Case Report: Differential Genomics and Evolution of a Meningeal Melanoma Treated With Ipilimumab and Nivolumab

Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

NTRK Gene Fusion Detection in Atypical Spitz Tumors

Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.

Benign Skin Neoplasms among the Histopathological Specimens of Skin Neoplasm in a Teaching Hospital: A Descriptive Cross-sectional Study

Introduction: Skin tumors are relatively uncommon malignancies worldwide, but its incidence has been progressively increased over the last few decades. Skin tumor belongs to a diverse group of neoplasms arising from the epidermis, adnexal structures and dermis rendering the classification difficult. The study aims to find out the prevalence of benign skin neoplasm among the histopathological specimens of skin neoplasm of a teaching hospital. Methods: A descriptive cross-sectional study among the hospital records of histopathological samples of skin neoplasm in the Department of Pathology of a tertiary care center from January 2017 to December 2020. Ethical approval was taken from the Institutional Review Committee (Ref: MEMG/IRC/427/GA). Convenient sampling was done. Data were entered in Microsoft Excel and analyzed using Statistical Package for the Social Sciences version 21 software. Point estimate at 95% Confidence Interval was calculated with frequency and descriptive statistics. Results: Out of total skin neoplasm samples, 121 (57.34%) (50.67-64.01 at 95% Confidence Interval) benign skin neoplasms were present. Among them, the majority were keratinocytic tumor 81 (66.9%) followed by skin appendageal 23 (19.0%) and melanocytic tumors 17 (14.0%). Acrochordan 18 (14.9%) and pilomatricoma 12 (9.9%) were the predominant keratinocytic and appendageal neoplasms respectively. Most of the cases occurred in head and neck region 64 (52.9%). Conclusions: The study concluded that the prevalence of benign skin neoplasm was slightly lower compared to the other studies. Most of the benign skin neoplasms were keratinocytic tumors followed by appendageal and melanocytic tumors. Acrochordan was the commonest benign keratinocytic tumor.

Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses

The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.

Deep Learning in Opthalmology: Iris Melanocytic Tumor Intelligent Diagnosis

Recently, Convolutional neural networks (CNN) have shown a growth due to their ability of learning different level image representations that helps in image classification in different fields. These networks have been trained on millions of images, so they gained a powerful ability of extracting the rightful features from input images, which results in accurate classification. In this research, we investigate the effects of transfer learning based convolutional neural networks for the iris tumor malignancy identification as it is notoriously hard to distinguish an iris nevus from an iris tumor. Features are transferred from a CNN trained on a source task, i.e. ImageNet, to a target task, i.e. iris tumor datasets. We transfer features learned from AlexNet and VGG-16 that are trained on ImageNet, to classify three different iris images types which are: iris nevus unaffected, iris cysts, and iris melanocytic tumors. The employed pre-trained models are modified by replacing their feedforward neural network classifier, Softmax, by a support vector machine (SVM) that is expected to slightly boost their performance (AlexNet-SVM and VGG16-SVM). All employed models are trained (fine-tuned) on a 60% of the available large dataset of iris images in order to investigate their power of generalization when trained using large amount of data. The networks are also tested on 40% of the data. The best performance was achieved by the VGG16-SVM which scored a high accuracy of 96.27% and strong features extraction capability as compared to the other models. Experimentally, it was seen that adding SVM contributed in improving the network performance compared to original models which use a feedforward neural network classifier.

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

BackgroundMelan-A/MART-1 is a melanocytic differentiation marker, which is recognized as an antigen on melanoma cells. It is relevant for pathologists as a useful diagnostic marker in the diagnosis of melanocytic tumors. However, the expressional pattern of Melan-A in poorly differentiated carcinoma of lung has never been reported so far.Case presentationHere, we report a 77-year-old female patient who presented with a large mass in the right lung and was subsequently diagnosed with a poorly differentiated carcinoma of lung. We unexpectedly found that the carcinoma in this patient exhibited diffuse Melan-A expression. ConclusionThis is the first case reported of a poorly differentiated carcinoma of lung with Melan-A expression. This report shows that Melan-A can express in poorly differentiated carcinoma, and highlights a potential diagnostic pitfall in the diagnosis of carcinoma, which urges pathologists to exercise caution in cases where Melan-A positivity and illustrates the need for further immunohistochemical or molecular examination to avoid misdiagnosis.