Photoacoustic imaging for cutaneous melanoma assessment: a comprehensive review.

Significance: Cutaneous melanoma (CM) has a high morbidity and mortality rate, but it can be cured if the primary lesion is detected and treated at an early stage. Imaging techniques such as photoacoustic (PA) imaging (PAI) have been studied and implemented to aid in the detection and diagnosis of CM. Aim: Provide an overview of different PAI systems and applications for the study of CM, including the determination of tumor depth/thickness, cancer-related angiogenesis, metastases to lymph nodes, circulating tumor cells (CTCs), virtual histology, and studies using exogenous contrast agents. Approach: A systematic review and classification of different PAI configurations was conducted based on their specific applications for melanoma detection. This review encompasses animal and preclinical studies, offering insights into the future potential of PAI in melanoma diagnosis in the clinic. Results: PAI holds great clinical potential as a noninvasive technique for melanoma detection and disease management. PA microscopy has predominantly been used to image and study angiogenesis surrounding tumors and provide information on tumor characteristics. Additionally, PA tomography, with its increased penetration depth, has demonstrated its ability to assess melanoma thickness. Both modalities have shown promise in detecting metastases to lymph nodes and CTCs, and an all-optical implementation has been developed to perform virtual histology analyses. Animal and human studies have successfully shown the capability of PAI to detect, visualize, classify, and stage CM. Conclusions: PAI is a promising technique for assessing the status of the skin without a surgical procedure. The capability of the modality to image microvasculature, visualize tumor boundaries, detect metastases in lymph nodes, perform fast and label-free histology, and identify CTCs could aid in the early diagnosis and classification of CM, including determination of metastatic status. In addition, it could be useful for monitoring treatment efficacy noninvasively.

Next-generation sequencing in dermatology.

Over the past decade, Next-Generation Sequencing (NGS) has advanced our understanding, diagnosis, and management of several areas within dermatology. NGS has emerged as a powerful tool for diagnosing genetic diseases of the skin, improving upon traditional PCR-based techniques limited by significant genetic heterogeneity associated with these disorders. Epidermolysis bullosa and ichthyosis are two of the most extensively studied genetic diseases of the skin, with a well-characterized spectrum of genetic changes occurring in these conditions. NGS has also played a critical role in expanding the mutational landscape of cutaneous squamous cell carcinoma, enhancing our understanding of its molecular pathogenesis. Similarly, genetic testing has greatly benefited melanoma diagnosis and treatment, primarily due to the high prevalence of BRAF hot spot mutations and other well-characterized genetic alterations. Additionally, NGS provides a valuable tool for measuring tumor mutational burden, which can aid in management of melanoma. Lastly, NGS demonstrates promise in improving the sensitivity of diagnosing cutaneous T-cell lymphoma. This article provides a comprehensive summary of NGS applications in the diagnosis and management of genodermatoses, cutaneous squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma, highlighting the impact of NGS on the field of dermatology.

PRAME immunohistochemistry compared to traditional FISH testing in spitzoid neoplasms and other difficult to diagnose melanocytic neoplasms.

PRAME (PReferentially expressed Antigen in Melanoma) is a gene first identified in melanoma. It has been proposed as a useful marker to differentiate melanoma from benign melanocytic neoplasms. Recently genomic testing using fluorescence in situ hybridization has been used to aid in the diagnosis of difficult melanocytic neoplasms. We have compared PRAME staining to FISH testing results in 83 difficult to classify melanocytic neoplasms which showed spitzoid histologic features. A relatively low sensitivity of 29.6% and high specificity of 76.8% is seen with PRAME staining as compared to genomic testing with fluorescence in situ hybridization. This study highlights the limitations of PRAME staining in spitzoid neoplasms.

Woringer-Kolopp disease (localized pagetoid reticulosis): a systematic review.

OBJECTIVE: Woringer-Kolopp disease (WKD), also known as localized pagetoid reticulosis, is a rare variant of mycosis fungoides as described by the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification system for cutaneous lymphomas. Our objective was to conduct a comprehensive review that describes and evaluates patient demographics, clinical presentation, immunohistochemical findings, management, and outcomes of WKD. METHODS: The databases PubMed, Embase, and Cochrane Library were searched for relevant literature. Patient demographics, imaging, treatments, and other clinical characteristics were obtained. The literature search was conducted on December 7, 2020. Studies were included if they contained primary data related to WKD. Non-pertinent studies, non-English studies, non-human studies, review articles, or studies with insufficient case information were excluded. The quality of the included studies and the risk of bias were evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation Group (GRADE) criteria (2016), Oxford Centre for Evidence-Based Medicine: Levels of Evidence (OCEBM) (March 2009), and the Methodological Index for Non-Randomized Studies (MINORS) criteria (2003). RESULTS: A total of 84 studies with 143 patients met the inclusion criteria for this study. The most common chief complaint was an asymptomatic, slow-growing, and erythematous plaque. The average time from initial skin eruption to presentation was 97.6 months. Histologically, 128 cases of WKD displayed epidermotropism (97.7%). Various therapies, including radiotherapy, surgery, and local chemotherapy, were used. In total, 92 (78.6%) cases had complete remission and 11 (9.4%) cases recurred. CONCLUSIONS: WKD is a rare cutaneous T-cell lymphoma that often presents as a single plaque on the extremities with an indolent course and a favorable prognosis. However, it is often misdiagnosed, leading to delays in treatment. The diagnosis of WKD involves clinical appraisal, a biopsy of suspicious lesions, and immunohistochemistry. Monotherapy appears to be preferred compared to combination therapy for WKD with radiotherapy demonstrating among the highest cure rates and lowest recurrence. Future retrospective and prospective studies are needed to accurately determine the epidemiology, prognosis, and effective treatments for WKD. Limitations include a possibility of missed studies, heterogeneity in reporting methods, publication, and selection bias.

Multicenter, prospective feasibility study of Nano-Pulse Stimulation™ technology for the treatment of both nodular and superficial low-risk basal cell carcinoma.

Background: Nano-Pulse Stimulation™ (NPS™) therapy is a new, non-thermal bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death (RCD) in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell's own self-destruct pathway of programmed or regulated cell death. Unlike cryotherapeutic procedures that can both damage structural tissues and diffuse into the periphery beyond the margins of the lesion, NPS therapy only affects cells within the treated zone leaving surrounding tissue and acellular components unaffected. Methods: In this study we treated 37 basal cell carcinoma lesions on 30 subjects (NCT04918381). The treated lesions were photographed on 3-, 7-, 14-, 30- and 60-days after treatment. All subjects then underwent surgical excision for histological examination of the treated tissue. Results: 92% of the BCC lesions (34 of 37) showed complete histological clearance of BCC. Histologic analysis of the 3 cases where residual BCC was noted indicated that full energy coverage was not achieved, which could be remedied with an improved treatment guide to standardize and optimize the CellFX® procedure based on NPS technology. Conclusion: The CellFX procedure was shown to be safe and effective for the treatment of low-risk nodular and superficial BCC lesions.

Treatment of Self-Harm Scars: A Scoping Review.

BACKGROUND: Self-harm scars are a consequence of deliberate self-injury, serving as a visual reminder for involved individuals. Patients often reach out to their providers seeking treatment for their scars. However, there is currently no standard for treating self-harm scars, because multiple options are being explored. OBJECTIVE: A scoping review was conducted to identify and characterize the body of literature on different treatments for self-harm scars, including surgical, laser, and vitamin A management. METHODS: Thorough literature searches were conducted in PubMed/MEDLINE, EMBASE, and CINAHL Complete. The search strategy was designed and implemented by a medical librarian. RESULTS: Of 510 retrieved articles, 4 described laser treatments, 8 described surgical treatments, and 2 described vitamin A treatments. CONCLUSION: A multidisciplinary approach is critical for the selection and outcome of the treatment of self-harm scars.

Ethnic distribution of populations in the highest and lowest dermatologist-dense areas: is there more to the story?

Several studies in the past decade have highlighted the lack of adequate dermatological care in skin of color (SOC) patients. This inquiry has led to further research to identify the sources of this disparity. Previous studies have highlighted the uneven geographic distribution of dermatologists, with a higher density of dermatologists in urban areas compared to other areas. However, the exact ethnic populations served by these dermatologists has remained largely uncharacterized. The purpose of this study was to compare the ethnic distributions in the ten highest and lowest dermatologist-dense areas across the United States to determine if there is equal access to dermatological care for minorities. Stratified by ethnicities, the highest dermatologist-dense areas consisted of 60% White alone (not Hispanic or Latino), 13% Hispanic or Latino, 13% Asian alone, and 12% Black or African American. Conversely, the least dermatologist-dense areas consisted of 45% White alone (not Hispanic or Latino), 28% Black or African American, 21% Hispanic or Latino, and 4% Asian alone. Our analysis highlights the presence of larger proportions of SOC patients in the lowest dermatologist-dense areas and this lack of access to dermatologists may contribute to inferior dermatological care and outcomes in Hispanic or Latino, and Black or African American minorities.

Melanoma developing in a nevoid melanocytoma with myxoid changes: a case report.

Nevoid and myxoid melanoma are rare variants of melanoma; association of the two is a unique finding. Nevoid melanoma is characterized by morphologic resemblance to a nevus, whereas myxoid melanoma demonstrates a basophilic mucinous matrix. We present an atypical case of a melanoma progressing from a nevoid melanocytoma with myxoid changes. A 78-year-old female presented with a pigmented growth on her right thigh. Biopsy demonstrated a biphenotypic melanocytic proliferation composed of a nodule showing epithelioid melanocytes with enlarged nuclei, prominent nucleoli, lack of maturation, and abundant amphophilic cytoplasm with a rare mitotic figure. These findings were suggestive of melanoma along with a nevoid dermal component and myxoid stroma. FISH testing revealed a homozygous loss of 9p21 in the atypical component. SNP-microarray from the nevoid component demonstrated three abnormalities including a gain of whole chromosome 8, as well as loss of a copy of nearly an entire chromosome 9 and 16q most consistent with a melanocytoma.

Use of PRAME immunostaining to distinguish early melanoma in situ from benign pigmented conditions.

BACKGROUND: PRAME (PReferentially expressed Antigen in MElanoma) is an antigen that shows marked overexpression in melanoma compared to normal skin melanocytes. PRAME immunohistochemistry has proven effective in distinguishing melanocytic nevi from melanoma, but it is unclear if it may be used to distinguish melanoma in situ from other benign pigmented lesions. In particular, differentiating from melanocytic hyperplasia in sun-damaged skin is sometimes clinically and histopathologically challenging. We hypothesized that PRAME staining of solar lentigo, sun-damaged skin, and melanoma in situ would aid in setting a threshold of positivity that could be useful in evaluating such conditions. METHODS: We collected and stained typical examples of solar lentigo, melanoma in situ, and non-lesional sun-damaged skin by PRAME immunohistochemistry to assess a potential cutoff of PRAME positivity. RESULTS: Solar lentigo and non-lesional sun-damaged skin had 10 or fewer PRAME-positive cells per millimeter (mean 1.2), on the other hand melanoma in situ had at least 16 (mean 75.1). CONCLUSIONS: PRAME immunostaining appears sensitive and specific in the current series. This could be clinically useful for distinguishing melanoma in situ from benign melanocytic hyperplasia in sun-damaged skin. However, further studies are required to determine if 10 cells per millimeter is an acceptable threshold of positivity.

Primary cutaneous extraskeletal osteosarcoma of the pretibial leg: A case report and summary of the literature.

Primary cutaneous extraskeletal osteosarcoma is a rare tumor, with fewer than 30 known cases worldwide. We report the case of a 60-year-old female who presented with a solitary right pretibial nodule of 3 mm. She had no known comorbidities, trauma to the area, or prior malignancy. The biopsy specimen showed abundant mineralized osteoid, in which pleomorphic and spindled cells with anaplastic features were embedded. The osteoid matrix in this case contained overtly malignant cells, with frequent mitotic figures, as well as multinucleated giant cells. Immunohistochemistry and imaging led to the conclusion that this nodule represented a primary cutaneous extraskeletal osteosarcoma. The previously reported cases are variable in location, size, gross appearance, and clinical course. The prognosis of osteosarcoma is typically poor, with aggressive behavior; this, however, may be less severe in these strictly cutaneous tumors, though additional follow-up would be beneficial to determine long-term outcomes for the known cases. Ultimately, despite the fact that this is an extremely rare entity, primary cutaneous extraskeletal osteosarcomas should be considered when relevant.

Malignant Proliferating Trichilemmal Tumor of the Scalp: A Systematic Review.

OBJECTIVES: Malignant proliferating trichilemmal tumors of the scalp can exhibit aggressive presentation and recurrences. Our objective was to perform an evidence-based systematic review evaluating clinical presentation, tumor characteristics, and treatment modalities used to determine which treatment strategies had the best outcomes. METHODS: The databases PubMed, Embase, and Cochrane Library were searched for relevant literature by the authors. Patient demographics, imaging, treatments, and other clinical characteristics were obtained. The results were reported using the Preferred Reporting Systems for Systematic Reviews and Meta-Analysis guidelines. RESULTS: Thirty-nine studies with a total of 65 patients were identified. The most common presentation was a history of slow-growing, painless swollen mass on the scalp. In total, 10 patients (15.4%) presented with spread to the regional lymph nodes and 6 (9.2%) additional patients presented with metastasis to distant locations. In total, 61 patients (93.8%) underwent surgery. Various chemotherapy and radiation therapy regimens were used. Of the 45 cases with documented follow-up, 11 (24.4%) patients had one or multiple instances of local, lymph node or metastatic tumor recurrence. CONCLUSIONS: Surgery is favored, and the exact approach should be based on clinical judgment. However, Mohs micrographic surgery should strongly be considered because of its superior margin control against such an invasive tumor. Radiotherapy and chemotherapy have been used as adjuvant therapy in aggressive cases or recurrence. Patients should be followed closely and examined often to frequently assess recurrence or metastasis. Randomized controlled trials are needed to further clarify these findings.

The status of treatment for plantar warts in 2021: No definitive advancements in decades for a common dermatology disease.

Plantar warts are among the most common skin conditions and are classically resistant to treatment. To perform an evidence-based evaluation of the efficacy and safety of available treatment options for plantar warts, we conducted a systematic review of PubMed and Cochrane databases to identify large interventional and observational studies involving more than 100 patients who were treated for plantar warts from inception to October 2020. We identified only nine contributions meeting our inclusion criteria (N ≥ 100), representing 1,657 adult and pediatric patients with plantar warts. Treatments included in this review were topical keratolytic agents, cryotherapy, laser therapies, and intralesional and systemic treatments. Our evidence-based review of the larger studies suggests keratolytic agents and destructive treatments, in particular salicylic acid and cryotherapy, remain the primary treatments for plantar warts. Treatment with pulsed dye laser had the lowest rate of recurrence. Newer treatments and intralesional treatments were not represented owing to lack of large studies involving these modalities.