Bullous hemorrhagic dermatosis (BHD) is a rare cutaneous manifestation characterized by tense hemorrhagic bullae that appear at sites distant from low molecular weight heparin (LMWH) injections, typically within seven days of exposure. As of March 2022, only 94 cases have been reported. It most commonly affects elderly males with predisposing factors for thromboembolism, such as carcinoma, and usually involves the extremities.

This case highlights the importance of maintaining a high index of suspicion for bullous hemorrhagic dermatosis (BHD) in patients receiving low molecular weight heparin, even beyond the typical 7-day window and in demographics not commonly affected. Early recognition and prompt discontinuation of the offending agent, as demonstrated in this atypical presentation involving a Filipino elderly woman with multiple comorbidities and no malignancy, can lead to favorable outcomes. Clinicians should be aware of this rare but reversible complication to avoid misdiagnosis and ensure appropriate management.

Human ; Female ; Aged: 65-79 Yrs Old ; Affect ; Aged ; Blister ; Carcinoma ; Causality ; Demography ; Diagnostic Errors ; Enoxaparin ; Extremities ; Heparin ; Heparin, Low-molecular-weight ; Index ; Injections ; Lead ; Male ; Molecular Weight ; Neoplasms ; Patients ; Research Report ; Skin Diseases ; Thromboembolism ; Women

OBJECTIVE: To evaluate the effectiveness of the innervated medial plantar flap for reconstructing soft tissue defects, particularly in the weight-bearing zone, after resection of foot tumors. METHODS: A retrospective analysis was conducted on 12 patients with malignant skin and soft tissue tumors of the foot treated between October 2023 and December 2024. The cohort included 8 males and 4 females, aged 42-67 years (mean, 57.5 years). Tumor types comprised malignant melanoma (5 cases), squamous cell carcinoma (4 cases), arsenical keratosis (2 cases), and tumor-induced osteomalacia (1 case). Soft tissue defects located in the heel weight-bearing region in 10 cases and non-weight-bearing ankle region in 2 cases, with defect sizes ranging from 4.0 cm×3.0 cm to 6.0 cm×4.0 cm. Preoperative photon-counting CT angiography (PC-CTA) was performed to assess the medial plantar artery and its perforators. All patients underwent radical tumor resection with confirmed negative margins. The resulting defects were reconstructed using a innervated medial plantar flap incorporating sensory branches of the medial plantar nerve. The flap donor site was covered with a split-thickness skin graft harvested from the ipsilateral inguinal region. RESULTS: The operation was successfully completed in all 12 patients. All flaps survived completely without vascular compromise, partial necrosis, or total loss. Incisions healed primarily without dehiscence or infection. Minor skin graft necrosis occurred at the donor site in 3 patients, which healed within 2-3 weeks with routine dressing changes. No donor site complication (e.g., tendon or nerve injury) occurred. Patients were followed up 2-16 months (mean, 10.3 months). At last follow-up, there was no tumor recurrence. Flaps exhibited good color and texture match with surrounding tissue, restored sensation, and all feet achieved normal weight-bearing activity. CONCLUSION The innervated medial plantar flap, precisely designed based on PC-CTA localization, provides reliable blood supply and effective sensory restoration. It is an ideal method for reconstructing soft tissue defects after foot tumor resection, especially in the heel weight-bearing region.
Humans ; Male ; Middle Aged ; Female ; Plastic Surgery Procedures/methods* ; Adult ; Aged ; Retrospective Studies ; Soft Tissue Neoplasms/surgery* ; Surgical Flaps/blood supply* ; Foot/surgery* ; Skin Neoplasms/surgery* ; Soft Tissue Injuries/surgery* ; Carcinoma, Squamous Cell/surgery* ; Treatment Outcome ; Skin Transplantation/methods* ; Melanoma/surgery*

BACKGROUND: Skin cancer is a common skin disease whose incidence and mortality rates have been showing yearly increases. In this report, we update the most recent data on skin cancer as obtained from GLOBOCAN 2022. METHODS: The incidence and mortality rates of skin cancer (melanoma of skin and non-melanoma skin cancer) in GLOBOCAN 2022 were reviewed. These data were analyzed and the characteristics of incidence and mortality across five continents and top five countries and regions in each continent are presented. In addition, correlations between Human Development Index (HDI) and age-standardized incidence and mortality rates of these two skin cancers are described. RESULTS: The GLOBOCAN 2022 data indicated that melanoma was the 17th most common cancer. An estimated 331,722 people were diagnosed with melanoma globally and approximately 58,667 died from this disease. For non-melanoma skin cancer, it ranks as the 5th most common cancer, and an estimated 1,234,533 people were diagnosed with non-melanoma skin cancer globally and approximately 69,416 died from this disease. The incidence of skin cancer varies across geographic regions and countries, with a predominance observed in Oceania, North America, and Europe. Australia was ranked first in terms of incidence, while incidence rates in Africa and Asia were very low. Despite these regional differences in incidence, there was little geographic variation in mortality rates. Currently, the number of deaths from non-melanoma skin cancer exceeds that of melanoma of skin. HDI was positively associated with the incidence of both types of skin cancers, with a positive correlation obtained between HDI and mortality from melanoma of skin and a negative correlation between HDI and mortality from non-melanoma skin cancer. CONCLUSIONS Skin cancer remains a major disease burden worldwide. Substantial variations are observed across countries and regions. Further research on skin cancer will be required to provide a rationale for more effective preventions and treatments of this condition.
Humans ; Skin Neoplasms/mortality* ; Incidence ; Melanoma/mortality* ; Prevalence ; Global Health ; Male ; Female

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity* ; Sodium Compounds/toxicity* ; Humans ; Cell Transformation, Neoplastic/drug effects* ; PTEN Phosphohydrolase/metabolism* ; Cell Proliferation ; Skin/cytology* ; RNA-Binding Proteins ; Skin Neoplasms/chemically induced* ; Cell Line

OBJECTIVES: To analyze the disease burden of melanoma among middle-aged and elderly populations in China, and to predict the future trend. METHODS: Data from the Global Burden of Disease (GBD) 2021 were utilized to collect incidence and mortality rates of melanoma, disability-adjusted life years (DALYs), and corresponding age crude rates among the middle-aged and elderly population in China during 1990 and 2021. Additionally, the estimated annual percentage change (EAPC) was employed to assess the temporal trends. Age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models were utilized to compute age, period, and cohort effects on incidence and mortality rates of melanoma, as well as to predict future trends up to 2035. RESULTS: During 1990-2021, the incidence rate of melanoma for males was higher than that for females among the middle-aged and elderly population in China, and the overall incidence rate increased annually with an EAPC of 2.13 (1.90-2.36), while the overall mortality rate and DALY rate showed a declining trend with an EAPC of －0.28 (－0.41-－0.15) and －0.54 (－0.68-－0.41), respectively. The results of the APC model analysis revealed that age effects on both incidence and mortality rates of melanoma in China's middle-aged and elderly population were significant, with both increasing with age. Period and cohort effects showed an upward trend for incidence rates but a downward trend for mortality rates. Moreover, the period and cohort effects for mortality rates were not significant among females. In the BAPC prediction model, the number of incidences of melanoma in middle-aged and elderly people in China would increase dramatically. By 2035, the number of incidence cases is expected to reach approximately 9600 (males) and 10 300 (females), corresponding to an incidence rate of 2.66/10⁵ and 2.67/10⁵, respectively. The number of deaths is projected to be about 2600 (males) and 3500 (females) by 2035, corresponding to a mortality rate of 0.72/10⁵ and 0.91/10⁵, respectively. CONCLUSIONS The disease burden of melanoma among the middle-aged and elderly population in China remains substantial and is expected to increase over the next decade.
Humans ; Melanoma/mortality* ; China/epidemiology* ; Aged ; Middle Aged ; Male ; Female ; Incidence ; Disability-Adjusted Life Years ; Bayes Theorem ; Cost of Illness ; Skin Neoplasms/epidemiology*

OBJECTIVE: To report the clinical characteristics, diagnosis, treatment and prognosis of one patient with primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8⁺ PCAECTL), and to strengthen the understanding of this extremely rare type of lymphoma. METHODS: The clinical manifestations, diagnosis, treatment course, and prognosis of one patient with CD8⁺ PCAECTL admitted to our hospital were retrospectively analyzed. RESULTS: The patient is a 42-year-old female, with infiltrative skin rash on naso-facial and back as the main clinical manifestations. After pathological examination of the affected skin tissue, immunohistochemistry, molecular biology, and imaging, the diagnosis was confirmed as CD8⁺ PCAECTL, T3aN₀M₀ stage. Alternating chemotherapy with CHOP/HD-MTX (methotrexate, 6 g/m²) regimen was administered, and achieved complete remission (CR) after 4 cycles. After undergoing chemotherapy with DHAP regimen (cisplatin 100 mg/m², d 1 + cytarabine 2 g/m², q 12h, d 2 + dexamethasone 40 mg/d, d 1-4), the patient was mobilized for peripheral blood stem cells using recombinant human granulocyte colony-stimulating factor (G-CSF), and a sufficient number of CD34⁺ cells were successfully collected. Preconditioning was conducted with the BEAM regimen, followed by consolidation therapy with autologous hematopoietic stem cell transplantation (AHSCT). The patient remained in a disease-free survival state after 20 months of follow-up post-AHSCT. CONCLUSION CD8⁺ PCAECTL is extremely rare in clinical practice, with insidious onset and difficult early diagnosis. It is mainly characterized by the proliferation of epidermotropic CD8⁺ cytotoxic T cells and aggressive clinical course. At present, there is still no unified standard for the optimal treatment regimen, and the prognosis is very poor. Consolidation therapy with AHSCT after achieving remission through induction chemotherapy can improve the survival and prognosis of the CD8⁺ PCAECTL patients.
Humans ; Female ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Lymphoma, T-Cell, Cutaneous/diagnosis* ; Retrospective Studies ; Prognosis ; CD8-Positive T-Lymphocytes ; Skin Neoplasms/diagnosis* ; T-Lymphocytes, Cytotoxic

OBJECTIVES: Verrucous epidermal nevus (VEN), seborrheic keratosis (SK), verruca plana (VP), verruca vulgaris (VV), and nevus sebaceous (NS) are common verrucous proliferative skin diseases with similar clinical appearances, often posing diagnostic challenges. Dermoscopy and reflectance confocal microscopy (RCM) can aid in their differentiation, yet their specific features under these tools have not been systematically described. This study aims to summarize and analyze the dermoscopic and RCM features of VEN, SK, VP, VV, and NS. METHODS: A total of 121 patients with histopathologically confirmed verrucous proliferative skin diseases were enrolled. Dermoscopy and RCM imaging was used to observe and analyze the microscopic features of these conditions. RESULTS: Under dermoscopy, the 5 diseases displayed distinct characteristics: VEN typically showed gyriform structures; SK was characterized by gyriform structures, comedo-like openings, and milia-like cysts; VP and VV featured dotted vessels and frogspawn-like structures; NS presented as brownish-yellow globules. RCM revealed shared features such as hyperkeratosis and acanthosis across all 5 diseases. Specific features included gyriform structures and elongated rete ridges in VEN; pseudocysts and gyriform structures in SK; evenly distributed ring-like structures in VP; vacuolated cells and papillomatous proliferation in VV; and frogspawn-like structures in NS. CONCLUSIONS These 5 verrucous proliferative skin conditions exhibit distinguishable features under both dermoscopy and RCM. The combination of these 2 noninvasive imaging modalities holds significant clinical value for the differential diagnosis of verrucous proliferative skin diseases.
Humans ; Dermoscopy/methods* ; Diagnosis, Differential ; Microscopy, Confocal/methods* ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Keratosis, Seborrheic/pathology* ; Young Adult ; Warts/diagnosis* ; Child ; Aged ; Skin Diseases/pathology* ; Nevus, Sebaceous of Jadassohn/diagnosis* ; Skin Neoplasms/diagnosis* ; Child, Preschool

Currently, research on N⁶-methyladenine (m⁶A) is extensive in the field of oncology, while studies involving m⁶A and skin diseases remain relatively limited. Based on existing reports, we searched PubMed and Web of Science for literature related to m⁶A and dermatological conditions. Analysis of citation counts and journal impact factors revealed a significant upward trend in the volume of m⁶A-related research. Term frequency analysis of titles and abstracts indicated that studies mainly focus on skin tumors and inflammatory or immune-related skin diseases, particularly melanoma, psoriasis, and skin development. Transcriptomic data from the Gene Expression Omnibus (GEO) were analyzed, revealing differential expression of m⁶A-related genes in 4 types of skin tumors (including squamous cell carcinoma and basal cell carcinoma) as well as in inflammatory skin diseases such as psoriasis and atopic dermatitis, and potential mechanisms of action were also explored. Findings suggest that m⁶A modifications exhibit heterogeneity between neoplastic and non-neoplastic skin diseases. However, the regulatory mechanisms of m⁶A dynamic modifications on key genes involved in dermatological disorders remain unclear and warrant further investigation.
Humans ; Skin Neoplasms/metabolism* ; Skin Diseases/metabolism* ; Adenosine/genetics* ; Psoriasis/genetics* ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Basal Cell/genetics* ; Melanoma/genetics*

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*