Human papillomavirus-related carcinoma with adenoid cystic-like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract

Abstract

Human papillomavirus (HPV)-related carcinomas of the head and neck are characterized by a predilection for the oropharynx, a nonkeratinizing squamous morphology, and infection with the HPV 16 type; but comprehensive HPV testing across all head and neck sites has shown that the pathologic features of HPV-related carcinoma may be more wide ranging than initially anticipated. In particular, a subset of sinonasal carcinomas are HPV positive, and these include a variant that is histologically similar to adenoid cystic carcinoma (ACC). Cases were identified by retrospective and prospective analyses of head and neck carcinomas with ACC features. HPV analysis was performed using p16 immunohistochemistry and high-risk HPV in situ hybridization. HPV-positive cases were confirmed and typed using HPV type-specific quantitative polymerase chain reaction and further characterized on the basis of their immunohistochemical profile and MYB gene status. HPV was detected in 8 carcinomas of the sinonasal tract, but it was not detected in any ACCs arising outside of the sinonasal tract. The HPV types were 33 (n=6), 35 (n=1), and indeterminate (n=1). Six patients were women, and 2 were men, ranging in age from 40 to 73 years (mean 55 y). The carcinomas were characterized by a nested growth, a prominent basaloid component showing myoepithelial differentiation and forming microcystic spaces, and a minor epithelial component with ductal structures. Squamous differentiation, when present, was restricted to the surface epithelium. The carcinomas were not associated with the MYB gene rearrangement that characterizes a subset of ACCs. These cases draw attention to an unusual variant of HPV-related carcinoma that has a predilection for the sinonasal tract. Despite significant morphologic overlap with ACC, it is distinct in several respects including an association with surface squamous dysplasia, absence of the MYB gene rearrangement, and an association with HPV, particularly type 33. As HPV positivity confers distinct clinicopathologic characteristics when encountered in the oropharynx, a more comprehensive analysis of risk factors, response to therapy, and clinical outcomes is warranted for HPV-related carcinomas of the sinonasal tract.

Figure 1

HPV-related carcinomas with ACC-like features exhibit a consistent lobular pattern of growth. All four of these cases (A–D) show a proliferation of basaloid cells that are compacted into nests and lobules separated by a fibrous stroma.

Figure 2

Unlike basaloid variants of squamous cell carcinoma, HPV-related carcinomas with ACC often exhibited cribriform structures (A and B) and true ductal formations (C and D).

Figure 3

Six of the eight carcinomas were associated with squamous dysplasia of the surface epithelium.

Figure 4

HPV-related ACC-like carcinomas tend to exhibit both myoepithelial and ductal components (A) and these can be highlighted by immunohistochemistry. The ducts show stronger staining for AE1/AE3 (B), while the myoepithelial cells are strongly positive for p63 (C), calponin (D), and muscle specific actin (E). Both components are p16 positive (F) and exhibit hybridization signals for HPV 33 (inset of F).

Figure 5

An HPV-related adenoid cystic-like carcinoma (A) demonstrating strong p16 immunohistochemical staining (B) and high risk HPV in situ hybridization signals (C). Quantitative PCR using general consensus (GP) and an HPV type specific probes confirms the presence of HPV 33 (lane 1 = HPV 16 positive CaSki cell line; and lane 2 = sinonasal carcinoma).