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| Year : 2023 | Volume
: 66
| Issue : 2 | Page : 352-355 |
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| SMARCB1 (INI-1) – Deficient sinonasal carcinoma: Report of two cases |
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Geetha Vasudevan1, Srilatha Parampalli Srinivas1, Bhavna Nayal1, Padmapriya Jayaprakash1, Balakrishnan Ramaswamy2
1 Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Otorhinolaryngology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
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| Date of Submission | 25-Mar-2021 |
| Date of Decision | 17-Jun-2021 |
| Date of Acceptance | 16-Jul-2021 |
| Date of Web Publication | 27-Apr-2022 |
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 Abstract | | |
SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare, poorly differentiated carcinoma defined by complete loss of tumor suppressor gene SMARCB1 (INI-1) within the neoplastic cell nuclei demonstrated by the immunohistochemical stain. SMARCB1 (INI-1) gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share “rhabdoid” morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma was first reported by Agaimy et al. in 2014. These tumors are often basaloid with focal rhabdoid differentiation, prominent necrosis, increased mitotic activity, and aggressive behavior. Other than being INI-1 and NUT negative, they are positive for pancytokeratin and express variable immunoreactivity for squamous markers like p63 and neuroendocrine markers like synaptophysin. Most patients present with locally advanced disease and hence a combination of chemotherapy, radiotherapy, and surgery is usually recommended.
Keywords: Maxillary sinus neoplasms, rhabdoid tumor, SMARCB1 protein
How to cite this article:
Vasudevan G, Srinivas SP, Nayal B, Jayaprakash P, Ramaswamy B. SMARCB1 (INI-1) – Deficient sinonasal carcinoma: Report of two cases. Indian J Pathol Microbiol 2023;66:352-5 |
How to cite this URL:
Vasudevan G, Srinivas SP, Nayal B, Jayaprakash P, Ramaswamy B. SMARCB1 (INI-1) – Deficient sinonasal carcinoma: Report of two cases. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Jun 1];66:352-5. Available from: https://www.ijpmonline.org/text.asp?2023/66/2/352/344187 |
| Introduction | |  |
SMARCBI (INI-1)-deficient sinonasal carcinoma (SDSNC) is a poorly differentiated recently described tumor with loss of SMARCB1 (INI-1) tumor suppressor gene. Patients usually present with symptoms of nasal obstruction, eye pain, blurring of vision, and headache. These tumors are often basaloid with at least partial rhabdoid differentiation, prominent necrosis, increased mitotic activity, and aggressive behavior.[1] In this report, we will be discussing the details of two cases of SDSNC.
| Case History | | |
Case 1
A 66-year-old woman presented to the otorhinolaryngology outpatient department with swelling in the left cheek of two months duration and occasional bleeding from the left nostril. MRI (magnetic resonance imaging) revealed a mass in the left maxillary sinus extending superiorly to the floor of the orbit and inferiorly to the upper alveolus. Histopathology of the biopsy showed a tumor composed of discohesive sheets and perivascular pseudopapillae lined by cells with basaloid morphology [Figure 1] which included a high nucleus to cytoplasmic ratio, hyperchromatic nuclei, anisonucleosis, prominent nucleoli, mitoses, and scant cytoplasm surrounded by fibro collagenous stroma with lymphocytic infiltrate. Focal rhabdoid appearance of cells [Figure 2], cytoplasmic vacuolation, and areas of comedo-type necrosis were noted. On immunohistochemistry, the tumor cells were diffuse positive for cytokeratin AE1/AE3 [Figure 3], focal positive for p63 [Figure 4], and negative for desmin and SMARCB1 (INI-1) [Figure 5]. A diagnosis of SMARCB1 (INI-1)-deficient sinonasal carcinoma was rendered. Left total maxillectomy with anterior ethmoidectomy was performed. The tumor measured 3 × 3.6 × 2.8 cm [Figure 6] and was filling the left maxillary sinus. Since the margins were involved neoadjuvant chemo-radiotherapy was administered. | Figure 1: Perivascular pseudopapillae lined by cells with basaloid morphology (H and E; ×100)
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 | Figure 2: Sheets of basaloid cells along with scattered cells showing rhabdoid morphology (arrow) (H and E; ×200)
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Case 2
A 58-year-old gentleman presented to the otorhinolaryngology outpatient department with complaints of deep-seated pain on the left side of the face and left side nose block of 8 months duration. He also noticed bulging of his left eye for one month and had 3 episodes of epistaxis during this period. Computed tomography (CT) revealed a large mass in the left maxillary sinus with an erosion of the bone and extension into the nasal cavity, left orbit, and infratemporal fossa. Diagnostic nasal endoscopy was performed and biopsy was sent for histopathological examination. The biopsy showed an extensively necrotic tumor composed of nests, lobules, trabeculae, pseudo glandular, and papillae lined by polygonal cells with large round nuclei, frequent mitosis, numerous apoptotic bodies, and a moderate amount of eosinophilic to clear cytoplasm. Tumor cells showed immunoreactivity to cytokeratin AE1/AE3, synaptophysin, p63 (focally) along with loss of nuclear expression of SMARCB1 (INI-1). Tumor cells were negative for desmin. Final diagnosis of SMARCB1 (INI-1)-deficient sinonasal carcinoma was proferred. The patient was offered curative combined chemo-radiotherapy for further management.
| Discussion | | |
Sinonasal carcinoma accounts for only 3% of all tumor arising in the head and neck region. Poorly differentiated carcinoma accounts for a substantial number of sinonasal tumors. Differential diagnoses include sinonasal undifferentiated carcinoma (SNUC), non-keratinizing squamous cell carcinoma (NKSCC) (viral and non-viral), olfactory neuroblastoma, small cell undifferentiated neuroendocrine carcinoma, NUT-midline carcinoma, myoepithelial carcinoma, adamantinoma-like Ewing sarcoma, and sinonasal adenocarcinoma.[2],[3] In 2014 Agaimy et al. described a novel entity called SMARCB1 (INI-1)-deficient sinonasal basaloid carcinoma.[4] Possibly that many of the tumor classified as the above differentials would have been this novel entity.[4]
SMARCB1 (INI-1) mutation is also associated with the pathogenesis of many other tumors including malignant rhabdoid tumor, atypical teratoid rhabdoid tumor, epithelioid sarcoma, renal medullary carcinoma, extraskeletal chondrosarcoma, epithelioid malignant peripheral nerve sheath tumor, and myoepithelial carcinoma of soft tissue.[5],[6]
SMARCBI (SW1/SNF related matrix associated actin-dependent regulator of chromatin subfamily B member 1), also known as INI-1 (Integrase interactor 1), is a tumor suppressor gene at chromosomal position 22q11.2 and present in all normal cells. Its gene product regulates transcription and maintenance of chromatin structure. The loss of SMARCB1 activity leads to tumorigenesis through overexpression of cyclin D1 which promotes cell cycle progression by phosphorylating and inactivating the retinoblastoma protein (RB) and induces a rhabdoid morphology in the cells. Loss of SMARCB1 also leads to epigenetic alterations including the silencing of genes necessary for normal lineage-specific differentiation and maturation.[2],[4],[7]
SDSNC have certain interesting characteristics which encompass large tumors with cells exhibiting basaloid morphology, foci of rhabdoid differentiation (dense eosinophilic cytoplasm and eccentric nucleus), prominent necrosis, usually of comedo pattern, increased mitotic activity, clear or empty appearing cytoplasmic vacuoles, absence of glandular or squamous differentiation, oncocytic-tubuloglandular (mucin absent) pattern and aggressive behavior.[3],[8] Most patients present with locally advanced disease and a higher rate for metastasis to the lungs. They have decreased disease-free survival and need to be treated with a combination of surgery, chemotherapy, and radiotherapy.[2],[9]
SDSNC demonstrates loss of INI-1 expression, diffuse positivity for pancytokeratin, variable immunoreactivity for P40, P63, and CK5/6, and focal positivity for S100, synaptophysin, and chromogranin.[6] CK7, actin, and NUT are negative. It expresses diffuse or focal P16, but PCR analysis or in-situ hybridization for high-risk HPV is negative. It is also negative for EBV in-situ hybridization.[10]
All the tumors considered in the differential diagnosis of SDSNC show preserved SMARCB1 (INI-1) expression. Small cell neuroendocrine carcinoma have cells with scant cytoplasm inconspicuous nucleoli, nuclear molding and are diffusely positive for neuroendocrine markers including synaptophysin, chromogranin, and CD56. NKSCC demonstrates greater nuclear pleomorphism, surface dysplasia, and diffuse, strong P53 and P40 staining. NUT carcinoma exhibits undifferentiated basaloid cells with abrupt keratinization and strong P40 staining along with nuclear NUT staining. Myoepithelial carcinoma exhibits a spindled morphology and strongly expresses S100. Olfactory neuroblastoma has a neurofibrillary stroma with rosetting and expresses S100, synaptophysin, NSE, neurofilament and CD56. Adamantinoma-like Ewing sarcoma shows peripheral palisading of basaloid cells which show membranous CD99 and nuclear FL1 positivity. SNUC and SDSNC have almost similar basaloid undifferentiated cells and immunohistochemical features except for SMARCB1 (INI-1) being positive in SNUC. Sinonasal adenocarcinoma of intestinal-type comprise of mucinous and goblet cells and show strong CD20 and CDX2 positivity. Sinonasal adenocarcinoma of non-intestinal type shows CK7 positivity.[2],[3]
| Conclusion | | |
Diagnosis of SDSNC is made by a diligent search for certain characteristic histological features and confirmed by loss of SMARCB1 (INI-1) expression. Most patients present with locally advanced disease and hence a combination of chemotherapy, radiotherapy, and surgery is usually recommended.
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 | | |
| 1. | Trieu V, Aulet RM, Ciolino A, Rimash T. SMARCB1-deficient sinonasal carcinoma: A case report and discussion of the clinical implications. Ann Otol Rhinol Laryngol 2019;128:676-80.  |
| 2. | Wasserman JK, Dickson BC, Perez-Ordonez B, de Almeida JR, Irish JC, Weinreb I. INI1 (SMARCB1)-Deficient sinonasal carcinoma: A clinicopathologic report of 2 cases. Head Neck Pathol 2017;11:256-61. |
| 3. | Kakkar A, Antony VM, Pramanik R, Sakthivel P, Singh CA, Jain D. SMARCB1 (INI1)-Deficient sinonasal carcinoma: A series of 13 cases with assessment of histologic patterns. Hum Pathol 2019;83:59-67. |
| 4. | Agaimy A, Koch M, Lell M, Semrau S, Dudek W, Wachter DL, et al. SMARCB1(INI-1)-Deficient sinonasal basaloid carcinoma: A novel member of the expanding family of SMARCB1-deficient neoplasms. Am J Surg Pathol 2014;38:1274-81. |
| 5. | Guilmette J, Sadow PM. High-grade sinonasal carcinoma: Classification through molecular profiling. Arch Pathol Lab Med 2019;143:1416-9. |
| 6. | Bell D, Hanna EY, Agaimy A, Weissferdt A. Reappraisal of sinonasal undifferentiated carcinoma: SMARCB1 (INI1)-deficient sinonasal carcinoma: A single-institution experience. Virchows Arch 2015;467:649-56. |
| 7. | Bishop JA, Antonescu CR, Westra WH. SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol 2014;38:1282-9. |
| 8. | Agaimy A, Hartmann A, Antonescu CR, Chiosea SI, El-Mofty SK, Geddert H, et al. SMARCB1 (INI-1)-deficient sinonasal carcinoma: A series of 39 cases expanding the morphological and clinicopathological spectrum of a recently described entity. Am J Surg Pathol 2017;41:458-71. |
| 9. | Parsel SM, Jawad BA, McCoul ED. SMARCB1-Deficient sinonasal carcinoma: Systematic review and case report. World Neurosurg 2020;136:305-10. |
| 10. | Zeng M, Chen C, Yang S, Chen X. SMARCB1 (INI1)-Deficient sinonasal carcinoma: A newly described entity. Int J Clin Exp Pathol 2016;9:3454-8. |
Correspondence Address:
Srilatha Parampalli Srinivas
Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijpm.ijpm_313_21
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6] |
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