Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®): Genetics - Health Professional Information [NCI] - Multiple Endocrine Neoplasia Type 2
Table 3. Percentage of Patients with Clinical Features of MEN2 by Subtype continued...
A small number of families with MEN2A have pruritic skin lesions known as cutaneous lichen amyloidosis. This lichenoid skin lesion is located over the upper portion of the back and may appear before the onset of MTC.[74,75]
Familial medullary thyroid carcinoma (FMTC)
The FMTC subtype makes up 5% to 35% of MEN2 cases and is defined as families with four or more cases of MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. Families with two or three cases of MTC and incompletely documented screening for pheochromocytoma and parathyroid disease may actually represent MEN2A; it has been suggested that these families should be considered unclassified.[7,76] Misclassification of families with MEN2A as having FMTC (because of too-small family size or later onset of other manifestations of MEN2A) may result in overlooking the risk of pheochromocytoma, a disease with significant morbidity and mortality. For this reason, there is debate about whether FMTC represents a separate entity or is a variation of MEN2A in which there is a lack of or delay in the onset of the other (nonthyroidal) manifestations of the MEN2A syndrome. Some authors recommended, therefore, that patients thought to have pure FMTC also be screened for pheochromocytoma and hyperparathyroidism. (Refer to the Screening of at-risk individuals for pheochromocytoma and Screening of at-risk individuals for hyperparathyroidism sections of this summary for more information.)
MEN2B is diagnosed clinically by the presence of mucosal neuromas of the lips and tongue, medullated corneal nerve fibers, distinctive facies with enlarged lips, an asthenic Marfanoid body habitus, and MTC.[78,79,80]
The MEN2B subtype makes up about 5% of MEN2 cases. The MEN2B subtype was initially called mucosal neuroma syndrome or Wagenmann-Froboese syndrome. MEN2B is characterized by the early development of an aggressive form of MTC in all patients.[81,82] Patients with MEN2B who do not undergo thyroidectomy at an early age (at approximately age 1 year) are likely to develop metastatic MTC at an early age. Before intervention with early risk-reducing thyroidectomy, the average age at death in patients with MEN2B was 21 years. Pheochromocytomas occur in about 50% of MEN2B cases; about half are multiple and often bilateral. Clinically apparent parathyroid disease is very uncommon.[5,62,83] Patients with MEN2B may be identified in infancy or early childhood by a distinctive facial appearance and the presence of mucosal neuromas on the anterior dorsal surface of the tongue, palate, or pharynx. The lips become prominent over time, and submucosal nodules may be present on the vermilion border of the lips. Neuromas of the eyelids may cause thickening and eversion of the upper eyelid margins. Prominent thickened corneal nerves may be seen by slit lamp examination.