TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E-Positive Langerhans Cell Histiocytosis.

Background: In various malignancies, the co-occurrence of BRAF V600E and TERT promoter mutations (C228T and C250T) has been associated with tumor aggressiveness and poor prognosis. However, the presence of these TERT promoter mutations in Langerhans cell histiocytosis (LCH) remains unexplored.

Methods: We investigated the prevalence of TERT promoter C228T and C250T mutations in 40 formalin-fixed, paraffin-embedded (FFPE) LCH samples positive for BRAF V600E.

Deep learning on histological slides accurately predicts Consensus Molecular Subtypes and spatial heterogeneity in colon cancer.

Colon cancer (CC) is the third most prevalent cancer type. It is highly heterogeneous, particularly in terms of molecular profiles, which have both prognostic and predictive impacts on the treatment efficacy. However, CC treatment in adjuvant situations is currently guided solely by T and N staging.

Soluble PD-L1 (sPD-L1) as a biomarker of durable response and survival in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitors (ICIs).

Introduction: There is a need for biomarkers to predict response and survival to immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Soluble PD-L1 (sPD-L1) has shown biomarker potential. The objective of this study was to evaluate sPD-L1 in patients with advanced NSCLC treated with first-line ICIs.

Evaluation of gut leakage and bacterial translocation as efficacy biomarkers of immunotherapy in advanced non-small cell lung cancer (NSCLC).

Background: Despite the therapeutic advancements achieved through immunotherapy [immune checkpoint inhibitors (ICIs)] in treating advanced non-small cell lung cancer (NSCLC), the majority of patients will experience tumor progression. There is an urgent need for new predictive biomarkers of ICI efficacy in this setting. Our study aims to demonstrate the role of gut leakage, evaluated by plasma citrulline, and bacterial translocation, through blood microbiome assessment, as predictive markers of response to ICIs in advanced NSCLC.

Advancing sarcoma diagnostics with expanded DNA methylation-based classification.

Purpose: Sarcomas pose a severe diagnostic challenge. A wide variety of these distinct entities need to be distinguished from each other and from less aggressive types of mesenchymal tumors, to ensure correct clinical management. A machine learning based classifier for sarcomas utilizing DNA methylation data from 1077 tumors recognizing 62 sarcoma types has already been developed and termed the sarcoma classifier, which we published in 2021.

Plasmacytoid dendritic cell proliferations, malignant histiocytic (macrophage/dendritic cell) neoplasms and follicular dendritic cell neoplasms: report from the 2024 Joint CSHP/EA4HP/SH workshop.

Histiocytic and dendritic cell neoplasms of hematopoietic origin are derived from or show differentiation towards the cells of the mononuclear phagocyte system. Plasmacytoid dendritic cell proliferations/neoplasms include mature plasmacytoid dendritic cell proliferations identified in the context of a defined myeloid neoplasm and blastic plasmacytoid dendritic cell neoplasm, an aggressive tumor with a poor outcome. Malignant histiocytic (macrophage/dendritic cell) neoplasms occur de novo or in the setting of another hematological malignancy, typically "transdifferentiated" from associated lymphoid neoplasia.

Cluster analysis reveals the clinical spectrum of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a clonal-inflammatory neoplasm driven by mutations in MAPK pathway proto-oncogenes, such as BRAF. Clinical manifestations are protean, affecting virtually every system. This cohort study analyzed 661 patients with ECD to classify them based on clinical features and mutational profiles using unsupervised clustering.

NTRK1-rearranged histiocytosis: clinicopathologic and molecular features.

Non-Langerhans cell histiocytoses are a diverse group of histiocytic diseases. Different entities are defined based on clinical, histopathologic, and/or molecular characteristics. This study aimed to define NTRK-rearranged histiocytosis.

Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma.

Background: Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial.

Methods: ctDNA was evaluated before treatment (baseline) and at 4 weeks (before the third cycle of treatment, C3) using droplet-digital PCR assays based on the detection of CpG methylation.

Histiocytoses and reactive proliferations of histiocytes: current state of the art and evolving concepts-a report from the joint CSHP-EA4HP-SH workshop 2024, Hefei, China.

Reactive and clonal proliferations of histiocytes (macrophages/dendritic cells) represent a broad spectrum of disorders, which can affect virtually any organ of the body. The clinical spectrum ranges from benign, localized and self-limiting manifestations to severe multi-system disease. Hemophagocytic lymphohistiocytosis (HLH) is a frequently life-threatening, systemic hyperinflammatory process triggered by massive cytokine release by activated, reactive macrophages.

Monocytic meningitis complicating histiocytosis and response to MEK-inhibitor: a case series.

Central nervous system (CNS) involvement is common in histiocytosis, yet cerebrospinal fluid (CSF) analysis often yields normal results. We present three cases of monocytic meningitis associated with histiocytosis. The first patient was diagnosed with Erdheim-Chester disease (ECD) and exhibited evidence of a MAP2K1 mutation, concomitant with chronic myelomonocytic leukemia.

Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France.

Malignant histiocytoses (MH) are rare and poorly understood cancers, with no established therapeutic guidelines. We conducted a national retrospective study of MH diagnosed in France between 2000 and 2023. All cases underwent centralized histological review, and several malignant tumors with a stroma highly enriched in histiocytes were excluded.

Diagnosis and treatment of dermatofibrosarcoma protuberans. European interdisciplinary guideline - update 2024.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Union of Medical Specialists (UEMS) and the European Academy of Dermatology and Venereology (EADV) was formed to update recommendations on DFSP diagnosis and treatment, based on current literature reviews and the experts' consensus. Diagnosis is suspected clinically and confirmed by pathology report, which should specify whether a transformation in higher-grade fibrosarcoma occurred.

Combined Analyses of Circulating Tumor DNA and Immunoscore in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France/HORG-IDEA-Greece Trials.

Purpose: Immunoscore (IS) and circulating tumor DNA (ctDNA) are two emerging technologies in improving prognostication and tailoring adjuvant treatments in patients resected from a stage III colon cancer (CC). Here, we analyzed the prognostic value of the two biomarkers in patients who participated in the randomized phase III IDEA-France and HORG trials.

Methods: Plasma samples were collected after surgery and before adjuvant chemotherapy.

Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials.

Purpose: The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials.

Patients And Methods: 3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score.

Synchronous clonally related anaplastic large cell lymphoma and malignant histiocytosis.

Background: Synchronous malignant histiocytoses are rare conditions that occur concurrently with another hematologic neoplasm. Most reported cases are associated with B-cell lymphoproliferative disorders, while associations with T-cell hemopathies are less common. These two diseases may share mutations and/or cytogenetic anomalies, which can lead to malignant proliferations.

Role of the HGF/c-MET pathway in resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Most of advanced non-small cell lung cancer (NSCLC) patients will experience tumor progression with immunotherapy (IO). Preliminary data suggested an association between high plasma HGF levels and poor response to IO in advanced NSCLC. Our study aimed to evaluate further the role of the HGF/MET pathway in resistance to IO in advanced NSCLC.