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A test dedicated to teaching and education for all staff working in cytology laboratories is presented on the topic of pleural effusion.

A study of the effects of impurities evolving from a hot (1350–1500 °C) empty effusion cell on the residual doping concentrations in GaAs grown by molecular beam epitaxy (MBE) has been made. The influence of these impurities on electron concentrations in highly doped GaAs:Si has also been investigated. p-type residual doping was seen in all cases, with 1×1016/cm3 being the highest level observed. More typical were concentrations in the mid-to-high 1014 range after the empty cell had been properly degassed. While most of the acceptors appear to be C, there is some evidence that N may be involved at the higher concentrations. No effect from the hot source on the doping level of GaAs:Si with n=4×1018/cm3 was seen, showing that effusion cell evolved impurities are not responsible for limiting high electron concentrations in MBE-grown GaAs:Si. [ABSTRACT FROM AUTHOR]

T cells are generally sparse in hormone receptor-positive (HR+) breast cancer, potentially due to limited antigen presentation, but the driving mechanisms of low T cell abundance remains unclear. Therefore, we defined and investigated programs ('gene modules'), related to estrogen receptor signaling (ERS) and immune signaling using bulk and single-cell transcriptome and multiplexed immunofluorescence of breast cancer tissues from multiple clinical sources and human cell lines. The ERS gene module, dominantly expressed in cancer cells, was negatively associated with immune-related gene modules TNFα/NF-κB signaling and type-I interferon (IFN-I) response, which were expressed in distinct stromal and immune cell types, but also, in part, expressed and preserved as a cancer cell-intrinsic mechanisms. Spatial analysis revealed that ERS strongly correlated with reduced T cell infiltration, potentially due to its association with suppression of TNFα/NF-κB-induced angiogenesis and IFN-I-induced HLA expression in macrophages. Preoperative endocrine therapy in ER+/HER2-breast cancer patients produced better responses in ERS-high patients, with TNFα/NF-κB expression associated with reduced ERS. Targeting these pathways may enhance T cell infiltration in HR+ breast cancer patients., Statement of Significance: This study elucidates the immunosuppressive role of ER signaling in breast cancer, highlighting a complex interplay between cancer, stromal, and immune cells and reveals potential approaches to enhance immunogenicity in HR+ breast cancer. These findings offer crucial insights into immune evasion in breast cancer and identify strategies to enhance T cell abundance.

Introduction: The risk of malignancy (ROM) remains an area of interest for further evaluation in reporting systems including in International System for reporting serous fluid cytopathology (TIS), which is a standardized system for reporting effusion cytology. Herein, we report our findings in further investigation of ROM in TIS by studying on paired pleural effusion specimens and corresponding pleural biopsies with emphasis on negative for malignancy, and atypia of undetermined significance categories., Materials and Methods: The  Johns Hopkins Hospital pathology database was retrospectively searched for patients with a pleural biopsy (PBX) and a paired pleural effusion (PF) cytology specimens over a 4-year period. We employed the TIS categories. The following statistical parameters were evaluated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM., Results: A total of 223 patient cases were included. Effusions TIS reclassification and ROM were as follows: 1.8% non-diagnostic (ROM 75%), 75.8% negative for malignancy (ROM 23%), 4.9% atypical cells of undetermined significance (ROM 45%), 2.2% suspicious for malignancy (ROM 80%), and 15.2% malignant (ROM 100%). Overall accuracy, sensitivity, specificity, PPV and NPV were calculated and were 79.4%, 45%, 97.7%, 91.2% and 77%, respectively. Among, discordant cases diagnosed negative for malignancy on PF and positive for malignancy on PBX, there were significant number of lymphomas, mesotheliomas, and sarcomas. Lung cancer was the most common carcinoma; however, rare types of carcinomas were noted. Cells blocks and immunohistochemistry (IHC) studies were utilized to confirm either malignant conditions or rule out malignancy in both cell blocks and histology biopsies., Conclusion: This study demonstrates the high specificity and ROM for 'malignant' and 'suspicious for malignancy' categories in the TIS reporting system and highlights the modest negative predictive value for the 'negative for malignancy' category. Although Tissue biopsies are usually considered as 'gold standard', any definitive diagnosis of malignancy of body fluid should be considered positive for malignancy in further clinical decision-making., (© 2024 John Wiley & Sons Ltd.)

NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery., Prevention Relevance: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence., (©2023 American Association for Cancer Research.)

Background: Additional risk-stratification measures are needed in breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC). We aimed to describe oncologic outcomes in a modern cohort treated with NAC, and evaluate the prognostic value of histologic pattern of residual tumor., Patients and Methods: We included patients with stage I-III breast cancer treated with NAC and surgery from 2004 to 2014. Histologic pattern of residual tumor was evaluated by central pathology review when slides were available. Multivariable Cox regression was performed to evaluate factors associated with locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS)., Results: Among 975 patients, median follow-up was 74.0 months and 10-year rates of LRR, RFS, and OS were 9.8%, 67.6% and 74.4%, respectively. Biologic subtype, pathologic node-positive disease, and pathologic complete response (pCR) were associated with outcomes. Among 666 (68.3%) patients with central pathology review, pattern of residual disease was not significantly associated with LRR. However, both scattered residual tumor and no/minimal response relative to a concentric pattern of response were significantly associated with inferior RFS (scattered: hazard ratio 2.0, p = 0.015; no/minimal response: hazard ratio 2.2, p = 0.021) and OS (scattered: hazard ratio 2.2, p = 0.026; no/minimal response: hazard ratio 2.5, p = 0.023). This finding was most prominent in patients with triple-negative breast cancer., Conclusions: Patients with a scattered relative to concentric pattern of residual tumor after NAC had inferior RFS and OS, nearly as poor as those with no/minimal response. Histologic pattern of residual tumor may represent a novel prognostic measure, particularly in the triple-negative breast cancer population., (© 2022. Society of Surgical Oncology.)

Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but patients relapse, highlighting the need to understand the mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that resist T cell attack are quiescent. Quiescent cancer cells (QCCs) form clusters with reduced immune infiltration. They also display superior tumorigenic capacity and higher expression of chemotherapy resistance and stemness genes. We adapted single-cell RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside the QCC niche. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T cells, tumor-protective fibroblasts, and dysfunctional dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their intra-tumor location. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that blocks T cell function. Eliminating QCCs holds the promise to counteract immunotherapy resistance and prevent disease recurrence in TNBC., Competing Interests: Declaration of interests S.A.S.: non-financial support (Bristol-Myers Squibb), equity (Agenus Inc., Agios Pharmaceuticals, Breakbio Corp., Bristol-Myers Squibb, and Lumos Pharma). E.A.M.: SAB compensation (Merck, Genentech, and Genomic Health), uncompensated steering committees (Bristol-Myers Squibb, Lilly, and Genentech). K.W.W.: scientific advisory board (TCR2 Therapeutics, T-Scan Therapeutics, SQZ Biotech, and Nextechinvest), sponsored research funding (Novartis), co-founder (Immunitas Therapeutics). S.M.T.: institutional research funding (AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Cyclacel, Odonate, and Seattle Genetics); adviser/consultant (AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Bristol-Myers Squibb, Eisai, Nanostring, Puma, Sanofi, Celldex, Paxman, Puma, Silverback Therapeutics, G1 Therapeutics, Gilead, AbbVie, Anthenex, OncoPep, Outcomes4Me, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, Ellipsis, Infinity, and Samsung Bioepsis Inc). R.B.-S.: consulting (AstraZeneca, Elli Lilly, Libbs, Merck, Roche, and Zodiac), non-CME services received directly from commercial interest or their Agents (Bard Access, BMS, Eli Lilly, Libbs, Merck, Novartis, and Pfizer, Roche), contracted research funding (Roche and BMS), travel/accommodation/expenses (Eli Lilly, Roche, Daichi Sankyo, and Merck). M.H.: co-founder and adviser (Neomer Diagnostics). P.B., A.B.-M., Y.H., A.W., J.-W.C., G.E., I.A., S.M., J.S., X.Z., X.S., Z.K., A.R., E.T.R., R.P., and J.A. have no conflicts of interest to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: We report results from a phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC)., Patients and Methods: Patients with mTNBC treated with 0-1 prior lines of chemotherapy received cisplatin 75 mg/m 2 i.v. followed 21 days later by cisplatin plus adavosertib 200 mg oral twice daily for five doses every 21 days. The study had 90% power to detect the difference between null (20%) and alternative (40%) objective response rates (ORR) with a one-sided type I error of 0.1: an ORR >30% was predefined as making the regimen worthy of further study. RNA sequencing and multiplex cyclic immunofluorescence on pre- and post-adavosertib tumor biopsies, as well as targeted next-generation sequencing on archival tissue, were correlated with clinical benefit, defined as stable disease ≥6 months or complete or partial response., Results: A total of 34 patients initiated protocol therapy; median age was 56 years, 2 patients (6%) had BRCA2 mutations, and 14 (41%) had one prior chemotherapy. ORR was 26% [95% confidence interval (CI), 13-44], and median progression-free survival was 4.9 months (95% CI, 2.3-5.7). Treatment-related grade 3-5 adverse events occurred in 53% of patients, most commonly diarrhea in 21%. One death occurred because of sepsis, possibly related to study therapy. Tumors from patients with clinical benefit demonstrated enriched immune gene expression and T-cell infiltration., Conclusions: Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%. The finding of immune-infiltrated tumors in patients with clinical benefit warrants validation., (©2020 American Association for Cancer Research.)

Introduction: Pulmonary adenocarcinoma is a major cause of mortality worldwide. The majority of patients present with advanced stage disease, and minimally invasive procedures are desirable for diagnosis and treatment plans. Herein, we report our experience with percutaneous/transthoracic needle aspiration (TT-NA) in the cytologic diagnosis of pulmonary adenocarcinoma., Material and Methods: After institutional review board approval, the cytopathology electronic data system was searched for all consecutive TT-NA of the lung masses from January 2011 to November 2015. Patients' medical records were reviewed and cytologic materials were evaluated., Results: A total of 151 specimens were identified, with a mean age of 62.8 years; 62.9% of the patients had a prior history of malignancy. Carcinoma/adenocarcinoma was the most common (80%) diagnosis. The targeted lesions were predominantly located in the lung (56.3%, 81/151) and pleural based (27.8%, 42/151). The mean size of the lesions was 3.6 cm. Cytology specimens were adequate in 70.9% of the cases, while 72.8% (110/151) of the cases also had concurrent core biopsy. A malignant diagnosis was rendered in the majority of the cases (64.9%). In 71% of the cases, immunohistochemistry/histochemistry studies were successfully performed. Molecular/genetic studies were requested in 80% of the cases and had adequate material. Complications of the procedure were seen in 9.9% of the patients including pneumothorax (7.9%) and hemoptysis (1.9%)., Conclusion: TT-NA is a relatively safe and reliable technique in the assessment of pulmonary lesions., (© 2019 S. Karger AG, Basel.)

Introduction: Locoregional recurrence of thyroid carcinoma has a negative impact on patient prognosis. In the current study, we retrospectively reviewed cases of thyroid bed lesions in the last 3 years, correlating cytologic diagnoses with clinical findings and, whenever available, final surgical diagnosis., Materials and Methods: Cytologic results and needle wash thyroglobulin results from patients with fine-needle aspiration (FNA) of thyroid bed lesions were retrospectively collected from our electronic files. Additional retrieved data included sex, age at diagnosis, previous thyroidectomy diagnosis, time lapse since surgery, and corresponding surgical diagnosis (whenever available)., Results: A total of 91 cases from 72 patients (54 F, 18 M) were retrieved from the electronic files, with a median age of 49 years. Average interval between surgery and thyroid bed FNA was 5 years. Thyroglobulin levels were available for 60 (65.2%) cases. The average level was 276.2 ug/mL, with a range of <0.1 to 4720 ug/mL. Information on final surgical diagnosis was available for 31 samples. Complete agreement between final cytologic and histologic diagnoses was achieved in 28 of 31 (90.3%) of the cases, with 1 false negative and 2 false positives. Cytology sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.2%, 71.4%, 90.9%, 83.3%, and 89.1%, respectively., Conclusions: Ultrasound-guided FNA is an accurate and minimally invasive diagnostic method for suspicious thyroid bed lesions, with high sensitivity and positive predictive value., (Copyright © 2018 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

This paper describes the Biomedical Services Department of Deaconess Hospital, which is centrally located in Oklahoma City, OK. The hospital provides family-centered general and acute care with practically all medical specialties represented. The Department consists of one department supervisor, one technician, and one part-time shared-service secretary. The Department is responsible for the repair, safety testing, and calibration of over 600 instruments, and serves an important role in the selection and support of patient care equipment. Training of users is another major role for this department.