Salivary gland cancer in patients younger than 30 years.
Previous research has shown that salivary gland tumors are rare in the young population. A clinical diagnosis has to be made very carefully because the proportion of malignancies is higher in children than in adults. We present a review of cases of malignant salivary gland carcinoma (SGC) in patients younger than 30 years of age. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 17 Registry. A total of 763 patients younger than 30 years with carcinoma of a major salivary gland from 1973 to 2004 were identified within the SEER database. The most common salivary gland cancer was mucoepidermoid parotid gland carcinoma. The incidence of all major salivary gland carcinomas increased with increasing patient age. The 5-year relative survival rate for salivary gland carcinomas in our population was calculated according to the Kaplan-Meier analysis in each age group. Relative 5-year survival was 100% in the 1 patient younger than 1 year, 50.0% in the 1- to 4-year-old group; 87.2% among the 5- to 9-year-olds; 97.0% among the 10- to 14-year-olds; 95.0% among the 15- to 19-yearolds; 95.1% among the 20- to 24-year-olds; and 93.6% in the 25- to 29-year-old group. We found that SGC affects patients of all ages, even children in the first year of life. It is essential for physicians to detect salivary gland neoplasms promptly and to evaluate them thoroughly when they are found in children.
Salivary gland tumors are uncommon in children and adolescents. However, when they do occur, the proportion that are malignant is higher than that of adults, so a prompt and accurate diagnosis is essential. Eneroth studied tumors of the major and minor salivary glands in 2,632 patients and found that the incidence of malignant neoplasms in adults was 15 to 25%. (1) However, many teams reported a higher percentage of malignancies among young patients. (2-6) For example, among patients aged 0 to 18 years studied by Ellies et al, 50% of all salivary gland tumors were malignant when hemangiomas and lymphangiomas were not included. (2) Schuller and McCabe reported a slightly higher incidence of 57.1%. (3) Finally, Byers et al found that 65 to 75% of epithelial neoplasms in adults were benign and that the percentage in children was smaller. (4)
Eneroth reported that 80 to 90% of all malignant lesions of the salivary glands in children were mucoepidermoid, adenoid cystic, or acinic cell carcinomas; the corresponding figure in adults was only 45%. (1) Many studies have found that mucoepidermoid carcinoma is the most common malignant salivary gland tumor in young patients. (7,8) Seifert et al reported that the highest incidence of mucoepidermoid carcinoma occurred in the second decade of life, (7) and Loy et al found that tumors in the first decade were rare. (9) Chomette and colleagues studied a series of 331 minor salivary gland tumors and found that malignancies accounted for 55.3% of cases.l[degrees] In that study, mucoepidermoid tumors were the second most common malignant tumor after adenoid cystic carcinomas. The average age at presentation was 52.2 years, and tumors were much more common in women than men.
According to Vrielinck et al, the characteristic and determining factor in a group of patients with adenoid cystic carcinoma was a tendency toward perivascular and perineural infiltration. (11) An analysis by Kim et al found that infiltration made the prognosis less favorable, with a 5-year survival rate of 60% and a 10-year survival rate of 40% in all age groups. (12) In their survey of patients younger than 20 years, Byers et al found a 5-year survival rate of 50% in patients with acinic cell carcinoma, including high-grade tumors. (4)
The objective of this study was to analyze and summarize data from the National Cancer Institutes (NCI) Surveillance, Epidemiology, and End Results (SEER) database regarding salivary gland carcinoma (SGC) among patients younger than 30 years. We sought to determine if the SEER data support a trend toward an increased incidence of SGC from childhood through adolescence and into young adulthood.
Patients and methods
Since 1973, the NCI has monitored cancer incidence in 10% of the U.S. population through the SEER program. (13) This program obtains data from population-based cancer registries covering the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah and from the metropolitan areas of Atlanta, Detroit, Oakland, San Francisco, and Seattle. SEER files contain information on the initial type of treatment given for each tumor within broad categories; subsequent treatments and the details of radiation and chemotherapy dosages are not recorded.
We searched the SEER incidence files for cases of carcinomas of the major salivary glands. Our search was limited to patients younger than 30 years of age. The reference population was generated by SEER Stat 2.0 (NCI; Bethesda, Md.) from the 1973-2004 SEER database, which was extracted from the SEER 17 Registry released in November 2007. Patients with a diagnosis of SGC were identified through SEER via codes from the third edition of the International Classification of Disease for Oncology (ICD-O). (14)
Tumors of all histologies were included, but tumors of the minor salivary glands were not included in this study because of limitations imposed by the ICD-O system. Patients with B cell/pre-B/B-precursor lesions were removed from the analysis because as lymphomas, they are biologically different from carcinomas. The group of patients with salivary gland carcinoma not otherwise specified (SGC-NOS) was also removed from the analysis because of uncertainties about the underlying site of origin.
For each patient, data were obtained on age at diagnosis, sex, the site and type of SGC, and tumor grade. Patients were classified by age into seven groups: younger than 1 year, 1 to 4 years, 5 to 9 years, 10 to 14 years, 15 to 19 years, 20 to 24 years, and 25 to 29 years. Locations of SGC included the parotid, submandibular, and sublingual glands. Tumors were graded according to the following scale: grade 1 was characterized as well differentiated, grade 2 as moderately differentiated, grade 3 as poorly differentiated, and grade 4 as undifferentiated anaplastic.
Statistical analysis included the chi-square test to compare the distribution of SGC type by age and sex. Kaplan-Meier survival analysis methods were used to estimate survival rates for each age group.
A total of 763 SGC patients younger than 30 years from 1973-2004 were identified in the SEER 17 database.
Demographic data. Of the 763 patients, 333 were males (43.6%) and 430 were females (56.4%). With regard to race, 580 patients (76.0%) were white, 97 (12.7%) were black, 75 (9.8%) were identified as "other" (i.e., American Indian, Alaska Native, Asian/Pacific Islander), and 11 (1.4%) were unknown. The age distribution was 1 patient (0.1%) younger than 1 year, 3 (0.4%) at 1 to 4 years, 30 (3.9%) at 5 to 9 years, 85 (11.1%) at 10 to 14 years, 137 (18.0%) at 15 to 19 years, 207 (27.1%) at 20 to 24 years, and 300 (39.3%) at 25 to 29 years.
Site, type, and grade of tumors. Parotid carcinoma was found in 672 patients (88.1%), submandibular gland carcinoma in 88 (11.5%), and sublingual gland carcinoma in 3 (0.4%). There were no overlapping lesions of the major salivary glands in any of these patients.
The most common types of parotid cancer (n = 672) were mucoepidermoid carcinoma (n = 270 [40.2%]), acinic cell carcinoma (n = 200 [29.8%]), and adenoid cystic carcinoma (n = 61 [9.1%]). Other less common types of parotid cancer included adenocarcinoma, rhabdomyosarcoma, and squamous cell carcinoma, among many others (n = 141 [21.0%]).
Among the known cases of SGC, the most common tumor grades were grade 2 for parotid mucoepidermoid carcinoma (48.1%), grade 1 for both parotid acinic cell carcinoma (15.0%) and parotid adenoid cystic carcinomas (8.2%), and grade 2 for submandibular carcinoma (23.9%) (table 1).
Comparisons by sex. The site of carcinoma did not differ by sex (table 2). For both sexes, the parotid gland was involved in more than 87% of cases. Sublingual carcinomas were by far the least common.
There was a statistically significant difference between the sexes within the parotid category with respect to the "other" category of parotid tumors (table 3).
Comparison by race. No significant differences were
noted in terms of overall prevalence or tumor site according to race (table 4).
Comparison by age. The incidence of all types of parotid SGC and submandibular SGC generally increased with age (table 5). Even though there were only 3 cases of sublingual SGC, the trend was maintained, as all 3 cases occurred in the oldest group.
With respect to parotid involvement only (n = 672), there was 1 case (0.1%) of carcinoma in the youngest group, 2 cases (0.3%) in the 1- to 4-year-old group, 29 cases (4.3%) in the 5-to-9 group, 76 cases (11.3%) in the 10-to- 14 group, 121 cases (18.0%) in the 15-to- 19 group, 183 cases (27.2%) in the 20-to-24 group, and 260 cases (38.7%) in the 25-to-29 group.
Survival. Survival information was available on only 720 of the 763 patients. Survival was calculated at 1-year intervals up to 5 years. Relative 5-year survival was 100% in the 1 patient younger than 1 year, 50.0% in the 1- to 4-year-old group; 87.2% among the 5- to 9-year-olds; 97.0% among the 10- to 14-year-olds; 95.0% among the 15- to 19-year-olds; 95.1% among the 20- to 24-year-olds; and 93.6% in the 25- to 29-year-old group.
Malignant neoplasms account for approximately 35% of all salivary gland tumors in children. (14) Of these cases, approximately 60% are either mucoepidermoid carcinomas or acinic cell carcinomas. (14-16) Less common malignant tumors include adenoid cystic carcinomas, adenocarcinomas, squamous cell carcinomas, undifferentiated carcinomas, and rhabdomyosarcomas. Malignant salivary gland neoplasms are more often symptomatic than are benign tumors, and most occur in the parotid gland. (17) Indicators that a salivary gland lesion is likely to be malignant include a rapid increase in the size of the mass, facial nerve paralysis, and lymphadenopathy. Most of these lesions are heterogeneous and hypoechoic compared with the normal glandular parenchyma, and they may have indistinct borders. (18) Mucoepidermoid carcinoma appears in approximately 7% of pediatric cases; it may involve, in order of frequency, the parotid, submaxillary, and sublingual glands. (19,20) Acinic cell carcinoma is more frequently located in the parotid and sublingual glands, most often in patients near 10 years of age. (17)
The etiology of SGC is not well known, although correlations with some possible risk factors have been found. For example, therapeutic radiation has been linked to an increased risk. Schneider et al found an increased incidence of salivary gland carcinoma among patients who had been exposed to head, face, or neck radiation. (21) Hall and colleagues found an increased risk among patients who had been treated with iodine- 131 for hyperthyroidism. (22) Using 1973-1981 data from the SEER program, Spitz et al noted an increased incidence of salivary gland carcinoma in southern registries, suggesting an association between SGC and exposure to ultraviolet B radiation. (23)
Several viruses have been implicated in the etiology of SGC. Epstein-Barr virus and human papillomavirus (HPV) types 16 and 18 have been found in SGCs, (19,24) and HPV-1 has been found in cystic lymphoepitheliallesions of the salivaryglands. (25) Polyomavirus and cytomegalovirus have been shown to induce salivary gland tumors in mice. (26)
Occupational factors--including exposure to rubber manufacturing, plumbing, and woodworking in the automobile industry--also pose an increased risk. (27) Moreover, Graham et al found an increased risk of SGC among people living in asbestos mining provinces in Quebec; this risk was inversely related to the distance from the asbestos mines. (28)
In contrast with other head and neck cancers, the risk of malignant salivary gland tumors is not increased by the consumption of tobacco or alcohol. Chronic inflammation of the salivary glands is not clearly defined as a risk factor. Nutrition may be a risk factor, as a low intake of vitamins A and C correlates with a high incidence of tumors. Patients with a histologically benign tumor that occurs at a young age have a higher risk of developing a malignant parotid carcinoma later in life because these tumors have the potential for malignant transformation. (29)
Malignancies of the salivary glands are not limited to a certain age. To the best of our knowledge, ours is the first study that has looked only at patients younger than 30 years with malignant SGC. In most cases, adults in the fifth or sixth decade of life are affected. (30) However, when children are affected, most tumors appear to be low-grade mucoepidermoid carcinomas. (31-34) In a study by Sun et al, the age-specific incidence of SGC was plotted on a log scale from 1973 to 1992; they found that the incidence increased markedly with age. (35)
In 2002, Jansisyanont et al (36) reported that epithelial malignancies were more common in females, but 2 years later Kokemuller et al (37) reported no difference between the sexes. Blot et al found that the incidence of SGC was slightly higher among females than males until the ages of 40 to 44 years, when males then assumed a higher risk. (38) Much earlier reports by Fitzpatrick and Black, (39) Chaudhry et al, (40) Cameron, (41) and Gore et al (42) all revealed that malignant tumors were more common in men than women.
Gunhan et al studied a series of 703 patients (mean age: 47.1 yr; range: 2 to 80) with primary epithelial tumors that involved both the major and minor salivary glands. (43) They found that males were more affected than females by a margin of 59 to 41%. The peak incidence of malignant tumors occurred in the sixth decade. The parotid gland carried a tumor burden greater than that of all the other salivary glands combined. Tumors were present in the major salivary glands in 76.6% of cases, a figure that is similar to those reported in many other series. (42, 44, 45) Malignant tumors were found in 26% of patients. Mucoepidermoid tumor was the most frequently encountered malignant SGC, accounting for 42% of all malignant tumors in this series. The mean age for parotid mucoepidermoid SGC was 43.5 years in females and 46.4 years in males. Among patients with submandibular adenoid cystic carcinoma, the mean age was 72.5 years in females and 54.0 years in males.
Ribeiro Kde et al studied SGC in 38 children and adolescents (mean age: 11.8 yr) and found a female preponderance. (34) In 25 of these cases (65.8%), the parotid gland was affected. A total of 27 patients presented with a malignant tumor and 11 with a benign neoplasm. Mucoepidermoid carcinoma was the most common malignancy, occurring in 17 of the 27 cases (63.0%). The overall 5-year survival rate was 81.6% for patients with malignant tumors. The grade of differentiation was the only significant prognostic factor for patients with mucoepidermoid carcinomas.
In children and adolescents, the proportion of salivary gland malignancies among all neoplasms is relatively high. In his study of incidence and prognosis in 2,632 patients with tumors of the major and minor salivary glands, Eneroth found an incidence of 15 to 25% of malignant neoplasms for adults. (1) Many teams have reported a significantly higher relative proportion in young patients.
Byers et al identified patients younger than 20 years with SGC and found 5-year survival rates of 50% among patients with acinic cell carcinoma, including high-grade carcinomas. (4) Ellies et al found that patients with low-grade acinic cell carcinoma had a 5-year survival rate of 100%. (2)
In summary, there is no agreement in the literature about sex and the rate of malignant tumors. SGCs are rare in childhood and adolescence, and their incidence and malignity are different in juvenile and adult patients. This is especially true of parotid malignancies, which are more common in young patients. SGCs constitute the most heterogeneous group of neoplasms in the body, and therefore their cellular morphology varies greatly.
In our study of patients younger than 30 years, we found more females with SGC than males. The 25- to 29year-old group was the most affected of the age groups, and mucoepidermoid SGC was the most common SGC. Still, we found that SGC affects patients of all ages, even children in the first year of life. Therefore, it is essential that physicians detect salivarygland neoplasms promptly and evaluate them thoroughly when they are found in children who are at high risk of having a malignant etiology for salivary gland masses.
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From the Department of Otolaryngology-Head and Neck Surgery, Detroit Medical Center/Michigan State University, Detroit (Dr. Rutt); the Department of Otolaryngology-Head and Neck Surgery, Drexel University College of Medicine, Philadelphia (Ms. Hawkshaw and Dr. Sataloff); and the Department of Mathematics; Saint Joseph's University, Philadelphia (Dr. Lurie).
Corresponding author: Robert T. Sataloff, MD, DMA, FACS, Department of Otolaryngology-Head and Neck Surgery, Drexel University College of Medicine, 1721 Pine St., Philadelphia, PA 19103. E-mail: RTSataloff@PhillyENT.com
Table 1. Distribution of tumor grade by the site/type of SGC Site/type Grade 1 Grade 2 Grade 3 Parotid mucoepidermoid 59 (21.9%) 130 (48.1%) 9 (3.3%) Parotid acinic cell 30 (15.0%) 22 (11.0%) 1 (0.5%) Parotid adenoid cystic 5 (8.2%) 2 (3.3%) 0 Parotid other NR * NR NR Submandibular 4 (4.5%) 21 (23.9%) 6 (6.8%) Sublingual NR NR NR Total 98 (12.8%) 175 (22.9%) 16 (2.1%) Site/type Grade 4 Unknown Total Parotid mucoepidermoid 14 (5.2%) 58 (21.5%) 270 (35.4%) Parotid acinic cell 0 147 (73.5%) 200 (26.2%) Parotid adenoid cystic 1 (1.6%) 53 (86.9%) 61 (8.0%) Parotid other NR 141 (100%) 141 (18.5%) Submandibular 9 (10.2%) 48 (54.5%) 88 (11.5%) Sublingual NR 3 (100%) 3 (0.4%) Total 24 (3.1%) 450 (59.0%) 763 (100%) * NR = not reported. Table 2. Distribution of sex by tumor site * Site Male Female Total Parotid 295 (88.6%) 377 (87.7%) 672 (88.1%) Submandibular 37 (11.1%) 51 (11.9%) 88 (11.5%) Sublingual 1 (0.3%) 2 (0.5%) 3 (0.4%) Total 333 (43.6%) 430 (56.4%) 763 (100%) * None of the differences between the sexes was statistically significant (p > 0.05, chi-square test). Table 3. Distribution of sex by the type of parotid carcinoma Type Male Female Total Mucoepidermoid 111 (37.6%) 159 (42.2%) 270 (40.2%) Acinic cell 77 (26.1%) 123 (32.6%) 200 (29.8%) Adenoid cystic 20 (6.8%) 41 (10.9%) 61 (9.1%) Other 87 (29.5%) * 54 (14.3%) * 141 (21.0%) Total 295 (43.9%) 377 (56.1%) 672 (100%) * Statistically significant difference (p < 0.01, chi-square test). Table 4. Distribution of tumor site by race * Race Parotid Submandibular Sublingual Total White 517 (76.9%) 61 (69.3%) 2 (66.7%) 580 (76.0%) Black 82 (12.2%) 15 (17.0%) 0 97 (12.7%) Other 64 (9.5%) 11 (12.5%) 0 75 (9.8%) Unknown 9 (1.3%) 1 (1.1 %) 1 (33.3%) 11 (1.4%) Total 672 (88.1%) 88(11.5%) 3 (0.4%) 763 (100%) * None of the differences in overall prevalence or tumor site among the races was statistically significant (p > 0.05, chi-square test). Table 5. Distribution of the type of carcinoma by age group Parotid Age (yr) MED * Acinic cell Adenocystic Other <1 0 0 0 1 (0.7%) 1 to 4 1 (0.4%) 0 0 1 (0.7%) 5 to 9 12 (4.4%) 5 (2.5%) 0 12 (8.5%) 10 to 14 35 (13.0%) 21 (10.5%) 2 (3.3%) 18 (12.8%) 15 to 19 48 (17.8%) 48 (24.0%) 6 (9.8%) 19 (13.5%) 20 to 24 75 (27.8%) 54 (27.0%) 22 (36.1%) 32 (22.7%) 25 to 29 99 (36.7%) 72 (36.0%) 31 (50.8%) 58 (41.1%) Total 270 (35.4%) 200 (26.2%) 61 (8.0%) 141 (18.5%) Age (yr) Submandibular Sublingual Total <1 0 0 1 (0.1%) 1 to 4 1 (1.1 %) 0 3 (0.4%) 5 to 9 1 (1.1 %) 0 30 (3.9%) 10 to 14 9 (10.2%) 0 85 (11.1%) 15 to 19 16 (18.2%) 0 137 (18.0%) 20 to 24 24 (27.3%) 0 207 (27.1%) 25 to 29 37 (42.0%) 3 (100%) 300 (39.3%) Total 88 (11.5%) 3 (0.4%) 763 (100%) * MED = mucoepidermoid.
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|Title Annotation:||ORIGINAL ARTICLE|
|Comment:||Salivary gland cancer in patients younger than 30 years.(ORIGINAL ARTICLE)|
|Author:||Rutt, Amy L.; Hawkshaw, Mary J.; Lurie, Deborah; Sataloff, Robert T.|
|Publication:||Ear, Nose and Throat Journal|
|Date:||Apr 1, 2011|
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