Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation
<b>Background</b>: Multiple endocrine neoplasia type 2A (MEN2A) is a rare, hereditary syndrome resulting from a germline mutation in the <i>RET</i> proto-oncogene and characterized primarily by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and hyperparathyroidism....
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MDPI AG
2021-08-01
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| Online Access: | https://www.mdpi.com/2075-4418/11/8/1448 |
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| author | Agnieszka Walczyk Kajetan Zgubieński Grzegorz Chmielewski Kinga Hińcza-Nowak Artur Kowalik Jarosław Jaskulski Aldona Kowalska |
| author_facet | Agnieszka Walczyk Kajetan Zgubieński Grzegorz Chmielewski Kinga Hińcza-Nowak Artur Kowalik Jarosław Jaskulski Aldona Kowalska |
| author_sort | Agnieszka Walczyk |
| collection | DOAJ |
| description | <b>Background</b>: Multiple endocrine neoplasia type 2A (MEN2A) is a rare, hereditary syndrome resulting from a germline mutation in the <i>RET</i> proto-oncogene and characterized primarily by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and hyperparathyroidism. Types of <i>RET</i> mutation have been associated with age at onset, clinical outcomes of MTC, and the penetrance of other components. Patients classified as ‘high-risk’ by the American Thyroid Association (ATA), based on the aggressiveness of MTC and the penetrance of other components, are recommended to undergo early prophylactic thyroidectomy at age ≤ 5 years and to be screened for PHEO at age ≥ 11 years. Patients with <i>RET</i> codon C634R mutations have been classified as high-risk. <b>Case presentation</b>: The present study describes a 71-year-old woman newly diagnosed with hereditary MTC related to a <i>RET</i> C634R germline mutation. Her basal serum calcitonin level was high, but there was no evidence of distant metastases. Surgery revealed bilateral MTC with two metastatic lymph nodes. Because microscopic resection was incomplete and extranodal extension was observed, the patient underwent adjuvant external beam radiotherapy. Response to therapy was excellent. Follow-up after 1.5 years showed no evidence of disease or other manifestations of MEN2A. <b>Conclusion</b>: Despite <i>RET</i> C634R carriers being classified as high-risk by the ATA, this patient did not present with either distant MTC or PHEO until her seventies. To our knowledge, only one other patient has shown a similar late identification of a <i>RET</i> C634R mutation, but MTC could not be diagnosed because the patient was lost to follow-up. Further research is required to develop optimal protocols that could allow patients requiring prophylactic thyroidectomy to be differentiated from those who can be monitored closely without early surgery. |
| first_indexed | 2024-03-10T08:54:04Z |
| format | Article |
| id | doaj.art-e2528710dae84f3c8fa520b05772df7b |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T08:54:04Z |
| publishDate | 2021-08-01 |
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| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-e2528710dae84f3c8fa520b05772df7b2023-11-22T07:20:39ZengMDPI AGDiagnostics2075-44182021-08-01118144810.3390/diagnostics11081448Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R MutationAgnieszka Walczyk0Kajetan Zgubieński1Grzegorz Chmielewski2Kinga Hińcza-Nowak3Artur Kowalik4Jarosław Jaskulski5Aldona Kowalska6Endocrinology Clinic, Holycross Cancer Center, S. Artwińskiego St. 3, 25-734 Kielce, PolandCollegium Medicum, Jan Kochanowski University, IX Wieków Kielc Av. 19, 25-319 Kielce, PolandCollegium Medicum, Jan Kochanowski University, IX Wieków Kielc Av. 19, 25-319 Kielce, PolandDepartment of Molecular Diagnostics, Holycross Cancer Center, S. Artwińskiego St. 3, 25-734 Kielce, PolandDepartment of Molecular Diagnostics, Holycross Cancer Center, S. Artwińskiego St. 3, 25-734 Kielce, PolandCollegium Medicum, Jan Kochanowski University, IX Wieków Kielc Av. 19, 25-319 Kielce, PolandEndocrinology Clinic, Holycross Cancer Center, S. Artwińskiego St. 3, 25-734 Kielce, Poland<b>Background</b>: Multiple endocrine neoplasia type 2A (MEN2A) is a rare, hereditary syndrome resulting from a germline mutation in the <i>RET</i> proto-oncogene and characterized primarily by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and hyperparathyroidism. Types of <i>RET</i> mutation have been associated with age at onset, clinical outcomes of MTC, and the penetrance of other components. Patients classified as ‘high-risk’ by the American Thyroid Association (ATA), based on the aggressiveness of MTC and the penetrance of other components, are recommended to undergo early prophylactic thyroidectomy at age ≤ 5 years and to be screened for PHEO at age ≥ 11 years. Patients with <i>RET</i> codon C634R mutations have been classified as high-risk. <b>Case presentation</b>: The present study describes a 71-year-old woman newly diagnosed with hereditary MTC related to a <i>RET</i> C634R germline mutation. Her basal serum calcitonin level was high, but there was no evidence of distant metastases. Surgery revealed bilateral MTC with two metastatic lymph nodes. Because microscopic resection was incomplete and extranodal extension was observed, the patient underwent adjuvant external beam radiotherapy. Response to therapy was excellent. Follow-up after 1.5 years showed no evidence of disease or other manifestations of MEN2A. <b>Conclusion</b>: Despite <i>RET</i> C634R carriers being classified as high-risk by the ATA, this patient did not present with either distant MTC or PHEO until her seventies. To our knowledge, only one other patient has shown a similar late identification of a <i>RET</i> C634R mutation, but MTC could not be diagnosed because the patient was lost to follow-up. Further research is required to develop optimal protocols that could allow patients requiring prophylactic thyroidectomy to be differentiated from those who can be monitored closely without early surgery.https://www.mdpi.com/2075-4418/11/8/1448multiple endocrine neoplasia type 2Ahereditary medullary thyroid cancergermline C634R <i>RET</i> mutationgenotype-phenotype correlationrisk stratification |
| spellingShingle | Agnieszka Walczyk Kajetan Zgubieński Grzegorz Chmielewski Kinga Hińcza-Nowak Artur Kowalik Jarosław Jaskulski Aldona Kowalska Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation Diagnostics multiple endocrine neoplasia type 2A hereditary medullary thyroid cancer germline C634R <i>RET</i> mutation genotype-phenotype correlation risk stratification |
| title | Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation |
| title_full | Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation |
| title_fullStr | Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation |
| title_full_unstemmed | Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation |
| title_short | Late-Onset Medullary Thyroid Cancer in a Patient with a Germline <i>RET</i> Codon C634R Mutation |
| title_sort | late onset medullary thyroid cancer in a patient with a germline i ret i codon c634r mutation |
| topic | multiple endocrine neoplasia type 2A hereditary medullary thyroid cancer germline C634R <i>RET</i> mutation genotype-phenotype correlation risk stratification |
| url | https://www.mdpi.com/2075-4418/11/8/1448 |
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