Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Li Fraumeni Syndrome and phaeochromocytoma (#196)

Amanda Seabrook 1
  1. Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia

We report the case of a 43 year old gentleman with a diagnosis of Li-Fraumeni syndrome, a germline mutation of the TP53 tumour suppressor gene, admitted for resection of a retroperitoneal leiomyosarcoma. Annual screening MRI revealed the malignancy, which was mildly FDG-avid on PET/CT. The proband identified breast cancer in his mother and brother, also carriers of the TP53 mutation, with no knowledge of other malignancies within his family.

An incidental right adrenal lesion was identified intra-operatively. Histopathology was consistent was a phaeochromocytoma measuring 20 x 15 x 9mm with positive immunostaining for chromogranin and SDHB. Of note this lesion was not identified on previous imaging. 

He denied a prodromal illness consistent with catecholamine excess, with a paucity of hyperadrenergic spells or hypertension. Peri- and intra-operative blood pressure remained normal despite no alpha or beta blockade. Day 3 post-operative plasma fractionated metanephrines were within normal range (metanephrines 0.12nmol/L, normetanephrines 0.42nmol/L).


Phaeochromocytoma are predominantly sporadic in nature with only 30% occurring as part of a familial syndrome. Common germline mutations have been grouped into a hypoxic pathway (i.e. SDHD, SDHB, VHL) and kinase pathway (i.e.MEN2, NF1)1.The mutation of the TP53 tumour suppressor gene is known to result in an autosomal dominant cluster of malignancies, including adrenocortical carcinoma2 . The implication of this genetic mutation in the development of phaeochromocytoma is unknown with no cases of concurrent Li Fraumeni and phaeochromocytoma reported in the literature.

Luchetti et al identified two sporadic phaeochromocytoma displaying somatic TP53 gene mutations via Sanger Sequencing in 20153. This finding has been supported by Krijer et al. who reported TP53 immuno-expression between 10-50% in malignant phaeochromocytoma4. Another study found TP53 abnormalities were more frequently observed in topographically heterogenous and malignant phaeochromocytoma and a collection of 202 resected phaeochromocytoma, TP53 was altered in 10% of cases5,6.

  1. Castro-Vega LJ, Buffet A, De Cubas AA, et al. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet 2014; 23:2440.
  2. Libe, R. Bertherat, J. Molecular genetics of adrenocortical tumours, from familial to sporadic disease. European Journal of Endocrinology. 2005. 153 477-487
  3. Luchettia, A et al. Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis. Int.Journal of Endocrinology. 2015.
  4. Kriger rijger RR, van der Harst E, van der Ham F, Stijnen T, Dinjen WNM, Koper JW, Bruining HA, Lamberts SWJ, Bosman FT 1999 Prognostic value of p53, bcl-2, and c-erbB-2 protein expression in phaeochromocytomas. J Pathol 188: 51–55
  5. Blanes, Alfredo. Topographic Molecular Profile of Phaeochromocytoma dn role of somatic down regulariton of Mismatch Repair
  6. Luis, J. Multi-omics analysis defines core genomic alterations in phaeocrhomocytomas and pargalgiomas. Nature Communications. January, 2015