Published online Oct 28, 2020. doi: 10.13105/wjma.v8.i5.375
Peer-review started: October 7, 2020
First decision: October 22, 2020
Revised: October 26, 2020
Accepted: October 27, 2020
Article in press: October 27, 2020
Published online: October 28, 2020
Processing time: 20 Days and 20.1 Hours
Pheochromocytomas are tumors arising from the chromaffin cell of the adrenal gland and paragangliomas as tumors from extra-adrenal sympathetic chromaffin cells. The combined yearly incidence of pheochromocytoma and paraganglioma (PPGL) is approximately 0.8 per 100000 person/year. Malignant pheochro-mocytoma is defined only by the presence of metastasis, as there is no confirmatory histology or biomarkers. The most common metastatic sites of these chromaffin tumors are the lymph node, bone, lungs, and liver. This review focuses on relevant clinical and immunohistological factors that are predictive of malignant PPGL or metastasis and determinants of prognosis. Findings showed that the risk of malignant PPGL, along with disease survival, is closely associated with age, primary tumor size, gender, synchronous metastasis, and absence of surgical excision. Other essential biomarkers or immunohistology investigated were galectin-3, COX-2, nm-23, microRNA-210, ERBB-2 overexpression and succinate dehydrogenase subunit mutation, which were predictive of malignancy as well as disease prognosis. Curative resection is possible but most metastatic diseases are amenable to radiopharmaceuticals and chemotherapy due to late presentation. Other therapeutic options, like molecular-targeted therapy, are still undergoing clinical trials.
Core Tip: The diagnosis of malignant pheochromocytoma/paraganglioma (PPGL) is challenging. To date, confirmatory histology and biomarkers are still lacking. Data from recent studies have shown various biomarkers and genetic mutations that are predictive of malignancy, metastasis and disease prognosis of PPGL, but primary tumor size, male sex and synchronous metastasis have revealed consistent association with malignant PPGL and its prognostication.