Unusual location of a common dermatosis

A case of bilateral areolar and periareolar pityriasis versicolor is described. Neither clinical features nor dermoscopy observation were diagnostic for this atypical picture. In spite of a single previous report which described specific dermoscopic features of pityriasis versicolor, it may be hypothesized that polymorphic dermoscopic patterns may be observed in this superficial fungal disease

Diffuse pulmonary meningothelial like nodules simulating metastatic thymoma

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Association of retinoic acid receptor ß gene with onset and progression of lichen sclerosus-associated vulvar squamous cell carcinoma

IMPORTANCE Molecular alterations in lichen sclerosus-associated vulvar squamous cell carcinoma (LS-VSCC) are largely unknown. OBJECTIVE To determine whether the retinoic acid receptor ß (RARß) tumor-suppressor gene is involved in the onset and/or progression of LS-VSCC. DESIGN, SETTING, AND PARTICIPANTS The case-control study, conducted at University- Hospital of Ferrara, Italy, included 20 LS-VSCC (mean [SD] age, 75 [3] years) and 20 cancer-associated vulvar LS (caVLS; mean [SD] age, 62 [11] years) formalin-fixed embedded tissue specimens, 20 cancer-free vulvar LS (cfVLS), and 20 normal skin fresh specimens from diagnostic biopsies and women surgically treated for nonmalignant skin lesions, respectively. RARß gene expression and promoter methylation were investigated in LS-VSCC and caVLS adjacent to VSCC specimens, and in cfVLS and normal skin specimens, as controls, by RT-Q real-time polymerase chain reaction (PCR) analysis, and sequencing of PCR-amplified bisulfite-treated DNA. C-Jun expression, an RARß pathway-related gene, was also investigated. MAIN OUTCOMES AND MEASURES RARß expression, correlation with its promoter methylation and c-Jun expression, and association with onset or progression of LS-VSCC. RESULTS In LS-VSCC, RARß messenger RNA was 3.4-, 3.6-, and 4.8-fold lower than in caVLS (P = .001), cfVLS (P = .005), and normal skin (P < .001), respectively. The RARß mRNA levels were similar in caVLS, cfVLS, and normal skin. The RARß promoter was hypermethylated in 18 (90%) of 20 LS-VSCC, 11 (55%) of 20 cfVLS, 10 (50%) of 20 caVLS, and 5 (25%) of 20 in the normal skin group. The degree of methylation of RARß promoter was higher in LS-VSCC, ranging from 5 to 9 (full promoter methylation) CpGs methylated, than in caVLS (P = .02), cfVLS (P = .03), or normal skin (P < .001), which was up to 5 CpGs methylated. Importantly, 0 of 8 LS-VSCC with 5 to 6 CpGs methylated and 5 (63%) of 8 LS-VSCC with 7 to 8 CpGs methylated were from patients with lymph node metastasis at diagnosis, respectively, whereas there were 2 of 2 (100%) LS-VSCC samples with 9 CpG methylated from patients with lymph node metastasis at diagnosis and subsequent recurrence. In LS-VSCC c-Jun mRNA was 4.3-, 1.4-, and 2.6-fold higher than in caVLS (P < .001), cfVLS (P = .001), and normal skin (P < .001), respectively. The expression of c-Jun was similar in caVLS, cfVLS, and normal skin. CONCLUSIONS AND RELEVANCE Hypermethylation-induced RARß down-expression was associated with LS-VSCC and correlates with the upregulation of c-Jun. The degree of methylation of RARß promoter increased with the malignancy of LS-VSCC. Therefore, RARß gene dysregulation may play a role in progression of LS-VSCC, and RARß promoter methylation status may be used as a prognostic marker in clinical treatment of patients with LS-VSCC

HYPERMETHYLATION-INDUCED INACTIVATION OF IRF6 AND RARΒ GENES AS POTENTIAL PROGNOSTIC BIOMARKER IN VULVAR SQUAMOUS CELL CARCINOMA

Objectives: Vulvar squamous cell carcinoma (VSCC) represents 5% of gynecological malignancies. About 80% of VSCCs arises from inflammatory diseases, such as lichen sclerosus (LS). The molecular alterations involved in onset/progression of LS-associated VSCC are unknown. Interferon regulatory factor 6 (IRF6) and retinoic acid receptor β (RARβ) tumor-suppressor genes have been found downregulated by promoter methylation in different cancers.1,2 We aimed to evaluate the possible involvement of the IRF6 and RARβ in the development of VSCC from LS. Methods: IRF6 and RARβ mRNA expressions and promoter methylations were investigated by quantitative PCR (qPCR) and bisulphite-sequencing, respectively, in VSCC (n=20) and the adjacent LS (n=20), vulvar intraepithelial neoplasia (VIN; n=5, only for IRF6), cancer-free LS (cfLS, n=20) and normal skin (NS, n=20). IRF6 and RARβ pathway-related genes p63 and c-Jun mRNAs were also investigated.3,4 Results: IRF6 resulted downregulated in LS, VIN, VSCC and cfLS specimens, compared to NS, whereas p63 was overexpressed. IRF6 promoter was hypermethylated in 9/20 (45%) LS, 1/5 (20%) VIN, 16/20 (80%) VSCC, 2/20 (10%) cfLS, and 0 NS.3 RARβ was downregulated in VSCC compared to LS, cfLS and NS, whereas c-jun resulted overexpressed in VSCC compared to LS, cfLS and NS. RARβ promoter was hypermethylated in 18/20 (90%) VSCC, 11/20 (55%) cfLS, 10/20 (50%) LS and 5/20 (25%) NS. Interestingly, 2/18 (11.1%) VSCC showed full methylation of RARβ promoter were from women with tumor recurrence.4 Conclusions: IRF6 and RARβ are down expressed by promoter methylation in LS-associated VSCC and may be involved in the development/progression of VSCC from LS. IRF6 and RARβ promoter hypermethylation may be a biomarker of cancer-risk in LS patients, and a prognostic biomarker of cancer progression in LS-associated-VSCC patients.3,4 References: 1.Ivanova T et al. BMC Cancer.2:4,2002. 2.Botti E et al. PNAS.108:13710-15,2011. 3.Rotondo JC et al. JAMA Dermatol.152:928-33,2016. 4.Rotondo JC et al. JAMA Dermatol.154:1-5,2018