Tetralogy of Fallot and SDHB mutation together resulted in severe PGL with skin lesions, accelerated tumor growth, and ultimately contributed to the patient's death from arrhythmia.
This case highlights a rare hypoxia-related paraganglioma phenotype with cutaneous vascular manifestations in a patient with tetralogy of Fallot and an SDHB mutation.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Paragangliomas (PGLs) are rare neuroendocrine tumors. Atypical manifestations such as skin lesions mimicking vasculitis secondary to catecholamine-induced vasoconstriction are extremely rare. Both hypoxia observed in cyanotic congenital heart disease, like tetralogy of Fallot (TOF), and succinate dehydrogenase B (SDHB) germline mutations can activate hypoxia-inducible factor (HIF) pathways, leading to tumor proliferation. Clinical Case A 34-year-old female patient, with a history of TOF repair, hypothyroidism, hypertension, carotid body tumor surgery, and autoamputation of two toes in the right foot, presented with necrotic, ulcerative lesions on her extremities. The patient was treated with steroids and methotrexate for 3 months. Examination revealed blood pressure of 100/70 mmHg, a diastolic murmur in the pulmonary area, pretibial edema, right third toe gangrene, and multiple skin lesions (Figure 1). Rheumatologic tests for vasculitis were negative, and the skin biopsy was inconclusive. Abdominopelvic CT performed for vascular imaging and detected a retroperitoneal mass (80x46 mm) in the posterior of the pancreas. 18F-FDG PET/CT showed intense uptake. Significant increase in urinary normetanephrine (10-fold) and norepinephrine (18-fold) levels was detected. 68Ga Dotatate PET/CT revealed intense somatostatin receptor activity. Focal uptake was seen on the MIBG scan. The tumor was inoperable due to involvement of the superior mesenteric and celiac arteries. Genetic analysis identified a pathogenic heterozygous SDHB gene variant (c.262AC; p.Thr88Pro). Given the ineffectiveness of vasculitis treatment, it was discontinued. The gangrenous toe was amputated, and the patient was managed with hyperbaric oxygen therapy along with alpha blockade therapy. The treatment resulted in the healing of necrotic lesions. 177Lu-Dotatate therapy resulted in partial tumor regression and biochemical response, but it was discontinued due to pancytopenia. Therapy was resumed with thrombopoietin receptor agonist support but later discontinued due to recurrent cytopenia. 131I-MIBG therapy was administered. However, despite these interventions, the patient developed progressive cardio-renal complications and died due to sudden arrhythmia. Conclusion This case highlights the rare hypoxia-related PGL phenotype in a patient with TOF and SDHB mutation. Although SDHB mutations are sufficient to initiate PGL development via pseudohypoxia, the accompanying chronic systemic hypoxia due to TOF may have exerted a synergistic effect by further stabilizing HIF signaling, thereby accelerating tumorigenesis and contributing to the unusual clinical presentation. Cutaneous lesions mimicking vasculitis may be attributed to catecholamine-induced vasoconstriction and ischemia. Recognition of atypical findings may allow for early diagnosis and intervention. Multidisciplinary management is essential in inoperable cases with complex comorbidities.Figure 1:Necrotic cutaneous lesions of the patient’s lower extremity
Mutlu et al. (Thu,) reported a other. Tetralogy of Fallot and SDHB mutation together resulted in severe PGL with skin lesions, accelerated tumor growth, and ultimately contributed to the patient's death from arrhythmia.