Hyalinizing Clear Cell Carcinoma of the Head and Neck: A Multicenter Retrospective Study of 87 Cases Focusing on Prognostic Pathologic Features and Grading Scheme.

Hyalinizing clear cell carcinoma (HCCC) is a salivary gland carcinoma characterized by the presence of clear and eosinophilic cells within a hyalinized stroma and the EWSR1 rearrangement. Aiming to identify prognostic factors and establish a grading system, we herein conducted a detailed clinicopathology review of a large retrospective cohort of 87 HCCCs from 7 tertiary centers. Most HCCCs (91%) originated from minor salivary glands, although major salivary glands were affected in 8%.

Tumor-Intrinsic and Microenvironmental Determinants of Impaired Antitumor Immunity in Chromophobe Renal Cell Carcinoma.

Purpose: While immune checkpoint inhibition (ICI) has transformed the management of many advanced renal cell carcinomas (RCCs), the determinants of effective antitumor immunity for chromophobe RCC (ChRCC) and renal oncocytic tumors remain an unmet clinical and scientific need.

Methods: Single-cell transcriptomic and T-cell receptor profiling was performed on tumor and adjacent normal tissue of patients with ChRCC and renal oncocytic neoplasms. Using machine learning, the cellular origin of renal oncocytic neoplasms was evaluated, with analysis of associated oncogenic pathways.

Morphologically In Situ Solid Papillary Carcinoma of the Breast With Lymph Node and Lung Metastasis: A Rare Case Report and Literature Review.

Solid papillary carcinoma (SPC) is rare, accounting for less than 1% of all breast cancers. According to the 5th edition of the WHO Classification of Breast Tumors (2019), SPC is divided into invasive (ISPC) and in situ (SPC in situ) subtypes. ISPC is characterized by an irregular or jigsaw pattern lacking myoepithelial cells, while SPC in situ is well-circumscribed, regardless of myoepithelial cell presence.

Presence of Tertiary Lymphoid Structures and Exhausted Tissue-Resident T Cells Determines Clinical Response to PD-1 Blockade in Renal Cell Carcinoma.

We describe a paradigm wherein combined high TLS and low tissue-resident exhausted CD8+ T cells are required for optimal response to PD-1 blockade in RCC. This analysis identifies key determinants of response to PD-1 blockade in advanced RCC and suggests avenues for future immune modulation through rational combination therapy strategies.

Oncogenic TFE3 fusions drive OXPHOS and confer metabolic vulnerabilities in translocation renal cell carcinoma.

Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by TFE3 gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic nature of most other renal cancers. Reliance on this TFE3 fusion-driven OXPHOS programme renders tRCCs vulnerable to NADH reductive stress, a metabolic stress induced by an imbalance of reducing equivalents.

Generation and Characterization of Ex Vivo Expanded Tumor-infiltrating Lymphocytes From Renal Cell Carcinoma Tumors for Adoptive Cell Therapy.

Autologous therapeutic tumor-infiltrating lymphocyte (TIL) therapy is a promising strategy to enhance antitumor immunity. Optimization of ex vivo TIL expansion could expand current immunotherapy options. Previous attempts to generate TIL in renal cell carcinoma (RCC) have been technically challenging.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers.

PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients.

Purpose: Programmed cell death protein 1 (PD-1) expression on CD8+TIM-3-LAG-3- tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear-cell renal cell carcinoma (mccRCC). Because inhibition of PD-1 signaling in regulatory T cells (Treg) augments their immunosuppressive function, we hypothesized that PD-1 expression on tumor-infiltrating Tregs would predict resistance to PD-1 inhibitors.

Experimental Design: PD-1+ Tregs were phenotyped using multiparametric immunofluorescence in ccRCC tissues from the CheckMate-025 trial (nivolumab: n = 91; everolimus: n = 90).

The Role of the Pathologist in Renal Cell Carcinoma Management.

Recent advances in our understanding of the molecular alterations underlying different types of renal cell carcinoma (RCC), as well as the implementation of immune checkpoint inhibitors in the treatment of patients with advanced disease, have significantly expanded the role of pathologists in the management of RCC patients and in the identification of predictive biomarkers that can guide patient treatment. In this chapter, we examine pathologists' evolving role in patient care and the development of precision medicine strategies for RCC.

Chronic diarrhea as a presentation of Behçet's disease.

Key Clinical Messages: Behçet's disease (BD) or syndrome is a chronic, recurrent, multisystem, inflammatory vasculitis disorder with findings of oral aphthous ulcers, genital ulcers, and uveitis. Gastrointestinal (GI) involvement can be the initial presentation as presented in this case.

Abstract: Behçet's disease (BD) or syndrome is a chronic, recurrent, multisystem, inflammatory vasculitis disorder of unknown etiology with classical findings of oral aphthous ulcers, genital ulcers, and ocular involvements including chronic anterior, intermediate, posterior, and even panuveitis.

Epigenomic charting and functional annotation of risk loci in renal cell carcinoma.

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC.

Ga-Prostate-Specific Membrane Antigen, A Potential Radiopharmaceutical in PET/CT To detect primary Cholangiocarcinoma.

  Ga Prostate-specific membrane antigen (PSMA) is an increasingly popular radiopharmaceutical tracer in prostate cancer and is becoming increasingly researched in other cancers such as breast cancer, renal cell carcinoma, glioblastoma multiforme, among others. Cholangiocarcinoma is the second most common primary hepatic malignant tumor; it is an aggressive tumor with a 5-year survival rate of less than 5 %. We herein report a case of primary cholangiocarcinoma detected on Ga-PSMA PET-CT conducted as part of follow up for prostate cancer and confirmed by biopsy and immunohistochemistry.