Clinicopathological characteristics of low-dose methotrexate-induced epidermal dysmaturation: A study of 22 patients.

BACKGROUND AND OBJECTIVE: Erosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low-dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations. PATIENTS AND METHODS: A database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low-dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS. RESULTS: Patients were predominantly female with a mean age of 69.1 years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes. CONCLUSIONS: This study proposes clinicopathological criteria for the diagnosis of MTX-associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life-threatening progression.

Tumescent local anesthesia in geriatric patients with head and neck skin cancer - a retrospective study of 782 patients.

BACKGROUND AND OBJECTIVES: Due to frailty, dermatosurgery in the elderly is preferably performed under tumescent local anesthesia, but data is limited. The aim was to evaluate tumescent local anesthesia for skin cancer surgery in the elderly with focus on clinical benefits (treatment processes, pain management) and local postoperative complication risk. PATIENTS AND METHODS: Investigation of patients ≥ 75 years with inpatient head and neck skin cancer surgery under tumescent local anesthesia. RESULTS: 2,940 procedures in 782 patients (mean age 83.3 years) were performed with the aim of complete tumor resection during the inpatient stay. 3.8 (range: 1-20) interventions were done over an average of 4.9 days (range: 1-28). 43.2% did not require any postoperative analgesia. 53.5% received NSAIDs, 3.3% opioids. Infection (13.6%) was the most common local postoperative complication. Surgical intervention due to bleeding was required in 2.8%. None was hemoglobin relevant or life-threatening. Suture dehiscence and necrosis were rare (0.6%). CONCLUSIONS: Tumescent local anesthesia is an effective method for skin cancer surgery in the elderly. By avoiding general anesthesia, treatment processes can be optimized and anesthesiologic risks minimized. Local postoperative complications are still low and well treatable. The long-lasting analgesia results in a reduced need for analgesics and drug interactions.

Risk analysis of systemic side effects of tumescent local anaesthesia in the surgical treatment of geriatric and multimorbid patients with skin cancer.

BACKGROUND: Due to demographic change and increased UV exposure, the number of dermatosurgical procedures in the elderly is increasing. Data on the occurrence of systemic side effects during and after treatment with tumescent local anaesthesia are limited and do not refer to details such as volume and composition of local anaesthetics or epinephrine additive. OBJECTIVES: The aim of this study was to investigate the risk of systemic side effects in elderly patients undergoing skin tumour surgery with tumescent local anaesthesia. METHODS: Investigation of systemic complications in patients (≥75 years) who underwent head and neck skin tumour surgery under tumescent local anaesthesia at the Department of Dermatology, University Medical Centre Tübingen, between October 2018 and March 2020. RESULTS: In total 782 patients (479 males, 303 females) with a mean age of 83.3 years (range: 75.1-102.2 years) could be included. A total of 2940 procedures were performed. Patients were assigned to two groups. The old-old group (≥75-84 years) included 491 patients and the oldest-old group (≥85 years) included 291 patients. The total inpatient stay and thus mean follow-up period was 4.9 days (range 1-28 days). 92.0% (719/782) suffered from pre-existing comorbidities. Systemic complications occurred in 10.2% (80/782; old-olds: 8.6%, oldest-olds: 13.1%). Hypertensive crisis (>180/120 mmHg) requiring intervention (6.7%) that occurred intraoperatively or during the inpatient stay was the most frequent systemic complication. Cardiac arrhythmias occurred postoperatively in 0.8% of cases. No life-threatening complications directly related to tumescent local anaesthesia were found. CONCLUSIONS: Skin tumour surgery in tumescent local anaesthesia for the elderly is safe, and complications caused by general anaesthesia can be avoided. Systemic complications can occur, but are usually mild, are caused by pre-existing diseases and perioperative excitement, and can be rapidly detected and well treated by monitoring. There is no direct correlation of complications to high-tumescent concentrations or volume quantities.

An Automated Real-Time PCR Assay versus Next-Generation Sequencing in the Detection of BRAF V600 Mutations in Melanoma Tissue Samples.

BACKGROUND: Next-generation sequencing (NGS) is the most commonly used method for determining BRAF mutational status in patients with advanced melanoma. Automated PCR-based methods, such as the IdyllaTM system, are increasingly used for mutation diagnostics, but it is unclear what impact the choice of diagnostic method has on the management of melanoma. OBJECTIVES: To compare the concordance rate of BRAF V600 mutational analysis using IdyllaTM and NGS and to analyze the technical and clinical turnaround time. The clinical relevance is compared by analyzing the impact on the treatment decision. METHODS: In this monocentric prospective cohort study, the BRAF mutation status of 51 patients was determined using both methods in parallel. RESULTS: BRAF V600 mutation was detected in 23/51 cases (45%). IdyllaTM showed a 100% concordant result with a faster turnaround time (0.2 days) compared to NGS (12.2 days). In general, less tumor material was required for IdyllaTM than for NGS. Most patients received immunotherapy as a first-line therapy regardless of the BRAF V600 status. CONCLUSIONS: IdyllaTM testing proved to be a reliable and rapid alternative to NGS in the determination of BRAF V600 mutation. Although BRAF. status was available earlier, this had no influence on the treatment decision in most cases.

Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma.

Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18-30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0-18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study.

Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.

[Verrucous exophytic tumor of the glans penis]. / Verruköser exophytischer Tumor der Glans penis.

A 59-year-old man presented with a growing tumor on the glans penis, which we excised. Histologically, there was an acanthotic epidermis under which the papillary dermis was filled with foamy macrophages, best seen in a CD 68 stain. Verruciform xanthoma was diagnosed. Knowledge of this benign diagnosis may prevent an overly hasty, aggressive approach, since the differential diagnosis of penile carcinoma requires much more radical therapy, and mutilating penile surgery is associated with considerable psychosexual distress for patients.

Histopathologic abundance of pigmentation correlates with disease-specific survival in malignant melanoma but is not independent of current AJCC pT stage.

The increasing number of melanoma patients makes it necessary to develop best possible strategies for prognosis assessment in order to recommend appropriate therapy and follow-up. The prognostic significance of tumor cell pigmentation has not been fully elucidated. Hematoxylin and eosin (H&E)-stained sections of 775 melanomas diagnosed between 2012 and 2015 were independently assessed for melanin pigment abundance by two investigators, and the impact on melanoma-specific survival was calculated. Unpigmented melanomas (n = 99) had a melanoma-specific survival of 67.7%, melanomas with moderate pigmentation (n = 384) had a melanoma-specific survival of 85.9%, and strongly pigmented melanomas (n = 292) had a melanoma-specific survival of 91.4% (p < .001). In an analysis of melanoma-specific survival adjusted for pT stage and pigmentation, we found a nonsignificant impact of pigmentation abundance with a hazard ratio of 1.277 (p = .74). The study presented here provides evidence in a German cohort that patients with pigmented melanomas have a more favorable prognosis than those diagnosed with nonpigmented melanomas. Moreover, the abundance of pigmentation already seems to provide a first prognostic estimate. However, it does not appear to provide significant additional value for prognostic assessment according to the AJCC 2017 pT classification.