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Background/Objectives: Mohs micrographic surgery (MMS) is a precise skin surgery technique that is particularly useful in the treatment of high-risk skin cancers and tumors located in challenging anatomical areas. Methods: we report two cases of basal cell carcinoma located in the acral areas effectively treated using MMS. Results: the presented cases demonstrate that MMS is an excellent surgical modality providing outstanding medical, cosmetic, and functional outcomes. Moreover, this study provides another dermoscopic presentation of acral basal cell carcinoma in a patient without the diagnosis of hereditary genetic syndromes associated with an increased risk of skin cancer. Conclusions: basal cell carcinoma located on hands and feet, albeit rare, should be included in the differential diagnosis of amelanotic skin tumors in acral areas. [ABSTRACT FROM AUTHOR]

Paraneoplastic acral vascular syndrome (PAVS) is a captivating enigma in the landscape of oncological pathology, characterized by vascular disturbances of the extremities. PAVS is linked to rapidly progressing trajectory and understanding the intricate interplay between cancer and this vascular dysfunction is imperative for timely diagnosis. We describe the case of a 45-year-old cachectic male who presented at the ICU with bilateral tumefied, cyanotic digits, accompanied by acute pain and numbness in both hands. A Digital Angiography described complete obstruction of the digital arteries. Imaging showed a laterocervical tumor mass with pulmonary metastases. This form of digital ischemia likely stems from endothelial dysfunction and prothrombotic effects induced by the tumor through a paraneoplastic mechanism. This case underscores the importance of recognizing acral vascular syndrome, prompting thorough investigation for an underlying malignancy. Ultimately, collective efforts aimed at enhancing our understanding of PAVS and optimizing its management hold promise for improving outcomes and alleviating the burden of this condition on affected patients.

Simple Summary: This study aimed to assess the 3-year time to relapse (TTR) and overall survival (OS) of melanoma, including acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or the combination of dabrafenib and trametinib. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). This study suggests that both acral and mucosal types in the adjuvant setting are less effective than non-acral cutaneous melanoma at the 3-year TTR. Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint. [ABSTRACT FROM AUTHOR]

Paraneoplastic acral vascular syndrome (PAVS) is a captivating enigma in the landscape of oncological pathology, characterized by vascular disturbances of the extremities. PAVS is linked to rapidly progressing trajectory and understanding the intricate interplay between cancer and this vascular dysfunction is imperative for timely diagnosis. We describe the case of a 45-year-old cachectic male who presented at the ICU with bilateral tumefied, cyanotic digits, accompanied by acute pain and numbness in both hands. A Digital Angiography described complete obstruction of the digital arteries. Imaging showed a laterocervical tumor mass with pulmonary metastases. This form of digital ischemia likely stems from endothelial dysfunction and prothrombotic effects induced by the tumor through a paraneoplastic mechanism. This case underscores the importance of recognizing acral vascular syndrome, prompting thorough investigation for an underlying malignancy. Ultimately, collective efforts aimed at enhancing our understanding of PAVS and optimizing its management hold promise for improving outcomes and alleviating the burden of this condition on affected patients. [ABSTRACT FROM AUTHOR]

Background: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. Methods: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. Results: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. Conclusion: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas.

Objective: Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each other. Materials and Methods: The demographic characteristics as well as cutaneous and extracutaneous findings of consecutive Gorlin syndrome patients diagnosed during 23 years were evaluated retrospectively. The relationship between palmoplantar pitting and basal cell carcinoma (BCC) in this localization and the relationship between odontogenic keratocysts (OKCs) and epidermoid cysts were investigated. Results: A total of 30 patients were diagnosed with Gorlin syndrome of whom 36.7% were children. BCC was the most common finding (90%) followed by OKCs (83.3%), skeletal system anomalies (76.7%), and palmoplantar pitting (76.7%). While classical BCC (63.3%) lesions were the predominant clinical subtype among all patients, acrochordon-like or small-sized papular BCCs were seen in 45.4% of pediatric patients. Three patients, 2 of whom were children, had BCC lesions in the palmoplantar region in association with palmoplantar pitting. Epidermoid cysts presenting clinically as solitary (n = 12) or a few nodules (n = 4) without punctum, located more commonly in acral areas (n = 10) were seen in 16 (53.3%) patients of whom 7 were children. Epidermoid cysts were seen in 60% of patients with OKCs, and the relationship between epidermoid cysts and OKCs was not statistically significant (P = .15). Extracutaneous tumors such as medulloblastoma (n = 3), cardiac fibroma (n = 1), and ameloblastoma (n = 1) were also recorded. Conclusion: The awareness of papular or acrochordon-like BCCs, palmoplantar BCCs, and acral epidermoid cysts without punctum may facilitate early diagnosis of Gorlin syndrome in children. [ABSTRACT FROM AUTHOR]

Background: Autologous noncultured, nontrypsinized melanocyte–keratinocyte grafting (Jodhpur technique [JT]) is an unconventional innovative surgical modality for the treatment of stable vitiligo. Acral vitiligo is considered an area that is difficult to treat with variable results in different studies. Purpose: The aim of this study was to assess the efficacy and safety of JT in stable acral vitiligo. Methods: This was an open, nonrandomized, and single-arm study. Ninety patches of stable acral vitiligo were included in this study. JT was performed over these patches. The total duration of the study was 48 weeks. The degree of repigmentation was graded into poor (

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods:Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results:Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM.

Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel immunotherapeutic regimes aiming to recover the antitumor function of immune cells. We studied a Mexican cohort of melanoma patients from the Mexican Institute of Social Security (IMSS) (n = 38) and found an overrepresentation of AM (73.9%). We developed a multiparametric immunofluorescence technique coupled with a machine learning image analysis to evaluate the presence of conventional type 1 dendritic cells (cDC1) and CD8 T cells in the stroma of melanoma, two of the most relevant immune cell types for antitumor responses. We observed that both cell types infiltrate AM at similar and even higher levels than other cutaneous melanomas. Both melanoma types harbored programmed cell death protein 1 (PD-1+) CD8 T cells and PD-1 ligand (PD-L1+) cDC1s. Despite this, CD8 T cells appeared to preserve their effector function and expanding capacity as they expressed interferon-γ (IFN-γ) and KI-67. The density of cDC1s and CD8 T cells significantly decreased in advanced stage III and IV melanomas, supporting these cells' capacity to control tumor progression. These data also argue that AM could respond to anti-PD-1-PD-L1 immunotherapy. [ABSTRACT FROM AUTHOR]

Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands. [ABSTRACT FROM AUTHOR]

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods: Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results: Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM. [ABSTRACT FROM AUTHOR]

Introduction: Nodular melanoma (NM) is a rare subtype of melanoma, responsible for more than 40% of melanoma deaths, characterized by rapid growth and high metastatic potential. Only a few case studies concerning the dermoscopic presentations of giant nodular melanoma have been reported so far. Objectives: The aim of the study was to assess dermoscopic features of giant nodular melanomas in special locations, along with their clinical and histopathologic aspects. Methods: Among 120 patients with histopathologically confirmed melanoma treated by the Skin Cancer and Melanoma Team between September 2020 and February 2021, we identified six patients with giant nodular melanoma in special locations. We retrospectively assessed the archived dermoscopic images to determine the dermoscopic features of these tumors. Results: The group consisted of six cases of giant melanoma in special locations, including the scalp (4/6) and the heel (2/6). The giant tumors were large in size (at least 5 cm in diameter). The most common dermoscopic structures in polarized light included asymmetric distribution of dermoscopic structures, the presence of structureless, multicolored zones (showing three or more colors), and the presence of white perpendicular lines or small, pink globules. Conclusions: It seems that there are no significant differences in dermoscopy between small and giant melanomas; however, further studies should be conducted on a larger scale. [ABSTRACT FROM AUTHOR]

Early recognition of a pituitary secretor tumor offers a better prognostic; thus acromegaly might be recognized before the actual clinical picture of acromegaly is detectable. This is a 59-year old, non-smoking female admitted for: post-operatory evaluation of acromegaly. The clinical evaluation is non-specific. One year prior she was diagnosed with acromegaly based on cerebral imaging assessment due to intermittent headache. She was treated with cabergoline a few months before neurosurgery was done; post-operatory panel showed complete remission of acromegaly. Prompt detection of the disease allowed the early intervention with a very good outcome. The remission of GH excess after neurosurgery depends on tumor size and practical experience of the surgeon. The longer time of high growth hormone levels exposure the higher is the risk of cardio-metabolic and oncologic complications.

Abstract Cellular digital fibroma is a benign fibrous lesion that typically occurred on either a finger or a toe. Cellular digital fibroma was introduced as a distinctive cluster of differentiation 34 (CD34)-positive lesion in July 2005. Cellular digital fibroma has been described in 20 patients: 12 men and 8 women. The patients ranged in age from 27 to 83 years old (median, 52 years old) at diagnosis. The tumor had been present from 2 months to 2 years (median, 11 months) prior to seeking medical attention. The cellular digital fibroma was usually slowly growing and asymptomatic; there has been no prior history of trauma at the tumor site. The lesion typically presented as either an erythematous or a flesh-colored, solitary papule of 5 mm or smaller. It frequently occurred on either the dorsal, lateral or ventral side of a digit. Yet, some of the lesions were located on the nail fold of the digit. Cellular digital fibroma shows a prominent cellular proliferation of spindle-shaped fibroblasts, without any atypia or mitoses, that extends from the papillary into the upper reticular dermis; diffuse and strongly positive CD34 staining is present throughout the entire tumor. There is no erosion by the tumor of the bony phalanx. Other acral tumors, such as superficial acral fibromyxoma (which also has diffuse strongly positive CD34 staining) and acquired digital fibrokeratoma (which is either CD34-negative or only focal CD34 positive), are in the clinical and pathologic differential diagnosis of cellular digital fibroma. Conservative complete excision is the treatment of cellular digital fibroma; however, even for tumors that have only been partially removed during biopsy, recurrence has not been observed. In conclusion, cellular digital fibroma is a unique CD34-positive acral lesion of the distal fingers and toes whose diagnosis requires correlation of the clinical morphology and the pathologic features of the tumor.

Abstract Background/objective Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma. Methods Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion. Results Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami’s criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami’s or Gaiser’s criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma. Conclusions We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1.

Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas., Competing Interests: C.S.H., D.H., T.J.P., S.R., J.D.W., T.M., and R.J.B. are inventors on multiple patents filed by MSK covering CAR T cell technology, including the CAR T cells discussed in this manuscript. S.R. serves on the Scientific Advisory Board of Celyad Oncology. R.J.B. has licensed intellectual property to and collects royalties from BMS, Caribou, and Sanofi. R.J.B. received research funding from BMS. R.J.B. is a consultant to BMS, Atara Biotherapeutics Inc., and Triumvira, and was a consultant for Cargo Tx and CoImmune but ended in the past 3 months, and Gracell Biotechnologies Inc. but ended employment in the past 24 months. R.J.B. is a member of the scientific advisory board for Triumvira and was a member of the scientific advisory board for Cargo Tx and CoImmune, but that ended in the past 6 months. J.D.W. is a consultant for Apricity, Ascentage Pharma, AstraZeneca, BeiGene, Bicara Therapeutics (ending 4/1/2024), Bristol Myers Squibb, Daiichi Sankyo, Dragonfly, Imvaq, Larkspur, Psioxus, Recepta, Takeda, Tizona, Trishula Therapeutics, and Sellas. J.D.W. received grant/research support from Bristol Myers Squibb and Enterome. J.D.W. has equity in Apricity, Arsenal IO/CellCarta, Ascentage, Imvaq, Linneaus, Larkspur, Georgiamune, Maverick, Tizona Therapeutics, and Xenimmune. J.D.W. is an inventor on the following patents: Xenogeneic DNA Vaccines, Newcastle Disease viruses for Cancer Therapy, Myeloid-derived suppressor cell (MDSC) assay, Prediction of responsiveness to treatment with immunomodulatory therapeutics and method of monitoring abscopal effects during such treatment, Anti-PD1 Antibody, Anti-CTLA4 antibodies, Anti-GITR antibodies and methods of use thereof. T.M. is a consultant for Immunos Therapeutics, Daiichi Sankyo Co, TigaTX, Normunity, and Pfizer. T.M. is a cofounder of and equity holder in Imvaq Therapeutics. T.M. receives research grant funding from Bristol Myers Squibb, Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals, Peregrine Pharmaceuticals, Adaptive Biotechnologies, Leap Therapeutics, and Aprea Therapeutics. T.M. is an inventor on patent applications related to work on oncolytic viral therapy, alpha virus-based vaccine, neo-antigen modeling, CD40, GITR, OX40, PD-1, and CTLA-4., (© 2024 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Synovial sarcoma is a malignant soft tissue tumor of uncertain differentiation. It is typically seen in the deep soft tissue of the extremities; however, it has been reported to occur anywhere in the body. Synovial sarcoma by histomorphology has multiple subtypes, including monophasic spindle cell, biphasic and poorly differentiated subtypes. Synovial sarcomas measuring less than one centimeter in diameter are termed "minute" synovial sarcomas. "Minute" synovial sarcomas have only been reported so far in the acral region of the hands and feet. They are extremely rare and can often be misinterpreted as benign neoplasms. Herein, we report the findings in a 30-year-old female presenting with a palpable mass within the deep subcutaneous tissue along the anterior aspect of her right rectus abdominis muscle. The mass was excised and measured 0.6 cm in greatest dimension with histomorphology findings, immunohistochemical and molecular workup confirming the diagnosis of "minute" synovial sarcoma. Our findings represent the first documented case of a "minute" synovial sarcoma occurring at an extra-acral site. With such unique finding not yet reported in the literature, this case highlights the importance of considering synovial sarcoma in the differential diagnosis of subcutaneous abdominal masses., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Grove et al.)

Early recognition of a pituitary secretor tumor offers a better prognostic; thus acromegaly might be recognized before the actual clinical picture of acromegaly is detectable. This is a 59-year old, non-smoking female admitted for: post-operatory evaluation of acromegaly. The clinical evaluation is non-specific. One year prior she was diagnosed with acromegaly based on cerebral imaging assessment due to intermittent headache. She was treated with cabergoline a few months before neurosurgery was done; post-operatory panel showed complete remission of acromegaly. Prompt detection of the disease allowed the early intervention with a very good outcome. The remission of GH excess after neurosurgery depends on tumor size and practical experience of the surgeon. The longer time of high growth hormone levels exposure the higher is the risk of cardio-metabolic and oncologic complications. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris is an autoimmune disorder with many clinical variants. In this report, we present a 57-year-old female patient who presented with unilateral acral erosions, pustulations, and crusts, which was diagnosed as localized pemphigus vulgaris, which is a very rare variant of pemphigus.

Abstract Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large‐scale Asian studies that include follow‐up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan‐Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease‐specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5‐year disease‐specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5‐year disease‐specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Pityriasis rosea (PR) is a common, selflimited inflammatory skin condition, usually affects the trunk and proximal extremities. A variety of atypical manifestations of PR have been recognized ranging from the difference in the morphology, distribution, and course. Herein, the rare form of acral PR in an adult has been illustrated as the 29- year-old Thai female who presented with generalized erythematous papules and plaques with peripheral collarette scales on the trunk and extremities, prominently on the hands and feet.[...]

Metastatic hand tumors are uncommon but important to include in the differential diagnosis for hand masses. In this study, we report the case of a patient presenting initially with hand pain and swelling with no other pertinent medical history except for an extensive smoking history. Subsequent mass biopsy and work-up revealed metastatic lung cancer. Acral metastases to the hand as the first manifestation of a primary tumor are a rare but debilitating condition with a poor prognosis. Hand surgeons must remain aware of the potential for metastatic hand tumors in patients without known malignancy and advocate for the prompt initiation of multidisciplinary care and treatment to maximize patient outcomes., Competing Interests: No benefits in any form have been received or will be received related directly to this article., (© 2024 The Authors.)

MicroRNAs (miRNAs) are small ∼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma.

Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas were examined for the BRAF V595E variant by digital droplet PCR (ddPCR), and for exon 11 mutations in c-kit. Furthermore, exons 2 and 3 of KRAS and NRAS were analysed by Sanger sequencing. Copy number variations (CNV) of KITLG in genomic DNA were analysed from nine dogs. The BRAF V595E variant was absent and in c-kit, a single nucleotide polymorphism was found in 16/70 tumours (23%). The number of copies of KITLG varied between 4 and 6. KRAS exon 2 codons 12 and 13 were mutated in 22/86 (25.6%) of the melanomas examined. Other mutually exclusive RAS mutations were found within the hotspot loci, i.e., KRAS exon 3 codon 61: 2/55 (3.6%); NRAS exon 2 codons 12 and 13: 2/83 (2.4%); and NRAS exon 3 codon 61: 9/86 (10.5%). However, no correlation could be established between histological malignancy criteria, survival times and the presence of RAS mutations. In summary, canine digital melanoma differs from molecular genetic data of canine oral melanoma and human melanoma, especially regarding the proportion of RAS mutations.

Background The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. Methods A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. Results The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870). Conclusions NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

The term “acral” means the distal portions of the limbs (hand, foot) and the head (ears, nose). The term acral melanosis is loosely applied to an increase in melanin pigmentation, in a diffuse, reticulate, or focal pattern over the distal parts of the arms and legs. There are various causes of acral pigmentation varying from genetic to acquired, benign to malignant, autoimmune to infectious, drug-induced, nutritional deficiencies, postinflammatory, and even exogenous reasons. The pigmentation may be occurring in isolation or associated with various systemic features. An earlier age of the onset of pigmentation, a positive family history, and a reticulate or mottled pattern usually point to a genetic cause. The diffuse pattern of pigmentation is usually seen in racial, endocrine diseases, and nutritional deficiencies. Postinflammatory acral pigmentation may follow both infectious and autoimmune diseases and may even be drug induced. A correct diagnosis is important to decide on the management which varies from reassurance and counseling to active treatment. This review paper is an attempt to classify acral pigmentation based on its diverse etiological causes.

Syringoma is a benign adnexal tumor of intraepidermal portion of the eccrine sweat ducts. Eruptive syringoma is a rare clinical variant characterized by small, flesh-colored papules with both follicular and nonfollicular distribution that occur in successive crops on the anterior body surface. We report a case of 35-year-old female with familial eruptive syringoma with predominant acral distribution. We report this case because of the rarity of disorder and acral predominance.

Pantoea agglomerans is a rare Gram-negative bacterium most often implicated in plant diseases and opportunistic organ system infections in immunocompromised humans. Because P. agglomerans uncommonly causes skin infections and presents with nonspecific clinical and histological findings, dermatologic diagnosis may be delayed. Our patient had a unique skin eruption that persisted after multiple treatment regimens and was finally diagnosed as P. agglomerans cutaneous infection. It is important for clinicians to consider this uncommon skin infection in their differential diagnosis of erythematous papules and vesicles with systemic symptoms. Diagnosis is via bacterial culture as histology is usually nonspecific and may not offer a conclusive diagnosis. Risk factors that may be clues to this infection include the occupation of farming, recent hospitalization, immunosuppression, and skin compromise in the form of open wounds.

Cellular digital fibroma is a benign fibrous lesion that typically occurred on either a finger or a toe. Cellular digital fibroma was introduced as a distinctive cluster of differentiation 34 (CD34)-positive lesion in July 2005. Cellular digital fibroma has been described in 20 patients: 12 men and 8 women. The patients ranged in age from 27 to 83 years old (median, 52 years old) at diagnosis. The tumor had been present from 2 months to 2 years (median, 11 months) prior to seeking medical attention. The cellular digital fibroma was usually slowly growing and asymptomatic; there has been no prior history of trauma at the tumor site. The lesion typically presented as either an erythematous or a flesh-colored, solitary papule of 5 mm or smaller. It frequently occurred on either the dorsal, lateral or ventral side of a digit. Yet, some of the lesions were located on the nail fold of the digit. Cellular digital fibroma shows a prominent cellular proliferation of spindle-shaped fibroblasts, without any atypia or mitoses, that extends from the papillary into the upper reticular dermis; diffuse and strongly positive CD34 staining is present throughout the entire tumor. There is no erosion by the tumor of the bony phalanx. Other acral tumors, such as superficial acral fibromyxoma (which also has diffuse strongly positive CD34 staining) and acquired digital fibrokeratoma (which is either CD34-negative or only focal CD34 positive), are in the clinical and pathologic differential diagnosis of cellular digital fibroma. Conservative complete excision is the treatment of cellular digital fibroma; however, even for tumors that have only been partially removed during biopsy, recurrence has not been observed. In conclusion, cellular digital fibroma is a unique CD34-positive acral lesion of the distal fingers and toes whose diagnosis requires correlation of the clinical morphology and the pathologic features of the tumor. [ABSTRACT FROM AUTHOR]

Background/objective: Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma. Methods: Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion. Results: Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami's criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami's or Gaiser's criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma. Conclusions: We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1. [ABSTRACT FROM AUTHOR]

Abstract Background Malignant acrospiroma is a rare tumor of the eccrine sweat glands accounting for around 6% of all malignant eccrine tumors. Typically, it presents as large ulcerated nodules, and diagnosis can be challenging as it has great overlap with its benign counterpart. Case presentation We herein report a case of acral malignant acrospiroma, initially treated with surgical excision and adjuvant radiotherapy. After metastatic disease was confirmed, subject received multiple lines of chemo- as well as targeted therapy. Genomic testing was also done using next generation sequencing. Conclusion To the best of our knowledge, this is the first case of acral malignant acrospiroma with reported next generation sequencing results.

Psoriasis is resistant to treatment and it shows frequent relapse; systemic treatment is often associated with toxicities, and long-term safety data are lacking for most of the newer drugs like biologics. Moreover, some body areas such as hands, feet, intertriginous areas, scalp, and nails are even more resistant. Frequently, systemic treatments are necessary considering the higher psychological impact on the patient. There is a lack of agreement on the best therapeutic modalities in the management of psoriasis involving difficult-to-treat locations. At present, there are no Indian guidelines for these conditions. Available literature has been reviewed extensively on the treatment of psoriasis involving difficult-to-treat locations; level of evidence has been evaluated as per the Oxford Centre for Evidence-Based Medicine 2011 guideline, and therapeutic suggestions have been developed. Best care has been employed to consider socioeconomic, cultural, genetic, and ethnic factors to prepare a therapeutic suggestion that is appropriate and logical to be used among Indian population and people of similar ethnic and socioeconomic background.

In situ squamous cell carcinoma of the skin (SCCis or Bowen's disease) is a common intraepidermal cutaneous malignancy with a low invasive potential. Acral Bowen's disease is usually solitary, but multiple acral SCCis have been reported. Pigmented Bowen's disease is typically unilesional and characterized by a hyperpigmented plaque with a velvety of keratotic surface, which can eventually simulate melanoma clinically. We describe two HIV-positive patients who presented with multiple pigmented SCCis involving the distal extremities. In patients with immunosuppression, the presence of multiple and hyperpigmented verrucae that clinically do not respond to adequate treatment should raise the differential diagnosis of SCC in situ.

Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49)., Competing Interests: Declaration of interests J.L. declares the following: honoraria: Eisai, Novartis, Incyte, Merck, touchIME, touchEXPERTS, Pfizer, Royal College of Physicians, Cambridge Healthcare Research, Royal College of General Practitioners, VJOncology, Agence Unik, BMS, Immatics, Insighter, and GCO; consultancy: iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm, Incyte, Pfizer, and Novartis; speaker’s fees: Pierre Fabre, BMS, Ipsen, Roche, EUSA Pharma, Novartis, Aptitude, AstraZeneca, GSK, Eisai, Calithera, Ultimovacs, Seagen, Merck, eCancer, Inselgruppe, Pfizer, Goldman Sachs, MSD, Regional British Society of Gastroenterology, and Agence Unik; institutional research support: BMS, MSD, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, and Aveo; grants: Achilles, BMS, MSD, Nektar, Novartis, Pfizer, Roche, Immunocore, Aveo, and Pharmacyclics. R.M. is an expert witness for Pfizer and may benefit financially from commercialized programs. P.L. declares the following: honoraria: Novartis, PierreFabre, Merck, BMS, MSD, NeraCare GmbH, Amgen, Roche, OncologyEducation Canada, and Nektar; consultancy: Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen, Pierre Fabre, Novartis, Nektar, and NeraCare GmbH; speakers’ bureaus: Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, and Pierre Fabre; institutional research funding: BMS and Pierre Fabre; travel, accommodations, expenses: Merck Sharp & Dohme and Bristol-Myers Squibb. T.R.J.E. reported the following competing interests: honoraria (payable to employing institution): Ascelia, AstraZeneca, Bicycle Therapeutics, BMS, Eisai, Medivir, MSD, Nucana, Roche/Genentech, and Seagen; advisory/consulting (payable to employing institution): Karus Therapeutics; speakers’ bureaus (payable to employing institution): AstraZeneca, BMS, Eisai, Medivir, MSD, Nucana, Roche/Genentech, and United Medical; research funding (payable to employing institution): Adaptimmune, Astellas Pharma, AstraZeneca, Athenex, Avacta, Basilea, Bayer, Beigene, Berg Pharma, Bicycle Therapeutics, BiolineRx, Boehringer Ingelheim, BMS, Celgene, Clovis Oncology, Codiak, CytomX Therapeutics, Eisai, GlaxoSmithKline, Halozyme, Immunocore, iOnctura, Iovance Biotherapeutics, Janssen, Johnson & Johnson, Lilly, Medivir, Merck Serono, MSD, MiNA Therapeutics, Modulate Pharma, Novartis, Nucana, Nurix, Plexxikon, Roche/Genentech, Sanofi/Aventis, Sapience Therapeutics, Seagen, Seattle Genetics, Sierra Pharma, Starpharma, T3P, UCB, Verastem, and Vertex; expert testimony (payable to employing institution): Medivir; support to attend international conferences (personal): BMS, Celgene, Eisai, MSD, Nucana, Pierre Fabre, and Roche; other relationship (payable to employing institution): Genmab. M.R.M. is supported by the NIHR Biomedical Research Center in Oxford and reports grants from Roche, AstraZeneca, GSK, GRAIL (outside the submitted work), grants and other from Immunocore, and other from Novartis, BMS, Pfizer, Merck/MSD, Regeneron, BiolineRx, and Replimune. P.N. reported having received funding for advisory boards and/or speakers’ bureau from the following sources: AstraZeneca, BMS, Esai, Ideaya, Immunocore, Ipsen, Medicenna, MSD, Merck, Novartis, and Pfizer. R.P. reported, in the last 4 years, having received honoraria for attending advisory boards from Pierre Faber, Bayer, Novartis, BMS, Cybrexa, Ellipses, CV6 Therapeutics, Immunocore, Genmab, Astex Therapeutics, Medivir, and Sanofi Aventis; honoraria as an IDMC member for Alligator Biosciences, GSK, Onxeo, SOTIO Biotech AG, and AstraZeneca; having been paid for delivery of educational talks or chairing educational meetings by AstraZeneca, Novartis, Bayer, MSD, and BMS; and received funds to support attendance at conferences from MSD and BMS. J. Bliss reported receiving grants to ICR-CTSU from AstraZeneca, Merck Sharp & Dohme, Puma Biotechnology, Pfizer, Roche, Novartis (previously GlaxoSmithKline), Eli Lilly, Janssen-Cilag, Clovis Oncology, and Cancer Research UK; and nonfinancial support from the National Institute for Health Research. S.V. is a recipient of a research grant from Amgen. S.T. is funded by CRUK (grant no. A29911), the Francis Crick Institute, which receives its core funding from CRUK (FC10988), the UK Medical Research Council (FC10988), the Wellcome Trust (FC10988), the National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant no. A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (grant no. A2204), Ventana Medical Systems (grant nos. 10467 and 10530), the National Institutes of Health (U01 CA247439), and the Melanoma Research Alliance (Award Ref no 686061). S.T. has received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen. S.T. has filed the following patents: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and P113326GB., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large‐scale Asian studies that include follow‐up data have been reported. Objectives: To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods: Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan‐Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease‐specific survival in patients with invasive melanoma. Results: In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5‐year disease‐specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions: Our study revealed the characteristics of melanoma in the Japanese population. The 5‐year disease‐specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations. [ABSTRACT FROM AUTHOR]

Pityriasis versicolor is a superficial mycosis affecting the skin. It is caused by malassezia species of fungi. Common sites of involvement are chest, neck and shoulders. We report a rare case of pityriasis versicolor affecting both arms and dorsum of both hands but sparing the commonly involved sites and masquerading vitiligo.

Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation) and internal (genetic) factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 %) or NRAS (20 %) mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The progress in melanoma studies allow to receive the positive results in melanoma treatment in particularly with targeted therapy. The molecular targets and future perspectives for targeted therapy of metastatic skin melanoma are discussed.

Resumen El sarcoma fibroblástico mixoinflamatorio es un tumor maligno de bajo grado de partes blandas, generalmente localizado en extremidades y que afecta a sujetos de mediana edad. Clínicamente, la lesión es infiltrativa, indolora y de curso evolutivo lento. Se presenta un caso que afecta la mano, haciendo una extensa revisión de la bibliografía, con especial atención a su diagnóstico y tratamiento.

BACKGROUND: Melanoma is the most aggressive form of epidermal-derived skin cancer. Cutaneous melanoma is the most common subtype, accounting for 91% cases. Even though it is reported less frequently than basal cell carcinoma or squamous cell carcinoma, it accounts for 70% mortality due to cutaneous neoplasms. In Mexico, data estimates a 500% incidence increment over the last decades. General Hospital of Mexico is a concentration hospital; however, melanoma frequency has not been reported previously. OBJECTIVE: To determine the frequency of melanoma cases at General Hospital of Mexico. MATERIAL AND METHOD: A retrospective, observational, descriptive, transversal study was carried out. All melanoma cases with biopsy confirmation from January 1st 2003 to December 31st 2014 were enrolled. Data was reviewed and posteriorly descriptive statistics were carried out using SPSS v 20.0. RESULTS: A total of 195 melanoma cases with histopathology confirmation were included from January 2003 to December 2014. Nineteen files were incomplete and were excluded, obtaining 176 cases: 119 females (68%). Acral lentiginous melanoma accounted for 105 cases (60%), followed by nodular melanoma with 36 cases (20%), lentigo maligna melanoma was seen in 23 cases (13%), and 12 superficial spreading melanoma cases (7%). Descriptive analysis was carried out for each melanoma subtype. CONCLUSION: Melanoma frequency per year was variable. Females were affected in a bigger proportion. Acral lentiginous melanoma was the most reported subtype followed by nodular melanoma. Importantly, subungueal melanoma was seen in 29% patients. Most cases were diagnosed at late stages. [ABSTRACT FROM AUTHOR]

Background: Malignant acrospiroma is a rare tumor of the eccrine sweat glands accounting for around 6% of all malignant eccrine tumors. Typically, it presents as large ulcerated nodules, and diagnosis can be challenging as it has great overlap with its benign counterpart.Case Presentation: We herein report a case of acral malignant acrospiroma, initially treated with surgical excision and adjuvant radiotherapy. After metastatic disease was confirmed, subject received multiple lines of chemo- as well as targeted therapy. Genomic testing was also done using next generation sequencing.Conclusion: To the best of our knowledge, this is the first case of acral malignant acrospiroma with reported next generation sequencing results. [ABSTRACT FROM AUTHOR]

Psoriasis is resistant to treatment and it shows frequent relapse; systemic treatment is often associated with toxicities, and long-term safety data are lacking for most of the newer drugs like biologies. Moreover, some body areas such as hands, feet, intertriginous areas, scalp, and nails are even more resistant. Frequently, systemic treatments are necessary considering the higher psychological impact on the patient. There is a lack of agreement on the best therapeutic modalities in the management of psoriasis involving difficult-to-treat locations. At present, there are no Indian guidelines for these conditions. Available literature has been reviewed extensively on the treatment of psoriasis involving difficult-to-treat locations; level of evidence has been evaluated as per the Oxford Centre for Evidence-Based Medicine 2011 guideline, and therapeutic suggestions have been developed. Best care has been employed to consider socioeconomic, cultural, genetic, and ethnic factors to prepare a therapeutic suggestion that is appropriate and logical to be used among Indian population and people of similar ethnic and socioeconomic background. [ABSTRACT FROM AUTHOR]