Mastocytosis and Skin Cancer: The Current State of Knowledge.

Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have demonstrated that patients suffering from mastocytosis face an increased risk of melanoma and non-melanoma skin cancer. The cause of this has not yet been clearly identified. In the literature, the potential influence of several factors has been suggested, including genetic background, the role of cytokines produced by mast cells, iatrogenic and hormonal factors. The article summarizes the current state of knowledge regarding the epidemiology, pathogenesis, diagnosis, and management of skin neoplasia in mastocytosis patients.

The impact of the COVID-19 pandemic on the characteristics of melanoma: a single-centre cohort study.

Introduction: The COVID-19 pandemic had, in a broad sense, a negative impact on populational health and well-being. Countries around the world struggled to address a spike in demand for the management of viral pneumonia and, at the same time, to efficiently treat the conditions which deteriorate severely when the treatment is delayed. Several studies published so far have analysed the impact of the COVID-19 pandemic on skin cancer epidemiology and management, however the results have been inconsistent. Aim: To examine the influence of the COVID-19 pandemic on the cutaneous melanoma epidemiology diagnosed in a tertiary referral centre in Northern Poland. Material and methods: This was a retrospective study that gathered the data on all the cutaneous melanoma cases treated in our facility during the official lockdown period in Poland and compared them to those diagnosed during the corresponding period from before the pandemic. Results: The number of cutaneous melanoma cases diagnosed during the pandemic decreased substantially. Interestingly, it was mostly due to a decrease in the number of patients with cutaneous melanoma localised on the trunk and early melanoma cases (melanoma in situ and pT1a stage). Conclusions: Our data suggest that, similarly to the reports emerging worldwide, the COVID-19 pandemic impaired the capability of our healthcare system to diagnose and treat cutaneous melanoma in our region. The data are limited, and further research will be necessary to determine the whole extent of those changes, especially the long-term effects.

Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

Tattoos Dermatological Complications: Analysis of 53 Cases from Northern Poland.

BACKGROUND: The frequency of tattoos varies from 10% to 30% across the population worldwide. The growing popularity of tattooing increases the number of cutaneous reactions connected with this procedure. As we have not found any previous studies in the literature concerning tattoo complications in Poland and other Eastern European countries, we believe this to be the first study of this kind. OBJECTIVE: The primary objective of this study was to evaluate the clinical spectrum of complications associated with the procedure of permanent tattooing among patients from Northern Poland. METHODS: Medical data of 53 patients who developed tattoo-related cutaneous conditions were analyzed. All of the patients were consulted in the Dermatology, Venereology and Allergology Clinic in Gdansk in the years 2018-2021. Medical history, dermatological assessment, and photographic documentation of skin lesions were performed in each case. Dermoscopic examination was carried out in 16 cases and 20 skin biopsies of the tattoo reactions were performed. RESULTS: Twenty-one patients (40%) presented tattoo ink hypersensitivity reactions, out of which 18 were triggered by the red ink. In 11 cases (21%), contact dermatitis has developed after tattooing, while 9 of the patients (17%) presented tattoo infectious complications, including local bacterial infections, common warts, molluscum contagiosum, and demodicosis. We collected 8 cases (15%) of papulonodular reactions in black tattoos, and in 6 of them, histology showed granuloma formation. In 2 cases (4%), symptoms of anaphylaxis were observed after the tattooing procedure, and in another 2 cases (4%), Koebner phenomenon in the tattoo was diagnosed. Dermoscopy was the clue to the diagnosis in 4 cases. CONCLUSIONS: This is the first report presenting multiple cases of tattoo complications from Eastern Europe. The results of the study are consistent with other researches, showing a similar distribution of tattoo complications and that across the different pigments used, the red ink is most frequently responsible for tattoo reactions. We emphasize the usefulness of dermoscopic examination in the diagnosis of tattoo-related infections and draw the reader's attention to the rare, yet hazardous complications connected with peri-tattooing anaphylaxis.

Dermoscopic Features of Actinic Cheilitis and Other Common Inflammatory Cheilitis: A Multicentric Retrospective Observational Study by the International Dermoscopy Society.

BACKGROUND: Clinical differentiation between different cheilitis variants may be difficult. Application of mucoscopy, in addition to clinical background, could provide additional diagnostic clues facilitating initial patient management. OBJECTIVES: To determine mucoscopic clues differentiating actinic cheilitis from the main forms of inflammatory cheilitis, including eczematous cheilitis, discoid lupus erythematosus, and lichen planus of the lips. METHODS: This was a retrospective, multicenter study being a part of an ongoing project "Mucoscopy - an upcoming tool for oral mucosal disorders" under the aegis of the International Dermoscopy Society. Cases included in the current study were collected via an online call published on the IDS website (www.dermoscopy-ids.org) between January 2019 and December 2020. RESULTS: Whitish-red background was found in actinic cheilitis as well as in cheilitis due to discoid lupus erythematous and lichen planus. Polymorphous vessels were more likely to be seen in actinic cheilitis compared to other causes of cheilitis. White scales, ulceration, and blood spots predominated in actinic cheilitis and lichen planus, whereas yellowish scales typified eczematous and discoid lupus erythematous cheilitis. Radiating white lines although most common in lichen planus patients were also seen in actinic cheilitis. CONCLUSION: Despite differences in the frequency of mucoscopic structures, we have not found pathognomonic features allowing for differentiation between analyzed variants of cheilitis.

Agminated blue nevi: a case series and updated dermoscopic review.

Blue nevi, usually presenting as solitary, bluish, asymptomatic macules or nodules, are formed by collections of dermal melanocytes that failed to complete their migration from the neural crest to the dermo-epidermal junction. The term "agminated blue nevi" refers to multiple lesions grouped, linear, or arranged in a blashkoid distribution. It is a relatively rare phenomenon with less than 35 cases reported in the literature, but only 14 cases with dermoscopic features. We report another 4 cases along with an updated dermoscopic review.

Clinical and histopathological characteristics of primary and recurrent basal cell carcinoma: a retrospective study of the patients from a tertiary clinical centre in the northern Poland.

Introduction: Basal cell carcinoma (BCC) is the most common malignant neoplasm of the skin. Management of patients with recurrent BCC remains a current clinical issue. Data concerning BCC recurrence rates as well as characteristics of this group of patients in the Polish population are scarce. Aim: Identification and analysis of clinical, epidemiological and histopathological factors influencing BCC recurrence. Material and methods: Histopathological diagnoses of BCC patients treated by surgical methods at the Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, between 2013 and 2018, were retrospectively analysed. The analysis included 1097 tumours diagnosed in 802 patients, of which 1061 were primary BCC (pBCC) and 36 - recurring BCC (rBCC). Results: In the analysed cohort, rBCCs constituted 3.3% of cases. 49.8% of pBCCs occurred in women; while in the rBCC group - 47.2%. The most common histopathological type was infiltrative BCC, however, it was significantly more prevalent in rBCCs (36.9% and 52.8%, respectively). The average maximum size of pBCC was 12.3 ±8.8 mm, while of rBCC 18.4 ±15.1 mm (p = 0.036). The most common location of both pBCC and rBCC was the nose (tumours in this localization constituted 23.2% and 25.0%, respectively). Conclusions: In the analysed cohort a relatively low percentage of rBCC was found. Among analysed risk factors, the most important ones were the infiltrative histopathological type of BCC and the non-radical treatment of the primary tumour.

Application of mucous membrane dermoscopy (mucoscopy) in diagnostics of benign oral lesions - literature review and preliminary observations from International Dermoscopy Society study.

Dermoscopy of mucosal surface termed "mucoscopy" is an upcoming offshoot of dermatological imaging. However, the literature on mucoscopy is limited to individual cases and small case series. An organized review or systematic analysis of mucoscopy is lacking. The aim of this review was to summarize the published literature on mucoscopic features of benign conditions affecting the oral mucosa and semi-mucosa. Additionally, the results of mucoscopic features of diseases, which have not been described before have been presented.

FOXP3 and CTLA-4 genetic variants' influence on the susceptibility and clinical course of basal cell carcinoma.

INTRODUCTION: The pathogenesis of basal cell carcinoma (BCC) is multifactorial and not fully elucidated. Previous studies showed that behaviour of the tumour may be influenced by the immune system and identified CD4+CD25+FoxP3+ regulatory T cells (Tregs) as dominant immune cells in BCC microenvironment. The function and development of Tregs is regulated by FOXP3, encoding transcription factor Forkhead box P3. FOXP3 regulates transcription of many genes, including up-regulation of cytotoxic lymphocyte-associated antigen-4 gene (CTLA-4). Expressed on Tregs, CTLA-4 interacts with antigen-presenting cells to inhibit T-cell activation. AIM: To investigate the role of two polymorphisms (rs3761548 and rs2232365) of FOXP3 and CTLA-4 polymorphism (rs5742909) in BCC patients from northern Poland. MATERIAL AND METHODS: We analysed 280 unrelated patients with BCC of mean age 70.93 ±11.53 (70.54 ±12.55 women, 71.38 ±10.26 men) and 200 healthy, unrelated age- and sex-matched volunteers. RESULTS: The differences in the occurrence of BCC between genotypes and alleles of the analysed polymorphisms were not statistically significant. In the studied group, the presence of the CC genotype in CTLA-4 rs5742909 polymorphism was statistically more frequent in patients with multiple BCCs. CONCLUSIONS: It seems that the analysed FOXP3 and CTLA-4 polymorphisms do not influence the BCC susceptibility. CTLA-4 rs5742909 polymorphism may influence the susceptibility to multiple BCCs.

Childhood longitudinal melanonychia: case series from Poland.

INTRODUCTION: Longitudinal melanonychia (LM) is characterized by a tan, brown or black longitudinal streak within nail plate caused by the presence of melanin. LM is relatively common in dark-skinned population, infrequent in Caucasian population, and rare in children. AIM: We report epidemiological, clinicopathological and dermoscopic analysis of 8 cases of childhood LM from Poland, which is the largest series in the Central and Eastern European population. MATERIAL AND METHODS: Three hundred and forty-eight patients presenting with various nail pigmentation (in 2010-2016) were analysed. 72 cases of LM have been identified, including 8 cases of childhood LM (< 16 years of age), which were included in further analysis. RESULTS: Seven patients were boys and one girl, with mean age of 9 years (range: 6-13). More than a half (n = 5) presented skin phototype II. The most common location of melanonychia was the first left fingernail. Dermoscopy revealed heterogeneity of longitudinal lines colour in 5 cases. The irregularity of longitudinal line thickness in 5 cases and irregularity of parallelism in 5 cases was observed. Histopathological evaluation was performed in 4 patients, in 3 cases it revealed the presence of nail matrix nevus, in one case the presence of melanocytic proliferation of the lentiginous pattern along the dermoepidermal junction. CONCLUSIONS: Despite the fact that melanoma was not recognised in any case, such a possibility should always be considered as the cause of LM, even in the paediatric population. Dermoscopy seems to be useful in patient follow-up and management.

The prevalence and etiological factors of onychomycosis in psoriatic patients.

INTRODUCTION: The role of a number of inherited, acquired and environmental factors has been identified to increase the risk of onychomycosis. The literature data on psoriasis as a risk factor are contradictory. The potential relationship between these pathologies is very important as it influences the patient management. AIM: To evaluate the frequency of onychomycosis and etiological factors in patients with psoriasis compared to controls. MATERIAL AND METHODS: The studied group (n = 2427) included 2325 patients with nail abnormalities raising a clinical suspicion of nail onychomycosis (with no history of psoriasis) and 102 psoriatic inpatients. The control group included 100 patients with clinically normal nails. The assessment of psoriasis severity using Nail Psoriasis Severity Index (NAPSI) and Psoriasis Area and Severity Index (PASI) was performed in all psoriatic patients. The presence of fungi was confirmed in direct microscopy and culture. RESULTS: A significantly higher incidence of onychomycosis was observed in psoriatic patients as well as in non-psoriatic patients with clinically abnormal nails compared to controls. The prevalence of onychomycosis did not differ significantly between psoriatic patients and non-psoriatic patients with nail alterations. The characteristics of isolated fungi differed significantly between psoriatic and non-psoriatic patients. NAPSI ≥ 40 and receiving systemic treatment increased the risk of onychomycosis in psoriatic patients. CONCLUSIONS: The presented study showed a relatively high prevalence of onychomycosis in patients with psoriasis, what confirms the accuracy of performing screening mycological examination in this group. Further studies are warranted to evaluate the role of specific risk factors, explain the differences observed in previous studies and to determine optimal patient management.

Differentiation of Keratinocytes Modulates Skin HPA Analog.

It is well established, that epidermal keratinocytes express functional equivalent of hypothalamus-pituitary-adrenal axis (HPA) in order to respond to changing environment and maintain internal homeostasis. We are presenting data indicating that differentiation of primary neonatal human keratinocytes (HPEKp), induced by prolonged incubation or calcium is accompanied by significant changes in the expression of the elements of skin analog of HPA (sHPA). Expression of CRF, UCN1-3, POMC, ACTH, CRFR1, CRFR2, MC1R, MC2R, and GR (coded by NR3C1 gene) were observed on gene/protein levels along differentiation of keratinocytes in culture with similar pattern seen by immunohistochemistry on full thickness skin biopsies. Expression of CRF was more pronounced in less differentiated keratinocytes, which corresponded to the detection of CRF immunoreactivity preferentially in the stratum basale. POMC expression was enhanced in more differentiated keratinocytes, which corresponded to detection of ACTH immunoreactivity, predominantly in the stratum spinosum and stratum granulosum. Expression of urocortins was also affected by induction of HPEKp differentiation. Immunohistochemical studies showed high prevalence of CRFR1 in well differentiated keratinocytes, while smaller keratinocytes showed predominantly CRFR2 immunoreactivity. MC2R mRNA levels were elevated from days 4 to 8 of in vitro incubation, while MC2R immunoreactivity was the highest in the upper layers of epidermis. Similar changes in mRNA/protein levels of sHPA elements were observed in HPEKp keratinocytes treated with calcium. Summarizing, preferential expression of CRF and POMC (ACTH) by populations of keratinocytes on different stage of differentiation resembles organization of central HPA axis suggesting their distinct role in physiology and pathology of the epidermis. J. Cell. Physiol. 232: 154-166, 2017. © 2016 Wiley Periodicals, Inc.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part I: Treg properties and functions.

Regulatory T cells (Treg) can be divided into two types: the natural cells (tTreg), which arise in the thymus, and the induced cells (iTreg), which are produced in peripheral tissues during immune response. The most recently published studies indicate that the supervisory functions of these cells are weakened in the pathogenesis of autoimmune and neoplastic diseases of the skin. This may be a result of the domination of other immune cells in the skin, such as Th1/Th17/Th22 and Tc1 type in psoriasis and Th2 in atopic dermatitis. The excessive activity of Treg cells can lead to immunosuppression and decrease in the number of Th1 cells, which promote the development and progression of skin cancers. In the case of cutaneous T-cell lymphomas, there are suggestions that tumor progression is associated with the acquisition of the suppressor phenotype of malignant cells. There is genetic background of Treg dysfunction in skin disorders. This article describes the types and functions of Treg cells.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part III: Polymorphisms of genes involved in Tregs' activation and function.

Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of several skin diseases like psoriasis, atopic dermatitis, systemic lupus erythematosus, cutaneous T-cell lymphomas, and skin cancer and is also important in rheumatoid arthritis, diabetes and other autoimmune diseases. In this review, we will summarize the role of mutations and/or polymorphisms of genes involved in Tregs development, and functions in the pathogenesis of selected skin diseases.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis.

Regulatory FOXP3+ T cells (Tregs) constitute 5% to 10% of T cells in the normal human skin. They play an important role in the induction and maintenance of immunological tolerance. The suppressive effects of these cells are exerted by various mechanisms including the direct cytotoxic effect, anti-inflammatory cytokines, metabolic disruption, and modulation of the dendritic cells function. The deficiency of Treg cells number or function are one of the basic elements of the pathogenesis of many skin diseases, such as psoriasis, atopic dermatitis, bacterial and viral infections. They also play a role in the pathogenesis of T cell lymphomas of the skin (cutaneous T cell lymphomas - CTCL), skin tumors and mastocytosis. Here, in the second part of the cycle, we describe dysfunctions of Tregs in selected skin diseases.

Diagnosis of Mastocytosis in Children and Adults in Daily Clinical Practice.

Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the majority of cases skin involvement is the first clinical manifestation of the disease. Clinical work-up consists of a combination of morphological, immunohistochemical, flow cytometric immunophenotyping and molecular examination. Cutaneous mastocytosis predominates in children, whereas systemic mastocytosis is the most common form of the disease in adults. Therefore, different diagnostic algorithms have to be applied in adult patients and children with suspected mastocytosis. This comprehensive review presents currently defined variants of the disease and recommendations to facilitate diagnostic work-up in children and adults with suspected mastocytosis in daily clinical practice.

Soluble interleukin-2 receptor α and interleukin-2 serum levels in patients with basal cell carcinoma.

INTRODUCTION: Basal cell carcinoma (BCC) is an immunogenic neoplasm and the imbalance in Th1/Th2 cytokines expression seems to play the major role in pathogenesis and clinical behaviour of the tumour. AIM: To investigate the association of soluble interleukin 2α receptor (sIL-2Rα) and interleukin-2 (IL-2) serum concentrations with BCC. MATERIAL AND METHODS: The study involved 110 individuals with BCC and 60 healthy age- and sex-matched volunteers. Serum levels of sIL-2Rα and IL-2 were measured using ELISA test. RESULTS: We found significantly (p = 0.027) increased sIL-2Rα serum levels in BCC patients, in comparison to healthy controls. Statistically (p = 0.04) higher sIL-2Rα levels were observed in patients with more advanced tumours. Serum levels of sIL-2Rα showed a significant linear (r = 0.24, p = 0.018) correlation with tumour size. The average IL-2 serum levels in BCC patients were statistically (p = 0.039) decreased compared to controls. Significantly (p = 0.0454) lower median IL-2 levels were observed in patients with more advanced tumours. A negative correlation between sIL-2Rα and IL-2 serum concentrations was revealed (r = -0.22; p = 0.027). CONCLUSIONS: Our results testify to the importance of the IL-2/sIL-2Rα signalling pathway in pathogenesis of BCC, suggesting that IL-2 and sIL-2Rα might be considered as potential markers of disease and targets for immunotherapy in BCC patients.

-2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma.

INTRODUCTION: Polymorphic variants of MCP-1 and RANTES genes and their protein serum levels have been implicated in the increased risk and severity of several malignancies. However, the subject has not been explored in basal cell carcinoma (BCC) patients so far. AIM: To investigate the association between monocyte chemoattractant protein 1 (MCP-1) (-2518 A/G) and RANTES (-403 G/A) polymorphism and risk and clinical course of BCC. MATERIAL AND METHODS: The study group consisted of 150 unrelated patients with BCC and 140 healthy, unrelated, age- and sex-matched volunteers. The polymorphisms were analysed using the amplification refractory mutation system polymerase chain reaction method (ARMS-PCR) and single specific primer-polymerase chain reaction (SSP-PCR). Serum cytokine levels were measured with ELISA. RESULTS: The presence of the MCP-1 -2518 GG genotype was statistically more frequent in BCC patients and it increased the risk of BCC (OR = 2.63, p = 0.003). Genotype -330 GG was statistically more common in patients with less advanced tumours (OR = 2.8, p = 0.017). Monocyte chemoattractant protein 1 serum level was statistically higher with GG genotype. In the BCC group MCP-1 serum levels were decreased. Neither polymorphic variants of RANTES nor the chemokine serum concentration differed significantly between the study groups. CONCLUSIONS: These findings suggest that -2518 A/G MCP-1 polymorphism may be involved in BCC pathogenesis.