Malignant Melanocytic Lesions Research Articles

Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.

CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status.

Background and Objectives: In the realm of the rising incidence of cutaneous and mucous melanoma, CDKN2A mutations characterize familial and multiple primary melanoma cases. The involvement of tumor-infiltrating lymphocytes (TILs) is interconnected with survival rates, but may extend even further. The aim of this study is to verify the accuracy of the classical "naked eye" count of CD8-positive T cells comprised within the tumoral population and peritumoral infiltrate versus that obtained via a special software run by the aid of artificial intelligence (AI), used to determine the percentage of CD8-positive TILs. Materials and Methods: The present retrospective cross-sectional study conducted over a period of 5 years (2018-2022) focused on patients diagnosed with mucous and/or cutaneous melanoma, with a positive family history for melanoma, or personal antecedents of primary malignant melanocytic lesions. The 23 selected cases were diagnosed histopathologically, tested for CDKN2A mutations through fluorescent hybridization in situ, and CD8 immunohistochemistry was performed. The included slides were evaluated both manually (naked-eye examination) and automatically (via QuPath platform) for quantifying the CD8-positive TILs. Results: The number of CD8-positive TILs in melanoma samples has been more accurately identified through the use of an AI-mediated software as compared to the human-eye evaluation performed by experimental pathologists. A higher percentage of CD8-positive intratumoral lymphocytes versus stromal lymphocytes was positively associated with more numerous metastatic sites. Conclusions: The CD8 lymphocytic phenotype harbors major significance in the context of familial and multiple primary melanoma and may comprise a cost-effective investigation meant to help in the establishment of melanoma prognosis and response to immunotherapy.

Line-Field Confocal Optical Coherence Tomography (LC-OCT) for Skin Imaging in Dermatology.

Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive optical imaging technique based on a combination of the principles of optical coherence tomography and reflectance confocal microscopy with line-field illumination, which can generate cell-resolved images of the skin in vivo. This article reports on the LC-OCT technique and its application in dermatology. The principle of the technique is described, and the latest technological innovations are presented. The technology has been miniaturized to fit within an ergonomic handheld probe, allowing for the easy access of any skin area on the body. The performance of the LC-OCT device in terms of resolution, field of view, and acquisition speed is reported. The use of LC-OCT in dermatology for the non-invasive detection, characterization, and therapeutic follow-up of various skin pathologies is discussed. Benign and malignant melanocytic lesions, non-melanocytic skin tumors, such as basal cell carcinoma, squamous cell carcinoma and actinic keratosis, and inflammatory and infectious skin conditions are considered. Dedicated deep learning algorithms have been developed for assisting in the analysis of LC-OCT images of skin lesions.

PRAME expression in 137 primary cutaneous melanomas and comparison with 38 related metastases

Melanocytic lesions have always represented a diagnostic challenge for surgical pathologists. According to the literature, PRAME showed great promise as an immunohistochemical tool in the distinction between benign and malignant melanocytic lesions. In the present study, we retrospectively analyzed 137 thicker (Breslow > 1 mm) primary cutaneous melanomas with the aim to better understand the utility of PRAME immunohistochemistry in daily practice and also to investigate if PRAME could represent a prognostic biomarker for cutaneous melanomas. PRAME immunohistochemistry was performed in all melanomas and in the metastases with antibodies to PRAME (dilution 1:1000, clone Ab219650) on an automated immunostainer (Ventana Benchmark Ultra) using a brown chromogen (DAB). We found that melanomas (59.1%) show diffuse PRAME expression (score 4 +). 99 (72.3%) primary cutaneous melanoma had no relapse during the follow-up. Of this group of melanomas, 61/99 (61.6%) were diffusely positive for PRAME. 38 (27.7%) primary cutaneous melanoma had relapses. Of this group, 28/36 (77.7%) were diffusely positive. We did not find any statistical correlation between diffuse PRAME expression and the presence of driver mutation in BRAF gene (p = 0.927), NRAS gene (p = 0.496) or either of the two (p = 0.138). We did not find a prognostic significance of diffuse PRAME expression for relapse (p = 0.462) or survival rate (p = 0.245). The prognostic value of PRAME has been only reported in mucosal, uveal and cutaneous thin melanomas. Here, we show statistical analyses on PRAME expression for melanoma with Breslow > 1 mm based on survival rate and long-term follow-up. According to our results, PRAME is a useful immunohistochemical ancillary tool in daily practice diagnosis of melanocytic lesions.

Refining the application of PRAME-a useful marker in high CSD and acral melanoma subtypes.

Pathologic discordance affecting patient management may approach 20% in melanocytic cases following specialist review. The diagnostic utility of PRAME has been highlighted in several studies but interpretative challenges exist including its use in severely dysplastic compound nevi showing progression to melanoma in situ, nevoid melanoma, and coexisting nevi with melanoma. We examine the PRAME status of a broad spectrum of melanocytic lesions including challenging, dysplastic nevi with severe atypia from a large Irish patient cohort. Retrospective review of the dermatopathology database was conducted to evaluate the PRAME staining characteristics of two hundred and twenty-one melanocytic lesions using a commercially available PRAME antibody (EPR20330). The proportion of nuclear labeling and intensity of staining was recorded. The sensitivity and specificity of PRAME for in situ and malignant melanocytic lesions was 77% and 100%, respectively. Virtually all of our melanoma in situ from high-cumulative sun damaged (CSD) skin (22/23) and all acral lentiginous melanoma (5/5) were PRAME positive while 80% (8/10) of our lentigo maligna melanoma showed diffuse expression. None of our benign subgroup showed diffuse immunoexpression (0/82), including thirty-seven moderate or severely dysplastic nevi. In all cases of melanoma in situ arising in association with a dysplastic compound nevus (0/10), no immunoexpression was observed in the nevic component while in five cases of melanoma in situ with coexistent, intradermal nevus immunostaining was confined to the in situ component. A total of 100% (2/2) of desmoplastic melanomas and 50% (4/8) of nodular melanomas were PRAME positive. PRAME is a sensitive and highly specific immunostain in the diagnosis of in situ and invasive melanoma and we emphasize its application in the evaluation of high CSD and acral melanoma subtypes as well as in challenging threshold cases.

PRAME/MELAN-A double immunostaining as a diagnostic tool for conjunctival melanocytic lesions: A South American experience

IntroductionPRAME (PReferentially expressed Antigen in Melanoma) is an antigen that is predominantly expressed in human melanomas. In cutaneous melanocytic lesions, PRAME expression is associated with malignancy. The objective of this study was to evaluate the co-expression of PRAME and Melan A to evaluate their diagnostic value in different conjunctival melanocytic lesions (CML). Methods37 CML (23 nevi, 9 primary acquired melanosis (PAM), and 5 conjunctival melanomas) were evaluated by immunohistochemistry for PRAME and Melan-A. The percentage of melanocytic cells co-expressing PRAME and Melan-A was qualitatively evaluated as follows: negative, 0%; 1 + , 1–25%; 2 + , 26–50%; 3 + , 51–75% and 4 + , ≥ 76%. ResultsOf the invasive melanoma cases, 80% showed a 4 + pattern of marking, whereas 20% showed a 3 + pattern. 11% of the PAMs showed a 4 + pattern and 88.9% showed a 1 + pattern. All the nevi showed a 1 + pattern. The sensitivity and specificity of PRAME 4 + for differentiating high-grade CML from the benign and low-grade grouped CML are 93% and 100%, respectively. ConclusionPRAME/MELAN-A double immunostain is particularly useful to differentiate benign from malignant conjunctival melanocytic lesions.

ATRX Loss in the Development and Prognosis of Conjunctival Melanoma.

Metastatic disease is linked to TERT promoter mutations in conjunctival melanomas (CM). Both TERT promoter and ATRX mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions. Eighty-six conjunctival melanocytic lesions from the Rotterdam Ocular Melanoma Study group were collected. ATRX status and TERT promoter status were determined using immunohistochemical staining and molecular diagnostics, respectively. None of the nevi (n = 16) and primary acquired melanosis (PAM) without atypia (n = 6) showed ATRX loss. ATRX loss was found in 2/5 PAM with atypia without CM and in 8/59 CM. No cases with a TERT promoter mutation (n = 26) showed ATRX loss. Eight/eleven metastatic CM harbored a TERT promoter mutation, two other metastatic CM showed ATRX loss and one metastatic case showed no TERT promoter/ATRX alterations. In conclusion ATRX loss and TERT promoter mutations are only found in (pre)malignant conjunctival melanocytic lesions, with most metastatic cases harboring one of these alterations, suggesting that both alterations are associated with adverse behavior. Similar to TERT promoter mutations, ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to having an adverse course.

Assessment of lipid and pigment content in suspicious melanocytic lesions to improve melanoma detection.

Melanoma is a highly aggressive form of skin cancer and the most frequent lethal malignancy diagnosed by dermatologists. Although there have been advances for predicting melanoma prognosis, there are few highly sensitive and specific diagnostic tools for clinically evaluating suspicious melanocytic lesions prior to biopsy. We have recently determined that alterations in cellular lipid and pigment content are associated with tumor progression and melanoma metastasis. Here, we seek to determine if lipid droplet and pigment content assessments near the skin's surface are able to distinguish benign from malignant melanocytic lesions. We obtained 14 benign melanocytic lesions, classified as Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) class 1, and 22 malignant melanomas, classified as MPATH-Dx class 4 or 5, from Boston Medical Center. The malignant melanomas had an average greatest thickness of 1.8 ± 2.1 mm with 7/22 biopsies showing the presence of ulceration. Tissues were stained with the Fontana Masson stain to detect pigment or immunohistochemically stained for adipophilin, the main protein component of lipid droplets, to detect lipid droplets. Pigment and lipid droplets were quantified using ImageJ and CellProfiler, respectively. We found no significant difference in total pigment area between benign melanocytic lesions and malignant melanoma, and a 66% decrease in lipid content and 68% reduction in lipid/pigment content between benign melanocytic lesions and malignant melanoma ( P < 0.05). Our results suggest that lipid content and lipid/pigment content ratios may distinguish benign and malignant melanocytic lesions, which may be useful as a diagnostic tool for histopathologically challenging pigmented lesions.

PRAME Expression in Mucosal Melanoma of the Head and Neck Region.

PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal melanocytic tumors of the head and neck region to compare 3 different scores and evaluate the most reliable one in this diagnostic set. Immunohistochemical analysis for PRAME was performed in 54 benign and malignant mucosal melanocytic tumors of the head and neck region collected from 41 patients. The best-performing cutoff of PRAME-positive cells (nuclear stain) to differentiate benign and malignant mucosal melanocytic tumors of the head and neck region is that proposed by Raghavan and colleagues (<60%/≥60% of PRAME-positive cells), with 100% and 77.8% of benign lesions and malignant tumors respectively correctly identified. Applying this score, PRAME stain showed the best results (sensitivity, specificity, accuracy, and positive and negative predictive values) for the diagnosis of head and neck melanocytic tumors. However, a subset of PRAME-negative malignant tumors was identified, especially located in the palatal area (hard and soft palate). Finally, high PRAME expression (≥60%) was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex.

The dark areas of esophagus: Esophageal melanocytosis

Esophageal melanocytosis characterized by melanocytic proliferation in the epithelium of esophagus is extremely rare disease. Aberrant migration of melanocytes during embryogenesis occurs in a small number of cases. Hence, the occurrence of benign and malignant melanocytic lesions is now known entities in esophagus. Melanocytosis is a benign entity and is very rare with an incidence of 0.07%–2.1%. The etiology of these lesions is not known. Endoscopic, histologic, and staining characteristics of two lesions are described. These cases were diagnosed from 450 endoscopic biopsies studied over a period of 10 months.

Dynamic Optical Coherence Tomography: A Non-Invasive Imaging Tool for the Distinction of Nevi and Melanomas

Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic lesions has become essential. Unclear cases may require the aid of non-invasive imaging to reduce unnecessary biopsies. This multicentric, case-control study evaluated the potential of dynamic optical coherence tomography (D-OCT) to identify distinguishing microvascular features in nevi. A total of 167 nevi, including dysplastic ones, on 130 participants of all ages and sexes were examined by D-OCT and dermoscopy with a histological reference. Three blinded analyzers evaluated the lesions. Then, we compared the features to those in 159 melanomas of a prior D-OCT study and determined if a differential diagnosis was possible. We identified specific microvascular features in nevi and a differential diagnosis of melanomas and nevi was achieved with excellent predictive values. We conclude that D-OCT overcomes OCT´s inability to distinguish melanocytic lesions based on its focus on microvascularization. To determine if an addition to the gold standard of a clinical-dermoscopic examination improves the diagnosis of unclear lesions, further studies, including a larger sample of dysplastic nevi and artificial intelligence, should be conducted.

Hyperspectral Imaging for Non-invasive Diagnostics of Melanocytic Lesions.

Malignant melanoma poses a clinical diagnostic problem, since a large number of benign lesions are excised to find a single melanoma. This study assessed the accuracy of a novel non-invasive diagnostic technology, hyperspectral imaging, for melanoma detection. Lesions were imaged prior to excision and histopathological analysis. A deep neural network algorithm was trained twice to distinguish between histopathologically verified malignant and benign melanocytic lesions and to classify the separate subgroups. Furthermore, 2 different approaches were used: a majority vote classification and a pixel-wise classification. The study included 325 lesions from 285 patients. Of these, 74 were invasive melanoma, 88 melanoma in situ, 115 dysplastic naevi, and 48 non-dysplastic naevi. The study included a training set of 358,800 pixels and a validation set of 7,313 pixels, which was then tested with a training set of 24,375 pixels. The majority vote classification achieved high overall sensitivity of 95% and a specificity of 92% (95% confidence interval (95% CI) 0.024-0.029) in differentiating malignant from benign lesions. In the pixel-wise classification, the overall sensitivity and specificity were both 82% (95% CI 0.005-0.005). When divided into 4 subgroups, the diagnostic accuracy was lower. Hyperspectral imaging provides high sensitivity and specificity in distinguishing between naevi and melanoma. This novel method still needs further validation.

Genetic and Methylation Analysis of CTNNB1 in Benign and Malignant Melanocytic Lesions.

Simple SummaryRecurrent CTNNB1 exon 3 mutations have been recognized in the distinct group of melanocytic tumors showing deep penetrating nevus-like morphology and in 1–2% of advanced melanoma. We performed a detailed genetic analysis of difficult-to-classify nevi and melanomas with CTNNB1 mutations and found that benign tumors (nevi) show characteristic morphological, genetic and epigenetic traits, which distinguish them from other nevi and melanoma. Malignant CTNNB1-mutant tumors (melanoma) demonstrated a different genetic profile, grouping clearly with other non-CTNNB1 melanomas in methylation assays. To further evaluate the role of CTNNB1 mutations in melanoma, we assessed a large cohort of clinically sequenced melanomas, identifying 38 tumors with CTNNB1 exon 3 mutations, including recurrent S45 (n = 13, 34%), G34 (n = 5, 13%), and S27 (n = 5, 13%) mutations. Locations and histological subtype of CTNNB1-mutated melanoma varied; none were reported as showing deep penetrating nevus-like morphology. The most frequent concurrent activating mutations were BRAF V600 (55%) and NRAS Q61 (34%).Melanocytic neoplasms have been genetically characterized in detail during the last decade. Recurrent CTNNB1 exon 3 mutations have been recognized in the distinct group of melanocytic tumors showing deep penetrating nevus-like morphology. In addition, they have been identified in 1–2% of advanced melanoma. Performing a detailed genetic analysis of difficult-to-classify nevi and melanomas with CTNNB1 mutations, we found that benign tumors (nevi) show characteristic morphological, genetic and epigenetic traits, which distinguish them from other nevi and melanoma. Malignant CTNNB1-mutant tumors (melanomas) demonstrated a different genetic profile, instead grouping clearly with other non-CTNNB1 melanomas in methylation assays. To further evaluate the role of CTNNB1 mutations in melanoma, we assessed a large cohort of clinically sequenced melanomas, identifying 38 tumors with CTNNB1 exon 3 mutations, including recurrent S45 (n = 13, 34%), G34 (n = 5, 13%), and S27 (n = 5, 13%) mutations. Locations and histological subtype of CTNNB1-mutated melanoma varied; none were reported as showing deep penetrating nevus-like morphology. The most frequent concurrent activating mutations were BRAF V600 (n = 21, 55%) and NRAS Q61 (n = 13, 34%). In our cohort, four of seven (58%) and one of nine (11%) patients treated with targeted therapy (BRAF and MEK Inhibitors) or immune-checkpoint therapy, respectively, showed disease control (partial response or stable disease). In summary, CTNNB1 mutations are associated with a unique melanocytic tumor type in benign tumors (nevi), which can be applied in a diagnostic setting. In advanced disease, no clear characteristics distinguishing CTNNB1-mutant from other melanomas were observed; however, studies of larger, optimally prospective, cohorts are warranted.

Application of immunohistochemical staining of PRAME in differential diagnosis between melanoma and melanocytic nevus

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) in differential diagnosis of benign and malignant cutaneous melanocytic lesions. Methods: Fifty-nine cases of melanoma (50 cases of skin primary melanoma, and 9 cases of metastatic melanoma) and 48 cases of melanocytic nevus (40 cases of common nevus and 8 cases of dysplastic nevus) were subject to PRAME immunohistochemistry staining.The difference of PRAME expression between melanoma and melanocytic nevus was analyzed. Results: Among the 50 patients with primary cutaneous melanoma, there were 23 males and 27 females ranging in age from 33 to 87 years (average age 62.4 years, median age 64.5 years). Among the 9 metastatic melanoma there were 7 males and 2 females ranging in age from 40 to 82 years (average age 64 years, median age 65 years). Twenty-six cases (26/50, 52.0%) of cutaneous primary melanoma and 4 cases (4/9) of metastatic melanoma showed diffuse positive PRAME staining. 40 cases (40/40, 100%) of common nevus and 8 (8/8) cases of dysplastic nevus were PRAME negative. Compared with melanocytic nevus group, the melanoma group included more cases with diffuse positive PRAME staining (P<0.05). The sensitivity and specificity of using PRAME to differentiate primary cutaneous melanoma from melanocytic nevus in the cohort is 52.0% and 100%. Conclusions: There is a significant difference in the expression of PRAME between melanoma and melanocytic nevus.Thus, PRAME can be used as an auxiliary diagnostic tool for differentiating benign from malignant cutaneous lesions.

Immunohistochemistry in melanocytic lesions: Updates with a practical review for pathologists.

This review provides a summary of the immunohistochemical markers pertinent to the diagnosis of melanocytic lesions. There is considerable morphologic overlap between benign and malignant melanocytic lesions, and given the significant differences in clinical management, the diagnostic workup becomes crucial. Immunohistochemistry aids in the distinction between various melanocytic proliferations and recent contributions to the literature have furthered our optimization of panels in the diagnostic workup. In recent years, SOX10 has been considered as the optimal marker for melanocytic lesions given the similar sensitivity but higher specificity than S100. HMB-45 is less sensitive than S100 but demonstrates utility in confirmation of deceptively banal small cell and nevoid melanoma variants where deep nests of melanocytes are highlighted. Melan-A (MART-1) and MiTF show similar sensitivity to S100 however there is a lack of expression in spindle cell and desmoplastic melanomas.

PRAME immunohistochemistry for melanoma diagnosis: A STARD-compliant diagnostic accuracy study.

Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that is frequently expressed in cutaneous melanoma and can be evaluated by immunohistochemistry. Earlier studies on PRAME utilized case-control study designs that may misestimate diagnostic accuracy and lack generalizability. Using retrospective cohort selection, a cross-sectional study of diagnostic accuracy of PRAME was conducted according to standards for reporting diagnostic accuracy studies requirements. Mean PRAME positive fraction was higher in 42 malignant melanocytic lesions than 101 benign melanocytic lesions (0.71 ± 0.30 vs. 0.13 ± 0.20, p < 0.01). Receiver operating characteristic curve showed the test was effective (area under the curve=0.90). Global PRAME 4+ scores (>75%) were associated with sensitivity of 0.63, specificity of 0.97, accuracy of 0.87, and excellent interrater concordance (Kappa=0.83). Lower cutoffs for PRAME of 2+ (>25%) and 3+ (>50%) produced higher joint sensitivity/specificity (Youden index) than PRAME 4+, but lower accuracy. PRAME as it is used in clinical practice is an effective test for melanoma. PRAME is best used as an ordinal variable to calculate the posttest probability of melanoma. PRAME ≤25% (0/1+) favors nevus, PRAME 26%-75% (2/3+) is noncontributory, and PRAME >75% (4+) favors melanoma.

Multicenter prospective clinical trial of molecular genetic markers for non-invasive differential diagnosis of benign and malignant melanocytic skin lesions.

e21581 Background: Improving the accuracy of non-invasive diagnosis of skin tumors is becoming an urgent problem, given the clear increase in the incidence of melanoma in many countries. Dermoscopy and examination by an experienced dermatologist can reduce the NNE to 5–10 per melanoma (M) detected, however, achieving even this, clearly suboptimal, rate requires a long specialist training. Methods: We report results of prospective nonrandomized trial evaluating sensitivity and specificity of RNA profiling of cytological samples from adhesive transparent patches (ATP) applied to skin lesions. Routine pathology reports were obtained for all surgery samples. RNA extracted from ATP specimens (N = 126) was tested for mRNA expression of PRAME and LINC00518 genes. GAPDH was used as a reference gene. Sample was considered marker-positive if either PRAME or LINC00518 expression was detected. Results: Between June 2021 and November 2021, 126 pts undegoing excisional biopsy of skin lesions were included in the study at 5 centers. On pathology, invasive M was detected in 49 (38.9%) patients (mean Breslow thickness was 2.41 mm [95%CI 1,44 to 3.37]), M in situ in 6 (4.8%), non-melanoma skin cancer in 4 (3.2%) and dysplastic nevus in 56 (44.4%). In the day of preplanned excision ATP was applied to the target lesion for 5–6 min and sent to the central lab. Amplifiable mRNA was found in all 126 ATP samples. 82 samples of 126 (65,1%) tested marker-positive. Sensitivity of RNA profiling for detection of skin cancers reached 88.14% (95% CI 77.07% – 95.09%), while specificity was only 53.85% (41.03% – 66.30%), with PPV of 63.41% (56.74% – 69.61%), NPV of 83.33% (70.65% – 91.22%) and accuracy of 70.16% (61.29% – 78.04%). Among the seven false negative results there were 3 M in situ and 4 invasive M. Conclusions: RNA profiling of skin ATP specimens is feasible and has high sensitivity but rather low specificity. Randomized studies are needed to evaluate if this technique can add anything to dermoscopy or other noninvasive diagnostic modalities. Clinical trial information: NCT04353050. [Table: see text]

070 (When) should we biopsy a vulvar naevus in a child or adolescent?

Objective: Decision-making regarding pigmented genital lesions in childhood or adolescence may be difficult. These are ‘special-site’ nevi1 and generally have a benign clinical course even when seeming clinically worrisome or showing disconcerting histological signs of atypia or dysplasia [ [1] Ahn C.S. Guerra A. Sangüeza O.P. Melanocytic nevi of special sites. Am J Dermatopathol. 2016; 38: 867-878 Crossref PubMed Scopus (15) Google Scholar ], especially when the naevus is in a background of vulvar lichen sclerosus (VLS) in a juvenile [ 2 Pinto A. McLaren S.H. Poppas D.P. Magro C.M. Genital melanocytic nevus arising in a background of lichen sclerosus in a 7-year-old female: The diagnostic pitfall with malignant Melanoma. A literature review. Am J Dermatopathol. 2012; 34: 838-843 Crossref PubMed Scopus (17) Google Scholar , 3 La Spina M. Meli M.C. De Pasquale R. Perrotta R.E. Lanzafame F. Caltabiano R. et al. Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and Literature Review. Pediatr Dermatol. 2016; 33: E190-E194 Crossref PubMed Scopus (17) Google Scholar ]. The clinician would like to rule out malignant melanoma. Few case studies of vulvar melanoma in juveniles have been published, and those cases reported were generally found with concomitant VLS, making histopathological analysis complex [ 2 Pinto A. McLaren S.H. Poppas D.P. Magro C.M. Genital melanocytic nevus arising in a background of lichen sclerosus in a 7-year-old female: The diagnostic pitfall with malignant Melanoma. A literature review. Am J Dermatopathol. 2012; 34: 838-843 Crossref PubMed Scopus (17) Google Scholar , 3 La Spina M. Meli M.C. De Pasquale R. Perrotta R.E. Lanzafame F. Caltabiano R. et al. Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and Literature Review. Pediatr Dermatol. 2016; 33: E190-E194 Crossref PubMed Scopus (17) Google Scholar , 4 Schaffer J.V. Orlow S.J. Melanocytic proliferations in the setting of vulvar lichen sclerosus: diagnostic considerations. Pediatr Dermatol. 2005; 22 (author reply 8–9): 276-278 Crossref PubMed Scopus (13) Google Scholar ]. Studying the prevalence of malignant melanocytic vulvar lesions in juveniles could support clinicians when deciding whether or not to biopsy.

Dermoscopic features of eyelid margin tumors: A single-center retrospective study.

Despite rapid growth in the significance of dermoscopy in dermatological oncology, relatively little is yet known about the dermoscopic patterns of eyelid margin tumors. The aim of the study was to analyze the dermoscopic features of eyelid margin tumors. This was a retrospective, single-center, consecutive study which included clinical and dermoscopic analysis of eyelid margin tumors diagnosed at the Department of Dermatology, Venereology and Allergology at the Medical University of Gdańsk from 1 June 2016 to 31 December 2020. Dermoscopic features significantly more prevalent in malignant non-melanocytic lesions compared to benign ones were alteration in eyelash growth, structureless pink areas, starry milia-like cysts, and perpendicular vessels. In contrast, there were no dermoscopic features that occurred significantly more frequently in malignant melanocytic lesions when compared to benign ones. Basal cell carcinoma, in comparison to hidrocystoma, more commonly presented with ulceration and structureless pink areas. The main features differentiating basal cell carcinoma from dermal nevus were the presence of ulceration, alteration in eyelash growth, structureless pink and structureless white areas, and perpendicular vessels within the tumor with each of these features observed more commonly in basal cell carcinoma. Blue nevus, hemangioma, or pigmented hidrocystoma presenting exclusively with blue structureless areas may be difficult to differentiate based on dermoscopy. The study offers additional dermoscopic clues in the assessment of eyelid margin tumors. Some observations reported previously to be typical of basal cell carcinoma (e.g., linear vessels arranged perpendicularly to the eyelid margin) were documented also within the normal eyelid margin accompanying other cases, and according to our study, cannot be useful as a pathognomonic feature. In contrast, it seems that yellow structures (half-moon sign, starry milia-like cysts) may be important dermoscopic features, though further studies are needed to confirm our observations.

PRAME immunohistochemistry of spitzoid neoplasms.

Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. Ten Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved, and PRAME IHC was scored on a scale of 1-4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36, respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. Previous reports revealed PRAME IHC as useful tool to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors.