Pathology-based Study Research Articles

Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols

BackgroundGrade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.MethodsKi67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed.ResultsIn initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001).ConclusionsG2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.

Clinical relevance of double heterozygosity revealed by next-generation sequencing of homologous recombination repair pathway genes in South African breast cancer patients

PurposeGenetically predisposed breast cancer (BC) patients represent a minor but clinically meaningful subgroup of the disease, with 25% of all cases associated with actionable variants in BRCA1/2. Diagnostic implementation of next-generation sequencing (NGS) resulted in the rare identification of BC patients with double heterozygosity for deleterious variants in genes partaking in homologous recombination repair of DNA. As clinical heterogeneity poses challenges for genetic counseling, this study focused on the occurrence and clinical relevance of double heterozygous BC in South Africa.MethodsDNA samples were diagnostically screened using the NGS-based Oncomine™ BRCA Expanded Research Assay. Data was generated on the Ion GeneStudio S5 system and analyzed using the Torrent Suite™ and reporter software. The clinical significance of the variants detected was determined using international variant classification guidelines and treatment implications.ResultsSix of 1600 BC patients (0.375%) tested were identified as being bi-allelic for two germline likely pathogenic or pathogenic variants. Most of the variants were present in BRCA1/2, including two founder-related small deletions in three cases, with family-specific variants detected in ATM, BARD1, FANCD2, NBN, and TP53. The scientific interpretation and clinical relevance were based on the clinical and tumor characteristics of each case.ConclusionThis study increased current knowledge of the risk implications associated with the co-occurrence of more than one pathogenic variant in the BC susceptibility genes, confirmed to be a rare condition in South Africa. Further molecular pathology-based studies are warranted to determine whether clinical decision-making is affected by the detection of a second pathogenic variant in BRCA1/2 and TP53 carriers.

Validating the Baveno Elastography Criteria of Advanced Liver Fibrosis in Two-Dimensional Shear Wave Elastography: A Prospective Pathology-Based Study

Introduction: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE. Method: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cutoff value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis. Results: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0–63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cutoffs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83–0.97) and 0.93 (95% CI: 0.84–0.98), respectively (p = 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82–0.97) and 0.93 (95% CI: 0.84–0.98), respectively (p = 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively. Conclusion: This study establishes the compatibility of the Baveno dual cutoff criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

Digital Pathology-based Study of Cell- and Tissue-level Morphologic Features in Serous Borderline Ovarian Tumor and High-grade Serous Ovarian Cancer

Background: Serous borderline ovarian tumor (SBOT) and high-grade serous ovarian cancer (HGSOC) are two distinct subtypes of epithelial ovarian tumors, with markedly different biologic background, behavior, prognosis, and treatment. However, the histologic diagnosis of serous ovarian tumors can be subjectively variable and labor-intensive as multiple tumor slides/blocks need to be thoroughly examined to search for these features. Materials and Methods: We developed a novel informatics system to facilitate objective and scalable diagnosis screening for SBOT and HGSOC. The system was built upon Groovy scripts and QuPath to enable interactive annotation and data exchange. Results: The system was used to successfully detect cellular boundaries and extract an expanded set of cellular features representing cell- and tissue-level characteristics. The performance of cell-level classification for both tumor and stroma cells achieved >90% accuracy. The performance of differentiating HGSOC versus SBOT achieved 91%—95% accuracy for 6485 imaging patches which have sufficient tumor and stroma cells (minimum of ten each) and 97% accuracy for classifying patients when aggregating the results to whole-slide image based on consensus. Conclusions: Cellular features digitally extracted from pathological images can be used for cell classification and SBOT v. HGSOC differentiation. Introducing digital pathology into ovarian cancer research could be beneficial to discover potential clinical implications. A larger cohort is required to further evaluate the system.

Correction to: Cerebellar Microbleed Distribution Patterns and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging and Pathology-Based Study.

HomeStrokeVol. 50, No. 8Correction to: Cerebellar Microbleed Distribution Patterns and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging and Pathology-Based Study Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection to: Cerebellar Microbleed Distribution Patterns and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging and Pathology-Based Study Originally published22 Jul 2019https://doi.org/10.1161/STR.0000000000000195Stroke. 2019;50:e240This article corrects the followingCerebellar Microbleed Distribution Patterns and Cerebral Amyloid AngiopathyIn the article by Pasi et al, “Cerebellar Microbleed Distribution Patterns and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging and Pathology-Based Study,” which published online on June 4, 2019, and appeared in the July 2019 issue of the journal (Stroke. 2019;50:1727–1733. doi: 10.1161/STROKEAHA.119.024843), a correction is needed.In the footnotes on page 1727, the first affiliation for Thanakit Pongpitakmetha reads “From the Department of Pharmacology, Chulalongkorn University, Bangkok, Thailand.” It should read “From the Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.”This correction has been made to the current online version of the article, which is available at https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.024843. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesCerebellar Microbleed Distribution Patterns and Cerebral Amyloid AngiopathyMarco Pasi, et al. Stroke. 2019;50:1727-1733 August 2019Vol 50, Issue 8 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/STR.0000000000000195PMID: 31329529 Originally publishedJuly 22, 2019 PDF download Advertisement

Incidence pattern and spatial analysis of breast cancer in Iranian women: Geographical Information System applications.

Breast cancer is the leading cancer in Iranian women, but no studies have yet been conducted on the distribution and pattern of its incidence. To perform a spatial analysis and determine the incidence pattern of breast cancer in the Islamic Republic of Iran. This was a cross-sectional, pathology-based study of all new female patients with breast cancer registered in the Islamic Republic of Iran in 2011 (n=10 233). Initially, crude incidence rates were calculated for each province and the whole country per 100 000 person-years. Then, a direct standardization method and World Health Organization standard population were used to adjust for age effects on a geographical scale. Stata and Arc GIS software were used to calculate incidence rates and conduct spatial analysis. The mean (standard deviation) age of the patients was 50.9 (12.6) years. The national age-standardized incidence rate for breast cancer in women was 29.88 per 100 000 person-years, with a range of 5-72 in different provinces. The clustering incidence pattern was observed in Mazandaran, Tehran, Alborz, Isfahan and Markazi Provinces (P < 0.01). There was a significant cluster of high incidence of breast cancer in Iranian women. These findings may help to establish etiological hypotheses of cancer causation and identify spatial anomalies in cancer incidence or registration in the Islamic Republic of Iran. Our findings may also aid further research on the possible explanations for these clusters and associations.

Frequency of Barrett’s neoplasia after initial negative endoscopy with biopsy: a long-term histopathological follow-up study

Barrett's adenocarcinoma is being diagnosed increasingly. We examine possible differences between long segment and short-segment Barrett esophagus (LSBE and SSBE) in long-term follow-up on the basis of our histopathology registry. All Barrett's esophagus patients diagnosed histologically between 1990 and 1995 (n = 1071) were selected. Long-term follow-up data from endoscopy with biopsy were sought on all patients without neoplasia on initial endoscopic biopsy (n = 1003). A total of 255 individuals (25.4 %) were regarded as drop-outs (201 lost and 54 without further endoscopy). Of the remaining 748 patients with follow up for more than 5 years, 315 had documented LSBE, 246 had SSBE, and 187 had no length of Barrett esophagus recorded (NLBE). In the study cases (male : female ratio 2.1 : 1, mean age +/- SD 60.9 +/- 14.2 years), the biopsy procedure was fully compliant with guidelines in only 32.5 %. Only 5 cases (0.6 %) had visible lesions reported on endoscopy, but all were negative for neoplasia. Over a mean follow-up of 78.2 +/- 35.6 months (range 0-240), 7 new cases of low grade intraepithelial neoplasia (LGIN) and 15 cancer cases developed, accounting for a yearly incidence of 0.2 % (LGIN) or 0.4 % (cancer) after an initial negative endoscopy. When the cases with initial diagnosis of neoplasia were included, this yearly incidence rose to 0.5 % (LGIN), 0.3 % (high grade intraepithelial neoplasia [HGIN]) or 1.7 % (cancer). Differences between SSBE and LSBE were only encountered for cancer incidence. The yearly incidence of Barrett esophagus cancer varies between 0.4 % and 1.7 %. Despite the limitations of this retrospective and pathology-based study, the observed risk of developing cancer in Barrett esophagus without neoplasia is comparable to that found in other studies, mainly from the US and the UK, and varies between 0.7 % and 1.0 % of yearly incidence.

Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease.

Recent appreciation of atherosclerosis as a chronic, inflammatory disease has rekindled efforts to examine the role that infectious agents may play in atherogenesis. In particular, much interest has focused on infection with Chlamydia pneumoniae. The possibility that a prokaryote contributes to atherogenesis has high clinical interest, as C pneumoniae infection may be a treatable risk factor. To review the evidence implicating C pneumoniae in the pathogenesis of atherosclerosis, we searched MEDLINE for articles published between January 1966 and October 2002 on the association of C pneumoniae and atherosclerosis. We also used online resources, texts, meeting abstracts, and expert opinion. We included 5 types of studies (epidemiological, pathology based, animal model, cell biology, and human antibiotic treatment trials) and extracted diagnostic, pathophysiologic, and therapeutic information from the selected literature; consensus was reached on interpretation discrepancies. Chlamydia pneumoniae is associated with atherosclerosis by epidemiological and pathology-based studies. Animal model and cell biology studies suggest that the pathogen can modulate atheroma biology, including lipid- and inflammatory-related processes. Although some preliminary antibiotic treatment trials in patients with coronary artery disease indicated a reduction in recurrent coronary events, larger studies have not shown benefits in individuals with stable coronary artery disease. It is unlikely that C pneumoniae infection is necessary to initiate atherosclerosis. Furthermore, conventional antibiotic therapy may not eradicate the organism or reduce mortality in individuals with atherosclerotic vascular disease. Nevertheless, the current body of evidence establishes this pathogen as a plausible, potentially modifiable risk factor in cardiovascular disease.

Reduced reactive hyperemia in HIV-infected patients.

Given that several pathology-based studies reported some degree of coronary and arterial vasculopathy in HIV-infected patients, we investigated whether abnormal vascular reactivity may also be found in these patients. Vascular reactivity was assessed noninvasively using finger-skin blood-flow monitoring by laser-Doppler flow measurement in 10 HIV-infected-patients (mean CD4 T-cell count, 350+/-84 cells/mm3) with cardiac symptoms (previous myocardial infarction or left-ventricular dysfunction) and/or HIV-related protease inhibitor-induced hyperlipemia (group 1, symptomatic), 19 HIV-infected patients free of cardiac disease, hyperlipemia, and previous opportunistic infections (mean CD4 T-cell count, 333+/-175 cells/mm3; group 2, asymptomatic), and 19 healthy control subjects (group 3). Laser-Doppler flow was measured at baseline, during postocclusive hyperemic response following transient interruption of brachial blood flow (reactive hyperemia), during transcutaneous delivery of acetylcholine (Ach) using iontophoresis (endothelium-dependent dilation) and after sublingual nitroglycerin administration (endothelium-independent dilation). During reactive hyperemia, the absolute increase in flow was found to be lower in asymptomatic HIV-infected patients than in controls (median values [25th-75th percentile]: asymptomatic: 300 [200-400]; versus controls: 600 [400-750] arbitrary units [AU]; p< or =.0001). This abnormality was more pronounced in symptomatic patients (100 [100-200]; p< or =.0001). There was also a reduced peak/baseline flow ratio (symptomatic: 1.14 [1.1-1.2]; asymptomatic: 1.40 [1.25-1.5]; versus controls: 1.83 [1.6-2.2]; p<.0001 for both comparisons) and a reduced hyperemic response, as assessed by the curve of area under the flow versus time from deflation to the end of the hyperemic response (symptomatic: 1850 [1100-2225]; asymptomatic: 6000 [2850-7950]; versus controls: 23,735 [16,000-31, 800] AU x sec; p<.0001 for both comparisons). Although there was no statistically significant difference in acetylcholine (Ach)-induced increases in flow between asymptomatic HIV patients and controls (peak/baseline flow ratio: 6 [4.4-10] versus 5.3 [4-8]; p =.47), a trend to lower values was seen in symptomatic patients (4.4 [1.2-5]; p =.06). Administration of 0.4 mg sublingual nitroglycerin resulted in increases in flow without statistically significant difference between patients and controls: peak/baseline flow ratio for symptomatic: 2.4 [1.9-2.7]; asymptomatic: 2.1 [1.75-2.34] versus controls: 1.97 [1.8-2.4]; p =.2 and.83, respectively). Postischemic reactive hyperemia is reduced in HIV-infected patients. In addition, there was is trend for a reduced response to Ach only in those with cardiac disease and/or hyperlipemia.