Unlocking the potential of organoids in cancer treatment and translational research: An application of cytologic techniques.

Patient-derived organoid models hold promise for advancing clinical cancer research, including diagnosis and personalized and precision medicine approaches, and cytology, in particular, plays a pivotal role in this process. These three-dimensional multicellular structures are heterogeneous, potentially maintain the cancer phenotype, and conserve the genomic, transcriptomic, and epigenomic patterns of the parental tumors. To ensure that only tumor tissue is used for organoid development, cytologic validation is necessary before initiating the process of organoid generation.

Incorporating cytologic adequacy assessment into precision oncology workflow using telepathology: An institutional experience.

Background: Tumor sample quality and quantity determine the success of somatic mutation analysis. Thus, a rapid on-site evaluation (ROSE) tumor cytology adequacy assessment was incorporated into the workflow of precision oncology at Weill Cornell Medicine in New York City. Optimal samples were obtained from 68 patients with metastatic cancer.

Assessing the diagnostic accuracy for pleomorphic adenoma and Warthin tumor by employing the Milan System for Reporting Salivary Gland Cytopathology: An international, multi-institutional study.

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported.

Interobserver variability between cytopathologists and cytotechnologists upon application and characterization of the indeterminate category in the Milan System for Reporting Salivary Gland Cytopathology.

Background: The indeterminate categories in the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) are diagnostically challenging because of inherent heterogeneity and complexity, with wide interobserver variability (IOV). Herein, the authors explore the concordance rate (CR) between cytopathologists (CPs) and cytotechnologists (CTs) in interpreting indeterminate salivary gland lesions using the MSRSGC.

Methods: Between 2011 and 2016, 86 indeterminate fine-needle aspirations had slides available for review, of which 48 had follow-up.

Cancer-Specific Thresholds Adjust for Whole Exome Sequencing-based Tumor Mutational Burden Distribution.

Purpose: To understand the clinical context of tumor mutational burden (TMB) when comparing a pan-cancer threshold and a cancer-specific threshold.

Materials And Methods: Using whole exome sequencing (WES) data from primary tumors in The Cancer Genome Atlas (TCGA) (n=3,534) and advanced/metastatic tumors from Weill Cornell Medicine (WCM Advanced) (n=696), TMB status was determined using a pan-cancer and cancer-specific threshold. Survival curves, number of samples classified as TMB high, and predicted neoantigens were used to evaluate the differences between thresholds.

Mucoepidermoid carcinoma, acinic cell carcinoma, and adenoid cystic carcinoma on fine-needle aspiration biopsy and The Milan System: an international multi-institutional study.

Background: We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC).

Materials And Methods: The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC.

Application of the Milan System for Reporting Submandibular Gland Cytopathology: An international, multi-institutional study.

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a 6-tier diagnostic category system with associated risks of malignancy (ROMs) and management recommendations. Submandibular gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a higher relative proportion of malignancy, and this may affect the ROM and subsequent management. This study evaluated the application of the MSRSGC and the ROM for each diagnostic category for 734 submandibular gland FNAs.

The role of BRCA1-associated protein 1 in the diagnosis of malignant mesothelioma in effusion and fine-needle aspiration cytology.

Background: Malignant mesothelioma (MM) is a diagnostically challenging entity in cytology specimens due to the lack of architectural context and a cytomorphologic overlap between malignant and reactive mesothelial cells (RMCs). A diagnostic marker with excellent specificity is not currently available in clinical practice. The newly appreciated BRCA1-associated protein 1 (BAP1) antibody may help distinguish MM from RMC based on its immunohistochemical (IHC) staining pattern but its role in cytopathology is controversial.

Immunohistochemical analysis of OTP and NKX6.1 in neuroendocrine tumors of the lung and pancreas.

Background: Homeobox transcription factors have demonstrated utility in diagnosing neuroendocrine tumors. Orthopedia homeobox protein (OTP) has a well-defined role in embryonic neurodevelopment and has also been described as a prognostic marker in lung neuroendocrine tumors (NET). Additionally, NK6 homeobox-1 (NKX6.

Improved correlation of urinary cytology specimens using The Paris System in biopsy-proven upper tract urothelial carcinomas.

Background: Urine cytology specimens are essential for screening and monitoring high-grade urothelial carcinomas. However, inconsistent reporting and equivocal diagnostic categories have remained a challenge. The Paris System for Reporting Urinary Cytology (TPS) was developed to provide clear cytomorphologic criteria for urine cytology specimens.

Patient derived organoids to model rare prostate cancer phenotypes.

A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer.

The role of the Milan System for Reporting Salivary Gland Cytopathology: A 5-year institutional experience.

Background: Fine-needle aspiration (FNA) is widely accepted in the preoperative management of salivary gland lesions. The proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) aims to standardize reporting terminology. Studies regarding the risk of malignancy (ROM) for the proposed categories continue to evolve.

Bone biopsy protocol for advanced prostate cancer in the era of precision medicine.

Background: Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or to identify emerging resistance mechanisms. Due to a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue for clinical and genomic studies is challenging.

Methods: Patients with prostate cancer bone metastases were enrolled between February 2013 and March 2017 on an institutional review board-approved protocol for prospective image-guided bone biopsy.

Acquired myospherulosis secondary to gluteal augmentation on fine needle aspiration cytology: A diagnostic challenge.

A 30-year-old female presented with a three-month history of a multilocular cystic lesion over the lumbosacral spine. Fine-needle aspiration biopsy (FNA) of the lesion was performed at an outside institution, and a cytologic diagnosis, suspicious for chordoma, was rendered. The patient presented for surgical consultation at our institution.

On-site Cytology for Development of Patient-Derived Three-dimensional Organoid Cultures - A Pilot Study.

Background/aim: Development of patient-derived three-dimensional (3D) organoid cultures is an emerging technique in the field of precision oncology. We aimed to integrate on-site adequacy evaluation using cytology into the tumor organoid development workflow to ensure precise characterization and growth of these cultures.

Patients And Methods: Cancer patients were consented to a Precision Medicine trial.

An emerging role for cytopathology in precision oncology.

Precision medicine is an emerging field in medicine for disease prevention and treatment that takes into account the individual variability in genes, environment, and lifestyle for each individual patient. The authors have developed a special program as part of the Englander Institute for Precision Medicine to grow patient-derived, 3-dimensional tumor organoids for tumor-specific drug testing, tailoring treatment strategies, and as models for studying drug resistance. Routine cytology preparations represent a cost-effective and powerful tool to aid in performing molecular testing in the age of personalized medicine.

Using the ASC:SIL ratio, human papillomavirus, and interobserver variability to assess and monitor cytopathology fellow training performance.

Background: The goal of this study was to assess objective measurements of cytopathology fellow performance during their training.

Methods: The authors examined cytopathology performance characteristics (the ratio of atypical squamous cells to squamous intraepithelial lesions [ASC:SIL], interobserver variability [IOV], high-risk human papillomavirus [hr-HPV]-positive atypical squamous cells of undetermined significance [ASC-US]) of cytopathology fellows and assessed whether they could be used as tools to further their education.

Results: The ASC:SIL ratio, the proportion of hr-HPV-positive ASC-US, and IOV were calculated for 5 consecutive cytopathology fellows.

Simultaneous bilateral fungal keratitis caused by different fungi.

Fungal keratitis is an important cause of corneal disease in the tropical world. We report a rare presentation of simultaneous bilateral corneal ulceration caused by different fungi.