Oral Presentation 5th International Symposium on Phaeochromocytoma and Paraganglioma 2017

Case: Metastatic paraganglioma with SDH C mutation (#45)

Luke Conway 1 2 , Kathryn Berkman 1 , Emily Mackenzie 1 , Liza Hayes 1
  1. Princess Alexandra Hospital, Brisbane, QLD, Australia
  2. Mater Hospital, Brisbane, QLD, Australia

SDHC mutations have now been described in a number of patients. These mutations are often associated with head and neck paragangliomas and are not usually malignant. We present an unusual case of a woman with an SDHC associated cervical paraganglioma with subsequent metastatic disease.

A 69 year female presented with a right neck mass.  Core biopsy in 2014 confirmed a paraganglioma.  Resection of the 31x31mm tumor occurred in 2016. Pre-operative 3-methoxytyramine, normetadrenaline and metadrenaline were within normal limits. Although the histology demonstrated clear margins and no evidence of malignancy in the resected lymph node, other suspicious features were present.  Atypical features including large cell nests, necrosis, high ki67, increased mitosis, high cellularity and vascular invasion were identified (Figure 1).  Immunohistochemistry suggested probable SDHx mutation. Next generation sequencing demonstrated a heterozygous pathogenic variant of the SDHC gene involving c.215G>A.

 

Figure 1: Paraganglioma histology
591d7da864246-SDHC+para+histo.png

She presented with a left humerus pathological fracture 30 months after the initial diagnosis.  Further imaging demonstrated extensive bone lesions that were confirmed on histology as paraganglioma metastasis.  She had a further pathological fracture and developed multi-organ dysfunction and died within weeks of presentation.

 

Figure 2: Neck Paraganglioma (top); Paraganglioma metastasis (bottom)
591d7da864246-imaging+combined+SDHC+mets.png

Genetic predisposition to pheochromocytoma and paraganglioma is identified in approximately 35% of cases1. Whilst SDHB gene mutations are more commonly associated with malignant paraganglioma, it is rare for individuals with SDHC gene mutations to have metastatic paragangliomas2-3. Seven percent of head and neck paragangliomas are malignant4.  Head and neck paraganglioma are functioning in 27% of malignant tumors, however this is a higher proportion when compared to the 5% of benign non-functioning paraganglioma4.   Complete surgical excision is the gold standard in treatment of paraganglioma. 

This case highlights the importance of active surveillance even in patients with SDHC mutations, especially in patients with atypical histology.    

  1. Martucci VL, Pacak K. 2014. Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, Management, and Treatment. Current Problems in Cancer. 38(1): 7–41
  2. Lefebvre M, Foulkes W. 2014. Pheochromocytoma and paraganglioma syndromes: genetics and management update. Current Oncology. 21:8-17
  3. Benn D, Robinson B, Roderick CB. 2015 Clinical manifestations of PGL1–5. Endocrine-related cancer 22:4 T91-T103
  4. Mediouni A, Ammari S, Wassef M, Gimenez-Roqueplo A, Laredo J, Duet M, Tran Ba Huy P, Oker N. 2013Malignant head/neck paragangliomas. Comparative Study European Annals of Otorhinolaryngology, Head and Neck Diseases. 131: 159-166