INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform.

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume.

Effects on lymph node size, staging and primary tumor histology on diagnostic accuracy of axillary lymph node aspirate of breast cancers.

Introduction: Fine-needle aspiration cytology is preferred for axillary lymph node metastasis with low costs and minimal risks. To improve diagnostic performance by incorporating clinical-radiological-pathological parameters, a large cohort pre-operative aspirates in were reviewed for parameters affecting adequacy rate and accuracy.

Methods: Axillary nodal aspirates from three institutions with histologic correlation were retrieved.

Clinical values of nuclear morphometric analysis in fibroepithelial lesions.

Background: Fibroepithelial lesions (FELs) of the breast encompass a broad spectrum of lesions, ranging from commonly encountered fibroadenomas (FAs) to rare phyllodes tumors (PTs). Accurately diagnosing and grading these lesions is crucial for making management decisions, but it can be challenging due to their overlapping features and the subjective nature of histological assessment. Here, we evaluated the role of digital nuclear morphometric analysis in FEL diagnosis and prognosis.

Measurement of Four Uterine NK Cell Subtypes Using Multiplexed Fluorescent Immunohistochemical Staining in Women with Repeated Implantation Failure.

Immunohistochemistry (IHC) plays a crucial role in biological research and clinical diagnosis, serving as the most commonly used method for identifying and visualizing tissue antigens. However, traditional IHC staining methods have limitations in distinguishing various subtypes of immune cells. This challenge has driven scientists to explore new technologies and methodologies for precise identification and differentiation of immune cell subtypes.

A Territory-Wide Follow-Up of Primary and Secondary Extramammary Paget Disease of 2 Decades: Effects of Local Disease on Survival.

Introduction: Extramammary Paget disease (EMPD) is an uncommon malignant cutaneous neoplasm that are divided into primary and secondary forms. In this multicenter study, histologically proven cases of primary and secondary EMPD were reviewed for clinical outcomes with subgroup analysis for secondary EMPD.

Methodology: Cases of EMPD were identified from pathology report of the involved institutions over a period of over 2 decades.

Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.

Introduction: Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma.

Methods: Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed.

Comparison of Claudin-4, BerEP4, Carcinoembryonic Antigen and MOC31 in Serous Fluids Metastases Demonstrate High Sensitivity of Claudin-4 at Low Cellularity.

Introduction: Claudin-4 has been described as a highly sensitive immunocytochemical marker for detection of metastatic carcinoma cells in effusion cytology specimens. This study aims to challenge the performance of claudin-4 in different types of malignancies and low cellularity specimens, by comparison with other markers in a large cohort of carcinomatous effusion specimens.

Methodology: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports.

Neuroendocrine Lesions Arising From Mediastinal Teratoma-A Case Report and Literature Review.

Neuroendocrine lesions arising from mediastinal teratomas are rare tumors with only small number of patients reported in literature. The behavior of these lesions appears to be different from traditional neuroendocrine neoplasms. A comprehensive review will be valuable for histologic assessment and treatment planning for similar cases.

Cytomorphologic comparison of upper urinary tract urothelial carcinomas and renal cell carcinomas on urine cytology.

Introduction: Compared to urothelial carcinomas (UCs), the cytomorphology of renal cell carcinomas (RCCs) is underdescribed. This study aims to investigate whether UCs and RCCS of the upper urinary tract can be differentiated cytologically, and to identify distinguishing cytomorphological features.

Methodology: Consecutive urine cytology specimens with atypical/C3, suspicious/C4 or malignant/C5 diagnoses matched with a nephrectomy or ureterectomy specimen with UC or RCC over a 15-year period were reviewed for cellularity, architecture, background composition and cytomorphologic features.

Cytokeratin 15 is a novel and independent predictor of poor outcome in luminal B HER2-negative breast carcinomas.

Cytokeratin 15 (CK15) has been described as a stem cell marker in human organs and its expression is seen in breast tissue. CK15 expression is associated with aggressive features in endometrial and oesophageal cancers, but data on the breast are lacking. This study aims to investigate the clinicopathological associations and prognostic significance of CK15 in breast carcinomas.

Comparison and review of abrasive bronchial brushing versus non-abrasive aspiration, lavage and washing - Higher sensitivity but with risk of over-diagnosis for bronchial brushing.

Bronchial exfoliative cytology is classified as non-abrasive (washing, aspiration and bronchoalveolar lavage) and abrasive (brushing). Brush abrasion dislodges epithelial cells but can induce bleeding and cytomorphologic artifacts. In this study, the largest cohort to date of bronchial cytology specimens were referenced against bronchial biopsy as the reference standard.

Digital Image Comparison of Cellular Yield in Bronchial Brushing: Pre- and Post-Biopsy Lavage Cytology.

Introduction: Bronchoscopy is a useful diagnostic tool capable of performing core biopsy, forceps biopsy, bronchoalveolar lavage, and bronchial brushing. This study compares the cellularity of bronchial cytology including pre- and post-biopsy lavage by digital image analysis, aiming to increase diagnostic and tumor yield by optimizing the sequence and combination of bronchial biopsy and cytology.

Methods: Alveolar macrophage, bronchial epithelium, and tumor cell cellularity from liquid-based cytology preparations of bronchial brushing and pre-biopsy and post-biopsy bronchoalveolar lavage were annotated on digitized whole-slide images and compared.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively.

The Malignant Potential of Ovarian Steroid Cell Tumors Revisited: A Multi-institutional Clinicopathologic Analysis of 115 Cases.

Steroid cell tumors (SCTs) of the ovary are rare and understudied, and as such, uncertainties remain about their malignant potential, as well as clinicopathologic predictors of patient outcome. Based on a multi-institutional cohort of cases, we present findings from the largest study of SCT reported to date. Clinicopathologic data were documented on 115 cases of SCT that were assembled from 17 institutions.

Urine cytology in the detection of renal cell carcinomas - a territory-wide multi-institutional retrospective review of more than 2 decades.

Introduction: Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi-institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas.

Methods: Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior.

Neutrophil-lymphocyte ratio reflects tumour-infiltrating lymphocytes and tumour-associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy.

Aims: The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumour microenvironment, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aimed to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC).

Cytomorphological Assessment in Aspirates of Ductal Carcinoma in situ: Correlations with Histopathologic Grade, Architectural Pattern, and Invasion.

Introduction: Fine-needle aspiration biopsy (FNAB) of the breast is an effective and widely adopted diagnostic technique. Histopathologic grading of ductal carcinoma in situ (DCIS) has prognostic significance. In this current study, FNAB of DCIS was reviewed to identify parameters that predict grading, histopathologic architecture, and presence of invasion in DCIS.

Prevalence and interpretation of AFF immunostain of DEK::AFF2 fusion-associated papillary squamous cell carcinoma in a retrospective cohort of recurrent sinonasal papillomas.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved.

Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma.

Fine-needle aspiration cytology (FNAC) is a versatile diagnostic procedure uniquely suited for tissue biopsy of breast carcinomas and axillary metastases and/or recurrences. With the expanding treatment options and accompanying theragnostic tests, it is crucial to recognize the developments on ancillary testing and digital cytopathology techniques related to aspiration cytology of metastatic breast carcinoma. In this review, we aim to summarize and update the evidence of immunocytochemistry, for the detection of carcinoma cells (epithelial markers), confirmation of breast primary (breast-specific markers), assessment of surrogate immunostains (hormone receptors, ki-67 proliferative index and HER2) and theragnostic biomarkers, with discussion on potential diagnostic pitfalls, followed by the application of molecular tests, and digital cytopathologic techniques for assessing metastatic breast carcinoma in cytology.

Keratinization in atypical glandular cell clusters as a cytological clue to endometrioid carcinoma on cervical cytology.

Introduction: Specific diagnosis of endometrial carcinomas on cervical cytology is difficult with few useful cytomorphological clues reported. This study reviews a cohort of cervical cytology to investigate the presence of keratinization in atypical glandular cells (AGC), an undescribed cytomorphological clue for identifying endometrial endometrioid carcinomas on cervical cytology.

Methods: Cervical cytology slides from patients with a histologic diagnosis of endometrial endometrioid carcinoma were reviewed for the presence of keratinization associated with AGCs.

The First Report of Cytology of DEK::AFF2 Fusion-Associated Papillary Squamous Cell Carcinoma on Fine-Needle Aspiration.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal malignancy defined by its unique translocation. DEK::AFF2 carcinomas may be deceptively monotonous and lack keratinization, resembling transitional epithelium. The lack of traditional cytological atypia presents diagnostic challenges.