text stringlengths 0 5.79k |
|---|
Phyllodes | 1 | 1 | 2 | 4 |
Fibrocystic disease | 0 | 1 | 3 | 4 |
DCIS | 1 | 0 | 2 | 3 |
Ductal hyperplasia | 0 | 0 | 3 | 3 |
Invasive disease | Invasive Carcinoma | 30 | 0 | 0 | 30 |
Total | 32 | 5 | 23 | 60 |
Fischer exact = 66.78, p < 0.0001 |
Histopathological images of the slides are shown in Figures 1-4 below. |
## Discussion |
This prospective study was conducted on 60 female patients in the upgraded Department of Pathology, at Osmania Medical College, Hyderabad. Out of 60 female patients with breast lesions, 30 presented with benign and non-invasive lesions and 30 with invasive lesions. In the present study, the mean age of patients with be... |
In our study, age groups of patients with invasive breast lesions were categorized in which 26.7% (8) belonged to the age group 61-70 years which was the elderly age group, 23.3% (7) belonged to the age group 41-50 years, and 51-60 years age group respectively, 10% (3) to age group 71-80 years and 31-40 years respectiv... |
Histopathological diagnosis |
In our study, among the benign and non-invasive breast diseases, 14 out of 30 were diagnosed as fibroadenoma, four cases were diagnosed as fibrocystic disease and phyllodes respectively, three cases were diagnosed as ductal hyperplasia and DCIS respectively and two cases were diagnosed as adenosis. Neeli et al. [6] hav... |
In the present study, DOG-1 expression in invasive and non-invasive breast diseases was compared with p63 expression. Out of 14 cases of fibroadenoma, 11 were strong positive for DOG1 and three were weak positive. Similarly, 11 were strong positive and three were weak positive for p63 expression which showed no signifi... |
Finally, out of 30 benign cases, 26 cases showed positivity for DOG1 expression which is 86.66% and 28 cases showed positivity for p63 expression with a specificity of 93.33%. Out of 30 cases of invasive carcinomas of the breast, 28 cases were negative but only two cases showed weak positivity, i.e, DOG1 expression was... |
## Conclusions |
DOG1 seems to be similar to p63 as a myoepithelial cell marker both in normal breast tissue and in benign lesions. It is useful as a myoepithelial marker in differentiating invasive breast carcinoma and non-invasive breast lesions. There was only occasional DOG1 immunoreactivity in stromal or vascular cells, which prov... |
## Human Ethics |
## Animal Ethics |
## References |
d944cfffbfcbb40b7787299ea0f3ab46cc9973255d5636ba3733e2e4845e8f91 pmc10309016.txt |
PMCID: PMC10358772 |
TITLE: Histological and molecular glioblastoma, IDH-wildtype: a real-world landscape using the 2021 WHO classification of central nervous system tumors |
LICENSE: https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the or... |
ABSTRACT: IntroductionGlioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors. This study aimed to characterize the clinical, radiological, molec... |
## Introduction |
Glioblastoma (GBM), the most common and lethal primary malignant brain tumor worldwide, is associated with a dismal prognosis (1, 2). Despite continuous efforts to improve glioblastoma-related outcomes, the median overall survival (mOS) is only 16 months, and the real-world 5-year survival rate is 6.8% (3). Moreover, g... |
Advancements in molecular testing have improved our understanding of the molecular categorization of gliomas, leading to a debate regarding whether GBM should be divided into isocitrate dehydrogenase (IDH)-mutant and IDH-wildtype subcategories (7, 8). IDH-mutant gliomas differ fundamentally from IDH-wildtype gliomas in... |
The present study aimed to comprehensively describe the clinical presentations, radiological features, pathological characteristics, and molecular alterations of GBMs according to the updated WHO CNS5 classification, as well as to assess patient survival and clinical determinants, and compare the aforementioned biologi... |
## Methods |
### Study participants |
Patients with IDH-wildtype and H3-wildtype diffuse gliomas who underwent surgical tumor resection at Peking Union Medical College Hospital Neurosurgery between January 2011 and January 2022 were retrospectively screened. Patients’ tumors were defined as GBM (WHO grade 4), anaplastic astrocytomas (WHO grade 3), and diff... |
The present study was approved by the institutional review board at Peking Union Medical College Hospital. Written informed consent was obtained from every subject. |
### Definition of histological and molecular glioblastomas |
Hist-GBMs were defined as IDH-wildtype and H3-wildtype high-grade diffuse gliomas with microvascular proliferation and/or intratumoral necrosis. Mol-GBMs were defined as histological WHO grade 2-3 IDH-wildtype and H3-wildtype diffuse gliomas with TERT promoter mutation, EGFR amplification, or +7/-10 chromosome variatio... |
### Data acquisition |
Clinical information, radiological characteristics, and histological data were extracted from the electronic medical record ( Supplementary Table 1 ). Sixty molecular markers of interest, including gene alterations and chromosome copy number variations, were analyzed using the next-generation sequencing method, the PCR... |
### Targeted sequencing |
Genomic DNA from formalin-fixed paraffin-embedded (FFPE) tissue was isolated using the DNA FFPE Tissue Kit (Qiagen #56404). A custom glioma next-generation sequencing (NGS) panel was designed to investigate detailed molecular alterations in these patients. The 60-gene NGS panel contains some interested well-known genes... |
### Validation dataset |
RNA-sequencing and clinicopathological data of GBMs were downloaded from the Chinese Glioma Genome Atlas (CGGA; http://www.cgga.org.cn/; Dataset ID: mRNAseq_693, mRNAseq_325) to obtain a validation dataset. A total of 280 patients who were diagnosed with hist-GBMs according to the WHO CNS5 classification were enrolled.... |
### Statistical analyses |
Clinical, radiological, and pathological data expressed as categorical variables were shown as numbers and percentages, and continuous variables were presented as the means ± standard deviations or medians plus interquartile range according to data distribution. Comparisons of categorical variables were performed using... |
## Results |
### Changes in the classification of IDH-wildtype diffuse gliomas |
Among 209 IDH-wildtype diffuse gliomas (146 GBM, 38 anaplastic astrocytomas, and 25 diffuse astrocytomas) according to the WHO CNS4 classification, 191 (91%) were reclassified as GBM (146 hist-GBMs and 45 mol-GBMs), 11 (5%) as H3-wildtype and IDH-wildtype pediatric-type high-grade diffuse gliomas, and 7 (3%) as MYB/MYB... |
### Clinical presentations |
The average age of GBM patients was 55.5 years, with males comprising 52.4% of all samples ( Table 1 ). At diagnosis, 67.5% of patients exhibited neurological symptoms, with motor dysfunction (37.2%) and aphasia (21.5%) being the most common. Intracranial hypertension was found in 48.2% of patients, while 20.9% had a h... |
[table] Table 1Clinical, radiological, and pathological features of patients with histological or molecular glioblastomas.All Glioblastomas (n=191)Histological Glioblastomas (n=146)Molecular Glioblastomas (n=45)P ValueAge at diagnosis, year55.5 ± 14.756.9 ± 14.150.8 ± 15.8 0.015 Age ≥ 60, n/%80, 41.9%66, 45.2%14, 31.1%... |
Compared with hist-GBMs, patients with mol-GBMs were diagnosed at a younger age (50.8 ± 15.8 vs. 56.9 ± 14.1 years, p=0.015), had a lower incidence of motor dysfunction (17.8% vs. 43.2%, p=0.002), a higher incidence of epilepsy (33.3% vs. 17.1%, p=0.019) before admission, and a lower rate of gross total resection (44.4... |
### Radiological features |
The frontal (46.3%) and temporal (42.0%) lobes were the most frequently affected regions, and 52.5% of tumors invaded more than one lobe ( Table 1 ). 22.2% of included GBMs invaded deep structures (thalamus or callosum), and two were originated from the subtentorial region. Functional brain regions were involved in 55.... |
Compared with hist-GBMs, mol-GBMs were less likely to have contrast-enhancement (78.8% vs. 95.3%, p=0.006) and intratumoral necrosis (63.6% vs. 85.3%, p=0.005), and the median diameter of necrosis inside mol-GBMs was smaller (1.0 vs. 2.3cm, p=0.002). |
### Under-the-microscope pathological characteristics |
The median ki-67 index was 30% for all GBMs ( Table 1 ). Hist-GBMs had a higher median ki-67 index compared to mol-GBMs (30% vs. 10%, p<0.001). Among mol-GBMs, 60% were upgraded from WHO grade 3 IDH-wildtype anaplastic astrocytomas, and the other 40% originated from WHO grade 2 IDH-wildtype diffuse astrocytomas. No dif... |
### Genetic alterations and IHC expression |
Mutation was considered the main type of genetic alteration in TERT promotor, TOP3A, and BRAF; while deletions were predominantly observed in chr-10p/10q/9p, CDKN2A/B, PTEN, PTPN11, and FGFR1/2/4. Amplification was most commonly seen in chr-7p/q, EGFR, CDK6/4, MYB/MYBL1, MET, PIK3CA, NTRK2, PDGFRA, PEG3, KIT, NOTCH1, P... |
Compared with mol-GBMs, hist-GBMs had higher rates of genetic alterations in PTEN, TOP3A, CDK4, MYB, KIT, KRAS, and NTRK3 ( Supplementary Table 2 ). |
### Overall survival of glioblastomas as defined by the WHO CNS5 classification system |
Our results showed that the median OS for all GBMs was 12.6 months (95%CI: 11.1-15.8); it was 15.6 months (95%CI: 12.5-21.9) for mol-GBMs and 11.4 months (95%CI: 10.7-15.8) for hist-GBMs ( Figure 3 ). However, despite that mol-GBMs showed better survival, no significant difference was found between the two subtypes (HR... |
Patients aged ≥60 years (11.4 vs. 14.3, months; p=0.008), male patients (11.3 vs. 15.2, months; p=0.044), and those who did not undergo the standard Stupp treatment protocol (9.9 vs. 18.0, months; p=0.012) had a shorter OS than the others. MGMT promotor unmethylation, FGFR3 alteration, CIC alteration, KMT5B alteration,... |
### Clinical correlations of OS in histological and molecular glioblastomas |
In hist-GBMs, older age (≥60 years), not receiving the Stupp treatment protocol, +7/-10 chromosome copy-number changes, MGMT unmethylation, and alterations in CDK6, TOP3A, PTEN, MYB, MYBL1, KRAS, FGFR2, and CIC were significantly correlated with a shorter OS. In mol-GBMs, male sex, ki-67 ≥30%, and alterations in TP53, ... |
Multivariable regression analyses showed that older age, male sex, tumor involvement of functional brain areas and deep brain structures, and alterations in CDK4, CDK6, and KMT5B were predictive of a decreased OS, while maximal surgical resection as compared to biopsy, treatment with the Stupp protocol, and MGMT promot... |
[table] Table 2Independent clinical, radiological, and pathological factors associated with overall survival of patients with glioblastomas.All GlioblastomasHistological GlioblastomasMolecular GlioblastomasHR (95% CI)P ValueHR (95% CI)P ValueHR (95% CI)P ValueAge at diagnosis1.017 (1.004, 1.030) 0.010 1.015 (1.000, 1.0... |
### Validation of the clinical correlations of OS using the CGGA dataset |
In the RNA-sequencing validation set, high expression in CDK6, CIC, CDK4, TOP3A, and MYB and low expression in TP53 and FGFR3 were all significantly correlated with a shorter OS in hist-GBMs ( Figure 4 ). |
## Discussion |
Since the release of the 5th edition of the WHO classification of CNS tumors, the categorization of adult-type gliomas has been altered drastically. Among primary CNS tumors, GBM has undergone the greatest changes. In the present study, over 70% of previously defined grade 2-3 IDH-wildtype diffuse gliomas were re-class... |
Based on this new classification, current GBMs were diagnosed at a younger age and were more predominant in male patients. Also, more than two-thirds were accompanied by neurological deficits, particularly motor dysfunction, which differed slightly from the prior studies (23, 24). Older age, especially in hist-GBMs, an... |
The frontal and temporal lobes are the most commonly involved areas in GBM, they are the largest brain lobes (28). In the present study, tumor involvement of functional brain regions was found to be an independent predictor of a worse prognosis, while the motor cortex/tract was the most affected functional area, consis... |
The identification of specific biomarkers plays a crucial role in determining the prognosis of a medical condition and selecting the most suitable therapeutic approach (31). The occurrence of IDH mutation is an early event in the development of glioma and has significant consequences for glioma progression and treatmen... |
The rates of alterations of PTEN, CDK4, MYB, TOP3A, KIT, KRAS, and NTRK3 were higher in hist-GBMs than in mol-GBMs. Previous studies have reported that PTEN alteration is associated with therapeutic resistance in GBMs (36). CDK4/6, which regulates the cell cycle, are an important factor for the tumorigenesis of GBMs (3... |
Few studies assessed the real-world survival of GBM patients based on the WHO CNS5 classification (17, 45, 46). In this cohort, the median OS of GBMs was 12.6 months, which is shorter than 16 months calculated using the WHO CNS4 classification (47). The shorter OS may be partly due to the exclusion of IDH-mutant astroc... |
The WHO CNS5 classification places greater emphasis on molecular markers than ever before. Beyond IDH mutation, EGFR amplification, TERT promotor mutation, and +7/-10 chromosome copy-number variations, it is important to find additional molecular changes associated with the prognosis of GBMs that could assist in distin... |
Subsequently, we attempted to utilize the TCGA, CGGA, and GEO datasets to confirm our findings. However, since the release of the WHO CNS5 classification was too recent, we could not find any available dataset of DNA sequencing for validation, so we finally used the RNA-sequencing dataset from the CGGA to access the as... |
The current investigation exhibits certain constraints. The screening of IDH-wildtype gliomas during a certain period was incomplete due to unsuccessful DNA extraction from some FFPE samples, which experienced DNA degradation over an extended period. Consequently, a selection bias was inevitable. Furthermore, it is not... |
## Conclusions |
According to the WHO CNS5 classification, GBMs are a new comprehensive entity that encompasses both hist-GBMs (histologically grade 4) and mol-GBMs (histologically grade 2-3). Clinicians should update their diagnostic and therapeutic approaches to this lethal brain malignancy, as the clinical, radiological, molecular, ... |
## Data availability statement |
The data presented in the study are deposited in the figshare repository (DOI: 10.6084/m9.figshare.23593203). This data can be found here: https://figshare.com/articles/dataset/Data_for_the_article_Histological_and_molecular_glioblastoma_IDH-wildtype_A_real-world_landscape_using_the_2021_WHO_classification_of_central_n... |
## Ethics statement |
The studies involving human participants were reviewed and approved by Ethics Review Committee of Peking Union Medical College Hospital. The patients/participants provided their written informed consent to participate in this study. |
## Author contributions |
Conceptualization: XG and WC. Methodology: XG, LG, YL, and ZZ. Formal analysis and investigation: XG, LG, YL, ZZ, WC, YNW, YKW, HX, YS, DL, YX, TY, JL, JW, TL, HW, XZ, QL, SJ, TQ, SG, HL, YG, CW, KZ, YW, and WM. Writing—original draft preparation: XG, LG, YL, and ZZ. Writing—review and editing: YW and WM. Supervision: ... |
532bb39eb9a9c5b8bb06153fb947ab6e8a03479c5709a7425c5d6aa80557770b pmc10358772.txt |
PMCID: PMC10764572 |
TITLE: The Japanese breast cancer society clinical practice guidelines for pathological diagnosis of breast cancer, 2022 edition |
LICENSE: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Com... |
## Introduction |
This article is an English digest of the guidelines for pathological diagnosis published in The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines in Japanese by Kanehara & Co., Ltd. in July 2022. In the 2022 edition, six Reviews, eight Basic Questions (BQs), and six Future Research Questions (FRQs) wer... |
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