Evaluating Treatment Patterns and the Role of Neoadjuvant Chemotherapy in Plasmacytoid Urothelial Carcinoma: Insights from a Combined National and Institutional Series.

Background: Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience.

Methods: The NCDB was queried for localized PUC cases between 2004 and 2020.

Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma.

JCO Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC.

TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.

Purpose: Immune checkpoint inhibitors have revolutionized the treatment of renal cell carcinoma (RCC), but many patients do not respond to therapy and the majority develop resistant disease over time. Thus, there is increasing need for alternative immunomodulating agents. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may play a role in resistance to approved immune checkpoint inhibitors and is being investigated as a potential therapeutic target.

GP100 expression is variable in intensity in melanoma.

Drugs or cellular products that bind to gp100 are being investigated for treatment of cutaneous melanoma. The relative specificity of gp100 expression in melanocytes makes it an attractive target to harness for therapeutic intent. For example, Tebentafusp, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, has generated significant enthusiasm in recent years due to its success in improving outcomes for uveal melanoma and is being studied in cutaneous melanoma.

Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma.

Objective: To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review.

Methods: Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma in voided urine samples: Distinction from benign and high-grade papillary urothelial carcinoma.

Objective: Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC.

Methods: We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC.

Reevaluation of ovarian cyst fine-needle aspiration cytology: A 10-year institutional experience.

Objectives: Fine-needle aspiration (FNA) of ovarian cyst fluid remains useful for certain clinical circumstances despite low sensitivity and potential safety concerns. The current study aimed to reevaluate the performance of ovarian cystic fluid cytology following American College of Obstetricians and Gynecologists guidelines using a single-institution cohort.

Methods: A total of 507 ovarian cyst FNA cases from 2013 to 2023 were reviewed.

Cytologic evaluation of upper urinary tract specimens: An institutional retrospective study using The Paris System for Reporting Urine Cytology second edition with histopathologic follow-up.

Objective: Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow-up.

Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases.

Background: The tumor microenvironment (TME) contributes to cancer progression and treatment response to therapy, including in renal cell carcinoma (RCC). Prior profiling studies, including single-cell transcriptomics, often involve limited sample sizes and lack spatial orientation. The TME of RCC brain metastases, a major cause of morbidity, also remains largely uncharacterized.

Utility of parathyroid hormone immunocytochemistry in fine needle aspiration diagnosis of parathyroid tissue.

Objective: The cytomorphological features of parathyroid tissue (PTT) may overlap with those of thyroid lesions, thus posing a diagnostic challenge. In this retrospective study, we reviewed our institutional experience in using parathyroid hormone (PTH) immunocytochemistry (ICC) to substantiate the diagnosis of PTT on fine needle aspiration (FNA).

Methods: Our pathology database was searched for FNA cases in which PTH ICC was performed between 1 January 2015 and 31 March 2022.

FGF-21 Conducts a Liver-Brain-Kidney Axis to Promote Renal Cell Carcinoma.

Metabolic homeostasis is one of the most exquisitely tuned systems in mammalian physiology. Metabolic homeostasis requires multiple redundant systems to cooperate to maintain blood glucose concentrations in a narrow range, despite a multitude of physiological and pathophysiological pressures. Cancer is one of the canonical pathophysiological settings in which metabolism plays a key role.

Germline genetic variants are associated with development of insulin-dependent diabetes in cancer patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have dramatically improved survival in patients with cancer but are often accompanied by severe immune-related adverse events (irAEs), which can sometimes be irreversible. Insulin-dependent diabetes is a rare, but life-altering irAE. Our purpose was to determine whether recurrent somatic or germline mutations are observed in patients who develop insulin-dependent diabetes as an irAE.

Diagnosis of acinic cell carcinoma of the salivary gland on cytology specimens: Role of NOR-1 (NR4A3) immunohistochemistry.

Objectives: Acinic cell carcinoma (AcCC) is often a challenging diagnosis on cytology. Recently, NOR-1 (NR4A3) has been demonstrated as a sensitive and specific marker for AcCC. Therefore, we conducted this study to evaluate NOR-1 expression in AcCC cytology specimens and to compare its reactivity in other salivary gland tumours (non-AcCC).

Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance.

While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with the emergence of immune checkpoint inhibitors (ICIs) and VEGFR-targeting drugs, sizable proportions of patients still do not respond to upfront therapy and long-term responses only occur in a minority of patients. There is therefore a great need for the development of better predictors of response and an increased understanding of mechanisms of resistance to these therapies. Alternative immune checkpoints outside the PD-1/PD-L1 axis, such as LAG3, have been implicated as one mechanism of resistance to ICIs.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 1: a review of the literature on available testing options.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is increasing in incidence and is often first diagnosed on a cytology fine needle aspiration (FNA) specimen of metastatic nodal disease of the neck. In the setting of oropharyngeal squamous cell carcinoma, HPV status defines the disease with HPV-associated tumors having better overall prognosis than those that are HPV negative. Furthermore, metastatic squamous cell carcinoma of the neck of unknown origin requires testing for HPV as a positive result suggests an oropharyngeal primary.

Evaluation of TRPS1 Expression in Pleural Effusion Cytology Specimens With Metastatic Breast Carcinoma.

Objectives: Recent studies have shown that trichorhinophalangeal syndrome type 1 (TRPS1) is a sensitive and specific marker that shows positive staining in breast carcinoma. We conducted this study to evaluate the role of TRPS1 immunohistochemistry (IHC) in differentiating breast primary vs tumors from other primary sites in malignant pleural effusion cytology specimens (MPECSs).

Methods: We selected 61 MPECS cases with cell block material available to analyze TRPS1 IHC staining.

Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma.

We aimed to study mechanisms controlling metastatic outgrowth of melanoma into clinically relevant lesions, a critical process responsible for the majority of melanoma deaths. To this end, we developed novel in vivo models and identified molecular events that can be ascribed to their distinct phenotypes, indolent or highly metastatic. Induction of a proliferative state at distant sites was associated with high levels of the stem-like/progenitor marker, SOX2, and required the upregulation of FMOD, an extracellular matrix component, which modulates tumor-stroma interactions.

Copy number variations identified in thyroid FNA specimens are associated with Hürthle cell cytomorphology.

Background: The fine-needle aspiration (FNA) diagnosis of thyroid Hürthle cell neoplasms (HCNs) remains challenging. This study explored a possible association of copy number variations (CNVs) with Hürthle cell lesions of the thyroid.

Methods: Thyroid FNA cases that were diagnosed as follicular lesion of undetermined significance (FLUS) or follicular neoplasm (FN)/HCN for which the ThyroSeq version 3 genomic classifier test was performed were retrieved.

Expression of NKX3.1, Prostatic Specific Antigen and Prostatic Specific Alkaline Phosphatase in Cytology Specimens of Metastatic Prostatic Carcinoma.

Background And Objectives: NKX3.1 is an emerging marker for tumors of prostatic origin; however, the utility and diagnostic values of NKX3.1 have not been broadly studied in cytology specimens.

Clinicopathological Review of Micropapillary Urothelial Carcinoma.

Purpose Of Review: This review will discuss micropapillary urothelial carcinoma with respect to biology, histopathologic characteristics, genetic and molecular features, diagnosis, clinical management, and future directions of research.

Recent Findings: Recent consensus opinion study showed only moderate interobserver reproducibility in the diagnostic criteria. The most reproducible criteria with the highest consensus were multiple nests in the same lacunar spaces.

RAS mutation and associated risk of malignancy in the thyroid gland: An FNA study with cytology-histology correlation.

Background: Activating point mutations of the RAS gene (NRAS, HRAS, and KRAS) can be seen in benign and malignant thyroid tumors; among these, NRAS mutations are more commonly seen. This study was conducted to evaluate the thyroid risk of malignancy (ROM) associated with RAS mutations in thyroid fine-needle aspiration (FNA) at the authors' institution.

Methods: The authors searched their electronic database system between January 2015 and May 2021 for thyroid FNA cases with any type of RAS mutation.

Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases.

Despite unique genetic alterations within brain metastases (BrMs) and an immunologically distinct surrounding microenvironment, the composition and functional properties of tumor-infiltrating lymphocytes within BrM remain largely unexplored. In particular, the expression of coinhibitory receptors, such as programmed cell death 1 (PD-1), T cell immunoglobulin mucin receptor 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3), within BrMs is unknown. Using multiplexed quantitative immunofluorescence (QIF), this study evaluates the localized expression of PD-L1, level and functional profile of major T cell subsets, and coinhibitory receptors within lung cancer-associated BrMs and primary lung tumors.

Impact of Transoral Endoscopic Vestibular Approach Thyroidectomy on Pathologic Assessment.

Context.—: Since 2016, transoral endoscopic thyroid resection with vestibular approach (TOETVA) has been increasingly performed in the United States. Although guidelines for the procedure are evolving, indeterminate and malignant preoperative cytopathologic diagnoses are not a contraindication.

Anaplastic Thyroid Carcinoma: Cytomorphologic Features on Fine-Needle Aspiration and Associated Diagnostic Challenges.

Objectives: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy, and early diagnosis, often aided by fine-needle aspiration (FNA), is key to improving patient prognosis. While the current literature describes some of the cytologic features (CFs) of this entity, a comprehensive examination of the CFs has not yet been performed.

Methods: We retrospectively searched our electronic database for ATC cases with available slides between January 2008 and December 2019.