Analytical and clinical validation of PATHWAY Anti-HER-2/neu (4B5) antibody to assess HER2-low status for trastuzumab deruxtecan treatment in breast cancer.

In DESTINY-Breast04 (DB-04), safety and efficacy of HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in previously treated HER2-low unresectable/metastatic breast cancer were established. This manuscript describes the analytical validation of PATHWAY Anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) to assess HER2-low status and its clinical performance in DB-04. Preanalytical processing and tissue staining parameters were evaluated to determine their impact on HER2 scoring.

An Unusual Cause of Large Bowel Obstruction in a Patient With Ulcerative Colitis.

Endometriosis is a rare cause of large bowel obstruction and has been infrequently reported in patients with inflammatory bowel disease. We present an unusual case of a young woman with ulcerative colitis, who presented with a large bowel obstruction with colonic stricture and peripancreatic mass concerning for malignancy. The evaluation revealed endometriosis, and her large bowel obstruction was successfully managed with leuprolide and colonic stenting.

Crizotinib-associated renal cyst development may be associated with prolonged progression-free survival in patients with -positive non-small-cell lung cancer: Case report and review of the literature.

Non-small cell lung cancer patients with anaplastic lymphoma kinase or c-ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib-associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression-free survival.

Taurine Is Covalently Incorporated into Alpha-Tubulin.

Taurine is the most abundant free amino acid in the human body. It is found in relatively high concentrations (1-10 mM) in many animal tissues but not in plants. It has been studied since the early 1800s but has not been found to be covalently incorporated into proteins in any animal tissue.

Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1.

Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls.

Immunolabeling of Cleared Human Pancreata Provides Insights into Three-Dimensional Pancreatic Anatomy and Pathology.

Visualizing pathologies in three dimensions can provide unique insights into the biology of human diseases. A rapid and easy-to-implement dibenzyl ether-based technique was used to clear thick sections of surgically resected human pancreatic parenchyma. Protocols were applicable to both fresh and formalin-fixed, paraffin-embedded tissue.

Paris Interobserver Reproducibility Study (PIRST).

Objectives: In concert with the 2015 publication of The Paris System for Urinary Cytopathology (TPS), a Web-based interobserver study, co-sponsored by the American Society of Cytopathology (ASC) and International Academy of Cytology (IAC), was performed to determine diagnostic agreement among volunteer participants and with the TPS author consensus.

Material And Methods: Participants at various levels of training and certification were recruited through national and international cytopathology professional societies. Although the survey was open to all comers, potential participants were screened by two basic cytopathology questions.

Adamantinoma-like Ewing sarcoma of the parotid gland: Cytopathologic findings and differential diagnosis.

Adamantinoma-like Ewing sarcoma (AES) is a rare variant of Ewing sarcoma family of tumors (EFTs), primarily affecting bone and soft tissue. AES has mixed features of Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) and adamantinoma with a complex immunoprofile and EWSR1 gene rearrangements. Herein, we report a 72-year-old male who presented with left parotid mass, right neck mass and thyroid nodules.

Intraoperative PTH May Not Be Necessary in the Management of Primary Hyperparathyroidism Even with Only One Positive or Only Indeterminate Preoperative Localization Studies.

Background: Intraoperative PTH (IOPTH) monitoring has been widely used to confirm the removal of the culprit lesion during operation. However, the true benefit of IOPTH in patients with preoperatively well-localized single adenoma has been questioned. The aim of this study was to examine how or if IOPTH changes the surgical management and outcomes in patients with only one positive or only indeterminate localization studies.

Unusual findings in thyroid cytology and histology.

Introduction: Although cytology and histopathology of thyroid lesions generally fall into common, well-defined categories, there are uncommon cases with unusual fine needle aspiration (FNA) findings or histology. Herein, we review the prevalence and characteristics of rare thyroid cytology and histopathology findings at a tertiary hospital.

Methods: Institutional data from >31,000 patients with a thyroid pathology from 1995 to 2013 were queried.

Adequacy of voided urine specimens prepared by ThinPrep and evaluated using The Paris System for Reporting Urinary Cytology.

Introduction: The Paris System for Reporting Urinary Cytology (TPS) currently includes a volume recommendation for voided urine specimens of 30 mL based on observations of performance with BD SurePath preparation system. Given that many labs use the Hologic ThinPrep methods for voided urines, an analysis of data acquired with this system is undertaken in this study.

Materials And Methods: We identified a total of 744 voided urine specimens.

Antiretroviral Drug Use in a Cross-Sectional Population Survey in Africa: NIMH Project Accept (HPTN 043).

Background: Antiretroviral (ARV) drug treatment benefits the treated individual and can prevent HIV transmission. We assessed ARV drug use in a community-randomized trial that evaluated the impact of behavioral interventions on HIV incidence.

Methods: Samples were collected in a cross-sectional survey after a 3-year intervention period.

ProteinProcessor: A probabilistic analysis using mass accuracy and the MS spectrum.

Current approaches to protein identification rely heavily on database matching of fragmentation spectra or precursor peptide ions. We have developed a method for MALDI TOF-TOF instrumentation that uses peptide masses and their measurement errors to confirm protein identifications from a first pass MS/MS database search. The method uses MS1-level spectral data that have heretofore been ignored by most search engines.

High prevalence of TERT promoter mutations in micropapillary urothelial carcinoma.

Somatic activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Little is known, however, about TERT-mutation status in the relatively uncommon but clinically aggressive micropapillary (MPC) variant. We evaluated the presence of TERT promoter mutations in MPC of the bladder and upper urinary tract.

Metastatic urinary tract cancers in pap test: Cytomorphologic findings and differential diagnosis.

Although the cervical Pap test was devised for the detection of primary cervical neoplasia, it can provide additional diagnostic information, and in some cases, be diagnostic for noncervical processes. The diagnosis of metastatic extrauterine cervical cancers on the Pap test is extremely rare; and in most cases, it is the result of an ovarian or fallopian tube primary. Further, urinary tract cancers, including renal and urinary primaries are exceedingly rare.

Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules.

Importance: Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated.

Objective: To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process.

High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder.

TERT promoter mutations (TERT-mut) are detectable in the majority of urothelial carcinomas. The detection of TERT-mut in urine is under investigation as a potential urine-based molecular-screening assay for bladder cancer. A small but significant number of bladder carcinomas are pure squamous cell carcinoma.

Should the BK polyomavirus cytopathic effect be best classified as atypical or benign in urine cytology specimens?

Background: According to The Paris System for Reporting Urinary Cytology (TPS), the category of atypical urothelial cells (AUC) should not be applied to specimens in which cellular changes can be entirely attributed to the polyoma (BK) virus cytopathic effect (CPE). Until recently, cases with BK CPE at The Johns Hopkins Hospital were categorized as atypical urothelial cells of uncertain significance (AUC-US), which is equivalent to the TPS AUC category. This study was performed to determine how significantly the rate of AUC-US specimens would decrease if specimens with only BK CPE were classified as benign.

Morphologically compatible mass spectrometric analysis of lipids in cytological specimens.

Introduction: Modern lipid analysis requires mass spectrometric techniques, though to date these have been developed and applied primarily to histological serial sections. As such, there has been little emphasis on using mass spectrometry in such a way that the same specimen can yield both chemical and morphological information. Here, we present a mass spectrometric method that enables measurement of lipids from cells on cytospin slides in a way that preserves the cells for subsequent cytomorphologic evaluation.

A specimen volume of ≥80 mL improves cytologic sensitivity for malignant ascites: a retrospective analysis of 2665 cases.

Introduction: Although paracentesis simultaneously allows cytologic evaluation of peritoneal fluid and symptomatic relief, its utility is limited by a paltry 50% to 60% sensitivity for malignancy. Specimen volume has recently been shown to affect cytologic diagnosis in other body fluids, but its role has never been examined in ascites. This study evaluates how specimen volume impacts cytologic diagnosis of malignant ascites.

A Minimum Volume of More Than 60 mL Is Necessary for Adequate Cytologic Diagnosis of Malignant Pericardial Effusions.

Objectives: This study aims to determine the minimum pericardial fluid volume necessary for adequate cytologic diagnosis.

Methods: We identified 480 pericardiocentesis specimens, divided them by volume into six bins, and calculated the malignancy fraction (percentage of malignant diagnoses) for each bin. We then combined bins at various cutoffs to determine a minimum threshold volume and evaluated their sensitivity.

Effect of Gene Expression Classifier Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules.

Importance: Commercial molecular testing, such as the gene expression classifier (GEC), is now being used in the work up of cytologically indeterminate thyroid nodules. While this test may be helpful in ruling out malignancy in a thyroid nodule, its effect on surgical decision making has yet to be fully defined.

Objective: We aimed to determine the effect and outcome of GEC test results on the decision-making process for patients with thyroid nodules presenting for surgical consultation.

Cytotechnologist Performance for Screening Hürthle Cell Atypia in Indeterminate Thyroid Fine-Needle Aspirates.

Objectives: We have previously shown that specimens diagnosed as containing Hürthle cells have a 12% chance of being malignant if they are classified as atypia of undetermined significance (AUS-HC). The identification of Hürthle cells by cytotechnologists (CTs) during screening can improve cytopathologist efficiency and may prevent diagnostic errors due to the oversights of focal findings. Here, we examine the performance of our institutional CTs when screening for Hürthle cell atypia in thyroid fine-needle aspiration (FNA) specimens.

Adequacy in voided urine cytology specimens: The role of volume and a repeat void upon predictive values for high-grade urothelial carcinoma.

Background: Adequacy assessment is one of the most controversial and overlooked components in the daily practice of cytopathology, because it is generally determined from limited samples. Because voided urine varies widely in terms of its volume and cellularity, there is little consensus about the proper role for these variables in assessing specimen adequacy. In this study, the authors explored the role of volume in voided urine specimens to determine whether it plays a role in determining adequacy for the detection of high-grade urothelial carcinoma.