A case of 123I-MIBG scintigram-negative functioning pheochromocytoma: immunohistochemical and molecular analysis with review of literature

International Journal of Clinical and Experimental Pathology

Aiko Kurisaki-Arakawa¹ 

关键词: Pheochromocytoma;    MIBG;    monoamine transporter;    VMAT1;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

A 70-year-old Japanese woman was referred to our hospital due to hyperhidrosis and rapid weight loss of 10 kg in a month. A lump measuring 26 mm in diameter was detected in the left adrenal gland by computed tomography. Biochemical tests showed high levels of serum and urinary norepinephrine and epinephrine. However, a 123I-MIBG scintigram failed to detect any accumulation in the left adrenal tumor. A left adrenalectomy was performed post clinical diagnosis of 123I-MIBG negative pheochromocytoma. Microscopically, the tumor exhibited pheochromocytoma compatible features. Immunohistochemical analysis revealed low expression of VMAT1 in the tumor compared to the normal, surrounding tissue. To test for a possible genetic alteration of the monoamine transporter genes, we performed whole-exome sequencing of the VMAT1, VMAT2, and NET genes in the tumor. No significant base sequence substitution or deletion/insertion was found in any transporter. This suggests that MIBG negativity is caused by a change that is independent of the base sequence abnormalities, such as an epigenetic change. Furthermore, a retrospective literature review of 123I-MIBG negative-scintigraphy cases indicates that a negative finding in the 123I-MIBG scintigram is frequently associated with metastatic pheochromocytomas or SDHB mutations. However, a SDHB/D gene mutation has not been identified in the reported case. Although the patient needs careful monitoring following the surgery, to date she has been disease free for 12 months. This study could not find clear reasons for negative conversion, however, investigations of the negative conversion mechanism might reveal significant insights towards the improvement of patient survival.

【 授权许可】

CC BY-NC