Biphenotypic human papillomavirus-associated head and neck squamous cell carcinoma: a report of two cases
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CASE REPORT
Open Access
Biphenotypic human papillomavirusassociated head and neck squamous cell carcinoma: a report of two cases Gayani Pitiyage1, Mary Lei2, Teresa Guererro Urbano2, Edward Odell1,3 and Selvam Thavaraj1,3*
Abstract Human papillomavirus-associated oropharyngeal squamous cell carcinoma is now recognised as a subtype of head and neck cancer with distinct clinical, molecular and histological characteristics. The majority of these carcinomas are of non-keratinising squamous type but there is a growing number of histomorphologic variants of this disease. Here we describe the clinical, histomorphologic and immunophenotypic features of two cases of human papillomavirus-associated oropharyngeal squamous cell carcinoma demonstrating a clearly delineated biphasic differentiated and undifferentiated phenotype. Keywords: Biphasic, Biphenotypic, Differentiated, Human papillomavirus, Oropharyngeal, Squamous cell carcinoma, Undifferentiated, Variant
Background Oropharyngeal squamous cell carcinoma (OpSCC) associated with high-risk subtypes of human papillomavirus (HPV) demonstrates distinct demographic and clinical characteristics. These carcinomas often arise in nonsmokers who do not consume alcohol to excess and present on average 5–6 years earlier than site and staged matched HPV-negative carcinomas [1]. Importantly, patients with HPV-associated OpSCC have significantly improved overall and disease-specific survival compared to HPV-negative controls. Alongside these observations, HPV-associated OpSCC have also been shown to contain fewer cumulative mutations and demonstrate particular histomorphological features [2, 3], recapitulating the reticulated crypt of Waldeyer’s ring and lacking keratin with little or absent squamous maturation [4]. Other microscopic features strongly predictive of HPVassociation are an architectural arrangement as broad interconnecting strands, large islands or sheets, a welldelineated invasive front and lack of significant stromal
* Correspondence: [email protected] 1 Head and Neck Pathology, 4th Floor Tower Wing, Guy’s and St. Thomas’ NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK 3 Mucosal and Salivary Biology, King’s College London Dental Institute, 4th Floor Tower Wing, Great Maze Pond, London SE1 9RT, UK Full list of author information is available at the end of the article
desmoplasia [5]. These clinicopathological features have led some authorities to call for recognition of HPVassociated OpSCC as a distinct entity in future classifications [6]. While the majority of HPV-associated OpSCC are of non-keratinising type, a growing number of divergent morphological types have been described recently. These include basaloid squamous cell carcinoma, papillary squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma, lymphoepithelial carcinoma and small cell neuroendocrine carcinoma [7–12]. These reports are limited to isolated cases or small series and the clinical and biological significance of these subtypes are yet to be elucidated, particularly whe
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