Department of Pathology

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Browsing Department of Pathology by Subject "Adrenal glands -- Tumors"

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    Prevalence of succinate dehydrogenase deficiency in paragangliomas and pheochromocytomas at Tygerberg Hospital: a retrospective review.
    (Stellenbosch : Stellenbosch University, 2020-12) Bruce-Brand, Cassandra; Van Wyk, A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Anatomical Pathology.
    IntroductionPheochromocytomas (PC) and paragangliomas (PGL) are rare neural crest-derived tumours that occur at adrenal and extra-adrenal sites. These tumours may be sporadic but a significant proportion are caused by familial syndromes due to germline mutations. Mutations of the succinate dehydrogenase (SDH) complex make up the bulk of syndromic cases in the international literature. SDH mutated cases are now known to have higher rates of metastatic disease, a younger age of onset, an association with other SDH mutated tumours as well as implicationsforfirst degree relatives. An immunohistochemical stain for SDHB that has excellent correlation with SDH mutation status has been developed and is routinely used in many centres to infer SDH mutation status. Loss of staining is seen when there is a mutation of any of the SDH subunit complexes. The prevalence of SDHmutated tumoursis not known in the South African setting. MethodsA retrospective laboratory-based study was conducted at Tygerberg Hospital in South Africa to assess the prevalence of SDH deficiency in all PC and PGLs between 2005 and 2015. These tumours were further stratified by other characteristics:tumour site, patient age, sex and presence of metastatic disease. Fifty-two cases met the inclusion criteria and the SDHB immunohistochemical stain was performed on these cases. Germline testing or sequencing of these cases was not performed. ResultsThirty-six percent of cases showed loss of staining of SDHB by immunohistochemistry. Head and neck PGLs made up the bulk of cases (50%) and females were strongly represented, particularly at head and neck sites (73%). Loss of staining was significantly correlated with a younger age at presentation(z= -3.59, p< .001).There was no correlation betweenloss of staining and tumour site or patient sex. The inter-observer agreement in interpretation of the immunohistochemical stain was excellent (Cohen’s kappa= 0.917, p< .001). Conclusion The prevalence of SDH deficiency in our setting, as shown by loss of immunohistochemical staining for SDHB, is comparable to the literature and makes up a significant proportion of our PC/PGL cases. This highlights the need for performance of this stain in our setting in order to recognise these syndromic cases. Many patients in South Africa do not have access to genetic testing upon diagnosis of a PC or PGL as this is costly and not widely available. Many studies have shown excellent correlation of the immunohistochemical stain with underlying SDH mutation status. Immunohistochemistry is widely available in South African pathology laboratories and is relatively affordable. Although interpretation of this stain can be challenging, we report excellent inter-observer agreement in a generalist pathology practice when following published guidelines for interpretation. We therefore advocate for routine use of this stain in all PC/PGL cases diagnosed in our setting.