Thyroid Bethesda Category AUS/FLUS in Our Microscopes : Three-Year-Experience and Cyto-Histological Correlation

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) introduced a new category: Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) comprising of heterogenous lesions with a lesser degree of atypia. Its routine use is a bit controversial. The study cohort included AUS/FLUS thyroid cytopathological diagnoses signed out at Fimlab Laboratories from the period of 1 October 2013 to 31 December 2016. We analyzed all the AUS/FLUS cases, their cytology subclassification, and their cyto-histological correlation, when available. In total, there were 331 AUS/FLUS cases from 252 patients. The mean age was 59.8 years and there were 196 females and 56 males. Repeated AUS/FLUS was diagnosed in 75 (29.8%) cases. Out of 252 patients, 118 (46.8%) were operated on. Sixty-eight were operated on after the first AUS/FLUS diagnosis, 46 after 2 AUS/FLUS diagnoses, and 4 after 3 AUS/FLUS diagnoses. In total, there were 37 (14.7%) malignancies and 40 benign tumors. The risk of malignancy for AUS/FLUS (14.7%) is in agreement with the original TBSRTC risk of malignancy. The risk of neoplasia was 30.6% in our series

Cyto-Histopathological Correlations in Pathology Diagnostics

publishedVersionNon peer reviewe

Salivary Gland FNA Diagnostics in a Real-Life Setting : One-Year-Experiences of the Implementation of the Milan System in a Tertiary Care Center

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 following other organ specific cytopathological reporting systems and it aimed at bringing a practical, evidence-based, user-friendly classification system with characterization and management algorithms. At the Department of Pathology, Fimlab Laboratories, Tampere, Finland all salivary fine needle aspirations (FNAs) have been given cytopathological diagnoses according to the MSRSGC since January 2018. Analyses of a one-year-period (January 2018–December 2018) consisted of 183 salivary FNA samples from 138 patients with correlation to histopathology in 90 cases with surgical follow-up. The MSRSGC performance in patient based analysis was as follows: accuracy was 90.9%, sensitivity was 61.5%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 89.4%, respectively. Risks of malignancy (ROMs) in MSRSGC categories were: 0.0% (0/15) in non-diagnostic category, 100.0% (1/1) in non-neoplastic category biased by only one falsely-negative lymphoma case, 14.3% (1/7) in atypia of undetermined significance category, 0.0% (0/28) in benign neoplasm category, 27.3% (3/11) in neoplasm of uncertain malignant potential category, and 100% for both suspicious for malignancy (4/4) and malignancy (4/4) categories, respectively. The MSRSGC has been proven as a reliable classification system in salivary gland FNA routine diagnostics in a tertiary care center

The diagnostic accuracy of pleomorphic adenoma in fine needle aspiration : Features leading to false positive and false negative diagnoses and the utility of cell blocks

Objective: Fine needle aspiration (FNA) is a well-established tool in preoperative diagnosis of salivary gland lesions with diagnostic accuracy of 90%. Pleomorphic adenoma (PA) is the most common salivary gland tumor comprising 45%–74% of all salivary gland tumors with FNA diagnostic accuracy of 89.5%–96.2%. The aim of the present study was to determine and analyze potential cytomorphological pitfalls and evaluate the diagnostic accuracy in FNA diagnosis of PA. Methods: Salivary gland specimens with both cytological and histological diagnoses were searched over a 10-year-period (2009–2018) from a laboratory information system of Pathology Department, Fimlab Laboratories, Tampere and matched to determine concordant and discordant PA cases. Sufficient material in histological and cytological sample was found in 401 cases. In 218 cases (54.4%) diagnosis was true-negative PA, in 169 cases (42.1%) diagnosis was true-positive PA and there were 14 discordant cases: 4 false-positive cases and 10 false-negative cases. False-negative cases were reclassified and subgrouped according to The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). Results: Cytomorphologically, cell type predominance was more often myoepithelial in true-positive cases (65%) and epithelial both in false-negative (70%, p =.007) and false-positive cases (75%, p =.027). Well-formed ducts were present in cytology in all true-positive cases (p <.001). Only 10% of true-positive cases did not show any matrix in cytology (p <.001). Nuclear changes were common in false-negative cases (80%, p =.002) and false-positive cases (75%, p =.003). Beneficial cell block (CB) was more common in true-positive cases (85%) than in false-negative cases (50%, p =.041) or in false-positive cases (50%, p =.116) and a lack of beneficial CB led more often to a false diagnosis (70% false diagnosis without beneficial CB versus 29% false diagnosis with beneficial CB). Conclusion: The present study showed diagnostic accuracy of 96.5% for FNA in PA diagnosis. Sensitivity, specificity, positive predictive value and negative predictive value were 94.4%, 98.2%, 97.7%, and 95.6%, respectively. The benefit of CBs was more evident in true-positive cases (85%).Peer reviewe

Autonomic nerves in myocardial sleeves around caval veins : Potential role in cardiovascular mortality?

Background: Quantitative changes in the cardiac autonomic nervous system may play an important role in the pathogenesis of various cardiovascular diseases. In the present morphological analysis, we aimed to study autonomic nerve density in myocardial sleeves and surrounding fibro-fatty tissue around caval veins. We correlated the nerve distribution with cardiovascular mortality and a history of atrial fibrillation. Materials and Methods: A total of 24 autopsied adult hearts were excised together with the superior and inferior vena cava and grouped according to the immediate and underlying causes of death (cardiovascular vs. non-cardiovascular), and documented heart rhythm history (atrial fibrillation vs. sinus rhythm). The density of autonomic nerves was quantified by measuring the area of immunohistochemical staining for sympathetic (tyrosine hydroxylase, TH) and parasympathetic (choline acetyltransferase, CHAT) nerves and ganglia. Growth-associated protein 43 (GAP43) was used as a neural growth marker. Results: The mean density of TH-positive nerves in the superior vena cava myocardial sleeves was significantly decreased between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean density ± standard deviation (SD): 704.81±1016.41 µm2/mm2 vs. 2391.01±1841.37 µm2/mm2; P =.008). Similarly, the nerve density of GAP43-positive nerves in the superior vena cava myocardial sleeves was significantly lower in subjects with documented underlying cardiovascular cause of death (mean density ± SD: 884.74±1240.16 µm2/mm2 vs. 2132.89±1845.89 µm2/mm2; P =.040). The mean age was significantly higher in subjects with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean age ± SD: 69.2±11.9 years, vs. 57.5±11.2 years, P =.016). No differences were found in nerve densities of TH-positive (953.01±1042.93 µm2/mm2 vs. 919.26±1677.58 µm2/mm2), CHAT-positive (180.8±532.9 µm2/mm2 vs. 374.22±894.76 µm2/mm2), and GAP43-positive nerves (593.58±507.97 µm2/mm2 vs. 1337.34±1747.69 µm2/mm2) in myocardial sleeves around the inferior vena cava between groups with documented immediate cardiovascular vs. non-cardiovascular cause of death. Similarly, no differences were found between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (TH: 717.23±887.31 µm2/mm2 vs. 1365.51±2149.10 µm2/mm2; CHAT: 256.18±666.86 µm2/mm2 vs. 368.53±959.47 µm2/mm2; GAP43: 661.21±839.51 µm2/mm2 vs. 1759.90±2008.80 µm2/mm2). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm2/mm2 vs. 1166.08±1563.84 µm2/mm2; CHAT: 648.59±1017.33 µm2/mm2 vs. 175.31±641.65 µm2/mm2; GAP43: 990.17±1315.18 µm2/mm2 vs. 1039.86±1467.23 µm2/mm2). Conclusions: Decrease of superior vena cava myocardial sleeve sympathetic nerves may be associated with cardiovascular mortality and/or aging. No difference in autonomic innervation was found between subjects with documented atrial fibrillation vs. sinus rhythm.publishedVersionPeer reviewe

Human Pulmonary Vein Myocardial Sleeve Autonomic Neural Density and Cardiovascular Mortality

Myocardial sleeves around pulmonary veins (PVs) are highly innervated structures with heterogeneous morphological and electrophysiological characteristics. Autonomic nerve dysfunction in the myocardium may be associated with an increased risk of cardiovascular morbidity and mortality. This article studied autonomic neural remodeling in myocardial sleeves around PVs and atrial-PV ostia with immunohistochemical and morphometric methods with clinicopathological correlations. PVs were collected from 37 and atrial-PV ostia from 17 human autopsy hearts. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43). In the PV cohort, subjects with immediate cardiovascular cause of death had significantly decreased sympathetic nerve density in fibro-fatty tissue vs those with non-cardiovascular cause of death (1624.53 vs 2522.05 µm2/mm2, p=0.038). In the atrial-PV ostia cohort, parasympathetic nerve density in myocardial sleeves was significantly increased in subjects with underlying cardiovascular cause of death (19.48 µm2/mm2) than subjects with underlying non-cardiovascular cause of death with no parasympathetic nerves detected (p=0.034). Neural growth regionally varied in sympathetic nerves and was present in most of the parasympathetic nerves. Heterogeneous autonomic nerve distribution and growth around PVs and atrial-PV ostia might play a role in cardiovascular morbidity and mortality. No association in nerve density was found with atrial fibrillation.acceptedVersionPeer reviewe

Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) : Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile

Since Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) was introduced as a new thyroid tumour entity, many studies, and meta-analyses on diag-nosing NIFTP have been published. NIFTP-revised histopathological criteria emerged in 2018. NIFTP is defined as a histological entity and its diagnosis requires a careful histological examination. Its molecular profile is similar to follicular-like tumours. Ultrasound features are unable to differentiate NIFTP. NIFTP is not a cytological diagnosis, but it influences the risk of malignancy in several categories of The Bethesda System for Reporting Thyroid Cytopathology terminology.publishedVersionPeer reviewe

Atypical urothelial cells classified according to the Paris System for Reporting Urinary Cytology : A 2-year experience with histological correlation from a Finnish tertiary care center—low rate and high risk of malignancy

Background: The Paris System for Reporting Urinary Cytology (TPS) was issued to shift the focus of urine cytology to high-grade lesions to increase the diagnostic accuracy of urine cytology. The aim of this study was to evaluate the power of TPS in the atypical urothelial cells (AUC) category with histological correlation and follow-up. Methods: The data cohort consisted of 3741 voided urine samples collected during a 2-year period between January 2017 and December 2018. All samples were prospectively classified using TPS. This study focuses on the subset of 205 samples (5.5%) classified as AUC. All cytological and histological follow-up data were analyzed until 2019, and the time between each sampling was documented. Results: Of the 205 AUC cases, cytohistological correlation was possible in 97 (47.3%) cases. Of these, 36 (12.7%) were benign in histology, 27 (13.2%) were low-grade urothelial carcinomas, and 34 (16.6%) were high-grade urothelial carcinomas. Overall, the risk of malignancy was 29.8% for all cases in the AUC category, and 62.9% in the histologically confirmed cases. The risk of high-grade malignancy was 16.6% in all the AUC category samples and 35.1% in the histological follow-up group. Conclusions: The performance of 5.5% AUC cases is considered good and within the limits proposed by TPS. TPS is widely accepted by cytotechnologists, cytopathologists, and clinicians; it improves communication and patient management.Peer reviewe

Left ventricular dysfunction with reduced functional cardiac reserve in diabetic and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice

BACKGROUND: Lack of suitable mouse models has hindered the studying of diabetic macrovascular complications. We examined the effects of type 2 diabetes on coronary artery disease and cardiac function in hypercholesterolemic low-density lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR(-/-)ApoB(100/100)). METHODS AND RESULTS: 18-month-old LDLR(-/-)ApoB(100/100 )(n = 12), diabetic LDLR(-/-)ApoB(100/100 )mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells (IGF-II/LDLR(-/-)ApoB(100/100), n = 14) and age-matched C57Bl/6 mice (n = 15) were studied after three months of high-fat Western diet. Compared to LDLR(-/-)ApoB(100/100 )mice, diabetic IGF-II/LDLR(-/-)ApoB(100/100 )mice demonstrated more calcified atherosclerotic lesions in aorta. However, compensatory vascular enlargement was similar in both diabetic and non-diabetic mice with equal atherosclerosis (cross-sectional lesion area ~60%) and consequently the lumen area was preserved. In coronary arteries, both hypercholesterolemic models showed significant stenosis (~80%) despite positive remodeling. Echocardiography revealed severe left ventricular systolic dysfunction and anteroapical akinesia in both LDLR(-/-)ApoB(100/100 )and IGF-II/LDLR(-/-)ApoB(100/100 )mice. Myocardial scarring was not detected, cardiac reserve after dobutamine challenge was preserved and ultrasructural changes revealed ischemic yet viable myocardium, which together with coronary artery stenosis and slightly impaired myocardial perfusion suggest myocardial hibernation resulting from chronic hypoperfusion. CONCLUSIONS: LDLR(-/-)ApoB(100/100 )mice develop significant coronary atherosclerosis, severe left ventricular dysfunction with preserved but diminished cardiac reserve and signs of chronic myocardial hibernation. However, the cardiac outcome is not worsened by type 2 diabetes, despite more advanced aortic atherosclerosis in diabetic animals

Lymph vessels:the forgotten second circulation in health and disease

The lymphatic circulation is still a somewhat forgotten part of the circulatory system. Despite this, novel insights in lymph angiogenesis in health and disease, application of immune markers for lymphatic growth and differentiation and also the introduction of new imaging techniques to visualize the lymphatic circulation have improved our understanding of lymphatic function in both health and disease, especially in the last decade. These achievements yield better understanding of the various manifestations of lymph oedemas and malformations, and also the patterns of lymphovascular spread of cancers. Immune markers that recognize lymphatic endothelium antigens, such as podoplanin, LYVE-1 and Prox-1, can be successfully applied in diagnostic pathology and have revealed (at least partial) lymphatic differentiation in many types of vascular lesion