The immune cell infiltrate in the tumour microenvironment of phaeochromocytomas and paragangliomas.

Emerging evidence suggests the composition of the tumour microenvironment (TME) correlates with clinical outcome and that each tumour type has a unique TME including a variable population of inflammatory cells. We performed immunohistochemistry on 65 phaeochromocytoma and paraganglioma (PPGL) tumour samples with 20 normal adrenal medulla samples for comparison. The immune cells assessed were macrophages, lymphocytes and neutrophils, and we compared the proportion of infiltration of these immune cells with clinical and histopathological factors. There was a higher proportion of immune cells in tumour tissue compared to non-neoplastic adrenal medulla tissue, with a predominance of macrophages. There was a higher proportion of M2:M1 macrophages and T-helper lymphocytes in aggressive tumours compared to indolent ones. For SDHB-associated tumours, there was a higher proportion of M2 macrophage infiltration, with higher M2:M1 in aggressive SDHB PPGLs compared to indolent tumours. These data demonstrate that immune cells do infiltrate the TME of PPGLs, confirming that PPGLs are immunologically active tumours. Differences in the TME of PPGLs were observed between aggressive and indolent tumours. These differences could potentially be exploited as an aid in predicting tumour behaviour.

Pregnancy and phaeochromocytoma/paraganglioma: clinical clues affecting diagnosis and outcome - a systematic review.

BACKGROUND: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child. OBJECTIVE: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL. SEARCH STRATEGY: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French. SELECTION CRITERIA: Case reports containing a predefined minimum of clinical data on PPGL and pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis. MAIN RESULTS: Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P < 0.0001), initial diagnosis of pre-eclampsia (OR 6.34, 95% CI 2.60-15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70-42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26-5.85, P = 0.011) were independent factors of postpartum diagnosis. CONCLUSION: Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome. TWEETABLE ABSTRACT: Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis.

Four generations of SDHB-related disease: complexities in management.

SDHB mutations are linked to the familial paraganglioma syndrome type 4 (PGL4), which is associated with predominantly extra-adrenal disease and has high metastatic rates. Despite the lower penetrance rates in carriers of SDHB mutations compared to mutations in other paraganglioma susceptibility genes, the aggressive behavior of SDHB-linked disease warrants intensive surveillance to identify and resect tumors early. Patients with similar SDHB genotypes in whom the PGL syndrome manifests often exhibit very heterogeneous phenotypes. Tumors can arise in various locations, and management can be considerably different, depending on tumor site and pathology. We present a case series of five SDHB mutation carriers over four generations from the same family to illustrate the complexities in management.

New-onset diabetes after renal transplantation.

Renal transplantation has important benefits in people with end-stage renal disease, with improvements in mortality, morbidity and quality of life. Whilst significant advances in transplantation techniques and immunosuppressive regimens have led to improvements in short-term outcomes, longer-term outcomes have not improved dramatically. New-onset diabetes after transplantation appears to be a major factor in morbidity and cardiovascular mortality in renal transplant recipients. The diagnosis of new-onset diabetes after renal transplantation has been hampered by a lack of clarity over diagnostic tests in early studies, although the use of the WHO criteria is now generally accepted. HbA1c may be useful diagnostically, but should probably be avoided in the first 3 months after transplantation. The pathogenesis of new-onset diabetes after renal transplantation is likely to be related to standard pathogenic factors in Type 2 diabetes (e.g. insulin resistance, ß-cell failure, inflammation and genetic factors) as well as other factors, such as hepatitis C infection, and could be exacerbated by the use of immunosuppression (glucocorticoids and calcineurin inhibitors). Pre-transplant risk scores may help identify those people at risk of new-onset diabetes after renal transplantation. There are no randomized trials of treatment of new-onset diabetes after renal transplantation to determine whether intensive glucose control has an impact on cardiovascular or renal morbidity, therefore, treatment is guided by guidelines used in non-transplant diabetes. Many areas of uncertainty in the pathogenesis, diagnosis and management of new-onset diabetes after renal transplantation require further research.

'Stockholm syndrome': psychiatric diagnosis or urban myth?

OBJECTIVE: 'Stockholm syndrome' is a term used to describe the positive bond some kidnap victims develop with their captor. High-profile cases are reported by the media although the diagnosis is not described in any international classification system. Here we review the evidence base on 'Stockholm syndrome'. METHOD: Databases (PubMED, EMBASE, PsycINFO, CINAHL) were systematically searched. We compared features of cases widely reported in the English language media to identify common themes which may form a recognizable syndrome. RESULTS: We identified 12 papers that met inclusion criteria. The existing literature consists mostly of case reports; furthermore there is ambiguity in the use of the term. No validated diagnostic criteria have been described. Four common features were found between the five cases studied. CONCLUSION: There is little published academic research on 'Stockholm syndrome' although study of media reports reveals similarities between well publicized cases. This may be due to reporting and publication bias.