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Jacek Calik,1 Monika Migdal,1 Tomasz Zawada,2 Torsten Bove2 1Old Town Clinic, Wrocław, Poland; 2TOOsonix A/S, Hoersholm, DenmarkCorrespondence: Torsten BoveTOOsonix A/S, Agern Alle 1, Hoersholm, DK-2970, Denmark, Tel +45- 2059 2999, Email torsten.bove@toosonix.comPurpose: High intensity focused ultrasound operating at 20 MHz has been demonstrated as a safe and efficient treatment modality for a range of dermatological indications. The method is potentially also applicable to removal of seborrheic keratosis.Patients and Methods: A total of 54 seborrheic keratoses in 11 volunteer subjects (8 women and 3 men, average age 51.5 ± 13.2 years) were treated in a single session with a medical 20 MHz high intensity focused ultrasound device developed for dermatological conditions. Handpieces with nominal focal depths of 0.8 mm below the skin surface were used to administer acoustic energy of 0.99– 1.2 J/dose. An integrated dermoscope in the handpiece was used to monitor the treatment in real-time. Treatment efficacy and side-effects were assessed directly after treatment and at follow-up 4– 15 weeks after treatment.Results: The treatment showed positive results in 96.3% of the cases. About 68.5% of the cases were classified as complete response and 27.8% of the cases as partial response. Two cases (3.7%) did not respond to treatment and were classified as stable condition. No subjects experienced worsening of their condition, and no treatment received the classification of progressive condition. Side effects were primarily redness in the treatment area due to superficial telangiectasia, mild scarring, and persisting and slow-healing lichen planus-like keratosis. No adverse events were observed.Conclusion: HIFU is concluded to be a safe and efficient skin treatment for seborrheic keratoses. It has advantages over conventional treatments that can lead to pain during treatment and scarring after healing.Keywords: seborrheic warts, solar lentigo, skin tumor, HIFU, dermoscopy, dermatology

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Background: Basal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis., Objective: This study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy., Methods: A total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants., Results: Dermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker., Conclusions: The lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Calik, Sauer, Giedziun, Piotrowska, Tumiłowicz, Wojnar and Dzięgiel.)

Melanocytic nevi, commonly known as moles, are benign skin lesions that often occur in children and adolescents. Overall, they are less common in children compared to adults. Understanding the diagnosis and management of melanocytic nevi and risk factors for melanoma development is crucial for their early detection and appropriate treatment. This paper presents children's most common melanocytic nevi, including their epidemiology, morphology, diagnostic methods, and treatment.

Background: Skin cancer incidence increases globally, requiring effective preventive measures and evidence-based treatment strategies. Current guidelines advocate for surgical excision as a first-line treatment for most early skin cancers. The study investigated practices regarding changing scalpel blades when excising multiple skin lesions in the same patient during the same visit (CSB) and explored how beliefs about iatrogenic seeding influence individual norms of practice., Methods: A multidisciplinary survey was conducted among 173 medical specialists involved in skin cancer care. Participants provided demographic information, years of experience, and practices regarding CSB in four clinical scenarios (first excised tumor: basal cell carcinoma, squamous cell carcinoma, melanoma suspect, and evident melanoma). Practice variations based on specialty, experience, and beliefs about seeding risk were statistically assessed., Results: Surgeons exhibited a significantly higher tendency to change blades compared to non-surgeons across all diagnoses. Iatrogenic seeding (56.52%) and clinical training (18.84%) were the main reasons provided for CSB. Beliefs about seeding risk did not differ significantly between specialties., Conclusions: Although the practice of CSB lacks strong scientific rationale, the approach to this practice significantly varies among different medical specialties. Healthcare professionals should critically evaluate and standardize evidence-based practices to ensure optimal patient care and mitigate potential harm., (© 2024 the International Society of Dermatology.)

Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor's aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Calik, Oślizło, Słocka-Romaniuk, Elsaftawy and Sauer.)

Background: The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally invasive treatment alternatives. Traditional surgical approaches, while effective, often result in notable cosmetic and functional limitations, particularly for lesions located on the face. This study explores High-Intensity Focused Ultrasound (HIFU) as a promising, non-invasive treatment option that aims to overcome these challenges, potentially revolutionizing BCC treatment by offering a balance between efficacy and cosmetic outcomes. Methods: Our investigation enrolled 8 patients, presenting a total of 15 BCC lesions, treated with a 20 MHz HIFU device. The selection of treatment parameters was precise, utilizing probe depths from 0.8 mm to 2.3 mm and energy settings ranging from 0.7 to 1.3 Joules (J) per pulse, determined by the lesion's infiltration depth as assessed via pre-procedure ultrasonography. A key component of our methodology included dermatoscopic monitoring, which allowed for detailed observation of the lesions' response to treatment over time. Patient-reported outcomes and satisfaction levels were systematically recorded, providing insights into the comparative advantages of HIFU. Results: Initial responses after HIFU treatment included whitening and edema, indicative of successful lesion ablation. Early post-treatment observations revealed minimal discomfort and quick recovery, with crust formation resolving within two weeks for most lesions. Over a period of three to six months, patients reported significant improvement, with lesions becoming lighter and blending into the surrounding skin, demonstrating effective and aesthetically pleasing outcomes. Patient satisfaction surveys conducted six months post-treatment revealed high levels of satisfaction, with 75% of participants reporting very high satisfaction due to minimal scarring and the non-invasive nature of the procedure. No recurrences of BCC were noted, attesting to the efficacy of HIFU as a treatment option. Conclusions: The findings from this study confirm that based on dermoscopy analysis, HIFU is a highly effective and patient-preferred non-invasive treatment modality for Basal Cell Carcinoma. HIFU offers a promising alternative to traditional surgical and non-surgical treatments, reducing the cosmetic and functional repercussions associated with BCC management. Given its efficacy, safety, and favorable patient satisfaction scores, HIFU warrants further investigation and consideration for broader clinical application in the treatment of BCC, potentially setting a new standard in dermatologic oncology care. This work represents a pilot study that is the first to describe the use of HIFU in the treatment of BCC.

Introduction: In dermatology, inflammatory skin conditions impose a substantial burden worldwide, with existing therapies showing limited efficacy and side effects. This report aims to compare a novel immunological activation induced by hyperthermic 20 MHz high intensity focused ultrasound (HIFU) with conventional cryotherapy. The bioeffects from the two methods are initially investigated by numerical models, and subsequently compared to clinical observations after treatment of a patient with the inflammatory disease granuloma annulare (GA)., Methods: Clinical responses to moderate energy HIFU and cryotherapy were analysed using numerical models. HIFU-induced pressure and heat transfer were calculated, and a three-layer finite element model simulated temperature distribution and necrotic volume in the skin. Model output was compared to 22 lesions treated with HIFU and 10 with cryotherapy in a patient with GA., Results: Cryotherapy produced a necrotic volume of 138.5 mm 3 at - 92.7 °C. HIFU at 0.3-0.6 J/exposure and focal depths of 0.8 or 1.3 mm generated necrotic volumes up to only 15.99 mm 3 at temperatures of 68.3-81.2 °C. HIFU achieved full or partial resolution in all treated areas, confirming its hyperthermic immunological activation effect, while cryotherapy also resolved lesions but led to scarring and dyspigmentation., Conclusion: Hyperthermic immunological activation of 20 MHz HIFU shows promise for treating inflammatory skin conditions as exemplified by GA. Numerical models demonstrate minimal skin necrosis compared to cryotherapy. Suggested optimal HIFU parameters are 1.3 mm focal depth, 0.4-0.5 J/exposure, 1 mm spacing, and 1 mm margin. Further studies on GA and other inflammatory diseases are recommended., (© 2024. The Author(s).)

This study investigates the impact of bisphosphonate therapy on the stomatognathic system in 80 patients with cancer of the breast and prostate with bone metastases. Bisphosphonates are integral for managing skeletal complications in these malignancies but are associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ), affecting 0.8-18.5% of patients. BRONJ manifests with pain, neuropathy, tissue swelling, mucosal ulceration, tooth mobility, and abscesses, yet its pathogenesis remains elusive, complicating risk prediction. The research employed comprehensive dental and radiological evaluations. Dental status was assessed using DMFT and OHI-S indices, Eichner's classification, and clinical periodontal measurements like the pocket depth (PD), clinical attachment loss (CAL), and modified Sulcus Bleeding Index (mSBI). A radiological analysis included panoramic X-rays for radiomorphometric measurements and TMJ lateral radiographs. Results indicated a significant decline in oral hygiene in patients with cancer after bisphosphonate therapy, marked by increased DMFT and OHI-S scores. Periodontal health also showed deterioration, with increased PD and CAL readings. The incidence of BRONJ symptoms was noted, although exact figures are not quantified in this abstract. The study also revealed changes in radiomorphometric parameters, suggesting bisphosphonates' impact on bone density and structure. No substantial alterations were observed in TMJ function, indicating a need for extended observation to understand bisphosphonates' long-term effects on the stomatognathic system. These findings highlight the importance of continuous dental monitoring and prophylaxis in patients undergoing bisphosphonate therapy. Implementing meticulous oral care protocols is essential for mitigating BRONJ risk and managing the complex oral health challenges in patients with cancer.

Background : High-Intensity Focused Ultrasound (HIFU) has emerged as a precise and non-invasive modality for tissue ablation and healing. This study presents a detailed dermoscopic analysis of skin healing post-High-Intensity Focused Ultrasound (HIFU) treatment, focusing on common benign skin lesions, such as seborrheic keratosis, sebaceous hyperplasia, vascular lesions, and sebaceous nevi. Methods : Prior to HIFU treatment, a comprehensive assessment was conducted, integrating ultrasound scanning and clinical evaluations. The TOOsonix System ONE-M was employed for HIFU treatments, with parameters tailored to each lesion type. Results : A common pattern observed across all lesions includes initial whitening post treatment, followed by scab formation and the development of a pink area with reparative vessels. This study, however, highlights distinct differences in fibrosis patterns and healing timelines across different lesion types. Each lesion type exhibited unique fibrosis patterns post treatment. Flatter variants of seborrheic keratosis healed within a month, displaying hypopigmentation and reparative vessels, alongside a distinct lattice fibrosis pattern in more verrucous forms, which took about two months to heal. Sebaceous hyperplasia, characterized by rapid healing within three weeks, demonstrated fibrosis with pink areas and perpendicular white lines, concluding with a slight depression. Vascular lesions varied in healing time based on depth, with superficial ones showing whitening and crust formation, while deeper lesions had vessel occlusion and size reduction accompanied by concentric fibrotic bands. Sebaceous nevi presented the longest healing duration of three months, characterized by amorphous white-gray structures, scab formation, and the emergence of pink areas with branching vessels, leading to clear skin with reduced white lines. Conclusions : in conclusion, this meticulous clinical evaluation highlights the unique healing characteristics and timelines for each skin lesion type treated with HIFU. These insights are invaluable for optimizing follow-up assessments, identifying potential complications, and refining treatment protocols. By providing detailed insights into the healing timelines and patterns for different types of lesions, patients can be better informed about their post-treatment journey.

Excessive epidermal hyperkeratosis in acral areas is a common occurrence in dermatology practice, with a notable prevalence of approximately 65% in the elderly, especially in plantar lesions. Hyperkeratosis, characterized by thickening of the stratum corneum, can have various causes, including chronic physical or chemical factors, genetic predispositions, immunological disorders, and pharmaceutical compounds. This condition can significantly impact mobility, increase the risk of falls, and reduce the overall quality of life, particularly in older individuals. Management often involves creams containing urea to soften hyperkeratotic areas. Currently, subjective visual evaluation is the gold standard for assessing hyperkeratosis severity, lacking precision and consistency. Therefore, our research group proposes a novel 6-point keratinization scale based on dermatoscopy with cross-polarization and parallel-polarization techniques. This scale provides a structured framework for objective assessment, aiding in treatment selection, duration determination, and monitoring disease progression. Its clinical utility extends to various dermatological conditions involving hyperkeratosis, making it a valuable tool in dermatology practice. This standardized approach enhances communication among healthcare professionals, ultimately improving patient care and research comparability in dermatology.

Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.

The aim of the study was to evaluate the effect of genotype on the productivity and egg quality of three hen strains included in the genetic resource protection program in Poland. The study encompassed populations of laying hens, i.e., Rhode Island Red/RIR (R-11 and K-22) and Rhode Island White (A-33). The analysis over five generations included the basic production traits, i.e., the weight of the birds at 20 weeks (g), egg weights at 33 and 53 weeks, sexual maturity, the number of eggs laid up to 56 weeks of age, and hatchability parameters. In addition, the effective population size (N e ) and flock homozygosity coefficient (F x ) were calculated for each breed. Population health during the rearing and production periods was also recorded. The study also determined egg content and shell quality traits in relation to the age of the hens. The birds were kept on litter at a stocking rate of 5 hens/m 2 and fed ad libitum with a standard feed mixture for hens. Based on the results, it was concluded that the evaluated hen populations (R-11, K-22, and A-33) are valuable strains, representing a reservoir of unique phenotypic and egg quality traits. It was shown that the random mating system used in the reproduction of flocks effectively protects the populations from an increase in the degree of inbreeding. An influence of hens' origin (genotype) and age on the performance results, as well as egg quality traits, was found. Over five generations, the evaluated hen strains were characterized by high survival rates (above 98%). The study also found a large variation between the R-11 and K-22 strains and the A-33 strain in terms of the evaluated performance traits, especially in the body and egg weights, sexual maturity age, and laying performance of hens. The earliest to start laying were hens from the K-22 strains, which also showed significantly ( p ≤ 0.05) higher laying performances compared to R-11 hens. The results also indicate that the quality of eggs from hens of the compared strains varied. This was particularly true for such traits as shell color; egg, shell, and yolk weight; and shell quality. It was also shown that many egg and shell quality traits change with the age of the hens. The analysis of the obtained data indicates that the adopted methods of conservative breeding for these populations have influenced the success of the conservation program.

Background: Existing therapeutic methods for reduction or removal of superficial vascular malformations and tumors have high risks of scarring and other complications that result in aesthetic appearance less favorable than the baseline. Patients are often cautioned against intervention, which can lead to psychosocial problems and low self-esteem. Improved treatment modalities are therefore relevant from both medical and aesthetic perspectives., Methods: Two volunteer subjects were treated with a medical 20 MHz high intensity focused ultrasound device developed for dermatological conditions. One patient was given three treatments to remove a superficial congenital hemangioma on the left middle cheek. The other patient was given a single treatment to remove seven cherry angiomas on the thighs. Handpieces with nominal focal depths of 0.8 - 1.8 mm below the skin surface were used to administer acoustic energy of 1.1 - 1.2 J/dose. An integrated dermoscope in the handpiece was used to monitor the treatment in real-time., Results: During treatment, blood in the capillary network of the lesions was coagulated immediately, and capillary walls were collapsed due to the thermal and mechanical effects of the high intensity focused ultrasound. During the healing phase, the areas regenerated a normal skin structure with very limited scar or dyspigmentation. At follow-up, a clear aesthetic improvement was observed over the baseline for all treated targets with the exception of two cherry angiomas, where focal depth and/or dose coverage had not been optimal., Conclusion: High intensity focused ultrasound is concluded to be a safe and efficient skin treatment for benign superficial vascular malformations and tumors., (© 2021 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory., Material and Methods: Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study., Results: Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS ( p  < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy ( p  = .0121, p  = .0014, p  < .0001; respectively) and PFS ( p  = .0369, p  = .0052, p  = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p  = .0183), brain metastasis (present vs. absent; p  = .0032), other locations (present vs. absent, p  = .0032), LDH (normal vs. elevated; p  = .0046) and stage according to TNM ( p  = .0093)., Conclusion: The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.

Background: Currently, limited data on targeted therapy and immunotherapy sequencing in patients with BRAF -mutant melanoma is available. Targeted therapy and immunotherapy are expected to be comparable in terms of overall survival (OS) when used as second-line therapies; therefore, understanding the characteristics of patients who completed sequential treatment is needed., Methods: The primary objective of this study was to analyze the efficacy of BRAFi/MEKi activity as second-line therapy in patients with advanced melanoma. We also aimed to describe the clinical characteristics of patients with advanced melanoma who were treated sequentially with immunotherapy and targeted therapy. We enrolled 97 patients treated between 1st December 2015 and 31st December 2020 with first-line immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors; and for the second-line treatment with at least one cycle of BRAFi/MEKi therapy with follow-up through 31 January 2022., Results: Median OS since first-line treatment initiation was 19.9 months and 12.8 months since initiation of BRAFi/MEKi treatment. All BRAFi/MRKi combinations were similarly effective. Median progression free survival (PFS) was 7.5 months since initiation of any BRAFi/MEKi treatment., Conclusions: BRAFi/MEKi therapy is effective in the second-line in advanced and metastatic melanoma patients. For the first time, the efficacy of all BRAFi/MEKi combinations as second-line therapy is shown.

The aim of the study was to compare the nutritive value of eggs from Polish Crested chickens (PCr) to that of eggs from commercial hybrid Hy-Line Brown (HLB) and to examine the effect of storage conditions on physical quality parameters. In total, 135 PCr (9 pens) and 75 (5 pens) HLB chickens were kept on litter and fed commercial feed. At laying peak (36 wk), all eggs (n = 66/ genotype) were collected on the same day and divided into 3 groups (n = 20): group I was assessed on the day after laying; group II was analyzed after 28 d of storage in a fridge; group III, after 28 d in storeroom conditions of 19.5 to 20.5°C. For group I, vitamin A and E content (n = 3 samples) and fatty acid (FA) profiles (n = 6 samples) were determined. For all groups, the physical quality parameters of the eggs were assessed. The vitamin E content was higher (P < 0.05) for PCr than HLB. The PUFA n-6 FA content was higher and the amount of MUFA was lower (P < 0.05) for PCr when compared to HLB. All physical parameters changed after storage, with more negative changes recorded for group III than for group II. Concerning egg weight, albumen height, Haugh unit score and the pH of the yolk and albumen, interaction between genotype and storage conditions (P < 0.001 - P < 0.05) was demonstrated. The lightest eggs with the lowest albumen height and the highest pH were recorded from PCr in group III. The lowest Haugh unit score was recorded from HLB eggs stored in the same conditions. Moreover, the eggs of PCr were characterized by a higher (P < 0.001) yolk content and yolk color (P < 0.05), whereas the weight of the yolk and content of albumen were lower (P < 0.001) for HLB. Eggs from PCr that are stored in appropriate conditions could possibly be offered as a niche product., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The diagnosis of melanoma is challenging for both dermatologists and oncologists. Incidence of melanoma increases at a rate of 3-7% per year. Usage of modern tools such as dermoscopy and in vivo reflectance confocal microscopy improve early diagnosis and can save a life. There are a few melanoma simulators which can cause confusion and mislead in the differential diagnosis. This study aims to present skin lesions which can be similar to melanoma in confocal microscopy and to emphasize the importance of a detailed differential diagnosis. We describe five melanocytic lesions similar to melanoma and misleading confocal features. Although in vivo reflectance confocal microscopy is very useful in differentiating melanocytic lesions, histopathology evaluation in cases of melanoma mimics is definitive., (© 2020 the International Society of Dermatology.)

Aim: To evaluate treatment results in advanced/metastatic melanoma patients treated with anti-PD-1 immunotherapy in routine practice in oncology centers in Poland. Methods: Multicenter retrospective analysis included 499 patients with unresectable/metastatic (stage IIIC-IV) melanoma treated with anti-PD-1 in first-line therapy. Results: Estimated median overall survival (OS) and progression-free survival (PFS) were 19.9 and 7.9 months, respectively. Multivariate analysis confirmed that ECOG 0, no brain metastases, normal lactate dehydrogenase level and occurrence of immune-related adverse events (irAEs) were statistically significantly associated with improved OS and PFS. Any irAE occurred in 24% of patients. Grade 3 or Grade 4 irAEs occurred in 6% of patients. Conclusion: Analysis revealed a slightly worse OS in real-world treatment in comparison to clinical trials (KEYNOTE-006 and CheckMate 066). Polish population treatment results are similar to other studies of real-world data. PFS and ORR are similar in our research and clinical trials.

Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three patients were aged 80-100, 218 patients were aged 65-79, and 208 patients were <65 years old. Baseline parameters were comparable. The median overall survival (OS) was 14.7, 18.7, 25.9, and the median progression-free survival (PFS) was 8.7, 7.7, and 6.2 months in the age groups of 80-100, 65-79, and <65 years, respectively. The median melanoma-specific survival (MSS) was 22.5, 27.8, and 31.6 months in the age groups of 80-100, 65-79, and <65 years, respectively. There was no statistically significant difference in OS (P = 0.2897), PFS (P = 0.7155), and MSS (P = 0.9235) between the group of 80-100 years old vs. 65-79 and vs. <65 years old patients. Overall response rate and disease control rate was similar in all groups (P = 0.06974 and P = 0.89435, respectively). Overall, the immune-related adverse event (irAE) rate was comparable in the three age groups (41, 34, and 37.5% in the groups of patients aged 80-100, 65-79, and <65 years, respectively). Also, the rates of G3 and G4 irAEs were comparable (4, 6, and 7% in the groups of patients, respectively). The efficacy and toxicity of anti-PD-1 therapy in octogenarians and nonagenarians with metastatic melanoma are similar as in patients aged <65 years and 65-79 years. The patients' age should not be considered as an exclusion criterion for anti-PD-1 treatment., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Laugier-Hunziker syndrome (LHS) is a rare, idiopathic pigmentary disorder especially affecting the lips and oral mucosa. At present, no more than 200 cases of patients diagnosed with LHS syndrome have been described worldwide. To date, three patients under the age of 20 have been described, including the youngest patient who is a 12-year-old child. The exact etiology of LHS still remains uncertain, as there is no evidence of systemic symptoms or increased cancer risk. The final diagnosis of LHS is possible after the exclusion of other, more serious diseases involving skin-mucosal hyperpigmentation, mainly Peutz-Jeghers syndrome (PJS) and Addison's disease (AD). Herein, we present a 16-year-old patient who has been diagnosed with oral hyperpigmentation since the age of 13. We reviewed the clinical and histological findings. In addition, we discussed the differential diagnosis of mucocutaneous hyperpigmentation., (© 2020 the International Society of Dermatology.)

Background: Neurite outgrowth inhibitor type B (NOGO-B) and its receptor (NGBR) were shown to regulate various crucial cellular processes and may be therefore potential factors influencing carcinogenesis., Materials and Methods: Expression of NOGO-A, NOGO-A/B and NGBR was studied in benign melanocytic lesions and primary tumors and metastases of malignant melanoma (MM)., Results: Cytoplasmic expression of the studied antigens was detected in melanocytes and MM cells. NOGO-A/B expression was significantly lower in metastatatic MM cases compared to primary MM tumors (p<0.01) and bening melanocytic lesions (p<0.001). In primary MM tumors, NOGO-A expression intensity positively correlated with NOGO-A/B (r=0.32, p<0.05) and NGBR expression (r=0.53, p<0.0001). NOGO-B and NGBR immunoreactivity correlated negatively with depth of primary MM infiltration (both p<0.01). Moreover, low NOGO-A/B expression was a factor of poor prognosis of primary MM., Conclusion: NOGO-A/B may be a negative prognostic factor of MM., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aims: It has recently been shown that podoplanin, a mucin-type glycoprotein, is expressed by cancer cells and cancer-associated fibroblasts (CAFs), and promotes cancer cell migration and invasiveness. The biological role of podoplanin expression in tumour stroma of invasive ductal carcinoma of the breast (IDC) has not been determined., Methods and Results: Podoplanin expression was analysed in 117 cases of IDC and 27 cases of fibrocystic change, as well as in breast cancer cell lines, with the use of immunohistochemistry and real-time polymerase chain reaction. In 82.1% of analysed tumours, podoplanin was found only in CAFs. Only two of 117 IDC cases (1.7%) were characterized by expression of this glycoprotein in cancer cells. None of the fibrocystic changes or stroma surrounding normal ducts showed podoplanin expression. Podoplanin-positive CAFs correlated with tumour size (P = 0.0125), grade of malignancy (P = 0.0058), lymph node metastasis (P = 0.0149), lymphovascular invasion (LVI) (P = 0.0486) and Ki67 expression in cancer cells (P = 0.0128). High-level podoplanin expression (>50% of positive stroma) in the tumour stroma was significantly associated with a negative oestrogen status (P = 0.0201). Univariate, but not multivariate, analysis showed that podoplanin expression by CAFs was associated with poor patient outcome (P = 0.0202)., Conclusions: Our results suggest that podoplanin expression by CAFs could be an unfavourable prognostic marker for IDC., (© 2011 Blackwell Publishing Limited.)