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Cancers Dec 2022Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic...
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.
PubMed: 36612016
DOI: 10.3390/cancers15010020 -
Cureus Oct 2022The Klippel-Trénaunay syndrome (KTS) is a rare form of a birth disorder that includes capillary malformation, hypertrophy of bones and soft tissues, and tortuous...
The Klippel-Trénaunay syndrome (KTS) is a rare form of a birth disorder that includes capillary malformation, hypertrophy of bones and soft tissues, and tortuous varicosities, as well as hypertrophy of the capillaries resulting in hemangiomas and port wine discoloration. KTS is also known as angio-osteohypertrophy syndrome and dysplastic angiopathy. In this case report, we describe the case of a 13-year-old female with multiple superficial varicosities on the medial aspect of her left leg since birth. Computed tomography angiogram assessed and identified abnormal venous drainage in the lower limb. Klippel-Trénaunay-Weber syndrome (KTWS) differs from KTS in that KTWS involves arteriovenous malformations.
PubMed: 36381931
DOI: 10.7759/cureus.30128 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Dysplastic Nevus Syndrome; Melanoma; Skin Neoplasms; Collagen; Nevus; Antigens, Neoplasm
PubMed: 36369201
DOI: 10.1016/j.abd.2022.02.002 -
Tidsskrift For Den Norske Laegeforening... Oct 2022Histopathological assessment of melanoma and other melanocytic skin lesions can be difficult and can vary between pathologists.
BACKGROUND
Histopathological assessment of melanoma and other melanocytic skin lesions can be difficult and can vary between pathologists.
MATERIAL AND METHOD
Histopathological slides of 196 melanocytic skin lesions from 2009 and 2018-2019 were obtained from the archive of the Department of Pathology at Oslo University Hospital and classified into six diagnostic categories: 1) benign nevus, 2) irregular/dysplastic nevus, i.e. dysplastic nevus with moderate atypia, 3) nevus with severe atypia, i.e. dysplastic nevus with severe atypia, 4) melanoma in situ, 5) superficial spreading or lentiginous melanoma and 6) nodular melanoma. The slides were then examined independently and blindly by three experienced pathologists and categorised in the same way. Interobserver agreement was assessed with Cohen's kappa, and agreement with the original diagnosis was assessed by the proportion of assessments in the same diagnostic category.
RESULTS
The kappa values for the assessments from the three pathologists ranged from 0.45 to 0.50. The proportion of reassessments in agreement with the original diagnostic category was 85.7 % (95 % CI 75.7 to 92.1), 29.2 % (19.9 to 40.5), 27.8 % (20.9 to 36.0), 78.3 % (70.4 to 84.5), 81.2 % (73.7 to 86.9) and 93.3 % (82.1 to 97.7), respectively, i.e. highest for nodular melanoma. The proportion of reassessments in which the diagnosis was more serious or less serious than the original diagnosis was higher and lower, respectively, for slides from 2009 than for slides from 2018-2019.
INTERPRETATION
The differences between the pathologists' assessments and deviations from the original diagnoses can be explained by poorly reproducible diagnostic criteria, diagnostic entities with overlapping morphology and increasing awareness of early signs of malignancy. Some evolution in diagnostic practice cannot be ruled out.
Topics: Humans; Dysplastic Nevus Syndrome; Melanoma; Skin Neoplasms; Nevus; Diagnosis, Differential; Melanoma, Cutaneous Malignant
PubMed: 36286556
DOI: 10.4045/tidsskr.22.0204 -
Acta Dermato-venereologica Nov 2022Malignant 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...
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.
Topics: Humans; Hyperspectral Imaging; Melanoma; Skin Neoplasms; Nevus, Pigmented; Sensitivity and Specificity; Melanoma, Cutaneous Malignant
PubMed: 36281811
DOI: 10.2340/actadv.v102.2045 -
Frontiers in Oncology 2022Pediatric CML is very rare. Before the introduction of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (HSCT) from a donor -if...
BACKGROUND
Pediatric CML is very rare. Before the introduction of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (HSCT) from a donor -if available- was the standard cure attempt. Data on the long-term outcome and health-related quality of life (HRQOL) in former pediatric CML patients undergoing HSCT are lacking.
STUDY QUESTION
We investigated long-term survivors' self-reporting to a questionnaire sent out to patients formerly enrolled in pediatric CML-HSCT trials.
METHODS
Individuals with CML transplanted at age <18 years were identified from the German Childhood Cancer Registry database. Long-term survivors received a questionnaire based on the SF-36 and FACT-BMT asking them to self-report HRQOL issues. (Ethical vote #541_20 B, Medical Faculty, University of Erlangen-Nürnberg).
RESULTS
111/171 (64.9%) individuals survived HSCT long-term and 86/111 (77.5%) fulfilled all inclusion criteria and received the questionnaire. 37/86 (43%) participants (24 female, 13 male, median age at HSCT 12 years [range 2-18], median age at the time of the survey 29 years [range 18-43]) responded after a median follow-up period of 19 years (range 4-27) after HSCT. 10/37 (27%) participants underwent no regular medical follow-up examinations. Self-reported symptoms like chronic graft-versus-host disease (cGvHD)-associated organ impairments and conditioning regimen consequences could causatively not sharply be separated in each case. Complains comprised hypothyroidism (N=11, 30%), infertility (N=9, 24%), lung problems, dry eyes (each N=7, 19%), skin alterations (N=6, 17%), hair problems (N=4, 11%), and sexual dysfunction (N=3, 9%). 10 (27%) participants experienced 13 CML relapses after a median interval from HSCT of 31 months (range 2-93). Only one patient underwent 2nd SCT after failure of relapse treatment with TKIs. Six secondary malignancies (dysplastic melanocytic nevus and ALL, basal cell carcinoma (N=2), rhabdomyosarcoma, and thyroid carcinoma developed in 5 (13%) participants. As assessed by the SF-36 questionnaire, impaired physical health was mainly associated with cGvHD. The mental component summary score showed that also participants without cGvHD scored significantly lower than the general population. When assessed by the FACT-BMT, participants with cGvHD scored significantly lower while participants without cGvHD scored even 5 points higher than the data from controls. 18 (49%) participants considered the sequelae of HSCT an obstacle to education. Out of the total cohort, N=20 (54%), N=7 (19%), N=5 (14%), and N=4 (11%) participants worked full time, part-time, were unemployed, or had not yet finalized their education, respectively. 20 (54%) participants lived as singles, 8 (22%) lived in a partnership, 6 (16%) were married, and 3 (8%) had been divorced. Four (11%) participants reported a total number of 7 children.
CONCLUSION
This first assessment of HRQOL in former pediatric patients with CML surviving HSCT for more than two decades demonstrates self-reported satisfactory well-being only in the absence of cGvHD. Research-based on self-reported outcomes sheds light on former patients' perspectives and provides an additional layer of valuable knowledge for pediatric and adult hematologists. Regular follow-up examinations are mandatory helping to avoid that late secondary neoplasias, CML-relapse, and disorders forming the broad range of possible long-term consequences of HSCT are not detected too late.
PubMed: 36276159
DOI: 10.3389/fonc.2022.963223 -
Journal of Cutaneous Pathology Feb 2023Spitzoid melanocytic neoplasms are diagnostically challenging; criteria for malignancy continue to evolve. The ability to predict chromosomal abnormalities with...
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.
Topics: Humans; Proto-Oncogene Proteins B-raf; In Situ Hybridization, Fluorescence; Melanoma; Skin Neoplasms; Chromosome Aberrations; Nevus, Epithelioid and Spindle Cell; Diagnosis, Differential; Antigens, Neoplasm
PubMed: 36261329
DOI: 10.1111/cup.14342 -
The Journal of Dermatological Treatment Dec 2023
Topics: Humans; Dysplastic Nevus Syndrome; Dermatologists; Follow-Up Studies; Surveys and Questionnaires; Skin Neoplasms
PubMed: 36256525
DOI: 10.1080/09546634.2022.2089324 -
Life (Basel, Switzerland) Aug 2022Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of... (Review)
Review
INTRODUCTION
Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of UV-induced somatic mutations in melanocytes present in normal skin or in CM precursor lesions (nevi or dysplastic nevi). In recent years, new NGS studies performed on CM tissue have increased the understanding of the genetic somatic changes underlying melanomagenesis and CM tumor progression.
METHODS
We reviewed the literature using all important scientific databases. All articles related to genomic mutations in CM as well as normal skin and nevi were included, in particular those related to somatic mutations produced by UV radiation.
CONCLUSIONS
CM development and progression are strongly associated with exposure to UV radiation, although each melanoma subtype has different characteristic genetic alterations and evolutionary trajectories. While and mutations are common in the early stages of tumor development for most CM subtypes, changes in and together with promoter mutations, are especially common in advanced stages. Additionally, large genome duplications, loss of heterozygosity, and copy number variations are hallmarks of metastatic disease. Finally, the mutations driving melanoma targeted-therapy drug resistance are also summarized. The complete sequential stages of clonal evolution leading to CM onset from normal skin or nevi are still unknown, so further studies are needed in this field to shed light on the molecular pathways involved in CM malignant transformation and in melanoma acquired drug resistance.
PubMed: 36143375
DOI: 10.3390/life12091339