p63-Positive Diffuse Large B-cell Lymphoma of Oropharynx: A Treacherous Mimic of HPV-Related Squamous Cell Carcinoma—A Report of Three Cases
- 01.12.2026
- Research
Erschienen in:
- Verfasst von
- Todd M. Stevens
- Dina Kokh
- Gian Piero Carames
- Manuel Lora Gonzalez
- Sarah DePew
- Elizabeth Manion
- Sayedamin Mostofizadeh
- John K. Choi
- Vishnu Reddy
- Erschienen in
- Head and Neck Pathology | Ausgabe 1/2026
Abstract
Background
Human papillomavirus-associated squamous cell carcinoma is the most common malignant neoplasm of the oropharynx, often expressing p16 and p63. However, these markers are not entirely specific, and rare lymphoid neoplasms can morphologically mimic nonkeratinizing squamous cell carcinoma and express these markers. College of American Pathologists guidelines for Human papillomavirus testing in Head and Neck squamous cell carcinoma emphasize that p16 positivity must be interpreted in the morphologic and anatomic context.
Methods
We report three cases of p63-positive diffuse large B-cell lymphoma of the oropharynx, initially thought to represent Human papillomavirus-associated squamous cell carcinoma due to p63 positivity in all and p16 positivity in one. Cases were evaluated with standard histologic, immunohistochemical, in-situ hybridization, and fluorescence in-situ hybridization studies.
Results
The three cases demonstrated sheets of large atypical lymphoid cells with high mitotic activity and prominent nucleoli; keratinization or squamous differentiation were absent. Diffuse CD20 and PAX5 positivity in all cases confirmed diffuse large B-cell lymphoma, while p16 was variably positive and p40 was negative in all cases. The misdiagnoses occurred due to reliance on p63 and p16 positivity in the setting of oropharyngeal tumors, highlighting the importance of interpreting immunohistochemical results in context.
Conclusions
Pathologists should be aware that p63 and p16 expression in an oropharyngeal neoplasm does not definitively indicate Human papillomavirus-associated squamous cell carcinoma Morphology evaluation, even in the present immunohistochemical and molecular age, remains a bedrock of accurate pathologic diagnosis.
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- Titel
- p63-Positive Diffuse Large B-cell Lymphoma of Oropharynx: A Treacherous Mimic of HPV-Related Squamous Cell Carcinoma—A Report of Three Cases
- Verfasst von
-
Todd M. Stevens
Dina Kokh
Gian Piero Carames
Manuel Lora Gonzalez
Sarah DePew
Elizabeth Manion
Sayedamin Mostofizadeh
John K. Choi
Vishnu Reddy
- Publikationsdatum
- 01.12.2026
- Verlag
- Springer US
- Erschienen in
-
Head and Neck Pathology / Ausgabe 1/2026
Elektronische ISSN: 1936-0568 - DOI
- https://doi.org/10.1007/s12105-025-01884-x
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