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Mucoepidermoid carcinoma of the tongue in a child
International Journal of Pediatric Otorhinolaryngology Extra 7 (2012) 6–8
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case report
Mucoepidermoid carcinoma of the tongue in a child Mosaad Abdel-Aziz 1,* Department of Otolaryngology, Faculty of Medicine, Cairo University, Egypt
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 June 2011 Received in revised form 22 July 2011 Accepted 24 July 2011 Available online 17 August 2011
Tongue base tumors are not common, they are mostly malignant and although the rarity of mucoepidermoid carcinoma of tongue base, it constitutes more than 50% of malignant lesions of salivary glands in this region. In this report, we present a 15-year old girl with mucoepidermoid carcinoma of tongue base with discussion of histopathological types of the tumor and its management. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Tongue base Mucoepidermoid carcinoma Minor salivary gland tumors Pediatric malignancy
1. Introduction Mucoepidermoid carcinoma (MEC) is a malignant, locally invasive neoplasm of the salivary glands. Its incidence rate has been reported to be 0.44 per 100,000. It is the most common malignant neoplasm of the salivary glands, especially in the parotid gland, but MEC also can occur in submandibular and minor salivary glands [1]. Minor salivary glands are scattered in different areas of the oral cavity; their tumors constitute a small proportion of all head and neck neoplasms, but are more frequently malignant [2]. Although tongue base tumors are not common, they are mostly malignant and although the rarity of MEC of tongue base, it constitutes more than 50% of malignant lesions of salivary glands in this region [3]. In this report, we present a 15-year old girl with MEC of tongue base with discussion of histopathological types of the tumor and its management.
was 5 cm 3 cm crossing the midline, it was reddish in color with irregular surface (Fig. 1). Neck examination showed no palpable lymph nodes. Computerized tomography (CT) was requested and it showed a soft tissue mass on the right side of tongue base and crossing the midline, it was infiltrating the muscles but was not involving the whole thickness of the tongue (Fig. 2). Biopsy was taken under local anesthesia, histopathological examination revealed the diagnosis of mucoepidermoid carcinoma of low grade type. As the morphological appearance of MEC share
2. Case presentation A 15-year-old girl referred to the Department of Otolaryngology of Kasr El-Aini Hospital (Cairo University) with tongue mass. The patient had complained of dysphagia, throat pain, and pain in her right ear for three months. Examination of the patient revealed an oval mass on the dorsal surface of the right side of tongue base that was seen easily when the patient protruded her tongue; the mass
* Correspondence address: 2 El-Salam St., King Faisal, Above El-Baraka Bank, Giza, Cairo, Egypt. Tel.: +20 105140161; fax: +20 225329113. E-mail address: [email protected]. 1 Study was carried out at Kasr El-Aini Hospital of Cairo University. 1871-4048/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pedex.2011.07.004
Fig. 1. The mass on the right side of tongue base.
M. Abdel-Aziz / International Journal of Pediatric Otorhinolaryngology Extra 7 (2012) 6–8
7
Fig. 4. Microscopic picture of the lesion, both element of the tumor are seen with mucus inside cystic spaces denoting the low-grade-nature (400).
Fig. 2. A CT scan showing soft tissue-mass on the right side of tongue base, the lesion is irregular and not involving the whole thickness of the tongue.
Follow-up of the patient for 3 years showed no recurrence. Informed consent was obtained from the parents to publish the case, and the work has been approved by the Institutional Ethical Committee, also the principles outlined in the Declaration of Helsinki were followed. 3. Discussion
similarities to metastatic clear cell renal adenocarcinoma and clear cell bronchogenic squamous carcinoma [4], ultrasonography of the kidneys and chest radiograph were performed to rule out metastatic carcinoma from these areas and they proved free kidneys and chest. Complete surgical excision was done under general anesthesia with nasal endotracheal intubation; a trans-oral excision was performed (Fig. 3). Post-operative antibiotic, analgesics and steroids were given to the patient for three days, the patient was informed to eat cold semisolid foods for one week and he had been discharged from hospital in the 3rd post-operative day. Histopathological examination of the specimen revealed a low grade mucoepidermoid carcinoma with negative margins (Fig. 4).
Fig. 3. The removed surgical specimen with the superficial part being covered with intact mucosa and larger irregular deep part.
Salivary gland tissues are distributed widely in the upper aerodigestive tract; the major salivary glands are the parotid, submandibular and sublingual glands, while minor salivary glands are distributed in many sites, such as the lips, cheek, palate, tongue, oropharynx, paranasal sinuses, parapharyngeal space and supraglottic larynx. Neoplasms originating from salivary glands comprise about 3–6% of all head and neck tumors, with an estimated global incidence of 0.4–13.5 per 100,000 persons annually [5,6]. Neoplasms of minor salivary gland origin occur much less commonly than those arising from major salivary glands; however, MEC is the commonest malignant tumor of major and minor salivary glands [1–3]. Malignant tumors of the intra-oral minor salivary glands constitute 2–3% of all malignant neoplasms of the upper aerodigestive tract [7]. MEC is composed histologically of epidermoid cells and mucin-producing cells, which take origin from the duct epithelial lining. The epidermoid cells proliferate in sheets or islands, and keratinizing may occur. When the epidermoid element predominates, the histological appearance of the tumor may closely resemble that of squamous cell carcinoma, and it is thus classified as a high-grade MEC tumor. Conversely, the presence of mucin-producing cells within a predominately cystic architecture is regarded as low-grade MEC tumors [2,4]. However, metastasis and tumor-related death have been noted with low-grade rather than high-grade tumors [8], in the Armed Forces Institute of Pathology series of 227 cases of MEC, 17 patients (7%) with low-grade tumors had local metastases (n = 7) or died of disease (n = 10) [9]. Dillard et al. [8] have suggested a role for transforming growth factor b1 (TGF-b1) in tumor behavior as elevated levels of TGF-b1 increase desmoplasia, angiogenesis, and tumor progression, with loss of expression of TGF-b RII (which is a receptor complex for TGF-b1) may define a transition from low- to high-grade MEC. Other factors that may affects tumor progression may be the proliferating cell nuclear antigen which may increases with the grade of malignancy [10], also, mucin expression patterns can be used as a prognostic index; membrane-bound mucins (MUC) are expressed on the cell surfaces
8
M. Abdel-Aziz / International Journal of Pediatric Otorhinolaryngology Extra 7 (2012) 6–8
of MEC. Studies have shown that the presence of MUC-1 is related to aggressive tumor, while MUC-4 represented greater cellular differentiation and better prognosis [11,12]. The treatment of the low grade MEC of the minor salivary glands involves wide local excision with adequate tumor-free margins, while high grade tumors require more aggressive surgery with or without postoperative radiotherapy and chemotherapy [13,14]. Leong et al. [2] reported MEC in a 27 year-old man that presented with severe bleeding per mouth necessitating emergency management to control bleeding and tracheostomy was performed to protect the airway. Surgical excision of the tumor was done trans-orally using CO2 laser, although there was no lymph node metastasis, the authors performed selective neck dissection on the side of the tumor as it was of high-grade type, also the patient received post-operative radiotherapy and chemotherapy. In our case, we did not need to perform neck dissection as the tumor was of low-grade type with no metastatic neck nodes. Conley and Tinsley [15] have reported that lymph node metastases occur in nearly three-quarter of patients at presentation with high grade-cancer, Jones [16] advised performance of selective neck dissection for patients with high-grade or large lesions N0 neck and radical neck dissection for patients with positive neck nodes. Although MEC is a radio-resistant tumor, post-operative irradiation is suggested by many authors in high-grade type and if the surgical margin was not free [13,14,17]. Follow up of our case for 3 years showed no recurrence. King and Fletcher [17] reported that the five-year survival rate is about 70% for low-grade tumor and a 47% survival for high-grade tumor, while other authors reported a higher rate of survival for low-grade type (96%) with death rate ten times higher in high-grade lesion [18]. However, some authors recommended follow up for life as recurrence may be delayed for years [2,19,20]. In summary, we report mucoepidermoid carcinoma of the tongue in a 15-year old girl; the tumor was of low-grade type. Less aggressive treatment in the form of local trans-oral excision was sufficient with no recurrence for 3 years follow up. Since metastasis is uncommon but not unheard of, long-term surveillance is recommended. Financial support There are no financial disclosures. Conflicts of interest There are no conflicts of interest.
References [1] J.A. Pinkston, P. Cole, Incidence rates of salivary gland tumors: results from a population-based study, Otolaryngol. Head Neck Surg. 120 (1999) 834–840. [2] S.C.L. Leong, E. Pinder, R. Sasae, S. Mortimore, Mucoepidermoid carcinoma of the tongue, Singapore Med. J. 48 (10) (2007) e272. [3] L.I. Goldblatt, G.L. Ellis, Salivary gland tumors of the tongue. Analysis of 55 new cases and review of the literature, Cancer 60 (1987) 74–81. [4] P.J. Bradley, Distant metastases from salivary glands cancer, ORL J. Otorhinolaryngol. Relat. Spec. 63 (2001) 233–242. [5] Z. Tian, L. Li1, L. Wang, Y. Hu, J. Li, Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population, Int. J. Oral Maxillofac. Surg. 39 (2010) 235–242. [6] J.G. Batsakis, Tumors of the Head and Neck: Clinical and Pathological Considerations, 2nd ed., Williams and Wilkins Co., Baltimore, 1979. [7] H. Rivera-Bastidas, R.A. Ocanto, A.M. Acevedo, Intraoral minor salivary gland tumors: a retrospective study of 62 cases in a Venezuelan population, J. Oral Pathol. Med. 25 (1) (1996) 1–4. [8] D.G. Dillard, S. Muller, C. Cohen, J.M.D. Gaudio, A.A. Gal, High tumor grade in salivary gland mucoepidermoid carcinomas and loss of expression of transforming growth factor b receptor type II, Arch. Otolaryngol. Head Neck Surg. 127 (2001) 683–686. [9] R.K. Goode, P.L. Auclair, G.L. Ellis, Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria, Cancer 82 (1998) 1217–1224. [10] W.P. Cardoso, O.V. Denardin, A. Rapoport, V.C. Araujo, M.B. Carvalho, Proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of salivary glands, Sao Paulo Med. J. 118 (2000) 69–74. [11] L. Alos, B. Lujan, M. Castillo, A. Nadal, M. Carreras, M. Caballero, C. de Bolos, A. Cardesa, Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands, Am. J. Surg. Pathol. 29 (2005) 806–813. [12] A. Handra-Luca, G. Lamas, J.C. Bertrand, P. Fouret, MUC1, MUC2, MUC4, and MUC5AC expression in salivary gland mucoepidermoid carcinoma, Am. J. Surg. Pathol. 29 (2005) 881–889. [13] P. Auclair, G. Ellis, Mucoepidermoid carcinoma, in: G.L. Ellis, P.L. Auclair, D.R. Gnepp (Eds.), Surgical Pathology of the Salivary Glands, WB Saunders Co, Philadelphia, 1991, pp. 269–298. [14] J. Hicks, C. Flaitz, Mucoepidermoid carcinoma of salivary glands in children and adolescents: assessment of proliferation markers, Oral Oncol. 36 (5) (2000) 454– 460. [15] J. Conley, P.P. Tinsley, Treatment and prognosis of mucoepidermoid carcinoma in the paediatric age group, Arch. Otolaryngol. 111 (1985) 322–324. [16] A.S. Jones, Malignant tumours of the salivary glands, in: M. Gleeson, G.G. Browning, M.J. Burton, R. Clarke, J. Hibbert, N.S. Jones, V.J. Lund, L.M. Luxon, J.C. Watkinson (Eds.), 7th ed., Scott-Brown’s Otorhinolaryngology, Head and Neck Surgery, vol. 5, Arnold Hodder, Birmingham, 2008, pp. 2493–2521. [17] J.J. King, G.H. Fletcher, Malignant tumors of the major salivary glands, Radiology 100 (1971) 381–384. [18] A.L. Clode, I. Fonseca, J.R. Santo, J. Soares, Mucoepidermoid carcinoma of the salivary glands. A reappraisal of the influence of tumor differentiation on prognosis, J. Surg. Oncol. 46 (1991) 100–106. [19] J.I. Yook, S.A. Lee, Y.C. Chun, J. Huh, I.H. Cha, J. Kim, The myoepithelial cell differentiation of mucoepidermoid carcinoma in a collagen gel-based coculture model, J. Oral. Pathol. Med. 33 (2004) 237–242. [20] B.T. Varghese, M.M. Jacob, J. Madhavan, M.K. Nair, Late scar recurrence in mucoepidermoid carcinoma of base of tongue, J. Laryngol. Otol. 114 (4) (2000) 299–301.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case report
Mucoepidermoid carcinoma of the tongue in a child Mosaad Abdel-Aziz 1,* Department of Otolaryngology, Faculty of Medicine, Cairo University, Egypt
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 June 2011 Received in revised form 22 July 2011 Accepted 24 July 2011 Available online 17 August 2011
Tongue base tumors are not common, they are mostly malignant and although the rarity of mucoepidermoid carcinoma of tongue base, it constitutes more than 50% of malignant lesions of salivary glands in this region. In this report, we present a 15-year old girl with mucoepidermoid carcinoma of tongue base with discussion of histopathological types of the tumor and its management. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Tongue base Mucoepidermoid carcinoma Minor salivary gland tumors Pediatric malignancy
1. Introduction Mucoepidermoid carcinoma (MEC) is a malignant, locally invasive neoplasm of the salivary glands. Its incidence rate has been reported to be 0.44 per 100,000. It is the most common malignant neoplasm of the salivary glands, especially in the parotid gland, but MEC also can occur in submandibular and minor salivary glands [1]. Minor salivary glands are scattered in different areas of the oral cavity; their tumors constitute a small proportion of all head and neck neoplasms, but are more frequently malignant [2]. Although tongue base tumors are not common, they are mostly malignant and although the rarity of MEC of tongue base, it constitutes more than 50% of malignant lesions of salivary glands in this region [3]. In this report, we present a 15-year old girl with MEC of tongue base with discussion of histopathological types of the tumor and its management.
was 5 cm 3 cm crossing the midline, it was reddish in color with irregular surface (Fig. 1). Neck examination showed no palpable lymph nodes. Computerized tomography (CT) was requested and it showed a soft tissue mass on the right side of tongue base and crossing the midline, it was infiltrating the muscles but was not involving the whole thickness of the tongue (Fig. 2). Biopsy was taken under local anesthesia, histopathological examination revealed the diagnosis of mucoepidermoid carcinoma of low grade type. As the morphological appearance of MEC share
2. Case presentation A 15-year-old girl referred to the Department of Otolaryngology of Kasr El-Aini Hospital (Cairo University) with tongue mass. The patient had complained of dysphagia, throat pain, and pain in her right ear for three months. Examination of the patient revealed an oval mass on the dorsal surface of the right side of tongue base that was seen easily when the patient protruded her tongue; the mass
* Correspondence address: 2 El-Salam St., King Faisal, Above El-Baraka Bank, Giza, Cairo, Egypt. Tel.: +20 105140161; fax: +20 225329113. E-mail address: [email protected]. 1 Study was carried out at Kasr El-Aini Hospital of Cairo University. 1871-4048/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pedex.2011.07.004
Fig. 1. The mass on the right side of tongue base.
M. Abdel-Aziz / International Journal of Pediatric Otorhinolaryngology Extra 7 (2012) 6–8
7
Fig. 4. Microscopic picture of the lesion, both element of the tumor are seen with mucus inside cystic spaces denoting the low-grade-nature (400).
Fig. 2. A CT scan showing soft tissue-mass on the right side of tongue base, the lesion is irregular and not involving the whole thickness of the tongue.
Follow-up of the patient for 3 years showed no recurrence. Informed consent was obtained from the parents to publish the case, and the work has been approved by the Institutional Ethical Committee, also the principles outlined in the Declaration of Helsinki were followed. 3. Discussion
similarities to metastatic clear cell renal adenocarcinoma and clear cell bronchogenic squamous carcinoma [4], ultrasonography of the kidneys and chest radiograph were performed to rule out metastatic carcinoma from these areas and they proved free kidneys and chest. Complete surgical excision was done under general anesthesia with nasal endotracheal intubation; a trans-oral excision was performed (Fig. 3). Post-operative antibiotic, analgesics and steroids were given to the patient for three days, the patient was informed to eat cold semisolid foods for one week and he had been discharged from hospital in the 3rd post-operative day. Histopathological examination of the specimen revealed a low grade mucoepidermoid carcinoma with negative margins (Fig. 4).
Fig. 3. The removed surgical specimen with the superficial part being covered with intact mucosa and larger irregular deep part.
Salivary gland tissues are distributed widely in the upper aerodigestive tract; the major salivary glands are the parotid, submandibular and sublingual glands, while minor salivary glands are distributed in many sites, such as the lips, cheek, palate, tongue, oropharynx, paranasal sinuses, parapharyngeal space and supraglottic larynx. Neoplasms originating from salivary glands comprise about 3–6% of all head and neck tumors, with an estimated global incidence of 0.4–13.5 per 100,000 persons annually [5,6]. Neoplasms of minor salivary gland origin occur much less commonly than those arising from major salivary glands; however, MEC is the commonest malignant tumor of major and minor salivary glands [1–3]. Malignant tumors of the intra-oral minor salivary glands constitute 2–3% of all malignant neoplasms of the upper aerodigestive tract [7]. MEC is composed histologically of epidermoid cells and mucin-producing cells, which take origin from the duct epithelial lining. The epidermoid cells proliferate in sheets or islands, and keratinizing may occur. When the epidermoid element predominates, the histological appearance of the tumor may closely resemble that of squamous cell carcinoma, and it is thus classified as a high-grade MEC tumor. Conversely, the presence of mucin-producing cells within a predominately cystic architecture is regarded as low-grade MEC tumors [2,4]. However, metastasis and tumor-related death have been noted with low-grade rather than high-grade tumors [8], in the Armed Forces Institute of Pathology series of 227 cases of MEC, 17 patients (7%) with low-grade tumors had local metastases (n = 7) or died of disease (n = 10) [9]. Dillard et al. [8] have suggested a role for transforming growth factor b1 (TGF-b1) in tumor behavior as elevated levels of TGF-b1 increase desmoplasia, angiogenesis, and tumor progression, with loss of expression of TGF-b RII (which is a receptor complex for TGF-b1) may define a transition from low- to high-grade MEC. Other factors that may affects tumor progression may be the proliferating cell nuclear antigen which may increases with the grade of malignancy [10], also, mucin expression patterns can be used as a prognostic index; membrane-bound mucins (MUC) are expressed on the cell surfaces
8
M. Abdel-Aziz / International Journal of Pediatric Otorhinolaryngology Extra 7 (2012) 6–8
of MEC. Studies have shown that the presence of MUC-1 is related to aggressive tumor, while MUC-4 represented greater cellular differentiation and better prognosis [11,12]. The treatment of the low grade MEC of the minor salivary glands involves wide local excision with adequate tumor-free margins, while high grade tumors require more aggressive surgery with or without postoperative radiotherapy and chemotherapy [13,14]. Leong et al. [2] reported MEC in a 27 year-old man that presented with severe bleeding per mouth necessitating emergency management to control bleeding and tracheostomy was performed to protect the airway. Surgical excision of the tumor was done trans-orally using CO2 laser, although there was no lymph node metastasis, the authors performed selective neck dissection on the side of the tumor as it was of high-grade type, also the patient received post-operative radiotherapy and chemotherapy. In our case, we did not need to perform neck dissection as the tumor was of low-grade type with no metastatic neck nodes. Conley and Tinsley [15] have reported that lymph node metastases occur in nearly three-quarter of patients at presentation with high grade-cancer, Jones [16] advised performance of selective neck dissection for patients with high-grade or large lesions N0 neck and radical neck dissection for patients with positive neck nodes. Although MEC is a radio-resistant tumor, post-operative irradiation is suggested by many authors in high-grade type and if the surgical margin was not free [13,14,17]. Follow up of our case for 3 years showed no recurrence. King and Fletcher [17] reported that the five-year survival rate is about 70% for low-grade tumor and a 47% survival for high-grade tumor, while other authors reported a higher rate of survival for low-grade type (96%) with death rate ten times higher in high-grade lesion [18]. However, some authors recommended follow up for life as recurrence may be delayed for years [2,19,20]. In summary, we report mucoepidermoid carcinoma of the tongue in a 15-year old girl; the tumor was of low-grade type. Less aggressive treatment in the form of local trans-oral excision was sufficient with no recurrence for 3 years follow up. Since metastasis is uncommon but not unheard of, long-term surveillance is recommended. Financial support There are no financial disclosures. Conflicts of interest There are no conflicts of interest.
References [1] J.A. Pinkston, P. Cole, Incidence rates of salivary gland tumors: results from a population-based study, Otolaryngol. Head Neck Surg. 120 (1999) 834–840. [2] S.C.L. Leong, E. Pinder, R. Sasae, S. Mortimore, Mucoepidermoid carcinoma of the tongue, Singapore Med. J. 48 (10) (2007) e272. [3] L.I. Goldblatt, G.L. Ellis, Salivary gland tumors of the tongue. Analysis of 55 new cases and review of the literature, Cancer 60 (1987) 74–81. [4] P.J. Bradley, Distant metastases from salivary glands cancer, ORL J. Otorhinolaryngol. Relat. Spec. 63 (2001) 233–242. [5] Z. Tian, L. Li1, L. Wang, Y. Hu, J. Li, Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population, Int. J. Oral Maxillofac. Surg. 39 (2010) 235–242. [6] J.G. Batsakis, Tumors of the Head and Neck: Clinical and Pathological Considerations, 2nd ed., Williams and Wilkins Co., Baltimore, 1979. [7] H. Rivera-Bastidas, R.A. Ocanto, A.M. Acevedo, Intraoral minor salivary gland tumors: a retrospective study of 62 cases in a Venezuelan population, J. Oral Pathol. Med. 25 (1) (1996) 1–4. [8] D.G. Dillard, S. Muller, C. Cohen, J.M.D. Gaudio, A.A. Gal, High tumor grade in salivary gland mucoepidermoid carcinomas and loss of expression of transforming growth factor b receptor type II, Arch. Otolaryngol. Head Neck Surg. 127 (2001) 683–686. [9] R.K. Goode, P.L. Auclair, G.L. Ellis, Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria, Cancer 82 (1998) 1217–1224. [10] W.P. Cardoso, O.V. Denardin, A. Rapoport, V.C. Araujo, M.B. Carvalho, Proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of salivary glands, Sao Paulo Med. J. 118 (2000) 69–74. [11] L. Alos, B. Lujan, M. Castillo, A. Nadal, M. Carreras, M. Caballero, C. de Bolos, A. Cardesa, Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands, Am. J. Surg. Pathol. 29 (2005) 806–813. [12] A. Handra-Luca, G. Lamas, J.C. Bertrand, P. Fouret, MUC1, MUC2, MUC4, and MUC5AC expression in salivary gland mucoepidermoid carcinoma, Am. J. Surg. Pathol. 29 (2005) 881–889. [13] P. Auclair, G. Ellis, Mucoepidermoid carcinoma, in: G.L. Ellis, P.L. Auclair, D.R. Gnepp (Eds.), Surgical Pathology of the Salivary Glands, WB Saunders Co, Philadelphia, 1991, pp. 269–298. [14] J. Hicks, C. Flaitz, Mucoepidermoid carcinoma of salivary glands in children and adolescents: assessment of proliferation markers, Oral Oncol. 36 (5) (2000) 454– 460. [15] J. Conley, P.P. Tinsley, Treatment and prognosis of mucoepidermoid carcinoma in the paediatric age group, Arch. Otolaryngol. 111 (1985) 322–324. [16] A.S. Jones, Malignant tumours of the salivary glands, in: M. Gleeson, G.G. Browning, M.J. Burton, R. Clarke, J. Hibbert, N.S. Jones, V.J. Lund, L.M. Luxon, J.C. Watkinson (Eds.), 7th ed., Scott-Brown’s Otorhinolaryngology, Head and Neck Surgery, vol. 5, Arnold Hodder, Birmingham, 2008, pp. 2493–2521. [17] J.J. King, G.H. Fletcher, Malignant tumors of the major salivary glands, Radiology 100 (1971) 381–384. [18] A.L. Clode, I. Fonseca, J.R. Santo, J. Soares, Mucoepidermoid carcinoma of the salivary glands. A reappraisal of the influence of tumor differentiation on prognosis, J. Surg. Oncol. 46 (1991) 100–106. [19] J.I. Yook, S.A. Lee, Y.C. Chun, J. Huh, I.H. Cha, J. Kim, The myoepithelial cell differentiation of mucoepidermoid carcinoma in a collagen gel-based coculture model, J. Oral. Pathol. Med. 33 (2004) 237–242. [20] B.T. Varghese, M.M. Jacob, J. Madhavan, M.K. Nair, Late scar recurrence in mucoepidermoid carcinoma of base of tongue, J. Laryngol. Otol. 114 (4) (2000) 299–301.