Atypical Melanocytic Proliferation Research Articles

In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis.

Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma insitu in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies. To assess the role of invivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna. A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. Studies involving RCM for AIMP, LM and LMM diagnosis published until 1 December 2023, were selected for analysis. Publications on other non-invasive imaging techniques, other skin diseases or those addressing only RCM surgical margins and therapeutic response without reporting RCM features were excluded. Each article was reviewed by two experts, with disagreements resolved by a third expert. Data for each RCM feature were pooled, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Features were stratified for architecture, cellular morphology and distribution. Twenty-seven articles involving 303 lesions were included. Features favouring LM over AIMP included (1) Architecture: the presence of non-edged papillae (OR 4.50, 95% CI 1.92-10.52) and (2) Cellular distribution: widespread pagetoid cells and junctional atypical cells (OR 25.06, 95% CI 4.19-148.45) and junctional nests (OR 18.06, 95% CI 3.04-106.32). Features favouring LMM over LM included (1) Architecture: epidermal disarray (OR 5.03, 95% CI 1.90-13.22), junctional disarray (OR 4.19, 95% CI 1.54-11.33) and destroyed collagen fibres (OR 3.91, 95% CI 1.80-8.44) and (2) cellular distribution: widespread pagetoid and junctional atypical cells (OR 2.71, 95% CI 1.27-5.75) and junctional nests (OR 4.48, 95% CI 2.12-9.43). This study identifies the RCM features associated with the LM/LMM spectrum.

Subungual melanoma: molecular analysis of 31 cases from early stage to invasive melanoma.

The distinction between the benign subungual melanocytic lesions and an early lesion of subungual melanoma (SUM) remains a diagnostic challenge. We evaluated the routine diagnostic utility of array Comparative Genomic Hybridization (aCGH) to detect whole-genome copy number variations (CNV) as well as targeted next-generation sequencing (NGS) in SUM. This retrospective study included 20 cases of in situ SUM and 11 cases of invasive SUM. Analysis by aCGH detected common oncogene amplifications in all but one case of invasive SUM (n = 10) and in all cases of in situ SUM with a melanocyte count (MC) >45/mm (n = 4 true positive) and the average number of CNV was 8.5. Thirteen remaining cases of in situ SUM gave false negative results (n = 13), owing to a lack of sufficient melanocytes to analyse (median MC of 35.35; range: 10.16-39.5). Molecular analysis failed in four cases (three in situ SUM and one invasive SUM) due to insufficient amounts of DNA. Across the whole cohort, the sensitivity of aCGH was 52%, but when adjusting the cutoff to MC >45/mm, the sensitivity was 93%. Targeted NGS was less informative than aCGH analyses in our series of SUM. To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45 melanocytes per linear millimetre. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.

Staged Excision Technique for Periocular Cutaneous Melanoma: Long-Term Outcomes of the Square Procedure.

To examine the long-term outcome of the staged excision via the square procedure for the treatment of periocular thin cutaneous melanoma. A retrospective chart review of 95 periocular cutaneous melanoma-in-situ and microinvasive melanoma tumors that were treated with the square procedure between April 1, 1994 and December 31, 2018 at the University of Michigan. Demographic and clinical data were evaluated. Of 95 cases, 19 (20%) were atypical junctional melanocytic proliferation with features of early melanoma-in-situ, 63 (66.3%) were melanoma-in-situ and 13 (13.7) were microinvasive melanoma with Breslow depth less than 1 mm. Tumor-free margins were achieved with a median margin of 10 mm (range 5-40 mm). Most cases (68.4%) required multiple excision stages. Surgical revision was necessary in 17.9% of cases and was associated with larger defect size. Local recurrence was noted in 8 patients (8.4%) at a median of 42 months postreconstruction. No tumor characteristics were found to predict recurrence. The square procedure for periocular melanoma offers an 8.4% recurrence rate, consistent with literature reports on similar staged excision approaches. The staged excision provides an excellent option for comprehensive margin review and tumor control with acceptable cosmetic results after reconstruction.

The Expression of PRAME as an Aid for Diagnosis and Evaluation of Histologic Margins of Intraepidermal Cutaneous Melanoma in Xeroderma Pigmentosum Patients.

Xeroderma Pigmentosum (XP) is a genetic disorder characterized by photosensitivity, dyschromia, and high risk of skin cancer. From a clinical and histologic view, it can be difficult to diagnose cutaneous melanoma (CM) in XP patients and to define its resection margins. We aimed to study the role of PRAME (PReferentially Expressed Antigen in MElanoma) in differentiating intraepidermal CM from superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and evaluating the histological margins of CMs. We included XP patients. melanocitic and nonmelanocytic lesions with adjacent skin, and, as control groups, sun-damaged skin from non-XP individuals. Melanocytic lesions with a consensus diagnosis were grouped into CM, SAMPUS, or benign. The selected samples were PRAME-immunoshistochemically stained, and the ratio between immuno-positive cells/mm was recorded, according to Olds and colleagues for intraepidermal lesions. Lezcano and colleagues' method was used for intradermal lesions. Clinical data from XP patients were reviewed. All 9 patients were alive and well at the study closure, even those who developed melanoma metastases. Positive/diffuse PRAME expression was found in 29% (7/24) of intraepidermal CMs and 20% (1/5) SAMPUS samples. All 103 XP control samples and 24 adjacent lesions skin of non-XP patients were PRAME negative. This was a single-center and retrospective study, using a relatively small sample, limiting our conclusions. In XP patients' lesions, PRAME expression could help in the setting of challenging melanocytic tumors and surgical margins evaluation. It is also possible that the method can avoid overdiagnosis and, consequently, more aggressive treatment recommendation in unequivocal CM cases.

Clinical and Histopathological Investigation of Pediatric Melanonychia: A Single-Center Retrospective Case Series.

The natural history of pediatric melanonychia and the necessity of biopsy for ruling out melanoma are debated in the literature. We hypothesize that there is a low rate of malignant nail pathology among pediatric patients undergoing nail bed biopsy for melanonychia. We performed a retrospective chart review of 54 pediatric patients (age <18 years) at a single institution who presented with melanonychia and underwent nail bed biopsy from 2007 to 2022. Data points collected included patient demographics, medical history, physical exam findings, pathology reports, and clinical photos. Univariate and multivariate analyses were performed to assess for risk factors associated with high-risk pathology findings. The average age of melanonychia onset was 5.5 years (SD 4.4). The average age of first biopsy was 7.8 years (SD 4.3). On physical exam, 27 patients had at least four features concerning for melanoma (asymmetry, border irregularity, color heterogeneity, diameter > 1/3 of nail, evolving color, evolving diameter, Hutchinson's sign). The most common pathology diagnoses were melanocytic nevus (35%), atypical intraepidermal melanocytic proliferation (AIMP) with benign features (24%), subungual lentigo (22%), and AIMP with concerning features (17%). There were no cases of melanoma in situ or invasive malignant melanoma. On multivariate regression, the only significant risk factor associated with more concerning pathology (AIMP with concerning features) was the calendar year in which biopsy was performed (coefficient = -0.34, P = 0.016). There was no association between physical exam features and high-risk pathology. Twelve patients had surgical re-excision of the lesion, 6 of which were due to incomplete excision of AIMP with concerning features and 6 of which were due to recurrence. Our case series did not find any cases of melanoma in situ or malignant melanoma arising from pediatric melanonychia. Atypical intraepidermal melanocytic proliferation with concerning features was associated only with the year in which the biopsy was performed, which may reflect the improved understanding of pediatric melanonychia as often benign despite concerning features on pathology. The decision to perform a nail matrix biopsy in pediatric melanonychia should be based on a collaborative discussion between the patient's parents, dermatologist, and plastic surgeon.

TERT promoter mutations in atypical melanocytic lesions: A series of seven cases with adverse melanoma-specific outcome

The majority of melanocytic proliferations can be readily categorized as benign or malignant based on histologic assessment under the microscope by a trained dermatopathologist. However, a subset of lesions, termed Atypical Melanocytic Proliferations (AMPs), are histologically ambiguous, leading to possible diagnostic error and suboptimal treatment. Mutations in the promoter region of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), are commonly found in melanomas but are rare in melanocytic nevi. In this study, we aimed to determine the prevalence of hot spot TERT promoter (TERT-p) mutations in AMPs with adverse melanoma-specific outcome. Studies were approved by respective institutional review boards. Using a multi-center database, we identified seven cases of melanocytic proliferations with a clinical follow-up period of at least 4 years, which were initially diagnosed as AMPs, and which recurred either as melanoma at site of prior biopsy or as metastatic melanoma. Sequencing of the TERT-p region showed hotspot mutations in three cases (43 %), suggesting that TERT-p mutations are enriched and could aid in the identification of AMPs with adverse outcome. In comparison with existing ancillary techniques for prognostication of AMPs, TERT-p mutation analysis may have advantages in terms of cost effectiveness and turnaround time, and is a promising diagnostic parameter with potential widespread utility.

Using Artificial Intelligence as a Melanoma Screening Tool in Self-Referred Patients.

Early detection of melanoma requires timely access to medical care. In this study, we examined the feasibility of using artificial intelligence (AI) to flag possible melanomas in self-referred patients concerned that a skin lesion might be cancerous. Patients were recruited for the study through advertisements in 2 hospitals in Halifax, Nova Scotia, Canada. Lesions of concern were initially examined by a trained medical student and if the study criteria were met, the lesions were then scanned using the FotoFinder System®. The images were analyzed using their proprietary computer software. Macroscopic and dermoscopic images were evaluated by 3 experienced dermatologists and a senior dermatology resident, all blinded to the AI results. Suspicious lesions identified by the AI or any of the 3 dermatologists were then excised. Seventeen confirmed malignancies were found, including 10 melanomas. Six melanomas were not flagged by the AI. These lesions showed ambiguous atypical melanocytic proliferations, and all were diagnostically challenging to the dermatologists and to the dermatopathologists. Eight malignancies were seen in patients with a family history of melanoma. The AI's ability to diagnose malignancy is not inferior to the dermatologists examining dermoscopic images. AI, used in this study, may serve as a practical skin cancer screening aid. While it does have technical and diagnostic limitations, its inclusion in a melanoma screening program, directed at those with a concern about a particular lesion would be valuable in providing timely access to the diagnosis of skin cancer.

Pediatric Atypical Melanocytic Proliferations: Single-Site Retrospective Cohort Assessment of Treatment and Long-Term Follow-Up.

Atypical and malignant cutaneous tumors are understudied in the pediatric population, with limited data on long-term follow-up. This study examines pediatric (0-18 years) atypical melanocytic proliferations over a twenty-year period (January 2002-December2022) using the EPIC SlicerDicer at our institution. Over a twenty-year period, there were 55 cases of pediatric melanoma (53 patients). The median follow-up time was 8 years, 11 months. A proportion of 96% were treated with wide local excision (WLE), and 47% had a sentinel lymph node biopsy (SLNB) (35% positive rate). There were 101 atypical Spitz tumor cases (85% atypical Spitz tumors, 15% Spitz melanoma), with a median follow-up duration of 9 years. A proportion of 77% were treated with WLE (with one patient dying of metastatic disease). There were 10 cases of atypical melanocytic proliferations not otherwise specified, including 5 pigmented epithelioid melanocytomas (PEM), 4 deep-penetrating nevi, and 1 atypical cellular blue nevus. This study adds to the growing body of knowledge on pediatric atypical cutaneous melanocytic proliferations, aligning with many described characteristics such as disease location and overall survival rates, with distinct exceptions (higher melanoma positive SLNB rate, lower atypical Spitz tumor WLE rate, and a case of fatal metastatic atypical Spitz tumor).

Malignant Melanoma of the jaw and oral mucosa - A rare diagnosis to consider when assessing high-grade tumors on small biopsies

Abstract Introduction/Objective Malignant melanoma arises from neural crest-derived cells called melanocytes. These melanocytes migrate to several sites, including the skin and the mucous membranes. Oral melanoma (OM) cases account for &amp;lt;1% of all melanoma cases and &amp;lt;2% of all oral malignancies. Primary malignant melanoma of the jaw is an even rarer entity. Most OM cases arise in the palate and the maxillary alveolar gingivae. Other sites, such as mandibular gingiva and buccal mucosa, are rarely involved. The etiopathogenesis remains unclear, with stimulation of melanoblasts being one of the proposed hypotheses. The incidence is highest in the fifth and sixth decades of life and occurs more commonly in males than females. Clinically, it remains an asymptomatic pigmented growth until it reaches advanced stages. Diagnosis in advanced stages leads to OM having an overall survival (OS) rate of just 15.4% at 10 years with an abysmal prognosis. These neoplasms are highly invasive and metastasize quickly. Of mutations, KIT (14.6%), BRAF (7%) and NRAS (5.6%) were the most frequently encountered in OM cases. Methods/Case Report We searched for “oral melanoma” in our healthcare system for the last 10 years- from 2013 to 2022. 4 cases were selected for this case series, and pertinent information was pulled from CoPath and Epic software. The cases were then analyzed, and the results were reported. Results (if a Case Study enter NA) In our case series, we found the mean age to be 78.5 years, with 75% (3 of 4) of the patients being male and the rest 25% (1 of 4) female. Three cases were diagnosed with melanoma or malignant melanoma, while the 4th case had atypical melanocytic proliferation favoring malignant melanoma as the diagnosis. Regarding the tumour site, 1 case arose in the right anterior maxilla, 2 cases involved the mandible (left mandible and right anterior mandibular vestibule, respectively), and 1 case was present in the buccal mucosa. Microscopic findings and immunohistochemistry results concurred with the diagnoses. Conclusion Herein, we present 3 cases (out of the 4) from rarer sites, such as the mandible and oral mucosa, as opposed to the typical sites- the palate and the maxilla. Discussing rarer cases helps physicians to keep these in the differential while examining similar tumors. Additionally, having rarer cases adds to the literature and focuses attention on entities that require more study and research. Since these neoplasms are highly invasive and metastasize quickly, they necessitate an early diagnosis for effective management.

Pathologist Characteristics Associated With Rendering Higher-Grade Diagnoses for Melanocytic Lesions

The incidence of melanoma diagnoses has been increasing in recent decades, and controlled studies have indicated high histopathologic discordance across the intermediate range of melanocytic lesions. The respective causes for these phenomena remain incompletely understood. To identify pathologist characteristics associated with tendencies to diagnose melanocytic lesions as higher grade vs lower grade or to diagnose invasive melanoma vs any less severe diagnosis. This exploratory study used data from 2 nationwide studies (the Melanoma Pathology [M-Path] study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations [REMI] study, conducted from August 2018 to March 2021) in which participating pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. Each pathologist was randomly assigned to interpret a set of study cases from a repository of skin biopsy samples of melanocytic lesions; each case was independently interpreted by multiple pathologists. Data were analyzed from July 2022 to February 2023. The association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs any less severe diagnosis was assessed using logistic regression. Characteristics included demographics (age, gender, and geographic region), years of experience, academic affiliation, caseload of melanocytic lesions in their practice, specialty training, and history of malpractice suits. A total of 338 pathologists were included: 113 general pathologists and 74 dermatopathologists from M-Path and 151 dermatopathologists from REMI. The predominant factor associated with rendering more severe diagnoses was specialist training in dermatopathology (board certification and/or fellowship training). Pathologists with this training were more likely to render higher-grade diagnoses (odds ratio [OR], 2.63; 95% CI, 2.10-3.30; P < .001) and to diagnose invasive melanoma (OR, 1.95; 95% CI, 1.53-2.49; P < .001) than pathologists without this training interpreting the same case. Nonmitogenic pT1a diagnoses (stage pT1a melanomas with no mitotic activity) accounted for the observed difference in diagnosis of invasive melanoma; when these lesions, which carry a low risk of metastasis, were grouped with the less severe diagnoses, there was no observed association (OR, 0.95; 95% CI, 0.74-1.23; P = .71). Among dermatopathologists, those with a higher caseload of melanocytic lesions in their practice were more likely to assign higher-grade diagnoses (OR for trend, 1.27; 95% CI, 1.04-1.56; P = .02). The findings suggest that specialty training in dermatopathology is associated with a greater tendency to diagnose atypical melanocytic proliferations as pT1a melanomas. These low-risk melanomas constitute a growing proportion of melanomas diagnosed in the US.

Impact of second opinion pathology review in the diagnosis and management of atypical melanocytic lesions: A prospective study of the Italian Melanoma Intergroup (IMI) and EORTC Melanoma Group

BackgroundThe clinical value of an expert pathological review in patients with an atypical melanocytic lesion diagnosis remains unclear. Herein, we evaluate its impact in a prospective clinical study. MethodsPatients with newly diagnosed or suspected atypical melanocytic proliferations and challenging skin tumours were reviewed prospectively by a specialised dermatopathologist through the nationwide ‘Second Opinion Platform’ of the Italian Melanoma Intergroup (IMI) network. The primary aim was the rate of major discrepancies that impacted patient management. Major discrepancies in diagnosis between referral and specialised review were blindly re-analysed by a panel of European Organisation for Research and Treatment (EORTC) Melanoma pathologists. ResultsThe samples submitted to central review included 254 lesions from 230 patients. The most frequent referral diagnoses were atypical melanocytic nevi of different subtypes (74/254, 29.2%), invasive melanomas (61/254, 24.0%), atypical melanocytic proliferations (37/254, 14.6%), AST (21/254, 8.3%) and in situ melanomas (17/254, 6.7%). There was disagreement between referral diagnosis and expert review in 90/254 cases (35.4%). Most importantly, 60/90 (66.7%) were major discordances with a change to the patient's clinical management. Among the 90 discordant cases, the most frequent new diagnosis occurred in World Health Organisation (WHO) Pathway I, followed by WHO Pathway IV (64/90 and 12/90, respectively). In total, 51/60 cases with major discrepancies were blindly re-evaluated by EORTC Melanoma pathologists with a final interobserver agreement in 90% of cases. ConclusionThe study highlights that a second opinion for atypical melanocytic lesions affects clinical management in a minor, but still significant, proportion of cases. A central expert review supports pathologists and clinicians to limit the risk of both over- and under-treatment.

Conjunctival Melanoma: Case Report

Conjunctival melanoma is a rare malignant tumor with a recurrent character and metastatic potential. It is characterized in anatomopathology by a tumoral proliferation of atypical melanocytes. It can develop on a pre-existing lesion or appear on a healthy conjunctiva called "de novo" melanoma. The clinical aspect of melanoma is variable. It often appears as a pigmented lesion in relief, more or less nodular and vascularized, but it can also be achromatic. It can involve any portion of the conjunctiva and extend to the surface of the cornea. The involvement can be plurifocal.

Top 10 Differential Diagnoses for Desmoplastic Melanoma.

Desmoplastic melanoma is a rare subtype of melanoma mainly appearing on sun-exposed skin. Clinically, it is many times non-pigmented and therefore the diagnosis is often not suspected. Review article. In this paper we review the main histopathological, immunohistochemical, and molecular features of desmoplastic melanoma, as well as the top 10 morphologic differential diagnoses which should be considered in most cases. The histopathological pattern can be many times deceptive, mimicking a scar, a fibrous reaction, a fibrohistiocytic tumor such as a dermatofibroma, a vascular tumor such as angiosarcoma, a smooth muscle tumor such as leiomyosarcoma, or a neural tumor. Although an overlying atypical junctional melanocytic proliferation may be seen in most cases, it is absent in a significant percentage (up to 30%) of cases, making the diagnosis even more difficult in those instances. The range of diagnostic pitfalls is wide, which may present disastrous prognostic consequences. Desmoplastic melanoma is often a difficult diagnosis to make, as it frequently shows nonspecific clinical findings and overlapping histologic features with many other tumors. However, the potential clinical and prognostic consequences of misdiagnosis as another entity are great. Therefore, this diagnosis must always be kept in mind when encountering spindle cell tumors affecting the head and neck area.

A clinical impact study of dermatologists’ use of the 23- or 35-gene expression profile tests to guide surgical excision and enhance management plan confidence

Purpose: To understand how dermatologists utilize the results from ancillary diagnostic gene expression profile (dGEP) testing with the 23- or 35-GEP tests to determine optimal patient management strategies. Study: Dermatologists who regularly treat patients with difficult-to-diagnose melanocytic lesions who had previously initiated dGEP testing at least 3 times were eligible to complete the questionnaire in this Institutional Review Board-approved study. There were 24 randomized vignettes presented covering a spectrum of cases with diagnostic/clinical uncertainty such as atypical melanocytic proliferation, dysplastic nevus with regression, deep penetrating melanocytic neoplasm, and atypical intraepidermal melanocytic proliferation. Respondents were provided with a clinical impression and diagnosis in the context of a narrative pathology report with/without a re-excision recommendation; cases were also described without (baseline) and with a dGEP test result (likely benign or likely malignant). Anonymous responses concerning the patient management plan including excision and follow-up recommendations and confidence were captured. Statistical significance was calculated by nonparametric Wilcoxon signed-rank test with continuity correction. Results: In total, 32 dermatologists (84% in a private practice setting) completed the survey, with 50% indicating additional dermatopathology specialization. Approximately 44% of respondents indicated they performed 10-50 biopsies of melanocytic lesions per month, and 31%, greater than 100 per month. When dGEP results were provided, there was an overall increase in management plan confidence, regardless of which dGEP result was provided (benign dGEP 26.2%, malignant dGEP 24.7%). Also, when dGEP results were provided, changes in surgical excision recommendations were statistically significant in 75% of scenarios tested (p &lt; 0.02). Clinical impact was assessed by quantifying the directional shift in treatment in relation to the dGEP result. With regard to excision recommendations across vignettes, benign dGEP results prompted 29.7% of clinicians to decrease their margins or forgo excision altogether. Malignant dGEP results prompted 63.5% of clinicians to increase their surgical excision recommendations. Appropriate alterations in patient follow-up frequency were observed, with 18.8% of clinicians reducing and 43.2% increasing follow-up frequency for patients receiving benign or malignant dGEP results, respectively. Conclusion: The addition of dGEP testing to diagnostic scenarios with confounding clinical features and uncertainty in optimal management prompted important changes in recommendations regarding the need for excision, appropriate margins, and follow-up-frequency. Overall, dGEP tests help to guide clinical decision-making for dermatologists in a variety of otherwise diagnostically ambiguous or clinicopathologically discordant scenarios.

Computer-Aided Diagnosis of Melanoma Subtypes Using Reflectance Confocal Images.

Lentigo maligna (LM) is an early form of pre-invasive melanoma that predominantly affects sun-exposed areas such as the face. LM is highly treatable when identified early but has an ill-defined clinical border and a high rate of recurrence. Atypical intraepidermal melanocytic proliferation (AIMP), also known as atypical melanocytic hyperplasia (AMH), is a histological description that indicates melanocytic proliferation with uncertain malignant potential. Clinically and histologically, AIMP can be difficult to distinguish from LM, and indeed AIMP may, in some cases, progress to LM. The early diagnosis and distinction of LM from AIMP are important since LM requires a definitive treatment. Reflectance confocal microscopy (RCM) is an imaging technique often used to investigate these lesions non-invasively, without biopsy. However, RCM equipment is often not readily available, nor is the associated expertise for RCM image interpretation easy to find. Here, we implemented a machine learning classifier using popular convolutional neural network (CNN) architectures and demonstrated that it could correctly classify lesions between LM and AIMP on biopsy-confirmed RCM image stacks. We identified local z-projection (LZP) as a recent fast approach for projecting a 3D image into 2D while preserving information and achieved high-accuracy machine classification with minimal computational requirements.

Performance of PRAME immunohistochemistry compared with that of c-Kit, c-Myc, or cyclin D1 for the diagnosis of acral melanocytic tumors.

The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)-favor benign (SAMPUS-FB), SAMPUS-favor malignant (SAMPUS-FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS-FB (n = 17), SAMPUS-FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c-Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c-Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms.

Ambiguous melanocytic lesions: A retrospective cohort study of incidence and outcome of melanocytic tumor of uncertain malignant potential (MELTUMP) and superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) in the Netherlands

Melanocytic tumor of uncertain malignant potential (MELTUMP) and superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) are descriptive and provisional terms for melanocytic tumors with ambiguous histopathological features that are not easily classified as either benign or malignant. To investigate the incidence and clinical outcome of MELTUMP and SAMPUS in the Netherlands. In this retrospective cohort study, we reviewed all diagnoses of MELTUMP and SAMPUS from the Dutch Nationwide Pathology Databank from 1991 to October 1, 2021. Clinical outcome was studied for cases diagnosed until October 1, 2018. A total of 1685 MELTUMP and 1957 SAMPUS were identified with an annual incidence of 150 to 300 cases. Metastatic behavior was seen in 0.7% of all initially diagnosed MELTUMP. All SAMPUS remained free of metastases. Reassessment of pathology slides and confirmation of clonality between primary and metastatic lesions remained outside the scope of this study. Despite the 'uncertainty' in the nomenclature, our results demonstrate a low malignant potential for MELTUMP and no malignant potential for SAMPUS. We emphasize the importance of consultation for ambiguous melanocytic lesions and to limit the MELTUMP/SAMPUS terminology to legitimately uncertain or unclassifiable cases.

Minocycline-induced Conjunctival Hyperpigmentation.

A 73-year-old woman presented with a 1-year history of pigmented conjunctival lesions in both eyes. She had been taking minocycline for decades for recurrent facial cysts. On examination, she had a larger pigmented cystic lesion of her right inferior fornix conjunctiva, and several smaller hyperpigmented lesions in her right inferior, left superior, and left inferior palpebral conjunctivae (Panel A; external photograph). She underwent an excisional biopsy of the large cyst. Pathology showed exogenous brownish-gray pigment granules (circle) deposited in macrophages surrounding vessels in the substantia propia (Panel B; hematoxylin & eosin-stained image at 40× magnification). The pigment granules were stained black (arrow) with Fontana-Masson stain (Panel C; image at 40×). There was no evidence of an atypical melanocytic proliferation. A diagnosis of minocycline-induced hyperpigmentation was made. Minocycline, a tetracycline antibiotic, can be used to treat dermatologic conditions. Extended use can lead to hyperpigmentation of the skin, nails, teeth, oral mucosa, sclera, and conjunctiva. There is a wide range of reported doses and duration of therapy associated with mucosal or cutaneous hyperpigmentation varying by type and site, occurring as early as days to weeks, with a median onset of 1–2 years. Cosmetic concerns should prompt discontinuation, although hyperpigmentation is likely permanent. These lesions were not visually significant nor bothersome, and therefore no additional treatment was recommended.

33044 Desmoplastic melanoma vs dermatofibroma: A challenging histopathologic case

A 67-year-old male presented with a 3-year history of a pigmented lesion on his posterior right shoulder which had recently become darker and bigger. On examination he had a 15- × 18-mm firm brown/pink nodule with central white-scar, dimpling sign positive and peripheral pigmentation (Figure 1). An excision biopsy was performed in view of the findings. Initial histology reported a lentiginous proliferation of atypical melanocytes with junction nests in varying sizes and pagetoid spread (Figure 2).

The use of digital dermoscopy in the surveillance of melanocytic skin lesions: A real-life retrospective study comparing university hospital and private practices

BackgroundFew studies have evaluated the role of digital dermoscopy (DD) in the surveillance of pigmented lesions in real-life practice. Patients and methodsPatients followed with DD by 4 hospital dermatologists (group 1) and 4 private dermatologists (group 2) were retrospectively included if they had had at least 2 DD examinations for a minimum of 4 pigmented lesions. Their characteristics, risk factors, history of excision of benign nevi and melanomas prior to and during the DD follow-up, and characteristics of detected melanomas, were recorded. ResultsOne hundred and ninety-six patients were included in group 1 and 205 in groups 2. A family history of melanoma (25% vs. 12%, p<0.01), a personal history of melanoma before DD follow-up (47% vs. 15%, p<0.01), and a family (3% vs. 0%, p=0.01) and personal (8% vs. 1%, p<0.01) germline CDKN2a mutation were more frequent in group 1 than in group 2. In both groups, the number of excisions of benign lesions was higher before DD follow-up (380 and 347, respectively) than during DD follow-up (194 and 132). During follow-up, 29 melanomas were detected in group 1, with a median Breslow thickness of 0.4mm, versus 1.3mm for melanomas diagnosed before DD follow-up (p<0.02). In group 2, 4 melanoma and 5 superficial atypical melanocytic proliferations of unknown significance were detected. The median Breslow thickness of newly diagnosed melanomas was 0.35mm vs. 0.6mm before DD follow-up (p=0.1). ConclusionIn both populations in real-life practice, DD seemed to allow the detection of thin melanomas and to decrease the rate of “futile” resections.