Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 3792
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

CASE REPORT Table of Contents  
Ahead of print publication
SMARCB1 (INI-1) – Deficient sinonasal carcinoma: Report of two cases


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

Click here for correspondence address and email

Date of Submission25-Mar-2021
Date of Decision16-Jul-2021
Date of Acceptance17-Jun-2021
Date of Web Publication27-Apr-2022
 

   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 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 [Epub ahead of print] [cited 2023 Feb 5]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=344187





   Introduction Top


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 Top


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)

Click here to view
Figure 2: Sheets of basaloid cells along with scattered cells showing rhabdoid morphology (arrow) (H and E; ×200)

Click here to view
Figure 3: Cytokeratin positive (×200)

Click here to view
Figure 4: Focal p63 positive (×200)

Click here to view
Figure 5: SMARCB1 (INI-1) negative (×200)

Click here to view
Figure 6: Gross picture of the tumor (arrow) in the maxillary sinus

Click here to view


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 Top


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 Top


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 Top

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.  Back to cited text no. 1
    
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.  Back to cited text no. 2
    
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.  Back to cited text no. 3
    
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.  Back to cited text no. 4
    
5.
Guilmette J, Sadow PM. High-grade sinonasal carcinoma: Classification through molecular profiling. Arch Pathol Lab Med 2019;143:1416-9.  Back to cited text no. 5
    
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.  Back to cited text no. 6
    
7.
Bishop JA, Antonescu CR, Westra WH. SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol 2014;38:1282-9.  Back to cited text no. 7
    
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.  Back to cited text no. 8
    
9.
Parsel SM, Jawad BA, McCoul ED. SMARCB1-Deficient sinonasal carcinoma: Systematic review and case report. World Neurosurg 2020;136:305-10.  Back to cited text no. 9
    
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.  Back to cited text no. 10
    

Top
Correspondence Address:
Srilatha Parampalli Srinivas,
Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_313_21



    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

Top
 
  Search
 
  
  
 Article in PDF
     Search Pubmed for
 
    -  Vasudevan G
    -  Srinivas SP
    -  Nayal B
    -  Jayaprakash P
    -  Ramaswamy B


    Abstract
   Introduction
   Case History
   Discussion
   Conclusion
    References
    Article Figures

 Article Access Statistics
    Viewed593    
    PDF Downloaded32    

Recommend this journal