Histopathological features for coexistent invasive cancer in large colorectal adenomatous polyps

Abstract Background Histopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma. Methods High-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated. Results Seventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma. Conclusion Several histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.

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Mutation Profiling of Premalignant Colorectal Neoplasia

Gastroenterology Research and Practice ◽

10.1155/2019/2542640 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Jakub Karczmarski ◽

Krzysztof Goryca ◽

Jacek Pachlewski ◽

Michalina Dabrowska ◽

Kazimiera Pysniak ◽

...

Keyword(s):

Cellular Proliferation ◽

Colorectal Neoplasia ◽

Copy Number Variant ◽

Genetic Alterations ◽

Colorectal Adenomas ◽

Colorectal Carcinogenesis ◽

High Grade Dysplasia ◽

Low Grade ◽

High Grade ◽

Allelic Variants

Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequencies similar to those of LGD adenomas. A significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples. The profiling of advanced CNADs demonstrated variations in mutation patterns among colorectal premalignancies. Only limited numbers of genes were repeatedly mutated while the majority were altered in single cases. Most genetic alterations in adenomas can be considered early contributors to colorectal carcinogenesis.

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AWE-02 Morphological and molecular markers for coexistent adenocarcinoma in low-grade dysplastic areas of high-grade colorectal adenomas

10.1136/gutjnl-2019-bsgabstracts.20 ◽

2019 ◽

Author(s):

Andrew Emmanuel ◽

Salvador Diaz-Cano ◽

Shraddha Gulati ◽

Savvas Papagrigoriadis ◽

Bu Hayee ◽

...

Keyword(s):

Molecular Markers ◽

Colorectal Adenomas ◽

Low Grade ◽

High Grade

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Immunohistochemical Expression of p53 and Ki67 in Colorectal Adenomas and Prediction of Malignancy and Development of New Polyps

The International Journal of Biological Markers ◽

10.1177/172460080802300205 ◽

2008 ◽

Vol 23 (2) ◽

pp. 89-95 ◽

Cited By ~ 1

Author(s):

R. Vernillo ◽

B. Lorenzi ◽

T. Banducci ◽

C. Minacci ◽

C. Vindigni ◽

...

Keyword(s):

Regression Analysis ◽

Statistical Significance ◽

Colorectal Adenomas ◽

Low Grade ◽

High Grade ◽

Immunohistochemical Expression ◽

Ki67 Expression ◽

P53 Immunoreactivity ◽

Clinicopathological Variables

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

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Epithelium Lining Rat Renal Papilla: Nomenclature and Association with Chronic Progressive Nephropathy (CPN)

Toxicologic Pathology ◽

10.1177/0192623318762694 ◽

2018 ◽

Vol 46 (3) ◽

pp. 266-272 ◽

Cited By ~ 6

Author(s):

Nathália P. Souza ◽

Gordon C. Hard ◽

Lora L. Arnold ◽

Kirk W. Foster ◽

Karen L. Pennington ◽

...

Keyword(s):

Immunohistochemical Staining ◽

Low Grade ◽

High Grade ◽

Aged Rats ◽

Renal Papilla ◽

Diagnostic Systems ◽

Ki 67 ◽

Kidney Pelvis ◽

Specific Proteins ◽

Mitotic Figures

Chronic progressive nephropathy (CPN) occurs commonly in rats, more frequently and severely in males than females. High-grade CPN is characterized by increased layers of the renal papilla lining, designated as urothelial hyperplasia in the International Harmonization of Nomenclature and Diagnostic Criteria classification. However, urothelium lining the pelvis is not equivalent to the epithelium lining the papilla. To evaluate whether the epithelium lining the renal papilla is actually urothelial in nature and whether CPN-associated multicellularity represents proliferation, kidney tissues from aged rats with CPN, from rats with multicellularity of the renal papilla epithelium of either low-grade or marked severity, and from young rats with normal kidneys were analyzed and compared. Immunohistochemical staining for uroplakins (urothelial specific proteins) was negative in the papilla epithelium in all rats with multicellularity or not, indicating these cells are not urothelial. Mitotic figures were rarely observed in this epithelium, even with multicellularity. Immunohistochemical staining for Ki-67 was negative. Papilla lining cells and true urothelium differed by scanning electron microscopy. Based on these findings, we recommend that the epithelium lining the papilla not be classified as urothelial, and the CPN-associated lesion be designated as vesicular alteration of renal papilla instead of hyperplasia and distinguished in diagnostic systems from kidney pelvis urothelial hyperplasia.

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HISTOPATHOLOGICAL SPECTRUM OF UROTHELIAL LESIONS: AN OBSERVATIONAL STUDY

10.36106/paripex/5201627 ◽

2020 ◽

pp. 1-4

Author(s):

Nishat Ahmad ◽

Saurabh Banerjee ◽

A K. Srivastava

Keyword(s):

Urinary Bladder ◽

Urothelial Carcinoma ◽

Bladder Tumour ◽

Histopathological Analysis ◽

Low Grade ◽

High Grade ◽

Urothelial Carcinomas ◽

Neoplastic Lesions ◽

Papillary Urothelial Carcinoma ◽

Muscle Invasion

BACKGROUND: Urinary bladder cancer is second most common cancer after prostate cancer in the genitourinary system. Urothelial Carcinoma is the commonest tumour type accounting for 90% of all primary tumours of the bladder Histopathological analysis of cystoscopic bladder biopsy and Transurethral resection of the bladder tumour (TURBT) material are the mainstay for cancer diagnosis. This study was aimed to determine the frequency of different types of neoplastic lesions of the urinary bladder and to determine the grade and stage of urothelial tumours. MATERIAL METHOD: The study was carried out in the Department of Pathology, Rajendra Institute of Medical Sciences (RIMS), Ranchi from January 2018 to June 2020 and included 30 cases of cystoscopic biopsies and TURBT specimens. RESULTS: Out of 30 cases of neoplastic lesions, majority were of high grade papillary urothelial carcinoma (n=14, 46.67%) followed by low grade papillary urothelial carcinoma (n=9, 30%), 3 cases (10%) were of PUNLMP, 2 cases (6.66%) of papilloma and 1 (3.33%) case each of moderately differentiated squamous cell carcinoma and extra nodal NHL. The most common age group was 41-50 years and 51-60 years with 9 (30%) cases each. Muscle invasion was seen only in high grade papillary urothelial carcinomas. CONCLUSION: High-grade urothelial carcinomas with lamina propria and muscle invasion are the most common neoplastic lesion of urinary bladder with significant morbidity and mortality. Muscle invasion and grading, as per TNM staging, are valuable prognostic factors.

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Preoperative Ultrasonographic Evaluation for Malignancy of Soft-Tissue Sarcoma: A Retrospective Study

The Open Orthopaedics Journal ◽

10.2174/1874325001812010075 ◽

2018 ◽

Vol 12 (1) ◽

pp. 75-83 ◽

Cited By ~ 4

Author(s):

Takeshi Morii ◽

Tomonori Kishino ◽

Naoko Shimamori ◽

Mitsue Motohashi ◽

Hiroaki Ohnishi ◽

...

Keyword(s):

Retrospective Study ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Odds Ratio ◽

Scoring System ◽

Operating Characteristic ◽

Low Grade ◽

High Grade ◽

Tumor Margin ◽

Malignant Soft Tissue

Background: Ultrasonography is useful for distinguishing between benign and malignant soft-tissue tumors. However, no study has focused on its usefulness in the differential diagnosis between low-grade and high-grade soft-tissue sarcomas. We conducted a retrospective study to determine the usefulness of the parameters of ultrasonograph and to develop a practical scoring system for distinguishing between high-grade and low-grade sarcomas. Methods: Twenty-two cases of low-grade and 43 cases of high-grade malignant soft-tissue sarcoma were enrolled. Ultrasonography parameters including the longest diameter, depth of the tumor, echogenicity, tumor margin, and vascularity defined according to Giovagnorio’s criteria were analyzed as factors to distinguish between the two types of sarcoma. Significant factors were entered into a multivariate model to define the scores for distinction according to the odds ratio. The usefulness of the score was analyzed via receiver operating characteristic analyses. Results: In univariate analysis, tumor margin, echogenicity, and vascularity were significantly different between low- and high-grade sarcomas. In the multivariate regression model, the odds ratio for high-grade vs. low-grade sarcoma was 8.8 for tumor margin, 69 for echogenicity, and 8.3 for vascularity. Scores for the risk factors were defined as follows: 1, ill-defined margin; 2, hypoechoic echogenicity; and 1, type IV in Giovagnorio’s criteria. The sum of each score was confirmed by receiver operating characteristic analysis. The area under the curve was 0.95, with a cut-off score of 3, indicating that the scoring system was useful. Conclusion: The ultrasonography parameters of tumor margin, echogenicity, and vascularity are useful for distinguishing between low- and high-grade sarcomas.

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Progesterone and estrogen receptor expression by canine cutaneous soft tissue sarcomas

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-6103 ◽

2020 ◽

Vol 40 (4) ◽

pp. 284-288 ◽

Cited By ~ 1

Author(s):

Fabricia H. Loures ◽

Lissandro G. Conceição ◽

Renee L. Amorim ◽

Juliano Nobrega ◽

Rafael T. Neto ◽

...

Keyword(s):

Soft Tissue ◽

Progesterone Receptors ◽

Soft Tissue Sarcomas ◽

Metastatic Potential ◽

Receptor Expression ◽

Low Grade ◽

Nerve Sheath Tumor ◽

Histopathological Features ◽

New Treatment ◽

Mitotic Figures

ABSTRACT: Canine soft tissue sarcomas (STS) comprise a heterogeneous group of malignancies that share similar histopathological features, a low to moderate recurrence rate and low metastatic potential. In human medicine, the expression of estrogen receptors (ER) and progesterone receptors (PR) in sarcomas has been studied to search for prognostic factors and new treatment targets. Similar studies have yet to be conducted in veterinary medicine. The objective of this study was therefore to investigate by immunohistochemistry (IHC) the ER and PR expression in a series of 80 cutaneous and subcutaneous sarcomas in dogs with histopathological features of peripheral nerve sheath tumor (PNST) and perivascular wall tumor (PWT). All cases were positive for PR and negative for ER. Tumors of high malignancy grade (grade III) exhibited higher PR expression than low-grade tumors (grade I). Tumors with mitotic activity greater than 9 mitotic figures/10 high power fields also exhibited higher PR expression. In addition, there was a positive correlation between cell proliferation (Ki67) and PR expression. Therefore, it is possible that progesterone plays a greater role than estrogen in the pathogenesis of these tumors. Future studies should explore the potential for selective progesterone receptor modulators as therapeutic agents in canine STS, as well as evaluating PR expression as a predictor of prognosis.

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Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00456-8 ◽

2021 ◽

Author(s):

Erik Margolis ◽

Gordon Brown ◽

Alan Partin ◽

Ballentine Carter ◽

James McKiernan ◽

...

Keyword(s):

Prostate Cancer ◽

Predictive Value ◽

Validation Studies ◽

Characteristic Curve ◽

Randomized Study ◽

Specific Antigen ◽

Low Grade ◽

High Grade ◽

Grade Group ◽

Initial Biopsy

Abstract Background The ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2–10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision. Methods Pooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated using the area under the receiver-operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity for discriminating ≥ GG2 from GG1 and benign pathology. Results The combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values <0.001) for discriminating GG2 from GG1 and benign histology. The validated cutoff of 15.6 would avoid 23% of all prostate biopsies and 30% of “unnecessary” (benign or Gleason 6/GG1) biopsies, with an NPV of 90%. Conclusions EPI is a noninvasive, easy-to-use, urine exosome–RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.

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An extent of resection threshold for seizure freedom in patients with low-grade gliomas

Journal of Neurosurgery ◽

10.3171/2016.12.jns161682 ◽

2018 ◽

Vol 128 (4) ◽

pp. 1084-1090 ◽

Cited By ~ 20

Author(s):

David S. Xu ◽

Al-Wala Awad ◽

Chad Mehalechko ◽

Jeffrey R. Wilson ◽

Lynn S. Ashby ◽

...

Keyword(s):

Operating Characteristic ◽

Seizure Control ◽

Characteristic Curve ◽

Tumor Resection ◽

Extent Of Resection ◽

Class I ◽

Seizure Freedom ◽

Low Grade ◽

Newly Diagnosed

OBJECTIVESeizures are the most common presenting symptom of newly diagnosed WHO Grade II gliomas (low-grade glioma [LGG]) and significantly impair quality of life. Although gross-total resection of LGG is associated with better seizure control, it remains unclear whether an extent of resection (EOR) “threshold” exists for long-term seizure control. Specifically, what proportion of FLAIR-positive tissue in patients with newly diagnosed LGG must be removed to achieve Engel Class I seizure freedom? To clarify the EOR threshold for long-term seizure control, the authors analyzed data from a consecutive series of patients with newly diagnosed LGG who presented with seizures and subsequently underwent microsurgical resection.METHODSThe authors identified consecutive patients with newly diagnosed LGG who presented with seizures and were treated at the Barrow Neurological Institute between 2002 and 2012. Patients were dichotomized into those who were seizure free postoperatively and those who were not. The EOR was calculated by quantitative comparison of pre- and postoperative MRI. Univariate analysis of these 2 groups included the chi-square test and the Mann-Whitney U-test, and a multivariate logistic regression was constructed to predict the impact of multiple independent variables on the likelihood of postoperative seizure freedom. To determine a threshold of EOR that optimizes seizure freedom, a receiver operating characteristic curve was plotted and the optimal point of discrimination was determined.RESULTSData from 128 patients were analyzed (male/female ratio 1.37:1; mean age 40.8 years). All 128 patients presented with seizures, usually generalized (n = 57, 44.5%) or simple partial (n = 57, 44.5%). The median EOR was 90.0%. Of 128 patients, 46 (35.9%) had 100% volumetric tumor resection, 64 (50.0%) had 90%–99% volumetric tumor resection, and 11 (8.6%) had 80%–89% volumetric tumor resection. Postoperatively, 105 (82%) patients were seizure free (Engel Class I); 23 (18%) were not (Engel Classes II–IV). The proportion of seizure-free patients increased in proportion to the EOR. Predictive variables included in the regression model were preoperative Karnofsky Performance Scale score, seizure type, time from diagnosis to surgery, preoperative number of antiepileptic drugs, and EOR. Only EOR significantly affected the likelihood of postoperative Engel Class I status (OR 11.5, 95% CI 2.4–55.6; p = 0.002). The receiver operating characteristic curve generated based on Engel Class I status showed a sensitivity of 0.65 and 1 – specificity of 0.175, corresponding to an EOR of 80%.CONCLUSIONSFor adult patients with LGG who suffer seizures, the results suggest that seizure freedom can be attained when EOR > 80% is achieved. Improvements in both the proportion of seizure-free patients and the durability of seizure freedom were observed beyond this 80% threshold. Interestingly, this putative EOR seizure-freedom threshold closely approximates that reported for the overall survival benefit in newly diagnosed hemispheric LGGs, suggesting that a minimum level of residual tumor burden is necessary for both disease and symptomatic progression.

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Glucose Loading Enhances the Value of 18F-FDG PET/CT for the Characterization and Delineation of Cerebral Gliomas

Cancers ◽

10.3390/cancers12071977 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1977

Author(s):

Dongwoo Kim ◽

Hae Young Ko ◽

Sangwon Lee ◽

Yong-ho Lee ◽

Sujin Ryu ◽

...

Keyword(s):

Fdg Pet ◽

Characteristic Curve ◽

Low Grade ◽

High Grade ◽

Glucose Loading ◽

Pet Ct ◽

Significant Difference ◽

18F Fdg ◽

Fdg Pet Ct ◽

Normal Cortex

This study aimed to assess how to enhance the value of 18F-Fluorodeoxyglucose (FDG) PET/CTs for glioma grading and better delineation of the tumor boundary by glucose loading. In mouse models of brain tumor using U87MG cells, 18F-FDG-PET images were obtained after fasting and after glucose loading. There was a significant difference in the tumor-to-normal cortex-uptake ratio (TNR) between the fasting and glucose-loading scans. 14C-2-Deoxy-D-glucose (14C-DG) uptake was measured in vitro using U87MG, U373MG and primary neurons cultured with different concentrations of glucose. The tumor-to-neuron ratio of 14C-DG uptake increased with up to 10 mM of glucose. Finally, 10 low-grade and 17 high-grade glioma patients underwent fasting and glucose loading 18F-FDG PET/CT and the TNR was compared between scans. The effect of glucose loading was significant in high-grade but not in low-grade gliomas. The receiver operating characteristic curve analyses with a cut-off TNR of 0.81 showed a higher area under the curve after glucose loading than fasting for differentiating low-grade versus high-grade gliomas. In addition, the glucose loading PET/CT was more useful than the fasting PET/CT for the discrimination of oligodendrogliomas from IDH-wildtype glioblastomas. Glucose loading resulted in a greater reduction in 18F-FDG uptake in the normal cortex than in tumors, which increases the usefulness of 18F-FDG PET/CT for grading.

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