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Oral and maxillofacial cancer in pediatric patients: 30 years experience from a Brazilian reference center
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
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Oral and maxillofacial cancer in pediatric patients: 30 years experience from a Brazilian reference center
T
Lady Paola Aristizabal Arboledaa,∗, Iva Loureiro Hoffmannb, Izilda Aparecida Cardinallib, Karen Patricia Dominguez Gallaghera, Alan Roger Santos-Silvaa, Regina Maria Holanda de Mendonçaa,b a b
Oral Diagnosis Department, Piracicaba Dental School, University of Campinas, Brazil Boldrini Children's Center, Campinas, Brazil
A R T I C LE I N FO
A B S T R A C T
Keywords: Children Malignancies Neoplasms Oral Maxillofacial
Objective: The aim of this study is to determine the relative frequency, demographic distribution and clinicopathological features of pediatric oral and maxillofacial cancer (POMC). Methods: Medical records were retrospectively reviewed for all cancer cases diagnosed from 1986 to 2016 affecting patients aged 19 years and younger. Demographic variables, anatomical site, and histopathological diagnoses were collected and analyzed by descriptive statistics. Results: Fifty-five (0.77%) POMCs were found among 7181 pediatric malignancies. Mean age at diagnosis was 8 years and patients aged 5–9 years presented the higher prevalence of malignant tumors (40%). White male patients were more frequently affected (78.18% and 65.45%, respectively). The most common cancer type was lymphomas (52.73%) followed by sarcomas (27.27%) and carcinomas (20%). Burkitt lymphoma (32.73%), rhabdomyosarcoma (14.55%), diffuse large B-cell lymphoma (9.09%), and mucoepidermoid carcinoma (9.09%) were the most common histopathological diagnoses. The main affected anatomical site was the oropharynx (38.18%), followed by salivary glands (30.91%), maxillofacial bone (20%), and oral cavity (10.91%). Conclusion: POMC has a low incidence; however, highly aggressive tumors, such as lymphomas and sarcomas, are common in this scenario. A better knowledge about the clinicopathological distribution of POMC may contribute to early diagnosis and improve survival rates.
1. Introduction Childhood cancer continues to be a public health problem due to the high global incidence rates (385,509 cases per year in patients aged 0–19 years), and they have increased since the 1980s (124.0–140.6 per million person-years) [1]. In Brazil, it is estimated that in the 2018–2019 biennium about 12,000 new cases of cancer will occur among pediatric patients [2]. Leukemia (18–41%), lymphoma (13–24%), and central nervous system tumors (7–17%) remain the most prevalent types of pediatric cancer in developing countries [3]; however, focusing on specific anatomical regions such as the head and neck, the percentage of malignant tumors is relatively low (5%) [4]. Additionally, the occurrence of oral and maxillofacial cancer (OMC) is uncommon in pediatric populations, ranging from approximately 0.5 to 6% [5–8]. The literature has given greater emphasis to OMC in adult patients
because, unlike pediatrics, oral carcinomas represent a significant proportion in adults, being an important cause of mortality. In addition, specific risk factors, such as alcohol, tobacco, and human papillomavirus infection, play a key role in the etiology [9]. In this sense, pediatric oral and maxillofacial cancer (POMC) represents a wide histopathological variety, whose etiology remains unknown and the identification of risk factors becomes essential. Although the majority of oral and maxillofacial lesions in pediatric patients are of an inflammatory or benign origin, it should be recognized that highly aggressive malignant tumors can be found in daily clinical practice [10–15]. Previous literature has shown that the most common types of POMC are: Burkitt lymphoma (BL), rhabdomyosarcoma (RMS), mucoepidermoid carcinoma (MEC), and osteosarcoma (OS) [7,10,12,13]. Few international studies have performed a clinicopathological distribution of POMC. Asian and African countries have more studies in this context when compared to other continents [7,8,10–16]. In Latin
∗ Corresponding author. Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, 901. Areão, Piracicaba, São Paulo, 13414- 903, Brazil. E-mail address: [email protected], [email protected] (L.P.A. Arboleda).
https://doi.org/10.1016/j.ijporl.2020.109879 Received 13 August 2019; Received in revised form 6 December 2019; Accepted 8 January 2020 Available online 10 January 2020 0165-5876/ © 2020 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
L.P.A. Arboleda, et al.
Fig. 1. Main pediatric oral and maxillofacial cancer per age group.
Microsoft Office Excel 2013 software (Microsoft Corporation, Redmond, Washington, USA) and further analyzed by descriptive statistics by using absolute numbers, percentages, mean values and standard deviations.
America, there are only a few Brazilian studies that have been published on POMC [17]; however, the majority of these studies consider benign, malignant and reactive lesions [18,19]. Despite the existing studies, there is a lack of POMC research worldwide; therefore, there is a need for more international studies in this area, as the knowledge of its frequency and distribution may help the clinician with early diagnosis. This study aimed to determine the relative frequency and clinicopathological features of POMC from a tertiary referral center in Brazil.
3. Results During a 30-year period, for all childhood cancer diagnosed at Boldrini Children's Center (7,181), 367 (5.11%) malignancies corresponded to head and neck topography, of which 55 (0.77%) were located in the oral and maxillofacial region. The mean age at diagnosis was 8 years old ± 4.63 years. OMC cases were most frequently diagnosed among patients between 5 and 9 years old (22 [40%]), followed by patients aged 10–14 years old (14 [25.45%]); 1–4 years old (12 [21.82%]); 15–19 years old (5 [9.09%]), and younger than 1 year (2 [3.64%]). Fig. 1 shows the most common OMC per age group. BL was the tumor found in all age groups, with the exception of patients under 1 year. Analysis by gender showed that 36 (65.45%) patients were male and 19 (34.55%) were female. In terms of race, 43 (78.18%) were white, 11 (20%) were ‘other races,’ and 1 (1.82%) was black. Table 1 gives the frequency rates and percentage of all POMCs according to gender, mean age, and age group affected. Lymphoma was the most common type of OMC, followed by sarcomas, and carcinomas. BL, RMS, MEC, and diffuse large B-cell lymphoma (DLBCL), were the most common histopathological diagnoses. Following the ICD-O-3 codes, the oropharynx was the leading site category followed by major salivary glands, and maxillofacial bones. Table 2 shows the histopathological OMC distribution per anatomical topography in pediatric patients.
2. Material and methods This study was approved by the ethics committee of the Boldrini Center (protocol number 1.947.295). The medical records of the Boldrini Children's Center, Campinas, São Paulo, Brazil, were reviewed for all primary oral and maxillofacial malignant tumors diagnosed in pediatric patients from January 1986 to December 2016. The demographic variables (age, gender and race), anatomical location of tumors, and histopathological diagnosis were collected. The cut-off age of 19 was used following the definition of childhood provided by the World Health Organization (WHO) [20], and then categorized into five groups: < 1 year; 1–4 years; 5–9 years; 10–14 years; and 15–19 years [4]. In addition, patient's race was classified as white, black and other. All tumors were grouped and classified according to specific localization in the oral and maxillofacial area based on the international classification of diseases for oncology ICD-O-3: oral cavity (external upper lip C00.0; buccal mucosa, C06.0; palate, C05); oropharynx (base of tongue, C01; tonsil, C09); salivary glands (parotid gland, C07; submandibular gland, C08.0; sublingual gland, C08.1; major salivary gland, NOS, C08.9; minor salivary gland, C06.9); maxillofacial bones (mandible, C41.1; maxilla, C40.0) [21]. Inclusion criteria included primary solid tumors in the oral and maxillofacial region diagnosed in patients 19 years old and younger presenting complete medical records with confirmed histopathological diagnoses. Benign tumors, malignant tumors diagnosed outside the oral and maxillofacial region, tumors diagnosed in patients older than 19 years old, patients with incomplete medical records, second primary tumors, and metastases affecting the oral and maxillofacial region were excluded from the analyses. Data were collected in a datasheet, systematically organized in
4. Discussion Boldrini Children's Center is considered a tertiary referral center in pediatric oncology in Brazil, where a large number of childhood cancer cases are diagnosed and treated; nevertheless, in the 30-year period investigated, only 0.77% corresponded to POMC. Although some studies have shown the low prevalence of OMC in this population; most of them performed comparisons with benign lesions or included all age groups [6,10,15,17]; thus, our study shows a more accurate percentage of OMC, because it was focused only on malignant tumors affecting 2
3
NOS: no other specification.
55
TOTAL
a
29 25 18 5 1 1 4 3 1 15 8 1 3 1 1 1 11 11 5 2 1 1 1 1
(100.00)
(52.73) (45.45) (32.73) (9.09) (1.82) (1.82) (7.27) (5.45) (1.82) (27.27) (14.55) (1.82) (5.45) (1.82) (1.82) (1.82) (20.00) (20.00) (9.09) (3.64) (1.82) (1.82) (1.82) (1.82) 36
21 17 14 2 – 1 4 3 1 10 6 1 2 – – 1 5 5 2 – 1 1 – 1
No.
No.
(%)
Male
Total
Lymphomas Non-Hodgkin lymphoma Burkitt lymphoma Diffuse large B-cell lymphoma Lymphoblastic lymphoma Anaplastic large-cell lymphoma Hodgkin lymphoma Nodular sclerosis Nodular lymphocyte predominant Sarcomas Rhabdomyosarcoma Infantile myofibrosarcoma Ewing sarcoma Osteosarcoma Undifferentiated sarcoma Sarcoma, NOSa Carcinomas Salivary gland carcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Sebaceous adenocarcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Adenocarcinoma, NOS
Histologic Types
(65.45)
(38.18) (30.91) (25.45) (3.64) – (1.82) (7.27) (5.45) (1.82) (18.18) (10.91) (1.82) (3.64) – – (1.82) (9.09) (9.09) (3.64) – (1.82) (1.82) – (1.82)
(%)
19
8 8 4 3 1 – – – – 5 2 – 1 1 1 – 6 6 3 2 – – 1 –
No.
Female
(34.55)
(14.55) (14.55) (7.27) (5.45) (1.82) – – – – (9.09) (3.64) – (1.82) (1.82) (1.82) – (10.91) (10.91) (5.45) (3.64) – – (1.82) –
(%)
8
8 7.96 7.66 10 – – 8.25 7.66 – 6.71 5.75 – 15 – – – 8.81 8.81 12 10 – – – –
Mean age
4.63
4.33 4.58 4.48 5.56 – – 2.87 3.21 – 4.73 3.73 – 1.73 – – – 4.75 4.75 3.8 1.41 – – – –
Standard deviation
Table 1 Histopathological distribution of OMC according to gender, mean age, and age group in pediatric patients.
2
– – – – – – – – 1 – – – – 1 – 1 – – – – 1 – –
No.
<1 Y
(3.64)
– – – – – – – – (1.82) – – – – (1.82) – (1.82) – – – – (1.82) – –
(%)
Age group
12
7 6 5 – 1 – 1 1 – 4 3 1 – – – – 1 – – – – – – 1
No.
1–4 Y
(21.82)
(12.73) (10.91) (9.09) – (1.82) – (1.82) (1.82) – (7.27) (5.45) (1.82) – – – – (1.82) – – – – – – (1.82)
(%)
22
12 11 7 3 – 1 1 1 – 5 4 – – – – 1 5 – 2 1 1 – 1 –
No.
5−9 Y
(40.00)
(21.82) (20.00) (12.73) (5.45) – (1.82) (1.82) (1.82) – (9.09) (7.27) – – – – (1.82) (9.09) – (3.64) (1.82) (1.82) – (1.82) –
(%)
14
8 6 5 1 – – 2 1 1 4 1 – 2 1 – – 2 – 1 1 – – – –
No.
(25.45)
(14.55) (10.91) (9.09) (1.82) – – (3.64) (1.82) (1.82) (7.27) (1.82) – (3.64) (1.82) – – (3.64) – (1.82) (1.82) – – – –
(%)
10−14 Y
5
2 2 1 1 – – – – – 1 – – 1 – – – 2 – 2 – – – – –
No.
(9.09)
(3.64) (3.64) (1.82) (1.82) – – – – – (1.82) – – (1.82) – – – (3.64) – (3.64) – – – – –
(%)
15−19 Y
L.P.A. Arboleda, et al.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
L.P.A. Arboleda, et al.
Table 2 Histopathological pediatric oral and maxillofacial cancer distribution per anatomical topography based on the international classification of diseases for oncology ICD-O-3. Tumor Type
Total
Anatomical topography Oropharynx
Lymphomas Burkitt lymphoma Diffuse large B-cell lymphoma Lymphoblastic lymphoma Anaplastic large-cell lymphoma Nodular sclerosing Nodular lymphocyte predominant Sarcomas Rhabdomyosarcoma Infantile myofibrosarcoma Ewing sarcoma Osteosarcoma Undifferentiated sarcoma Sarcoma NOS Carcinomas Salivary gland carcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Sebaceous adenocarcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Adenocarcinoma. NOS TOTAL
Salivary glands
Odontogenic and maxillofacial bone
Oral cavity
C09
C01
C07
C08.0
C08.1
C06.9
C08.9
C41.1
C40.0
C06.0
C05
C00.0
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
29 18 5
11 (20.00) 4 (7.27)
-
1 (1.82) –
– –
– –
– –
– –
2 (3.64) –
3 (5.45) –
1 (1.82) –
– 1 (1.82)
– –
1 1
– –
–
1 (1.82) –
– –
– –
– –
– –
– –
– –
– 1 (1.82)
– –
– –
3 1
3 (5.45) 1 (1.82)
– –
– –
– –
– –
– –
– –
– –
– –
– –
– –
– –
15 8 1 3 1 1 1 11 11 5
– – – – – – – –
1 (1.82) – – – – 1 (1.82) – –
2 (3.64) – 1 (1.82) – – – – – 3 (5.45)
– – – – – – – – –
1 (1.82) – – – – – – – –
– – – – – – – – 2 (3.64)
– – – – – – – – –
2 1 2 1 – – – – –
– – – – – – – – – –
1 (1.82) – – – – – – – –
– – – – – 1 (1.82) – – – –
1 (1.82) – – – – – – – –
2 1 1 1
– – – –
– – – –
1 (1.82) 1 (1.82) 1 (1.82) –
1 (1.82) – – 1 (1.82)
– – – –
– – – –
– – – -
– – – –
– – – –
– – – –
– – – –
– – – –
1
–
–
–
–
–
–
1 (1.82)
–
–
–
–
–
55
19 (34.55)
2 (3.64)
11 (20.00)
2 (3.64)
1 (1.82)
2 (3.64)
1 (1.82)
8 (14.55)
3 (5.45)
3 (5.45)
2 (3.64)
1 (1.82)
21 (38.18)
17 (30.91)
(3.64) (1.82) (3.64) (1.82)
11 (20.00)
6 (10.91)
patients between the ages of 0 and 4 [13], 6 and 10 [8], and patients over the age of 10 [16]. The predominance in these age groups may be due to the high incidence of BL and RMS in the oral and maxillofacial region [13]. We found a homogeneous distribution of BL among the age groups of 1–4 years, 5–9 years, and 10–14 years; however, the highest percentage was found in patients between 5 and 9 years old (12.73%). RMS were most common in the ages groups of 1–4 years and 5–9 years, and bone sarcomas such as Ewing sarcoma (EWS) and OS were more frequently observed in patients over the age of 10. This agrees with reports in the literature [13,16]. Patients aged 15–19 years are most affected by tumors such as carcinomas and bone sarcomas; thus, in agreement with previous reports, our study showed a high frequency of salivary gland carcinomas, specifically MEC [12,13,16,17,19]. Male patients were more affected by POMC than females (65.45% vs. 34.55%, respectively); these results are in accordance with previous reports in the literature [8,10,13,16]. This result may be due to the high prevalence of non-Hodgkin's lymphoma (NHL), which is more common in male patients. However, one study showed an equal sex predilection among BL [13]. Lymphoma was the leading type of tumor in the present study (52.73%), and this was also reported in eight studies from Asia and Africa [7,8,10,12–16]. Interestingly, three Brazilian studies showed predominance for sarcomas [17–19], and our study was the only one that showed lymphomas as the main type of POMC in Brazil. This may be because lymphoma is the second most common type of childhood cancer in Brazilian patients [22], and our study was conducted in a tertiary referral center, where a large number of patients are referred
pediatric patients. The frequency of OMC among pediatric patients ranged from 0.53% to 13.3% [5–8,10–19]. Despite the low prevalence of POMC worldwide, there are clear differences between countries. Table 3 summarizes previous OMC publications in pediatric patients, showing data on OMC frequency, main types of OMC and their principal anatomical sites. The frequency percentages in African studies varied widely due to their methodology of comparison with benign tumors; however, the frequency of lymphoma, specifically BL remains high in Nigeria [8,10,16]. Five Asian studies showed percentages ranging from 2.9% to 10%, none of them distinguishing a difference between benign and malignant lesions located in this anatomical site [11–15]. However, Levi et al. [7] reported a prevalence of 2.6% POMC of all OMC seen in all age groups. Australia [5], UK [6], and Brazil [17,19], showed a frequency of POMC lower than 1%, which are similar results to our findings. The present study was composed of children from 0 to 19 years old, and the mean age at the time of OMC diagnosis was 8 years; this is similar to an Australian study [5], while other reports found mean ages ranging from 10 to 12 years old [7,10,16]. Because some studies analyzed did not focus merely on malignant tumors, they generalized demographic outcomes such as gender, age and average age with benign lesions in the oral and maxillofacial region of pediatric patients [6,8,11–15,17–19]. This generated a difficulty in interpreting the results between studies. Due to the need to standardize the age groups, the present study classified patients into five groups [4]; thus, patients between 5 and 9 years old were identified as being more affected by OMC (40%). This result differs from other studies, in which OMC was more common in 4
< 18 years < 19 years
– 1942–2017
19
5
1991–2007 1970–2011 1965–1992
1976–1997
Libya13 Israel7 Japan15
Japan14
< 15 years
< 19 years < 19 years < 15 years
< 16 years < 19 years < 16 years
< 16 years
3
8 357 18
31 26 11
9
3 27
58
74 65
47
55
Sample
(2.9%)
(3.7%) (2.6%) (7.0%)
(0.70%) (10%) (2.91%)
(0.68%)
(0.53%) (1.12%)
(0.61%)
(51%) (6.41%)
(13.3%)
(0.77%)
%*
C (29%), S (25.8%), L (6.5%) S (58%), C (42%) L (45.4%), S (36.3%), C (18.1%) L (50%), S (40%), C (10%) L (20.7%), C (19.9%) L (50%), S (27.7%), C (16.6%) L (33.3%), S (33.3%), C (33.3%)
L (52.7%), S (27.2%), C (20%) L (53.2%), S (36.2%), C (10.6%) L (90%), S (7%), C (3%) L (78.5%), S (10.8%), C (7.7%) S (34.5%), C (32.5%), L (12.1%) S (75%), C (25%) S (40.7%), L (25.9%), C (14.8%) –
Tumor type
malignant lymphoma, malignant mesenchymal tumor, acinic cell carcinoma
BL, RMS, MEC, OS. BL, MEC, SCC, RMS. L, fibrosarcoma, MEC.
Langerhans cell histiocytosis, malignant tumor unspecified, undifferentiated carcinoma. Langerhans cell histiocytosis, MEC, neurosarcoma, RMS. NHL, RMS, basal cell carcinoma BL, OS, MEC, RMS, PNET.
MEC, OS, malignant peripheral nerve sheath tumor. BL, RMS, OS, DLBCL
MEC, OS, SCC, BL.
BL, RMS. BL, NHL, RMS, SCC, MEC.
NHL, RMS, OS.
BL, RMS,DLBCL,MEC
Most prevalent tumor subtype
mandible, maxilla: 3, palate – mandible, buccal mucosa, maxilla
– face, postnasal space, mandible. –
–
– –
palate, mandible, maxilla
maxilla, mandible, cheek, palate maxilla, mandible, soft tissue.
oropharynx, salivary glands, maxillofacial bone, oral cavity maxilla/maxillary antrum, mandible
Anatomical site
%* the percentage is according with the different methodologies of each study. Abbreviations: L: lymphomas; S, sarcomas; C, carcinomas; NHL, non-Hodgkin lymphoma; RMS, rhabdomyosarcoma; OS, osteosarcoma; BL, Burkitt lymphoma; MEC, mucoepidermoid carcinoma; PNET, primitive neuroectodermal tumor.
1973–2002 1991–2000 1990–2004
UK Jordan11 Thailand12
6
Australia5
Brazil Brazil18
1945–2003
< 19 years
1990–2016
Brazil17
< 19 years < 16 years
1991–2001 1990–2010
Nigeria10 Nigeria8
Nigeria
< 19 years
< 19 years
1992–2003
1986–2016
Current study
Age limited
16
Period of study (years)
Country
Table 3 Previous studies on pediatric oral and maxillofacial cancer.
L.P.A. Arboleda, et al.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
L.P.A. Arboleda, et al.
Acknowledgement
for diagnosis and treatment. Sarcomas remain a prevalent group in the head and neck region of pediatric patients. We observed that in nine series, including the present study, sarcomas ranked as the second most common POMC [6,8,10,12–16]. In disagreement with our study, sarcomas were the leading POMC type in four previous reports [11,17–19]. Oral and maxillofacial carcinomas in pediatric patients are less frequently diagnosed when compared to adult patients [9]. However, the present study demonstrated 20% of these tumors, which is similar to reports in the literature (Table 3). A single study from a UK study reported carcinomas such as the most common type of tumor [6]. BL, RMS, MEC, and DLBCL were the most common POMC diagnoses in the present study, which is consistent with previous literature. Also present in other reports were tumors such as OS, squamous cell carcinoma (SCC), basal cell carcinoma, and EWS [7,13,16,18]. Extranodal NHLs are common in the oral cavity and maxillofacial region, mainly affecting the salivary glands [23]. On the contrary, we found that the oropharynx was the main anatomical site involved (38.18%), mainly affected by NHL. Likewise, Levi et al. (2017) showed 43.4% of BL located in the tonsils [7]. Salivary glands represented the second anatomical site affected by OMC, and MEC was the most prevalent tumor. However, there was a wide variety of histopathological types of tumors, such as acinic cell carcinoma, sebaceous adenocarcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Cesmebasi et al. (2014) studied a large number of pediatric cases of head and neck cancer, where salivary gland carcinomas were the most commonly seen tumors among pediatric patients [24]. Although for some studies the maxillofacial region is the main anatomical site of OMC, affecting most commonly the maxilla [8,16], we found a predominance of tumors in the mandible, such as RMS, BL and OS. The oral cavity was the least affected anatomical site in the present study. In addition to several studies agreeing with this result [10,13,16], we also observed that the oral cavity was only affected by tumors such as BL, DLBCL, anaplastic large cell lymphoma, RMS, and undifferentiated sarcoma. These results demonstrate that oral cavity carcinomas are rarely diagnosed in pediatric patients. The possible risk factors for some histopathological subtypes of POMC such as BL may be associated with the presence of the EpsteinBarr virus, often found in developing countries. However, there is evidence that the virus needs genetic and environmental support factors for tumor development [23,24]. Although the Boldrini Children's Center is known as a reference institution in Brazil, it is necessary to have a quality national cancer registry to obtain accurate epidemiological data. In addition, the ICD-O is fundamental for studies that analyze specific anatomical regions. In the present study, the interpretation of some medical records was difficult due to the retrospective character of the investigation, and occasionally analysis of the primary site was challenging when the tumor affected more than one anatomical region. Our study presents relevant data on the frequency and distribution of POMC and shows the need for more worldwide studies, especially in Latin America, as the scarcity of studies in this specific area inhibits our ability to determine the most frequent histological types and consequently their possible risk factors.
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Akpata, Paediatric orofacial tumours: new oral health concern in paediatric patients, Ghana Med. J. 1 (2014) 14–19. [9] A.A. Hussein, M.N. Helder, J.G. de Visscher, C.R. Leemans, B.J. Braakhuis, H.C.W. de Vet, T. Forouzanfar, Global incidence of oral and oropharynx cancer in patients younger than 45 years versus older patients: a systematic review, Eur. J. Cancer 82 (2017) 115–127, https://doi.org/10.1016/j.ejca.2017.05.026. [10] S.B. Aregbesola, V.I. Ugboko, J.A. Akinwande, G.F. Arole, O.O. Fagade, Orofacial tumours in suburban Nigerian children and adolescents, Br. J. Oral Maxillofac. Surg. 3 (2005) 226–231, https://doi.org/10.1016/j.bjoms.2004.11.006. [11] T. Al-Khateeb, A. Al-Hadi Hamasha, N.M. Almasri, Oral and maxillofacial tumours in north Jordanian children and adolescents: a retrospective analysis over 10 years, Int. J. Oral Maxillofac. Surg. 1 (2003) 78–83. [12] K. Dhanuthai, M. Banrai, S. Limpanaputtajak, A retrospective study of paediatric oral lesions from Thailand, Int. J. Paediatr. Dent. 4 (2007) 248–253, https://doi. org/10.1111/j.1365-263X.2007.00828.x. [13] M. Elarbi, R. El-Gehani, K. Subhashraj, M. Orafi, Orofacial tumors in Libyan children and adolescents. A descriptive study of 213 cases, Int. J. Pediatr. Otorhinolaryngol. 2 (2009) 237–242, https://doi.org/10.1016/j.ijporl.2008.10. 013. [14] N. Tanaka, A. Murata, A. Yamaguchi, G. Kohama, Clinical features and management of oral and maxillofacial tumors in children, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1 (1999) 11–15. [15] M. Sato, N.T. anaka, T. Sato, T. Amagasa, Oral and maxillofacial tumours in children: a review, Br. J. Oral Maxillofac. Surg. 2 (1997) 92–95. [16] O.F. Ajayi, W.L. Adeyemo, A.L. Ladeinde, et al., Malignant orofacial neoplasms in children and adolescents: a clinicopathologic review of cases in a Nigerian tertiary hospital, Int. J. Pediatr. Otorhinolaryngol. 71 (2007) 959–963, https://doi.org/10. 1016/j.ijporl.2007.03.008. [17] J.A.A. de Arruda, L.V.O. Silva, C.N.A.O. Kato, L.F. Schuch, A.C. Batista, N.L. Costa, S.B.C. Tarquinio, E.R.C. Rivero, V.C. Carrard, M.D. Martins, A.P.V. Sobral, R.A. Mesquita, A multicenter study of malignant oral and maxillofacial lesions in children and adolescents, Oral Oncol. 75 (2017) 39–45, https://doi.org/10.1016/j. oraloncology.2017.10.016. [18] M.L. Prosdócimo, M. Agostini, M.J. Romañach, B.A. de Andrade, A retrospective analysis of oral and maxillofacial pathology in a pediatric population from Rio de Janeiro-Brazil over a 75-year period, Med. Oral Patol. Oral Cir. Bucal 5 (2018) e511–e517, https://doi.org/10.4317/medoral.22428. [19] P.R. Martins-Filho, T. de Santana Santos, M.R. Piva, H.F. da Silva, L.C. da Silva, A.C. Mascarenhas-Oliveira, E.S. de Souza Andrade, A multicenter retrospective cohort study on pediatric oral lesions, J Dent Child (Chic). 82 (2) (2015) 84–90. [20] S. Diane, F. Sheri, G. Eudice, et al., Age limits and adolescents, Paediatr. Child Health 8 (2003) 577. [21] A. Fritz, C. Percy, A. Jack, K. Shanmugaratnam, L. Sobin, D. Parkin, S. Whelan (Eds.), International Classification of Diseases for Oncology, 3rd Ed. ICD-O-3, World Health Organization, 2013. [22] B. de Camargo, S.M. de Oliveira, M.S. Rebelo, et al., Cancer incidence among children and adolescents in Brazil: first report of 14 population-based cancer registries, Int. J. Cancer 126 (2010) 715–720. [23] K. Triantafillidou, J. Dimitrakopoulos, F. Iordanidis, A. Gkagkalis, Extranodal nonHodgkin lymphomas of the oral cavity and maxillofacial region: a clinical study of 58 cases and review of the literature, J Oral Maxillofac Surg. Dec 70 (12) (2012) 2776–2785, https://doi.org/10.1016/j.joms.2012.01.018. [24] A. Cesmebasi, A. Gabriel, D. Niku, et al., Pediatric head and neck tumors: an intrademographic analysis using the SEER* database, Med. Sci. Monit. 20 (2014) 2536−–2542, https://doi.org/10.12659/MSM.891052.
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest The authors declared no conflict of interest with respect to this research, authorship, and/or publication of this article. 6
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Oral and maxillofacial cancer in pediatric patients: 30 years experience from a Brazilian reference center
T
Lady Paola Aristizabal Arboledaa,∗, Iva Loureiro Hoffmannb, Izilda Aparecida Cardinallib, Karen Patricia Dominguez Gallaghera, Alan Roger Santos-Silvaa, Regina Maria Holanda de Mendonçaa,b a b
Oral Diagnosis Department, Piracicaba Dental School, University of Campinas, Brazil Boldrini Children's Center, Campinas, Brazil
A R T I C LE I N FO
A B S T R A C T
Keywords: Children Malignancies Neoplasms Oral Maxillofacial
Objective: The aim of this study is to determine the relative frequency, demographic distribution and clinicopathological features of pediatric oral and maxillofacial cancer (POMC). Methods: Medical records were retrospectively reviewed for all cancer cases diagnosed from 1986 to 2016 affecting patients aged 19 years and younger. Demographic variables, anatomical site, and histopathological diagnoses were collected and analyzed by descriptive statistics. Results: Fifty-five (0.77%) POMCs were found among 7181 pediatric malignancies. Mean age at diagnosis was 8 years and patients aged 5–9 years presented the higher prevalence of malignant tumors (40%). White male patients were more frequently affected (78.18% and 65.45%, respectively). The most common cancer type was lymphomas (52.73%) followed by sarcomas (27.27%) and carcinomas (20%). Burkitt lymphoma (32.73%), rhabdomyosarcoma (14.55%), diffuse large B-cell lymphoma (9.09%), and mucoepidermoid carcinoma (9.09%) were the most common histopathological diagnoses. The main affected anatomical site was the oropharynx (38.18%), followed by salivary glands (30.91%), maxillofacial bone (20%), and oral cavity (10.91%). Conclusion: POMC has a low incidence; however, highly aggressive tumors, such as lymphomas and sarcomas, are common in this scenario. A better knowledge about the clinicopathological distribution of POMC may contribute to early diagnosis and improve survival rates.
1. Introduction Childhood cancer continues to be a public health problem due to the high global incidence rates (385,509 cases per year in patients aged 0–19 years), and they have increased since the 1980s (124.0–140.6 per million person-years) [1]. In Brazil, it is estimated that in the 2018–2019 biennium about 12,000 new cases of cancer will occur among pediatric patients [2]. Leukemia (18–41%), lymphoma (13–24%), and central nervous system tumors (7–17%) remain the most prevalent types of pediatric cancer in developing countries [3]; however, focusing on specific anatomical regions such as the head and neck, the percentage of malignant tumors is relatively low (5%) [4]. Additionally, the occurrence of oral and maxillofacial cancer (OMC) is uncommon in pediatric populations, ranging from approximately 0.5 to 6% [5–8]. The literature has given greater emphasis to OMC in adult patients
because, unlike pediatrics, oral carcinomas represent a significant proportion in adults, being an important cause of mortality. In addition, specific risk factors, such as alcohol, tobacco, and human papillomavirus infection, play a key role in the etiology [9]. In this sense, pediatric oral and maxillofacial cancer (POMC) represents a wide histopathological variety, whose etiology remains unknown and the identification of risk factors becomes essential. Although the majority of oral and maxillofacial lesions in pediatric patients are of an inflammatory or benign origin, it should be recognized that highly aggressive malignant tumors can be found in daily clinical practice [10–15]. Previous literature has shown that the most common types of POMC are: Burkitt lymphoma (BL), rhabdomyosarcoma (RMS), mucoepidermoid carcinoma (MEC), and osteosarcoma (OS) [7,10,12,13]. Few international studies have performed a clinicopathological distribution of POMC. Asian and African countries have more studies in this context when compared to other continents [7,8,10–16]. In Latin
∗ Corresponding author. Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, 901. Areão, Piracicaba, São Paulo, 13414- 903, Brazil. E-mail address: [email protected], [email protected] (L.P.A. Arboleda).
https://doi.org/10.1016/j.ijporl.2020.109879 Received 13 August 2019; Received in revised form 6 December 2019; Accepted 8 January 2020 Available online 10 January 2020 0165-5876/ © 2020 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
L.P.A. Arboleda, et al.
Fig. 1. Main pediatric oral and maxillofacial cancer per age group.
Microsoft Office Excel 2013 software (Microsoft Corporation, Redmond, Washington, USA) and further analyzed by descriptive statistics by using absolute numbers, percentages, mean values and standard deviations.
America, there are only a few Brazilian studies that have been published on POMC [17]; however, the majority of these studies consider benign, malignant and reactive lesions [18,19]. Despite the existing studies, there is a lack of POMC research worldwide; therefore, there is a need for more international studies in this area, as the knowledge of its frequency and distribution may help the clinician with early diagnosis. This study aimed to determine the relative frequency and clinicopathological features of POMC from a tertiary referral center in Brazil.
3. Results During a 30-year period, for all childhood cancer diagnosed at Boldrini Children's Center (7,181), 367 (5.11%) malignancies corresponded to head and neck topography, of which 55 (0.77%) were located in the oral and maxillofacial region. The mean age at diagnosis was 8 years old ± 4.63 years. OMC cases were most frequently diagnosed among patients between 5 and 9 years old (22 [40%]), followed by patients aged 10–14 years old (14 [25.45%]); 1–4 years old (12 [21.82%]); 15–19 years old (5 [9.09%]), and younger than 1 year (2 [3.64%]). Fig. 1 shows the most common OMC per age group. BL was the tumor found in all age groups, with the exception of patients under 1 year. Analysis by gender showed that 36 (65.45%) patients were male and 19 (34.55%) were female. In terms of race, 43 (78.18%) were white, 11 (20%) were ‘other races,’ and 1 (1.82%) was black. Table 1 gives the frequency rates and percentage of all POMCs according to gender, mean age, and age group affected. Lymphoma was the most common type of OMC, followed by sarcomas, and carcinomas. BL, RMS, MEC, and diffuse large B-cell lymphoma (DLBCL), were the most common histopathological diagnoses. Following the ICD-O-3 codes, the oropharynx was the leading site category followed by major salivary glands, and maxillofacial bones. Table 2 shows the histopathological OMC distribution per anatomical topography in pediatric patients.
2. Material and methods This study was approved by the ethics committee of the Boldrini Center (protocol number 1.947.295). The medical records of the Boldrini Children's Center, Campinas, São Paulo, Brazil, were reviewed for all primary oral and maxillofacial malignant tumors diagnosed in pediatric patients from January 1986 to December 2016. The demographic variables (age, gender and race), anatomical location of tumors, and histopathological diagnosis were collected. The cut-off age of 19 was used following the definition of childhood provided by the World Health Organization (WHO) [20], and then categorized into five groups: < 1 year; 1–4 years; 5–9 years; 10–14 years; and 15–19 years [4]. In addition, patient's race was classified as white, black and other. All tumors were grouped and classified according to specific localization in the oral and maxillofacial area based on the international classification of diseases for oncology ICD-O-3: oral cavity (external upper lip C00.0; buccal mucosa, C06.0; palate, C05); oropharynx (base of tongue, C01; tonsil, C09); salivary glands (parotid gland, C07; submandibular gland, C08.0; sublingual gland, C08.1; major salivary gland, NOS, C08.9; minor salivary gland, C06.9); maxillofacial bones (mandible, C41.1; maxilla, C40.0) [21]. Inclusion criteria included primary solid tumors in the oral and maxillofacial region diagnosed in patients 19 years old and younger presenting complete medical records with confirmed histopathological diagnoses. Benign tumors, malignant tumors diagnosed outside the oral and maxillofacial region, tumors diagnosed in patients older than 19 years old, patients with incomplete medical records, second primary tumors, and metastases affecting the oral and maxillofacial region were excluded from the analyses. Data were collected in a datasheet, systematically organized in
4. Discussion Boldrini Children's Center is considered a tertiary referral center in pediatric oncology in Brazil, where a large number of childhood cancer cases are diagnosed and treated; nevertheless, in the 30-year period investigated, only 0.77% corresponded to POMC. Although some studies have shown the low prevalence of OMC in this population; most of them performed comparisons with benign lesions or included all age groups [6,10,15,17]; thus, our study shows a more accurate percentage of OMC, because it was focused only on malignant tumors affecting 2
3
NOS: no other specification.
55
TOTAL
a
29 25 18 5 1 1 4 3 1 15 8 1 3 1 1 1 11 11 5 2 1 1 1 1
(100.00)
(52.73) (45.45) (32.73) (9.09) (1.82) (1.82) (7.27) (5.45) (1.82) (27.27) (14.55) (1.82) (5.45) (1.82) (1.82) (1.82) (20.00) (20.00) (9.09) (3.64) (1.82) (1.82) (1.82) (1.82) 36
21 17 14 2 – 1 4 3 1 10 6 1 2 – – 1 5 5 2 – 1 1 – 1
No.
No.
(%)
Male
Total
Lymphomas Non-Hodgkin lymphoma Burkitt lymphoma Diffuse large B-cell lymphoma Lymphoblastic lymphoma Anaplastic large-cell lymphoma Hodgkin lymphoma Nodular sclerosis Nodular lymphocyte predominant Sarcomas Rhabdomyosarcoma Infantile myofibrosarcoma Ewing sarcoma Osteosarcoma Undifferentiated sarcoma Sarcoma, NOSa Carcinomas Salivary gland carcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Sebaceous adenocarcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Adenocarcinoma, NOS
Histologic Types
(65.45)
(38.18) (30.91) (25.45) (3.64) – (1.82) (7.27) (5.45) (1.82) (18.18) (10.91) (1.82) (3.64) – – (1.82) (9.09) (9.09) (3.64) – (1.82) (1.82) – (1.82)
(%)
19
8 8 4 3 1 – – – – 5 2 – 1 1 1 – 6 6 3 2 – – 1 –
No.
Female
(34.55)
(14.55) (14.55) (7.27) (5.45) (1.82) – – – – (9.09) (3.64) – (1.82) (1.82) (1.82) – (10.91) (10.91) (5.45) (3.64) – – (1.82) –
(%)
8
8 7.96 7.66 10 – – 8.25 7.66 – 6.71 5.75 – 15 – – – 8.81 8.81 12 10 – – – –
Mean age
4.63
4.33 4.58 4.48 5.56 – – 2.87 3.21 – 4.73 3.73 – 1.73 – – – 4.75 4.75 3.8 1.41 – – – –
Standard deviation
Table 1 Histopathological distribution of OMC according to gender, mean age, and age group in pediatric patients.
2
– – – – – – – – 1 – – – – 1 – 1 – – – – 1 – –
No.
<1 Y
(3.64)
– – – – – – – – (1.82) – – – – (1.82) – (1.82) – – – – (1.82) – –
(%)
Age group
12
7 6 5 – 1 – 1 1 – 4 3 1 – – – – 1 – – – – – – 1
No.
1–4 Y
(21.82)
(12.73) (10.91) (9.09) – (1.82) – (1.82) (1.82) – (7.27) (5.45) (1.82) – – – – (1.82) – – – – – – (1.82)
(%)
22
12 11 7 3 – 1 1 1 – 5 4 – – – – 1 5 – 2 1 1 – 1 –
No.
5−9 Y
(40.00)
(21.82) (20.00) (12.73) (5.45) – (1.82) (1.82) (1.82) – (9.09) (7.27) – – – – (1.82) (9.09) – (3.64) (1.82) (1.82) – (1.82) –
(%)
14
8 6 5 1 – – 2 1 1 4 1 – 2 1 – – 2 – 1 1 – – – –
No.
(25.45)
(14.55) (10.91) (9.09) (1.82) – – (3.64) (1.82) (1.82) (7.27) (1.82) – (3.64) (1.82) – – (3.64) – (1.82) (1.82) – – – –
(%)
10−14 Y
5
2 2 1 1 – – – – – 1 – – 1 – – – 2 – 2 – – – – –
No.
(9.09)
(3.64) (3.64) (1.82) (1.82) – – – – – (1.82) – – (1.82) – – – (3.64) – (3.64) – – – – –
(%)
15−19 Y
L.P.A. Arboleda, et al.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
L.P.A. Arboleda, et al.
Table 2 Histopathological pediatric oral and maxillofacial cancer distribution per anatomical topography based on the international classification of diseases for oncology ICD-O-3. Tumor Type
Total
Anatomical topography Oropharynx
Lymphomas Burkitt lymphoma Diffuse large B-cell lymphoma Lymphoblastic lymphoma Anaplastic large-cell lymphoma Nodular sclerosing Nodular lymphocyte predominant Sarcomas Rhabdomyosarcoma Infantile myofibrosarcoma Ewing sarcoma Osteosarcoma Undifferentiated sarcoma Sarcoma NOS Carcinomas Salivary gland carcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Sebaceous adenocarcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Adenocarcinoma. NOS TOTAL
Salivary glands
Odontogenic and maxillofacial bone
Oral cavity
C09
C01
C07
C08.0
C08.1
C06.9
C08.9
C41.1
C40.0
C06.0
C05
C00.0
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
29 18 5
11 (20.00) 4 (7.27)
-
1 (1.82) –
– –
– –
– –
– –
2 (3.64) –
3 (5.45) –
1 (1.82) –
– 1 (1.82)
– –
1 1
– –
–
1 (1.82) –
– –
– –
– –
– –
– –
– –
– 1 (1.82)
– –
– –
3 1
3 (5.45) 1 (1.82)
– –
– –
– –
– –
– –
– –
– –
– –
– –
– –
– –
15 8 1 3 1 1 1 11 11 5
– – – – – – – –
1 (1.82) – – – – 1 (1.82) – –
2 (3.64) – 1 (1.82) – – – – – 3 (5.45)
– – – – – – – – –
1 (1.82) – – – – – – – –
– – – – – – – – 2 (3.64)
– – – – – – – – –
2 1 2 1 – – – – –
– – – – – – – – – –
1 (1.82) – – – – – – – –
– – – – – 1 (1.82) – – – –
1 (1.82) – – – – – – – –
2 1 1 1
– – – –
– – – –
1 (1.82) 1 (1.82) 1 (1.82) –
1 (1.82) – – 1 (1.82)
– – – –
– – – –
– – – -
– – – –
– – – –
– – – –
– – – –
– – – –
1
–
–
–
–
–
–
1 (1.82)
–
–
–
–
–
55
19 (34.55)
2 (3.64)
11 (20.00)
2 (3.64)
1 (1.82)
2 (3.64)
1 (1.82)
8 (14.55)
3 (5.45)
3 (5.45)
2 (3.64)
1 (1.82)
21 (38.18)
17 (30.91)
(3.64) (1.82) (3.64) (1.82)
11 (20.00)
6 (10.91)
patients between the ages of 0 and 4 [13], 6 and 10 [8], and patients over the age of 10 [16]. The predominance in these age groups may be due to the high incidence of BL and RMS in the oral and maxillofacial region [13]. We found a homogeneous distribution of BL among the age groups of 1–4 years, 5–9 years, and 10–14 years; however, the highest percentage was found in patients between 5 and 9 years old (12.73%). RMS were most common in the ages groups of 1–4 years and 5–9 years, and bone sarcomas such as Ewing sarcoma (EWS) and OS were more frequently observed in patients over the age of 10. This agrees with reports in the literature [13,16]. Patients aged 15–19 years are most affected by tumors such as carcinomas and bone sarcomas; thus, in agreement with previous reports, our study showed a high frequency of salivary gland carcinomas, specifically MEC [12,13,16,17,19]. Male patients were more affected by POMC than females (65.45% vs. 34.55%, respectively); these results are in accordance with previous reports in the literature [8,10,13,16]. This result may be due to the high prevalence of non-Hodgkin's lymphoma (NHL), which is more common in male patients. However, one study showed an equal sex predilection among BL [13]. Lymphoma was the leading type of tumor in the present study (52.73%), and this was also reported in eight studies from Asia and Africa [7,8,10,12–16]. Interestingly, three Brazilian studies showed predominance for sarcomas [17–19], and our study was the only one that showed lymphomas as the main type of POMC in Brazil. This may be because lymphoma is the second most common type of childhood cancer in Brazilian patients [22], and our study was conducted in a tertiary referral center, where a large number of patients are referred
pediatric patients. The frequency of OMC among pediatric patients ranged from 0.53% to 13.3% [5–8,10–19]. Despite the low prevalence of POMC worldwide, there are clear differences between countries. Table 3 summarizes previous OMC publications in pediatric patients, showing data on OMC frequency, main types of OMC and their principal anatomical sites. The frequency percentages in African studies varied widely due to their methodology of comparison with benign tumors; however, the frequency of lymphoma, specifically BL remains high in Nigeria [8,10,16]. Five Asian studies showed percentages ranging from 2.9% to 10%, none of them distinguishing a difference between benign and malignant lesions located in this anatomical site [11–15]. However, Levi et al. [7] reported a prevalence of 2.6% POMC of all OMC seen in all age groups. Australia [5], UK [6], and Brazil [17,19], showed a frequency of POMC lower than 1%, which are similar results to our findings. The present study was composed of children from 0 to 19 years old, and the mean age at the time of OMC diagnosis was 8 years; this is similar to an Australian study [5], while other reports found mean ages ranging from 10 to 12 years old [7,10,16]. Because some studies analyzed did not focus merely on malignant tumors, they generalized demographic outcomes such as gender, age and average age with benign lesions in the oral and maxillofacial region of pediatric patients [6,8,11–15,17–19]. This generated a difficulty in interpreting the results between studies. Due to the need to standardize the age groups, the present study classified patients into five groups [4]; thus, patients between 5 and 9 years old were identified as being more affected by OMC (40%). This result differs from other studies, in which OMC was more common in 4
< 18 years < 19 years
– 1942–2017
19
5
1991–2007 1970–2011 1965–1992
1976–1997
Libya13 Israel7 Japan15
Japan14
< 15 years
< 19 years < 19 years < 15 years
< 16 years < 19 years < 16 years
< 16 years
3
8 357 18
31 26 11
9
3 27
58
74 65
47
55
Sample
(2.9%)
(3.7%) (2.6%) (7.0%)
(0.70%) (10%) (2.91%)
(0.68%)
(0.53%) (1.12%)
(0.61%)
(51%) (6.41%)
(13.3%)
(0.77%)
%*
C (29%), S (25.8%), L (6.5%) S (58%), C (42%) L (45.4%), S (36.3%), C (18.1%) L (50%), S (40%), C (10%) L (20.7%), C (19.9%) L (50%), S (27.7%), C (16.6%) L (33.3%), S (33.3%), C (33.3%)
L (52.7%), S (27.2%), C (20%) L (53.2%), S (36.2%), C (10.6%) L (90%), S (7%), C (3%) L (78.5%), S (10.8%), C (7.7%) S (34.5%), C (32.5%), L (12.1%) S (75%), C (25%) S (40.7%), L (25.9%), C (14.8%) –
Tumor type
malignant lymphoma, malignant mesenchymal tumor, acinic cell carcinoma
BL, RMS, MEC, OS. BL, MEC, SCC, RMS. L, fibrosarcoma, MEC.
Langerhans cell histiocytosis, malignant tumor unspecified, undifferentiated carcinoma. Langerhans cell histiocytosis, MEC, neurosarcoma, RMS. NHL, RMS, basal cell carcinoma BL, OS, MEC, RMS, PNET.
MEC, OS, malignant peripheral nerve sheath tumor. BL, RMS, OS, DLBCL
MEC, OS, SCC, BL.
BL, RMS. BL, NHL, RMS, SCC, MEC.
NHL, RMS, OS.
BL, RMS,DLBCL,MEC
Most prevalent tumor subtype
mandible, maxilla: 3, palate – mandible, buccal mucosa, maxilla
– face, postnasal space, mandible. –
–
– –
palate, mandible, maxilla
maxilla, mandible, cheek, palate maxilla, mandible, soft tissue.
oropharynx, salivary glands, maxillofacial bone, oral cavity maxilla/maxillary antrum, mandible
Anatomical site
%* the percentage is according with the different methodologies of each study. Abbreviations: L: lymphomas; S, sarcomas; C, carcinomas; NHL, non-Hodgkin lymphoma; RMS, rhabdomyosarcoma; OS, osteosarcoma; BL, Burkitt lymphoma; MEC, mucoepidermoid carcinoma; PNET, primitive neuroectodermal tumor.
1973–2002 1991–2000 1990–2004
UK Jordan11 Thailand12
6
Australia5
Brazil Brazil18
1945–2003
< 19 years
1990–2016
Brazil17
< 19 years < 16 years
1991–2001 1990–2010
Nigeria10 Nigeria8
Nigeria
< 19 years
< 19 years
1992–2003
1986–2016
Current study
Age limited
16
Period of study (years)
Country
Table 3 Previous studies on pediatric oral and maxillofacial cancer.
L.P.A. Arboleda, et al.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109879
L.P.A. Arboleda, et al.
Acknowledgement
for diagnosis and treatment. Sarcomas remain a prevalent group in the head and neck region of pediatric patients. We observed that in nine series, including the present study, sarcomas ranked as the second most common POMC [6,8,10,12–16]. In disagreement with our study, sarcomas were the leading POMC type in four previous reports [11,17–19]. Oral and maxillofacial carcinomas in pediatric patients are less frequently diagnosed when compared to adult patients [9]. However, the present study demonstrated 20% of these tumors, which is similar to reports in the literature (Table 3). A single study from a UK study reported carcinomas such as the most common type of tumor [6]. BL, RMS, MEC, and DLBCL were the most common POMC diagnoses in the present study, which is consistent with previous literature. Also present in other reports were tumors such as OS, squamous cell carcinoma (SCC), basal cell carcinoma, and EWS [7,13,16,18]. Extranodal NHLs are common in the oral cavity and maxillofacial region, mainly affecting the salivary glands [23]. On the contrary, we found that the oropharynx was the main anatomical site involved (38.18%), mainly affected by NHL. Likewise, Levi et al. (2017) showed 43.4% of BL located in the tonsils [7]. Salivary glands represented the second anatomical site affected by OMC, and MEC was the most prevalent tumor. However, there was a wide variety of histopathological types of tumors, such as acinic cell carcinoma, sebaceous adenocarcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Cesmebasi et al. (2014) studied a large number of pediatric cases of head and neck cancer, where salivary gland carcinomas were the most commonly seen tumors among pediatric patients [24]. Although for some studies the maxillofacial region is the main anatomical site of OMC, affecting most commonly the maxilla [8,16], we found a predominance of tumors in the mandible, such as RMS, BL and OS. The oral cavity was the least affected anatomical site in the present study. In addition to several studies agreeing with this result [10,13,16], we also observed that the oral cavity was only affected by tumors such as BL, DLBCL, anaplastic large cell lymphoma, RMS, and undifferentiated sarcoma. These results demonstrate that oral cavity carcinomas are rarely diagnosed in pediatric patients. The possible risk factors for some histopathological subtypes of POMC such as BL may be associated with the presence of the EpsteinBarr virus, often found in developing countries. However, there is evidence that the virus needs genetic and environmental support factors for tumor development [23,24]. Although the Boldrini Children's Center is known as a reference institution in Brazil, it is necessary to have a quality national cancer registry to obtain accurate epidemiological data. In addition, the ICD-O is fundamental for studies that analyze specific anatomical regions. In the present study, the interpretation of some medical records was difficult due to the retrospective character of the investigation, and occasionally analysis of the primary site was challenging when the tumor affected more than one anatomical region. Our study presents relevant data on the frequency and distribution of POMC and shows the need for more worldwide studies, especially in Latin America, as the scarcity of studies in this specific area inhibits our ability to determine the most frequent histological types and consequently their possible risk factors.
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Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest The authors declared no conflict of interest with respect to this research, authorship, and/or publication of this article. 6