DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity.

Abstract

A novel DEK-AFF2 fusion was recently reported in 4 nonkeratinizing squamous cell carcinomas of the sinonasal region and skull base, including 1 with exceptional response to immunotherapy, but it is not yet clear if this rearrangement defines a unique clinicopathologic category or represents a rare event. This study aims to characterize a larger cohort of carcinomas with DEK-AFF2 fusions to assess whether they truly constitute a distinctive entity. Among 27 sinonasal and skull base nonkeratinizing squamous cell carcinoma that were negative for human papillomavirus and Epstein-Barr virus, RNA sequencing identified DEK-AFF2 fusions in 13 cases (48%). Nine were centered in the nasal cavity, 2 in the middle ear/temporal bone, 1 in the nasopharynx, and 1 in the orbit. These tumors displayed recurrent histologic features including (1) complex endophytic and exophytic, frequently papilloma-like growth, (2) transitional epithelium with eosinophilic to amphophilic cytoplasm, (3) absent or minimal keratinization with occasional compact keratin pearls, (4) monotonous nuclei, and (5) prominent tumor-infiltrating neutrophils or stromal lymphocytes. This appearance not only overlaps with high-grade basaloid sinonasal carcinomas but also with benign papillomas and tumors reported as low-grade papillary Schneiderian carcinoma. However, DEK-AFF2 carcinomas showed frequent local recurrence, cervical lymph node metastases, and distant metastasis with 2 deaths from disease, confirming they are aggressive malignancies despite relatively bland histology. Overall, the distinctive molecular, histologic, and clinical features of DEK-AFF2 carcinomas suggest they represent a unique entity in the sinonasal region. This tumor merits increased pathologic recognition to better understand its prognostic and therapeutic implications.

• Authors: Lisa M Rooper, Abbas Agaimy, Brendan C Dickson, Julie C Dueber, Charles G Eberhart, Jeffrey Gagan, Arndt Hartmann, Armen Khararjian, Nyall R London, Christina M MacMillan, Doreen N Palsgrove, J Stephen Nix, Ann Sandison, Robert Stoehr, Tra Truong, Ilan Weinreb, Justin A Bishop
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 45 Issue 12 Pg. 1682-1693 (12 01 2021) ISSN: 1532-0979 [Electronic] United States
• PMID: 34049316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• AFF2 protein, human
• Biomarkers, Tumor
• Chromosomal Proteins, Non-Histone
• DEK protein, human
• Nuclear Proteins
• Oncogene Proteins
• Poly-ADP-Ribose Binding Proteins

Topics

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor (analysis, genetics)
• Chromosomal Proteins, Non-Histone (genetics)
• Female
• Gene Fusion
• Genetic Predisposition to Disease
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Male
• Middle Aged
• Nuclear Proteins (genetics)
• Oncogene Proteins (genetics)
• Paranasal Sinus Neoplasms (chemistry, genetics, pathology)
• Phenotype
• Poly-ADP-Ribose Binding Proteins (genetics)
• RNA-Seq
• Skull Base Neoplasms (chemistry, genetics, pathology)
• Squamous Cell Carcinoma of Head and Neck (chemistry, genetics, pathology)
• Young Adult