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Pathology, Research and Practice Jun 2024The Preferentially Expressed Antigen in Melanoma (PRAME) immunostain has seen significant diagnostic use in confirming malignancy for melanocytic lesions. However, the...
INTRODUCTION
The Preferentially Expressed Antigen in Melanoma (PRAME) immunostain has seen significant diagnostic use in confirming malignancy for melanocytic lesions. However, the expression of PRAME in genital melanocytic lesions have not been reported. In this study, PRAME staining was performed on a cohort of genital melanocytic lesions, aiming to investigate the diagnostic role of PRAME in genital melanocytic lesions and its expression in atypical genital nevi.
METHODOLOGY
A cohort including genital invasive melanoma, melanoma-in-situ, atypical genital nevus (AGN), compound nevus, intradermal nevus, blue nevus, lentigo and melanosis was retrieved with histology reviewed and PRAME immunostaining performed.
RESULTS
A total of 66 cases were reviewed. The average proportion expression of PRAME were 56.75 % and 57.43 % for invasive melanoma and melanoma-in-situ, with average H-scores of 153.5/300 and 163.14/300 respectively, which were greater than AGN (3.25 %, 7.75/300, p<0.001), compound/intradermal nevi, lentigo/melanosis, and background junctional melanocytes (<1 %, <1/300, p<0.001). The different cutoffs of PRAME expression, the sensitivity and specificity were 65.22 % and 100 % (>100/300); 69.57 % and 95.83 % (>10/300); and 82.61 % and 93.75 % (≥1/300) respectively. Low level PRAME expression was seen in half of the cases of AGN (n=2/4, 50 %), and at low cutoffs (>10/300 and ≥1/300) unable to differentiate invasive melanoma from AGN (p>0.05).
CONCLUSIONS
For genital melanocytic lesions, PRAME immunostain shows high specificity at strong and diffuse staining. AGN not uncommonly display low level expression. Focal and/or weak PRAME expression should not be considered as an absolute indication of malignancy, and comprehensive histological assessment remains the key to accurate diagnosis of melanocytic lesions.
PubMed: 38878667
DOI: 10.1016/j.prp.2024.155404 -
Histopathology May 2024PKC-fused blue naevi are a recently described group of melanocytic tumours that have distinctive morphological features, including a pigmented epithelioid...
BACKGROUND AND AIMS
PKC-fused blue naevi are a recently described group of melanocytic tumours that have distinctive morphological features, including a pigmented epithelioid melanocytoma-like junctional component or a dermal biphasic architecture associating with naevocytoid nests surrounded by dendritic and spindled pigmented melanocytes (so-called 'combined common and blue naevus'). There have been reports of smooth muscle hyperplasia in a hamartoma-like pattern in cases of combined blue naevi without genetic exploration.
MATERIALS AND METHODS
Herein, we describe 12 cases of protein kinase C (PKC)-fused blue tumours associated with a co-existing smooth muscle hyperplasia, identified from a total of 98 PKC-fused melanocytic tumours. Archived slides of PKC-fused blue naevi with haematoxylin, eosin and phloxin staining, immunohistochemistry and molecular confirmation of a PKC-fusion by fluorescence in-situ hybridisation (FISH) or RNAseq were re-evaluated for identification of notable smooth muscle hyperplasia. Fifty-one of these slides had already been studied in a previous publication from our group.
RESULTS
The hyperplasia ranged from hypertrophic arrector pili muscles to extensive horizontal bundles of disorganised fibres constantly associated and limited within a biphasic dermal melanocytic component. At least one arrector pili muscle was always visible within the tumour, with occasionally direct extension of the hyperplastic fibres from the main muscle body. These muscle fibres were devoid of a PKC-fusion signal by FISH. PKC molecules are involved in the regulation of smooth muscle function, offering an explanatory framework.
CONCLUSIONS
These data suggest incorporating smooth muscle hyperplasia as a diagnostic morphological feature of PKC-fused blue melanocytic tumours.
PubMed: 38747196
DOI: 10.1111/his.15211 -
The Malaysian Journal of Pathology Apr 2024Spitz tumour with ALK rearrangement is a recently described entity and a rare tumour. The incidence of Spitz tumour was estimated at 3.63 per 100,000 persons in American... (Review)
Review
Spitz tumour with ALK rearrangement is a recently described entity and a rare tumour. The incidence of Spitz tumour was estimated at 3.63 per 100,000 persons in American paediatric population; while there is no data in Asian population. Here we reported a case of an eleven-year-old Asian boy who presented with a left shin nodule of two months' duration. The skin biopsy revealed a Spitz tumour with predominantly spindle cell morphology arranged in fascicles, vertically orientated nests and radial growth pattern. Junctional component, melanin pigment or Kamino bodies were not identified. Immunohistochemical study displayed homogenous cytoplasmic staining for ALK. Fluorescence in-situ hybridisation (FISH) analysis confirmed ALK rearrangement. Review of the literatures demonstrated that positive ALK immunohistochemistry may not correlate with ALK rearrangement. ALK-rearranged Spitz tumour confirmed with FISH analysis favour clinically benign behaviour despite atypical histomorphology or positive sentinel lymph node. Therefore, correlation of histomorphology, immunohistochemical stain and molecular study are important for the definitive diagnosis of this entity.
Topics: Humans; Male; Nevus, Epithelioid and Spindle Cell; Anaplastic Lymphoma Kinase; Child; Gene Rearrangement; Skin Neoplasms; In Situ Hybridization, Fluorescence; Immunohistochemistry; Receptor Protein-Tyrosine Kinases; Biomarkers, Tumor
PubMed: 38682850
DOI: No ID Found -
Pathology, Research and Practice Apr 2024Among nevus-associated melanomas, which overall account for 20%-30% of all melanomas, those arising specifically in congenital melanocytic nevi are infrequent, but can... (Review)
Review
Among nevus-associated melanomas, which overall account for 20%-30% of all melanomas, those arising specifically in congenital melanocytic nevi are infrequent, but can be disproportionately frequent in childhood and adolescence. Congenital melanocytic nevi (CMNi) are common benign melanocytic tumors that are present at birth or become apparent in early childhood. They are classified based on the projected adult size. Small and medium-sized CMNi are frequent, whereas large/giant CMNi (over 20 cm in diameter) are rare, but can be associated with high morbidity due to marked aesthetic impairment and the risk of neurocutaneous syndrome or melanoma development. In this setting, melanomas can appear in early childhood and are very aggressive, while the risk of small-medium CMNi of developing melanoma is low and similar to non-congenital melanocytic nevi. Histologically, most melanomas on CMNi initiate their growth at the epidermal-dermal junction, but in large/giant CMNi they can develop entirely in the dermis, in deeper tissues, or in extracutaneous sites (especially in the central nervous system). Most CMNi harbour an NRAS mutation, but other genes are rarely involved, and gene translocations have recently been described. However, no prognostic implications have been associated with the CMN genotype. Melanomas developed on CMNi harbour additional molecular alterations to which the aggressive clinical course of these tumors has been attributed. This review covers the distinctive clinical and pathological aspects of melanomas on CMNi, and includes the epidemiology, etiopathogenesis, clinical and dermoscopic presentation, histological and molecular characteristics, as well as tumour behaviour.
Topics: Adult; Infant, Newborn; Adolescent; Humans; Child, Preschool; Melanoma; Skin Neoplasms; Nevus, Pigmented; Nevus, Epithelioid and Spindle Cell; Nitroimidazoles
PubMed: 38518732
DOI: 10.1016/j.prp.2024.155262 -
Journal of Clinical Imaging Science 2024Neural crest cells (NCCs) are transient structures in the fetal life in vertebrates, which develop at the junctional site of the non-neural and neural ectoderm, sharing...
OBJECTIVES
Neural crest cells (NCCs) are transient structures in the fetal life in vertebrates, which develop at the junctional site of the non-neural and neural ectoderm, sharing a common developmental origin for diverse diseases. After Epithelio-mesenchymal (EMT) of the NCCs within the neural tube, delamination of NCCs occurs. After delamination, the transformation of these cells into various cell lineages produces melanocytes, bones, and cartilage of the skull, cells of the enteric and peripheral nervous system. After the conversion, these cells migrate into various locations of the entire body according to the cell lineage. Abnormalities in neural crest (NC) formation and migration result in various malformations and tumors, known as neurocristopathy.
MATERIAL AND METHODS
Herein, this case series describes a single-center experience in cephalic NC disorders over the past 3 years, including 17 cases of varying composition (i.e., vascular, dysgenetic, mixed, and neoplastic forms) involving the brain and occasionally skin, eyes, and face of the patients.
RESULTS
In our study of 17 patients with cephalic NC disease, 6 (35.3%) patients had vascular form, 5 (29.4%) had dysgenetic form, 4 (23.5%) had mixed form, and 2 (11.7%) had neoplastic form. Brain involvement in the form of vascular or parenchyma or both vascular and parenchymal was seen in all of our patients (100%), skin in 6 (35.3%) patients, eye in 2 (11.7%), and face in 1 (5.9%) patient. Treatment was planned according to the various manifestations of the disease.
CONCLUSION
Neural crest diseases (NCDs) are a rare and under-recognized group of disorders in the literature and may have been under-reported due to a lack of awareness regarding the same. More such reporting may increase the repertoire of these rare disorders such that clinicians can have a high degree of suspicion leading to early detection and timely counseling and also improve preventive strategies and help in developing new drugs for these disorders or prevent them.
PubMed: 38469176
DOI: 10.25259/JCIS_87_2023 -
Journal of the European Academy of... Jun 2024Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate...
BACKGROUND
Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions.
OBJECTIVES
The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions.
METHODS
Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches.
RESULTS
69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made.
CONCLUSIONS
LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.
Topics: Humans; Dermoscopy; Tomography, Optical Coherence; Skin Neoplasms; Melanoma; Male; Female; Middle Aged; Nevus, Pigmented; Adult; Aged
PubMed: 38131528
DOI: 10.1111/jdv.19771 -
The American Journal of Dermatopathology Jan 2024Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used to facilitate distinction of benign and malignant melanocytic proliferations.... (Review)
Review
Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used to facilitate distinction of benign and malignant melanocytic proliferations. We hypothesized that evaluation of 1 institution's experience with PRAME labeling in a large number of consecutive cases might elucidate additional strengths and potential pitfalls and reveal base rates of positivity versus negativity in 1 academic practice. Pathology reports for all specimens on which PRAME labeling was performed at our institution between January 2021 and May 2022 were retrieved from our database. Eighty percent of conventional malignant melanomas were labeled diffusely positive with PRAME; there were no significant differences in mean age, sex, site, Breslow depth, ulceration status, or American Joint Committee on Cancer pathological tumor stage when comparing diffusely PRAME-positive malignant melanomas with those that lack diffuse labeling. Although no banal melanocytic nevi were labeled with PRAME, 13% of dysplastic nevi were diffusely PRAME positive, with junctional proliferations, severe atypia, male gender, and older age being associated with PRAME positivity. As some but not all ambiguous melanocytic lesions in which malignancy could not be excluded based on morphology alone were diffusely PRAME positive, PRAME's accuracy in predicting malignancy remains unclear to the authors; further study is needed to assess the precision to which PRAME immunohistochemistry can separate benign borderline lesions from their malignant counterparts. Among nonmelanocytic lesions, some poorly differentiated tumors, including atypical fibroxanthomas, can be PRAME positive. This series underscores the importance of clinicopathologic correlation and shows that diffuse PRAME positivity is highest in conventional malignant melanomas (∼80%, or 8 of 10 lesions), is seen in about half of challenging borderline lesions at our institution, and can be observed in lesions diagnosed as dysplastic nevi by our group (∼10% or 1 in 10 lesions), as well as in rare poorly differentiated malignancies.
Topics: Humans; Male; Antigens, Neoplasm; Diagnosis, Differential; Dysplastic Nevus Syndrome; Immunohistochemistry; Melanocytes; Melanoma; Skin Neoplasms; Transcription Factors; Female
PubMed: 37982498
DOI: 10.1097/DAD.0000000000002584 -
Journal of Cosmetic Dermatology Mar 2024The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin,...
BACKGROUND
The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin, pathogenesis, and GCMN progression are not yet completely clear. Unlike other medium or small superficial lesions, histomorphological evaluation is significant for GCMN pathological classification, malignant transformation assessment, and early detection of prognosis.
AIMS
This study aimed to investigate the pathological features of GCMN, including its satellite lesions.
PATIENTS/METHODS
Twenty-three giant naevi and seventeen "satellite lesions" were collected from children aged 1 to 10 in Shanghai Ninth People's Hospital from 2018 to 2020. A histological study was conducted to evaluate their histological appearance. All the data observed and recorded data were statistically analyzed.
RESULTS
In 23 cases of GCMN primary nevus, nevus cells were mainly distributed in the dermal region, with melanocyte proliferation and the presence of nevus nests at the dermal-epidermal junction. However, in satellite nevus, a junctional growth pattern was noted. Additionally, other histopathologic features, including epidermal contour, cell morphology, and architecture disorder also showed significant differences between primary nevus and satellite nevus.
CONCLUSIONS
We demonstrated that the congenital pattern of the main nevus is more obvious than one of the satellite nevus, suggesting that the satellite nevus and the main nevus may occur slightly later than the main nevus. "Satellite nevus" happens as a result of a separate genetic event.
Topics: Child; Humans; China; Skin Neoplasms; Nevus, Pigmented; Cell Proliferation
PubMed: 37933518
DOI: 10.1111/jocd.16065 -
Acta Dermatovenerologica Croatica : ADC Aug 2023Dear Editor, Approximately 25-33% of cutaneous melanomas arise from nevi (1). Shitara et al. suggested that junctional and compound nevi are more likely give rise to...
Dear Editor, Approximately 25-33% of cutaneous melanomas arise from nevi (1). Shitara et al. suggested that junctional and compound nevi are more likely give rise to melanoma than intradermal nevi, but this has not been definitively confirmed (2). Based on these results and our own clinical observation on rare malignant transformation in intradermal nevi, we present two patients with melanoma developing from an intradermal nevus. The first patient, a 63-year-old woman, presented with a suspicious lesion in 2017 on the upper back in the form of a dark brown macula juxtapositioned next to the dermal nevus (Figure 1, a). Dermoscopy of a flat part showed a dark-brown reticular, slightly structureless pattern (Figure 1, b). The patient was therefore referred to surgical excision. Histopathology of the elevated part showed aggregates of intradermal nevus cells of normal morphological characteristics. Atypical and irregularly sized melanocytes were observed in the flat part, infiltrating the entire depth of the epidermis and the upper parts of the papillary dermis. The diagnosis of malignant melanoma developing from a dermal nevus was established (Breslow 0.4 mm, pT1A) (Figure 1, c). The second patient, a 71-year-old man, presented in 2018 with a pendular non pigmented intradermal nevus on middle part of the back. The left-hand lateral side of the intradermal nevus showed a brown to dark-brown spot which measured 12 mm (Figure 2, a). A central blue white veil, atypical pigment network, and dots and globules of various sizes and shapes were observed on dermoscopy (Figure 2, b). The base of the nevus showed an asymmetric pigmentation. Because the lesion was highly suspicious of melanoma, an urgent excision was indicated. The histopathology of the elevated part (dermal nevus) showed a regular maturation of the nest of nevus cells in the dermis. The histopathology of the dark-brown macule showed proliferation of atypical melanocytes with well-marked nucleoli throughout the epidermis with the infiltration of the suprabasal epidermal layers and papillary dermis. The lesion was classified as melanoma with a partial regression (Breslow 1.3 mm, pT2A), arising in association with an acquired intradermal nevus (Figure 2, c). Case reports with melanoma developed from a small congenital or acquired dermal nevus are extremely rare in the literature. In all published cases, histopathology revealed a melanoma component situated below or laterally, next to the merging dermal nevus (3) and in one case next to and above the dermal component (4), which is very similar to our cases. In both of our cases, melanoma presented an epidermal component with atypical, large melanocytes next to or above the typical and small intradermal melanocytes of the Unna nevus. Despite the fact that the reported statistical occurrence of malignant transformation of every individual nevus is very low in the elderly population (>60 years of age), 1 in 33,000 (5), we believe our two presented cases show a striking similarity in the melanoma manifesting in the vicinity of a previously existing lesion, indicating nevus-associated melanoma (NAM). This letter presents an interesting finding of two cases, with a form of melanoma (NAM) that is statistically very rare in older patients but occurred twice within the span of a year within the same town and was diagnosed in the same hospital. Intradermal nevi are most commonly considered to be benign skin lesions. However, previous research and our two cases shows that intradermal nevi are not immune to malignant alteration. Based on these results, we suggest a detailed clinical and dermoscopic evaluation of each skin lesion, including intradermal nevi. Flat melanocytic parts in the vicinity of intradermal nevi should always raise suspicion and warrant excision with histopathological evaluation of the lesion so as to allow timely response to any malignant alteration.
Topics: Male; Female; Humans; Aged; Middle Aged; Nevus, Intradermal; Melanoma; Skin Neoplasms; Nevus; Nevus, Pigmented; Melanoma, Cutaneous Malignant
PubMed: 37843090
DOI: No ID Found -
International Journal of Molecular... Sep 20235-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC...
5-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC levels in melanoma. However, the interpretation of the intensity and distribution of 5-hmC immunoreactivity is not very standardized, which makes its interpretation difficult. In this study, 5-hmC-stained histological slides of superficial spreading melanomas (SSM) and dysplastic compound nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. Receiver operating characteristic/area under the curve (ROCAUC) and t-tests were performed. A -value of <0.05 was used for statistical significance, and a ROCAUC score of >0.8 was considered a "good" result. In total, 92 5-hmC-stained specimens were analyzed, including 42 SSM (45.7%) and 50 DN (54.3%). The mean of 5-hmC-positive cells/mm for the epidermis and dermo-epidermal junction and the entire lesion differed significantly between DN and SSM ( = 0.002 and = 0.006, respectively) and showed a trend towards higher immunoreactivity in the dermal component ( = 0.069). The ROCAUC of 5-hmC-positive cells of the epidermis and dermo-epidermal junction was 0.79, for the dermis 0.74, and for the entire lesion 0.76. These results show that the assessment of the epidermal with junctional expression of 5-hmC is slightly superior to dermal immunoreactivity in distinguishing between DN and SSM.
Topics: Humans; Dysplastic Nevus Syndrome; Skin Neoplasms; Melanoma; Computers; Melanoma, Cutaneous Malignant
PubMed: 37834158
DOI: 10.3390/ijms241914711