A Recurrent with RET and SDHC Mutations Natasha Malkani MD, Umar Ahmad DO, Mary Beth Hodge MD Lahey Hospital and Medical Center, Tufts University School of Medicine

Introduction Discussion are rare neuroendocrine tumors arising from sympathetic or Our literature review did not yield any cases of simultaneous RET and parasympathetic extra-adrenal paraganglia.1 These tumors are closely related SDHC mutations in patients diagnosed with a paraganglioma. The SDHC to and are derived from neural crest cells. A para- mutation is in itself rare – found to occur in 4% of patients with ganglioma that arises from a sympathetic chain can secrete catecholamines, parasympathetic paragangliomas. The SDHC mutation rarely leads to while those arising from a parasympathetic chain tend to be nonfunctional.1 hereditary paraganglioma syndromes compared to the SDHB and SDHD The majority of paragangliomas diagnosed are sporadic, however, 1/3 were gene mutations.2 The SDHC is one of four subunits that associated with an inherited syndrome.2 In particular, hereditary constitute , which functions as complex II of paragangliomas in the head and neck region are associated with SDH the mitochondrial .3 complex mutations.2 These tumors have also occurred with NF1 and VHL tumor The RET gene variant is a proto- which encodes a syndromes. Paragangliomas are rarely seen in the MEN2 syndrome secondary transmembrane tyrosine kinase expressed in neural crest to a RET gene mutation.3 We present a rare occurrence of recurrent precursor cells. A gain-of-function mutation in this gene leads to the paraganglioma with simultaneous RET and SDHC mutations. autosomal dominant tumor syndromes known as MEN2A and MEN2B.3 Bilateral adrenal pheochromocytomas are common in these syndromes, 3 Figure 1: MRI findings of a but paragangliomas are rarely seen. Case Presentation jugulotympanic paraganglioma Of note, the patient did not have any symptoms or signs concerning for catecholamine excess. This is not unusual for paragangliomas especially A 50-year-old female presents with right ear pain and tinnitus for multiple weeks. in the head and neck region, as the tumor arises from parasympathetic She was treated with several antibiotic courses for presumed otitis media. paraganglia. A recent case series found that 31% of patients with However, her symptoms persisted and she was referred to an ENT specialist who paragangliomas had catecholamine hypersecretion.5 obtained a CT scan of her sinuses and temporal bone. This revealed a large glomus tumor of the middle ear with extension into the hypotympanic air cells Conclusion and jugular bulb. She underwent a transcanal excision of the tumor and a tympanoplasty. Pathology confirmed a jugulotympanic paraganglioma. She was Our case demonstrates the unusual presentation of simultaneous RET symptom-free until she presented with pre-auricular swelling and tinnitus a few and SDHC mutations in an individual with a recurrent paraganglioma. It months later. She underwent a head MRI that revealed a 2.3 cm lobulated highlights the importance of genetic testing and screening for tumor enhancing tissue within the right jugular foramen, concerning for residual tumor syndromes in patients diagnosed with a paraganglioma. (Figure 1). She underwent excision and pathology was positive for synaptophysin tumor cells consistent with recurrence. References The patient’s history was negative for any history of hypertension, headaches, 1. Costa S, Carvalho T, Violante A, Vaisman M. Pheochromocytomas and Paragangliomas: Clinical and Genetic excessive sweating or palpitations. She had normal metanephrine levels and an I- Approaches. Frontiers in Endocrinology. 2015;6:126. 2. Fishbein L, Merrill S, Fraker DL, et al. Inherited mutations in and paraganglioma. Annals of 123 MIBG scan had no scintigraphic evidence of a pheochromocytoma. Genetic Figure 2: Depiction of a glomus Surgical Oncology. 2013;20(5):1444-9. testing revealed a RET gene and a SDHC gene mutation. In addition, the patient’s jugulare tumor 3. Welander J, Soderkvist P, Gimm O. Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer 2011;18:R253-76. family history is relevant for a daughter with MEN2 syndrome secondary to a RET 4. Schiavi F, Boedeker C, Bausch B, et al. Predictors and Prevalence of Paraganglioma Syndrome Associated With Mutations of the SDHC Gene. JAMA. 2005;294(16):2057-2063. gene mutation. 5. Erickson D, Kudva Y, Ebersold M, et al. Benign Paragangliomas: Clinical Presentation and Treatment Outcomes in 236 Patients, The Journal of Clinical Endocrinology & . 2001; 86(11):5210-6.