Sporadic medullary thyroid carcinoma: clinical data from a university hospital.
BACKGROUND
Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored.


OBJECTIVE
To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended.


METHODS
Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations.


RESULTS
The average age at diagnosis was 43.9 years (+/- 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene.


CONCLUSIONS
Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were highly useful for diagnosing s-medullary thyroid carcinoma. The rate of complete patient recovery was low, and none of the parameters analyzed were useful predictors of the thyroid tumor size. Our findings support previous recommendations for routine serum calcitonin evaluation and immunostaining analysis involving single thyroid nodules.
Correia-Deur
Joya Emilie M
JE
Unidade de Endocrinologia Genética, Laboratórios de Investigação Médica (LIM-25), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Toledo
Rodrigo A
RA
Imazawa
Alice T
AT
Lourenço
Delmar M
DM
Ezabella
Marilza C L
MC
Tavares
Marcos R
MR
Toledo
Sergio P A
SP
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000097:blood / Q000235:genetics / Q000473:pathology*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D047368:Tumor Burden
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human