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The American Journal of Pathology Jul 2023Early detection and treatment of melanoma, the most aggressive skin cancer, improves the median 5-year survival rate of patients from 25% to 99%. Melanoma development...
Early detection and treatment of melanoma, the most aggressive skin cancer, improves the median 5-year survival rate of patients from 25% to 99%. Melanoma development involves a stepwise process during which genetic changes drive histologic alterations within nevi and surrounding tissue. Herein, a comprehensive analysis of publicly available gene expression data sets of melanoma, common or congenital nevi (CN), and dysplastic nevi (DN), assessed molecular and genetic pathways leading to early melanoma. The results demonstrate several pathways reflective of ongoing local structural tissue remodeling activity likely involved during the transition from benign to early-stage melanoma. These processes include the gene expression of cancer-associated fibroblasts, collagens, extracellular matrix, and integrins, which assist early melanoma development and the immune surveillance that plays a substantial role at this early stage. Furthermore, genes up-regulated in DN were also overexpressed in melanoma tissue, supporting the notion that DN may serve as a transitional phase toward oncogenesis. CN collected from healthy individuals exhibited different gene signatures compared with histologically benign nevi tissue located adjacent to melanoma (adjacent nevi). Finally, the expression profile of microdissected adjacent nevi tissue was more similar to melanoma compared with CN, revealing the melanoma influence on this annexed tissue.
Topics: Humans; Melanoma; Nevus; Skin Neoplasms; Dysplastic Nevus Syndrome; Gene Expression Profiling
PubMed: 37146966
DOI: 10.1016/j.ajpath.2023.03.016 -
Acta Dermato-venereologica May 2023
Topics: Humans; Turner Syndrome; Melanoma; Skin Neoplasms; Dysplastic Nevus Syndrome
PubMed: 37144513
DOI: 10.2340/actadv.v103.5586 -
Skin Research and Technology : Official... Apr 2023Phacomatosis pigmentokeratotica (PPK) is a distinct and rare type of epidermal nevus syndrome characterized by coexisting nonepidermolytic organoid sebaceous nevus (SN)...
Noninvasive imaging exploration of phacomatosis pigmentokeratotica using high-frequency ultrasound and optical coherence tomography: Can biopsy of PPK patients be avoided?
BACKGROUND
Phacomatosis pigmentokeratotica (PPK) is a distinct and rare type of epidermal nevus syndrome characterized by coexisting nonepidermolytic organoid sebaceous nevus (SN) with one or more speckled lentiginous nevi (SLN). Atypical nevi including compound Spitz and compound dysplastic may manifest within regions of SLN. Patients with PPK, or similar atypical nevus syndromes, may be subject to a significant lifetime number of biopsies, leading to pain, scarring, anxiety, financial burden, and decreased quality of life. The current literature includes case reports, genetics, and associated extracutaneous symptoms of PPK, but use of noninvasive imaging techniques have not been explored. We aim to investigate the value of high-frequency ultrasound (HFUS) and optical coherence tomography (OCT) in discriminating morphological features of pigmented lesions and nevus sebaceous within one patient with PPK.
MATERIALS AND METHODS
Two modalities, (1) HFUS imaging, based on acoustic properties and (2) OCT imaging, based on optical properties, were used to image a patient with PPK. Benign pigmented lesions, which may raise clinical suspicion for significant atypia, and nevus sebaceous, were selected on different areas of the body to be studied.
RESULTS
Five pigmented lesions and one area of nevus sebaceous were imaged and analyzed for noninvasive features. Distinct patterns of hypoechoic features were seen on HFUS and OCT.
CONCLUSION
HFUS provides a deep view of the tissue, with ability to differentiate gross structures beneath the skin. OCT provides a smaller penetration depth and a higher resolution. We have described noninvasive features of atypical nevi and nevus sebaceous on HFUS and OCT, which indicate benign etiology.
Topics: Humans; Tomography, Optical Coherence; Quality of Life; Skin Neoplasms; Nevus; Biopsy
PubMed: 37113090
DOI: 10.1111/srt.13279 -
Biomedical Optics Express Apr 2023Early detection of skin pathologies with current clinical diagnostic tools is challenging, particularly when there are no visible colour changes or morphological cues...
Early detection of skin pathologies with current clinical diagnostic tools is challenging, particularly when there are no visible colour changes or morphological cues present on the skin. In this study, we present a terahertz (THz) imaging technology based on a narrow band quantum cascade laser (QCL) at 2.8 THz for human skin pathology detection with diffraction limited spatial resolution. THz imaging was conducted for three different groups of unstained human skin samples (benign naevus, dysplastic naevus, and melanoma) and compared to the corresponding traditional histopathologic stained images. The minimum thickness of dehydrated human skin that can provide THz contrast was determined to be 50 µm, which is approximately one half-wavelength of the THz wave used. The THz images from different types of 50 µm-thick skin samples were well correlated with the histological findings. The per-sample locations of pathology vs healthy skin can be separated from the density distribution of the corresponding pixels in the THz amplitude-phase map. The possible THz contrast mechanisms relating to the origin of image contrast in addition to water content were analyzed from these dehydrated samples. Our findings suggest that THz imaging could provide a feasible imaging modality for skin cancer detection that is beyond the visible.
PubMed: 37078035
DOI: 10.1364/BOE.480615 -
International Journal of Molecular... Mar 2023PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen that is frequently expressed in melanoma compared to benign melanocytic proliferations...
PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen that is frequently expressed in melanoma compared to benign melanocytic proliferations and nevi. However, the interpretation of the intensity and distribution of PRAME immunostaining is not standardized a lot, which makes interpretation difficult. PRAME-stained histological slides of superficial spreading melanomas (SSM) and dysplastic nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. -tests and ROC AUCs were performed with SPSS. A -value of <0.05 was used for statistical significance, and a ROC AUC score of >0.8 was considered a good result. A cut-off score was defined in an evaluation cohort and subsequently analyzed in an independent validation cohort. In total, 81 PRAME-stained specimens were included. The evaluation cohort included 32 (50%) SSM and 32 (50%) DN, and the mean of PRAME-positive cells/mm for the entire lesion was 455.3 (SD 428.2) in SSM and 60.5 (SD 130.1; < 0.001) in DN. The ROC AUC of PRAME-positive cells of the entire lesion was 0.866, and in the epidermis it was 0.901. The defined cut-off score to distinguish between DN and SSM was 97.67 cells/mm. In the validation cohort, 16 out of 17 cases (94.1%) were correctly classified by the cut-off score. The computer-aided assessment of PRAME immunostaining is a useful tool in dermatopathology to distinguish between DN and SSM. Lesions with a moderate expression and indifferent morphologic features will remain a challenge for dermatopathologists.
Topics: Male; Humans; Dysplastic Nevus Syndrome; Skin Neoplasms; Melanoma; Nevus; Transcription Factors; Antigens, Neoplasm; Diagnosis, Differential; Melanoma, Cutaneous Malignant
PubMed: 37047361
DOI: 10.3390/ijms24076388 -
Dermatology Practical & Conceptual Apr 2023Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi.
INTRODUCTION
Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi.
OBJECTIVES
This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi.
METHODS
From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal.
RESULTS
Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna.
CONCLUSIONS
Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.
PubMed: 36947065
DOI: 10.5826/dpc.1302a122 -
The Journal of Clinical Investigation May 2023Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a mosaic RASopathy characterized by the association of dysplastic skeletal lesions, congenital skin nevi of...
Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a mosaic RASopathy characterized by the association of dysplastic skeletal lesions, congenital skin nevi of epidermal and/or melanocytic origin, and FGF23-mediated hypophosphatemia. The primary physiological source of circulating FGF23 is bone cells. However, several reports have suggested skin lesions as the source of excess FGF23 in CSHS. Consequently, without convincing evidence of efficacy, many patients with CSHS have undergone painful removal of cutaneous lesions in an effort to normalize blood phosphate levels. This study aims to elucidate whether the source of FGF23 excess in CSHS is RAS mutation-bearing bone or skin lesions. Toward this end, we analyzed the expression and activity of Fgf23 in two mouse models expressing similar HRAS/Hras activating mutations in a mosaic-like fashion in either bone or epidermal tissue. We found that HRAS hyperactivity in bone, not skin, caused excess of bioactive intact FGF23, hypophosphatemia, and osteomalacia. Our findings support RAS-mutated dysplastic bone as the primary source of physiologically active FGF23 excess in patients with CSHS. This evidence informs the care of patients with CSHS, arguing against the practice of nevi removal to decrease circulating, physiologically active FGF23.
Topics: Animals; Mice; Disease Models, Animal; Fibroblast Growth Factors; Hypophosphatemia; Nevus; Skin Neoplasms; Syndrome
PubMed: 36943390
DOI: 10.1172/JCI159330 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Dysplastic Nevus Syndrome; Melanoma; Skin Neoplasms; Nevus
PubMed: 36922333
DOI: 10.1016/j.abd.2021.12.011 -
Acta Dermato-venereologica Mar 2023
Topics: Humans; Dysplastic Nevus Syndrome; Skin Neoplasms; Melanoma; Neural Networks, Computer; Melanoma, Cutaneous Malignant
PubMed: 36916955
DOI: 10.2340/actadv.v103.4822 -
Cancers Jan 2023: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears for 70% of tumors.... (Review)
Review
: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. : To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. : A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I statistic. : A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39-63%) with high heterogeneity at I: 95.8% ( < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51-77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36-75%). Only 2 studies are found reporting NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63-78%). : The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype.
PubMed: 36765817
DOI: 10.3390/cancers15030856