Background. Whole slide imaging (WSI) represents a paradigm shift in pathology, serving as a necessary first step for a wide array of digital tools to enter the field. It utilizes virtual microscopy ...wherein glass slides are converted into digital slides and are viewed by pathologists by automated image analysis. Its impact on pathology workflow, reproducibility, dissemination of educational material, expansion of service to underprivileged areas, and institutional collaboration exemplifies a significant innovative movement. The recent US Food and Drug Administration approval to WSI for its use in primary surgical pathology diagnosis has opened opportunities for wider application of this technology in routine practice. Main Text. The ongoing technological advances in digital scanners, image visualization methods, and the integration of artificial intelligence-derived algorithms with these systems provide avenues to exploit its applications. Its benefits are innumerable such as ease of access through the internet, avoidance of physical storage space, and no risk of deterioration of staining quality or breakage of slides to name a few. Although the benefits of WSI to pathology practices are many, the complexities of implementation remain an obstacle to widespread adoption. Some barriers including the high cost, technical glitches, and most importantly professional hesitation to adopt a new technology have hindered its use in routine pathology. Conclusions. In this review, we summarize the technical aspects of WSI, its applications in diagnostic pathology, training, and research along with future perspectives. It also highlights improved understanding of the current challenges to implementation, as well as the benefits and successes of the technology. WSI provides a golden opportunity for pathologists to guide its evolution, standardization, and implementation to better acquaint them with the key aspects of this technology and its judicial use. Also, implementation of routine digital pathology is an extra step requiring resources which (currently) does not usually result increased efficiency or payment.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm that is genetically characterized by the presence of the Philadelphia (Ph) chromosome. Variant Ph translocation has been ...observed in 5% to 10% of the CML cases. In the previous studies, many different types of variant Ph translocations have been observed involving chromosomes 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, and 10p15. According to the published literature, only two cases with the complex translocations involving long arm of chromosome 16 at band q24 have been reported. We report two female patients with complex translocation (three-way) involving chromosomes 9, 22, and 16 at breakpoint q24 and both patients responded well to Imatinib. The present study included 469 patients of clinically diagnosed CML patients who were referred for cytogenetic analysis to our laboratory. Cytogenetic analysis was performed by GTG banding, and the karyotype was designated according to the International System for Human Cytogenetic Nomenclature. Fluorescence in situ hybridization (FISH) analysis was performed for complex and variant BCR-ABL cases. Of total 469 cases, 248 patients showed classical Ph chromosome t(9;22)(q34;q11.2), 198 cases were normal, and 23 patients had variant and complex Ph chromosome translocation. Two patients showed three-way translocation involving long arm of chromosomes 9, 22, and 16 at band 9q34, 22q11.2, and 16q24. In this report, patients with variant Ph translocation did not have a significantly different outcome as compared to the classical translocation. Both cases responded well to Imatinib.
Low‐grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows ...diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next‐generation sequencing panel of 324 cancer‐associated genes from formalin‐fixed, paraffin‐embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer‐related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow‐up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.
Sclerosing Angiomatoid Nodular Transformation (SANT) of the spleen is a rare benign lesion of the spleen with unknown etiology. SANT is classically considered to be a female-predominant disease, with ...most of the patients in the 30- to 60-year age group. Most lesions are found incidentally on imaging. Although SANT has specific imaging findings, the differential diagnosis from other splenic tumors or malignant lesions is very difficult. Histopathologically, these tumors reveal multiple confluent angiomatoid nodules; these nodules are surrounded by concentric collagen fibers exhibiting an inflammatory and myofibroblastic response and are accompanied by numerous erythrocytes and siderophages. The nodules are populated by endothelial cells, phenotypically recapitulating normal splenic vasculature, such as sinusoids, capillaries, and small veins. Nuclear atypia is minimal, mitotic figures are extremely rare, and necrosis is consistently absent. This lesion has a unique immunohistochemical profile characterized by CD34(-)CD31(+)CD8(+) sinusoids, CD34(+)CD31(+)CD8(-) capillaries, and CD34(-)CD31(+)CD8(-) small veins. CD68 is positive in macrophages. Splenectomy is a useful and effective technique for the management of SANT. SANT patients have a good prognosis, with no recurrence after splenectomy. In this review, we discuss the current knowledge of SANT of the spleen and its clinical relevance.
Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare morphologic entity. This tumor is usually associated with familial adenomatous polyposis (FAP), but rarely may be ...sporadic. This neoplasm commonly occurs in young females. The majority of patients present with gradually enlarging painless neck mass. There is no specific imaging finding of CMV-PTC, and the diagnosis is exclusively made on pathologic examination. A multitude of cytologic features of CMV-PTC are described, which includes hypercellularity, cribriform pattern, papillary arrangement of tall columnar cells, morules, spindle cells, clear and ground-glass nuclei, hyaline material, hemosiderin-laden histiocytes, and absence of colloid in the background. CMV-PTC is histologically characterized by the papillary growth of tall columnar cells, cribriform pattern without colloid, spindle cells, squamoid morules, and nuclear clearing. The immunoreactivity for beta-catenin and biotin-positive nuclear clearing may indicate CMV-PTC. Total thyroidectomy for familial or lobectomy for sporadic cases is usually the treatment for CMV-PTC. It carries a better prognosis than the other aggressive variants of papillary thyroid carcinoma. In this review, we discuss the current knowledge on CMV-PTC and its clinical relevance.
The first single-cell penile cancer atlas identified 83 682 single cells within 14 major cell types and 65 cell subpopulations, offering unprecedented insights into penile cancer biology. TP53 ...mutations might be a driver of worse prognosis, irrespective of human papillomavirus (HPV) status, challenging the currently used stratification by HPV only. Our work reveals key molecular pathways underlying poor prognosis and therapy resistance. These insights might facilitate patient selection for clinical trials and enable development of personalized therapies, sparing patients from the currently used highly toxic chemotherapies.
TP53 loss-of-function (TP53LOF) mutations might be a driver of poor prognosis and chemoresistance in both human papillomavirus (HPV)-independent (HPV–) and HPV-associated (HPV+) penile squamous cell carcinoma (PSCC). Here, we aim to describe transcriptomic differences in the PSCC microenvironment stratified by TP53LOF and HPV status.
We used single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing to obtain a comprehensive atlas of the cellular architecture of PSCC. TP53LOF and HPV status were determined by targeted next-generation sequencing and sequencing HPV-DNA reads. Six HPV+ TP53 wild type (WT), six HPV– TP53WT, and four TP53LOF PSCC samples and six controls were included. Immunohistochemistry and hematoxylin-eosin confirmed the morphological context of the observed signatures. Prognostic differences between patient groups were validated in 541 PSCC patients using Kaplan-Meier survival estimates.
Patients with aberrant p53 staining fare much worse than patients with either HPV– or HPV+ tumors and WT p53 expression. Using scRNA-seq, we revealed 65 cell subtypes within 83 682 cells. TP53LOF tumors exhibit a partial epithelial-to-mesenchymal transition, immune-excluded, angiogenic, and morphologically invasive environment, underlying their aggressive phenotype. HPV– TP53WT tumors show stemness and immune exhaustion. HPV+ TP53WT tumors mirror normal epithelial maturation with upregulation of antibody-drug-conjugate targets and activation of innate immunity. Inherent to the scRNA-seq analysis, low sample size is a limitation and validation of signatures in large PSCC cohorts is needed.
This first scRNA-seq atlas offers unprecedented in-depth insights into PSCC biology underlying prognostic differences based on TP53 and HPV status. Our findings provide clues for testing novel biomarker-driven therapies in PSCC.
Here, we analyzed tissues of penile cancer at the level of individual cells, which helps us understand why patients who harbor a deactivating mutation in the TP53 gene do much worse than patients lacking such a mutation. Such an analysis may help us tailor future therapies based on TP53 gene mutations and human papillomavirus status of these tumors.
Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and ...may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well-differentiated neuroendocrine tumors often showed immunoreactivity for site-specific markers. Although the histologic and immunohistochemical features of a breast tumor may raise the suspicion of a metastatic neuroendocrine neoplasm, the pathologic findings should be interpreted in the context of the clinical history and imaging findings in order to establish an accurate diagnosis.
Pathology education is a core component of medical training, and its literature is critical for refining educational modalities. We performed a cross-sectional bibliometric analysis to explore ...publications on pathology education, focusing on new medical education technologies.
The analysis identified 64 pathology journals and 53 keywords. Relevant articles were collected using a web application, PaperScraper, developed to accelerate literature search. Citation data were collected from multiple sources. Descriptive statistics, with time period analysis, were performed using Microsoft Excel and visualised with Flourish Studio. Two article groups were further investigated with a bibliometric software, VOSViewer, to establish co-authorship and keyword relationships.
8946 citations were retrieved from 905 selected articles. Most articles were published in the last decade (447, 49.4%). The top journals were
(184),
(122) and the
(117). The highest number of citations was found for
(2120), followed by
(2098) and
(1142). Authors with different backgrounds had the greatest number of articles and citations. 12 co-authorship, 3 keyword and 8 co-citation clusters were found for the social media/online resources group, 8 co-authorship, 4 keyword and 7 co-citation clusters for the digital pathology/virtual microscopy/mobile technologies group.
The analysis revealed a significant increase in publications over time. The emergence of digital teaching and learning resources played a major role in this growth. Overall, these findings underscore the transformative potential of technology in pathology education.
Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is ...implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH). We demonstrated that PC cells express varying levels of STAT3 and STAT5A transcripts. In addition, we demonstrate that pimozide, a psychotropic drug and an indirect inhibitor of STAT5, attenuated PC cells growth, and induced apoptosis in a dose-dependent manner. Furthermore, our analysis of the PC public data revealed that the STAT3/5A genes were frequently amplified in metastatic CRPC. These findings suggest that STAT3/5A potentially serves as a predictive biomarker to evaluate the therapeutic efficacy of a cancer drug targeting the JAK/STAT pathway. Since the JAK/STAT and AR pathways are suggested to be functionally synergistic, inhibition of the JAK/STAT signaling alone or together with AR may lead to a novel treatment modality for patients with advanced PC.
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm known to occur at various soft tissue and visceral locations. Kidney is one of the rare locations for these tumors with around 64 cases ...being available in the literature. Most of the renal SFTs are tan-white, solid, firm, unencapsulated, and lobulated masses. A predominantly cystic renal SFT has never been reported in the literature. Herein we describe a case of multicystic renal SFT in a 44-year-old male with the characteristic CD34 + /STAT6 + immunophenotype. A careful gross and microscopic examination is warranted while dealing with cystic spindle cell neoplasms of the kidney and SFT should always be considered in the differential diagnosis. STAT6 immunohistochemistry is quite specific for the diagnosis. Moreso, a detailed immunopanel is necessary to exclude other spindle cell neoplasms of the kidney because of significant therapeutic and prognostic implications.
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