Recent advances in molecular genetics and genomics have led to increased understanding of the aetiopathogenesis of pheochromocytomas and paragangliomas (PPGLs). Thus, pangenomic studies now provide a comprehensive integrated genomic analysis of PPGLs into distinct molecularly defined subtypes concordant with tumour genotypes. In addition, new embryological discoveries have refined the concept of how normal paraganglia develop, potentially establishing a developmental basis for genotype-phenotype correlations for PPGLs.The challenge for modern pathology is to translate these scientific discoveries into routine practice, which will be based largely on histopathology for the foreseeable future. Here, we review recent progress concerning the cell of origin and molecular pathogenesis of PPGLs, including pathogenetic mechanisms, genetic susceptibility and molecular classification. The current roles and tools of pathologists are considered from a histopathological perspective, including differential diagnoses, genotype-phenotype correlations and the use of immunohistochemistry in identifying hereditary predisposition and validating genetic variants of unknown significance. Current and potential molecular prognosticators are also presented with the hope that predictive molecular biomarkers will be integrated into risk stratification scoring systems to assess the metastatic potential of these intriguing neoplasms and identify potential drug targets.

Background Various diagnostic tests are available to establish the primary aldosteronism (PA) diagnosis and to determine the disease laterality. Combined with the controversies in the literature, unawareness of guidelines and technical demands and high costs of some of these diagnostics, this could lead to significant differences in work-up strategies worldwide. Therefore, we investigated the work-up before surgery for PA in daily clinical practice within a multicenter study. Methods Patients who underwent unilateral adrenalectomy for PA within 16 centers in Europe, Canada, Australia and the USA between 2010 and 2016 were included. We did not exclude patients based on the performed diagnostic tests during work-up to make our data representative for current clinical practice. Adherence to the Endocrine Society Guideline and variables associated with not performing adrenal venous sampling (AVS) were analyzed. Results In total, 435 patients were eligible. An aldosterone-to-renin ratio, confirmatory test, computed tomography (CT), magnetic resonance imaging and AVS were performed in 82.9%, 32.9%, 86.9%, 17.0% and 65.3% of patients, respectively. A complete work-up, as recommended by the guideline, was performed in 13.1% of patients. Bilateral disease or normal adrenal anatomy on CT (OR 16.19; CI 3.50-74.99), smaller tumor size on CT (OR 0.06; CI 0.04-0.08) and presence of hypokalemia (OR 2.00; CI 1.19-3.32) were independently associated with performing AVS. Conclusions This study is the first to examine the daily clinical practice work-up of PA within a worldwide cohort of surgical patients. The results demonstrate significant variability in work-up strategies and low adherence to The Endocrine Society guideline.

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Background Cure of hypertension after adrenalectomy for primary aldosteronism is no certainty and therefore preoperative patient counseling is essential. The Primary Aldosteronism Surgical Outcome (PASO) Score is a useful prediction model with an area under the curve (AUC) of 0.839. The PASO Score includes ‘Target Organ Damage’ (TOD) (i.e., left ventricular hypertrophy and/or microalbuminuria), which is often unavailable during preoperative counseling and might therefore limit its use in clinical practice. We hypothesized that the PASO score would still be useful if TOD is unknown at time of counseling. Therefore, we aimed to examine the predictive performance of the simplified PASO Score, without taking TOD into account. Materials and methods In this retrospective cohort study, patients who underwent unilateral adrenalectomy between 2010 and 2016 in 16 medical centers from North America, Europe and Australia were included. TOD was unknown in our database and therefore assigned as absent. Patients were classified as complete, partial or absent clinical success using the PASO consensus criteria. Results A total of 380 (73.9%) patients were eligible for analysis. Complete, partial and absent clinical success were observed in 29.5%, 55.8% and 14.7% of patients, respectively. The simplified PASO Score had an AUC of 0.730 (95% confidence interval 0.674–0.785) in our total cohort. Conclusion Without taking TOD into account, the simplified PASO Score had a lower predictive value as compared to the original derivation cohort. Ideally, the complete PASO Score should be used, but when data on TOD are not readily available, the simplified PASO Score is a useful and reasonable alternative.

Objective: We aimed to investigate the postoperative trend in blood pressure (BP)-related outcomes [BP and antihypertensive (AHT) drug use] during the year following adrenalectomy for primary aldosteronism (PA) to determine the optimal timing for outcome assessment and to determine the necessary follow-up length. Background: Since the course of BP-related outcomes after adrenalectomy is unknown, the optimal timing of outcome assessment and follow-up duration are not clear. Methods: In this retrospective single center cohort study, we used a prospectively collected database with all patients referred for difficult-to-control-hypertension-analysis. All patients diagnosed with PA who underwent adrenalectomy were included. AHT drug use [in defined daily dose (DDD)] and home blood pressure measurements (HBPMs) during the first postoperative year were collected. A mixed-effects model was developed to assess the stability of DDD and HBPM over time and adjust for potential confounders. Results: In total 1784 patients were assessed for difficult-to-control-hypertension of whom 41 were included. Both the DDD and HBPM showed the strongest decrease in the first postoperative month (mean 1.6DDD; mean 140/85 mm Hg) compared with preoperative values (4.5DDD; 153/92 mm Hg). Thereafter, both outcomes showed a stable course from 4 to 6 months (1.6DDD; 136/86 mm Hg) up to 12 months postoperatively (2.0DDD; 136/83 mm Hg). Conclusions: This study showed that AHT drug use and HBPM decreased substantially within the first month after adrenalectomy for PA and afterwards generally remained stable during the year following adrenalectomy. We propose that BP-related outcomes can be assessed reliably early after adrenalectomy and question the need for routine long-term follow-up in referral centers.

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