The pathologist is involved in many diagnostic steps together with the clinical infectious disease team in the management of COVID-19-affected patients. In particular, cytological and ...histopathological procedures as well as autoptic findings may represent useful tools to better understand the pathobiology of the disease as well as to correctly define causes of death. Moreover, pathologists have been forced to reconsider the usual laboratory workflow and introduce adequate guidelines against virus diffusion in the COVID-19 pandemic, requiring high biosafety levels.
Purpose
The incidence of thyroid carcinoma has increased globally in the past years. Papillary thyroid carcinoma (PTC) is the most frequent neoplasm of the thyroid gland comprehending the 90% of the ...thyroid carcinoma and has an indolent clinical behaviour. However, some variants of follicular cell-derived thyroid carcinoma, including variants of classic of PTC, have been identified that show a more aggressive biological behaviour. An accurate diagnosis of these entities is crucial for planning a more aggressive treatment and improving patients’ prognosis of patients. The aim of this review is to present the main clinical, histological, and molecular features of aggressive variants of follicular cell-derived thyroid carcinoma, and to provide useful histological parameters for determining the most suitable therapeutic strategy for patients affected by these forms.
Results
Variants of classic PTC such as the diffuse sclerosing variant (DSV), the tall cell variant (TCV), the columnar cell variant (CCV), the solid/trabecular variant (STV) and the hobnail variant (HV), and other variants of follicular cell-derived thyroid carcinoma, such as poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC), are associated with aggressive behaviour.
Conclusions
The correct identification and diagnosis of aggressive variants of follicular cell-derived thyroid carcinoma is important, as they allow the clinician to adopt the most refined therapeutic strategies in order to the survival of the patients.
The cerebellum and its functional multiplicity and heterogeneity have been objects of curiosity and interest since ancient times, giving rise to the urge to reveal its complexity. Since the first ...hypothesis of cerebellar mere role in motor tuning and coordination, much more has been continuously discovered about the cerebellum's circuitry and functioning throughout centuries, leading to the currently accepted knowledge of its prominent involvement in cognitive, social, and behavioral areas. Particularly in childhood, the cerebellum may subserve several age-dependent functions, which might be compromised in several Central Nervous System pathologies. Overall, cerebellar damage may produce numerous signs and symptoms and determine a wide variety of neuropsychiatric impairments already during the evolutive age. Therefore, an early assessment in children would be desirable to address a prompt diagnosis and a proper intervention since the first months of life. Here we provide an overview of the cerebellum, retracing its morphology, histogenesis, and physiological functions, and finally outlining its involvement in typical and atypical development and the age-dependent patterns of cerebellar dysfunctions.
Summary Histologic grading is commonly assessed in colorectal cancer preoperative biopsies. Nevertheless, its clinical impact is limited by low interobserver reproducibility and poor concordance with ...grading found in the final resection specimen. In the present study, we aimed to investigate the reproducibility, accuracy, and predictive value on lymph node status or pTNM stage of a novel grading system based on the number of poorly differentiated clusters in colorectal cancer preoperative endoscopic biopsies. Grading based on counting poorly differentiated clusters was assessed in 163 colorectal cancer endoscopic biopsies and corresponding surgical specimens. With this system, 152 biopsies could be graded with good interobserver agreement ( κ = 0.735). In comparison with the surgical specimens, 75% of colorectal cancers were correctly graded in the biopsy, and 81% of poorly differentiated colorectal cancers were identified at initial biopsy. High poorly differentiated clusters grade in the biopsy was significantly associated with nodal metastasis, high pTNM stage ( P < .0001), or histologic features suggestive of more aggressive behavior (tumor budding, perineural invasion, vascular invasion, and infiltrating tumor border) in the surgical specimen. Furthermore, this system identified colorectal cancer with nodal involvement or high pTNM stage with a 78% positive predictive value and 71% and 69% negative predictive values, respectively. Our findings suggest that a grading system based on the quantification of poorly differentiated clusters is feasible in most colorectal cancer endoscopic biopsies. In view of its good reproducibility, accuracy, and predictive value on the anatomical extent of the disease, it may be taken into account for decision-making in colorectal cancer treatment.
Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating ...the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.
HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ ...hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed to exactly distinguish HER2-low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody–drug conjugates (ADCs) in treating these groups of tumors. In particular, trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC, has been recently approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06 trial, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally, we hope that new guidelines may help to codify HER2-low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.
Summary Mucinous adenocarcinoma (MAC) of the colon and rectum is a histological entity with still indefinite prognostic significance. Although it was previously designated as poorly differentiated by ...convention, the most recent World Health Organization guidelines indicate that the level of maturation of the epithelium determines differentiation in MAC and that microsatellite instability status should be taken into account for its histological grading. Nonetheless, precise criteria for grading are not provided, and the prognostic value of histological grading in MAC still remains unclear. In the present study we aimed to investigate the prognostic value of a grading system based on the counting of poorly differentiated clusters (PDC) of neoplastic cells in 108 colorectal MACs and to compare its reproducibility and significance with those of a grading system based on glandular differentiation. We found that PDC grade was more reproducible and significantly associated with disease progression ( P = .0089) as well as with death from colorectal cancer ( P = .0035) in our MACs, as compared to the grade based on glandular differentiation, which was not associated with any of the clinicopathologic variables. Moreover, PDC grade emerged as a significant, independent prognostic factor of recurrence-free survival ( P = .0198) and cancer-specific survival ( P = .0293) in MAC. Interestingly, the prognostic value of PDC grade was unaltered following incorporation of mismatch repair system status in grading. In conclusion, we demonstrated for the first time that PDC grading is feasible, reproducible, and prognostically relevant in MAC, which may support its use in routine practice.
Brachyury is a transcription factor which is required for posterior mesoderm formation and differentiation as well as for notochord development during embryogenesis. Due to its expression in the ...neoplastic cells of chordoma, a malignant tumour deriving from notochordal remnants, but not in tumors showing a similar histology, brachyury has been proposed as a diagnostic marker of this neoplasia. Though commonly considered a hallmark of chordoma, the expression of brachyury has been also documented in the stromal cells of hemangioblastoma (HBL), a slow growing tumor which may involve the central nervous system (CNS) and, rarely, the kidney. Herein we review the role of brachyury immunohistochemical detection in the identification and differential diagnosis of chordoma and HBL towards histological mimickers and suggest that brachyury is added to the panel of immunohistochemical markers for the recognition of HBL in routinary practice, principally in unusual sites.
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden ...unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.
PDF
