Mismatch repair deficiency: how reliable is the two-antibody approach? A national real-life study.

Aims: Traditionally, mismatch repair (MMR) status is determined by a panel of four antibodies (MLH1, PMS2, MSH2, MSH6). If all proteins are retained, cases are MMR proficient (pMMR), while loss of one or more proteins is indicative of MMR deficiency (dMMR). This approach has been challenged in favour of a two-antibody approach, using PMS2 and MSH6 as a first screening.

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.

European experience with the Afirma Gene Expression Classifier for indeterminate thyroid nodules: A clinical utility study in the Netherlands.

Background: The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical utility in a European population with restrictive diagnostic workup.

Methods: Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules.

Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions.

 In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool. All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018.

The longitudinal association between depressive symptoms and functional abilities in older patients.

Objectives: To investigate the course of depressive symptoms, and basic and instrumental activities of daily living (collectively described as, (I)ADL functioning) from acute admission until one year post-discharge, the longitudinal association between depressive symptoms and (I)ADL functioning, and to disaggregate between- and within-person effects to examine whether changes in depressive symptoms are associated with changes in (I)ADL functioning.

Methods: Prospective multicenter cohort of acutely hospitalized patients aged ≥70. Data gathered over a one-year period were assessed using validated measures of depressive symptoms (GDS-15) and physical functioning (Katz-ADL index).

New national recommendations for the treatment of pediatric differentiated thyroid carcinoma in the Netherlands.

Background: Currently, there are no European recommendations for the management of pediatric thyroid cancer. Other current international guidelines are not completely concordant. In addition, medical regulations differ between, for instance, the US and Europe.

Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel.

Aims: Thymic tumours are rare in routine pathology practice. Although the World Health Organization (WHO) classification describes a number of well-defined categories, the classification remains challenging. The aim of this study was to investigate the reproducibility of the WHO classification among a large group of international pathologists with expertise in thymic pathology and by using whole slide imaging to facilitate rapid diagnostic turnover.

Hopelessness and Other Depressive Symptoms in Adults 70 Years and Older as Predictors of All-Cause Mortality Within 3 Months After Acute Hospitalization: The Hospital-ADL Study.

Objective: Depression among older adults predicts mortality after acute hospitalization. Depression is highly heterogeneous in its presentation of symptoms, whereas individual symptoms may differ in predictive value. This study aimed to investigate the prevalence of individual cognitive-affective depressive symptoms during acute hospitalization and investigate the predictive value of both overall and individual cognitive-affective depressive symptoms for mortality between admission up to 3-month postdischarge among older patients.

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls.

Background: For progressive metastatic medullary thyroid carcinoma (MTC), the available treatment options with tyrosine kinase inhibitors result in grade 3-4 adverse events in a large number of patients. Peptide Receptor Radionuclide Therapy (PRRT), which has also been suggested to be a useful treatment for MTC, is usually well tolerated, but evidence on its effectivity is very limited.

Methods: Retrospective evaluation of treatment effects of PRRT in a highly selected group of MTC patients, with progressive disease or refractory symptoms.

Expression of Contactin 4 Is Associated With Malignant Behavior in Pheochromocytomas and Paragangliomas.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine, usually benign, tumors. Currently, the only reliable criterion of malignancy is the presence of metastases.

Objective: The aim of this study was to identify genes associated with malignancy in PPGLs.

An International Ki67 Reproducibility Study in Adrenal Cortical Carcinoma.

Despite the established role of Ki67 labeling index in prognostic stratification of adrenocortical carcinomas and its recent integration into treatment flow charts, the reproducibility of the assessment method has not been determined. The aim of this study was to investigate interobserver variability among endocrine pathologists using a web-based virtual microscopy approach. Ki67-stained slides of 76 adrenocortical carcinomas were analyzed independently by 14 observers, each according to their method of preference including eyeballing, formal manual counting, and digital image analysis.

Complex MAX Rearrangement in a Family With Malignant Pheochromocytoma, Renal Oncocytoma, and Erythrocytosis.

Context: Familial pheochromocytoma (PCC) has been associated with germline mutations in 16 genes. Here we investigated three siblings presenting with bilateral pheochromocytomas. In addition, the index patient also exhibited renal oncocytoma and erythrocytosis, whereas the second sibling presented with a lymph node metastasis.

[Guideline thyroid cancer including diagnostics of the nodule].

Thyroid cancer is comparatively rare. Thyroid nodules, on the other hand, are frequently diagnosed as a result of increasing use of diagnostic imaging. Cytological investigation of small nodules that have been found by chance often reveals micropapillary carcinoma that is probably not clinically relevant.

Vascular pattern analysis for the prediction of clinical behaviour in pheochromocytomas and paragangliomas.

Pheochromocytomas (PCCs) are neuroendocrine tumors arising from chromaffin cells of the adrenal medulla. Related tumors that arise from the paraganglia outside the adrenal medulla are called paragangliomas (PGLs). PCC/PGLs are usually benign, but approximately 17% of these tumors are malignant, as defined by the development of metastases.

Parathyroid hormone-related peptide (PTHrP) secretion by gastroenteropancreatic neuroendocrine tumors (GEP-NETs): clinical features, diagnosis, management, and follow-up.

Context: Only a small number of case reports has been published on patients with PTHrP-hypersecreting metastatic gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).

Objective: The objective of this study was to evaluate the clinical, biochemical, and radiological features, management, and treatment outcome of patients with PTHrP-hypersecreting GEP-NETs.

Design: Retrospective case series.

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular analysis.

Objective: Although the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated.

ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11β-hydroxylase.

Background: Adrenal Cushing's syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro.

Methods: In vivo cortisol responses to hormonal stimuli were studied in 35 patients with ACTH-independent bilateral adrenal enlargement and (sub-)clinical hypercortisolism.

Genetics of hereditary head and neck paragangliomas.

Background: The purpose of this study was to give an overview on hereditary syndromes associated with head and neck paragangliomas (HNPGs).

Methods: Our methods were the review and discussion of the pertinent literature.

Results: About one third of all patients with HNPGs are carriers of germline mutations.

Protein kinase C-induced activin A switches adrenocortical steroidogenesis to aldosterone by suppressing CYP17A1 expression.

Functional zonation of the adrenal cortex is a consequence of the zone-specific expression of P450c17 (CYP17A1) and its cofactors. Activin and inhibin peptides are differentially produced within the zones of the adrenal cortex and have been implicated in steroidogenic control. In this study, we investigated whether activin and inhibin can function as intermediates in functional zonation of the human adrenal cortex.

SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors.

Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in KIT or platelet-derived growth factor receptor-α. However, a small subset of GISTs lacks such mutations and is termed 'wild-type GISTs'. Germline mutation in any of the subunits of succinate dehydrogenase (SDH) predisposes individuals to hereditary paragangliomas and pheochromocytomas.

Regulation of steroidogenesis in a primary pigmented nodular adrenocortical disease-associated adenoma leading to virilization and subclinical Cushing's syndrome.

Context: Primary pigmented nodular adrenocortical disease (PPNAD) can lead to steroid hormone overproduction. Mutations in the cAMP protein kinase A regulatory subunit type 1A (PRKAR1A) are causative of PPNAD. Steroidogenesis in PPNAD can be modified through a local glucocorticoid feed-forward loop.

[A man with thyroid abnormalities: ectopic parathyroid adenoma and multifocal thyroid carcinoma].

Background: Thyroid abnormalities are found in 70% of patients with primary hyperparathyroidism. The simultaneous occurrence of a parathyroid adenoma and non-medullary thyroid carcinoma is rare.

Case Description: A parathyroid adenoma was suspected in a 39-year-old man with hypertension and a previous history of nephrolithiasis on the basis of laboratory results and scintigraphic investigations of the thyroid gland.

Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing.

T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T-lymphocyte proliferation. However, quantitative insight into thymocyte and T-lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR excision circle (TREC) assay, the Vγ-Jγ TREC assay, which we used together with an adjusted δREC-ψJα TREC assay to quantify the proliferative history of human thymocyte and T-lymphocyte subpopulations from children and adults.