Multiple neuroma- a rare case report

CASE REPORT

A 32 year old female patient visited our outpatient department with a complaint of multiple growths in the buccal mucosa. She gave a history of burning sensation associated with multiple growths present in the buccal mucosa since 1 year. On intra oral examination buccal mucosa showed bilateral small multiple papillary / nodular growths that were firm in consistency. (Figure 1&2) Incisional biopsy was performed, gross specimen was measuring 3x4cm, showing brownish white colour (figure 3). On histopathological examination, the subepithelial connective tissue showed numerous fascicles of neural component surrounded by fibrous tissue (figure 4). Initial diagnosis of multiple neuroma was made. Later the patient was sent to Endocrinologist for evaluation of hormonal levels. There was an elevation of Thyroid stimulating hormone levels. As there were multiple neuromas along with abnormal Thyroid hormone levels, the patient was suspected for MEN -2 syndrome and regular follow-up was advised.

DISCUSSION

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare disease caused by germline mutations in the RET proto-oncogene and is transmitted in an autosomal dominant fashion. It is characterized by medullary thyroid carcinoma, pheochromocytoma and mucosal neuroma developing in the tongue, lip, intestinal tract, palate etc.¹

Mucosal neuroma is the most characteristic clinical phenotype and the earliest sign of MEN 2B and develops at birth or at around one to two years in almost all MEN patients.² Mucosal neuroma generally develops in the lips, tongue and buccal mucosa and less commonly in the palate, intestinal mucous membrane and conjunctiva.³ As time goes by, mucosal neuromas can increase in size and number or show no change. Because it has no specific symptoms and no malignant changes, no further treatment is needed except for cosmetic purposes.^4-6 Our patient also had multiple papules and nodules on her buccal mucosa bilaterally and complained of burning sensation.

These patients have characteristics such as the elongated face with thickened lips and mucosal neuromas, but not the classical marfanoid habitus, represented by an arm span bigger than the height. The mucosal neuromas are the earliest signs and are present in almost all patients with MEN2B.

Even in the absence of other signs or symptoms, the presence of mucosal neuromas in the early ages should motivate a MEN-2B investigation.⁷

The complete syndrome with mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma occurs in only 50% of the cases and when present is already too late for a prophylactic approach. The identification of early manifestations such as intestinal ganglioneuromatosis and oral mucosal neuromas should prompt the physician to initiate an investigation for multiple endocrine neoplasia type 2B.⁷

In conclusion, MEN 2B is often caused by de novo mutations of the RET proto oncogene. Therefore, DNA analysis is necessary for confirmation. However, it is hard to do routine DNA analysis in newborns, except for patients who have a family history of MEN 2B. Therefore, mucosal neuroma, a distinctive manifestation of MEN 2B (as in our patient), can be the definitive early diagnostic clue. Hence, the dentist should play a key role in pursuing further genetic investigations and prompt treatment.