INTRODUCTION

Multiple endocrine neoplasia type 2 (MEN 2) comprises three clinically distinct dominantly inherited neuroendocrine cancer syndromes: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma, which share medullary thyroid carcinoma (MTC) as part of the disease spectrum.¹ MEN 2A patients are characterized by the additional occurrence of pheochromocytoma and/or parathyroid hyperplasia. MEN 2B patients also have pheochromocytomas and, very rarely, parathyroid hyperplasia; in addition, they have mucosal neuromas, mainly of the buccal mucosa and tongue, ganglioneuromatosis of the gastrointestinal tract, skeletal and ophthalmologic abnormalities, and a Marfanoid habitus² (Table 1). All MEN 2 syndromes are caused by missense mutations in different areas of the RET proto-oncogene,^3-5 which encodes a receptor tyrosine kinase, for which glial cell-line derived neurotrophic factor and neurturin are the ligands.^6-8 A single, identical point mutation in the catalytic core of the RET tyrosine kinase domain (codon 918^MetThr) has been found in 94% of inherited and de novo cases of MEN 2B, which makes this disorder well-suited for genetic testing.⁹ Because of this and because 50% of MEN 2B cases present de novo, it is important to be aware of possible presenting symptoms in combination with the typical features of MEN 2B patients. Very rarely, patients with typical MEN 2B features do not have RET codon 918 (exon 16) mutations.^9-11 Those cases are most probably caused by mutations elsewhere in the RET gene, eg, at codon 883 of RET exon 15.¹²

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In this report, we present a case of a girl with dysmorphic features, chronic constipation, and abnormal histology of the enteric nervous system in early childhood. Sixteen years later, she presented with MTC and was found to harbor a de novo RET mutation, characteristic of MEN 2B.

	MATERIALS AND METHODS

Histology and Immunohistochemistry

Five-micron sections of paraffin-embedded tissue (resected colon and MTC) were deparaffinized. Hematoxylin and eosin and sirius red . . . [Full Text of this Article]