Long-term outcome of "prophylactic therapy" for familial medullary thyroid cancer.
BACKGROUND
About one quarter of all medullary thyroid cancers (MTC) are determined genetically due to a mutation in the RET proto-oncogene. The most common site of mutation is in codon 634. Therapeutic approaches toward patients at risk for the development of MTC identified by family screening programs range from total thyroidectomy to total thyroidectomy with lymphadenectomy of all 4 compartments.


METHODS
We report 17 patients (median age, 13 years; range, 4-36) carrying a mutation in codon 634 of the RET proto-oncogene who were operated on prophylactically at our department. All patients underwent thyroidectomy with bilateral cervicocentral lymphadenectomy. Current calcitonin level, overall survival, and disease-free survival were analyzed by contacting general practitioners and patients.


RESULTS
Tumor classification was as follows: C-cell hyperplasia, 18% (n = 3); T1 (<1 cm), 71% (n = 12); and T1 (>1 cm), 12% (n = 2). Only 2 patients had lymph node metastases (12%). These patients developed recurrent disease (median observation time, 147 months; range, 90-181). In 1 patient, the calcitonin level normalized after unilateral cervicolateral lymphadenectomy. The other patient (9 years old at primary operation) still has a persistently increased serum calcitonin level after 140 months of follow-up despite several operations for MTC.


CONCLUSIONS
Total thyroidectomy with bilateral cervicocentral lymphadenectomy is sufficient as routine "prophylactic therapy" for patients with mutations in codon 634 of the RET proto-oncogene. Cervicolateral lymphadenectomy is indicated if calcitonin remains elevated after primary surgery. Prophylactic thyroidectomy should be performed before the development of lymph node metastases.
Schellhaas
Elisabeth
E
Department of Surgery I, Charité Medical School, Campus Benjamin Franklin, Berlin, Germany.
König
Charlotte
C
Frank-Raue
Karin
K
Buhr
Heinz-J
HJ
Hotz
Hubert G
HG
D000293:Adolescent; D000328:Adult; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D009154:Mutation; D009333:Neck / Q000000981:diagnostic imaging / Q000601:surgery; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012008:Recurrence; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D013965:Thyroidectomy / Q000009:adverse effects; D016896:Treatment Outcome; D014463:Ultrasonography; D055815:Young Adult
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret