Nasal cavity, paranasal sinuses, nasopharynx

Sinonasal carcinoma

Sinonasal undifferentiated carcinoma


Resident / Fellow Advisory Board: Kyle Devins, M.D.
Deputy Editor-in-Chief: Kelly Magliocca, D.D.S., M.P.H.
Abeer Salama, M.D.
Bin Xu, M.D., Ph.D.

Topic Completed: 14 July 2021

Minor changes: 14 July 2021

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PubMed Search: Sinonasal undifferentiated carcinoma [title] pathology

Abeer Salama, M.D.
Bin Xu, M.D., Ph.D.
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Cite this page: Salama A, Xu B. Sinonasal undifferentiated carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/nasalsnuc.html. Accessed September 21st, 2021.
Definition / general
Essential features
  • Undifferentiated carcinoma demonstrating epithelial differentiation but lacking specific squamous, glandular, neuroectodermal, mesenchymal, melanocytic or other lines of differentiation
  • Lacks specific viral etiologies, such as HPV and EBV
  • Lacks other specific genotypes, such as NUT (NUTM1) fusions, SWI/SNF deficiency and others (JNCI Cancer Spectr 2019;4:pkz094, Semin Diagn Pathol 2021;38:175, Hum Pathol 2020;104:105)
  • Lacks neuroendocrine differentiation that would justify for high grade neuroendocrine carcinoma, including large cell and small cell neuroendocrine carcinoma
  • Displays oncogenic IDH2 or IDH1 mutations in 80% of cases: IDH2 R172T is the most common mutation (Mod Pathol 2019;32:205, Am J Surg Pathol 2018;42:1067)
Terminology
  • Sinonasal undifferentiated carcinoma (SNUC)
ICD coding
  • ICD-10:
    • C30.0 - malignant neoplasm of nasal cavity
    • C31.1 - malignant neoplasm of ethmoid sinus
Epidemiology
Sites
Etiology
  • No consistent etiology has been reported
Clinical features
  • Presenting symptoms are variable, including nasal obstruction, epistaxis, facial pain and headache to severe visual symptoms (proptosis, diplopia and impaired visual acuity) and cranial nerve palsies (J Otolaryngol Head Neck Surg 2013;42:2)
  • Usually presents with stage 4 disease and involves the skull base and orbit (Curr Oncol Rep 2019;21:26)
Radiology images

Contributed by Bin Xu, M.D., Ph.D. and Abeer Salama, M.D.

MRI

Prognostic factors
Case reports
Treatment
  • Multimodal therapy regimens incorporating intensified radiotherapy or chemotherapy after surgery (Head Neck 2017;39:1819)
Gross description
Microscopic (histologic) description
  • Nests, lobules, trabeculae and sheets of medium sized cells
  • Cells contain small amounts of eosinophilic cytoplasm, medium to large sized hyperchromatic to vesicular nuclei, inconspicuous to prominent nucleoli and poorly defined cell membrane
  • Mitotic activity is very high
  • Tumor necrosis and apoptoses are frequent
  • Lymphovascular invasion and perineural invasion are common
  • Lacks any definite lineage of differentiation
    • Squamous differentiation (e.g. keratin pearls and intracellular bridges)
    • Glandular differentiation (e.g. glandular lumen or acinar architecture)
    • Neuroectodermal differentiation (e.g. neurofibrillary material and true neural rosettes)
  • Reference: Adv Anat Pathol 2020;27:51
Microscopic (histologic) images

Contributed by Bin Xu, M.D., Ph.D. and Abeer Salama, M.D.
Lobules and sheets of malignant cells

Lobules and sheets of malignant cells

Cytologic features of malignant epithelial cells

Cytologic features of malignant epithelial cells

High grade features: mitosis and apoptosis

High grade features: mitosis and apoptosis

Cytokeratin AE1/AE3

Cytokeratin AE1 / AE3

IDH2 R172T immunohistochemistry

IDH2 R172T immunohistochemistry

Positive stains
Negative stains
Molecular / cytogenetics description
  • IDH2 or IDH1 mutations in > 80% cases, the most common being IDH2 R172 mutation (Mod Pathol 2019;32:1447)
    • IDH2 mutant large cell neuroendocrine carcinoma is genetically similar to the IDH2 mutant SNUC
  • In situ hybridization for high risk HPV and EBV is consistently negative
Sample pathology report
  • Nasal cavity, biopsy:
    • Poorly differentiated carcinoma, most consistent with sinonasal undifferentiated carcinoma (SNUC), at least 1.15 cm in greatest dimension, invading bone (see comment)
    • Comment: Immunohistochemical stains show that the tumor cells are focal staining of AE1 / AE3, Cam 5.2 and IDH2 R172S, while they are negative for CK5/6, synaptophysin, chromogranin, IDH1-R132H, calretinin, NUT, P40, S100 and calponin. The immunostaining for BAF47, BRM and BRG1 is retained in the tumor. In situ hybridization for high risk HPV and EBV (EBER) are negative in the tumor.
Differential diagnosis
Board review style question #1
Which of the following statement about sinonasal undifferentiated carcinoma (SNUC) is true?

  1. 20% of SNUC are positive for high risk HPV
  2. It is a diagnosis of exclusion
  3. It is commonly diffusely positive for synaptophysin
  4. SMARCB1 (INI1) immunostain is lost in this tumor
Board review style answer #1
B. It is a diagnosis of exclusion. SNUC can be focally positive for neuroendocrine markers (e.g. synaptophysin). However, diffuse synaptophysin positivity hints towards olfactory neuroblastoma, paraganglioma or neuroendocrine neoplasm. SMARCB1 loss is characteristic for SMARCB1 deficient sinonasal carcinoma. SNUC has no association with high risk HPV. The correct answer is B (SNUC is a diagnosis of exclusion).

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Reference: Sinonasal undifferentiated carcinoma
Board review style question #2

Which of the following sinonasal carcinoma harbors frequent IDH2 mutation?

  1. Nasopharyngeal carcinoma
  2. NUT carcinoma
  3. Sinonasal undifferentiated carcinoma (SNUC)
  4. SMARCA4 and SMARCB1 deficient carcinoma
Board review style answer #2
C. Sinonasal undifferentiated carcinoma (SNUC)

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Reference: Sinonasal undifferentiated carcinoma
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