"SMARCB1/INI1-deficient sinonasal carcinoma"

Authors of the case:
Resident doctor Veslava Senina; MD Dr. Pathologist Justinas Besusparis; MD Consultant Pathologist Ugnius Mickys
Case report
61 years old woman presented with acute sinusitis. Imaging examination showed a mass in left maxillary sinus. Expanded biopsy was performed. Tumor fragments were received for pathological examination.
Histopathological evaluation
Microscopically tumor was composed of solid sheets, trabecules and nests of basaloid cells within scant desmoplastic stroma. Tumor cells had small amount of cytoplasm, relatively large nuclei with focally visible nucleoli. Despite the resemblance to basaloid or non-keratizing squamous cell carcinoma there was no overt squamous differentiation. Few tumor areas showed cribriform/glandular-like structures. Tumor demonstrated prominent areas of necrosis.
Immunohistochemistry
Tumor cells were diffusely positive for pancytokeratins (PanCK) and revealed focal p40/p63, CK5, p16, CD99 and EMA staining.
Tumor was negative for lymphoma (LCA, CD20, CD3, CD30) and melanoma (MelanA, S100) markers, there were no immunohistochemical signs of neuroendocrine (Synaptophysin, ChromograninA, CD56), vascular (CD31, CD34) or rhabdomyosarcomatous (Desmin) differentation. EBER-CISH was also negative.
Lastly, 100% of tumor cells revealed loss of INI1 in immunohistochemistry.
Diagnosis
SMARCB1/INI1-deficient sinonasal carcinoma.
Discusion
Sinonasal undifferentiated carcinoma (SNUC) is a rare sinonasal tract malignancy comprising up to 5% of all sinonasal carcinomas. According to WHO Classification of Head and Neck Tumors, SNUC is a carcinoma lacking glandular or squamous differentiation and that is not otherwise classifiable. Generally, SNUC is considered a diagnosis of exclusion. Despite aggressive management patients survival rates remain low (1).
Novel molecular testing (especially next-generation sequencing platforms) allowed to investigate SNUC more precisely. Recently few new molecular SNUC subtypes were descibed: IDH-mutant SNUC, SMARCB1(INI1)-deficient sinonasal carcinoma, SMARCA4-deficient sinonasal carcinoma and NUT carcinoma.
SMARCB1(INI1)-deficient sinonasal carcinoma shows basaloid cell morphology with variable number of plasmacytoid or rhabdoid cells. Tumor may show focal adenoid, sarcomatoid or oncocytoid/adenocarcinoma-like pattern and may focally produce mucin. The neoplastic cells demonstrate negative INI1 immunohistochemical staining (2).
Recently IDH-mutant SNUC was described. Morphologic features of IDH-mutated SNUC overlap with other types of SNUC. Tumor cells may be immunoreactive for IDH1 or IDH2 immunohistochemical marker. Positive IHC staining correlates with IDH1/2 mutation. It is important to note, that tumor harbouring IDH mutation may be negative for IDH1/2 marker (3).
NUT carcinoma is a rare, highly aggressive head and neck region tumor. Characteristically, tumor cells show poorly differentiated/undifferentiated pattern with abrupt foci of squamous differentiation. NUT carcinoma is defined by chromosomal translocation associated with NUTM1 gene. NUT immunohistochemical marker is a reliable surrogate for identification of the mutation (4).
Only few cases of SMARCA4-deficient sinonasal carcinoma were described in literature. It is defined as separate entity due to specific SMARCA4 gene mutation. Histologically tumor shows the same features as other SNUC (4).
Identification of genetic alterations in SNUC may help to discover new targeted therapeutic agents, therefore improve overall disease survival.
References
1. WHO Classification of Head and Neck Tumours, 4th edition. 2017.
2. Abbas Agaimy, MD et al. SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphological and Clinicopathological Spectrum of a Recently Described Entity. https://www.ncbi.nlm.nih.gov/. [Online] 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354087/.
3. Mito JK, MD et al. Immunohistochemical Detection and Molecular Characterization of IDH-mutant Sinonasal Undifferentiated Carcinomas. https://www.ncbi.nlm.nih.gov/. [Online] 2018. https://www.ncbi.nlm.nih.gov/pubmed/29683816.
4. Guilmette J, Sadow PM. High-Grade Sinonasal Carcinoma: Classification Through Molecular Profiling. https://www.ncbi.nlm.nih.gov/. [Online] 2018. https://www.ncbi.nlm.nih.gov/pubmed/30779592.
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