Intraoperative Immunohistochemistry During Mohs Micrographic Surgery and Staged Excision Decreases Local Recurrence Rates for Invasive Cutaneous Melanoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Mohs micrographic surgery (MMS) is increasingly used to treat cutaneous melanoma. However, it is unclear whether intraoperative immunohistochemistry (IHC) improves surgical outcomes. OBJECTIVE: To determine whether intraoperative IHC during MMS and staged excision is associated with a decreased risk of poor surgical outcomes. MATERIALS AND METHODS: Search of 6 databases identified comparative and noncomparative studies that reported local recurrence after MMS or staged excision with or without IHC for melanoma. Random-effects meta-analysis was used to estimate pooled local recurrence rates, nodal recurrence, distant recurrence, and disease-specific mortality. RESULTS: Overall, 57 studies representing 12,043 patients with cutaneous melanoma and 12,590 tumors met inclusion criteria. Combined MMS and staged excision with IHC was associated with decreased local recurrence in patients with invasive melanoma (0.3%, 95% CI: 0-0.6) versus hematoxylin and eosin alone (1.8%, 95% CI: 0.8%-2.8%) [ p < .001]. Secondary outcomes including nodal recurrence, distant recurrence, and disease-specific mortality were not significantly different between these 2 groups. Study heterogeneity was moderately-high. CONCLUSION: Local recurrence of invasive melanoma is significantly lower after MMS and staged excision with IHC as opposed to without IHC. These findings suggest that the use of intraoperative IHC during MMS or staged excision should strongly be considered, particularly for invasive melanoma.Trial Registration PROSPERO Identifier: CRD42023435630.

Disease-Specific Mortality of Dermatofibrosarcoma Protuberans After Mohs Surgery Versus Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Although advances have been made in the understanding of recurrence patterns in dermatofibrosarcoma protuberans, the current understanding of disease-specific mortality after surgical management is limited. OBJECTIVE: To understand disease-specific mortality rates associated with dermatofibrosarcoma protuberans treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic literature search was conducted on March 6, 2023, to identify patients treated with MMS or WLE for dermatofibrosarcoma protuberans. RESULTS: A total of 136 studies met inclusion criteria. Overall, the disease-specific mortality rate was not significantly different after treatment with MMS (0.7%, confidence interval [CI] 0.1-1.2, p : 0.016) versus WLE (0.9%, CI 0.6-1.2, p < .001). For recurrent tumors, the MMS treatment group had a statistically significantly lower disease-specific mortality rate (1.0%, CI 0.0-2.0, p 0.046) compared with the WLE treatment group (3.5%, CI 2.0-5.1, p < .001). The mean follow-up for all studies was 57.6 months. CONCLUSION AND RELEVANCE: The authors' meta-analysis suggests there is no substantial difference in disease-specific mortality between MMS and WLE in patients with dermatofibrosarcoma protuberans, except in the case of recurrent tumors, where MMS seems to confer a survival advantage.

A novel method to assess copy number variation in melanoma: Droplet digital PCR for precise quantitation of the RREB1 gene in formalin-fixed, paraffin-embedded melanocytic neoplasms, a proof-of-concept study.

BACKGROUND: Melanocytic neoplasms can be challenging to diagnose. One well-established diagnostic aid is the detection of copy number variation (CNV) in a few key genetic loci using conventional methods such as fluorescence in situ hybridization (FISH) and chromosomal microarray (CMA). Droplet digital polymerase chain reaction (ddPCR) is a novel, cost-effective, rapid, and automated method to detect CNV. METHODS: We perform the first investigation of ddPCR to assay Ras-responsive element-binding protein-1 (RREB1), the most common CNV in melanoma using formalin-fixed, paraffin-embedded (FFPE) melanocytic lesion samples; CMA data are used as the gold standard. Archival samples from 2013 to 2021 were analyzed, including 153 data points from 39 FFPE samples representing 34 patients. Benign, borderline, malignant, and metastatic melanocytic neoplasms were examined. RESULTS: ddPCR showed a sensitivity and specificity of 93.8% and 95.7% using one reference gene, and 87.5% and 100% using a different reference gene for RREB1 gain detection. CONCLUSIONS: Here we show that ddPCR can provide inexpensive, rapid, and robust data on the commonest copy number alteration in melanoma. Future development and validation could provide a useful ancillary tool in the diagnosis of challenging melanocytic lesions.

A Novel Method to Detect Copy Number Variation in Melanoma: Droplet Digital PCR for Quantitation of the CDKN2A Gene, a Proof-of-Concept Study.

ABSTRACT: A definitive diagnosis of nevus or melanoma is not always possible for histologically ambiguous melanocytic neoplasms. In such cases, ancillary molecular testing can support a diagnosis of melanoma if certain chromosomal aberrations are detected. Current technologies for copy number variation (CNV) detection include chromosomal microarray analysis (CMA) and fluorescence in situ hybridization. Although CMA and fluorescence in situ hybridization are effective, their utilization can be limited by cost, turnaround time, and inaccessibility outside of large reference laboratories. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and relatively inexpensive technology for CNV detection. We investigated the ability of ddPCR to quantify CNV in cyclin-dependent kinase inhibitor 2A ( CDKN2A ), the most commonly deleted tumor suppressor gene in melanoma. CMA data were used as the gold standard. We analyzed 57 skin samples from 52 patients diagnosed with benign nevi, borderline lesions, primary melanomas, and metastatic melanomas. In a training cohort comprising 29 randomly selected samples, receiver operator characteristic curve analysis revealed an optimal ddPCR cutoff value of 1.73 for calling CDKN2A loss. In a validation cohort comprising the remaining 28 samples, ddPCR detected CDKN2A loss with a sensitivity and specificity of 94% and 90%, respectively. Significantly, ddPCR could also identify whether CDKN2A losses were monoallelic or biallelic. These pilot data suggest that ddPCR can detect CDKN2A deletions in melanocytic tumors with accuracy comparable with CMA. With further validation, ddPCR could provide an additional CNV assay to aid in the diagnosis of challenging melanocytic neoplasms.

A retrospective review of facility-level obstetric complications and stillbirths in southern Haiti, 2013 - 2016.

OBJECTIVE: To assess the incidence of obstetric complications-eclampsia, dystocia, cesarean section, postpartum hemorrhage, and stillbirths-in hospitals in southern Haiti in 2013 - 2016 and to discuss implications for improvements to the surveillance of birth outcomes. METHODS: This was a cross-sectional, retrospective study of data for 32 442 deliveries recorded in 2013 - 2016 by the Integrated Monitoring, Evaluation, and Surveillance System for facilities across three departments and one high-volume hospital in southern Haiti. Annual incidence rates of eclampsia, dystocia, cesarean section, postpartum hemorrhage, and stillbirths (both macerated and fresh) were calculated. RESULTS: The incidence of eclampsia in the study sample was 2% - 3% and of dystocia approximately 5%, comparable to elsewhere in Haiti and other low-income countries. Cesarean delivery rates averaged about 15% annually. Postpartum hemorrhage rates were lower than published data from similar settings. Stillbirth rates ranged from 30 - 62 per 1 000 births at all facilities, higher than previously recorded by the country's population surveys. The rates of macerated stillbirths were remarkably high, close to 50% of total stillbirths, indicating severe delays in seeking or receiving emergency obstetric care. CONCLUSIONS: This study provides important benchmarks for the current burden of preventable labor- and delivery-related complications in Haiti. Surveillance data suggest an urgent need for the management of hypertensive disorders during pregnancy, timely cesarean sections for dystocia, and management and treatment of postpartum hemorrhage in Haiti. Frequent data reviews may help address facility-specific bottlenecks.

A Droplet Digital Polymerase Chain Reaction-Based Tool to Aid in Melanoma Diagnosis.

CONTEXT.­: Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma. OBJECTIVE.­: To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms. DESIGN.­: One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard. RESULTS.­: ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth. CONCLUSIONS.­: With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.

Isothiazolinones Common in Children's Toy Slime.

BACKGROUND: Contact dermatitis to homemade slime has been frequently reported, with isothiazolinones as a likely sensitizer. Little is known on the presence of these preservatives in commercial, store-bought slime products. OBJECTIVES: The aims of the study were to review the literature on "slime dermatitis" and to assess for the presence of isothiazolinones in commercially available slime products and homemade slime components. METHODS: An experimental, colorimetric spot test was used to verify the presence of isothiazolinones in 38 slime products of the 16 best-selling commercial slime kits, 1 finished homemade slime, and 4 common components of homemade slime. High-performance liquid chromatography with UV detection was performed on 8 commercial slime products. RESULTS: According to the spot test, 27 (71%) of the 38 commercial slime products contained isothiazolinones. High-performance liquid chromatography with UV detection analyses indicated, however, that false-positives and false-negatives readily occur: isothiazolinone content was correctly identified in only 4 (50%) of the 8 samples. CONCLUSIONS: This study is the first to demonstrate the presence of isothiazolinones in commercial slime toys. Although the colorimetric spot test may have some utility as a screening assay, it is far from specific and likely not sensitive enough to reliably identify methylisothiazolinone.

Fine-needle aspiration biopsy for the diagnosis of bone and soft tissue lesions: a systematic review and meta-analysis.

INTRODUCTION: The workup of musculoskeletal (MSK) lesions utilizes a range of diagnostic tests including incisional biopsy, core needle biopsy, and fine-needle aspiration (FNA). FNA is the most cost-effective and least invasive biopsy method, but variation in its reported diagnostic performance has constrained its use for MSK lesions. Herein, we undertake a meta-analysis to clarify the diagnostic performance of FNA for bone and soft tissue lesions. MATERIALS AND METHODS: A systematic search was run in MEDLINE, EMBASE, and CINAHL. Included studies were aggregated for pooled estimates of adequacy, accuracy, and sensitivity/specificity for all MSK lesions as well as bone and soft tissue independently. Analysis of heterogeneity and risk of bias were assessed across studies. Covariate subgroup analyses were attempted to investigate potential influences on diagnostic accuracy. RESULTS: Twenty-five articles met inclusion criteria, representing 4604 FNAs. Adequacy was 92.3% (range: 59.2%-98.0%, S = 9.4%), and sensitivity/specificity for the nature (malignant or benign) of the lesion was 95.6% (95% CI: 94.5%-96.5%) and 96.9% (95% CI: 95.9%-97.7%). FNA was 75.8% accurate (range: 42.5%-99.3%, S = 17.3%) for definitive diagnosis. FNA provides higher accuracy for benign versus malignant nature in bone lesions but achieves a definitive diagnosis more frequently in soft tissue lesions. CONCLUSIONS: The results of this meta-analysis support the expanded use of FNA in the diagnostic workup of bone and soft tissue lesions, particularly in light of a sensitivity and specificity comparable to incisional and core needle biopsy.