- Email: [email protected]
Multiple endocrine neoplasia type 2B: Maxillofacial finding in one case
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Multiple endocrine neoplasia type 2B: Maxillofacial finding in one case Abdullah Bashara, Museedi Omara,*, Saif Jumab, Basima Alib, Saja Malikb a b
Oral Pathology Department, Collage of Dentistry, Baghdad University, Iraq Periodontology Department, Collage of Dentistry, Baghdad University, Iraq
A R T I C LE I N FO
A B S T R A C T
Keywords: Multiple endocrine neoplasia type 2B MEN 2B Oral mucosal neuroma
Multiple Endocrine Neoplasia type 2B (MEN 2B) is a very rare autosomal dominant disease in which the oral lesions may be the first clue that leads to the diagnosis. We describe a case of A 18 year old male diagnosed as MEN 2B due to multiple oral lesions of the tongue and the lips. The presenting feature was a nodular fibrous lesion at a central diastema. Histopathological and Immunohistochemical examination revealed multiple mucosal neuroma. The case report highlights the importance of oral lesions in early detection of such life threatening conditions.
1. Introduction Multiple endocrine adenomatosis was firstly proposed by Wermer in 1963 to assemble a group of endocrine disorder involving pituitary gland, parathyroid gland and pancreas [1]. The classification of this endocrine disturbance as multiple endocrine neoplasia type 1 (MEN type 1) was suggested in 1968 by Steiner to differentiated from other hormonal disorder reflecting in parathyroid tumors, phenochromocytoma and medullary thyroid carcinoma (MTC) by referring to the latter as multiple endocrine neoplasia type 2 (MEN type2) [2]. The multiple mucosal neuromas associated with MTC and phenochromocytoma was describe by William and Pollock in 1966 and confirms by other studies [3–5]. In 1975 The MEN type 2B was named by chong et al. to MTC, phenochromocytoma with multiple mucosal neuromas and to distinguish there from parathyroid tumors, phenochromocytoma and MTC syndrome that’s called MEN type 2A [6]. MEN type 2A, MEN type 2B share the presence of MTC and phenochromcytoma but the multiple oral neuroma, marfanoid habitus, intestinal ganglioneuromatosis and ophthalmic abnormalities are characteristics phenotype of MEN type 2B and distinguished from MEN type 2A [7]. Mandibular prognathia, presence of distema, true or relative macroglossia considered an orofacial finding for MEN type 2B [8–10]. 2. Case report A 18 year old male was referred by his orthodontist for surgical removal of gingival distma nodule. At examination, he exhibited multiple nodular mucosal lesions of
⁎
tongue, lip and buccal mucosa, and typical marfanoid habitus; lips were generally full and relative macroglossia. The patient had a family history of MTC of his grandmother. (Figs. 1 and 2 ) The histopathology sections for nodule showed numerous nerve bundles with marked thickening of the perineurium, the immunohistochemistry showed positive S-100 protein antibody in the nerve bundles with positive EMA in the perineurium. (Figs. 3, 4 and 5 ) The thyroid function test and ultrasound were normal, with normal Serum calcium and creatinine. 3. Discussion The patient in our case report had characteristics oral and maxillofacial manifestations of MEN 2B. The marfanoid habitus, thickened lips, relative macroglossia, dental distama and multiple neuroma consider a striking features of MEN 2B. The phenochromcytoma become evident in approximately 50% of patients which is negative in our patient [11]. The MTC affects 90% to 100% of MEN 2B patients but may be negative at time of diagnosis11, although the presence of positive family history of MTC without associated with endocrine abnormalities seen in patients with MEN 2B as revealed in history our case [12]. The S-100 protein for oral mucosal neuroma was positive in all MEN 2B cases and also EMA was positive in most cases of MEN 2B that agree with histopathological diagnosis of our case [13]. Finally, the recognition of the oral and maxillofacial characteristics of MEN 2B should alert the clinician because the syndrome have high morbidity rate due to MTC which is considered the most important component of this syndrome.
Corresponding author at: Baghdad University, Collage of Dentistry, Bab Al-Moatham Campus, Iraq. E-mail address: [email protected] (O. Museedi).
https://doi.org/10.1016/j.ajoms.2019.11.003 Received 26 August 2019; Received in revised form 10 October 2019; Accepted 6 November 2019 2212-5558/ © 2019 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Abdullah Bashar, et al., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, https://doi.org/10.1016/j.ajoms.2019.11.003
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
B. Abdullah, et al.
Fig. 4. S-100 protein immunohistochemtistry showed strong positivity. Fig. 1. Multiple nodular lesions on the lateral side of the tongue.
Fig. 2. Multiple nodular lesions on the upper and lower lips.
Fig. 5. EMA immunohistochemtistry showed positive perineuruim.
Conflict of interest This research did not receive any specific grant from funding agencies in the public, commercial, or not for profit sectors. References [1] Wermer P. Endocrine adenomatosis and peptic ulcer in a large kindred: inherited multiple tumors and mosaic pleiotropism in man. Am J Med 1963;35:205–12. [2] Steiner AL, Goodman AD, Powers SR. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and gushing’s disease: multiple endocrine neoplasia, Type 21. Medicine (Baltimore) 1968;47:371–409. [3] Williams ED, Pollock DJ. Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen’s disease. J Pathol Bacteriol 1966;91:71–80. [4] Gorlin RJ, Sedano HO, Vickers RA, Červenka J. Multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid—a syndrome. Cancer 1968;22:293–9. [5] Schimke RN, Hartmann WH, Prout TE, Rimoin DL. Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas: a possible
Fig. 3. H & E section showed thickened perineuruim with neural hyperplasia.
Ethical approval The case report was approved by ethical committee at collage of Dentistry/Baghdad University.
2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
B. Abdullah, et al.
[6] [7] [8] [9]
[10]
manifestations of the multiple endocrine neoplasia syndrome. Oral Surgery Oral Med Oral Pathol 1981;51:516–23. [11] MacIntosh RB, Shivapuja P-K, Krzemien MB, Lee M. Multiple endocrine neoplasia type 2B: maxillofacial significance in 5 cases. J Oral Maxillofac Surg 2014;72. 2498-e1. [12] Farndon JR, Leightt GS, Dilley WG, Baylin SB, Smallridge RC, Harrison TS, et al. Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity. Br J Surg 1986;73:278–81. [13] Misago N, Toda S, Narisawa Y. The relationship between palisaded encapsulated neuroma and the mucocutaneous neuroma seen in multiple endocrine neoplasia 2b syndrome: a histopathologic and immunohistochemical study. Am J Dermatopathol 2014;36:562–9.
regulatory defect in the differentiation of chromaffin tissue. N Engl J Med 1968;279:1–7. Chong GC, Beahrs OH, Sizemore GW, Woolner LH. Medullary carcinoma of the thyroid gland. Cancer 1975;35:695–704. Lee NC, Norton JA. Multiple endocrine neoplasia type 2B—genetic basis and clinical expression. Surg Oncol 2000;9:111–8. Accurso B, Mercado A, Allen CM. Multiple endocrine neoplasia-2B presenting with orthodontic relapse. Angle Orthod 2010;80:585–90. Usami Y, Takenobu T, Kurihara R, Imai Y, Shinohara S, Fukuda Y, et al. Neural hyperplasia in maxillary bone of multiple endocrine neoplasia type 2B patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 2011;112:783–90. Casino AJ, Sciubba JJ, Ohri GL, Rosner F, Winston J, Yunis M, et al. Oral-facial
3
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Multiple endocrine neoplasia type 2B: Maxillofacial finding in one case Abdullah Bashara, Museedi Omara,*, Saif Jumab, Basima Alib, Saja Malikb a b
Oral Pathology Department, Collage of Dentistry, Baghdad University, Iraq Periodontology Department, Collage of Dentistry, Baghdad University, Iraq
A R T I C LE I N FO
A B S T R A C T
Keywords: Multiple endocrine neoplasia type 2B MEN 2B Oral mucosal neuroma
Multiple Endocrine Neoplasia type 2B (MEN 2B) is a very rare autosomal dominant disease in which the oral lesions may be the first clue that leads to the diagnosis. We describe a case of A 18 year old male diagnosed as MEN 2B due to multiple oral lesions of the tongue and the lips. The presenting feature was a nodular fibrous lesion at a central diastema. Histopathological and Immunohistochemical examination revealed multiple mucosal neuroma. The case report highlights the importance of oral lesions in early detection of such life threatening conditions.
1. Introduction Multiple endocrine adenomatosis was firstly proposed by Wermer in 1963 to assemble a group of endocrine disorder involving pituitary gland, parathyroid gland and pancreas [1]. The classification of this endocrine disturbance as multiple endocrine neoplasia type 1 (MEN type 1) was suggested in 1968 by Steiner to differentiated from other hormonal disorder reflecting in parathyroid tumors, phenochromocytoma and medullary thyroid carcinoma (MTC) by referring to the latter as multiple endocrine neoplasia type 2 (MEN type2) [2]. The multiple mucosal neuromas associated with MTC and phenochromocytoma was describe by William and Pollock in 1966 and confirms by other studies [3–5]. In 1975 The MEN type 2B was named by chong et al. to MTC, phenochromocytoma with multiple mucosal neuromas and to distinguish there from parathyroid tumors, phenochromocytoma and MTC syndrome that’s called MEN type 2A [6]. MEN type 2A, MEN type 2B share the presence of MTC and phenochromcytoma but the multiple oral neuroma, marfanoid habitus, intestinal ganglioneuromatosis and ophthalmic abnormalities are characteristics phenotype of MEN type 2B and distinguished from MEN type 2A [7]. Mandibular prognathia, presence of distema, true or relative macroglossia considered an orofacial finding for MEN type 2B [8–10]. 2. Case report A 18 year old male was referred by his orthodontist for surgical removal of gingival distma nodule. At examination, he exhibited multiple nodular mucosal lesions of
⁎
tongue, lip and buccal mucosa, and typical marfanoid habitus; lips were generally full and relative macroglossia. The patient had a family history of MTC of his grandmother. (Figs. 1 and 2 ) The histopathology sections for nodule showed numerous nerve bundles with marked thickening of the perineurium, the immunohistochemistry showed positive S-100 protein antibody in the nerve bundles with positive EMA in the perineurium. (Figs. 3, 4 and 5 ) The thyroid function test and ultrasound were normal, with normal Serum calcium and creatinine. 3. Discussion The patient in our case report had characteristics oral and maxillofacial manifestations of MEN 2B. The marfanoid habitus, thickened lips, relative macroglossia, dental distama and multiple neuroma consider a striking features of MEN 2B. The phenochromcytoma become evident in approximately 50% of patients which is negative in our patient [11]. The MTC affects 90% to 100% of MEN 2B patients but may be negative at time of diagnosis11, although the presence of positive family history of MTC without associated with endocrine abnormalities seen in patients with MEN 2B as revealed in history our case [12]. The S-100 protein for oral mucosal neuroma was positive in all MEN 2B cases and also EMA was positive in most cases of MEN 2B that agree with histopathological diagnosis of our case [13]. Finally, the recognition of the oral and maxillofacial characteristics of MEN 2B should alert the clinician because the syndrome have high morbidity rate due to MTC which is considered the most important component of this syndrome.
Corresponding author at: Baghdad University, Collage of Dentistry, Bab Al-Moatham Campus, Iraq. E-mail address: [email protected] (O. Museedi).
https://doi.org/10.1016/j.ajoms.2019.11.003 Received 26 August 2019; Received in revised form 10 October 2019; Accepted 6 November 2019 2212-5558/ © 2019 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Abdullah Bashar, et al., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, https://doi.org/10.1016/j.ajoms.2019.11.003
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
B. Abdullah, et al.
Fig. 4. S-100 protein immunohistochemtistry showed strong positivity. Fig. 1. Multiple nodular lesions on the lateral side of the tongue.
Fig. 2. Multiple nodular lesions on the upper and lower lips.
Fig. 5. EMA immunohistochemtistry showed positive perineuruim.
Conflict of interest This research did not receive any specific grant from funding agencies in the public, commercial, or not for profit sectors. References [1] Wermer P. Endocrine adenomatosis and peptic ulcer in a large kindred: inherited multiple tumors and mosaic pleiotropism in man. Am J Med 1963;35:205–12. [2] Steiner AL, Goodman AD, Powers SR. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and gushing’s disease: multiple endocrine neoplasia, Type 21. Medicine (Baltimore) 1968;47:371–409. [3] Williams ED, Pollock DJ. Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen’s disease. J Pathol Bacteriol 1966;91:71–80. [4] Gorlin RJ, Sedano HO, Vickers RA, Červenka J. Multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid—a syndrome. Cancer 1968;22:293–9. [5] Schimke RN, Hartmann WH, Prout TE, Rimoin DL. Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas: a possible
Fig. 3. H & E section showed thickened perineuruim with neural hyperplasia.
Ethical approval The case report was approved by ethical committee at collage of Dentistry/Baghdad University.
2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
B. Abdullah, et al.
[6] [7] [8] [9]
[10]
manifestations of the multiple endocrine neoplasia syndrome. Oral Surgery Oral Med Oral Pathol 1981;51:516–23. [11] MacIntosh RB, Shivapuja P-K, Krzemien MB, Lee M. Multiple endocrine neoplasia type 2B: maxillofacial significance in 5 cases. J Oral Maxillofac Surg 2014;72. 2498-e1. [12] Farndon JR, Leightt GS, Dilley WG, Baylin SB, Smallridge RC, Harrison TS, et al. Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity. Br J Surg 1986;73:278–81. [13] Misago N, Toda S, Narisawa Y. The relationship between palisaded encapsulated neuroma and the mucocutaneous neuroma seen in multiple endocrine neoplasia 2b syndrome: a histopathologic and immunohistochemical study. Am J Dermatopathol 2014;36:562–9.
regulatory defect in the differentiation of chromaffin tissue. N Engl J Med 1968;279:1–7. Chong GC, Beahrs OH, Sizemore GW, Woolner LH. Medullary carcinoma of the thyroid gland. Cancer 1975;35:695–704. Lee NC, Norton JA. Multiple endocrine neoplasia type 2B—genetic basis and clinical expression. Surg Oncol 2000;9:111–8. Accurso B, Mercado A, Allen CM. Multiple endocrine neoplasia-2B presenting with orthodontic relapse. Angle Orthod 2010;80:585–90. Usami Y, Takenobu T, Kurihara R, Imai Y, Shinohara S, Fukuda Y, et al. Neural hyperplasia in maxillary bone of multiple endocrine neoplasia type 2B patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 2011;112:783–90. Casino AJ, Sciubba JJ, Ohri GL, Rosner F, Winston J, Yunis M, et al. Oral-facial
3