Disentangling of Malignancy from Benign Pheochromocytomas/Paragangliomas.

Seong Yeon Kim,Chan Soo Shin,Kyong Young Kim,Sang Wan Kim,Jung Hee Kim,Kyu Eun Lee,Su-Jin Kim,A. Ram Hong,Moon-Woo Seong

doi:10.1371/journal.pone.0168413

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.

Highlights

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare tumors of the chromaffin tissue that occur in the adrenal medulla or the extra-adrenal glands
Nineteen patients with recurrent PHEOs and PGLs (PPGLs) consisted of ones with malignant PPGLs (n = 17) and multifocal PPGLs (n = 2) who had VHL and RET mutations
We aimed to identify the clinical, histopathological, and genetic factors that predict benign vs. malignant PPGLs; this would be helpful for predicting whether PPGLs that are initially diagnosed as benign will subsequently become malignant

Summary

Introduction

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare tumors of the chromaffin tissue that occur in the adrenal medulla or the extra-adrenal glands. PHEOs and PGLs (PPGLs) are not necessarily malignant; if metastasis is detected at non-chromaffin sites such as the lymph node or bone, the tumor is reclassified as malignant. PPGLs may recur months or years after the initial surgery, and many investigators have suggested predictive factors for recurrent or malignant tumors. There are some reports that younger patients have a higher risk for malignancy [3]. Tumor size has been suggested as a significant risk factor for metastasis, and patients with PGLs rather than PHEOs reportedly tend to have lower survival rates [4]. The known predictive factors for malignancy are not reliable; it is recommended that all patients receive lifelong follow-up after the initial surgery [14]

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Conclusion