Disentangling of Malignancy from Benign Pheochromocytomas/Paragangliomas

Abstract

ObjectiveMany malignant tumors initially appear benign but subsequently exhibit extensive metastases. Early identification of malignant pheochromocytomas and paragangliomas (PPGLs) before metastasis is important for improved prognosis. However, there are no robust prognostic indices of recurrence and malignancy. The aim of this study was to identify the clinical and histopathological factors that predict malignant PPGLs.DesignRetrospective follow-up study.MethodsIn this study, we included 223 patients with pathologically confirmed PPGLs who were treated between 2000 and 2015 at the Seoul National University Hospital in South Korea.ResultsOf these patients, 29 were diagnosed with malignancy, 12 of whom presented with metastatic lesions at the initial diagnosis while 17 developed metastases during follow-up. Nineteen patients with recurrent PPGLs consisted of ones with malignant PPGLs (n = 17) and multifocal PPGLs (n = 2) who had VHL and RET mutations. The mean age at presentation for malignant PPGLs was significantly younger than that for benign PPGLs (43.0 vs. 49.0 years, respectively; p = 0.023). Tumor size was not a distinguishing factor between malignant and benign PPGLs (5.0 vs. 4.5 cm, respectively; p = 0.316) nor did it predict recurrence. Of 119 patients with available pheochromocytoma of adrenal gland scaled score (PASS) data, those with malignant PPGLs presented PASS values ≥4. Of 12 parameters of PASS, necrosis, capsular invasion, vascular invasion, cellular monotony, high mitosis, atypical mitotic figures, and nuclear hyperchromasia were significant predictors of malignancy.ConclusionsTumor size did not predict malignancy or recurrence of PPGLs. PPGL patients with characteristic pathologic findings and PASS ≥4 or germline mutations require close follow-up.

Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours

“…could be seen [65,73]. Approximately 5 to 10% of phaeochromocytoma metastasize [74] Paraganglioma Paragangliomas are extra-adrenal non-epithelial tumours originating from neural crest-derived paraganglion cells situated in the region of autonomic nervous system ganglia and accompanying nerves. The histology is similar to pheochromocytoma.…”

“…The histology is similar to pheochromocytoma. As a group, they had higher frequency of metastases when compared to pheochromocytoma [74] Instead of having four sections of paragangliomas from different sites in the 2004 version, the current WHO classification of endocrine tumours presents the information in one section for paraganglioma. Paraganglioma is divided into two groups; one from the parasympathetic system and one from the sympathetic system based on the clinical and biological behaviour.…”

What determines mortality in malignant pheochromocytoma? – Report of a case with eighteen-year survival and review of the literature

“…There is no available method to accurately predict the malignant potential of these tumors when they present without metastases. Tumors larger than 5 cm, location of the primary lesion, local invasion, tumor necrosis, high cellularity, nuclear pleomorphism and hyperchromasia are some characteristics that may suggest malignancy, but distant metastases remain the only widely accepted malignancy criterion (3,5). The pattern of cathecolamine secretion is also not useful to differentiate benign from malignant pheochromocytomas, despite previous reports claiming that dopamine levels may be higher in malignant cases (6).…”

Surgery for pheochromocytoma: A 20-year experience of a single institution

“…It should be highlighted that tumor size has not been conclusively proven to be a reliable predictor of recurrence or malignant potential, with different studies yielding opposing conclusions. 10,40 In our study the largest PHEO excised laparoscopically was 11.0 cm in diameter. We had 4 conversions to an open procedure because of periadrenal tumor invasion.…”