C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients.
Routine calcitonin (CT) assay programs and genetic testing for RET proto-oncogene mutations have consistently modified the management and understanding of C-cell proliferative disorders. We report a series of 66 consecutive patients with C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) observed in our institution within an 8-year time period. All the patients had a preoperative basal CT assay and an RET proto-oncogene sequencing. Seventeen patients (F-M ratio: 8:9, mean age: 29.7 y) had a multiple endocrine neoplasia Type 2: 3 children <10 years of age had CCH only, and 14 patients had an MTC, with neoplastic CCH in 10/14 cases. Twenty-seven patients (F-M ratio: 18:9, mean age: 56.6 y) had a sporadic MTC, with physiological CCH in 8 and neoplastic CCH in 3 cases. Twenty-two men (mean age: 46.2 y) had CCH only (physiological CCH in 17 men and neoplastic CCH in 5). We conclude that (1) clinical and pathological characteristics (familial MTC, tumor multifocality, neoplastic CCH) usually associated with hereditary MTC may be misleading and that on the contrary, RET sequencing gives no false positive result; (2) sporadic neoplastic CCH accompanies (and probably precedes) a number of sporadic MTC; and (3) women presenting with a sporadic elevated basal CT have a 100% risk of having an MTC (15/15), but this risk is 3-fold less in men (31%), who will most often have CCH only (69%).
Guyétant
Serge
S
Department of Pathology, Centre Hospitalier Universitaire, Angers, France. guyetant@med.univ-tours.fr
Josselin
Nicolas
N
Savagner
Fréderique
F
Rohmer
Vincent
V
Michalak
Sophie
S
Saint-André
Jean-Paul
JP
D000293:Adolescent; D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013961:Thyroid Gland / Q000166:cytology* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases