Aim: Cutaneous melanocytic neoplasms with diagnostic and/or clinical ambiguity pose patient management challenges. Methods: Six randomized case scenarios with diagnostic/clinical uncertainty were described with/without a benign or malignant diagnostic gene expression profile (GEP) result. Results: Clinical impact was assessed by reporting the mean increase/decrease of management changes normalized to baseline (n = 32 dermatologists). Benign GEP results prompted clinicians to decrease surgical margins (84.2%). Malignant GEP results escalated surgical excision recommendations (100%). A majority (72.2%) reduced and nearly all (98.9%) increased follow-up frequency for benign or malignant GEP results, respectively. There was an overall increase in management plan confidence with GEP results. Conclusion: Diagnostic GEP tests help guide clinical decision-making in a variety of diagnostically ambiguous or clinicopathologically discordant scenarios.
Dermatologists\' use of diagnostic gene expression profiles for personalized patient care. When your doctor takes a piece of a mole, that mole is looked at under the microscope by a pathologist. The pathologist is responsible for figuring out if the mole is dangerous or not. Dangerous moles are removed with surgery to make sure all the dangerous tissue is gone. Moles without a health threat are left alone. Sometimes figuring out how dangerous a mole is is difficult. The pathologist may not provide the doctor with enough information for them to know how to treat your mole. There is a test that can provide information on whether your mole is unsafe. This test is called diagnostic gene expression profiling or GEP. In this study, GEP is used to help doctors figure out how to treat a mole and how often the patient should be seen in the office for skin checks. With GEP, important changes in patient treatment were identified. These include the need for an additional surgery, how much healthy tissue should be removed during surgery and how often the patient should be seen in the office. For suspicious moles where the pathology report is unclear, GEP can provide information that leads to more appropriate and personalized patient care.
Ancillary diagnostic gene expression profile testing for ambiguous cutaneous melanocytic lesions helps optimize dermatologist recommendations for excision margin and follow-up.

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share histomorphological features of both, nevi and melanoma. Melanocytomas represent a group of them separated on the basis of recent molecular-biological studies. The article summarizes benign, intermediate, malignant and combined melanocytic skin lesions and offers practical recommendations for diagnosis.

OBJECTIVE: Pathologists often use immunohistochemical staining of the proliferation marker Ki67 in their diagnostic assessment of melanocytic lesions. However, the interpretation of Ki67 can be challenging. We propose a new workflow to improve the diagnostic utility of the Ki67-index. In this workflow, Ki67 is combined with the melanocytic tumour-cell marker SOX10 in a Ki67/SOX10 double nuclear stain. The Ki67-index is then quantified automatically using digital image analysis (DIA). The aim of this study was to optimise and test three different multiplexing methods for Ki67/SOX10 double nuclear staining.
METHODS: Multiplex immunofluorescence (mIF), multiplex immunohistochemistry (mIHC), and multiplexed immunohistochemical consecutive staining on single slide (MICSSS) were optimised for Ki67/SOX10 double nuclear staining. DIA applications were designed for automated quantification of the Ki67-index. The methods were tested on a pilot case-control cohort of benign and malignant melanocytic lesions (n = 23).
RESULTS: Using the Ki67/SOX10 double nuclear stain, malignant melanocytic lesions could be completely distinguished from benign lesions by the Ki67-index. The Ki67-index cut-offs were 1.8% (mIF) and 1.5% (mIHC and MICSSS). The AUC of the automatically quantified Ki67-index based on double nuclear staining was 1.0 (95% CI: 1.0;1.0), whereas the AUC of conventional Ki67 single-stains was 0.87 (95% CI: 0.71;1.00).
CONCLUSIONS: The novel Ki67/SOX10 double nuclear stain highly improved the diagnostic precision of Ki67 interpretation. Both mIHC and mIF were useful methods for Ki67/SOX10 double nuclear staining, whereas the MICSSS method had challenges in the current setting. The Ki67/SOX10 double nuclear stain shows potential as a valuable diagnostic aid for melanocytic lesions.

暂无摘要。

UNASSIGNED: Some melanocytic neoplasms suspicious for melanoma require additional workup to arrive at a final diagnosis. Within the last eight years, gene expression profiling (GEP) has become an important ancillary tool to aid in the diagnosis of melanocytic neoplasms with uncertain malignant potential. As the usage of two commercially available tests (23-GEP and 35-GEP) evolves, it is important to answer key questions about optimal utilization and their impact on patient care.
UNASSIGNED: Recent and relevant articles answering the following questions were included in the review. First, how do dermatopathologists synthesize the available literature, the latest guidelines, and their clinical experience to determine which cases would be most likely to benefit from GEP testing? Second, how best can a dermatologist convey to their dermatopathologist that the use of GEP in the diagnostic process could provide a more clearly defined result and thereby help empower the dermatologist to provide higher-quality patient care when making specific patient management decisions for otherwise pathologically ambiguous lesions?
UNASSIGNED: When interpreted in the context of the clinical, pathologic, and laboratory information, GEP results can facilitate the rendering of timely, accurate, and definitive diagnoses for melanocytic lesions with otherwise uncertain malignant potential to inform personalized treatment and management plans.
UNASSIGNED: This was a narrative review focused on clinical use of GEP compared to other ancillary diagnostic tests performed postbiopsy.
UNASSIGNED: Open communication between dermatopathologists and dermatologists, especially regarding GEP testing, can be a vital component to achieve appropriate clinicopathologic correlation for otherwise ambiguous melanocytic lesions.

暂无摘要。

BACKGROUND:   Worldwide, the incidence of melanoma is increasing, while late diagnosis is related to poor prognosis. A significant risk marker for melanoma is the presence of atypical nevi; therefore, it is of outstanding importance to make accurate clinical classification of common benign nevi, atypical nevi, and melanomas. The non-invasive method of dermoscopy allowed for the visualization of structures invisible to the naked eye and undoubtedly advanced the assessment of melanocytic lesions to a new dimension. This study aimed to evaluate the sensitivity and specificity of naked-eye examination and dermoscopy in diagnosing melanocytic lesions compared to the histopathological results, constituting the gold standard of diagnosis.
METHODS: One hundred eighteen melanocytic lesions were clinically evaluated via the naked eye and dermoscopic examination, using Pattern Analysis Methodology, and afterward, they were excised. The histopathological results were correlated with the findings.
RESULTS: According to the final histopathological analysis, 63 common benign nevi, 41 dysplastic nevi, and 14 cutaneous melanomas were excised in total. Clinical examination via the naked eye showed 78.2 % sensitivity and 71.4 % specificity in identifying the clinical atypia, while dermoscopy demonstrated 89.1 % sensitivity and 93.7 % specificity.
CONCLUSIONS: The results of the present study indicate a higher sensitivity and specificity of dermoscopy in evaluating and diagnosing melanocytic lesions compared to the naked-eye examination. HIPPOKRATIA 2021, 25 (4):156-161.

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.
CONCLUSIONS: Reassessment of pathology slides and confirmation of clonality between primary and metastatic lesions remained outside the scope of this study.
CONCLUSIONS: 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.

Melanocytic lesions occur on the surface of the skin, in which the malignant type is melanoma with a high fatality rate, seriously endangering human health. The histopathological analysis is the gold standard for diagnosis of melanocytic lesions. In this study, a fully automated intelligent diagnosis method based on deep learning was proposed to classify the pathological whole slide images (WSI) of melanocytic lesions. Firstly, the color normalization based on CycleGAN neural network was performed on multi-center pathological WSI; Secondly, ResNet-152 neural network-based deep convolutional network prediction model was built using 745 WSI; Then, a decision fusion model was cascaded, which calculates the average prediction probability of each WSI; Finally, the diagnostic performance of the proposed method was verified by internal and external test sets containing 182 and 54 WSI, respectively. Experimental results showed that the overall diagnostic accuracy of the proposed method reached 94.12% in the internal test set and exceeded 90% in the external test set. Furthermore, the color normalization method adopted was superior to the traditional color statistics-based and staining separation-based methods in terms of structure preservation and artifact suppression. The results demonstrate that the proposed method can achieve high precision and strong robustness in pathological WSI classification of melanocytic lesions, which has the potential in promoting the clinical application of computer-aided pathological diagnosis.
黑色素细胞病变发生于皮肤表层，恶性病变即为致死率极高的黑色素瘤，严重危害人类健康，病理组织学分析是其诊断的金标准。本文对黑色素细胞病变病理全切片图像（WSI）进行分类研究，提出一种基于深度学习的黑色素细胞病变全流程智能化诊断方法。首先，基于CycleGAN神经网络对多中心病理WSI进行颜色校正；其次，通过745张WSI构建以ResNet-152神经网络为架构的深度卷积网络预测模块；然后，级联以预测概率平均值计算为核心的决策融合模块；最终，分别采用包含182张和54张WSI的内外部测试集验证所提方法的诊断性能。实验结果显示，所提方法的整体准确率在内部测试集上达到94.12%，在外部测试集上超越90%；采用的颜色校正方式在组织结构保持、伪影抑制方面均优于传统基于颜色统计或染色分离的方式。研究证实了本文所提方法可实现高精度、强鲁棒的黑色素细胞病变病理WSI分类，对推动临床病理人工智能辅助诊断具有重要的指导意义。.