Severe insulin resistance in a patient with diabetes after treatment with brentuximab vedotin.

A man in his late 60s with a history of well-controlled type 2 diabetes and hepatic cirrhosis presented to the emergency department due to uncontrollable hyperglycaemia following the initial brentuximab vedotin (BV) infusion. BV was initiated as a treatment for mycosis fungoides, a form of cutaneous T-cell lymphoma. The patient was diagnosed with severe hyperglycaemia with ketosis. Empiric treatment with amoxicillin-clavulanic acid, hydration and intravenous insulin infusion was initiated. Hyperglycaemia persisted despite receiving massive amounts of insulin and was corrected only after treatment with high-dose methylprednisolone for suspected type B insulin resistance. Extremely high and difficult-to-treat hyperglycaemia is a rare side effect of BV. Unfortunately, the patient died of upper gastrointestinal bleeding 22 days after discharge. In patients with obesity and/or diabetes mellitus, the blood glucose levels should be carefully monitored when treated with BV.

Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma.

PURPOSE: Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated in clinical trials in patients with melanoma, yet large studies investigating the rate and degree of MC1R expression in primary and metastatic human melanoma tissue are lacking. METHODS: Using tissue microarrays containing three large cohorts of 225 cases of benign nevi, 189 with primary melanoma, and 271 with metastatic melanoma, we applied quantitative immunofluorescence and immunohistochemistry to comprehensively study MC1R protein expression. RESULTS: We show a stepwise elevation of MC1R expression in different stages of melanoma progression (nevi, primary, metastasis). Higher MC1R expression was seen in deeper (>1 mm) primary lesions and ulcerated lesions and was associated with shorter survival in primary and metastatic tumors. On multivariable analysis, Breslow thickness, male sex, and chronic sun exposure were independent predictors of worse overall survival in the primary melanoma cohort. CONCLUSION: Our data suggest that MC1R might be a valuable drug target in aggressive melanoma. Additional studies are warranted to determine its functional significance in melanoma progression and its utility as a predictive biomarker in patients receiving MC1R-directed therapies.

Intracranial hemorrhage caused by dabrafenib and trametinib therapy for metastatic melanoma.

Although generally well tolerated compared with chemotherapy, molecular targeted therapy used in metastatic melanoma may be associated with life-threatening toxicity. We report the case of a patient with metastatic melanoma treated by dabrafenib plus trametinib who developed intracranial hemorrhage. Physicians should be aware of this rare but life-threatening adverse event of B-rapidly accelerated fibrosarcoma (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. However, they should be also careful about the bleeding origin, which can prove to be a new onset of melanoma metastasis or anticoagulation overdose, or even an uncontrolled arterial hypertension.

Primary cutaneous anaplastic large-cell lymphoma resembling infratemporal space infection: a case report.

BACKGROUND: Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma belonging to the CD30 + T-cell lymphoproliferative disorders. The case of PC-ALCL in the temporal region is exceedingly rare. Herein, we report a case of PC-ALCL involving the temporal region mimicking infratemporal space infection. CASE PRESENTATION: A 78-year-old woman presented to maxillofacial surgery service with a 6-month history of swelling and pain in the left side of her face. Laboratory investigations found an elevated C-reactive protein (CRP). Imaging findings showed enlarged lymph nodes and extensive thickening of subcutaneous tissue of the left temples. Based on these findings, the infratemporal space infection was suspected initially. The patient underwent incision and drainage, and we unexpectedly found no pus in the lesion area. Incisional biopsy showed necrosis and extensive involvement of the left temples by a diffuse infiltrate containing large, atypical cells. The tumor cells were positive for CD30, CD3, Ki67. They were negative for ALK (SP8), CD5, CD8, CD20 and PAX5. After considering these findings, a diagnosis of PC-ALCL was rendered. The patient was admitted to the lymphoma department for systemic chemotherapy and no relapse occurred during a follow-up period of six months. CONCLUSIONS: This report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.

Dermoscopic-Guided Shave Removal of Acquired Facial Melanocytic Nevi in Dark-Skinned Individuals.

BACKGROUND: Acquired melanocytic nevi are common benign skin lesions that require removal under certain circumstances. Shave removal is a straightforward treatment modality with a risk of recurrence. OBJECTIVE: To evaluate the outcome of dermoscopy-guided shave removal of acquired melanocytic nevi in the face of dark-skinned individuals who are more liable to postsurgical complications. METHODS: The study was conducted on 64 patients with acquired facial melanocytic nevi. Serial shave removal using a razor blade guided by dermoscopic examination was done until nevus-free tissue was seen, followed by electrocauterization of the base. Cosmetic outcome, patients' satisfaction, and recurrence rate were evaluated during follow-up. RESULTS: Excellent cosmetic outcome was achieved in 54.69% of patients, while 39.06% had an acceptable outcome, and 6.25% of patients had poor cosmetic outcome. Meanwhile, the recurrence rate was noticed in 5 cases only (7.8%). CONCLUSION: Dermoscopic-guided shave removal provides an easy procedure of treating common melanocytic nevi with an acceptable cosmetic result and a lower rate of recurrence even in patients with darker skin phenotypes.

Modulation of the skin microbiome in cutaneous T-cell lymphoma delays tumour growth and increases survival in the murine EL4 model.

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.

The Level of Agreement between Self-Assessments and Examiner Assessments of Melanocytic Nevus Counts: Findings from an Evaluation of 4548 Double Assessments.

Cutaneous melanoma (CM) is a candidate for screening programs because its prognosis is excellent when diagnosed at an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and examiner assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a "nevometer" to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels, defining a nevus score. Cohen's weighted kappa coefficient (κ) was estimated to measure the level of agreement. In the total sample, the agreement between self-assessments and examiner assessments was moderate (weighted κ = 0.596). Self-assessed nevus counts were higher than those determined by trained examiners (mean difference: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants' eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and examiner-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

Merkel cell carcinoma overlapping Bowen's disease: two cases report and literature review.

PURPOSE: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin, which mainly occurs in the sun exposed sites of white patients over 65 years, with a higher recurrence and metastasis rate. Clinically, MCC overlapping Bowen's disease (BD) is a very rare subtype of MCC. Few cases in the literature have been described and the management is not well defined. We summarize and update the epidemiology, clinical and histopathological features, metastasis characteristics, local recurrence rate and management of it by presenting two cases of MCC overlapping BD and reviewing the literature over the last 11 years. DESIGN: We consulted databases from PubMed, ResearchGate and Google Scholar by MeSh "Merkel cell carcinoma" and "Bowen's disease", "Bowen disease" or "squamous cell carcinoma in situ", from January 2013 to December 2023 and reviewed the literatures. We reported two additional cases. RESULTS: Total 13 cases of MCC overlapping BD were retrospectively analyzed, in whom mainly in elderly women over 70 years, the skin lesions were primarily located on the faces, followed by the extremities and trunk. Most of them were asymptomatic, firm, dark red nodules arising on rapidly growing red or dark brown patches, or presenting as isolated nodules. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. All cases were confirmed by histopathology and immunohistochemistry. The most definitive treatment was extended local excision, but local recurrences were common. Of the 13 cases, 4 cases experienced local or distant metastasis. One suffered from an in-transit recurrence of MCC on the ipsilateral leg after local excision and lymph node dissection, whose metastasis completely subsided after avelumab treatment and without recurrence or metastasis during 6 months of follow-up. CONCLUSIONS: MCC overlapping BD is a very rare skin tumor mainly predisposed on the faces, with high misdiagnosis rate and recurrence rate. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. The acronym, AEIOUN, has been proposed to aid in clinical identification. Our reports and the literature review can provide a better awareness and management of it.

Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.

BACKGROUND: Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. METHODS AND RESULTS: The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. CONCLUSIONS: These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm with Orbital Tumor as the Initial Symptom.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.

Could the mitotic count improve personalized prognosis in melanoma patients?

A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.

The importance of caregivers for patients with advanced basal cell carcinoma treated with hedgehog-pathway inhibitors: an observational prospective study.

Oral targeted therapy with hedgehog pathway inhibitors has revolutionized the standard of care for patients with advanced basal cell carcinoma (BCC). These patients are frail and elderly, have various comorbidities, and receive pharmacological polytherapy. Moreover, adverse events may have a significant impact on therapeutic adherence, which must be managed by the clinician. We evaluated the impact of caregivers on the treatment of patients with advanced BCC in terms of continuation of therapy over time. All patients included in this observational prospective study had histologically confirmed metastatic or locally advanced BCC (LaBCC) and were treated with hedgehog pathway inhibitors from January 2016 to December 2021 at the Department of Dermatology at the University of Florence, Italy. The collected patient data included: age, sex, BCC site and area of spread; number of cycles, dose, duration and tolerability of therapy; marital status (single, divorced, married/living with a partner, widow/widower); and information such as living with someone, and the presence of any caregivers. Of the 34 patients included, 33 had LaBCC and one metastatic BCC. There were 11 females (32.4%) and 23 males (67.6%). Patients who were married or living with a caregiver -tolerated therapy better than single patients who lived alone. Indeed, patients with married/live-in caregivers and/or those with an adequate caregiver experienced greater therapeutic adherence and tolerance of adverse events. Given the greater therapeutic adherence of patients with live-in caregivers as partners, it is essential to consider patients' marital status. It is advisable to involve the caregiver early on, and there should be a training discussion on the various possible adverse events and the best way to mitigate them. Therapeutic success is linked not only to patients being informed but also to training of caregivers.

A systematic review of the risk of cutaneous malignancy associated with ultraviolet nail lamps: what is the price of beauty?

Gel manicures have become part of a popular personal care service in the last two decades due to increased longevity of the polish and the added strength to the nail plate. Prolonged exposure to nail ultraviolet (UV) lamps is required to cure the gel polish. Despite the increased use of UV nail lamps, there is limited consensus in the literature on the risk of skin malignancy associated with UV nail lamps. The objective of this article was to provide a systematic review of the risk of skin malignancy associated with the use of UV nail lamps and to synthesize evidence-based recommendations on their safe usage. A systematic review of the literature was conducted on the databases, Medline and Embase, in accordance with PRISMA guidelines. The search yielded 2,331 non-duplicate articles. Nine were ultimately included, of which three were case reports, one was a cross-sectional study, and five were experimental studies. The risk of bias per the Joanna Briggs Institute guidelines was high or unclear, likely due to the number of case reports included. Prolonged and repeated exposure to UV nail lamps may pose a low risk of skin cancer. It is important to note that the available evidence is weak, and patients should be informed about the limited data to make their own decisions. Dermatologists and other healthcare providers should be updated with the latest evidence to address patients' concerns about gel manicures and suggest practices which can effectively reduce the risk of cutaneous malignancy associated with gel manicures, such as the use of UV-blocking gloves or properly applied sunscreens.

[Application of V-Y advancement flap with facial artery perforator for the repair of midface skin defects].

Objective: To investigate the efficacy of V-Y advancement flap with facial artery perforator for the repair of midface skin defects. Methods: A retrospective analysis was performed on 18 patients with facial skin cancer, including 11 males and 7 females, aged 65-83 years, who underwent the repair of midface skin defects using V-Y advancement flap with facial artery perforator in the Department of Head and Neck Surgery, Affiliated Cancer Hospital of Nantong University from January 2020 to April 2023. Medium, large or complex midface skin defects developed after surgical resections of the primary lesions. According to the defect site, size, location information of facial vessels, a V-Y advancement flap with appropriate shape was designed for each case. During the operation, the facial vessels and their perforators were retained in the pedicle of the flap, the facial nerve branches were dissected and protected, and the further denuded pedicle was determined according to actual amount of advancement. After the flap was advanced, the facial defect area was repaired without tension, and the anatomical positions and functions of the eyes, nose and mouth were restored as far as possible. Postoperative follow-ups were conducted to observe the survival rate of the flaps, postoperative complications, recurrences and metastases of tumors. Results: Midface defects of 3.0 cm×3.5 cm-6.5 cm×7.5 cm were observed after tumor resections, which involved one or more subregions. The sizes of the flaps were 3.5 cm×9.0 cm-7.0 cm×18.0 cm. All flaps were completely alive except for one with temporary local bruising. With following-up of 4-40 months, 5 of the 12 patients with lower eyelid and inner canthus invasions had lower eyelid ectropion, but no exposed keratitis was found; one case with poorly differentiated squamous cell carcinoma had lymph node metastasis in the submandibular region and underwent neck dissection again; no recurrence or metastasis occurred in the remaining cases. Conclusion: The V-Y advancement flap with facial artery perforator can be used to repair medium, large or complex midface skin defects, with a high survival rate, and the operation method is safe and reliable.

Double Immunohistochemical Labelling of PRAME and Melan A in Slow Mohs Biopsy Margin Assessment of Lentigo Maligna and Lentigo Maligna Melanoma.

Introduction: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) predominantly affect the head and neck areas in elderly patients, presenting as challenging ill-defined pigmented lesions with indistinct borders. Surgical margin determination for complete removal remains intricate due to these characteristics. Morphological examination of surgical margins is the key form of determining successful treatment in LM/LMM and underpin the greater margin control provided through the Slow Mohs micrographic surgery (SMMS) approach. Recent assessments have explored the use of immunohistochemistry (IHC) markers, such as Preferentially Expressed Antigen in Melanoma (PRAME), to aid in LM/LMM and margin evaluation, leveraging the selectivity of PRAME labelling in malignant melanocytic neoplasms. Methods: A Novel double-labelling (DL) method incorporating both PRAME and MelanA IHC was employed to further maximise the clinical applicability of PRAME in the assessment of LM/LMM in SMMS biopsies. The evaluation involved 51 samples, comparing the results of the novel DL with respective single-labelling (SL) IHC slides. Results: The findings demonstrated a significant agreement of 96.1% between the DL method and SL slides across the tested samples. The benchmark PRAME SL exhibited a sensitivity of 91.3% in the SMMS specimens and 67.9% in histologically confirmed positive margins. Discussion: This study highlights the utility of PRAME IHC and by extension PRAME DL as an adjunctive tool in the assessment of melanocytic tumours within staged excision margins in SMMS samples.