Metastatic Malignant Pheochromocytoma Driven by DNMT3A Somatic Mutation
https://doi.org/10.15605/jafes.041.S1
- Author:
Vijayrama Rao Sambamoorthy
1
;
Zanariah Hussein
1
;
Anthony Louis Kindu
2
Author Information
1. Endocrine Unit, Medical Department, Hospital Putrajaya
2. Nuclear Medicine Department, Institut Kanser Negara
- Publication Type:Journal Article
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):26-27
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:Pheochromocytomas and paragangliomas (PPGL) are
rare neuroendocrine tumors with high heritability. While
most are benign, approximately 25% are malignant,
defined by distant metastases. Molecular classification has
identified three clusters, with Cluster 3 (Wnt-signaling)
being exclusively somatic and associated with aggressive
behavior. We report a rare case of metastatic malignant
pheochromocytoma driven by a somatic DNMT3A
mutation, highlighting its unique imaging characteristics
and rapid clinical progression.
Case:A 55-year-old female presented with paroxysmal hypertension, headache, and a 10-kg weight loss. Biochemical
workup revealed markedly elevated 24-hour urine
metanephrines (163 × ULN) and normetanephrines (47 ×
ULN). Imaging confirmed a 15-cm left adrenal mass with
liver and widespread skeletal metastases. Functional
imaging demonstrated a striking mixed avidity: liver
metastases were predominantly fluorodeoxyglucoseavid (SUVmax 7.0), skeletal lesions showed high Ga-68
DOTATATE avidity (SUVmax 6.9), and the primary tumor
exhibited the strongest avidity on 131 I-MIBG scan. Whole
Exome Sequencing identified a rare pathogenic somatic
variant in the DNMT3A gene (c.2645G>A) with no other
germline or somatic mutations in known susceptibility
genes. Despite adequate alpha-blockade and supportive
care, the patient developed acute liver failure and
coagulopathy, rendering her unfit for any form of invasive
intervention and finally succumbing to the disease within
3 months of presentation.
Conclusion:This case underscores the aggressive nature of Cluster
3 PPGLs associated with DNMT3A mutations, which
likely promote tumorigenesis via Wnt-pathway activation
and epigenetic dysregulation. The discordant functional
imaging reflects significant tumor heterogeneity, which
may complicate diagnostic and therapeutic strategies. Given the rarity of DNMT3A-mutated PPGL (<1% of cases),
this case report emphasizes the necessity of comprehensive
molecular profiling in advanced disease to refine risk
stratification and guide the development of precisionbased palliative management in rapidly progressive cases.
- Full text:2026072813501259113EP_A015.pdf
