Inverted papilloma of the conjunctiva.

OBJECTIVE: The purpose of the present study is to describe the clinical and histopathological features of conjunctival inverted papilloma, to analyse for the presence of human papillomavirus (HPV), and to determine if HPV infection is associated with this type of tumour and its inverted growth pattern. METHODS AND ANALYSIS: Cases of conjunctival inverted papillomas were retrieved from the archives of the Department of Pathology, Rigshospitalet, Denmark. Patient records and pathology reports were reviewed. Formalin-fixed and paraffin-embedded tissue was analysed for the presence of HPV by immunohistochemistry, in situ hybridisation (ISH), PCR and HPV typed by sequencing. RESULTS: A total of four cases were retrieved. The age at diagnosis ranged from 41 to 77 years, with an equal sex distribution. All lesions were localised to the bulbar conjunctiva and two of the cases were pigmented. Histopathological examination did not reveal areas of dysplasia. All lesions were p16-positive and p53-positive by immunohistochemistry. High-risk HPV 58 was demonstrated in one lesion by ISH and PCR. CONCLUSION: Here we present four cases of conjunctival inverted papilloma, which is an exceedingly rare tumour with only 11 previously reported cases in the literature. Both clinically and histopathologically, the tumours show distinct features compared with exophytic conjunctival papillomas. Furthermore, this is the first description of high-risk HPV 58 in a conjunctival tumour. The biological behaviour of the tumour is uncertain due to its rareness. However, a complete removal of the lesion and a careful observation are recommended. The finding of HPV 58 underlines the necessity of this precaution.

Human papillomavirus and pterygium. Is the virus a risk factor?

BACKGROUND: Pterygium is a disease of unknown origin and pathogenesis that might be vision threatening. It is characterised by a wing-like conjunctival overgrowth of the cornea. Several studies have investigated human papillomavirus (HPV) as a risk factor for the development of pterygia, but the results are inconclusive. AIM: To investigate a large sample of pterygia for the presence of HPV in order to clarify the putative association between pterygia and HPV. METHODS: 100 specimens of pterygium from Danish patients and 20 normal conjunctival biopsy specimens were investigated for the presence of HPV with PCR technique using beta-globin primers to access the quality of the extracted DNA and the HPV primers MY09/11 and GP5+/6+. HPV-positive specimens underwent subsequent HPV typing with type-specific HPV primers and further investigation with DNA in situ hybridisation (ISH). RESULTS: 90 of 100 investigated pterygia proved suitable for HPV analysis by PCR. As beta-globin could not be amplified, 10 specimens were excluded from the study. 4 of 90 pterygia harboured HPV. HPV type 6 was identified in all four HPV-positive pterygia. The 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. All four pterygia that were HPV type 6 positive were DNA ISH negative. CONCLUSIONS: The low presence of HPV DNA in pterygia does not support the hypothesis that HPV is involved in the development of pterygia in Denmark.

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

AIM: To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). METHODS: Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. RESULTS: HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. CONCLUSION: There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

Squamous cell dysplasia and carcinoma of the conjunctiva. A nationwide, retrospective, epidemiological study of Danish patients.

PURPOSE: To investigate the epidemiology of squamous cell dysplasia and carcinoma of the conjunctiva in Denmark. METHODS: Review of the histopathological case reports at the Eye Pathology Institute (EPI), University of Copenhagen, and the National Danish Pathology Bank from 1980 to 2011. Information regarding distribution of age and sex, localization, earlier pathology, comorbidity and recurrence of the condition was registered. The Cause of Death Registry at Statens Serum Institut was used to obtain information regarding cause of death. RESULTS: A total of 143 cases were identified. Ninety-five (61%) had epithelial dysplasia, 19 (13%) had carcinoma in situ, and 29 (20%) had squamous cell carcinoma. A significantly higher proportion of men were found. The median age at diagnosis was 65 years. The risk of recurrence was 10.0% [95% confidence interval (CI): 5.0-15.0] after 1 year and 17.2% (95% CI: 10.8-23.7) after 5 years. The lesions were most often localized to the corneal limbus. In our records, one patient had a lymph node metastasis and the disease necessitated enucleation in two patients. No patients had died from squamous cell carcinoma of the conjunctiva. CONCLUSION: Overall, our data are in agreement with the results of previous studies in Northern, high-latitude countries. There is a low incidence rate; the lesions are predominantly seen in men in their seventh decade and localized to the corneal limbus. The risk of recurrence is high, and the benign lesions have potential to progress to frank carcinoma.

Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six carcinomas of the lacrimal sac were investigated for the presence of HPV using the polymerase chain reaction (PCR) technique. Fifteen specimens of dacryocystitis were included in the PCR reactions as controls. Furthermore, DNA in situ hybridization (ISH) and RNA ISH were performed. RESULTS: Low-risk HPV types 6 or 11 were identified in all four lacrimal sac papillomas suitable for PCR analysis and in situ hybridization. Four of six lacrimal sac carcinomas harboured HPV. One carcinoma was positive for HPV 11 only, two carcinomas had concomitant infection with HPV 6 or 11 and high-risk HPV 16, and the remaining carcinoma was positive for HPV 16. All specimens of dacryocystitis were betaglobin-positive and HPV-negative. Using DNA ISH, two papillomas and a single carcinoma showed evidence for vegetative HPV 11 DNA replication, whereas no HPV 16 DNA replication was found in the five carcinomas tested. HPV 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas.