An estrogen receptor signaling transcriptional program linked to immune evasion in human hormone receptor-positive breast cancer.

Unlabelled: 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.

Application of the international system for reporting serous fluid cytopathology on pleural effusion cytology with paired pleural biopsy: A new insight and novel approach on risk of malignancy.

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.

Qualification of a multiplexed tissue imaging assay and detection of novel patterns of HER2 heterogeneity in breast cancer.

Emerging data suggests that HER2 intratumoral heterogeneity (ITH) is associated with therapy resistance, highlighting the need for new strategies to assess HER2 ITH. A promising approach is leveraging multiplexed tissue analysis techniques such as cyclic immunofluorescence (CyCIF), which enable visualization and quantification of 10-60 antigens at single-cell resolution from individual tissue sections. In this study, we qualified a breast cancer-specific antibody panel, including HER2, ER, and PR, for multiplexed tissue imaging.

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ.

Unlabelled: 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.

Impact of the Histologic Pattern of Residual Tumor After Neoadjuvant Chemotherapy on Recurrence and Survival in Stage I-III Breast Cancer.

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.

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche.

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.

Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study.

This single-arm phase II study investigated the efficacy and safety of cabozantinib combined with nivolumab in metastatic triple-negative breast cancer (mTNBC). The primary endpoint was objective response rate (ORR) by RECIST 1.1.

The Immunology of Hormone Receptor Positive Breast Cancer.

Immune checkpoint blockade (ICB) has revolutionized the treatment of cancer patients. The main focus of ICB has been on reinvigorating the adaptive immune response, namely, activating cytotoxic T cells. ICB has demonstrated only modest benefit against advanced breast cancer, as breast tumors typically establish an immune suppressive tumor microenvironment (TME).

Comparison of Breast Cancer Staging Systems After Neoadjuvant Chemotherapy.

Background: No consensus exists for optimal staging following neoadjuvant chemotherapy (NAC). We compared the performance of the American Joint Committee on Cancer (AJCC) pathologic prognostic staging system, Residual Cancer Burden (RCB) Index, and the Neo-Bioscore in breast cancer patients after NAC.

Methods: Patients with stage I-III breast cancer who received NAC at Dana-Farber Cancer Institute from 2004 to 2014 were identified.

Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer.

Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) who do not experience a pathologic complete response (pCR), the pattern of residual disease in the breast varies. Pre-treatment clinico-pathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, we performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stage I-III breast cancer treated with NAC followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review.

Experience on the use of The Paris System for Reporting Urinary Cytopathology: review of the published literature.

Introduction: The Paris System for Reporting Urinary Cytology (TPS) was first published in 2016 with clear objectives to standardize cytologic diagnostic criteria and provide uniform reporting, in order to improve patient stratification and associated clinical management. The aim of this paper is to evaluate the performance of TPS and review the literature published since TPS was introduced.

Materials And Methods: Original articles focusing on the utilization and performance of TPS in urinary cytology specimens were identified using PubMed for publications from January 2016 to July 2020, using the keywords "Paris System", "urine cytology", and "urinary cytology".

Should we wait 3 months for a repeat aspiration in non-diagnostic/indeterminate thyroid nodules? A cancer centre experience.

Introduction: The Bethesda System recommends repeat fine needle aspiration (rFNA) as a management option for nodules classified under the non-diagnostic (ND) and atypia of undetermined significance (AUS/FLUS) categories. We evaluated the impact of an rFNA in diagnostic resolution and the role of early (≤3 months) vs delayed (more than 3 months) rFNA of nodules initially diagnosed as ND and AUS/FLUS.

Methods: We retrospectively collected all thyroid FNA performed in a 4-year period with repeat aspiration.

Suspicious for Malignancy Diagnoses on Pleural Effusion Cytology.

Objectives: A definitive diagnosis of malignancy may not be possible in pleural effusions. We report our experience with the diagnosis of suspicious for malignancy (SFM) in pleural effusion.

Methods: A search for pleural effusions diagnosed as SFM (2008-2018) was performed.

Application of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) on Reporting Pericardial Effusion Cytology.

Introduction: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) has recently been announced. Pericardial effusion (PE) is a clinical manifestation of a large variety of both neoplastic and non-neoplastic conditions. Herein, we have applied the ISRSFC on reporting PE cytopathology and report our experience in a large academic institution.

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer.

Background: The purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR) metastatic breast cancer (MBC).

Patients And Methods: Eligible patients had HR/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles.

Number of mesothelial cells as a measure of adequacy criteria for pleural effusions: A multi-institutional study.

Background: The development of a terminology system is essential to allow uniformity in reporting serous fluid specimens. An important topic to cover is the issue of specimen adequacy. In the present study, we aimed to evaluate whether there is a correlation between number of mesothelial cells and overall improved sensitivity and adequacy control of tests.

Ultrasound-Guided Transthoracic Fine-Needle Aspiration: A Reliable Tool in Diagnosis and Molecular Profiling of Lung Masses.

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.

The usefulness of fine-needle aspirates for detection of recurrent carcinoma in the thyroid bed.

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.

Metastases to the Thyroid: Potential Cytologic Mimics of Primary Thyroid Neoplasms.

Secondary tumors of the thyroid gland, although uncommon, can sometimes pose as diagnostic dilemmas on fine-needle aspiration cytology, frequently mimicking primary thyroid neoplasms. An accurate diagnosis of such lesions, however, is critical for patient management and prognosis. The present study reviews the cytologic aspects of secondary involvement of the thyroid, listing the most common primary malignancies that metastasize to this gland.

The impact of rapid on-site evaluation on thyroid fine-needle aspiration biopsy: A 2-year cancer center institutional experience.

Background: The impact of rapid on-site evaluation (ROSE) on thyroid aspirates has been a matter of extensive debate. In the current study, the authors reviewed all thyroid fine-needle aspiration biopsies (FNABs) performed in their service in recent years to evaluate the impact of ROSE on final adequacy and diagnostic rates.

Methods: All ultrasound-guided FNABs of the thyroid performed between July 2015 and July 2017 were included retrospectively.

Use of a low-cost telecytopathology method for remote assessment of thyroid FNAs.

Background: Rapid on-site evaluation is a great tool for optimizing the adequacy and quality of cytologic samples. The objective of the current study was to analyze a low-cost telecytopathology method for the remote assessment of thyroid fine-needle aspiration biopsies (FNABs), with comparison of the primarily rendered adequacy and diagnosis with the final conventional analysis.

Methods: Material collected from thyroid FNABs was immediately smeared onto glass slides and stained with Diff-Quik.

Disseminated toxoplasmosis in a patient with advanced acquired immunodeficiency syndrome.

Extracerebral toxoplasmosis, with pulmonary involvement and shock, is a rare form of toxoplasmosis in patients with advanced AIDS. It can mimic pneumocystosis, histoplasmosis, and disseminated tuberculosis, and should be considered in the differential diagnosis of causes of respiratory failure and fulminant disease in this group of individuals, especially in areas where the infection is highly prevalent and in those without proper use of antimicrobial prophylaxis. We report the case of a 46-year-old male patient who presented to the emergency department with uremia, requiring urgent dialysis.