False-negative ¹²³I-MIBG SPECT is most commonly found in SDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease

Jay S Fonte, Jeremyjones F Robles, Clara C Chen, James Reynolds, Millie Whatley, Alexander Ling, Leilani B Mercado-Asis, Karen T Adams, Victoria Martucci, Tito Fojo, Karel Pacak
Endocrine-related Cancer 2012, 19 (1): 83-93
The purpose of this study was to present the characteristics and outcome of patients with proven pheochromocytoma or paraganglioma who had false-negative iodine-123 metaiodobenzylguanidine single photon emission computed tomography ((123)I-MIBG SPECT). Twenty-one patients with false-negative (123)I-MIBG SPECT (7 males, 14 females), aged 13-55 years (mean: 41.40 years), were included. We classified them as nonmetastatic or metastatic according to the stage of the disease at the time of false-negative (123)I-MIBG SPECT study, the location and size of the tumor, plasma and urinary catecholamine and metanephrine levels, genetic mutations, and outcome in terms of occurrence and progression of metastases and death. Thirteen patients were evaluated for metastatic tumors, while the remaining eight were seen for nonmetastatic disease. All primary tumors and multiple metastatic foci did not show avid (123)I-MIBG uptake regardless of the tumor diameter. The majority of patients had extraadrenal tumors with hypersecretion of normetanephrine or norepinephrine. SDHB mutations were present in 52% (n=11) of cases, RET mutation in 4% (n=1), and the rest were apparently sporadic. Twenty-four percent (n=5) had metastatic disease on initial presentation. Fourteen patients were followed for 3-7 years. Of them, 71% (n=10) had metastatic disease and the majority had SDHB mutations. Nine are still alive, while five (four with SDHB) died due to metastatic disease. We concluded that false-negative (123)I-MIBG SPECT is frequently related to metastatic tumors and usually due to SDHB mutations with unfavorable prognosis. We therefore recommend that patients with false-negative (123)I-MIBG SPECT be tested for SDHB mutations and undergo more regular and close follow-up.

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