Work

SUN-348 Late Onset Familial Medullary Thyroid Cancer Arising from a Germline RET Polymorphism: The Need for Germline Screening and an Individualized Approach

Year: 2024

Type: article

Abstract: J. Student: None. P. Guido: None. C. Vaz Wicks: None. Introduction: Medullary Thyroid Cancer (MTC) is frequently the result of sporadic, somatic mutations that give rise to isolated cases. Up to 25% of cases are the result of germline mutations that produce heritable endocrine syndromes. Familial Medullary Thyroid Carcinoma (FMTC) and Multiple Endocrine Neoplasia (MEN) describe a spectrum of neoplastic disease arising from germline mutations of the RET protooncogene, which typically exhibit autosomal dominant inheritance. Numerous polymorphisms of the RET protooncogene have been identified and characterized according to their transforming activity and risk profile of producing MTC or other sequelae of MEN. Here we describe a case of late onset FMTC with confirmed germline RET mutation presenting in the seventh decade of life. Case Presentation: An asymptomatic 60 year old man presented for evaluation after his brother, was diagnosed with FMTC at the age of 72 with the pathogenic RET germline variant p.Val804Leu. A blood sample was sent for genetic testing (CustomNext-Cancer®, Ambry Genetics) which revealed that he was heterozygous for the same p.Val804Leu polymorphism. Calcitonin was elevated at 16.6 pg/ml (n < 8.4 pg/ml) and work up for pheochromocytoma and hyperparathyroidism was negative. Neck ultrasound revealed normal sized thyroid with homogenous echotexture and no evidence of thyroid nodules, as well as a left supraclavicular lymph node with an enlarged fatty hilum. The patient underwent total thyroidectomy with central lymph node dissection. Pathology showed a 16.9 g thyroid with multifocal C-cell hyperplasia. There was no evidence of lymph node metastasis. The patient’s family was referred for genetic testing.Discussion/Conclusion: Sporadic MTC is typically diagnosed in patients during the 4th and 6th decades of life and is attributed to somatic mutations within tumor cells. It is not apparent what proportion of patients with clinically apparent sporadic MTC have an unsuspected germline mutation in the RET gene conferring heritable disease. This case highlights the importance of screening all patients with MTC for germline RET mutations so family members can be appropriately referred for testing. Furthermore, the risk profile of the specific RET variant should be considered. The p.Val804Leu variant has been characterized as “moderate risk,” and has been associated with a low transforming activity but there is inconsistent guidance regarding the timing of prophylactic thyroidectomy for those who have inherited these variants. While some recommend that even moderate risk variants should be treated with urgent prophylactic thyroidectomy, others have argued a conservative approach, of deferring surgery in favor of yearly biochemical and sonographic monitoring, may be suitable provided there is no familial history of aggressive MTC and it is consistent with the patient/family’s goals of care. Sunday, June 2, 2024

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvae163.2467

Authors: J Student, P Guido, C Vaz Wicks

Institution: Temple University Hospital

Language: English

Topic: Thyroid Cancer Diagnosis and Treatment

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,418