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Melanocytic nevi existing in lymph nodes create a diagnostic challenge by mimicking metastases. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) stain can differentiate one from another. FLI-1 IHC expression has been shown in malignant melanoma with variable sensitivity while melanocytic nevi were reported to be negative. We hypothesized that FLI-1/Melan-A dual IHC staining may be used in the distinction of metastatic melanoma from nodal nevi and can be an alternative and/or complementary to PRAME. In this study, we examined 13 lymph nodes with metastatic melanoma and 13 lymph nodes with benign deposits. We stained all of the lymph nodes with FLI-1, FLI-1/Melan-A dual, and PRAME IHC stains. In addition, we stained paired skin samples of the metastatic lymph nodes with FLI-1 and PRAME. In primary cutaneous melanomas, 11 of 13 were positive for FLI-1 and PRAME expression (85%). Malignant cells in 12 and 13 lymph nodes showed positive expression of PRAME and FLI-1, respectively. Only one case with a nevic cell deposit was weakly positive for FLI-1 and the remaining benign cases were negative for both FLI-1 and PRAME. Our results show that FLI-1/Melan-A dual stain is as sensitive and specific as PRAME in distinguishing lymph nodes with metastatic melanoma from nodal nevi. Further studies with larger case numbers are needed to support our significant results., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although spongiotic (eczematous), psoriatic and cutaneous skin infections are among the most common in dermatology consultations, melanocytic lesions - including the different types of nevi and melanomas - are among those that cause a great deal of concern and stress to patients and their clinicians. A diagnosis of benign melanocytic nevus carries a very good prognosis. However, a diagnosis of melanoma might indicate more aggressive treatment, lifelong surveillance and a worse prognosis. Differentiating between these conditions is not always a straightforward process for clinicians and pathologists. Therefore, knowledge of melanoma mimickers is very important for clinicians in general, and dermatologists and pathologists in particular. In this review, we called attention to some of the more frequent benign but unusual melanocytic lesions that are of diagnostic concern for clinicians evaluating these cutaneous proliferations., (Copyright: © Singapore Medical Association.)

A 26-year-old female presented with a 7 mm irritated pink-red papule on the left posterior shoulder. A shave biopsy revealed a dermal proliferation of epithelioid cells arranged in small nests with central lumen-like structures resembling glands set in a densely sclerotic stroma. S100 and Melanoma antigen recognized by T cells 1 (MART-1) immunohistochemical positivity confirmed a dermal melanocytic neoplasm. Pan-cytokeratin and cytokeratin 7 were negative within the nests ruling out an adnexal neoplasm or metastatic adenocarcinoma. A Spitz nevus variant characterized by the presence of focal tubular structures (tubular epithelioid cell nevus) has rarely been described in the literature and is of uncertain biological significance. Similar structures have also been observed in Clark/dysplastic nevi and melanoma. Glandular differentiation is seen in a wide variety of benign and malignant epithelial neoplasms; however, melanocytes are not known to be capable of forming true glands. The exact mechanism and significance of this phenomenon are currently unknown. Certain postulations include central melanocyte apoptosis, autocrine or paracrine factor secretion or retraction artifact caused by tissue fixation. This distinctive finding is important to recognize in order to avoid misdiagnosis as a glandular neoplasm., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

DNA double-strand breaks are increased in human melanoma tissue as detected by histone H2AX phosphorylation.(1-3) We investigated two of the downstream effectors of DNA double-strand breaks, Rad50 and 53BP1 (tumor suppressor p53 binding protein 1), to determine if they are altered in human primary melanoma cells. Melanoma cases showed high Rad50 staining (81.8%; 9/11) significantly more frequently than conventional or atypical melanocytic nevi (0%; 0/18). In contrast, the staining pattern for 53BP1 appears similar between melanoma and nevi. This is the first study that shows activation and misregulation of the DNA repair pathway in human melanoma cells. The staining features of Rad50, a component of an essential DNA double-strand break repair complex, are clearly increased in melanoma cells with regards to both staining intensity and the number of positive melanoma cells. Interestingly, among the melanoma cases with increased Rad50 staining, most demonstrated cytoplasmic rather than nuclear staining (88.9%, 8/9). Further studies are needed to determine the cause of this mislocalization and its affects, if any, on DNA double-strand break repair in melanoma., (Copyright © 2012 John Wiley & Sons A/S.)

Mortality from melanoma, the deadliest of skin cancers, continues to increase in all age groups. A small number of melanomas spontaneously regress. In vitro studies suggest a role for the natural killer cell in effecting regression. In this study, the goal was to determine if natural killer cells are preferentially involved in the cytotoxic response in regressing lesions. Forty-two cases were selected: nevi with regression, nonregressing melanoma with brisk inflammation, and regressing melanoma. Sections were stained with hematoxylin and eosin and immunostained for CD8, CD56, and T-cell intracytoplasmic antigen 1. Numbers of total lymphocytes, CD8-positive lymphocytes, and T-cell intracytoplasmic antigen 1-positive lymphocytes did not differ among the 3 populations or based on location. CD56 positivity was significantly different among the 3 populations. Regressing melanomas showed the greatest CD56 activity, followed by regressing nevi, whereas inflamed, nonregressing melanomas showed the least. CD56(+) lymphocytes were mostly counted in areas of early regression. The natural killer cell could plausibly play a role in the occurrence of regression as a cytotoxic effector cell or as a mediator of the cytotoxic mechanism., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: One major risk factor for cutaneous melanoma is chronic sun-exposure and oxidative stress. Among various oxidative DNA damages, 8-oxoquanine is the most abundant and is potentially mutagenic if not sufficiently repaired. The human 8-oxoquanine DNA glycosylase 1 (hOGG1) gene specifically repairs 8-oxoguanine, and this gene shows frequent loss of heterozygosity (LOH) in human tumors. In this study, we investigate whether hOGG1 LOH occurs in melanoma in situ (MIS) and adjacent atypical melanocytic hyperplasia (AMH)., Methods: Twelve skin biopsies with MIS and adjacent AMH were included. DNA samples derived from manual microdissection of tissues were subjected to polymerase chain reaction amplification using three fluorescent-labeled microsatellite makers, followed by fragment analysis., Results: Five of 12 cases were informative for both telomeric (3S1297) and centromeric (3S1289 or 3S1300) markers, bordering the hOGG1 locus. Among them, four (80%) MIS and three (60%) AMH showed hOGG1 LOH at both markers., Conclusions: These results shows that LOH at hOGG1 gene is associated with MIS and AMH and suggest that the hOGG1 gene may play a role in melanocytic tumor progression.

Malignant melanoma accounts for the largest number of deaths attributed to skin cancer. It also provides the most diagnostic challenges for the histopathologist. This article, attempts to describe the histologic features most closely associated with the various growth patterns of the most common subtypes of melanoma. While it has been shown repeatedly that histologic subtypes likely provide clinicians and patients with minimal to no prognostic information, it is useful to separate these entities in order to elucidate the varied histologic features seen within the class of tumors known as melanoma. The discussion centers around a checklist of changes seen at the microscope that are associated with this diagnosis. The goal of this chapter is to provide the reader with one perspective on the series of changes that are used in order to establish (or exclude) a diagnosis of melanoma. There is a comprehensive literature that critically evaluates histologic parameters associated with this collection of tumors and relates them to prognostic information, and no attempt will be made to correlate the histologic change with prognostic information. This will be discussed in another chapter in this volume. Similarly, more esoteric subtypes of melanoma are characterized by histologic features that differ from the common types of melanoma and will be addressed in another chapter.

Malignant melanoma is known for the wide range of histological patterns it can assume mimicking other malignant tumors. We present a review of most of the unusual histological variants of cutaneous melanoma and describe their immunohistochemical features, associate clinical findings, and possible behavior related to the histological subtype. In addition, we propose their classification into four groups corresponding to the (1) architectural patterns; (2) cytologic features; (3) stromal changes; and (4) the possible association of these findings (i.e. architectural + cytologic features). Although most of these unusual variants have the same prognosis as conventional melanomas, with Breslow thickness and ulceration, being the most important predictor of survival in clinical stage I, some of them have a peculiar biologic behavior that the clinicians and the dermatopathologists should know in order to give melanoma patients all educational information available.

Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in melanocytic lesions. A series of 10 cutaneous melanomas and 24 benign melanocytic lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle upon Tyne, UK) was scored by an average of the mean labeling intensity; no nuclear staining = 0, weak nuclear staining = 1, moderate = 2, and intense = 3. Ets-1 expression was statistically assessed by the one-way analysis of variance (ANOVA) comparing the mean labeling intensity of melanoma to benign melanocytic nevi. All of the benign melanocytic lesions exhibited negative to weak nuclear staining, with an average mean labeling intensity of 0.4. Melanoma in situ exhibited moderate nuclear staining, for a mean labeling intensity of 2.0, whereas all conventional invasive melanomas exhibited moderate to strong nuclear staining, with a mean labeling intensity of 2.7. Metastatic melanoma exhibited very strong nuclear staining, with a mean labeling intensity of 3.0. Invasive desmoplastic melanoma, like melanoma in situ, showed moderate nuclear staining with a mean labeling intensity of 2.1. There was a trend toward more intense staining with melanoma progression. A statistically significant difference in the mean labeling intensity of Ets-1 was seen between invasive melanoma and benign melanocytic nevi (P <.0001). Ets-1 oncoprotein expression, however, does not distinguish among benign melanocytic lesions. Staining intensity and pattern might be a useful adjunct with histomorphology in distinguishing invasive melanoma from benign melanocytic nevi. Furthermore, Ets-1 expression may be an important pathogenic mechanism and predictor of aggressive biologic behavior of cutaneous melanoma, with a trend toward staining intensity increasing as Clark stage increases.

Over the past decade, molecular and genomic discoveries have experienced unprecedented growth, fundamentally reshaping our comprehension of melanocytic tumors. This review comprises three main sections. The first part gives an overview of the current genomic landscape of cutaneous melanocytic tumors. The second part provides an update on the associated molecular tests and immunohistochemical stains that are helpful for diagnostic purposes. The third section briefly outlines the diverse molecular pathways now utilized for the classification of cutaneous melanomas. The primary goal of this review is to provide a succinct overview of the molecular pathways involved in melanocytic tumors and demonstrate their practical integration into the realm of diagnostic aids. As the molecular and genomic knowledge base continues to expand, this review hopes to serve as a valuable resource for healthcare professionals, offering insight into the evolving molecular landscape of cutaneous melanocytic tumors and its implications for patient care. [ABSTRACT FROM AUTHOR]

Abstract Background Acquired melanocytic proliferations (AMPs) are excised throughout the year. Questions exist concerning seasonal variation in these excisions. Objective To investigate whether AMPs are removed more often during the spring–summer seasons than in the fall–winter and whether the percentage of benign nevi, dysplastic nevi and melanoma varies according to season. Design Retrospective analysis of 4794 histologically confirmed biopsies of AMPs was performed. Results A total of 2802 of the 4794 lesions (58%) were removed during the spring–summer season. These results confirm that seasonal variation in removal of AMPs does occur, and that removal peaks during the warmer months. In addition, the increased numbers of removals were accounted for by increases in benign pigmented lesion removals. Conclusions Many etiologic factors can be suggested for increased removal of AMPs during the warmer months. Reasons may include the cosmetic desires of the patient and clothing choices resulting in increased awareness of pigmented lesions. Increases in the number of skin cancer prevention programs offered by dermatologists in the spring also have a large impact on the awareness of the general population and potentially contribute to the seasonal variation. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a disease with a broad spectrum of clinical presentations. All of the variants have in common the proliferation of cells which are morphologically, biochemically, and immunophenotypically indistinguishable from Langerhans cells. A retrospective study of three elderly patients revealed the unique presentation of cutaneous Langerhans cell histiocytosis limited to the genitalia. These cases produced a diagnostic challenge because of their unusual clinical presentation and their morphological similarity to certain other entities, including extramammary Paget's disease and malignant melanoma, which may also show S-100-positive atypical cells. All three cases showed infiltrates of histiocytic-appearing cells with folded nuclei and moderate amounts of cytoplasm which involved the epidermis, dermis, or both. Immunoperoxidase studies using antibody to S-100, CD1a and CD68 in each case showed positive staining. [ABSTRACT FROM AUTHOR]