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Primary epithelial salivary gland tumours in children and adolescents
YIJOM-3717; No of Pages 5
Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2017.06.004, available online at http://www.sciencedirect.com
Clinical Paper Head and Neck Oncology
Primary epithelial salivary gland tumours in children and adolescents
ska-Pawelec, M. Gontarz, G. Wyszyn J. Zapaa Department of Cranio-Maxillofacial Surgery, Jagiellonian University Medical College, Rydygier Hospital, Cracow, Poland
M. Gontarz, G. Wyszy nska-Pawelec, J. Zapaa: Primary epithelial salivary gland tumours in children and adolescents. Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx– xxx. ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. Primary epithelial tumours of the salivary glands are very rare in paediatric patients. The aim of this study was to evaluate the clinical course, treatment, and outcomes of these uncommon neoplasms based on the authors’ experience and the recent literature. The medical charts of 12 female patients and seven male patients with primary epithelial salivary gland tumours were reviewed. All were under 19 years of age and underwent surgical treatment between 1994 and 2016. The results of this group of paediatric patients were compared with those of 621 adult patients. The two most common tumours in the paediatric patients were pleomorphic adenoma and mucoepidermoid carcinoma (89.4%; P = 0.004). The incidence of facial nerve palsy following surgery of the parotid tumours was similar in the two groups (P = 1.000). The most common primary cancer in the paediatric group was mucoepidermoid carcinoma (77.8%), while in the adult group, adenoid cystic carcinoma was most common (P < 0.001). The paediatric group had only lowgrade cancers in early stages (P < 0.001), with an overall 5-year survival rate of 100%. These results show that the incidence of malignant salivary gland tumours is higher in paediatric patients than in adult patients. This should be taken into account during diagnosis and therapy.
Salivary gland tumours are a heterogeneous group of neoplasms that can present diagnostic and therapeutic challenges for both the pathologist and surgeon. The incidence of all salivary gland tumours varies from 0.4 to 13.5 cases per 100,000 population, and close to 80% of these cases are benign1. Thus salivary malignancies are quite rare; they comprise only 0.3% of all malignancies and 6% of 0901-5027/000001+05
head and neck cancers in the USA1. Even rarer are malignant epithelial tumours of the salivary glands in paediatric patients, with an annual incidence of 0.8 cases per 1 million children and adolescents2. In fact, most salivary gland neoplasms occur in adults, with less than 5% developing in children and adolescents3. The distribution of benign and malignant tumours differs in adults and
Key words: salivary gland tumours; pleomorphic adenoma; mucoepidermoid carcinoma; children; adolescents. Accepted for publication 7 June 2017
children. In paediatric patients, malignant neoplasms can reach 73% of epithelial salivary gland tumours4. For this reason, knowledge regarding the pathological aspects and treatment options in this group of patients is very important. A few large series of salivary gland tumours in paediatric patients have been published in the English language literature. However, only Sultan et al. compared the results from a
ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
YIJOM-3717; No of Pages 5
2
Gontarz et al.
group of children and adolescents to a group of adult patients suffering from malignant salivary gland tumours2. This study presents 23 years of experience with primary benign and malignant salivary gland tumours in patients under 19 years of age. Additionally, a review of the recent literature was conducted in order to evaluate the clinical course, treatment, and outcomes of these rare neoplasms. Materials and methods
Between January 1994 and July 2016, 776 patients were treated for salivary gland tumours in the Department of CranioMaxillofacial Surgery of the Jagiellonian University in Cracow. The tumours were primary epithelial salivary gland neoplasms in 640 cases, 19 (2.9%) of which were diagnosed in children and adolescents. One 15-year-old girl was excluded from the study due to a secondary tumour in the parotid gland (metastasis of the mucoepidermoid carcinoma of the upper eyelid). The medical charts of the patients were evaluated according to demographic characteristics, clinical presentation, histopathological aspects, methods of treatment, recurrences, follow-up, and outcomes. Results from the group of paediatric patients were compared with those of 621 adults older than 19 years of age. This study was approved by the institutional review board. Because only medical files were obtained, the review board approved the study without the need for patient consent as long as all personal information was kept confidential and any facial features or other identifying marks were removed and/or covered. In addition to the review of medical charts, the English language literature published from January 2000 to July 2016 was reviewed to identify epidemiological data for these uncommon tumours. An analysis of the relationship between clinicopathological parameters in both groups of patients was performed for categorical variables by means of the x2 test and Fisher’s exact test for small groups. All analyses were performed using R software version 3.3.1 (R Foundation for Statistical Computing) and a P-value of <0.05 was considered statistically significant. Results
The paediatric group comprised 12 female patients and seven male patients (female to male ratio 1.7:1). The age of the patients
ranged from 8 to 18 years, with an average of 15.9 years. The mean age of patients with benign tumours was 15.6 years and of patients with malignant tumours was 16.3 years. All of the patients were of white ethnicity. Tumour size varied from 7 mm to 36 mm in diameter, with an average of 22.6 mm. The mean duration of signs and symptoms of the tumour before surgery was 14 months, ranging from 3 months to 48 months. Patient characteristics and the comparison with those of adults are presented in Table 1. Major and minor salivary gland tumours were observed almost equally in children and adolescents. When compared with the adult population, a tendency for higher involvement of the minor salivary glands was observed in the paediatric group (P = 0.078). Malignancies also occurred more frequently in the paediatric group (P = 0.165). Still, these differences were not statistically significant. The parotid gland was the most common site of origin in both groups. The incidence of facial nerve palsy following surgery of the parotid tumours was similar in the two groups (P = 1.000).
When comparing the paediatric group with the adult group, a different distribution of histological types was observed. In children and adolescents, the majority of tumours were pleomorphic adenoma and mucoepidermoid carcinoma (89.4%, P = 0.004). The most common primary epithelial tumour was pleomorphic adenoma, which comprised 52.6% (10/19) of all tumours and 100% (10/10) of benign tumours in young patients. Radical excision was performed in 70% (7/10) of patients, and three (30%) patients underwent a second operation due to inadequate surgical margins. None of the patients had local recurrence during a mean follow-up time of 43 months (Table 2). The most common site of pleomorphic adenoma was the parotid gland. A different distribution of malignant tumours was also found when comparing the two age groups of patients. The most common primary cancer in children and adolescents was mucoepidermoid carcinoma (7/9; 77.8%), whereas in adults, the most common cancer was adenoid cystic carcinoma (35.1%), followed by
Table 1. Characteristics of the paediatric patients and comparison to adults; results are presented as the number of patients (%). Characteristic
Children/adolescents
Sex Female Male
12 (63.2) 7 (36.8)
353 (56.8) 268 (43.2)
0.755
Site Major salivary gland Minor salivary gland
10 (52.6) 9 (47.4)
457 (73.6) 164 (26.4)
0.078
Tumour type Benign Malignant
10 (52.6) 9 (47.4)
436 (70.2) 185 (29.8)
0.165
Histological type Pleomorphic adenoma Warthin’s tumour Mucoepidermoid carcinoma Adenoid cystic carcinoma Others
10 (52.6) 0 (0) 7 (36.8) 0 (0) 2 (10.5)
289 (46.5) 95 (15.3) 39 (6.3) 65 (10.5) 133 (21.4)
0.004
Benign tumours Pleomorphic adenoma Others
n = 10 10 (100) 0 (0)
n = 436 289 (66.3) 147 (33.7)
0.057
Malignant tumour Mucoepidermoid carcinoma Others
n=9 7 (77.8) 2 (22.2)
n = 185 39 (21.1) 146 (78.9)
<0.001
Stage I II III IV
n=9 6 (66.7) 3 (33.3) 0 (0) 0 (0)
n = 152a 20 (13.2) 29 (19.1) 26 (17.1) 77 (50.6)
Facial nerve palsy Yes No
n=8 2 (25.0) 6 (75.0)
n = 412 91 (22.1) 321 (77.9)
a
Adults
P-value
<0.001
1.000
33 patients without stage assessment.
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
YIJOM-3717; No of Pages 5
ACC, acinic cell carcinoma; BM, buccal mucosa; Ca ex PA, carcinoma ex pleomorphic adenoma; F, female; M, male; MEC, mucoepidermoid cancer; NED, no evidence of disease; P, palate; PG, parotid gland; RR, retromolar region.
NED/48 NED/77 NED/117 NED/70 NED/15 NED/121 NED/12 NED/82 NED/27 No No No No No No No No No No No No No No No No No No Superficial parotidectomy Non-radical excision No Superficial parotidectomy Non-radical excision No Excision Radical excision No Excision Radical excision No Excision Radical excision Yes/no Excision Radical excision No Excision Non-radical excision No Excision Radical excision No Excision Non-radical excision No 12 12 8 4 4 6 36 6 10 20 15 30 23 12 7 30 8 18 MEC low grade ACC low grade Ca ex PA MEC low grade MEC low grade MEC low grade MEC low grade MEC low grade MEC low grade PG PG P BM P P P P RR 12 13 16 17 17 18 18 18 18 F F F M F F F F F
Margin Treatment Size Symptom (mm) duration (months) Histological type Case Age No. Sex (years) Site
Table 3. Summary of nine cases of malignant tumours in children and adolescents.
BM, buccal mucosa; F, female; M, male; NED, no evidence of disease; P, palate; PG, parotid gland; SLG, sublingual gland; SMG, submandibular gland.
1 2 3 4 5 6 7 8 9
Neck dissection/ Recurrence/ Follow-up/ positive nodes Adjuvant therapy time (months) time (months)
NED/13 NED/35 NED/47 NED/56 NED/25 NED/73 NED/49 NED/65 NED/38 NED/30 No No No No No No No No No No Radical excision Radical excision Radical excision Radical excision Radical excision Non-radical excision Non-radical excision Non-radical excision Radical excision Radical excision Excision Partial superficial parotidectomy Excision Total parotidectomy Partial superficial parotidectomy Partial superficial parotidectomy Superficial parotidectomy Excision Excision Superficial parotidectomy M F F M M M F F M M 1 2 3 4 5 6 7 8 9 10
8 11 14 15 18 18 18 18 18 18
P PG SLG PG PG PG PG SMG BM PG
Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic
adenoma adenoma adenoma adenoma adenoma adenoma adenoma adenoma adenoma adenoma
29 20 25 30 36 18 22 27 30 30
3 24 18 3 12 3 48 48 6 4
Margin Treatment Symptom duration (months) Size (mm) Histological type Site Age (years) Sex Case No.
Table 2. Summary of 10 cases of benign tumours in children and adolescents.
Recurrence/ time (months)
Follow-up/time (months)
Salivary gland tumours in childhood
3
mucoepidermoid carcinoma (21.1%) (P < 0.001). All mucoepidermoid carcinomas in paediatric patients were lowgrade cancers. All of the cancers in children and adolescents were treated at an early stage, which was in contrast to the adult group (P < 0.001). All patients in the paediatric group underwent surgical excision of the cancer without adjuvant therapy. One patient received elective neck dissection due to enlarged lymph nodes observed during a computed tomography scan, although metastasis was not found in the surgical specimen. Radical excision of the tumour was performed in 55.5% of patients and four patients were operated on again due to inadequate surgical margins. No locoregional recurrence or distant metastasis was observed in the paediatric group and there was an overall 5-year survival rate of 100% (Table 3). Discussion
Primary epithelial salivary gland neoplasms are rare in childhood and adolescence. A few large series showing histological type and site distributions of these tumours have been published in the recent literature (Table 4). Most of these studies present data from the Chinese population and do not include a comparison with adult patients. Similar to other research, this study included patients under 19 years of age5–7. In paediatric patients, epithelial salivary gland tumours are uncommon in children under 10 years of age. They are more common in the 10–18 years age group, and more than 70% of the tumours are benign5,7,8. In fact, in this review, there was only one child (5.3%) under 10 years of age with pleomorphic adenoma of the palate. The female to male ratio in the present study was 1.7:1, which is similar to that reported by Ribeiro et al.9, who reported a female to male ratio of 1.9:1. The current study, however, revealed a much higher disproportion in the malignant group (8:1), which was not observed in other studies. In comparing these results with those of adults, there was a higher risk of malignant tumours among female paediatric patients, although it was not significant (P = 0.081). The results of this study showed that major and minor salivary glands were affected almost equally in paediatric patients, 52.6% and 47.4%, respectively. The review of recent studies revealed that the major salivary glands, in particular the parotid, were the most common site of occurrence (63.4%, 306/483). The present study found that 42.1% of all neoplasms in
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
YIJOM-3717; No of Pages 5
0 2 0 0 0 1 1 0 4 (0.8) Total 8 (1.7) 2 5 1 4 2 10 0 3 3 13 0 21 0 11 0 1 8 (1.7) 68 (14.1) Total 76 (15.7) 5 1 3 1 13 7 0 0 7 22 1 10 8 6 7 2 44 (9.1) 49 (10.1) Total 93 (19.2) 20 5 9 32 31 21 9 22 9 25 15 73 17 10 2 6 112 (23.2) 194 (40.2) Total 306 (63.4) MSGT, minor salivary gland tumour; SMG, submandibular gland.
11 (28.9) 37 (71.2) 40 (46.5) 25 (73.5) 60 (75.9) 105 (86.1) 27 (50.9) 10 (52.6) 315 (65.2) 27 (71.1) 15 (28.8) 46 (53.5) 9 (26.5) 19 (24.1) 17 (13.9) 26 (49.1) 9 (47.4) 168 (34.8) 0.9 1.8 3.3 0.8 6.1 4.9 1.2 0.8 38 52 86 34 79 122 53 19 483 1953–1997 1975–2004 1974–1999 1966–2000 1992–2004 1987–2011 1953–1997 1994–2016 Ribeiro 9 Guzzo5 Yu8 Ellies6 Laikui10 Fang7 da Cruz Perez3 Present series Total No.
Sublingual malignant SMG benign SMG malignant MSGT benign MSGT malignant Table 4. Distribution of epithelial salivary gland tumours in children and adolescents: review of the literature. No. of Cases Number of cases (%) First author Years cases (%) per year Parotid Parotid Malignant Benign malignant benign
0 0 2 0 0 1 0 1 4 (0.8)
Gontarz et al. Sublingual benign
4
children and adolescents occurred in the parotids and 75% (6/8) were benign, which is similar to the findings of Laikui et al.10, who reported 73.5%. However, the review of the literature revealed a malignancy rate of 36.6% (112/306) in neoplasms found in the parotids in paediatric patients. The literature on the distribution of neoplasms in the minor salivary glands is limited. Summarizing multiple studies, it is concluded that minor salivary gland tumours are found to be benign or malignant at almost equal rates in paediatric patients; however, the incidence of malignant tumours ranges from 9% to 83.3%. In the current series, 77.8% (7/9) of cases involved malignant tumours, which was similar to the adult group (64%, 105/164; P = 0.496). The review of the literature also showed that 10.5% (8/76) of submandibular tumours and 50% (4/8) of sublingual tumours in paediatric patients are malignant. This is in contrast to malignancy rates reported by the World Health Organization of 41% to 45% for submandibular tumours and 70% to 90% for sublingual tumours1. The most common histological type of benign lesions, both in children/adolescents and adults, is pleomorphic adenoma. The rate of pleomorphic adenoma among benign tumours in paediatric patients varies from 63.6% to 100%5,7–10. In the current case series, no local recurrence of pleomorphic adenoma was observed; however, all patients with non-radical excision were operated on again. The local recurrence of pleomorphic adenoma varies from 9.4% to 18.2% in different studies5,7,9,10. Fang et al. suggested that relapse is more frequent in the parotid location and is due to a higher risk of rupture of the tumoural capsule during surgery7. In the current study, pleomorphic adenoma was a single histological type of benign tumour, similar to the report by Guzzo et al.5. According to the literature, the second benign tumour is myoepithelioma, followed by basal cell adenoma3,5–10. The results of the current study confirm that mucoepidermoid carcinoma is the most common primary epithelial salivary gland malignancy in paediatric patients (77.8%; P < 0.001). The incidence of mucoepidermoid carcinoma in paediatric patients ranges from 45.6% to 80.7%3,5,7–10. In comparison with the adult group, the paediatric group revealed only low-grade cancers in the early stage (P < 0.001). According to the literature, the second malignancy is acinic cell carcinoma, followed by adenoid
cystic carcinoma2,3,5,7,11,12. In the current series, the majority of malignancies were observed in the minor salivary glands (77.8%, 7/9), particularly on the palate, where 83.3% (5/6) of tumours were malignant. The treatment of choice for salivary gland tumours is surgery, both for adults and paediatric patients. For benign neoplasms, local extracapsular dissection is sufficient; however, for malignancies, local resection with adequate surgical margins is necessary. According to some authors, elective neck dissection for the clinically negative neck and low-grade cancers is unnecessary due to a low risk of occult metastasis5,9,11. Neck dissection should be indicated in patients with highgrade cancers and clinically positive neck lymph nodes10. Today, facial nerve monitoring during parotid tumour surgery is a standard of care7. In this study, all of the parotid surgeries were performed under facial nerve monitoring. In the paediatric group, facial palsy was observed in 25% of cases, which was similar to the adult group (22.1%; P = 1.000). Facial nerve weakness in paediatric patients varies in different studies from 14% to 50% and, according to some authors, is more common in children than adults5–7,13,14. Youngsters are more prone to facial nerve palsy due to higher nerve sensitivity to dissection and stretching. Additionally, the facial nerve in children is located more superficially, which leads to greater risk of injury7. Postoperative radiotherapy (PORT) in children with malignancies should be considered carefully. Post-irradiation complications can cause impaired facial growth, dental problems, trismus, and osteoradionecrosis9,11. It is also important to note that because there is a higher risk of second malignancies in the irradiated field, PORT is indicated only in highly selected cases2,5,9,11,15. Sultan et al. suggest that indications for PORT include high-grade, advanced cancers with incomplete resection, and multiple lymph node metastases2. The prognosis in primary salivary gland cancers in children and adolescents is good. The overall 5-year and 10-year survival rates in most studies range from 81.1% to 100% and 66.7% to 94%, respectively2,7,9,11. The current study noted a 100% 5-year overall survival rate with no recurrence of the disease. This favourable outcome is a result of early stage and low-grade cancers, some of which, in the cases of non-radical excision, underwent a second operation. Sultan et al. reported
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
YIJOM-3717; No of Pages 5
Salivary gland tumours in childhood risk factors associated with worse outcomes and these include male sex, lymph node involvement, advanced stage, grade III/IV, a diameter of more than 25 mm, and cancers other than mucoepidermoid carcinoma or acinic cell carcinoma2. The results of the current study show that the incidence of malignant salivary gland tumours appears to be higher in paediatric patients than in adult patients. This should be taken into account in diagnosis and therapy. Fortunately, the majority of malignancies are low-grade cancers with favourable outcomes. For this reason, surgical excision with adequate margins is necessary in the treatment planning. Neck dissection and PORT should only be considered in selected cases of high-grade cancers and lymph node involvement. Funding
2.
3.
4.
5.
None. Competing interests
None declared.
6.
Ethical approval
Approval was obtained from the Ethics Committee of Jagiellonian University (No. 122.6120.287.2016).
7.
Patient consent
Not required.
8.
References 1. Eveson JW, Auclair P, Gnepp DR, El-Naggar AK. Tumours of the salivary glands. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. Pathology and Genetics of Head and Neck Tumours, third ed., vol. 9. Lyon:
9.
IARC Press; 2005. p. 212–5. WHO/IARC classification of tumours. Sultan I, Rodriguez-Galindo C, Al-Sharabati S, Guzzo M, Casanova M, Ferrari A. Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 2011;33:1476–81. http://dx.doi.org/ 10.1002/hed.21629. da Cruz Perez DE, Pires FR, Alves FA, Almeida OP, Kowalski LP. Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 2004;68:895–902. Muenscher A, Diegel T, Jaehne M, Ussmu¨ller J, Koops S, Sanchez-Hanke M. Benign and malignant salivary gland diseases in children. A retrospective study of 549 cases from the Salivary Gland Registry, Hamburg. Auris Nasus Larynx 2009;36:326–31. http:// dx.doi.org/10.1016/j.anl.2008.07.006. Guzzo M, Ferrari A, Marcon I, Collini P, Gandola L, Pizzi N, Casanova M, Mattavelli F, Scaramellini G. Salivary gland neoplasms in children: the experience of the Istituto Nazionale Tumori of Milan. Pediatr Blood Cancer 2006;47:806–10. Ellies M, Schaffranietz F, Arglebe C, Laskawi R. Tumors of the salivary glands in childhood and adolescence. J Oral Maxillofac Surg 2006;64:1049–58. Fang QG, Shi S, Li ZN, Zhang X, Liu FY, Sun CF. Epithelial salivary gland tumors in children: a twenty-five-year experience of 122 patients. Int J Pediatr Otorhinolaryngol 2013;77:1252–4. http://dx.doi.org/10.1016/ j.ijporl.2013.04.034. Yu GY, Li ZL, Ma DQ, Zhang Y. Diagnosis and treatment of epithelial salivary gland tumours in children and adolescents. Br J Oral Maxillofac Surg 2002;40:389–92. Ribeiro Kde C, Kowalski LP, Saba LM, de Camargo B. Epithelial salivary glands neoplasms in children and adolescents: a fortyfour-year experience. Med Pediatr Oncol 2002;39:594–600.
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10. Laikui L, Hongwei L, Hongbing J, Zhixiu H. Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases. J Oral Pathol Med 2008;37:201–5. http://dx.doi. org/10.1111/j.1600-0714.2007.00618.x. 11. Aro K, Leivo I, Gre´nman R, Ma¨kitie AA. Paediatric salivary gland cancer in Finland. Int J Pediatr Otorhinolaryngol 2012;76: 1304–7. http://dx.doi.org/10.1016/j.ijporl. 2012.05.024. 12. Shapiro NL, Bhattacharyya N. Clinical characteristics and survival for major salivary gland malignancies in children. Otolaryngol Head Neck Surg 2006;134:631–4. 13. Garcia-Perla A, Mun˜oz-Ramos M, InfanteCossio P, Mayorga-Jimenez F, GutierrezPerez JL, Garcia-Perla A. Pleomorphic adenoma of the parotid in childhood. J Craniomaxillofac Surg 2002;30:242–5. 14. Ethunandan M, Ethunandan A, Macpherson D, Conroy B, Pratt C. Parotid neoplasms in children: experience of diagnosis and management in a district general hospital. Int J Oral Maxillofac Surg 2003;32:373–7. 15. Ve´drine PO, Coffinet L, Temam S, Montagne K, Lapeyre M, Oberlin O, Orbach D, Simon C, Sommelet D. Mucoepidermoid carcinoma of salivary glands in the paediatric age group: 18 clinical cases, including 11e´second malignant neoplasms. Head Neck 2006;28:827–33.
Address: Micha Gontarz Department of Cranio-Maxillofacial Surgery Jagiellonian University Medical College Rydygier Hospital 1 Zota Jesie n Street 31-826 Cracow Poland Tel.: +48 12 6468539 fax: +48 12 6468836 E-mail: [email protected]
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2017.06.004, available online at http://www.sciencedirect.com
Clinical Paper Head and Neck Oncology
Primary epithelial salivary gland tumours in children and adolescents
ska-Pawelec, M. Gontarz, G. Wyszyn J. Zapaa Department of Cranio-Maxillofacial Surgery, Jagiellonian University Medical College, Rydygier Hospital, Cracow, Poland
M. Gontarz, G. Wyszy nska-Pawelec, J. Zapaa: Primary epithelial salivary gland tumours in children and adolescents. Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx– xxx. ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. Primary epithelial tumours of the salivary glands are very rare in paediatric patients. The aim of this study was to evaluate the clinical course, treatment, and outcomes of these uncommon neoplasms based on the authors’ experience and the recent literature. The medical charts of 12 female patients and seven male patients with primary epithelial salivary gland tumours were reviewed. All were under 19 years of age and underwent surgical treatment between 1994 and 2016. The results of this group of paediatric patients were compared with those of 621 adult patients. The two most common tumours in the paediatric patients were pleomorphic adenoma and mucoepidermoid carcinoma (89.4%; P = 0.004). The incidence of facial nerve palsy following surgery of the parotid tumours was similar in the two groups (P = 1.000). The most common primary cancer in the paediatric group was mucoepidermoid carcinoma (77.8%), while in the adult group, adenoid cystic carcinoma was most common (P < 0.001). The paediatric group had only lowgrade cancers in early stages (P < 0.001), with an overall 5-year survival rate of 100%. These results show that the incidence of malignant salivary gland tumours is higher in paediatric patients than in adult patients. This should be taken into account during diagnosis and therapy.
Salivary gland tumours are a heterogeneous group of neoplasms that can present diagnostic and therapeutic challenges for both the pathologist and surgeon. The incidence of all salivary gland tumours varies from 0.4 to 13.5 cases per 100,000 population, and close to 80% of these cases are benign1. Thus salivary malignancies are quite rare; they comprise only 0.3% of all malignancies and 6% of 0901-5027/000001+05
head and neck cancers in the USA1. Even rarer are malignant epithelial tumours of the salivary glands in paediatric patients, with an annual incidence of 0.8 cases per 1 million children and adolescents2. In fact, most salivary gland neoplasms occur in adults, with less than 5% developing in children and adolescents3. The distribution of benign and malignant tumours differs in adults and
Key words: salivary gland tumours; pleomorphic adenoma; mucoepidermoid carcinoma; children; adolescents. Accepted for publication 7 June 2017
children. In paediatric patients, malignant neoplasms can reach 73% of epithelial salivary gland tumours4. For this reason, knowledge regarding the pathological aspects and treatment options in this group of patients is very important. A few large series of salivary gland tumours in paediatric patients have been published in the English language literature. However, only Sultan et al. compared the results from a
ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
YIJOM-3717; No of Pages 5
2
Gontarz et al.
group of children and adolescents to a group of adult patients suffering from malignant salivary gland tumours2. This study presents 23 years of experience with primary benign and malignant salivary gland tumours in patients under 19 years of age. Additionally, a review of the recent literature was conducted in order to evaluate the clinical course, treatment, and outcomes of these rare neoplasms. Materials and methods
Between January 1994 and July 2016, 776 patients were treated for salivary gland tumours in the Department of CranioMaxillofacial Surgery of the Jagiellonian University in Cracow. The tumours were primary epithelial salivary gland neoplasms in 640 cases, 19 (2.9%) of which were diagnosed in children and adolescents. One 15-year-old girl was excluded from the study due to a secondary tumour in the parotid gland (metastasis of the mucoepidermoid carcinoma of the upper eyelid). The medical charts of the patients were evaluated according to demographic characteristics, clinical presentation, histopathological aspects, methods of treatment, recurrences, follow-up, and outcomes. Results from the group of paediatric patients were compared with those of 621 adults older than 19 years of age. This study was approved by the institutional review board. Because only medical files were obtained, the review board approved the study without the need for patient consent as long as all personal information was kept confidential and any facial features or other identifying marks were removed and/or covered. In addition to the review of medical charts, the English language literature published from January 2000 to July 2016 was reviewed to identify epidemiological data for these uncommon tumours. An analysis of the relationship between clinicopathological parameters in both groups of patients was performed for categorical variables by means of the x2 test and Fisher’s exact test for small groups. All analyses were performed using R software version 3.3.1 (R Foundation for Statistical Computing) and a P-value of <0.05 was considered statistically significant. Results
The paediatric group comprised 12 female patients and seven male patients (female to male ratio 1.7:1). The age of the patients
ranged from 8 to 18 years, with an average of 15.9 years. The mean age of patients with benign tumours was 15.6 years and of patients with malignant tumours was 16.3 years. All of the patients were of white ethnicity. Tumour size varied from 7 mm to 36 mm in diameter, with an average of 22.6 mm. The mean duration of signs and symptoms of the tumour before surgery was 14 months, ranging from 3 months to 48 months. Patient characteristics and the comparison with those of adults are presented in Table 1. Major and minor salivary gland tumours were observed almost equally in children and adolescents. When compared with the adult population, a tendency for higher involvement of the minor salivary glands was observed in the paediatric group (P = 0.078). Malignancies also occurred more frequently in the paediatric group (P = 0.165). Still, these differences were not statistically significant. The parotid gland was the most common site of origin in both groups. The incidence of facial nerve palsy following surgery of the parotid tumours was similar in the two groups (P = 1.000).
When comparing the paediatric group with the adult group, a different distribution of histological types was observed. In children and adolescents, the majority of tumours were pleomorphic adenoma and mucoepidermoid carcinoma (89.4%, P = 0.004). The most common primary epithelial tumour was pleomorphic adenoma, which comprised 52.6% (10/19) of all tumours and 100% (10/10) of benign tumours in young patients. Radical excision was performed in 70% (7/10) of patients, and three (30%) patients underwent a second operation due to inadequate surgical margins. None of the patients had local recurrence during a mean follow-up time of 43 months (Table 2). The most common site of pleomorphic adenoma was the parotid gland. A different distribution of malignant tumours was also found when comparing the two age groups of patients. The most common primary cancer in children and adolescents was mucoepidermoid carcinoma (7/9; 77.8%), whereas in adults, the most common cancer was adenoid cystic carcinoma (35.1%), followed by
Table 1. Characteristics of the paediatric patients and comparison to adults; results are presented as the number of patients (%). Characteristic
Children/adolescents
Sex Female Male
12 (63.2) 7 (36.8)
353 (56.8) 268 (43.2)
0.755
Site Major salivary gland Minor salivary gland
10 (52.6) 9 (47.4)
457 (73.6) 164 (26.4)
0.078
Tumour type Benign Malignant
10 (52.6) 9 (47.4)
436 (70.2) 185 (29.8)
0.165
Histological type Pleomorphic adenoma Warthin’s tumour Mucoepidermoid carcinoma Adenoid cystic carcinoma Others
10 (52.6) 0 (0) 7 (36.8) 0 (0) 2 (10.5)
289 (46.5) 95 (15.3) 39 (6.3) 65 (10.5) 133 (21.4)
0.004
Benign tumours Pleomorphic adenoma Others
n = 10 10 (100) 0 (0)
n = 436 289 (66.3) 147 (33.7)
0.057
Malignant tumour Mucoepidermoid carcinoma Others
n=9 7 (77.8) 2 (22.2)
n = 185 39 (21.1) 146 (78.9)
<0.001
Stage I II III IV
n=9 6 (66.7) 3 (33.3) 0 (0) 0 (0)
n = 152a 20 (13.2) 29 (19.1) 26 (17.1) 77 (50.6)
Facial nerve palsy Yes No
n=8 2 (25.0) 6 (75.0)
n = 412 91 (22.1) 321 (77.9)
a
Adults
P-value
<0.001
1.000
33 patients without stage assessment.
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004
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ACC, acinic cell carcinoma; BM, buccal mucosa; Ca ex PA, carcinoma ex pleomorphic adenoma; F, female; M, male; MEC, mucoepidermoid cancer; NED, no evidence of disease; P, palate; PG, parotid gland; RR, retromolar region.
NED/48 NED/77 NED/117 NED/70 NED/15 NED/121 NED/12 NED/82 NED/27 No No No No No No No No No No No No No No No No No No Superficial parotidectomy Non-radical excision No Superficial parotidectomy Non-radical excision No Excision Radical excision No Excision Radical excision No Excision Radical excision Yes/no Excision Radical excision No Excision Non-radical excision No Excision Radical excision No Excision Non-radical excision No 12 12 8 4 4 6 36 6 10 20 15 30 23 12 7 30 8 18 MEC low grade ACC low grade Ca ex PA MEC low grade MEC low grade MEC low grade MEC low grade MEC low grade MEC low grade PG PG P BM P P P P RR 12 13 16 17 17 18 18 18 18 F F F M F F F F F
Margin Treatment Size Symptom (mm) duration (months) Histological type Case Age No. Sex (years) Site
Table 3. Summary of nine cases of malignant tumours in children and adolescents.
BM, buccal mucosa; F, female; M, male; NED, no evidence of disease; P, palate; PG, parotid gland; SLG, sublingual gland; SMG, submandibular gland.
1 2 3 4 5 6 7 8 9
Neck dissection/ Recurrence/ Follow-up/ positive nodes Adjuvant therapy time (months) time (months)
NED/13 NED/35 NED/47 NED/56 NED/25 NED/73 NED/49 NED/65 NED/38 NED/30 No No No No No No No No No No Radical excision Radical excision Radical excision Radical excision Radical excision Non-radical excision Non-radical excision Non-radical excision Radical excision Radical excision Excision Partial superficial parotidectomy Excision Total parotidectomy Partial superficial parotidectomy Partial superficial parotidectomy Superficial parotidectomy Excision Excision Superficial parotidectomy M F F M M M F F M M 1 2 3 4 5 6 7 8 9 10
8 11 14 15 18 18 18 18 18 18
P PG SLG PG PG PG PG SMG BM PG
Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic Pleomorphic
adenoma adenoma adenoma adenoma adenoma adenoma adenoma adenoma adenoma adenoma
29 20 25 30 36 18 22 27 30 30
3 24 18 3 12 3 48 48 6 4
Margin Treatment Symptom duration (months) Size (mm) Histological type Site Age (years) Sex Case No.
Table 2. Summary of 10 cases of benign tumours in children and adolescents.
Recurrence/ time (months)
Follow-up/time (months)
Salivary gland tumours in childhood
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mucoepidermoid carcinoma (21.1%) (P < 0.001). All mucoepidermoid carcinomas in paediatric patients were lowgrade cancers. All of the cancers in children and adolescents were treated at an early stage, which was in contrast to the adult group (P < 0.001). All patients in the paediatric group underwent surgical excision of the cancer without adjuvant therapy. One patient received elective neck dissection due to enlarged lymph nodes observed during a computed tomography scan, although metastasis was not found in the surgical specimen. Radical excision of the tumour was performed in 55.5% of patients and four patients were operated on again due to inadequate surgical margins. No locoregional recurrence or distant metastasis was observed in the paediatric group and there was an overall 5-year survival rate of 100% (Table 3). Discussion
Primary epithelial salivary gland neoplasms are rare in childhood and adolescence. A few large series showing histological type and site distributions of these tumours have been published in the recent literature (Table 4). Most of these studies present data from the Chinese population and do not include a comparison with adult patients. Similar to other research, this study included patients under 19 years of age5–7. In paediatric patients, epithelial salivary gland tumours are uncommon in children under 10 years of age. They are more common in the 10–18 years age group, and more than 70% of the tumours are benign5,7,8. In fact, in this review, there was only one child (5.3%) under 10 years of age with pleomorphic adenoma of the palate. The female to male ratio in the present study was 1.7:1, which is similar to that reported by Ribeiro et al.9, who reported a female to male ratio of 1.9:1. The current study, however, revealed a much higher disproportion in the malignant group (8:1), which was not observed in other studies. In comparing these results with those of adults, there was a higher risk of malignant tumours among female paediatric patients, although it was not significant (P = 0.081). The results of this study showed that major and minor salivary glands were affected almost equally in paediatric patients, 52.6% and 47.4%, respectively. The review of recent studies revealed that the major salivary glands, in particular the parotid, were the most common site of occurrence (63.4%, 306/483). The present study found that 42.1% of all neoplasms in
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0 2 0 0 0 1 1 0 4 (0.8) Total 8 (1.7) 2 5 1 4 2 10 0 3 3 13 0 21 0 11 0 1 8 (1.7) 68 (14.1) Total 76 (15.7) 5 1 3 1 13 7 0 0 7 22 1 10 8 6 7 2 44 (9.1) 49 (10.1) Total 93 (19.2) 20 5 9 32 31 21 9 22 9 25 15 73 17 10 2 6 112 (23.2) 194 (40.2) Total 306 (63.4) MSGT, minor salivary gland tumour; SMG, submandibular gland.
11 (28.9) 37 (71.2) 40 (46.5) 25 (73.5) 60 (75.9) 105 (86.1) 27 (50.9) 10 (52.6) 315 (65.2) 27 (71.1) 15 (28.8) 46 (53.5) 9 (26.5) 19 (24.1) 17 (13.9) 26 (49.1) 9 (47.4) 168 (34.8) 0.9 1.8 3.3 0.8 6.1 4.9 1.2 0.8 38 52 86 34 79 122 53 19 483 1953–1997 1975–2004 1974–1999 1966–2000 1992–2004 1987–2011 1953–1997 1994–2016 Ribeiro 9 Guzzo5 Yu8 Ellies6 Laikui10 Fang7 da Cruz Perez3 Present series Total No.
Sublingual malignant SMG benign SMG malignant MSGT benign MSGT malignant Table 4. Distribution of epithelial salivary gland tumours in children and adolescents: review of the literature. No. of Cases Number of cases (%) First author Years cases (%) per year Parotid Parotid Malignant Benign malignant benign
0 0 2 0 0 1 0 1 4 (0.8)
Gontarz et al. Sublingual benign
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children and adolescents occurred in the parotids and 75% (6/8) were benign, which is similar to the findings of Laikui et al.10, who reported 73.5%. However, the review of the literature revealed a malignancy rate of 36.6% (112/306) in neoplasms found in the parotids in paediatric patients. The literature on the distribution of neoplasms in the minor salivary glands is limited. Summarizing multiple studies, it is concluded that minor salivary gland tumours are found to be benign or malignant at almost equal rates in paediatric patients; however, the incidence of malignant tumours ranges from 9% to 83.3%. In the current series, 77.8% (7/9) of cases involved malignant tumours, which was similar to the adult group (64%, 105/164; P = 0.496). The review of the literature also showed that 10.5% (8/76) of submandibular tumours and 50% (4/8) of sublingual tumours in paediatric patients are malignant. This is in contrast to malignancy rates reported by the World Health Organization of 41% to 45% for submandibular tumours and 70% to 90% for sublingual tumours1. The most common histological type of benign lesions, both in children/adolescents and adults, is pleomorphic adenoma. The rate of pleomorphic adenoma among benign tumours in paediatric patients varies from 63.6% to 100%5,7–10. In the current case series, no local recurrence of pleomorphic adenoma was observed; however, all patients with non-radical excision were operated on again. The local recurrence of pleomorphic adenoma varies from 9.4% to 18.2% in different studies5,7,9,10. Fang et al. suggested that relapse is more frequent in the parotid location and is due to a higher risk of rupture of the tumoural capsule during surgery7. In the current study, pleomorphic adenoma was a single histological type of benign tumour, similar to the report by Guzzo et al.5. According to the literature, the second benign tumour is myoepithelioma, followed by basal cell adenoma3,5–10. The results of the current study confirm that mucoepidermoid carcinoma is the most common primary epithelial salivary gland malignancy in paediatric patients (77.8%; P < 0.001). The incidence of mucoepidermoid carcinoma in paediatric patients ranges from 45.6% to 80.7%3,5,7–10. In comparison with the adult group, the paediatric group revealed only low-grade cancers in the early stage (P < 0.001). According to the literature, the second malignancy is acinic cell carcinoma, followed by adenoid
cystic carcinoma2,3,5,7,11,12. In the current series, the majority of malignancies were observed in the minor salivary glands (77.8%, 7/9), particularly on the palate, where 83.3% (5/6) of tumours were malignant. The treatment of choice for salivary gland tumours is surgery, both for adults and paediatric patients. For benign neoplasms, local extracapsular dissection is sufficient; however, for malignancies, local resection with adequate surgical margins is necessary. According to some authors, elective neck dissection for the clinically negative neck and low-grade cancers is unnecessary due to a low risk of occult metastasis5,9,11. Neck dissection should be indicated in patients with highgrade cancers and clinically positive neck lymph nodes10. Today, facial nerve monitoring during parotid tumour surgery is a standard of care7. In this study, all of the parotid surgeries were performed under facial nerve monitoring. In the paediatric group, facial palsy was observed in 25% of cases, which was similar to the adult group (22.1%; P = 1.000). Facial nerve weakness in paediatric patients varies in different studies from 14% to 50% and, according to some authors, is more common in children than adults5–7,13,14. Youngsters are more prone to facial nerve palsy due to higher nerve sensitivity to dissection and stretching. Additionally, the facial nerve in children is located more superficially, which leads to greater risk of injury7. Postoperative radiotherapy (PORT) in children with malignancies should be considered carefully. Post-irradiation complications can cause impaired facial growth, dental problems, trismus, and osteoradionecrosis9,11. It is also important to note that because there is a higher risk of second malignancies in the irradiated field, PORT is indicated only in highly selected cases2,5,9,11,15. Sultan et al. suggest that indications for PORT include high-grade, advanced cancers with incomplete resection, and multiple lymph node metastases2. The prognosis in primary salivary gland cancers in children and adolescents is good. The overall 5-year and 10-year survival rates in most studies range from 81.1% to 100% and 66.7% to 94%, respectively2,7,9,11. The current study noted a 100% 5-year overall survival rate with no recurrence of the disease. This favourable outcome is a result of early stage and low-grade cancers, some of which, in the cases of non-radical excision, underwent a second operation. Sultan et al. reported
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YIJOM-3717; No of Pages 5
Salivary gland tumours in childhood risk factors associated with worse outcomes and these include male sex, lymph node involvement, advanced stage, grade III/IV, a diameter of more than 25 mm, and cancers other than mucoepidermoid carcinoma or acinic cell carcinoma2. The results of the current study show that the incidence of malignant salivary gland tumours appears to be higher in paediatric patients than in adult patients. This should be taken into account in diagnosis and therapy. Fortunately, the majority of malignancies are low-grade cancers with favourable outcomes. For this reason, surgical excision with adequate margins is necessary in the treatment planning. Neck dissection and PORT should only be considered in selected cases of high-grade cancers and lymph node involvement. Funding
2.
3.
4.
5.
None. Competing interests
None declared.
6.
Ethical approval
Approval was obtained from the Ethics Committee of Jagiellonian University (No. 122.6120.287.2016).
7.
Patient consent
Not required.
8.
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Address: Micha Gontarz Department of Cranio-Maxillofacial Surgery Jagiellonian University Medical College Rydygier Hospital 1 Zota Jesie n Street 31-826 Cracow Poland Tel.: +48 12 6468539 fax: +48 12 6468836 E-mail: [email protected]
Please cite this article in press as: Gontarz M, et al. Primary epithelial salivary gland tumours in children and adolescents, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.06.004