Immunotherapy response and resistance in patients with advanced uveal melanoma: a retrospective cohort study.

Metastatic uveal melanoma (mUM) is associated with poor prognosis. Ipilimumab/nivolumab has shown antitumor efficacy in phase II studies. Tebentafusp resulted in longer overall survival (OS) compared to investigator`s choice in a phase III study.

A targetable type III immune response with increase of IL-17A expressing CD4 T cells is associated with immunotherapy-induced toxicity in melanoma.

Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry.

A Novel Technique of Aseptic Manufacture of Autologous Serum Eye Drops (ASEDs) and Sterility Analysis of the Bottled Ophtioles.

Purpose: To introduce a novel technique of the aseptic manufacture of autologous serum eye drops (ASEDs) with a prefiltered closed system and to analyze the sterility of the produced ophtioles between 2018 and 2022.

Methods: This is a prospective single-center study conducted at the Department of Ophthalmology at a Swiss University Hospital between 2018 and 2022. For regulatory reasons, closed systems for manufacturing ASEDs are strongly recommended.

Episodic Abdominal Pain-An Unexpected Cause for a Common Clinical Problem.

A previously healthy 55-year-old male patient presented repeatedly to the emergency department with severe episodic periumbilical abdominal pain. After an extensive diagnostic work-up and subsequent clinical deterioration, appendiceal diverticulitis was diagnosed. We identified a correlation of white blood cell counts and possibly faecal calprotectin with the clinical presentation.

Clinical, histopathological and molecular features of dedifferentiated melanomas: An EORTC Melanoma Group Retrospective Analysis.

Purpose: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement.

Importance: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.

Objective: To revise the MPATH-Dx version 1.

Rare Choristoma of the Tarsal Conjunctiva: Critical Inspection Prevents Unnecessary Mutilation.

We report a case of a 26-year-old male patient with an incidental finding of a flesh-colored tumor with few vellus hairs on its surface, located on the fornix and the tarsal conjunctiva of the left lower eyelid. Histology of the biopsy showed a choristoma consisting of abundant vellus hairs, sebaceous glands, and sparse lacrimal gland tissue. Recognition of conjunctival vellus hairs is significant and raises the suspected diagnosis of choristoma, which can be confirmed by a small sample biopsy.

Hypoxia and Ezrin Expression in Primary Melanoma Have High Prognostic Relevance.

Hypoxia affects tumor aggressiveness and activates pathways associated with epithelial mesenchymal transition (EMT) which are crucial for tumor progress. In this study, the correlation of hypoxia and EMT with sentinel lymph node status and tumor-specific survival was investigated in primary melanomas. CD34 for capillary count and Hypoxia inducible factor-1α (HIF-1α) as hypoxia indicators as well as Ezrin and L1-Cell Adhesion Molecule (L1CAM), both critical proteins contributing to EMT, were analyzed using immunohistochemistry in 49 melanoma patients with long follow-up (F/U, mean 110 months; range 12−263 months).

Correction: Kudura et al. Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients. 2021, , 3830.

The authors wish to make the following corrections to this paper [...

Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms.

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features.

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients.

We aimed to investigate, whether F2-fluoro-2-desoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans performed at baseline (time point 0; TP 0) and three months after initiation of immunotherapy (time point 1; TP 1) can be used on a metastasis- and patient-level to predict the response to immune-checkpoint inhibition using FDG-PET/CT six months after treatment start (time point 2; TP 2) in metastatic melanoma patients. This single-center retrospective study considered metastatic melanoma patients treated with immune checkpoint inhibition from TP 0 to TP 2. An analysis on a metastasis- and patient-level was carried out.

Intraneural fibrosis and loss of microvascular architecture - Key findings investigating failed human nerve allografts.

Background: Processed nerve allografts are increasingly used in clinical nerve reconstruction with promising results. However, allograft failure has been reported, leading to chronic pain and persistent loss of function. In the present work, we performed a histological and immunohistochemical analysis of two failed allograft reconstructions of a sensory human nerve one year after primary surgery.

Malignancy Rate of Indeterminate Findings on FDG-PET/CT in Cutaneous Melanoma Patients.

Background: The use of -2-Fluor-2-desoxy-D-glucose Positron Emission Tomography/Computed Tomography FDG-PET/CT in clinical routine for staging, treatment response monitoring and post treatment surveillance in metastatic melanoma patients has noticeably increased due to significant improvement of the overall survival rate in melanoma patients. However, determining the dignity of the findings with increased metabolic activity on FDG-PET/CT can be sometimes challenging and may need further investigation.

Purpose: We aimed to investigate the malignancy rate of indeterminate findings on FDG-PET/CT in metastatic cutaneous melanoma patients.

Improved detection of in-transit metastases of malignant melanoma with BSREM reconstruction in digital [F]FDG PET/CT.

Objectives: To compare block sequential regularized expectation maximization (BSREM) and ordered subset expectation maximization (OSEM) for the detection of in-transit metastasis (ITM) of malignant melanoma in digital [F]FDG PET/CT.

Methods: We retrospectively analyzed a cohort of 100 [F]FDG PET/CT scans of melanoma patients with ITM, performed between May 2017 and January 2020. PET images were reconstructed with both OSEM and BSREM algorithms.

Ocular Pathology and Occasionally Detectable Intraocular Severe Acute Respiratory Syndrome Coronavirus-2 RNA in Five Fatal Coronavirus Disease-19 Cases.

Introduction: In December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic broke out. The virus rapidly spread globally, resulting in a major world public-health crisis. The major disease manifestation occurs in the respiratory tract.

Dedifferentiated melanomas: Morpho-phenotypic profile, genetic reprogramming and clinical implications.

Phenotypic plasticity of malignant melanoma is a well-known phenomenon. Several translational studies and small case series have reported this clinical and biological entity, particularly in metastatic melanoma, showing frequent aberrant expression of non-melanocytic differentiation markers of different lineages, posing remarkable challenges due to several alternative differential diagnoses including undifferentiated carcinoma and sarcomas. When melanoma loses its typical morpho-phenotype by routinely used diagnostic immunohistochemical markers, it is defined as "dedifferentiated melanoma".

Progressive Disease in Sentinel-negative Melanoma Patients: Biological Differences and Importance of Sentinel Lymph Node Biopsy.

Background/aim: Among the most important prognostic factors in melanoma is the sentinel lymph node (SLN) status.

Materials And Methods: Using our electronic database we identified 109 of 890 SLN-negative patients with progressive disease (PD). These patients were characterized for melanoma type, molecular type, sequence and extent of metastatic spread.

Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis.

Background: Metastatic tumor spread is a complex multistep process. Due to the blood-brain barrier, metastasis to the central nervous system is restrictive with a distinct predilection for certain tumor types. In melanoma patients, brain metastasis is a common endpoint with the majority showing evidence of widespread disease at autopsy.

The value of axillary skin electron microscopic analysis in the diagnosis of lysosomal storage disorders.

Both lysosomal storage diseases and mitochondrial diseases are a group of genetic-inherited metabolic disorders. In an era, where "old fashioned methods" are apparently being replaced by evolving molecular techniques (i.e.