Incidence of lichen sclerosus and subsequent causes of death: a nationwide Finnish register study.

OBJECTIVE: To assess the incidence of lichen sclerosus (LS) in women and the all-cause and cause-specific mortality of women with LS. DESIGN: Population-based descriptive study. SETTING: Finland. POPULATION: All Finnish women, including 7790 women diagnosed with LS during the period 1969-2012. METHODS: Information gathered from the Finnish Hospital Discharge Register on women with LS was combined with dates and causes of death from Statistics Finland and the Finnish Cancer Registry. Population statistics are from Statistics Finland. MAIN OUTCOME MEASURES: Crude and age-adjusted incidence rates of LS and standardised mortality ratios (SMRs). RESULTS: The incidence rate of LS adjusted for age (European Standard Population) increased from 14 per 100 000 woman-years in 2003 to 22 per 100 000 woman-years in 2010-2012. The age-specific incidence rate was highest in postmenopausal women (24-53 per 100 000) but was also elevated in girls aged 5-9 years (seven per 100 000). The all-cause mortality of women with LS was lower than in the general female population (SMR 0.84, 95% CI 0.78-0.90), mostly as a result of decreased mortality from circulatory diseases (SMR 0.80, 95% CI 0.72-0.89) and dementia and Alzheimer's disease (SMR 0.75, 95% CI 0.62-0.88). The cancer mortality equalled that of the population, but the vulvar cancer mortality was increased (SMR 28.1, 95% CI 19.3-39.4). CONCLUSIONS: Lichen sclerosus is a common disease of elderly women. The overall mortality is decreased whereas the mortality as a result of vulvar cancer is increased. TWEETABLE ABSTRACT: The likelihood of getting LS by age 80 years is 1.6%. The mortality of women with LS is reduced compared with that of the population.

Histologic and immunohistochemical assessment of penile carcinomas in a North American population.

Penile squamous cell carcinoma (SCC) is sometimes an aggressive disease that has a variable worldwide incidence, in part due to differing rates of inflammatory and infectious risk factors. In the developed world, penile SCC is a rare malignancy, and most studies therefore originate in less developed countries. The current study was undertaken to examine the morphologic and immunohistochemical features of penile SCC from a region with low disease incidence. Sixty-two complete or partial penectomy specimens from 59 patients were reviewed. Twenty-six patients had metastasis, 3 had recurrent disease, and 7 were dead due to tumor. Most patients were uncircumcised (72%). Twenty-two percent of carcinomas were associated with lichen sclerosis. Perineural invasion was significantly associated with metastasis (P=0.007). Most SCCs (65%) had the usual keratinizing morphology, and these tumors were significantly associated with the differentiated form of intraepithelial lesion (P<0.0001), p53 positivity (P=0.002), cyclin D1 positivity (P=0.007), and EGFR overexpression (P=0.003). Human papilloma virus (HPV)-associated tumors accounted for 27% and were basaloid (8%), warty (10%), mixed (6%), or lymphoepithelioma-like carcinoma (4%) variants. These were significantly associated with p16 expression (P<0.0001) and the undifferentiated form of intraepithelial lesion (P<0.001). Among all SCCs, there was no difference in the immunohistochemical or in situ hybridization profile between primary tumors and metastases. Although penile SCC is rare in the United States, the tumor variants, immunohistochemical profiles, and proportion of HPV-associated tumors are similar to those in less developed countries. Two distinct pathways appear to lead to carcinogenesis; one is related to underlying chronic inflammatory states, involves p53 mutation, cyclin D1 overexpression, and culminates in classic keratinizing SCC. The other pathway involves high-risk HPV infection, demonstrates strong p16 expression, and results in SCC with varied, but distinctive morphologies.

Does the width of the surgical margin of safety or premalignant dermatoses at the negative surgical margin affect outcome in surgically treated penile cancer?

AIMS: To evaluate the prognostic impact of the width of negative surgical margins (NSM) and associated and preinvasive lesions at the NSM in patients with penile squamous cell cancer (PSC). METHODS: Enrolling 87 patients with NSM who underwent surgery for PSC, the archived margin slides and entirely wax-embedded surgical margins were retrieved from the pathology files. After step sections were cut, margins were stained with antibodies against CK5/6, p16, p53 and Ki-67 and subjected to in situ hybridisation for high-risk human papillomavirus (HPV). All NSM were histologically examined for squamous hyperplasia (SH), lichen sclerosus (LS) and subtypes of penile intraepithelial neoplasia (PeIN). Then, histological findings were correlated with cancer-specific mortality (CSM, median follow-up 34 months; IQR 6-70). RESULTS: All NSM were negative for high-risk HPV and exhibited SH (p16 and p53 negative, Ki-67 variably positive), LS (p16 negative, variable p53 and Ki-67 positivity) and differentiated PeIN (dPeIN; p16 negative, Ki-67 positive, variable p53 positivity) in 28 (32%), 30 (34%) and 22 (25%) cases, respectively, whereas PeIN subtypes other then dPeIN did not occur. Pathological tumour stage was the only independent predictive parameter with respect to CSM in the multivariable analysis (p=0.001). CONCLUSIONS: SH, LS and dPeIN are frequent histological findings at the NSM of surgically treated PSC. However, neither the width of the NSM nor dPeIN, LS or SH at the NSM influences prognostic outcome.