Limits...
Multiple endocrine neoplasias type 2B and RET proto-oncogene.

Martucciello G, Lerone M, Bricco L, Tonini GP, Lombardi L, Del Rossi CG, Bernasconi S - Ital J Pediatr (2012)

Bottom Line: The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T).A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases.When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Genova, DIPE, Via Gaslini, 5 Genova (16147), Italy. martucciello@yahoo.com

ABSTRACT
Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

Show MeSH

Related in: MedlinePlus

Enzymo-histochemical studies of MEN 2B intestinal innervation performed by acetylcholinesterase on suction rectal biopsies: multiple ganglioneuromas and ganglioneurofibromas are brown stained. SM = submucous layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3368781&req=5

Figure 5: Enzymo-histochemical studies of MEN 2B intestinal innervation performed by acetylcholinesterase on suction rectal biopsies: multiple ganglioneuromas and ganglioneurofibromas are brown stained. SM = submucous layer.

Mentions: The ganglioneuromas (GN) and the ganglioneurofibromas (GNf) are common conditions affecting peripheral nerves of MEN 2B intestinal wall. Their presence in the rectal mucosal and submucous layers is brown stained and AChE easily shows the enormous hypertrophy of nerve fibers (GNf) among ENS (Figure 4 and 5). Submucous ganglion cells are usually present in normal numbers or organized in giant ganglia (GN) and always associated with large trunks of ENS nervous fibers. Ectopic ganglia inside lamina propia mucosae are present in most of the cases. These peculiar AChE findings are so specific, that the diagnosis of MEN 2B is possible with the simple use of suction rectal biopsy.


Multiple endocrine neoplasias type 2B and RET proto-oncogene.

Martucciello G, Lerone M, Bricco L, Tonini GP, Lombardi L, Del Rossi CG, Bernasconi S - Ital J Pediatr (2012)

Enzymo-histochemical studies of MEN 2B intestinal innervation performed by acetylcholinesterase on suction rectal biopsies: multiple ganglioneuromas and ganglioneurofibromas are brown stained. SM = submucous layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368781&req=5

Figure 5: Enzymo-histochemical studies of MEN 2B intestinal innervation performed by acetylcholinesterase on suction rectal biopsies: multiple ganglioneuromas and ganglioneurofibromas are brown stained. SM = submucous layer.
Mentions: The ganglioneuromas (GN) and the ganglioneurofibromas (GNf) are common conditions affecting peripheral nerves of MEN 2B intestinal wall. Their presence in the rectal mucosal and submucous layers is brown stained and AChE easily shows the enormous hypertrophy of nerve fibers (GNf) among ENS (Figure 4 and 5). Submucous ganglion cells are usually present in normal numbers or organized in giant ganglia (GN) and always associated with large trunks of ENS nervous fibers. Ectopic ganglia inside lamina propia mucosae are present in most of the cases. These peculiar AChE findings are so specific, that the diagnosis of MEN 2B is possible with the simple use of suction rectal biopsy.

Bottom Line: The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T).A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases.When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Genova, DIPE, Via Gaslini, 5 Genova (16147), Italy. martucciello@yahoo.com

ABSTRACT
Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

Show MeSH
Related in: MedlinePlus