Malignant Pheochromocytoma and Paraganglioma: 272 Patients over 55 Years

Presentation Number: SUN 380
Date of Presentation: April 2nd, 2017

Oksana Hamidi*1, William F Young Jr.1, Nicole M Iniguez Ariza1, Nana Esi Nkuma Kittah1, Lucinda M Gruber2, Cristian Bancos1, Shrikant Tamhane1 and Irina Bancos1
1Mayo Clinic, Rochester, MN, 2Mayo Clinic School of Graduate Medical Education, Rochester, MN

Abstract

BACKGROUND

Malignant pheochromocytoma (PHEO) and paraganglioma (PGL) are rare and knowledge of the natural history is limited.

OBJECTIVES

Our aim was to describe the clinical course of patients with malignant PHEO/PGL and to identify predictive features of shorter survival.

METHODS

This is a retrospective review of patients with metastatic PHEO/PGL at Mayo Clinic, Rochester, from 1960 to 2016. Descriptive patterns of primary tumors and metastases were evaluated. To assess prognostic factors for disease progression, patients with sufficient follow-up were divided into Group 1 (died of malignant disease within 5 yrs of diagnosis, n=52) and Group 2 (alive for at least 5 yrs after diagnosis, n=123).

RESULTS

Malignant PHEO/PGL was diagnosed in 272 patients (51% women) at the median age of 44 yrs (range, 7 – 84). Patients presented with PHEO (100, 37%), PGL (156, 57%), or both (16, 6%). PHEOs were larger (median size of PHEO vs PGL was 9 cm [3 - 26] vs. 5.6 cm [0.9 – 19], P<.0001), more commonly functional (89 vs 62%, P<.001), but less frequently associated with a genetic mutation (15 vs 40%, P<.001). While 96 (35%) patients presented with synchronous metastases, 176 (65%) patients developed metastases at the median time of 5.5 yrs (0.3 - 53.4) following the initial tumor diagnosis.

Excluding deceased patients, median duration of follow-up from the primary tumor diagnosis was 9 yrs (0 - 54). At conclusion of the study, 154 (57%) patients were alive with disease and 18 (6%) patients had disease remission. One hundred (37%) patients died during follow-up (27, 10% unrelated to PHEO/PGL). In 73 (27%) patients who died of malignant PHEO/PGL, the median survival from the primary tumor diagnosis was 6 yrs (0 - 41) and 3 yrs (0 - 17) from metastatic diagnosis.

Compared to Group 2, patients in Group 1 (rapidly progressive) were diagnosed at an older age both with primary (46 vs 36 yrs, P=.003) and metastatic disease (54 vs 40 yrs, P=.002), were less likely to undergo surgery for the primary tumor (77 vs 96%, P=.0003), and more likely to have elevated dopamine (68 vs 37%, P=.004). There was no between-group difference in the year of diagnosis (1987 vs 1995), size of the primary tumor (8.0 vs 6.6 cm), proportion of synchronous metastases (42 vs 32%), or presence of SDHB mutation (11.5 vs 15.5%).

CONCLUSIONS

The clinical course of patients with malignant PHEO/PGL is remarkably variable. Detection of metastases can precede the primary disease, but it can also present 53 years after the discovery of primary tumor. Although death can occur within a year of diagnosis, the metastatic disease can be stable for 40 yrs. Our findings show that rapid disease progression is associated with: older age at the time of primary tumor discovery and at diagnosis of metastatic spread; absence of surgical resection of primary tumor; and excess dopamine secretion. An individualized approach to treatment of patients with metastatic PHEO/PGL is important.

 

Disclosure: WFY Jr.: Consultant, Nihon Medi-Physics. Nothing to Disclose: OH, NMI, NENK, LMG, CB, ST, IB