Monostotic fibrous dysplasia of a lumbar vertebral body with secondary aneurysmal bone cyst formation: a case report

We report the case of a 25-year-old Caucasian woman with symptomatic monostotic fibrous dysplasia of the fourth lumbar vertebral body. The patient suffered from a five-week history of progressive low back pain, radiating continuously to the left leg. Her medical history and physical and neurological examination did not demonstrate any significant abnormalities. Radiographs, computed tomography and magnetic resonance imaging revealed an osteolytic expansive lesion with a cystic component of the fourth lumbar vertebral body. Percutaneous transpedicular biopsy showed histological characteristics of fibrous dysplasia superimposed by the formation of aneurysmal bone cyst components. The patient was treated by subtotal vertebrectomy of the L4 vertebral body with anterior reconstruction and her postoperative course was uncomplicated. To our knowledge, this is the first reported case of a monostotic fibrous dysplasia with superimposed secondary aneurysmal bone cysts of a lumbar vertebral body

Predictors of treatment response in lymphogenic metastasized papillary thyroid cancer:a histopathological study

Background Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases. Methods A total of 1042 lymph node metastases, derived from 129 PTC patients, were reexamined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications, and the proportion of the lymph node taken up by tumor cells. Predictors for a failure to achieve a complete biochemical and structural response to treatment were determined. Results The presence of more than 5 lymph node metastases was the only independent predictor for a failure to achieve a complete response to treatment (odds ratio [OR] 3.39 [95% CI, 1.57-7.33], P < .05). Diameter nor any of the other evaluated lymph node features were significantly associated with the response to treatment. Conclusions Detailed reexamination of lymph nodes revealed that only the presence of more than 5 lymph node metastases was an independent predictor of failure to achieve a complete response to treatment. No predictive value was found for other histopathological features, including the diameter of the lymph node metastases. These findings have the potential to improve risk stratification in patients with PTC and clinically evident lymph node metastases

Predictors of treatment response in lymphogenic metastasized papillary thyroid cancer:a histopathological study

Background Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases. Methods A total of 1042 lymph node metastases, derived from 129 PTC patients, were reexamined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications, and the proportion of the lymph node taken up by tumor cells. Predictors for a failure to achieve a complete biochemical and structural response to treatment were determined. Results The presence of more than 5 lymph node metastases was the only independent predictor for a failure to achieve a complete response to treatment (odds ratio [OR] 3.39 [95% CI, 1.57-7.33], P < .05). Diameter nor any of the other evaluated lymph node features were significantly associated with the response to treatment. Conclusions Detailed reexamination of lymph nodes revealed that only the presence of more than 5 lymph node metastases was an independent predictor of failure to achieve a complete response to treatment. No predictive value was found for other histopathological features, including the diameter of the lymph node metastases. These findings have the potential to improve risk stratification in patients with PTC and clinically evident lymph node metastases

The Dutch National TissueArchive Portal enables efficient, consistent, and transparent procurement of diagnostic tissue samples for scientific use

Biobanks play a crucial role in enabling biomedical research by facilitating scientific use of valuable human biomaterials. The PALGA foundation-a nationwide network and registry of histo- and cytopathology in the Netherlands-was established to promote the provision of data within and between pathology departments, and to make the resulting knowledge available for healthcare. Apart from the pathology data, we aimed to utilize PALGA's nationwide network to find and access the rich wealth of Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples for scientific use. We implemented the Dutch National TissueArchive Portal (DNTP) to utilize PALGA's nationwide network for requesting FFPE tissue samples. The DNTP consists of (1) a centrally organized internet portal to improve the assessing, processing, harmonization, and monitoring of the procurement process, while (2) dedicated HUB-employees provide practical support at peripheral pathology departments. Since incorporation of the DNTP, both the number of filed requests for FFPE tissue samples and the amount of HUB-mediated support increased 55 and 29% respectively. In line, the sample procurement duration time decreased significantly (- 47%). These findings indicate that implementation of the DNTP improved the frequency, efficiency, and transparency of FFPE tissue sample procurement for research in the Netherlands. To conclude, the need for biological resources is growing persistently to enable precision medicine. Here, we access PALGA's national, pathology network by implementation of the DNTP to allow for efficient, consistent, and transparent exchange of FFPE tissue samples for research across the Netherlands

Impact of Reclassification of Oncocytic and Follicular Thyroid Carcinoma by the 2022 WHO Classification

Background The 2022 WHO Classification categorizes oncocytic (OTC) and follicular thyroid carcinoma (FTC), based on the degree of capsular and vascular invasion, into minimally invasive (MI), encapsulated angio-invasive (EA), and widely invasive tumors (WI). While associations with clinical outcomes have been studied extensively in FTC, robust clinical data are lacking for OTC. We aimed to investigate the impact of the reclassification of OTC and FTC by the 2022 WHO Classification on clinical outcomes.Methods All adult OTC and FTC patients treated at the Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. All tumors were extensively revised by 2 independent pathologists, facilitated by Palga: Dutch Pathology Databank. Kaplan-Meier curves were used to study the association of the 2004 and 2022 WHO Classification with overall survival, disease-specific survival (DSS), recurrence-free survival, and radioactive iodine (RAI)-refractory disease.Results Among 52 OTC and 89 FTC patients, 15 (28.8%) OTC and 34 (38.2%) FTC tumors were reclassified as EAOTC or EAFTC. The 2022 WHO Classification substantially improved risk stratification in both subtypes for DSS, compared to the 2004 edition. Ten-year DSS rates were 100% for MIOTC, 92.9% for EAOTC, and 56.5% for WIOTC, compared to 100% (MIOTC) and 64.2% (WIOTC) following the 2004 WHO Classification. For FTC and RAI-refractory disease, similar trends were observed.Conclusion Classification of OTC and FTC into 3 subcategories as defined by the 2022 WHO Classification substantially improves discrimination between low-, intermediate-, and high-risk patients, especially for DSS and RAI-refractory disease

Increase in venous thromboembolism in SARS-CoV-2 infected lung tissue:proteome analysis of lung parenchyma, isolated endothelium, and thrombi

Aims: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue. Methods: Liquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls. Results: Compared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins. Conclusions: The decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.</p

Reliable identification of women with CIN3+ using hrHPV genotyping and methylation markers in a cytology-screened referral population.

Cervical screening aims to identify women with high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 2-3 (HSIL/CIN2-3) or invasive cervical cancer (ICC). Identification of women with severe premalignant lesions or ICC (CIN3+) could ensure their rapid treatment and prevent overtreatment. We investigated high-risk human papillomavirus (hrHPV) detection with genotyping and methylation of FAM19A4/miR124-2 for detection of CIN3+ in 538 women attending colposcopy for abnormal cytology. All women had an additional cytology with hrHPV testing (GP5+/6+-PCR-EIA+), genotyping (HPV16/18, HPV16/18/31/45), and methylation analysis (FAM19A4/miR124-2) and at least one biopsy. CIN3+ detection was studied overall and in women <30 (n = 171) and ≥30 years (n = 367). Positivity for both rather than just one methylation markers increased in CIN3, and all ICC was positive for both. Overall sensitivity and specificity for CIN3+ were, respectively, 90.3% (95%CI 81.3-95.2) and 31.8% (95%CI 27.7-36.1) for hrHPV, 77.8% (95%CI 66.9-85.8) and 69.3% (95%CI 65.0-73.3) for methylation biomarkers and 93.1% (95%CI 84.8-97.0) and 49.4% (95%CI 44.8-53.9) for combined HPV16/18 and/or methylation positivity. For CIN3, hrHPV was found in 90.9% (95%CI 81.6-95.8), methylation positivity in 75.8% (95%CI 64.2-84.5) and HPV16/18 and/or methylation positivity in 92.4% (95%CI 83.5-96.7). In women aged ≥30, the sensitivity of combined HPV16/18 and methylation was increased (98.2%, 95%CI 90.6-99.7) with a specificity of 46.3% (95%CI 40.8-51.9). Combination of HPV16/18 and methylation analysis was very sensitive and offered improved specificity for CIN3+, opening the possibility of rapid treatment for these women and follow-up for women with potentially regressive, less advanced, HSIL/CIN2 lesions

Socio-demographic and cultural factors related to non-participation in the Dutch colorectal cancer screening programme

BackgroundHigh participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed. We investigated demographic differences between participants and non-participants in the Dutch faecal immunochemical test-based colorectal cancer (CRC) screening programme.MethodsIn this population-based cohort study, we included all invitees for CRC screening in 2018 and 2019. Participation status, birth year, and sex were extracted from the Dutch national screening information system and linked to demographic characteristics from Statistics Netherlands, including migration background, level of education, socioeconomic category, household composition, and household income. A multivariable logistic regression was used to assess the association between demographic factors and participation.ResultsA total of 4,383,861 individuals were invited for CRC screening in 2018 and 2019, of which 3,170,349 (72.3%) participated. Individuals were less likely to participate when they were single and/or living with others (single with other residents versus couple: odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.31–0.38), had a migration background (e.g. Moroccan migrant versus Dutch background: OR 0.43, 95% CI: 0.42–0.44), or had a low income (lowest versus highest quintile: OR 0.45, 95% CI: 0.44–0.45). Although to a lesser extent, non-participation was also significantly associated with being male, being younger, receiving social welfare benefits and having a low level of education.ConclusionWe found that individuals who were single and/or living with others, immigrants from Morocco or individuals with low income were the least likely to participate in the Dutch CRC screening programme. Targeted interventions are needed to minimise inequities in CRC screening.Cellular mechanisms in basic and clinical gastroenterology and hepatolog