The absence of FOXA2 and HNF1β expression in vasculogenic mesenchymal lesions of germ cell origin suggests an evolutionary pathway similar to that of sarcomatoid yolk sac tumor.

Vasculogenic mesenchymal lesions (VMLs) are uncommon phenotypes of germ cell tumor (GCT) origin that are mostly found after chemotherapy of mediastinal yolk sac tumor (YST). These lesions typically lack expression of classical YST markers [α-fetoprotein (AFP) and glypican-3 (GPC3)]. FOXA2 and HNF1β are key inducers of the YST phenotype and co-operate to promote transcription of genes involved in YST development (AFP, GPC3, GATA3, among others).

High-Grade Early-Onset Prostate Cancer: Assessment of TMPRSS2::ERG-Negative Tumors Suggests Low Frequency of Germline Alterations and a Pathogenic Role for HOXB13.

Early onset prostate cancer (EOPC; defined herein as prostate cancer [PCa] affecting men ≤ 55 years-old) tends to show low histologic grade, likely representing early detection of indolent tumors that would otherwise be diagnosed later in life. A small subset of EOPC exhibits Gleason scores consistent with high-risk disease (Grade Groups 4 to 5; high-grade EOPC [HG-EOPC] hereafter). In this study, we assess the clinicopathologic features of HG-EOPC, with genomic analysis of ERG-negative cases.

Merkel Cell Carcinoma: An Updated Review Focused on Bone and Bone Marrow Metastases.

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. Regional nodal metastases affect 40-50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood.

Phenotypic and Molecular Features of Somatically Derived "Yolk Sac Tumors": Similarities and Differences With Counterparts of Germ Cell Origin.

A subset of somatic carcinomas shows morphologic and immunophenotypic similarities to yolk sac tumor (YST) of germ cell origin, including fetal adenocarcinomas of the lung and somatic carcinomas with "YST"/enteroblastic differentiation. At least some of these tumors may result from reprogramming somatic cancer cells, leading to the acquisition of a "pluripotent" phenotype. Although these somatic tumors express markers such as SALL4, glypican 3, and alpha-fetoprotein, which are positive in germ cell-derived YST, it is currently uncertain to what degree their molecular features overlap with those of germ cell tumors (GCTs).

Computer-Based Detection of Colorectal Serrated Lesions: Digital Flatness, a Novel Metric Designed for Whole-Slide Images.

Colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) are characterized by sawtooth or stellate epithelial architecture. Distinguishing between SSLs and HPs is crucial as SSLs are precursors of colorectal carcinomas in 30% of cases, whereas HPs are likely precursors to SSLs. The differentiation of SSL from HP is primarily based on architectural features.

Insights into the impact of chromosome 3p mutations in advanced renal cell carcinoma treated with immune-based combinations or targeted therapy: A single-center experience.

Background: Immune-based combinations have transformed first-line treatment for metastatic renal cell carcinoma (mRCC), but reliable biomarkers for patient selection remain elusive. Chromosome 3p mutations (e.g.

Unveiling the molecular landscape and clinically relevant molecular heterogeneity of mucosal melanoma of the head and neck region.

Aims: Mucosal melanoma of the head and neck (MM-H&N) is an aggressive disease known for its frequent residual tumours/relapses (RT/R) at the surgical site, as well as eventual metastases. Our understanding of the MM-H&N mutational landscape, together with the correlation of specific mutations with clinical-pathological features, is significantly less comprehensive compared to that of cutaneous melanoma. Additionally, the mutational status of consecutive samples collected from single patients has not been investigated, which limits our ability to characterise the prognosis and treatment options for this patient subset.

Analysis of HNF1β expression suggests that its downregulation is involved in the sarcomatoid transformation of yolk sac tumor.

Sarcomatoid yolk sac tumor postpubertal-type (YSTpt) is a rare phenotype of germ cell tumor that occurs mostly after chemotherapy. Its diagnosis is clinically relevant but challenging, due to its somewhat inconspicuous histologic features and negative/low expression of classical YSTpt makers (α-fetoprotein (AFP), glypican-3 (GPC3), and GATA3)). HNF1β is likely a key inducer of the YSTpt phenotype, acting in part by regulating the binding of FOXA2 to its target genomic sequences.

Ultrasound-Guided Hydro-Dissection of the Superficial Fascia for Cervical Myofascial Pain: A Case Series.

The fascial system has recently gained attention for its potential role in various painful disorders. With the advancement of our understanding regarding the rich innervation of the fascia, it has emerged as a potential pain generator and a target for treatment in many cases. The superficial fascia presents a rich plexiform intrinsic neural network and runs within the subcutaneous fat tissue.

Sex Cord Stromal Tumors of the Testis: A Review with Molecular Updates.

This article reviews potential future changes in the classification of sex cord stromal tumors (SCST). The most useful immunohistochemical stains are summarized, and recent molecular developments are highlighted, considering their clinical impact on classification and the pathologists' daily practice.

Analysis of benign neoplasms of the rete testis formerly termed "Sertoliform cystadenomas" demonstrates that they are not Sertoli cell tumours with intra-rete growth.

Aims: Benign tumours of the rete testis include mostly cystadenomas and adenomas. A subset with tubular or tubulopapillary architecture shows morphological similarities to Sertoli cell tumours; these neoplasms were previously termed "Sertoliform cystadenomas of the rete testis". In the most recent WHO classification, they have been interpreted as Sertoli cell tumours, not otherwise specified (NOS), with pure intra-rete growth, and therefore excluded as an entity.

State of the art of adjuvant immunotherapy in urothelial cancer: New developments and upcoming changes.

In recent years, several clinical trials focused on the potential role of immune-checkpoint inhibitors (ICIs) in the adjuvant treatment of muscle-invasive urothelial cancer (UC). Heretofore, only the anti-programmed death protein 1 (anti-PD1) nivolumab received European Medical Agency (EMA) approval for cisplatin-unfit patients. In our work, we deeply analyzed the results of the three pivotal studies in view of the rapidly evolving therapeutic advanced UC's scenario.

Advances in Diagnosis of Skin and Superficial Tissue Disorders-"Old and Emerging" Diagnostic Tools.

Skin and superficial tissue disorders (SSTDs) are some of the most common diseases affecting humans [...

Line-Field Confocal Optical Coherence Tomography: A New Skin Imaging Technique Reproducing a "Virtual Biopsy" with Evolving Clinical Applications in Dermatology.

Background: Line-field confocal optical coherence tomography is a novel technology able to reproduce a "virtual biopsy" of the skin. The aim of this review is to explore the application of line-field confocal optical coherence tomography (LC-OCT) in various skin diseases, covering skin cancers, inflammatory and infectious skin diseases, genetic diseases, cosmetic procedures, and less common disorders.

Methods: Study selection was conducted based on LC-OCT and using pertinent MeSh terms, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to March 2024; to evaluate the quality and risk of bias of studies, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used.

Beta-Catenin Alterations in Postchemotherapy Yolk Sac Tumor, Postpubertal-Type With Enteroblastic Features.

Postchemotherapy postpubertal-type yolk sac tumors (YST) with glandular and solid phenotypes are aggressive and commonly resistant to systemic chemotherapy. These neoplasms show morphologic features that significantly overlap with those of somatic carcinomas with "enteroblastic" or "fetal" phenotype (the preferred terminology depends on the site of origin). They often present as late or very late recurrences, and their diagnosis is challenging because they frequently affect patients in an age group at risk for carcinomas of somatic origin.

Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas.

Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers.

Methods: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM).

Confocal Assessment of Pigmented-Mucosal Lesions: A Monocentric, Retrospective Evaluation of Lip and Genital Area.

Introduction: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial.

Objectives: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score.