Abstract
Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02–0.48) and 0.23 (range: 0.07–0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02–0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen’s kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors.
Highlights
Penile cancer is a rare malignancy, especially in developed countries
The best concordance in assessing tumor histological subtype in general was seen between the pathologists specializing in diagnosis of penile tumors
Our study shows that pathologists who have experience in working with penile cancer have a good concordance in identifying human papillomavirus (HPV)-related and non-HPVrelated histological subtypes of squamous cell carcinoma
Summary
Penile cancer is a rare malignancy, especially in developed countries. The annual age-standardized global incidence is 0.84 cases per 100,000. Known risk factors for penile cancer include human papillomavirus (HPV) infection, phimosis, lichen sclerosus and other inflammatory conditions, UVA phototherapy, smoking, and socioeconomic. 50% of cases of penile cancer are associated with HPV infection [9, 10]. It has been demonstrated that patients with HPV-associated squamous cell carcinoma of the head and neck region have a better prognosis than those with HPV-negative tumors [11,12,13]. Multiple histological subtypes of penile squamous cell carcinoma have been added to the classification over the years, and are included in the 2016 World Health Organization (WHO) classification of tumors [17] under two major categories: HPV-related and non-HPV-related subtypes. HPV-negative tumors are most often associated with inflammatory conditions such as lichen sclerosus et atrophicus and lichen planus, and usually show a verrucous or usual histological subtype
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