Auris Nasus Larynx 41 (2014) 389–391
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Laryngeal neuroma in multiple endocrine neoplasia type 2B Naomi Kudo, Atsushi Matsubara *, Takahisa Abe, Taku Inoue, Junko Takahata Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 2 August 2013 Accepted 11 December 2013 Available online 2 January 2014
Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease caused by mutations of the RET proto-oncogene, and is clinically divided into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. Although multiple mucosal neuromas are commonly observed in patients with MEN2B, there are only a few reports of laryngeal neuroma. We present here a rare case of laryngeal mucosal neuromas with MEN2B. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Multiple endocrine neoplasia Mucosal neuroma Laryngeal neuroma
1. Introduction Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease characterized by association with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. This syndrome is clinically classified into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. In patients with MEN2B, multiple mucosal neuromas on the lips, tongue, and buccal cavity are commonly observed [1]. However, it is assumed to be remarkably rare for neuromas to appear in the larynx [2,3]. We report here a case who was diagnosed as MEN2B with a rare presentation of laryngeal mucosal neuromas. 2. Case report The patient was a 20-year-old woman. When she was 16 years old, she began to be aware of swelling in the left side of her front neck, but did not visit a hospital at that time. Three years later, in July 2011, she visited the internal medicine unit of a general hospital with this complaint. From the results of ultrasonography and computed tomography (CT), a thyroid tumor was suspected, and in the blood testing, carcinoembryonic antigen (CEA) was high: more than 500 ng/ml. Also, positron emission tomography (PET) demonstrated a significant fluorodeoxyglucose (FDG) accumulation in the thyroid gland. About 10 days after her first presentation, aspiration biopsy cytology was performed and she was diagnosed with medullary thyroid carcinoma.
* Corresponding author. Tel.: +81 172 39 5099; fax: +81 172 39 5100. E-mail address: [email protected] (A. Matsubara). 0385-8146/$ – see front matter ß 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.anl.2013.12.007
Two weeks later, she visited the mammary and thyroid gland surgery in our hospital, in order to undergo thyroidectomy. She presented to the otorhinolaryngology unit for a checkup before the operation, and bilateral arytenoid tumors were found (Fig. 1A). We therefore planned the extirpation of the tumors after the thyroidectomy. She then had an examination for MEN syndrome by an endocrinologist. Genetic analysis of the Rearranged during Transfection (RET) proto-oncogene confirmed that she had MEN2B. In this case mucosal tumors were observed in her tongue and lips (Fig. 1B), and biopsy revealed that they were mucosal neuromas. The neuromas in her lips and tongue had been noticed from her childhood. After the thyroidectomy, we extirpated the laryngeal tumors (Fig. 2). The result of the pathological examination indicated they were mucosal neuromas as well (Fig. 3). After the operation, she was discharged with good course. About six months later, we examined her larynx with a fiberscope, and found no evident sign of recurrence of mucosal tumors (Fig. 4). 3. Discussion MEN type 2 is an inherited autosomal disease caused by mutations of the RET proto-oncogene, and it can be divided into three subtypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma [4,5]. Particularly, almost all patients with MEN type 2 subsequently develop medullary thyroid carcinoma [6]. Due to the early development and aggressive nature of medullary thyroid carcinoma, the prognosis of the disease depends crucially upon the extent of it [7]. Accordingly, several investigators have shown that prophylactic total thyroidectomy at an early age is useful for the management of the patients with MEN2 [8]. Also, mucosal
390
N. Kudo et al. / Auris Nasus Larynx 41 (2014) 389–391
Fig. 1. Preoperative findings. Laryngeal tumors seen by laryngeal fiberscope (A). Mucosal neuromas observed in the tongue (B).
Fig. 2. Operative findings. Before (A) and after (B) extirpation.
Fig. 3. Photomicrographs show irregular neural bundles beneath the surface epithelium. H–E staining under low power field (A) and under high power field (B). Immunohistochemically, these bundles were positive for anti neurofilament (C) and S-100 (D).
neuromas on the tongue and on the lips are observed in high frequency. Thus they can be an early clue for detecting MEN2B and more importantly, medullary thyroid carcinoma [9]. Among the three subtypes of MEN type 2, MEN2A is the most frequent (>90%), and MEN2B accounts for approximately 5% [2].
Moreover, as in the case reported here, MEN2B with laryngeal mucosal neuroma is extremely rare, and there has been limited documentation of mucosal neuromas in the larynx [2,3]. Although the laryngeal mucosal neuromas in our case were pointed out before thyroidectomy by chance, they would
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thyroidectomy. In any case, laryngeal mucosal neuromas can manifest as potentially airway compromising lesions. So far, we have not found recurrence of mucosal neuromas in our case, but it is possible that they will grow again and cause airway problems. Thus we consider that it is critically important for ENT specialists to recognize mucosal neuromas in the larynx, from the perspective of airway management. References
Fig. 4. Laryngeal fiberscope findings six months after surgery.
potentially cause airway obstruction. As a matter of fact, Ghosh et al. reported the case of an 11-year-old girl diagnosed with MEN2B [2] in which the laryngeal neuromas were accidentally pointed out during general anesthesia. The neuromas were urgently excised by the ENT team, but about one month later, she presented with acute stridor by the recurrent lesion in her larynx. A case of laryngeal mucosal neuroma without MEN2B was also reported by Shimazaki et al., in which there was hoarseness and prickly sensation in the throat [10]. MEN2B is a rare disease, and MEN2B with laryngeal mucosal neuromas seem to be even rarer, however, we presume that there are potentially more cases which have just not been pointed out clinically; in fact, our patient had no complaints of symptoms associated with the laryngeal mucosal neuroma. The laryngeal tumors were only accidentally pointed out in the checkup before
[1] Morrison PJ, Nevin NC. Multiple endocrine neoplasia type two B (mucosal neuroma syndrome, Wagenmann–Froboese syndrome). J Med Genet 1996;33: 779–82. [2] Ghosh S, Joy R, Hickey S. Rare presentation of laryngeal neuroma in a patient with multiple endocrine neoplasia type two B. J Laryngol Otol 2008;122: 1012–4. [3] Inoue H, Mibu K, Miyauchi A. A case of multiple endocrine neoplasia type 2B with laryngeal mucosal neuromatosis. Otolaryngol Head Neck Surg 2007;79: 583–7. [4] Mulligan LM, Kwok JBJ, Healy CS, Elsdon MJ, Eng C, Gardner E, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993;363:458–60. [5] Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, et al. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet 1994;3:237–41. [6] Howe JR, Norton JA, Wells Jr Sif. Prevalence of pheocromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: resulting of long term follow-up. Surgery 1993;114:1070–7. [7] Iihara M, Yamashita T, Okamoto T, Kanbe M, Yamazaki K, Egawa S, et al. A nationwide clinical survey of patients with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma in Japan. Jpn J Clin Oncol 1997;27:128–34. [8] Wells Jr SA, Chi DD, Toshima K, Dehner LP, Coffin CM, Dowton B, et al. Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A. Ann Sug 1994;220:237–50. [9] Ata F, Ioroi K, Yamaguchi K, Ishii T, Ohata H, Ogasawara T. A case of multiple endocrine neoplasia type 2B diagnosed on the basis of multiple mucosal neuromas in the oral cavity. Jpn J Oral Maxillofac Surg 2007;53:368–72. [10] Shimazaki T, Yoshida Y, Izumaru S, Nakashima T. Laryngeal solitary multiple neuromas without multiple endocrine neoplasia (MEN) type 2B. Auris Nasus Larynx 2003;30:191–5.
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Laryngeal neuroma in multiple endocrine neoplasia type 2B Naomi Kudo, Atsushi Matsubara *, Takahisa Abe, Taku Inoue, Junko Takahata Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 2 August 2013 Accepted 11 December 2013 Available online 2 January 2014
Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease caused by mutations of the RET proto-oncogene, and is clinically divided into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. Although multiple mucosal neuromas are commonly observed in patients with MEN2B, there are only a few reports of laryngeal neuroma. We present here a rare case of laryngeal mucosal neuromas with MEN2B. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Multiple endocrine neoplasia Mucosal neuroma Laryngeal neuroma
1. Introduction Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease characterized by association with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. This syndrome is clinically classified into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. In patients with MEN2B, multiple mucosal neuromas on the lips, tongue, and buccal cavity are commonly observed [1]. However, it is assumed to be remarkably rare for neuromas to appear in the larynx [2,3]. We report here a case who was diagnosed as MEN2B with a rare presentation of laryngeal mucosal neuromas. 2. Case report The patient was a 20-year-old woman. When she was 16 years old, she began to be aware of swelling in the left side of her front neck, but did not visit a hospital at that time. Three years later, in July 2011, she visited the internal medicine unit of a general hospital with this complaint. From the results of ultrasonography and computed tomography (CT), a thyroid tumor was suspected, and in the blood testing, carcinoembryonic antigen (CEA) was high: more than 500 ng/ml. Also, positron emission tomography (PET) demonstrated a significant fluorodeoxyglucose (FDG) accumulation in the thyroid gland. About 10 days after her first presentation, aspiration biopsy cytology was performed and she was diagnosed with medullary thyroid carcinoma.
* Corresponding author. Tel.: +81 172 39 5099; fax: +81 172 39 5100. E-mail address: [email protected] (A. Matsubara). 0385-8146/$ – see front matter ß 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.anl.2013.12.007
Two weeks later, she visited the mammary and thyroid gland surgery in our hospital, in order to undergo thyroidectomy. She presented to the otorhinolaryngology unit for a checkup before the operation, and bilateral arytenoid tumors were found (Fig. 1A). We therefore planned the extirpation of the tumors after the thyroidectomy. She then had an examination for MEN syndrome by an endocrinologist. Genetic analysis of the Rearranged during Transfection (RET) proto-oncogene confirmed that she had MEN2B. In this case mucosal tumors were observed in her tongue and lips (Fig. 1B), and biopsy revealed that they were mucosal neuromas. The neuromas in her lips and tongue had been noticed from her childhood. After the thyroidectomy, we extirpated the laryngeal tumors (Fig. 2). The result of the pathological examination indicated they were mucosal neuromas as well (Fig. 3). After the operation, she was discharged with good course. About six months later, we examined her larynx with a fiberscope, and found no evident sign of recurrence of mucosal tumors (Fig. 4). 3. Discussion MEN type 2 is an inherited autosomal disease caused by mutations of the RET proto-oncogene, and it can be divided into three subtypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma [4,5]. Particularly, almost all patients with MEN type 2 subsequently develop medullary thyroid carcinoma [6]. Due to the early development and aggressive nature of medullary thyroid carcinoma, the prognosis of the disease depends crucially upon the extent of it [7]. Accordingly, several investigators have shown that prophylactic total thyroidectomy at an early age is useful for the management of the patients with MEN2 [8]. Also, mucosal
390
N. Kudo et al. / Auris Nasus Larynx 41 (2014) 389–391
Fig. 1. Preoperative findings. Laryngeal tumors seen by laryngeal fiberscope (A). Mucosal neuromas observed in the tongue (B).
Fig. 2. Operative findings. Before (A) and after (B) extirpation.
Fig. 3. Photomicrographs show irregular neural bundles beneath the surface epithelium. H–E staining under low power field (A) and under high power field (B). Immunohistochemically, these bundles were positive for anti neurofilament (C) and S-100 (D).
neuromas on the tongue and on the lips are observed in high frequency. Thus they can be an early clue for detecting MEN2B and more importantly, medullary thyroid carcinoma [9]. Among the three subtypes of MEN type 2, MEN2A is the most frequent (>90%), and MEN2B accounts for approximately 5% [2].
Moreover, as in the case reported here, MEN2B with laryngeal mucosal neuroma is extremely rare, and there has been limited documentation of mucosal neuromas in the larynx [2,3]. Although the laryngeal mucosal neuromas in our case were pointed out before thyroidectomy by chance, they would
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thyroidectomy. In any case, laryngeal mucosal neuromas can manifest as potentially airway compromising lesions. So far, we have not found recurrence of mucosal neuromas in our case, but it is possible that they will grow again and cause airway problems. Thus we consider that it is critically important for ENT specialists to recognize mucosal neuromas in the larynx, from the perspective of airway management. References
Fig. 4. Laryngeal fiberscope findings six months after surgery.
potentially cause airway obstruction. As a matter of fact, Ghosh et al. reported the case of an 11-year-old girl diagnosed with MEN2B [2] in which the laryngeal neuromas were accidentally pointed out during general anesthesia. The neuromas were urgently excised by the ENT team, but about one month later, she presented with acute stridor by the recurrent lesion in her larynx. A case of laryngeal mucosal neuroma without MEN2B was also reported by Shimazaki et al., in which there was hoarseness and prickly sensation in the throat [10]. MEN2B is a rare disease, and MEN2B with laryngeal mucosal neuromas seem to be even rarer, however, we presume that there are potentially more cases which have just not been pointed out clinically; in fact, our patient had no complaints of symptoms associated with the laryngeal mucosal neuroma. The laryngeal tumors were only accidentally pointed out in the checkup before
[1] Morrison PJ, Nevin NC. Multiple endocrine neoplasia type two B (mucosal neuroma syndrome, Wagenmann–Froboese syndrome). J Med Genet 1996;33: 779–82. [2] Ghosh S, Joy R, Hickey S. Rare presentation of laryngeal neuroma in a patient with multiple endocrine neoplasia type two B. J Laryngol Otol 2008;122: 1012–4. [3] Inoue H, Mibu K, Miyauchi A. A case of multiple endocrine neoplasia type 2B with laryngeal mucosal neuromatosis. Otolaryngol Head Neck Surg 2007;79: 583–7. [4] Mulligan LM, Kwok JBJ, Healy CS, Elsdon MJ, Eng C, Gardner E, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993;363:458–60. [5] Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, et al. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet 1994;3:237–41. [6] Howe JR, Norton JA, Wells Jr Sif. Prevalence of pheocromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: resulting of long term follow-up. Surgery 1993;114:1070–7. [7] Iihara M, Yamashita T, Okamoto T, Kanbe M, Yamazaki K, Egawa S, et al. A nationwide clinical survey of patients with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma in Japan. Jpn J Clin Oncol 1997;27:128–34. [8] Wells Jr SA, Chi DD, Toshima K, Dehner LP, Coffin CM, Dowton B, et al. Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A. Ann Sug 1994;220:237–50. [9] Ata F, Ioroi K, Yamaguchi K, Ishii T, Ohata H, Ogasawara T. A case of multiple endocrine neoplasia type 2B diagnosed on the basis of multiple mucosal neuromas in the oral cavity. Jpn J Oral Maxillofac Surg 2007;53:368–72. [10] Shimazaki T, Yoshida Y, Izumaru S, Nakashima T. Laryngeal solitary multiple neuromas without multiple endocrine neoplasia (MEN) type 2B. Auris Nasus Larynx 2003;30:191–5.
