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PURPOSE OF REVIEW: Melanoma in younger individuals has different clinical presentations, histologic characteristics and prognosis from older patients. This review summarizes key differences and important new insights into pediatric and young adult melanoma, as well as recent evolutions in treatment. RECENT FINDINGS: Molecular techniques have improved the classification of melanocytic neoplasms, and are especially useful in the workup of the diagnostically challenging lesions frequent in this age group. Molecular evaluation highlights differences between melanoma and atypical lesions with Spitz-like morphology, and should routinely be incorporated for diagnosing and classifying Spitzoid melanocytic to guide prognostication and treatment. Once diagnosed, the management of bona fide melanoma in children and young adults is largely similar to older patients, while the optimal management of lesions such as atypical Spitz tumors remains uncertain. Increased awareness of the presentation and diagnostic characteristics of melanoma in young individuals will allow earlier detection, and improved diagnostic techniques will allow optimum management without over- or under-treatment.
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Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/patología , Melanoma/terapia , Melanoma/clasificación , Niño , Adulto Joven , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/clasificación , Pronóstico , Adolescente , Adulto , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/patología , Nevo de Células Epitelioides y Fusiformes/terapiaRESUMEN
The histopathological classification of melanocytic tumours with spitzoid features remains a challenging task. We confront the complexities involved in the histological classification of these tumours by proposing machine learning (ML) algorithms that objectively categorise the most relevant features in order of importance. The data set comprises 122 tumours (39 benign, 44 atypical and 39 malignant) from four different countries. BRAF and NRAS mutation status was evaluated in 51. Analysis of variance score was performed to rank 22 clinicopathological variables. The Gaussian naive Bayes algorithm achieved in distinguishing Spitz naevus from malignant spitzoid tumours with an accuracy of 0.95 and kappa score of 0.87, utilising the 12 most important variables. For benign versus non-benign Spitz tumours, the test reached a kappa score of 0.88 using the 13 highest-scored features. Furthermore, for the atypical Spitz tumours (AST) versus Spitz melanoma comparison, the logistic regression algorithm achieved a kappa value of 0.66 and an accuracy rate of 0.85. When the three categories were compared most AST were classified as melanoma, because of the similarities on histological features between the two groups. Our results show promise in supporting the histological classification of these tumours in clinical practice, and provide valuable insight into the use of ML to improve the accuracy and objectivity of this process while minimising interobserver variability. These proposed algorithms represent a potential solution to the lack of a clear threshold for the Spitz/spitzoid tumour classification, and its high accuracy supports its usefulness as a helpful tool to improve diagnostic decision-making.
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Aprendizaje Automático , Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Nevo de Células Epitelioides y Fusiformes/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Masculino , Femenino , Melanoma/patología , Melanoma/diagnóstico , Melanoma/genética , Adulto , Adolescente , Adulto Joven , Niño , Persona de Mediana Edad , Preescolar , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genética , Lactante , Mutación , AncianoRESUMEN
Childhood melanoma is a rare and biologically heterogeneous pediatric malignancy. The differential diagnosis of pediatric melanoma is usually broad, including a wide variety of spindle cell or epithelioid neoplasms. Different molecular alterations affecting the MAPK and PI3K/AKT/mTOR pathways, tumor suppressor genes, and telomerase reactivation have been implicated in melanoma tumorigenesis and progression. Here, we report a novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and an aggressive clinical course.
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Glicina , Melanoma , Nevo de Células Epitelioides y Fusiformes , Proteínas de Fusión Oncogénica , Pirroles , Neoplasias Cutáneas , Niño , Humanos , Diagnóstico Diferencial , Glicina/análogos & derivados , Complejo Mediador , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Fosfatidilinositol 3-Quinasas , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Proteínas de Fusión Oncogénica/genéticaRESUMEN
Drivers of Spitz neoplasms include activating point mutations in HRAS and Spitz-associated genomic fusions. It has become evident that some BRAF -mutated melanocytic neoplasms can morphologically mimic Spitz tumors (STs). These have been termed BRAF mutated and morphologically spitzoid (BAMS). In this study, 17 experts from the International Melanoma Pathology Study Group assessed 54 cases which included 40 BAMS and 14 true STs. The participants reviewed the cases blinded to the genomic data and selected among several diagnostic options, including BAMS, ST, melanoma, and other. A total of 38% of all diagnostic selections in the BAMS cases were for BAMS, whereas 32% were for ST. In 22 of the BAMS cases, the favored diagnosis was BAMS, whereas in 17 of the BAMS cases, the favored diagnosis was ST. Among the 20 cases in the total group of 54 with the highest number of votes for ST, half were BAMS. Of BAMS, 75% had a number of votes for ST that was within the SD of votes for ST seen among true ST cases. There was poor interobserver agreement for the precise diagnosis of the BAMS (kappa = 0.16) but good agreement that these cases were not melanoma (kappa = 0.7). BAMS nevi/tumors can closely mimic Spitz neoplasms. Expert melanoma pathologists in this study favored a diagnosis of ST in nearly half of the BAMS cases. There are BAMS cases that even experts cannot morphologically distinguish from true Spitz neoplasms.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Nevo , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Proteínas Proto-Oncogénicas B-raf/genética , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Nevo/diagnóstico , Diagnóstico DiferencialRESUMEN
Over the last 75 years, our understanding of Spitz lesions has undergone substantial evolution. Initially considered a specific type of melanoma, the perception has shifted towards recognizing Spitz lesions as a spectrum comprising Spitz nevi, Spitz melanocytomas, and Spitz melanomas. Spitz lesions are known for posing a significant diagnostic challenge regarding the distinction between benign neoplasms displaying atypical traits and melanomas. A comprehensive understanding of their molecular basis and genomic aberrations has significantly improved precision in classifying and diagnosing these challenging lesions. The primary aim of this review is to encapsulate the current understanding of the molecular pathogenesis and distinct clinicopathologic characteristics defining this intriguing set of tumors.
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Neoplasias Encefálicas , Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Genómica , SíndromeAsunto(s)
Antígenos de Neoplasias , Biomarcadores de Tumor , Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Nevo de Células Epitelioides y Fusiformes/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Antígenos de Neoplasias/análisis , Antígenos de Neoplasias/metabolismo , Melanoma/diagnóstico , Melanoma/patología , Melanoma/genética , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Masculino , Femenino , Inmunohistoquímica , Adulto , Persona de Mediana Edad , AdolescenteRESUMEN
Spitz lesions represent a spectrum of melanocytic proliferations, and they include Spitz nevi, atypical Spitz tumors, and Spitz melanomas. Atypical Spitz tumors are intermediate melanocytic lesions with features between benign Spitz nevi and malignant Spitz melanomas. They often present a diagnostic challenge to pathologists and dermatologists alike because they can mimic melanoma, especially high-grade atypical Spitz tumors. Importantly, they present a relevant clinical management challenge because definite recommendations for their management and treatment have not yet been established. Here we present the case of a young patient with a high-grade atypical Spitz tumor along with the diagnostic procedure and further management. We also review potential pitfalls in the literature that should alert clinicians to the more aggressive potential of the lesion, such as some BRAF fusions.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Incertidumbre , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Melanocitos , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo Pigmentado/diagnóstico , Diagnóstico DiferencialRESUMEN
Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Proteínas Tirosina Quinasas/genética , Homocigoto , Proteínas Proto-Oncogénicas/genética , Eliminación de Secuencia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
BACKGROUND: Previous studies suggest that Spitz neoplasms occur primarily in younger patients, leading pathologists to shy away from diagnosing a benign Spitz neoplasm in the elderly. With the advent of genomic sequencing, there is a need for reappraisal of the epidemiology of Spitz neoplasms in the modern molecular era. OBJECTIVE: We aim to reassess the epidemiology of Spitz neoplasms incorporating next-generation sequencing. METHODS: We looked at 53,814 non-Spitz neoplasms and 1260 Spitz neoplasms including 286 Spitz neoplasms with next-generation sequencing testing and collected various epidemiologic data. RESULTS: In our general pool of cases, the proportion of Spitz neoplasm cases occurring is relatively the same in each of the first 4 decades of life with a precipitous drop in the fifth decade. In assessing a group of genomically verified cases of Spitz neoplasms, the drop was much less significant and up to 20% of all Spitz neoplasm cases occurred in patients over 50 years of age. LIMITATIONS: Limitations included the number of genetically verified Spitz neoplasm cases available and a possible bias as to which cases undergo genomic testing. CONCLUSION: Genomic verification may allow more confident diagnosis of Spitz neoplasms in patients over 50 years of age and avoid melanoma overdiagnosis.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Persona de Mediana Edad , Anciano , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/genética , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/epidemiología , Nevo de Células Epitelioides y Fusiformes/genética , Estudios Retrospectivos , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/genética , Diagnóstico DiferencialRESUMEN
ABSTRACT: Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with ß-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME was negative in most DPN (n = 10/10, n = 9/10, one case with discrepancy between readers) and all BN (n = 16/16), while the 2 melanomas included were positive (n = 2/2). All DPN were positive for LEF1 (n = 9/9) while only a subset of BN were positive (n = 6/16, P = 0.0028; n = 5/16, P = 0.001, per both readers). LEF1 seemed to be easier to interpret than ß-catenin because of its nuclear pattern of expression. The expression of LEF1 in the regular nevus component of combined BN presents a potential pitfall in practice because it may lead to misinterpretation of LEF1 as positive in the BN component of the lesion. However, a subset (approximately one-third) of combined BN seemed to show true LEF1 expression. Taking into account pitfalls in interpretation, the combinatorial panel of PRAME and LEF1, in addition to conventional histopathological features, may be useful to distinguish CDPN from combined BN and other benign and malignant mimics.
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Melanoma , Nevo Azul , Nevo de Células Epitelioides y Fusiformes , Nevo , Neoplasias Cutáneas , Humanos , Nevo Azul/diagnóstico , Nevo Azul/patología , beta Catenina/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Factor de Unión 1 al Potenciador Linfoide , Melanoma/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo/diagnóstico , Nevo/patología , Factores de Transcripción , Diagnóstico Diferencial , Antígenos de NeoplasiasRESUMEN
ABSTRACT: Proliferative nodules (PNs) are benign melanocytic proliferations that typically develop within congenital melanocytic nevi. These tumors have overlapping histological features with melanoma. Ancillary immunohistochemistry and genomic sequencing are often used in diagnostically challenging cases. To assess the utility of preferentially expressed antigen in melanoma (PRAME) immunoreactivity and telomerase reverse transcriptase (TERT) promoter mutation analysis in distinguishing PNs from melanoma arising in congenital nevi cases. Twenty-one PNs and 2 melanomas arising in congenital nevi were immunohistochemically stained with PRAME. Cases with adequate tissue were also assessed for TERT promoter mutations through sequencing studies. The positivity rates in the PN cases were compared with those of the melanomas. Two of 21 PN cases were diffusely positive for PRAME (≥75% of the tumor cells positive). Two of 2 melanomas arising in congenital nevus cases were also diffusely PRAME positive. The difference was statistically significant using a Fisher exact test. None of the tumors harbored TERT promoter mutations. PRAME immunohistochemical marker may have diagnostic value in distinguishing diagnostically challenging PNs from melanoma, but diffuse expression is not specific for melanoma.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Neoplasias Cutáneas , Telomerasa , Humanos , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/genética , Nevo Pigmentado/congénito , Biomarcadores de Tumor/análisis , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Diagnóstico Diferencial , Telomerasa/genética , Antígenos de Neoplasias/análisisRESUMEN
BACKGROUND: PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that has been studied in various cutaneous melanocytic lesions. p16, on the other hand, has been proposed to aid in distinguishing between benign and malignant melanocytic neoplasms. Studies on the diagnostic utility of PRAME and p16 in combination in differentiating nevi from melanoma are limited. We aimed to assess the diagnostic utility of PRAME and p16 in melanocytic tumors and their role in distinguishing between malignant melanomas and melanocytic nevi. METHODS: This is a single-center retrospective cohort analysis over a 4-year period (2017-2020). We used the pathological database of malignant melanomas (77 cases) and melanocytic nevi (51 cases) specimens from patients who underwent shave/punch biopsies or surgical excisions and evaluated immunohistochemical staining percentage positivity and intensity for PRAME and p16. RESULTS: Most malignant melanomas showed positive/diffuse PRAME expression (89.6%); on the other hand, 96.1% of nevi did not express PRAME diffusely. p16 was expressed consistently in nevi (98.0%). However, p16 expression in malignant melanoma was infrequent in our study. PRAME had a sensitivity and specificity of 89.6% and 96.1%, respectively, for melanomas versus nevi; on the other hand, p16 had a sensitivity and specificity of 98.0% and 28.6%, respectively, for nevi versus melanoma. Also, a PRAME+/p16- melanocytic lesion is unlikely to be a nevus where most nevi were PRAME-/p16+. CONCLUSION: In conclusion, we confirm the potential utility of PRAME and p16 for distinguishing melanocytic nevi from malignant melanomas.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo , Melanoma/patología , Neoplasias Cutáneas/patología , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/patología , Nevo/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Antígenos de Neoplasias/análisis , Diagnóstico Diferencial , Melanoma Cutáneo MalignoRESUMEN
ABSTRACT: Telomerase reverse transcriptase promoter mutations (TPMs) have been shown to be common in melanoma and uncommon in benign nevi. To assess the use of TPMs as an ancillary diagnostic tool, we report the concordance of the TPM status with the final diagnosis in clinical cases with distinct differential diagnostic scenarios: dysplastic nevus versus melanoma, atypical Spitz nevus versus melanoma, atypical deep penetrating nevus (DPN) versus melanoma, and atypical blue nevus versus malignant blue nevus. In a control cohort, we found a positive TPM in 51/70 (73%) of the total melanomas with the highest frequency in vertical growth phase melanoma cases. Conversely, only 2/35 (6%) dysplastic nevi in our control cases were TPM-positive and b were severely atypical dysplastic nevi. Our clinical cohort of 257 cases had a positive TPM in 24% of cases diagnosed as melanoma and in 1% of cases with a benign diagnosis. The overall concordance of the TPM status with the final diagnosis was 86%. The TPM status had the greatest concordance (95%) with the final diagnosis in the atypical DPN versus melanoma group, with the rest of the groups ranging between 50% and 88%. Overall, our results suggest that TPMs are most useful in the differential diagnosis of atypical DPN versus melanoma. It also has some value in the differential diagnosis of atypical Spitz tumor versus melanoma and dysplastic nevus versus melanoma, whereas in our cohort, it did not contribute meaningfully to differentiating malignant blue nevus and atypical blue nevus.
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Síndrome del Nevo Displásico , Melanoma , Nevo Azul , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Neoplasias Cutáneas , Telomerasa , Humanos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Síndrome del Nevo Displásico/patología , Nevo Azul/diagnóstico , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Nevo Pigmentado/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Diagnóstico Diferencial , Telomerasa/genéticaAsunto(s)
Hemangioma , Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Diagnóstico Diferencial , Melanoma/diagnóstico , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Neoplasias Cutáneas/diagnóstico , Melanoma Cutáneo MalignoRESUMEN
Spitz neoplasms continue to be a diagnostic challenge for dermatopathologists and are defined by distinctive morphological and genetic features. With the recent advancements in genomic sequencing, the classification, diagnosis, and prognostication of these tumours have greatly improved. Several subtypes of Spitz neoplasms have been identified based on their specific genomic aberrations, which often correlate with distinctive morphologies and biological behaviour. These genetic driver events can be classified into four major groups, including: (1) mutations [HRAS mutations (with or without 11p amplification) and 6q23 deletions]; (2) tyrosine kinase fusions (ROS1, ALK, NTRK1-3, MET and RET); (3) serine/threonine kinase fusions and mutations (BRAF, MAP3K8, and MAP2K1); and (4) other rare genomic aberrations. These driver genomic events are hypothesised to enable the initial proliferation of melanocytes and are often accompanied by additional genomic aberrations that affect biological behaviour. The discovery of theses genomic fusions has allowed for a more objective definition of a Spitz neoplasm. Further studies have shown that the majority of morphologically Spitzoid appearing melanocytic neoplasms with aggressive behaviour are in fact BRAF or NRAS mutated tumours mimicking Spitz. Truly malignant fusion driven Spitz neoplasms may occur but are relatively uncommon, and biomarkers such as homozygous 9p21 (CDKN2A) deletions or TERT-p mutations can have some prognostic value in such cases. In this review, we discuss the importance and various methods of identifying Spitz associated genomic fusions to help provide more definitive classification. We also discuss characteristic features of the various fusion subtypes as well as prognostic biomarkers.
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Aberraciones Cromosómicas , Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Genómica , Melanoma/diagnóstico , Melanoma/genética , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genéticaRESUMEN
BACKGROUND: Spitzoid melanocytic neoplasms are diagnostically challenging; criteria for malignancy continue to evolve. The ability to predict chromosomal abnormalities with immunohistochemistry (IHC) could help select cases requiring chromosomal evaluation. METHODS: Fluorescence in situ hybridization (FISH)-tested spitzoid neoplasms at our institution (2013-2021) were reviewed. p16, BRAF V600E, and preferentially expressed antigen in melanoma (PRAME) IHC results were correlated with FISH. RESULTS: A total of 174 cases (1.9F:1M, median age 28 years; range, 5 months-74 years) were included; final diagnoses: Spitz nevus (11%), atypical Spitz tumor (47%), spitzoid dysplastic nevus (9%), and spitzoid melanoma (32%). Sixty (34%) were FISH positive, most commonly with absolute 6p25 gain (RREB1 > 2). Dermal mitotic count was the only clinicopathologic predictor of FISH. Among IHC-stained cases, p16 was lost in 55 of 134 cases (41%); loss correlated with FISH positive (p < 0.001, Fisher exact test). BRAF V600E (14/88, 16%) and PRAME (15/56, 27%) expression did not correlate with FISH alone (p = 0.242 and p = 0.359, respectively, Fisher exact test). When examined together, however, p16-retained/BRAF V600E-negative lesions had low FISH-positive rates (5/37, 14%; 4/37, 11% not counting isolated MYB loss); all other marker combinations had high rates (56%-75% of cases; p < 0.001). CONCLUSIONS: p16/BRAF V600E IHC predicts FISH results. "Low-risk" lesions (p16+ /BRAF V600E- ) uncommonly have meaningful FISH abnormalities (11%). PRAME may have limited utility in this setting.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Hibridación Fluorescente in Situ , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Aberraciones Cromosómicas , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Diagnóstico Diferencial , Antígenos de NeoplasiasAsunto(s)
Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Diagnóstico DiferencialRESUMEN
Although most melanocytic skin lesions are correctly diagnosed, numerous studies have shown interobserver disagreement. This review analyzes 20 molecules as immunohistochemical markers for distinguishing dysplastic and/or Spitz nevi from early melanomas (in situ, Clark level I or II and/or Breslow thickness at most 1 mm). The detected presence and/or level of tested molecules was significantly different in early melanomas than in dysplastic and Spitz nevi for six and seven potential markers, respectively. The most promising results were obtained for 5-hydroxymethylcytosine, cyclooxygenase-2 and PReferentially expressed Antigen in MElanoma whose levels were different in dysplastic and Spitz nevi compared to early melanomas.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Diagnóstico Diferencial , Inmunohistoquímica , Biomarcadores de Tumor , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Melanoma/diagnóstico , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Errores Diagnósticos , Melanoma Cutáneo MalignoAsunto(s)
Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Expresión Génica , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Diagnóstico Diferencial , Melanoma Cutáneo MalignoRESUMEN
OBJECTIVE: The integration of an artificial intelligence tool into pathologists' workflow may lead to a more accurate and timely diagnosis of melanocytic lesions, directly patient care. The objective of this study was to create and evaluate the performance of such a model in achieving clinical-grade diagnoses of Spitz nevi, dermal and junctional melanocytic nevi, and melanomas. METHODS: We created a beginner-level training environment by teaching our algorithm to perform cytologic inferences on 136,216 manually annotated tiles of hematoxylin and eosin-stained slides consisting of unequivocal melanocytic nevi, Spitz nevi, and invasive melanoma cases. We sequentially trained and tested our network to provide a final diagnosis-classification on 39 cases in total. Positive predictive value (precision) and sensitivity (recall) were used to measure our performance. RESULTS: The tile-classification algorithm predicted the 136,216 irrelevant, melanoma, melanocytic nevi, and Spitz nevi tiles at sensitivities of 96%, 93%, 94% and 73%, respectively. The final trained model was able to correctly classify and predict the correct diagnosis in 85.7% of unseen cases (n = 28), reporting at or near screening-level performances for precision and recall of melanoma (76.2%, 100.0%), melanocytic nevi (100.0%, 75.0%), and Spitz nevi (100.0%, 75.0%). CONCLUSIONS: Our pilot study proves that convolutional networks trained on cellular morphology to classify melanocytic proliferations can be used as a powerful tool to assist pathologists in screening for melanoma versus other benign lesions.