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Journal of the American Academy of... Aug 2016We recently demonstrated multilineage somatic mosaicism in cutaneous skeletal hypophosphatemia syndrome (CSHS), which features epidermal or melanocytic nevi, elevated... (Review)
Review
BACKGROUND
We recently demonstrated multilineage somatic mosaicism in cutaneous skeletal hypophosphatemia syndrome (CSHS), which features epidermal or melanocytic nevi, elevated fibroblast growth factor (FGF)-23, and hypophosphatemia, finding identical RAS mutations in affected skin and bone.
OBJECTIVE
We sought to: (1) provide an updated overview of CSHS; (2) review its pathobiology; (3) present a new patient with CSHS; and (4) discuss treatment modalities.
METHODS
We searched PubMed for "nevus AND rickets," and "nevus AND hypophosphatemia," identifying cases of nevi with hypophosphatemic rickets or elevated serum FGF-23. For our additional patient with CSHS, we performed histopathologic and radiographic surveys of skin and skeletal lesions, respectively. Sequencing was performed for HRAS, KRAS, and NRAS to determine causative mutations.
RESULTS
Our new case harbored somatic activating HRAS p.G13 R mutation in affected tissue, consistent with previous findings. Although the mechanism of FGF-23 dysregulation is unknown in CSHS, interaction between FGF and MAPK pathways may provide insight into pathobiology. Anti-FGF-23 antibody KRN-23 may be useful in managing CSHS.
LIMITATIONS
Multilineage RAS mutation in CSHS was recently identified; further studies on mechanism are unavailable.
CONCLUSION
Patients with nevi in association with skeletal disease should be evaluated for serum phosphate and FGF-23. Further studies investigating the role of RAS in FGF-23 regulation are needed.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genes, ras; Humans; Mosaicism; Nevus, Pigmented; Osteomalacia; Rickets, Hypophosphatemic; Skin Neoplasms; Syndrome
PubMed: 27444071
DOI: 10.1016/j.jaad.2015.11.012 -
Pathology Feb 2016Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the... (Review)
Review
Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas common acquired naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET. In Spitz naevi, which lack significant histological atypia, all of these mitogenic driver aberrations trigger rapid cell proliferation, but after an initial growth phase, various tumour suppressive mechanisms stably block further growth. In some tumours, additional genomic aberrations may abrogate various tumour suppressive mechanisms, such as cell-cycle arrest, telomere shortening, or DNA damage response. The melanocytes then start to grow in a less organised fashion and may spread to regional lymph nodes, and are termed atypical Spitz tumours. Upon acquisition of even more aberrations, which often activate additional oncogenic pathways or alter cell differentiation, the neoplastic cells become entirely malignant and may colonise and take over distant organs (spitzoid melanoma). The sequential acquisition of genomic aberrations suggests that Spitz tumours represent a continuous biological spectrum, rather than a dichotomy of benign versus malignant, and that tumours with ambiguous histological features (atypical Spitz tumours) might be best classified as low-grade melanocytic tumours. The number of genetic aberrations usually correlates with the degree of histological atypia and explains why existing ancillary genetic techniques, such as array comparative genomic hybridisation (CGH) or fluorescence in situ hybridisation (FISH), are usually capable of accurately classifying histologically benign and malignant Spitz tumours, but are not very helpful in the diagnosis of ambiguous melanocytic lesions. Nevertheless, we expect that progress in our understanding of tumour progression will refine the classification of spitzoid melanocytic tumours in the near future. By integrating clinical, pathological, and genetic criteria, distinct tumour subsets will be defined within the heterogeneous group of Spitz tumours, which will eventually lead to improvements in diagnosis, prognosis and therapy.
Topics: Animals; Chromosome Aberrations; Genomics; Humans; Melanoma; Mutation; Nevus, Epithelioid and Spindle Cell; Nevus, Pigmented; Phosphotransferases; Prognosis; Proto-Oncogene Proteins; Recombination, Genetic; Skin; Skin Neoplasms; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 27020384
DOI: 10.1016/j.pathol.2015.12.007 -
Bioscience Trends 2019We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different...
We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different distribution pattern of both lesions. Data on 8 patients with melanomas (4 male and 4 female) and 26 patients with melanocytic nevus (6 male and 20 female) of palm and finger pulp who visited Wakayama Medical University Hospital between 1986 and 2018 was retrospectively collected. We found that all of the 8 lesions of melanoma were located on the finger pulps and distal to the 'distal transverse crease' of the palm, and that melanomas were not present proximal to the transverse crease. On the other hand, melanocytic nevus was present in the proximal area to the distal transverse crease of the palm more frequently than melanomas (50.0% vs. 0%), and there was statistically significant difference (p = 0.011 by Fisher's exact probability test). From these observations, our findings may reveal the contribution of mechanical stress to the cause of palmar melanoma, and may facilitate clinical differentiation between malignant melanoma and melanocytic nevus by the localization. Further studies with increased number of patients are needed to validate the finding.
Topics: Female; Hand; Humans; Male; Melanoma; Nevus, Pigmented; Retrospective Studies; Skin; Skin Neoplasms; Stress, Mechanical
PubMed: 31527333
DOI: 10.5582/bst.2019.01221 -
Anais Brasileiros de Dermatologia 2017Recurrent melanocytic nevus is a proliferation of melanocytes arising from a melanocytic nevus removed partially. Asymmetry and irregular pigmentation may lead to...
Recurrent melanocytic nevus is a proliferation of melanocytes arising from a melanocytic nevus removed partially. Asymmetry and irregular pigmentation may lead to misdiagnosis of melanoma. We report a patient presented with a lesion on the lower abdomen, which was removed by shave excision. Anatomopathological examination revealed an intradermal melanocytic nevus. Two months later, a new irregular hyperpigmented lesion appeared in the surgical scar. Histopathology of the excisional biopsy revealed a recurrent melanocytic nevus. Recurrent melanocytic nevus manifests as a scar with hyper or hypopigmented areas, linear streaking, stippled pigmented halos, and/or diffuse pigmentation patterns. Histologically, the dermoepidermal junction and the superficial dermis show melanocytic proliferation overlying the scarred area. When a pathological report of the previous lesion is not available, complete excision is the gold standard. Otherwise, regular dermoscopic monitoring is a therapeutic option. The present report emphasizes the importance of histopathological examination of the excised material - even in cases of suspected benign lesions - and warns patients about the possibility of recurrence in case of incompletely removed lesions.
Topics: Biopsy; Cell Proliferation; Dermoscopy; Female; Humans; Melanocytes; Middle Aged; Neoplasm Recurrence, Local; Nevus, Pigmented; Skin Neoplasms
PubMed: 28954104
DOI: 10.1590/abd1806-4841.20176190 -
Dermatology (Basel, Switzerland) 2022Examination of subungual pigmented lesions is sometimes a diagnostic challenge for clinicians.
INTRODUCTION
Examination of subungual pigmented lesions is sometimes a diagnostic challenge for clinicians.
OBJECTIVES
The study was aimed to investigate characteristic patterns in optical coherence tomography (OCT) of subungual hematomas and determine distinctive features that can differentiate them from subungual melanocytic lesions.
METHODS
VivoSight® (Michelson Diagnostics, Maidstone, UK) was used to examine 71 subungual hematomas and 11 subungual melanocytic lesions in 69 patients (18 female and 51 male patients).
RESULTS
On OCT, bleeding was related to sharply defined black sickle-shaped (p < 0.001) or globular regions (not significant [ns]) with a hyperreflective margin (0.002), a grey center (0.013), hyperreflective lines in the area (ns) or periphery (p = 0.031), peripheral fading (p = 0.029), and red dots in the area (p = 0.001). In the 1 case of melanoma in situ examined, we found curved vessels with irregular sizes and distribution on the dermis of the nailbed, while subungual hematomas and subungual benign nevi presented as clustered red dots and/or regularly distributed curved vessels.
CONCLUSION
Our findings indicate that the use of OCT in addition to dermoscopy provides high-resolution optical imaging information for the diagnosis of subungual hematoma and facilitates the differential diagnosis of subungual hematomas and subungual melanocytic lesions.
Topics: Humans; Male; Female; Dermoscopy; Nevus, Pigmented; Tomography, Optical Coherence; Skin Neoplasms; Nail Diseases; Hematoma
PubMed: 35508112
DOI: 10.1159/000524347 -
BioMed Research International 2020Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing...
Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades. This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation. A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma. In addition, survival curves indicated that six hub genes, including , , , , , and , were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma. Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort. It suggested that significantly elevated , , , , , and proteins expressed in the CM than in the nevus tissues. Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include the pathway, signaling, estrogen response late, and estrogen response early. In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of , , , , , and provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma.
Topics: Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Genome, Human; Humans; Melanoma; Molecular Sequence Annotation; Neoplasm Proteins; Nevus, Pigmented; Oligonucleotide Array Sequence Analysis
PubMed: 32934956
DOI: 10.1155/2020/1840415 -
BioMed Research International 2016Digital dermoscopy aids dermatologists in monitoring potentially cancerous skin lesions. Melanoma is the 5th common form of skin cancer that is rare but the most...
Digital dermoscopy aids dermatologists in monitoring potentially cancerous skin lesions. Melanoma is the 5th common form of skin cancer that is rare but the most dangerous. Melanoma is curable if it is detected at an early stage. Automated segmentation of cancerous lesion from normal skin is the most critical yet tricky part in computerized lesion detection and classification. The effectiveness and accuracy of lesion classification are critically dependent on the quality of lesion segmentation. In this paper, we have proposed a novel approach that can automatically preprocess the image and then segment the lesion. The system filters unwanted artifacts including hairs, gel, bubbles, and specular reflection. A novel approach is presented using the concept of wavelets for detection and inpainting the hairs present in the cancer images. The contrast of lesion with the skin is enhanced using adaptive sigmoidal function that takes care of the localized intensity distribution within a given lesion's images. We then present a segmentation approach to precisely segment the lesion from the background. The proposed approach is tested on the European database of dermoscopic images. Results are compared with the competitors to demonstrate the superiority of the suggested approach.
Topics: Contrast Media; Dermatology; Hair; Humans; Image Enhancement; Melanoma; Nevus, Pigmented
PubMed: 27774454
DOI: 10.1155/2016/2082589 -
Journal of the American Academy of... Mar 2023Melanocytic tumor of uncertain malignant potential (MELTUMP) and superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) are descriptive and... (Review)
Review
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.
BACKGROUND
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.
OBJECTIVE
To investigate the incidence and clinical outcome of MELTUMP and SAMPUS in the Netherlands.
METHODS
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.
RESULTS
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.
LIMITATIONS
Reassessment of pathology slides and confirmation of clonality between primary and metastatic lesions remained outside the scope of this study.
CONCLUSION
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.
Topics: Humans; Melanoma; Skin Neoplasms; Nevus, Pigmented; Retrospective Studies; Netherlands; Incidence; Cell Proliferation
PubMed: 36403750
DOI: 10.1016/j.jaad.2022.11.019 -
Acta Dermatovenerologica Alpina,... Mar 2021We report the case of an adolescent girl that presented with an atypical melanocytic lesion on the left gluteal region, suspicious for melanoma. She was healthy with no... (Review)
Review
We report the case of an adolescent girl that presented with an atypical melanocytic lesion on the left gluteal region, suspicious for melanoma. She was healthy with no associated diseases, and there was no history of skin cancer in the family. The nevus had been present for several years, but she had noted a change and growth of it in the last few months. She reported that the nevus was injured about 2 years earlier and it had appeared different ever since. Although dermoscopic examination showed the lesion to be highly suspicious for melanoma and it was therefore surgically excised on the same day, pathohistological examination showed a compound melanocytic nevus with extensive dermal fibrosis/regression and overlying atypical junctional hyperplasia of melanocytes consistent with pseudomelanoma, also known as recurrent melanocytic nevus.
Topics: Adolescent; Female; Humans; Melanocytes; Melanoma; Nevus, Pigmented; Precancerous Conditions; Skin Neoplasms
PubMed: 33765760
DOI: No ID Found -
Archives of Pathology & Laboratory... Mar 2011Deep penetrating nevus is a distinctive melanocytic lesion that may simulate melanoma both clinically and histologically. (Review)
Review
CONTEXT
Deep penetrating nevus is a distinctive melanocytic lesion that may simulate melanoma both clinically and histologically.
OBJECTIVE
To review clinical and histologic features of deep penetrating nevi and discuss their differential diagnosis, especially regarding melanoma.
DATA SOURCES
The literature on deep penetrating nevi is reviewed and supplemented by our experiences with deep penetrating nevi.
CONCLUSIONS
One or more disturbing histologic features may frequently be found in deep penetrating nevi, including asymmetry, plump but fairly regular nests of melanocytes in the dermis, cytologic atypia with some nuclear pleomorphism, a small to medium-sized eosinophilic nucleolus, absence of maturation, occasional presence of normal dermal mitoses, and a patchy mononuclear inflammatory cell infiltrate. Although unusual, such histologic features should not be regarded as a sign of malignancy in deep penetrating nevi.
Topics: Adolescent; Adult; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Male; Melanocytes; Melanoma; Middle Aged; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Nevus, Intradermal; Nevus, Pigmented; Skin Neoplasms; Young Adult
PubMed: 21366455
DOI: 10.5858/2009-0493-RA.1