. Follow-up CT scan showed no residual tumor.
Figure 2: Sections show tumor composed of cystically dilated invaginations of epithelium (a), variably cellular spindly stroma (b) and bone invasion (c). Thin-walled, branching, hemangiopericytomatous blood vessels (d), intersecting bundles and fascicles of spindle cells (e and f) with entrapped epithelial elements and cysts lined by pseudostratified, ciliated, columnar, squamous (g) and oncocytic (h) epithelium are seen. Spindle cells are fairly monomorphic with fine chromatin and inconspicuous nucleoli (i). (Hematoxylin and eosin stain. a-c × 40, d-f × 100, g-h × 400)

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Figure 3: On immunohistochemistry, the tumor cells focally express S100 and SMA. They are also positive for Bcl2. CD34 highlights hemangiopericytomatous vasculature. (DAB. Antibodies are by PathnSitu. SMA, S100 and Bcl2- ×100; CD34- ×40)

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In view of infiltrative nature of the tumor, radiotherapy was advised. Patient tolerated the treatment well and is on regular follow-up for last 3 years with no evidence of recurrence.


   Discussion Top


BSNS was first described by Lewis et al.[3] in 2012 as a low-grade, sinonasal sarcoma with neural and myogenic differentiation having cellular spindle cell proliferation with uniform, elongate nuclei and infiltrative growth pattern. Two of their cases tested showed chromosomal translocation t (2;4). Subsequent studies demonstrated PAX3- MAML3 gene fusion in most cases with minority showing alternate PAX3 or MAML3 fusion genes including PAX3- FOXO1 and PAX3-NCOA1.[4] Apart from its role in oncogenesis, PAX3 as a transcription factor is involved in the development of skeletal muscles and tissues derived from neural crest and is an important promoter in nasal structure development. This can explain the myogenic and neural differentiation seen in this tumor along with its typical sinonasal location.[4],[5] The tumor predominantly affects females with female: male ratio of 2:1 and mean age of 52 years.[2] Symptoms are non-specific and are commonly related to the mass effect like nasal passage obstruction, difficulty in breathing, epistaxis, facial pressure, and congestion.[4] Tumor involves the sinonasal tract with frequent involvement of superior nasal cavity and ethmoid sinuses and can extend to involve orbit and cribriform plate.[2] Histologically, the tumors are unencapsulated and infiltrative. The tumor shows spindle cells arranged in medium to long fascicles and can show herring bone pattern, thereby mimicking synovial sarcoma and fibrosarcoma. The cells have spindly, slender, uniform nuclei with vesicular chromatin and tapered ends and syncytial cytoplasmic borders. Mitoses are sparse and necrosis is not seen. Other spindle cell tumors like smooth muscle tumors, neural tumors or spindle cell rhabdomyosarcoma can be differential diagnoses, especially in small biopsies. Background can show scant, delicate, collagen matrix.[2] Many tumors (70%) show concomitant proliferation of overlying epithelium along with its invagination in the tumor to form variously sized glandular or cystic spaces intimately related to the spindly tumor cells, thereby mimicking biphasic synovial sarcoma.[6] This epithelium can be pseudostratified, columnar, ciliated, respiratory epithelium, metaplastic squamous epithelium or oncocytic epithelium and when overt, can resemble sinonasal papilloma or respiratory epithelial hamartoma, which however lack spindle cell proliferation as seen in BSNS. Tumors also show dilated, branching, thin-walled blood vessels in hemangiopericytoma-like pattern, thereby mimicking SFT-HPC and glomangiopericytoma.[4] Rhabdomyoblastic differentiation can be seen in 11% of tumors and around 20% of tumors infiltrate the adjacent bone.[6] Thus, the morphological characteristics of BSNS although distinct, are not exclusive. Indeed, in our case, initial limited biopsy was reported as low-grade spindle cell neoplasm favoring SFT due to relatively low cellularity and the conspicuous vascular pattern. Morphological differentials of this tumor include schwannoma, low-grade, malignant peripheral nerve sheath tumor (MPNST), solitary fibrous tumor, synovial sarcoma, fibrosarcoma, inverted papilloma, and malignant melanoma; hence immunohistochemistry is necessary.[6] All of these tumors express S100 at least focally and around 96% of them express SMA suggesting neural and myogenic differentiation. The staining pattern for these markers may be focal, patchy, or diffuse. Focal, weak reactivity is also noted for CD34, desmin, MyoD1, myogenin, EMA, and CK.[2] Our case showed focal moderate reactivity for S100 and SMA. HMB45/MelanA, CD99, and CK were negative ruling out melanoma and synovial sarcoma. In addition, synovial sarcoma shows significantly higher mitotic activity and at least focal CK, EMA expression. CD34 highlighted the hemangiopericytomatous vascular pattern. Schwannomas diffusely express S100. MPNST can show focal positivity for S100 but shows nuclear pleomorphism, necrosis, and mitoses; hence was excluded. In addition, positive beta catenin and negative SOX10 stain can help to differentiate these tumors from low-grade nerve sheath tumors.[7] Negativity for STAT6 helps to differentiate these tumors from SFT. These tumors typically show rearrangement of PAX3 gene most commonly (79–96% cases) with MAML3 gene. Other fusion partners include FOXO1, NCOA1, and some unknown genes.[2],[8]

Although confirmation by demonstrating PAX3 fusion genes is not available widely, typical morphological features and immunohistochemistry can clinch the diagnosis of BSNS and aid in prognostication of this tumor, thus avoiding over treatment with chemotherapy used in its morphological mimics. This is important because this tumor, although locally invasive and highly cellular, is of low grade with indolent course and does not metastasize. Only two cases of death due to BSNS are reported.[7],[9] However, nearly 50% of the patients report local recurrences.[2] Due to paucity of data, the treatment options are not well-established. These tumors are generally treated with surgical excision and adjuvant radiotherapy rather than with adjuvant chemo radiation.[6] Another thing we would like to highlight is the importance of adequate biopsy sampling to avoid potential misdiagnosis of this typical tumor.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Gore MR. Treatment, outcomes, and demographics in sinonasal sarcoma: A systematic review of the literature. BMC Ear Nose Throat Disord 2018;18:4.  Back to cited text no. 1
    
2.
Lewis JE, Oliveira AM. Biphenotypic sinonasal sarcoma. In: EI-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO Classification of Head and Neck Tumours. 4th ed. Lyon: IARC; 2017. p. 39-41.  Back to cited text no. 2
    
3.
Lewis JT, Oliveira AM, Nascimento AG, Schembri-Wismayer D, Moore EA, Olsen KD, et al. Low-grade sinonasal sarcoma with neural and myogenic features: A clinicopathologic analysis of 28 cases. Am J Surg Pathol 2012;36:517-25.  Back to cited text no. 3
    
4.
Carter CS, East EG, McHugh JB. Biphenotypic sinonasal sarcoma: A review and update. Arch Pathol Lab Med 2018;142:1196-201.  Back to cited text no. 4
    
5.
Arasu A, Murugan S, Essa MM, Velusamy T, Guillemin GJ. PAX3: A molecule with oncogenic or tumor suppressor function is involved in cancer. BioMed Res Int 2018;2018:1095459, 12 pages. doi: 10.1155/2018/1095459.  Back to cited text no. 5
    
6.
Chitguppi C, Koszewski I, Collura K, Curtis M, Nyquist G, Rabinowitz M, et al. Biphenotypic sinonasal sarcoma-Case report and review of clinicopathological features and diagnostic modalities. J Neurol Surg B Skull Base 2019;80:51-8.  Back to cited text no. 6
    
7.
Rooper LM, Huang SC, Antonescu CR, Westra WH, Bishop JA. Biphenotypic sinonasal sarcoma: An expanded immunoprofile including consistent nuclear β-catenin positivity and absence of SOX10 expression. Hum Pathol 2016;55:44-50.  Back to cited text no. 7
    
8.
Andreasen S, Bishop JA, Hellquist H, Hunt J, Kiss K, Rinaldo A, et al. Biphenotypic sinonasal sarcoma: Demographics, clinicopathological characteristics, molecular features and prognosis of a recently described entity. Virchows Arch 2018;473:615-26.  Back to cited text no. 8
    
9.
Lin Y, Liao B, Han A. Biphenotypic sinonasal sarcoma with diffuse infiltration and intracranial extension: A case report. Int J Clin Exp Pathol 2017;10:11743-6.  Back to cited text no. 9
    

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Correspondence Address:
Abhijeet Ingle,
Department of Lab Medicine, Yashoda Hospital, Nalagonda X Roads, Malakpet, Hyderabad - 500036, Telangana
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_208_21



    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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