Nasal cavity, paranasal sinuses, nasopharynx
Sinonasal carcinoma
SMARCB1 deficient sinonasal carcinoma

Editor-in-Chief: Debra Zynger, M.D.
Lisa Rooper, M.D.

Topic Completed: 25 July 2019

Revised: 25 July 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: SMARCB1 deficient sinonasal carcinoma

Lisa Rooper, M.D.
Page views in 2019 to date: 622
Cite this page: Rooper L. SMARCB1 deficient sinonasal carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/nasalSMARCB1deficient.html. Accessed October 19th, 2019.
Definition / general
Essential features
  • Sinonasal carcinoma defined by inactivation of SMARCB1 gene
  • Loss of SMARCB1 (INI1) immunohistochemical expression is highly sensitive and specific for diagnosis in this site
  • Tumors are high grade but demonstrate cytological uniformity
  • Tumors have variable proportions of basaloid and rhabdoid / plasmacytoid cells
  • Highly aggressive clinical behavior
Terminology
  • SMARCB1 stands for SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1
  • The protein product of the SMARCB1 gene is also sometimes known as INI1, which stands for integrase interactor 1
ICD coding
  • ICD-10: C30.0 - malignant neoplasm of nasal cavity
  • ICD-10: C31.1 - malignant neoplasm of ethmoidal sinus
Epidemiology
Sites
  • Exclusively occurs in sinonasal tract
  • Most commonly arises in nasal cavity or ethmoid sinus but frequently involves multiple sites (Am J Surg Pathol 2017;41:458)
Clinical features
  • Most present with symptoms of mass effect such as nasal obstruction, headache, epistaxis, proptosis or visual deficits (Am J Surg Pathol 2017;41:458)
  • More than 80% present with stage T4 disease with bone, skull base or periorbital invasion
Radiology description
  • Avid contrast enhancement with intermediate to low T2 signal and fluorodeoxyglucose (FDG) avidity
  • Frequent calcification with occasional hair on end periosteal reaction (Am J Surg Pathol 2014;38:1274)
Radiology images

Images hosted on other servers:

Infiltration into orbit

Case reports
Treatment
Gross description
Microscopic (histologic) description
  • Although tumors show high grade histologic features including prominent necrosis and mitoses, cytology is relatively uniform
  • Nuclei are round to oval with smooth nuclear contours
  • Two common morphologic variants: plasmacytoid / rhabdoid (40% of cases) and basaloid (60% of cases) (Am J Surg Pathol 2017;41:458)
  • Plasmacytoid / rhabdoid variant composed entirely of sheets of plasmacytoid / rhabdoid cells with abundant eosinophilic cytoplasm and eccentric nuclei
  • Basaloid variant composed of nests and lobules of basaloid cells with high nuclear cytoplasmic ratio and peripheral palisading and scattered plasmacytoid / rhabdoid cells
  • No overt squamous differentiation should be identified (Am J Surg Pathol 2014;38:1282)
  • Frequent formation of nonspecific vacuoles and occasional overt glandular differentiation (Hum Pathol 2019;83:59)
  • Subset shows papillary / exophytic growth (Virchows Arch 2015;467:649)
  • No associated surface dysplasia but pagetoid spread in overlying epithelium can be seen (Am J Surg Pathol 2014;38:1274)
Microscopic (histologic) images

Contributed by Lisa Rooper, M.D.

Highly infiltrative growth

Cytologic uniformity despite high grade

Nests of basaloid cells

Interspersed
basaloid and
rhabdoid
plasmacytoid cells


Sheets of rhabdoid plasmacytoid cells

No surface dysplasia

Cytoplasmic vacuoles

Loss of SMARCB1 (INI1)

Cytology description
  • Hypercellular smears with clusters of cohesive polygonal cells
  • Variable proportion of individual rhabdoid / plasmacytoid cells with abundant cytoplasm
  • Uniform nuclei with fine chromatin and small nucleoli
  • No overt keratinization or other evidence of squamous differentiation (Diagn Cytopathol 2016;44:700)
  • Apoptotic bodies common with abundant background necrotic debris (Cancer Cytopathol 2018;126:567)
Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Nasal mass, biopsy:
    • SMARCB1 deficient sinonasal carcinoma (see comment)
    • Comment: Immunostains show that the tumor cells are positive for AE1/AE3 and p40, focally positive for synaptophysin and INSM1 and negative for NUT1, CD99, p16, S100 and calponin with loss of SMARCB1 (INI1) expression. SMARCB1 deficient sinonasal carcinoma is an aggressive tumor unique to the sinonasal tract that is defined by loss of SMARCB1 (INI1) expression (Am J Surg Pathol 2017;41:458).
Differential diagnosis
Board review question #1
A 30 year old man presented with a destructive sinonasal tumor. Biopsy findings are shown in the photomicrograph below. What molecular alteration is thought to be the driver of this tumor?

  1. Mutations in IDH2
  2. EWSR1 translocations
  3. NUT1 translocations
  4. Inactivation of SMARCB1
Board review answer #1
D. Inactivation of SMARCB1. This photomicrograph depicts a SMARCB1 deficient sinonasal carcinoma, an aggressive sinonasal tumor that is defined by genetic inactivation of the SMARCB1 gene with corresponding immunohistochemical loss of SMARCB1 (INI1) protein expression. The other genetic abnormalities listed here are characteristic of other high grade sinonasal tumors that fall into the differential diagnosis of SMARCB1 deficient sinonasal carcinoma, including IDH2 mutations in sinonasal undifferentiated carcinoma, EWSR1 translocation in adamantinoma-like Ewing sarcoma and NUT1 translocation in NUT carcinoma; these other tumor types all demonstrate retained immunohistochemical expression of SMARCB1.

Reference: Nasal cavity, paranasal sinuses, nasopharynx - SMARCB1 deficient sinonasal carcinoma

Comment here
Board review question #2
What feature would essentially exclude the diagnosis of SMARCB1 deficient sinonasal carcinoma?

  1. Basaloid cell nests with peripheral palisading and strong p40 positivity
  2. Diffuse positivity for p16 immunohistochemistry and high risk HPV RNA in situ hybridization
  3. Formation of glandular lumina with mucin production
  4. Retained SMARCB1 signals by FISH
Board review answer #2
B. Diffuse positivity for p16 immunohistochemistry and high risk HPV RNA in situ hybridization. SMARCB1 deficient sinonasal carcinoma can show a variety of morphologic features and a highly variable immunohistochemical profile. Histologically, SMARCB1 deficient sinonasal carcinoma is composed of various proportions of basaloid and plasmacytoid / rhabdoid cells; a subset of cases can show glandular differentiation. The most sensitive and specific feature for diagnosis is consistent loss of SMARCB1 (INI1) expression by immunohistochemistry; while FISH generally shows loss as well, signals can be retained in rare cases due to heterozygous mutations. Otherwise SMARCB1 deficient sinonasal carcinoma is immunohistochemically heterogeneous with variable positivity for p63 / p40 and synaptophysin / chromogranin; a subset of cases can even demonstrate diffuse p16 positivity. However, in situ hybridization for high risk HPV should be consistently negative.

Reference: Nasal cavity, paranasal sinuses, nasopharynx - SMARCB1 deficient sinonasal carcinoma

Comment here

Back to top