Multiple Endocrine Neoplasia Type 2B

Two multiple endocrine neoplasia (MEN) syndromes are described in the literature - MEN 1 and MEN 2, and multiple endocrine neoplasia type 2B, is one of the subtypes of MEN 2, presenting with several distinguishing features [1] [2] [3] [4] [5]:

• Medullary thyroid cancer (MTC) - Virtually all patients who suffer from MEN type 2B develop an aggressive MTC that appears during the first several months of life, which is why total thyroidectomy is often indicated, both as a prophylactic and as a therapeutic measure [5] [6] [7]. Main complaints related to MTC are localized pain in the neck, often accompanied by a palpable mass [3] [8].
• Pheochromocytoma - In approximately 50% of cases, tumors of the adrenal gland (either unilateral or bilateral) are recorded and cause blood pressure changes due to the ongoing production of catecholamines (norepinephrine and epinephrine) [3] [4] [6] [9].
• Mucosal neuromas - Defined as one of the crucial clinical features of MEN type 2B, these lesions appear in the oral cavity (the anterior dorsal surface of the tongue, the pharynx, the buccal surfaces, and the palate) in infancy and childhood [3] [6] [8] [10]. Neuromas might appear on the eyelids (causing eversion of the upper eyelid and thickening) and the lips, giving them a "blueberry" color [3].

In addition, other prominent findings are gastrointestinal complaints (feeding difficulties, vomiting, dysphagia, abdominal pain, and either constipation or diarrhea, presumably arising from excessive calcitonin secretion due to MTC), musculoskeletal changes (kyphosis, hip dislocation, a Marfanoid appearance, as well as flat foot and pes cavus), and a flat facies with hypertelorism [3] [6] [10]

The diagnosis of MEN type 2B rests on the ability of the physician to recognize the main signs and symptom that will raise clinical suspicion. Firstly, a detailed patient history and a thorough physical examination should be performed, during which mucosal neuromas must be identified. Although MEN syndromes exhibit an autosomal dominant pattern of inheritance (meaning that a family history can be crucial for making the diagnosis), many patients develop de novo mutations of the RET proto-oncogene, the main event in the pathogenesis of multiple endocrine neoplasia type 2B [5] [9]. As soon as clinical evidence is obtained, laboratory and imaging studies need to be performed. Serum levels of calcitonin and metanephrines (although urine can be a viable sample for the latter) are useful initial methods to suspect toward MTC and pheochromocytoma, respectively [4] [5] [10]. Computed tomography (CT) and magnetic resonance imaging (MRI) are recommended for internal organ evaluation and confirmation of the two tumors in the patients, whereas barium enema and other radiographic studies of the gastrointestinal tract commonly may reveal a megacolon and dilation of the small bowel [3] [4] [10]. MTC should be further solidified by performing a biopsy with subsequent histopathological examination and immunohistochemistry [3].

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7. Morrison PJ, Atkinson AB. Genetic aspects of familial thyroid cancer. The Oncologist. 2009;14:571–577.
8. Millar S, Bradley L, Donnelly DE, et al. Familial pediatric endocrine tumors. The Oncologist. 2011;16:1388–1396.
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10. Qualia CM, Brown MR, Ryan CK, Rossi TM. Oral Mucosal Neuromas Leading to the Diagnosis of Multiple Endocrine Neoplasia Type 2B in a Child With Intestinal Pseudo-obstruction. Gastroenterol Hepatol (N Y). 2007;3(3):208-211.