Actionable NSCLC Mutation Identification by Comprehensive Genomic Profiling for Clinical Trial Enrollment: The European Program for the Routine Testing of Patients With Advanced Lung Cancer (EPROPA).

Introduction: The advocacy Women Against Lung Cancer in Europe (WALCE) promoted the European Program for the Routine Testing of Patients With Advanced Lung Cancer (EPROPA) and provided a free-of-charge molecular profiling platform for NSCLC sample characterization with the aim of increasing the detection of targetable drivers and improving patients' access to clinical trials in Europe.

Methods: From January 2021 to December 2023, 20 centers located at five different European countries (Greece, Slovenia, Romania, Albania, and Italy) joined EPROPA, with 555 patients with advanced NSCLC registered to the program. Anonymized patients' clinical-pathological data were shared through the EPROPA web platform and tissue samples were collected at the Molecular Pathology Unit of the Reference Center (University of Turin) for molecular analyses.

Changes in categorization or nomenclature within neuroendocrine tumors.

Abstract: The 5th edition of the World Health Organization (WHO) classification of neuroendocrine neoplasms (NENs) is built to achieve a uniform terminology and to define a similar diagnostic scheme across different anatomic locations. Since the 4th edition, a chapter discussing NENs in nonneuroendocrine organs has been introduced, which proposes a binary system for classification segregating well-differentiated neoplasms, termed neuroendocrine tumors (NETs), and poorly differentiated neoplasms, termed neuroendocrine carcinomas (NECs). A grading system for NETs is based on mitotic index and/or Ki-67 index and/or necrosis, depending on the different locations.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index.

Germline NGS targeted analysis in adult patients with sporadic adrenocortical carcinoma.

Background: Adrenocortical carcinoma (ACC) is a rare cancer that arises sporadically or due to hereditary syndromes. Data on germline variants (GVs) in sporadic ACC are limited. Our aim was to characterize GVs of genes potentially related to adrenal diseases in 150 adult patients with sporadic ACC.

Polyoxometalate exerts broad-spectrum activity against human respiratory viruses hampering viral entry.

Human respiratory viruses have an enormous impact on national health systems, societies, and economy due to the rapid airborne transmission and epidemic spread of such pathogens, while effective specific antiviral drugs to counteract infections are still lacking. Here, we identified two Keggin-type polyoxometalates (POMs), [TiWCoO] (TiWCo) and [TiPWO] (TiPW), endowed with broad-spectrum activity against enveloped and non-enveloped human respiratory viruses, i.e.

Diagnostic Utility of a Modified Reticulin Algorithm in Pediatric Adrenocortical Neoplasms.

Pediatric adrenocortical neoplasms (ACNs) are extremely rare tumors in contrast to their adult counterparts. Distinguishing benign from malignant is challenging based on pure morphologic grounds. Previously, 2 scoring systems were proposed in pediatric ACN, including the Wieneke criteria (WC) and its modified version (modified WC [mWC]).

Optimising Radioligand Therapy for Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumours: Expert Opinion from an Italian Multidisciplinary Group.

Radioligand therapy (RLT) with lutetium (Lu) oxodotreotide is an approved therapy in combination with somatostatin analogues (SSAs) for patients with advanced, well-differentiated G1-G2, gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs) that progress on SSAs. We conducted a series of round table meetings throughout Italy to identify issues related to RLT delivery to patients with GEP-NETs. Four key issues were identified: (1) the proper definition of tumour progression prior to RLT initiation; (2) the impact of RLT in patients with bone metastases and/or high hepatic tumour burden; (3) the optimal follow-up protocol after RLT; and (4) organisational issues related to RLT use and managerial implications.

Pulmonary Low Malignant Potential Adenocarcinoma: A Validation of the Proposed Criteria for This Novel Subtype.

Adenocarcinoma (ADC) is the most common histologic type of lung cancer, including in situ (lepidic), minimally invasive, and invasive forms. While the former 2 types are associated with a favorable outcome, the latter includes tumors with variable behavior, often tumor stage-related. A recent study proposed strict morphologic criteria defining a new subgroup of resected stage I invasive ADC (16% of cases) with favorable outcomes (100% disease-specific survival), named "ADC of low malignant potential (LMP-ADC).

Updates on lung neuroendocrine neoplasm classification.

Lung neuroendocrine neoplasms (NENs) are a heterogeneous group of pulmonary neoplasms showing different morphological patterns and clinical and biological characteristics. The World Health Organisation (WHO) classification of lung NENs has been recently updated as part of the broader attempt to uniform the classification of NENs. This much-needed update has come at a time when insights from seminal molecular characterisation studies revolutionised our understanding of the biological and pathological architecture of lung NENs, paving the way for the development of novel diagnostic techniques, prognostic factors and therapeutic approaches.

Clinical impact of mixed pulmonary carcinoma and carcinoid: the driver from their mono-clonal origin.

The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described.

Heterogeneity of TPIT expression in ACTH-secreting extra-pituitary neuroendocrine tumors (NETs) supports the existence of different cellular programs in pancreatic and pulmonary NETs.

Extra-pituitary ACTH secretion is associated with a variety of neoplastic conditions and may cause the so-called ectopic ACTH-dependent Cushing syndrome (CS). The clarification of the mechanisms of extra-pituitary ACTH expression would provide potential therapeutic targets for this complex and severe disease. In the adenohypophysis, the transcription factor TPIT, co-operating with other molecules, induces POMC expression and ACTH production.

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for appendiceal neuroendocrine tumours (aNET).

The aim of the present guidance paper is to update the previous ENETS guidelines on well differentiated appendiceal neuroendocrine tumours (NET), providing practical guidance for the diagnosis and management of appendiceal NET (aNET); poorly differentiated neoplasms are dealt with in a separate guidance paper. This paper is structured on a question-answer format in order to also address controversial issues and areas where uncertainty regarding the management and follow-up of aNET exists. All recommendations are offered on the basis of the best available evidence, along with the authors' experiences in managing these neoplasms.

Clinical and Pathological Features and Gene Expression Profiles of Clinically Aggressive Papillary Thyroid Carcinomas.

Papillary thyroid carcinoma (PTC) is considered an indolent neoplasm but it may demonstrate aggressive behavior. We aimed to identify clinical and pathological characteristics and molecular signatures associated with aggressive forms of PTCs. We selected 43 aggressive PTC cases based on the presence of metastases at the time of diagnosis, the development of distant metastasis during follow-up, and/or biochemical recurrence, and 43 PTC patients that were disease-free upon follow-up, matching them according to age, sex, pT, and pN parameters.

Exploring circular MET RNA as a potential biomarker in tumors exhibiting high MET activity.

Background: MET-driven acquired resistance is emerging with unanticipated frequency in patients relapsing upon molecular therapy treatments. However, the determination of MET amplification remains challenging using both standard and next-generation sequencing-based methodologies. Liquid biopsy is an effective, non-invasive approach to define cancer genomic profiles, track tumor evolution over time, monitor treatment response and detect molecular resistance in advance.

The Driver Role of Pathologists in Endocrine Oncology: What Clinicians Seek in Pathology Reports.

Endocrine neoplasia represents an increasingly broad spectrum of disorders. Endocrine neoplasms range from incidental findings to potentially lethal malignancies. In this paper, we cover the impact of pathology in the interpretation of the clinic-pathological, genetic, and radiographic features underpinning these neoplasms.

Solitary fibrous tumor of the thyroid: report of three cases with a focus on cytological features and histological clues for malignancy.

Solitary fibrous tumor is a mesenchymal tumor of intermediate malignant potential characterized by a recurrent NAB2::STAT6 fusion and STAT6 nuclear expression. Primary thyroid solitary fibrous tumor is relatively uncommon, with 45 cases described in the English literature to date. Although its histologic features are characteristic, its diagnosis in the thyroid can be problematic, especially in small biopsies or cytology specimens.

Mixed mucinous adenocarcinoma/large cell neuroendocrine carcinoma of the uterine cervix: case report and molecular characterization of a rare entity.

Mixed neuroendocrine-non-neuroendocrine carcinomas of the cervix are rare and generally aggressive diseases. They often present at an advanced stage with hematogenous or lymphatic metastases. The prognosis is poor, mostly influenced by the neuroendocrine component.

Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review.

The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date.

Metastatic Adrenal PEComa: Case Report and Short Review of the Literature.

PEComa has become a widely accepted entity, and increased recognition has led to descriptions of this tumor in a wide variety of anatomic sites, including the adrenal gland. PEComa (perivascular epithelioid cell tumor) is a mesenchymal tumor composed of perivascular cells, and the most frequent sites of PEComas are the uterus and retroperitoneum. The incidence is <1 per 1,000,000 people.

The management of postoperative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients.

Objective: The management of adrenocortical carcinoma (ACC) recurrences remains controversial, and we present herein our experience with postoperative ACC recurrences.

Design And Methods: Retrospective analysis in a single reference center of 106 patients with ACC recurrence.

Results: The median follow-up was 45 months, the median recurrence-free survival (RFS) 12 months (IQR 6-23), and the median overall survival (OS) 45 months (IQR 29-75).

The EMT transcription factor ZEB1 governs a fitness-promoting but vulnerable DNA replication stress response.

The DNA damage response (DDR) and epithelial-to-mesenchymal transition (EMT) are two crucial cellular programs in cancer biology. While the DDR orchestrates cell-cycle progression, DNA repair, and cell death, EMT promotes invasiveness, cellular plasticity, and intratumor heterogeneity. Therapeutic targeting of EMT transcription factors, such as ZEB1, remains challenging, but tumor-promoting DDR alterations elicit specific vulnerabilities.

Prognostic Factors across Poorly Differentiated Neuroendocrine Neoplasms: A Pooled Analysis.

Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated.

Overexpression of INSM1, NOTCH1, NEUROD1, and YAP1 genes is associated with adverse clinical outcome in pediatric neuroblastoma.

Pediatric neuroblastoma is responsible for approximately 8-10% of pediatric tumors, and it is one of the leading causes of tumor-related deaths in children. Although significant progress has been made in the characterization of neuroblastoma in recent years, the mechanisms influencing the prognosis of neuroblastoma patients remain largely unknown. Our aim was to investigate if the major neuroendocrine-associated transcriptional drivers, including ASCL1, NEUROD1, DLL3, NOTCH1, INSM1, MYCL1, POU2F3 and YAP1 are correlated with specific clinical and pathological characteristics.

Histopathologic Features of Adrenal Cortical Carcinoma.

Adrenal cortical carcinoma (ACC) is a rare and aggressive malignancy that poses challenging issues regarding the diagnostic workup. Indeed, no presurgical technique or clinical parameters can reliably distinguish between adrenal cortical adenomas, which are more frequent and have a favorable outcome, and ACC, and the final diagnosis largely relies on histopathologic analysis of the surgical specimen. However, even the pathologic assessment of malignancy in an adrenal cortical lesion is not straightforward and requires a combined evaluation of multiple histopathologic features.