Original Research—Head and Neck Surgery
Survival and Prognosis for Malignant
Tumors of Odontogenic Origin
Sunil Agarwal, MS1, Jonathan Mark, MD1,2, Changchun Xie, PhD1,3,
Enas Ghulam3, and Yash Patil, MD1,2
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objective. Determine survival and factors affecting survival
for patients with malignant tumors of odontogenic origin.
Study Design. Retrospective analysis of the National Cancer
Institute’s SEER database (Surveillance, Epidemiology, and
End Results).
Setting. Tertiary medical center.
Subjects and Methods. All cases of malignant tumors of odontogenic origin were extracted from the SEER database for
the period of 1973 to 2011. Demographic, tumor-specific,
and survival data were tabulated and Kaplan-Meier survival
analysis conducted according to histopathologic results. Cox
regression analysis stratified for histopathology was conducted to determine factors that influenced survival.
Results. A total of 308 cases of malignant tumors with odontogenic origin were analyzed. Malignant ameloblastoma
accounted for 59.7% of cases, followed by malignant odontogenic tumor (35.4%; including odontogenic carcinoma,
odontogenic sarcoma, primary intraosseous carcinoma, and
ameloblastic carcinoma) and ameloblastic fibrosarcoma
(2.9%). The overall mean and median were 229 and 227
months, respectively, while the 5-year survival rate was 81%
for the entire cohort. Malignant ameloblastoma exhibited
the best mean survival (237 months), whereas malignant
odontogenic tumor (139 months) and ameloblastic fibrosarcoma (42 months) had lower mean survival rates. Younger
age, surgery with adjuvant radiation, and smaller tumor size
were found to improve survival.
Conclusions. Significantly different survival can be expected
depending on individual tumor histopathology, tumor size,
age at diagnosis, and treatment modality.
Otolaryngology–
Head and Neck Surgery
2016, Vol. 155(1) 113–116
Ó American Academy of
Otolaryngology—Head and Neck
Surgery Foundation 2016
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0194599816639540
http://otojournal.org
O
dontogenic tumors are a heterogeneous group of
tumors that arise from tooth-forming tissues in the
mandible and maxilla. Odontogenic tumors consist
of lesions with varying biological presentations, including
hamartomas and malignant tumors.1,2 Odontogenic tumors
constitute about 1% of all jaw tumors, and their geographic
distribution is variable.
In 1971, the World Health Organization released a classification system for odontogenic tumors; this system was
updated in 1992 and subsequently 2005. However, due to
the diverse nature of odontogenic tumors, controversies
remain regarding their classification, terminology, and diagnosis.3 Specifically, the literature reports a wide range in
the diagnosis of malignant tumors of odontogenic origin,
composing 0% to 6.1% of all odontogenic tumors.1-9
Malignant tumors of odontogenic origin often present with
similar histopathology to benign lesions, which can result in
a delayed diagnosis or misdiagnosis.4
Several studies have described the presentation of odontogenic tumors with attention to their clinical manifestation
and histopathologic features. However, these studies are
case studies or single-institution reviews resulting in regionspecific outcomes and lacking meaningful consensus. This
study uses the SEER database (Surveillance, Epidemiology,
and End Results) to investigate the demographic and oncologic characteristics of malignant tumors of odontogenic
origin in patients in the United States from 1973 to 2011.
Methods
This study examined the SEER database for the period of
1973 to 2011. Institutional Review Board approval was not
required per the standing policy of the University of
Cincinnati College of Medicine, as SEER does not disclose
sensitive patient information. For this period, all cases of
tumors of odontogenic origin with ICD-O-3 codes 9270 to
1
University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Department of Otolaryngology, University of Cincinnati Medical Center,
Cincinnati, Ohio, USA
3
Division of Biostatistics and Bioinformatics, University of Cincinnati,
Cincinnati, Ohio, USA
2
Keywords
malignant odontogenic tumor, malignant ameloblastoma,
ameloblastic fibrosarcoma
Received September 30, 2015; revised February 22, 2016; accepted
February 26, 2016.
Corresponding Author:
Sunil Agarwal, MS, University of Cincinnati College of Medicine, 234
Goodman Street, Cincinnati, OH, 45229 USA.
Email: [email protected]
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114
Otolaryngology–Head and Neck Surgery 155(1)
Table 1. Distribution of Histopathology for Malignant Tumors of
Odontogenic Origin.
ICD-O-3 Histology
9270/3: Odontogenic tumor, malignant
9282/3: Complex odontosarcoma
9290/3: Ameloblastic odontosarcoma
9310/3: Ameloblastoma, malignant
9312/3: Squamous odontogenic tumor, malignant
9321/3: Central odontogenic fibrosarcoma
9330/3: Ameloblastic fibrosarcoma
9342/3: Odontogenic carcinosarcoma
n
%
109
1
2
184
1
1
9
1
35.4
0.3
0.6
59.7
0.3
0.3
2.9
0.3
9342 with malignant behavior were included. Fields
extracted from the database included demographic information, such as year of diagnosis, age at diagnosis, sex, and
race. Clinical variables pertaining to the malignancy were
also extracted, including histopathology, primary site, and
size of the primary tumor. Treatment variables that were
extracted included type of cancer-directed surgery and
application of radiation therapy. The selected group of
patients was then further restricted to those without evidence of distant metastatic disease.
Data were then imported into SPSS (IBM, Chicago,
Illinois) for statistical analysis. Standard demographic information was computed. Kaplan-Meier survival analysis for each
tumor histopathology was conducted. Mean, median, and 5year survival values were determined. Cox regression analysis
for overall survival was performed for age, sex, race, histopathology, primary site, surgery, radiation, radiation sequence,
and tumor size.
Results
For the period under examination, a total of 308 cases of malignant tumors of odontogenic origin were identified. Malignant
ameloblastoma accounted for 59.7% of cases, followed by
‘‘malignant odontogenic tumor’’ (35.4%; including odontogenic
carcinoma, odontogenic sarcoma, primary intraosseous carcinoma, and ameloblastic carcinoma) and ameloblastic fibrosarcoma (2.9%). The complete distribution of histopathology is
depicted in Table 1.
Thirteen cases (4%) presented with distant metastatic disease and were excluded from subsequent survival analysis.
After exclusion of cases with \8 patients per histopathology, 290 cases remained for survival analysis. The median
age interval at diagnosis was 50 to 54 years with a slight
male predominance (62%). The average size of the primary
tumor was 4.4 cm; 86.9% of patients underwent cancerdirected surgery; and 62.1% of patients received postoperative radiation therapy. The results of the Kaplan-Meier survival analysis are shown in Table 2.
No statistically significant survival difference was noted
among the various histopathologies. Survival rates for malignant ameloblastoma trended toward being better than both
malignant odontogenic tumors and ameloblastic fibrosarcoma.
The Kaplan-Meier survival curves according to histopathology
are displayed in Figure 1.
Beyond 1983, tumor size data were maintained in the
SEER database, and 158 cases had this information documented. Patients with tumors from 0 to 20 mm had a better
survival rate than patients with tumors 21 to 40 mm. The
lowest survival rate was found for patients with tumors 41
mm. The Kaplan-Meier curves demonstrating survival based
on tumor size are shown in Figure 2.
The results of the Cox regression analysis are given in
Table 3.
Discussion
The diagnosis of a malignant odontogenic tumor is complicated because of its rare presentation, limited clinical information, and low index of suspicion.4 The majority of
retrospective studies on malignant odontogenic tumors have
been conducted in Asia,3 United States,10 Africa,11 and
Europe12 in the form of single-institution studies or case
reports. Our study benefits from the nationally representative SEER database to describe the incidence of malignant
odontogenic tumors in the United States from 1973 to 2011.
A total of 308 patients were isolated in this study, which
represents the largest collection of malignant odontogenic
tumor patients reported in the United States. This analysis
demonstrates a threefold increase in the annual number of
malignant odontogenic tumors diagnosed after 1992 as compared with that before. This increase in diagnoses coincides
with the update of the World Health Organization classification for odontogenic tumors in 1992.
Studies suggest that the selection of the type of treatment
should consider the clinical type of tumor, patient age, location of tumor, and tumor size.13,14 Increasing age at diagnosis, lack of radiation treatment after surgery, increasing
Table 2. Histopathologic Results of the Kaplan-Meier Survival Analysis for Each Tumor and the Overall Cohort.
Survival time, mo
Mean
Median
5-y survival rate, %
Entire Cohort
Malignant Odontogenic Tumor
Malignant Ameloblastoma
Ameloblastic Fibrosarcoma
229
227
80.6
139
179
72.8
237
234
86.5
42
52
44.4
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Agarwal et al
115
Table 3. Cox Regression Analysis for Overall Survival.a
Parameter
Pr .
ChiSq
Hazard
Ratio
Age: 75 y
Radiation: yes
Tumor size: 41 mm
0.0037
0.0041
0.0463
11.329
19.887
2.674
95% Confidence
Limits
2.196
2.583
1.016
58.433
153.086
7.035
a
Analysis performed for age, sex, race, histopathology, primary site, surgical
treatment, radiation treatment, and tumor size. The table depicts significant
differences in mortality for radiation, age, tumor size, and histology.
Figure 1. Kaplan-Meier showing improved survival for malignant
ameloblastoma as compared with malignant odontogenic tumors
and ameloblastic fibrosarcoma. Results did not reach significance
on Cox regression analysis (Pr . ChiSq: 0.0586, ameloblastic fibrosarcoma; 0.0584, malignant ameloblastoma).
Figure 2. Kaplan-Meier demonstrating patient survival by tumor
size: 0-20 mm, 21-40 mm, or 41 mm (Pr . ChiSq: 0.9847, tumor
size, 21-40 mm; 0.0463, tumor size 41 mm).
tumor size, and ameloblastic fibrosarcoma histopathology
were each found to exert a statistically significant negative
impact on survival. However, our analysis showed that primary site, sex, and race did not statistically influence survival. Our analysis with the Cox regression model shows a
significant difference in the mortality among different age
groups. Patients .75 years of age at the time of diagnosis
are 11 times more likely to die. This is relevant given that
of 343 reported malignant odontogenic tumors, more than
one-third of these cases presented in patients .60 years
old.1
The results of the analysis support a multimodality
approach to treatment. Only 1 patient received radiation
prior to surgery. Of the 44 patients who received radiation,
36 (81.8%) had prior surgery. Patients who were not treated
with radiation were almost 20 times more likely to die. Oral
cavity malignancies are typically treated with surgery followed by radiation therapy. Not enough patients were
treated with neoadjuvant radiation or radiation alone to
draw a conclusion about this therapeutic approach; however,
the addition of adjuvant radiation therapy to surgical resection was beneficial.
Patients diagnosed with malignant ameloblastoma had a
better survival rate than patients with malignant odontogenic
tumors or ameloblastic fibrosarcoma. Ameloblastic fibrosarcoma had the lowest 5-year survival rate of 44.4%. The persistent nature of these tumors depicted in the survival
curves supports the need for follow-up .10 years. To date,
\80 cases of ameloblastic fibrosarcoma have been published in the literature.15,16
Tumor size was found to be associated with survival.
Patients with tumors 41 mm in size were more than twice
as likely to die than patients with smaller tumors, after controlling all other covariates in the model.
Many of the limitations of this study stem from the relatively small number of cases spanning a long period. Over
the last 30 years, SEER has adapted reported variables such
as extent of disease, size, and other features, which resulted
in a heterogeneous data set with limited common features to
analyze. Lack of information regarding resection margins,
for example, leaves room for further investigation in future
case reports. Furthermore, our analysis on patient survival is
limited because the majority of our patient sample was diagnosed after 1992. Although we were able to assess 5-year
survival of patients with malignant odontogenic tumor, it
will be important to obtain long-term follow-up to determine the survival of these patients over a period of 25
years.
Rizzitelli et al also analyzed patients with malignant
ameloblastoma from the SEER database and reported that
an overall incidence rate of 1.79 per 10 million persons per
year. Our study considers all malignant tumors of odontogenic origin and reports the largest such series in the literature. Additionally, our study is unique from that of
Rizzitelli et al in that it analyzes the relationship between
tumor size and overall patient survival.17
In conclusion, we have reviewed information from the
SEER database to identify important characteristics of
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116
Otolaryngology–Head and Neck Surgery 155(1)
patients with malignant odontogenic tumors and to conduct
a Kaplan-Meier survival analysis of demographic, tumorspecific, and survival data. Its individualized risk assessment may assist in patient counseling on prognosis and can
help to identify factors that influence survival in these
patients.
Author Contributions
Sunil Agarwal, collected data, wrote article, revised article;
Jonathan Mark, collected data, wrote article, revised article;
Changchun Xie, analyzed data, wrote article; Enas Ghulam, analyzed data, wrote article; Yash Patil, designed study, revised
article.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None.
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