Abstract
Lacrimal sac malignancies are rare, with squamous cell carcinoma (SCC) being the most common type. High-risk human papillomavirus (HR-HPV) is a known driver of SCC in the oropharynx and other head and neck sites. This study investigated the prevalence of HR-HPV in primary lacrimal sac SCC using p16 immunohistochemistry and RNA in situ hybridization.
The pathology databases of the Florida Lions Eye Bank Ocular Pathology Laboratory and the Department of Pathology and Laboratory Medicine at the University of Miami Miller School of Medicine were reviewed for cases of primary lacrimal sac SCC with sufficient tissue for HR-HPV testing. P16 positivity was defined as strong, diffuse staining in >70% of tumor cells. RNA in situ hybridization was used to detect transcriptionally active HR-HPV.
Fifteen patients (mean age 63 years; 7 men and 8 women) with nonkeratinizing, papillary lacrimal sac SCC were identified. Twelve cases (80%) were positive for both p16 and HR-HPV by RNA in situ hybridization. All 3 HR-HPV negative cases were also p16-negative. Among HR-HPV-positive patients, 92% were Caucasian, with equal gender distribution. The most common presenting symptoms were epiphora (83%), erythema/edema (42%), and pruritus (33%). Most patients were treated with surgery and multimodal therapy. At follow-up (range 5-83 months), 92% of HR-HPV-positive patients were alive.
Primary lacrimal sac SCCs are frequently associated with HR-HPV and typically show nonkeratinizing, papillary morphology. p16 is a reliable surrogate marker for transcriptionally active HR-HPV in these tumors, supporting a potential etiologic role and diagnostic utility.