MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B
MEN 2B is similar to MEN 2A except that the mean age of Tumours development in the former is an average 10 years earlier than the latter (Schimke 1984; Eng et al. 2001). Interestingly, clinically apparent HPT is rarely, if ever, observed in individuals with MEN 2B (Zbuk and Eng 2007; Kloos et al. 2009). Instead, they have characteristic stigmata including multiple mucosal neuromas and intestinal ganglioneuromatosis. There is a thin, asthenic marfanoid build, with some muscle wasting and possibly weakness. Joint laxity, kyphoscoliosis, pectus excavatum, pes cavus, and genu valgum are common. The face is elongated, the eyebrows are large and prominent, and the lips are enlarged and nodular, secondary to the neuromata – “blubbery” (Gorlin et al. 1968; Schimke 1984) (see Fig. 11.4). There may be multiple mucosal neuromas, which can be plexiform, and are visible on the eyelids, conjunctivae, and corneas. Enlarged corneal nerves (medullated corneal nerve fibers) may be seen. Cutaneous neuromas may also occur, and rarely, there may be café-au-lait patches and facial lentigines. The skin features may thus resemble those of NF 1, from which MEN 2B must be distinguished. Bowel malfunction, usually presenting with constipation or even obstruction, may result from ganglioneuromatosis of the gut (Carney et al. 1976). This must be distinguished from Hirschsprung’s disease and Cowden syndrome, where ganglioneuromatous polyps are common (Zbuk and Eng 2007; Heald et al. 2010).
MTC and PC develop in virtually all patients with MEN 2B. The Tumours are bilateral and multicentric, and metastasize locally and distantly, often before the disease is recognized. MEN 2B-related MTC develops at a younger age (mean age at diagnosis, 20 years, often at very young ages) than MEN 2A and has been observed to be metastatic even before the age of 4 years (Wells et al. 1978; Eng et al. 2001; Kloos et al. 2009). While it is widely believed that the prognosis for MEN 2B-related MTC is worse than that in MEN 2A, well-controlled studies suggest that this is largely due to lead time bias.