Table 2.

Characteristics of Sporadic Medullary Thyroid Carcinoma, MEN2A, and MEN2B.^*

Disease	Associated_Phenotype	Mutations.†	Clinical_Characteristics
Sporadic MTC	None	RET (in approximately 50%), HRAS, NRAS, or KRAS (in 0 to 43%)68; rarely mutations in KIT or METor fusions of RET or ALK69,70	RET M918T associated with more aggressive MTC than RAS71
MEN2A
Classical	Pheochromocytoma (in 20 to 50%) and hyperparathyroidism (in 12 to 30%)	95% of RET mutations occur in exon 10 (codon 609, 611, 618, or 620) or exon 11 (codon 634)	Pheochromocytoma occurs in 30 to 50% of patients with RET mutations in exon 1172 and in 15% of those with RET mutations in exon 10; hyperparathyroidism occurs in 30% of patients with RET mutations in exon 11 and in <12% of those with RET mutations in exons other than 1173
With Hirschsprung’s disease	Hirschsprung’s disease	RET mutation in exon 10 at codon 620 (in 50%) and less often at codon 618, 609, or 61174	MEN2A in 2 to 5% of patients with Hirschsprung’s disease75
With cutaneous lichen amyloidosis	Cutaneous lichen amyloidosis	Usually RET mutation in codon 63476	In approximately 30% of patients with MEN2A; may precede onset of medullary thyroid carcinoma76
Familial MTC	None	Broad range of RET mutations	Appears to be less aggressive than the MTC associated with classical MEN2A
MEN2B	Typical facies, marfanoid habitus, medullated corneal nerves, and aerodigestive tract ganglioneuromatosis	RET M918T mutations in more than 95%, and RET A833F in the remainder	RET M918T associated with more aggressive MTC than RET A833F77

^*MEN2A denotes multiple endocrine neoplasia type 2A, and MEN2B multiple endocrine neoplasia type 2B.

^†Patients with sporadic MTC have somatic RET mutations, whereas patients with MEN2A or MEN2B have germline RET mutations.