Sinonasal Squamous Cell Carcinoma with DEK::AFF2 Rearrangement : An Aggressive Cancer with Bland Morphology

Am J Surg Pathol. 2024 Nov 1;48(11):1408-1416. doi: 10.1097/PAS.0000000000002281. Epub 2024 Aug 12.

Abstract

Aims: DEK::AFF2 squamous cell carcinoma is a recently described cancer entity, with 29 cases reported to date. Occasionally, these carcinomas appear deceptively indistinguishable; however, specific morphological and phenotypic features suggest the presence of this rearrangement. However, the prognostic value of this diagnosis remains unclear. We aimed to report a new case series with histological, molecular, and clinical features.

Methods: We collected data from 15 patients and investigated their phenotypes, including the expression profiles of CK7, P63/P40, PDL1, AFF2, and P16, morphological features, and associated prognostic data. We analyzed these data along with the previously published data.

Results: Most of these cases exhibited indicative morphological features, such as exophytic and endophytic papillary growth, nuclear monomorphism, and abundant neutrophil-rich inflammatory infiltrates. Immunohistochemical analysis revealed the expression of AFF2 and squamous cell markers in all the patients. Overexpression of P16 was not detected, whereas CK7 and PDL1 were expressed variably. In our study cohort, a 50% progression or recurrence rate, 25% lymph node metastasis, 17% distant metastasis, and 18% disease-related death were identified, with a short follow-up time.

Conclusion: DEK::AFF2 squamous cell carcinoma incidence is probably underestimated. The low-grade appearance of these tumors sometimes limits their detection. The rates of recurrence and metastasis seem to be high despite an often bland morphology. We propose AFF2 immunohistochemistry as an effective tool, and a diagnostic algorithm has been established to support accurate diagnosis of these tumors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Carcinoma, Squamous Cell* / chemistry
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / mortality
  • Carcinoma, Squamous Cell* / pathology
  • Chromosomal Proteins, Non-Histone* / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Rearrangement
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Oncogene Proteins* / genetics
  • Paranasal Sinus Neoplasms / chemistry
  • Paranasal Sinus Neoplasms / genetics
  • Paranasal Sinus Neoplasms / mortality
  • Paranasal Sinus Neoplasms / pathology
  • Phenotype
  • Poly-ADP-Ribose Binding Proteins* / genetics
  • Squamous Cell Carcinoma of Head and Neck / chemistry
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • DEK protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • Oncogene Proteins
  • DNA-Binding Proteins