J Oral Maxillofac Surg 66:308-311, 2008
Juvenile Intraoral Mucoepidermoid Carcinoma Danyel Elias Cruz Perez, DDS, PhD,* Fábio Ramôa Pires, DDS, PhD,† Fábio de Abreu Alves, DDS, PhD,‡ Márcio Ajudarte Lopes, DDS, PhD,§ Oslei Paes de Almeida, DDS, PhD,¶ and Luiz Paulo Kowalski, MD, PhD储 Purpose: The purpose of this study was to assess the clinicopathologic, treatment, and outcome
features of a series of intraoral mucoepidermoid carcinomas (MECs) affecting children and adolescents. Patients and Methods: Between 1953 and 2006, from 102 intraoral MECs, 9 (8.8%) affected patients
under 18 years of age. Clinical data were retrieved from the medical records, the microscopical slides reviewed, and the tumors graded in low, intermediate, and high grades of malignancy. Results: Five cases occurred in females and 4 in males, with a mean age of 14 years. Seven cases affected the palate, and the other 2 occurred in the buccal mucosa and retromolar area. Most patients presented in initial clinical stages and all cases were surgically treated. Microscopically, 7 tumors were classified as histologically low-grade malignancies. Eight patients did not show tumor recurrence after a mean follow-up of 98.4 months (range, 4 to 278 months), and 1 patient developed local and neck recurrences and died after 15 years of initial treatment. Conclusion: Juvenile MEC are rare tumors, most occur in the palate and present as a low-grade malignancy with excellent prognosis. Although rare, MEC should be considered in the differential diagnosis of intraoral submucous nodule in young patients. © 2008 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 66:308-311, 2008
Salivary gland tumors are relatively uncommon neoplasms and only approximately 3% to 10% of the affected patients are in the first 2 decades of life.1-6 Mucoepidermoid carcinoma (MEC) is the most prevalent malignant epithelial salivary gland neoplasm among adults, as well as in children and adolescents, with predilection for the parotids and intraoral minor salivary glands.7-14 Intraoral minor salivary gland MEC in patients under 18 years of age is highly uncommon, and only isolated cases and small series have been reported in the literature.3,12,15,16 Because of the rarity of these tumors, it is difficult to ascertain their clinicopathologic and behavioral characteristics, and consequently the most effective management for better prognosis. The aim of this report is to describe the clinicopathologic, treatment, and outcome features of 9 intraoral MECs affecting children and adolescents.
*Professor, Oral Pathology, Ribeirão Preto University, Ribeirão Preto, Brazil; and the Department of Stomatology, Center of Treatment and Research AC Camargo Cancer Hospital, São Paulo, Brazil. †Professor, Oral Pathology, School of Dentistry, State University of Rio de Janeiro, Rio de Janeiro, Brazil. ‡Director, Department of Stomatology, Center of Treatment and Research, AC Camargo Cancer Hospital, São Paulo, Brazil. §Professor, Oral Semiology, School of Dentistry of Piracicaba, State University of Campinas, Piracicaba, São Paulo, Brazil. ¶Professor, Oral Pathology, School of Dentistry of Piracicaba, State University of Campinas, Piracicaba, São Paulo, Brazil. 储Director, Department of Head and Neck Surgery and Otorhinolaryngology, Center of Treatment and Research, AC Camargo Cancer Hospital, São Paulo, Brazil. Address correspondence and reprint requests to Dr Perez: Hospital do Câncer AC Camargo – Departamento de Estomatologia, Rua Professor Antônio Prudente, 211, Liberdade, CEP 01509-900 Brazil; e-mail:
[email protected]
Patients and Methods
© 2008 American Association of Oral and Maxillofacial Surgeons
During a period of 53 years, from 1953 to June 2006, 102 intraoral minor salivary gland MECs were treated at the Department of Head and Neck Surgery
0278-2391/08/6602-0017$34.00/0 doi:10.1016/j.joms.2007.04.029
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Table 1. SUMMARY OF CLINICAL, TREATMENT, AND OUTCOME DATA FROM 9 JUVENILE INTRAORAL MUCOEPIDERMOID CARCINOMAS
Case No.
Age
Gender
Complaints
1 2 3
6 16 18
F M M
4
14
F
5 6
17 17
M F
7
12
F
8
14
M
Swelling Swelling Swelling and pain Swelling and pain Swelling Swelling and bleeding Swelling and ulceration Swelling
9
12
F
Swelling
Complaints (mos)
TNM
Site
Histologic Grade
Treatment
Follow-Up (mos)/Outcome
2 2 16
T1N0M0 T2N0M0 T2N0M0
Soft palate Hard palate Hard palate
LG LG LG
WLE WLE WLE
120/NED 113/NED 278/NED
4
T4N0M0
Hard palate
LG
WLE
96/NED
2 36
T4N0M0 T2N0M0
Hard palate Soft palate
LG LG
WLE WLE
156/NED 180/DOD
1
T2N0M0
Hard palate
LG
WLE
18/NED
2
T2N0M0
IG
TXN0M0
WLE WLE WLE WLE
9/NED
4
Buccal mucosa Retromolar region
IG
7/NED
Abbreviations: LG, low grade; IG, intermediate grade; WLE, wide local excision; NED, no evidence of disease; DOD, dead of disease. Perez et al. Juvenile Intraoral Mucoepidermoid Carcinoma. J Oral Maxillofac Surg 2008.
and Otorhinolaryngology, AC Camargo Cancer Hospital, São Paulo, Brazil. Nine of these cases (8.8%) involved the intraoral minor salivary glands of patients 18 years of age or younger. Clinical data including age, gender, complaints, site, and size of the tumors, TNM staging, treatment, and outcome/follow-up were recorded from the patients’ clinical charts. Histopathologic slides stained with hematoxylin and eosin, periodic acid-Schiff, and mucicarmine were reviewed by 4 of the authors (D.E.C.P., F.R.P., M.A.L., and O.P.A.), and the tumors graded in low, intermediate, or high histologic grade in conformity with Ellis and Auclair2 and Auclair et al17 considering 5 parameters: percentage of intracystic component, necrosis, perineural invasion, anaplasia, and mitotic activity (number of mitosis in 10 high-power fields).
the primary tumor (TX). All patients were treated with wide local excision with adequate tumor-free margins. None of the patients had a previous history of other malignancies, chemotherapy and head and neck radiotherapy, or any other possible etiologic factor for salivary gland tumors. Seven tumors were histologically classified as low grade, the other 2 as intermediate-grade malignancy. Histopathologic analysis of the surgical specimens showed numerous mucin-filled macrocysts lined by mucous cells and evident areas of intermediate and epidermoid cells (Fig 1). Perineural invasion and mitotic figures were absent. Necrosis was seen in 1 case
Results Clinical data are summarized in the Table 1. Five cases occurred in females and 4 in males; the youngest was 6 years old and the mean age of the affected patients was 14 years. Period of complaint ranged from 1 to 36 months, with a mean time of 7.6 months. Seven cases affected the palate (hard palate, 5; soft palate, 2), and 1 case each to the buccal mucosa and retromolar area. All patients complained of a swelling on the area. Four patients also reported other complaints: 2 patients complained of pain (cases 3 and 4), 1 complained of bleeding (case 6), and other ulceration (case 7). TNM staging showed no evidences of regional and distant metastasis at diagnosis, and 6 cases were classified as T1 or T2 tumors, while 2 were T4, and in the final case it was not possible to evaluate
FIGURE 1. Mucin-filled macrocysts lined by mucous cells and intermediate and epidermoid cells in low-grade MEC. (Hematoxylin-eosin stain; original magnification ⫻200.) Perez et al. Juvenile Intraoral Mucoepidermoid Carcinoma. J Oral Maxillofac Surg 2008.
310 and cellular pleomorphism was present in another case in small foci. Tumor-free microscopic margins were observed in all cases. Eight patients did not show tumor recurrence after a mean follow-up of 99.6 months (range, 7 to 278 months). However, 1 patient (case 6) developed local and neck recurrences and died of disease after 15 years of initial treatment (Table 1).
Discussion MEC is uncommon in the pediatric and juvenile populations, and in this group, similarly to adults, the parotid gland is the most affected site.1,5,18-21 However, when dealing with intraoral minor salivary gland tumors in this age group, it seems that MEC has a frequency similar to pleomorphic adenoma, or it is even more common than the latter.3-5,22 Despite its prevalence, intraoral MEC in patients under 18 years of age is rare, representing, as shown by our review, 8.8% of all intraoral MECs. Most MECs of childhood are diagnosed in the second decade of life,10,18,22,23 and as in adults, there is a slight female prevalence.1,24 MEC occurs most frequently in the parotid gland, followed by the minor and submandibular salivary glands.11 However, malignancy in the pediatric group is more commonly associated with tumors arising within the intraoral minor salivary glands.1 When involving the minor salivary glands of young people, the palate is the most common affected site,3,5,15 as confirmed by our findings, although other sites, such as the tongue, lips, buccal mucosa, and retromolar area can be also involved.12 It is worthwhile to note that, although this report specifically includes young patients and swellings on the oral cavity are easily identifiable, 22.2% of the cases represented T4 tumors, reinforcing the need for close attention to oral lesions also in this age group. Intraorally, the typical clinical presentation of this malignancy is a painless, long-lasting, persistent swelling, as confirmed by our results.3,16 Clinical differential diagnosis in juvenile patients includes reactive lesions, such as mucous extravasation, mesenchymal benign tumors (such as neurofibromas and schwannomas), and other benign and malignant salivary gland tumors, specifically pleomorphic adenoma. We previously reported 5 cases of juvenile intraoral pleomorphic adenoma from the same institution and most cases were clinically very similar to our MEC cases, reinforcing the importance of clinical differential diagnosis.4 Intraoral MEC in young people frequently shows an abundant cystic component, giving the tumor a cystic fluctuant aspect. Needle aspiration can be useful in aiding in the differential diagnosis. It is interesting that pain, bleeding, and ulceration were reported in some of our cases; these signs and symp-
JUVENILE INTRAORAL MUCOEPIDERMOID CARCINOMA
toms can be useful because they are not common in benign and reactive lesions, unless secondarily inflamed and ulcerated. Treatment of intraoral MECs should include wide local excision with tumor-free surgical margins. This has been reported as an important isolated prognostic factor in these tumors.3,5,10,14,16,18,22,25 Our results confirm these observations, since 8 out of 9 patients were alive without evidences of disease after a mean follow-up of 98.4 months. Case 6 showed the worst prognosis, with local and regional recurrence, and curiously, this patient also reported bleeding as her major complaint. MEC prognosis depends on several factors, such as TNM staging, gender, invasion and fixation of the tumors to adjacent structures, and histologic grading.11,26 It has also been reported in the literature that patients under 40 years of age present a better prognosis, reinforcing the findings that juvenile patients with MEC have an overall good prognosis.11 Favorable prognosis of pediatric and juvenile MEC, as in some studies in adults, is also associated to TNM I and II clinical staging and low-grade tumors, as confirmed by our findings.11-13,17,20,26,27 Overall survival for pediatric and juvenile patients with MEC, especially from parotids, ranges from 90% to 100%, after follow-up interval ranging from 24 to 104 months.12,18-20 Caccamese and Ord3 reported on 4 cases of intraoral MEC affecting patients 18 years old and younger, and there were no local recurrences after wide local excision. Although they have an overall favorable prognosis, it is considered that about 7% and 3% of low-grade MECs show local recurrence and regional metastasis, respectively.17 In our study, the importance of histologic grade on prognosis of juvenile intraoral MEC was highlighted by the fact that even T4 lesions (cases 4 and 5) showed an excellent prognosis after wide local excision, probably because of the free-tumor margins and low grade of malignancy. On the other hand, both cases 8 and 9 were intermediate-grade tumors and, although both were submitted to wide local excision with clinical and microscopic free margins, follow-up was too short to evaluate the importance of intermediate histologic grade on prognosis in this group. Salivary gland tumors are a heterogeneous group of lesions, some of them presenting very close microscopical features, leading to difficulties in correct final diagnosis. Most juvenile MECs are low- and intermediate-grade tumors,5,12 2 variants that are easier to diagnose in comparison to high-grade lesions. These tumors usually show multicystic spaces, composed of mucous, intermediate, and epidermoid cells and ductlike structures in a fibrous connective tissue, and microscopic differential diagnosis should include cystadenomas and salivary cysts.
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No etiologic factor is usually associated with most salivary gland tumors, but Vedrine et al6 reported that 11 out of their 18 juvenile patients affected by MEC (61%) presented with a previous history of radiotherapy and/or chemotherapy for another malignant tumor, specifically leukemia and lymphoma. This would suggest the susceptibility to multiple tumors in a subset of patients or radiation-induced secondary tumors. Hicks and Flaitz12 also reported on 2 cases of juvenile MEC with a previous history of leukemia and histiocytosis. None of our patients had a previous history of malignancies or radiotherapy. Interestingly, as reported by Vedrine et al,6 the survival rate is similar in both groups of patients presenting MEC as a primary or secondary tumor. In conclusion, pediatric and juvenile intraoral MECs are rare and usually affect the palate as long-lasting asymptomatic swellings. Most tumors are low-grade lesions and overall prognosis is good after wide local excision, but close follow-up is important to rule out local recurrence and late regional and distant metastasis.
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