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Melanoma is one of the most aggressive tumors, and in the setting of rising incidence and mortality, there is an urgent need to identify new prognostic markers. Toll-like receptors (TLRs), are aberrantly expressed in numerous cancers, including melanoma. TLR signaling provides a microenvironment that is involved in antitumor immune response, chronic inflammation, cancer cell proliferation and evasion of immune destruction. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) in TLR3 and TLR4 genes are associated with clinicopathologic features, progression and survival of melanoma patients. The study was conducted on 120 melanoma patients. DNA extracted from peripheral blood was genotyped for TLR3 polymorphisms rs5743312 and rs3775291 (L412F) and TLR4 polymorphisms rs4986790 (D299G) and rs4986791 (T399I), by TaqMan Real-Time PCR Assays. Kaplan-Meier survival curves were compared by the log-rank test. TLR3 polymorphism L412F was associated with a higher mitotic index ( P  = 0.035). TLR4 D299G and T399I polymorphisms were associated with indicators of melanoma severity, nodal metastases ( P  = 0.005 and P  = 0.007, respectively) and advanced stage III ( P  = 0.005 and P  = 0.004, respectively). Cox regression analysis showed that the presence of tumor-infiltrating lymphocytes (TILs) predicted better overall survival (HR = 0.318; P  = 0.004). TLR4 T399I polymorphism was significantly associated with worse survival, P  = 0.025. The overall survival rates were significantly lower for patients carrying variant allele T of TLR4 T399I SNP (TC and TT genotypes combined) ( P  = 0.008, log-rank test), compared to wild-type genotype CC. Our findings indicate that TLR4 polymorphisms T399I (rs4986791) and D299G (rs4986790) could be potential prognostic and survival markers for melanoma patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Dear editor, Condylomata accuminatum (CA) is a human papillomavirus (HPV) related sexually transmitted infection (STI), clinically characterized by solitary or even clustered dark red or pink lesions solely affecting the anogenital area (1). CA involving the extragenital, non-mucosal skin has been sporadically reported (2-4). Diagnosis of CA is usually straightforward when the lesions are located on the anogenital area. However, involvement of extragenital skin may pose a diagnostic challenge. Herein, we report a rare case of giant linear extragenital CA without coexisting genital lesions, diagnosed with a synergic intervention of dermatoscopy and clinics. A 70-year-old Caucasian man was referred to our department for an atypical asymptomatic seborrheic keratosis presenting as a linear verrucous plaque (20 × 2 cm) with few solitary reddish satellite papules on the abdomen (Figure 1, a). No similar lesions were present in both cutaneous and mucosal districts. Medical history was unremarkable, and the patient denied having recent sexual intercourse or any history of condylomas. Remarkably, the patient underwent a diet in the last 8 months that resulted in a loss of 30 kg. We employed dermatoscopy to further assess the lesions, highlighting a finger-like pattern on the main lesion (Figure 1, c), while satellite lesions presented a mosaic pattern (Figure 1, b). The clinical appearance and these dermatoscopic findings were suggestive of condyloma acuminatum (CA), but due to its extraordinary presentation we also performed an incisional biopsy. Histopathological examination reviled features compatible with the diagnosis of CA (Figure 1, d, e). To better characterized the HPV genotype (high-risk and low-risk HPV) a polymerase chain reaction (PCR) from lesional tissue sample was performed and found HPV type 6 positivity. The lesions were successfully removed by electrosurgery. Regular follow-up was scheduled. Sexually transmitted infections (STIs) were also screened, namely syphilis, gonorrhea, chlamydia trachomatis, and HIV status. In addition, laboratory tests and imaging examinations (radiography of the chest and ultrasound examination of the abdomen) revealed no pathological findings. CA involving the extragenital skin has been reported within intertriginous areas, including the inframammary fold, the groin, and the axillary vault, as well as mucosal surface such as intraoral and conjunctival mucosa (1-5). In most cases, extragenital CA coexisted with genital lesions. Staples et al. reported three obese patients with extragenital CA on the skin of the abdominal pannus (3). However, all of the patients had involvement of the inguinal folds, from where the CA had extended. Generally, CA is acquired by genital, oral, or anal sexual contact. Among the wide spectrum of HPV genotypes, types 6 and 11 are responsible of 90% of CA (1). Our paradigmatic case allows us reflect on the concept of transitory immune dysregulation due to a significant amount of weight loss, and the position of the lesions in particular seems to suggest that frictional triggers may disrupt the barrier integrity, leading to higher probability of infection. Dermoscopy is a noninvasive diagnostic tool with a significant role in the assessment of melanocytic and non-melanocytic skin tumors. Furthermore, the utility of dermatoscopy has expanded to the field of inflammatory and infectious skin disease, where dermoscopy enhances the differential diagnosis between them. Seborrheic keratosis, as the most common benign epithelial tumor, can occur anywhere in the skin excluding the palms, soles, and mucosa (6). In the anogenital area, seborrheic keratosis usually resembles CA. However, dermatoscopically, seborrheic keratosis can be immediately identified by the presence of milia-like cysts, comedo-like openings, fissures, finger-print structures, and sharply demarcated borders (6). In contrast, reports of CA dermoscopy suggested four different dermoscopic patterns: fingerlike, mosaic, knoblike, and the most commonly, an unspecific pattern (7). Our case showed that dermoscopy of extragenital CA presented a mosaic pattern in an early stage of CA, while fully developed lesions revealed a fingerlike pattern, as has previously been reported by Dong et al. (7), where two different stages of clinical development of CA exhibit distinctive dermoscopic patterns, which correlates with our case. We did not observe the typical dermoscopic features of seborrheic keratosis. CA arising in an extragenital area is very rare and perhaps also underestimated. Thus, dermatologists should be aware of this unusual presentation even in the absence of genital HPV involvement. Moreover, dermoscopy may facilitate CA recognition in a such uncommon location. To our knowledge, this is the first report of extragenital condyloma acuminatum documented dermoscopically.

The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer's protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P = 0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR) = 6.620, 95% confidence interval (CI): 2.214-19.791, P = 0.001]. DNMT1 rs2228612 was also associated with ulceration (P = 0.045), nodal status (P = 0.030), progression (P = 0. 007), and stage of disease (P = 0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR = 0.323, 95% CI: 0.127-0.855, P = 0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P = 0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR = 12.126, 95% CI: 2.345-62.715, P = 0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR = 37.888, 95% CI: 3.615-397.062, P = 0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.

Background: Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness., Methods: Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided., Results: In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis)., Conclusions: T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Toxoplasma gondii and cytomegalovirus (CMV) are pathogens associated with congenital anomalies., Methods: Serum was collected from 79 reproductive-age women and tested for IgM and IgG antibodies to T. gondii and CMV., Results: Seropositivity for T. gondii was detected in 24.1% of women and CMV in 96.2%. High seropositivity for CMV was found for all ages. The highest seropositivity for T. gondii was observed among older participants., Conclusions: T. gondii remains an important pathogen owing to low seropositivity.