Spitz_Genodermatoses, 3e

Multiple Endocrine Neoplasia Type IIB

Synonym(s)

Multiple endocrine neoplasia (MEN) type III Multiple mucosal neuroma syndrome Wagenmann-Froboese syndrome

Inheritance

AD; RET proto-oncogene on 10q11.21 Sporadic mutation in 50%

Prenatal Diagnosis

DNA analysis

Incidence

1:2,000,000; M = F

Age at Presentation

Birth to first few years of life (mucosal lesions may precede internal malignancies by a decade)

Pathogenesis

Gain-of-function mutation in RET proto-oncogene encoding a tyrosine kinase receptor in neural crest–derived tissue, promotes neoplasia

Key Features

Mucocutaneous Mucosal neuromas on tongue and lips; may involve buccal, palatal, gingival, nasal, and laryngeal mucosa Thickened “blubbery” lips Endocrine Highly aggressive medullary carcinoma of the thyroid Pheochromocytoma Musculoskeletal Marfanoid habitus (see Marfan Syndrome, p. 164) Proximal muscle wasting with weakness Eyes Conjunctival neuromas; upper eyelids thickened and everted; thickened white medul lated nerve fibers in cornea Gastrointestinal Ganglioneuromatosis with secondary megacolon, diarrhea, constipation

Differential Diagnosis

MEN IIA-Sipple syndrome Neurofibromatosis I (p. 86) Marfan syndrome (p. 164)

Laboratory Data

Serum/urine calcitonin level Serum catecholamine and metanephrine levels Thyroid scan/thyroid function tests Abdominal and chest computed tomography (CT) with contrast Barium enema

Management

Referral to endocrinologist/surgeon—thyroidectomy in the first 2 years if diagnosed at birth, removal of pheochromocytoma Referral to gastroenterologist, ophthalmologist, dermatologist Examine family members

Prognosis

If thyroid carcinoma detected early on, many have normal life span; otherwise, often fatal by 20-30 years of age

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Both MEN IIB and MEN IIA are caused by mutations in the RET proto-oncogene . . . Thick, full lips can be noticed first, and pedunculated neuromas can occur on the tongue and eye lids as well . . . Diagnosis is often made in early teenage years . . . Neuromas are not usually bothersome . . . Medullary thyroid carcinoma can occur very early in life, and some experts recommend treatment even in the first 6 months of life! LE

CLINICAL PEARLS

212