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. 2009 Apr 2;94(2):249–261. doi: 10.1007/s11060-009-9864-x

Incidence of first primary central nervous system tumors in California, 2001–2005

Monica Brown 1,2,✉, Rudolph Schrot 3, Katrina Bauer 1, Deanna LeTendre 1
PMCID: PMC2724635  PMID: 19340398

Abstract

We examined the incidence of first primary central nervous system tumors (PCNST) in California from 2001–2005. This study period represents the first five years of data collection of benign PCNST by the California Cancer Registry. California’s age-adjusted incidence rates (AAIR) for malignant and benign PCNST (5.5 and 8.5 per 100,000, respectively). Malignant PCNST were highest among non-Hispanic white males (7.8 per 100,000). Benign PCNST were highest among African American females (10.5 per 100,000). Hispanics, those with the lowest socioeconomic status, and those who lived in rural California were found to be significantly younger at diagnosis. Glioblastoma was the most frequent malignant histology, while meningioma had the highest incidence among benign histologies (2.6 and 4.5 per 100,000, respectively). This study is the first in the US to compare malignant to benign PCNST using a population-based data source. It illustrates the importance of PCNST surveillance in California and in diverse communities.

Keywords: Brain and other central nervous system neoplasms, Epidemiology, Cancer incidence, Ethnic groups, Health disparities

Introduction

Central nervous system (CNS) cancers are neoplasms of the neuroepithelial tissue and membranous coverings of the brain and spinal cord, tumors of the pituitary gland, and cancers arising from the cranial nerves and CNS hematopoietic cells. Compared to other forms of cancer, PCNST are rare. In California, these cancers generally represent only 1.5% of incident cancer cases and 2.6% of cancer deaths [1]. Despite these statistics, PCNST are an important source of cancer morbidity and mortality and generate intense interest from clinicians, researchers, the public health community, and the general public.

Many population-based epidemiologic studies of PCNST are methodologically inconsistent and potentially unreliable. CNS cancers are a heterogeneous group of diseases, comprising many histopathological forms and encompassing numerous gross anatomic sites. Their histopathological progression may be benign, malignant, or of uncertain tumor behavior. Although CNS tumor classification was standardized by the World Health Organization (WHO) in 1993, there remains variation in the organization of histologic codes for presentation and in the creation of histology sub-groups [2]. Coding trends by neuropathologists change with time, resulting in erroneous incidence fluctuations [3]. Furthermore, many epidemiologic studies are retrospective, have small sample sizes, or lack broad ethnic, cultural, and socioeconomic demographics.

With the enactment of federal Public Law 107-260 in 2004, the Benign Brain Tumor Cancer Registries Amendment Act, all state and metropolitan cancer registries are required to collect data on benign PCNST and those of uncertain tumor behavior [4]. Prior to 2004, many state and metropolitan cancer registries voluntarily collected these data, including the California Cancer Registry (CCR), which has been collecting data on benign and uncertain tumor behavior CNS tumors since 2001. In this study, we examined the incidence of first primary PCNST collected by the CCR from 2001–2005. For benign PCNST, this study period represents the first five years of data collection in California and the first population-based study of benign PCNST in the country. With a population of 36.5 million, California contains over 12% of the U.S. population, with broad ethnic, cultural, and socioeconomic representation [5]. Delineating the epidemiology of PCNST in California will create a backdrop for future basic, translational, clinical, and public health research and can be used as a baseline for monitoring incidence trends over time.

Materials and methods

Case identification

Cases used in these analyses were identified using the California Cancer Registry (CCR), a population-based registry composed of eight regional registries collecting cancer incidence and mortality data for the entire population of California. In 1985, California state law mandated the reporting of all newly diagnosed cancers in California, and statewide implementation began January 1, 1988. This state law was amended to require the collection of benign and uncertain behavior brain and other nervous system tumors beginning January 1, 2001. Cases are reported to the Chronic Disease Surveillance and Research Branch of the California Department of Public Health from all hospitals and any other facilities providing care or therapy to cancer patients residing in California (approximately 2,500 facilities) [6]. Cases diagnosed outside of California, at autopsy, or from death certificates were excluded.

For this study, first primary cases of malignant, benign and uncertain tumor behavior brain and other nervous system tumors diagnosed between January 1, 2001 and December 31, 2005 and reported to the CCR as of October 2007 were used [7]. Only cases diagnosed or treated at the reporting facility were included in these analyses. Diagnoses of 98% of the 24,944 cases were confirmed by histology (79.0%) and radiography (19.3%); the remaining 1.7% was confirmed by a variety of methods, including but not limited to cytology and clinical determination. Less than 0.5% of cases included in these analyses were confirmed by an unknown method. In this manuscript, the term “uncertain behavior” is used and synonymous with “borderline behavior”. These terms are defined similarly but their use is specific to certain classification systems. Uncertain behavior is used in the International Classification of Diseases (ICD) systems [7], while borderline behavior is the term used by the Centers for Disease Control and Prevention’s (CDC), National Programs for Central Cancer Registries (NPCR) [8], Surveillance, Epidemiology and End Results (SEER) [9] program of the National Cancer Institute, and thus the CCR. Additionally, primitive neuroectodermal tumors are abbreviated throughout the text and tables as PNET.

Only cases with anatomical sites, histology codes and tumor behavior defined as reportable in Cancer Reporting in California: Abstracting and Coding Procedures for Hospitals, Volume 1, Section II.1.9.1 and Appendix V were included in these analyses. Anatomical sites included were the meninges (C70.0–C70.9); brain (C71.0–C71.9); cerebrum (C71.0); brain lobes (C71.1–C71.4); ventricle, NOS (C71.5); cerebellum, NOS (C71.6); brain stem (C71.7); spinal cord (C72.0); cauda equina (C72.1); cranial nerves (C72.2); pituitary gland (C75.1); craniopharyngeal duct (C75.2); and pineal gland (C75.3) [10]. For other selected analyses, overlapping lesions of brain (C71.8); brain, NOS (C71.9); and/or nervous system, NOS (C72.9) were included. Although the use of some anatomical sites and histology codes differed, the 2007–2008 report of the Central Brain Tumor Registry of the United States (CBTRUS), 2000–2004, was used as a guide for the organization of histology codes in Table 2 [11]. In this study, pilocytic astrocytoma (ICD-O-3, 9421) is classified as having benign tumor behavior as is directed in ICD-O-3 [7]. This is contrary to the classification stipulated in Cancer Reporting in California: Abstracting and Coding Procedures for Hospitals, Volume 1, Section II.1.9.1 and Appendix V, in which it is classified as malignant, in accordance with SEER reporting requirements [10].

Table 2.

Number of cases and percent of first primary central nervous system tumors by behavior and histology, California, 2001–2005

Histology ICD-O3 histology codes Malignant Benign Uncertain Total
n % n % n % n %
Tumors of the neuroepithelial tissue
    Pilocytic astrocytoma 9421 0 0.0 488 3.5 0 0.0 488 2.0
    Diffuse astrocytoma (protoplasmic, fibrillary) 9410, 9420 87 0.9 0 0.0 0 0.0 87 0.3
    Anaplastic astrocytoma 9401, 9411 644 7.0 0 0.0 0 0.0 644 2.6
    Unique astrocytoma variants 9383, 9384, 9424 36 0.4 0 0.0 82 5.0 118 0.5
    Astrocytoma, NOS 9400, 9412 587 6.4 0 0.0 3 0.2 590 2.4
    Glioblastoma 9440, 9441, 9442 4,180 45.3 0 0.0 0 0.0 4,180 16.8
    Oligodendroglioma 9450 448 4.9 0 0.0 0 0.0 448 1.8
    Anaplastic oligodendroglioma 9451, 9460 207 2.2 0 0.0 0 0.0 207 0.8
    Ependymoma/Anaplastic ependymoma 9391, 9392, 9393 418 4.5 0 0.0 0 0.0 418 1.7
    Ependymoma variant, Myxopapillary 9394 0 0.0 0 0.0 146 9.0 146 0.6
    Mixed glioma 9382 313 3.4 0 0.0 0 0.0 313 1.3
    Glioma malignant, NOS 9380 497 5.4 0 0.0 0 0.0 497 2.0
    Choroid plexus 9390 20 0.2 68 0.5 5 0.3 93 0.4
    Neuroepithelial 9381, 9423, 9430, 9444 25 0.3 0 0.0 <5 0.2 27 0.1
    Neuronal/glial, neuronal and mixed 8680, 9413, 9490, 9492, 9493, 9500, 9501, 9505, 9506, 9508 59 0.6 91 0.6 200 12.3 350 1.4
    Pineal parenchymal 9360, 9361, 9362 34 0.4 0 0.0 26 1.6 60 0.2
    PNET/medulloblastoma 9470, 9471, 9472, 9473, 9474 399 4.3 0 0.0 0 0.0 399 1.6
Tumors of cranial & spinal nerves
    Nerve sheath tumors 9540, 9550, 9560, 9561, 9570 17 0.2 2,537 18.0 23 1.4 2,577 10.3
Tumors of meninges
    Meningioma 9530, 9531, 9532, 9533, 9534, 9537, 9538, 9539 138 1.5 7,257 51.6 424 26.0 7,819 31.4
    Other mesenchymal 8324, 8728, 8801, 8806, 8810, 8815, 8850, 8861, 8890, 8900, 8920, 9150, 9260 25 0.3 21 0.1 49 3.0 95 0.4
    Hemangioblastoma 9131, 9161, 9535 0 0.0 17 0.1 217 13.3 234 0.9
Lymphomas
9590, 9591, 9650, 9670, 9671, 9675, 9680, 9684, 9687, 9690, 9691, 9695, 9698, 9699, 9702, 9705, 9714, 9719, 9727, 9728, 9729, 9731, 9733, 9734, 9740, 9741, 9750, 9755, 9930 694 7.5 0 0.0 0 0.0 694 2.8
Germ cell tumors
9060, 9064, 9065, 9070, 9071, 9080, 9081, 9084, 9085 157 1.7 25 0.2 0 0.0 182 0.7
Tumors of sellar region
    Pituitary tumors 8270, 8271, 8272, 8280, 8290, 8300,9580 15 0.2 3,384 24.1 0 0.0 3,399 13.6
    Craniopharyngioma 9350, 9351, 9352 0 0.0 0 0.0 271 16.6 271 1.1
Local extensions from regional tumors
    Chordoma 9370, 9371, 9372 23 0.2 0 0.0 0 0.0 23 0.1
Unclassifed tumors
    Hemangioma 9120, 9121, 9122, 9130, 9133 0 0.0 93 0.7 3 0.2 96 0.4
    Neoplasm, unspecified 8000, 8005, 8010 208 2.3 76 0.5 179 11.0 463 1.9
    All other 8720, 8728, 9580, 9751 5 0.1 0 0.0 0 0.0 5 0.0
Total – 9,236 – 14,057 – 1,630 – 24,923 –
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PNET primitive neuroectodermal tumors

The collection of benign and borderline brain and other nervous system tumors became a statewide effort beginning in 2001; however, the nationwide effort did not begin until 2004. Inconsistencies in data collection may have occurred as a result of coding rule changes for cases diagnosed in 2004 and 2005. To utilize all eligible cases, we identified inconsistencies by cross tabulations of cases by histology, tumor behavior, and anatomical site; these were reviewed by the authors, a regional registry quality control coordinator, and a neurosurgeon to determine the accuracy of coding and the appropriate categorization for presentation. Based on their assessment, approximately 400 cases were reassigned histology, tumor behavior, and/or anatomical site codes, and approximately 100 cases were deleted from the research database entirely for this study. Specifically, all craniopharyngiomas were recoded to uncertain behavior of the craniopharyngeal duct. All cases coded as benign adenomas (ICD-O-3 8140) of the pituitary gland were recoded to pituitary adenomas (ICD-O-3 8272). Some cases (n = 65), were recoded based on visual review of the individual case abstract for various reasons. Cases with ICD-O-3 codes 9450, 9391-9393, 9380, 9370-9372, were recoded to malignant behavior. Myxopapillary ependymomas were recoded to uncertain behavior. The cases coded as hemangioblastic meningioma were recoded to hemangioblastoma.

Variables

The age, sex, race/ethnicity, and residential address of the patients that were used in these analyses were collected by the CCR from each patient’s medical record. Race/ethnicity was derived from patient self-identification, assumptions based on personal appearance, or inferences based on the race/ethnicity of the parents, birthplace, surname, or maiden name. Race/ethnicity was classified into four mutually exclusive categories of non-Hispanic white, non-Hispanic black, Hispanic, and Asian/Pacific Islander. Hispanic ethnicity identification was enhanced by the use of computerized comparisons to the 1980 U.S. census list of Hispanic surnames. Patients identified as Hispanic on the medical record, or patients identified as white, black, or of unknown race with a Hispanic surname were classified as Hispanic. Use of this method can misclassify some persons as Hispanic when they are not [12].

Residential census tracts of cases, including those who used post office boxes as residential addresses and the denominator population were classified by the 2000 Rural Urban Commuting Areas (RUCA) codes. The RUCAs were developed by the University of Washington’s Rural Health Research Center and the Economic Research Service [13]. The RUCAs are a census tract-based taxonomy that utilizes the standard Census Bureau Urbanized Area and Urban Cluster definitions in combination with other work that commuted data to characterize the nation’s census tracts regarding their urban and rural status and functional relationships [14]. For these analyses, urban and rural census tracks in California were dichotomized based on Categorization C as recommended in “Using RUCA Data,” published by the Rural Health Research Center [14].

Socioeconomic status (SES) was assigned based on the patient’s census block group (2000 U.S. census) derived from their address at time of initial diagnosis as reported in the medical record. This SES variable is an index that utilizes education, employment characteristics, median household income, proportion of the population living 200% below the Federal Poverty Level, median rent, and median housing value of census tract of residence for case and denominator population. A principal components analysis was used to identify quintiles of SES ranging from one, the lowest, to five, the highest [15].

Statistical analysis

Counts and proportions were calculated using SAS 9.0 (SAS Institute, Cary, NC). Age-adjusted incidence rates (AAIR) were adjusted by the direct method and standardized to the 2000 U.S. population [16]. Age-specific incidence rates (ASIR) were calculated specific to each 5 year age group. Denominators were based on the 2000 U.S. census. All rates were calculated using SEER*Stat 6.3.6 (National Cancer Institute, Silver Spring, MD). Statistical comparisons of incidence rates were assessed using their respective confidence intervals [16]. If two comparative AAIR or ASIR confidence intervals do not overlap, the difference in the rates is considered statistically significantly.

Results

We identified 24,923 cases of first PCNST in the CCR from 2001 to 2005. A total of 9,236 (37.1%) cases were malignant, 14,057 (56.4%) cases were benign, and 1,630 (6.5%) cases were of uncertain tumor behavior. As shown in Table 1, our study population was 59.5% adult, 20–64 years old; 54.5% female; 60.8% non-Hispanic white; 46.5% of high SES; and 93.5% urban residents at time of diagnosis. The proportion of cases by age groups, SES, and location of residence at diagnosis was similar across tumor behavior, although tumors of uncertain tumor behavior appeared to occur more in the 0–19 year old age group than malignant and benign. There were statistically significant differences in the median age at diagnosis of patients with PCNST by tumor behavior (P < 0.05). For malignant PCNST, males, ethnic minorities, those of low SES, and those who lived in urban areas were significantly younger at diagnosis than females, those of high SES, non-Hispanic whites, and those who lived in rural areas. For benign PCNST, Hispanics and Asian/Pacific Islanders, those of low SES, and those who lived in urban areas were significantly younger at diagnosis (P < 0.05). The proportional incidence of PCNST, regardless of tumor behavior, was highest among those at the highest SES.

Table 1.

Number of cases and percent of first primary central nervous system tumors, population demographic characteristics and median age at diagnosis by behavior, California, 2001–2005

Demographic characteristics Malignant Benign Uncertain Total
n % Median age n % Median age n % Median age n %
Age group, years
    0–19 1,114 12.1 698 5.0 284 17.4 2,096 8.4
    20–64 5,202 56.3 8,676 61.7 941 57.7 14,819 59.5
    65+ 2,920 31.6 4,683 33.3 405 24.8 8,008 32.1
Sex
    Male 5,232 56.6 53* 5,277 37.5 55 830 50.9 44* 11,339 45.5
    Female 4,004 43.4 57  8,780 62.5 56 800 49.1 50 13,584 54.5
Race/ethnicity
    Non-Hispanic White 5,965 64.6 58  8,266 58.8 58 919 56.4 53 15,150 60.8
    Non-Hispanic Black 378 4.1 51* 902 6.4 57 116 7.1 47* 1,396 5.6
    Hispanic 2,122 23.0 43* 3,092 22.0 47* 424 26.0 34* 5,638 22.6
    Asian-Pacific Islander 726 7.9 51* 1,605 11.4 57* 157 9.6 48* 2,488 10.0
    Other/unknown 45 0.5 40* 192 1.4 52* 14 0.9 49 251 1.0
Socioeconomic status
    Low 3,020 32.7 51* 4,573 32.5 54* 585 35.9 42* 8,180 32.8
    Medium 1,907 20.6 56  2,909 20.7 56 352 21.6 50  5,169 20.7
    High 4,309 46.7 56  6,575 46.8 56 693 42.5 49 11,579 46.5
Level of urbanization
    Rural 631 6.8 58  859 6.1 58 127 7.8 54 1,617 6.5
    Urban 8,605 93.2 54* 13,198 93.9 55* 1,503 92.2 47 23,306 93.5
Total
 		 9,236   14,057   1,630   24,923  
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* P-value < 0.05; female; Non-Hispanic white; SES high and rural were used as the referent catagories

The overall sex-specific AAIR for malignant PCNST was highest among males, at 6.6 per 100,000 (C.I., 6.4, 6.8). For benign PCNST, the AAIR was highest for females, at 10.0 per 100,000 (C.I., 9.8, 10.2). The sex-specific AAIR for PCNST of uncertain tumor behavior were nearly equal for males and females at 1.0 and 0.9 per 100,000.

Age-specific incidence of malignant tumors was lowest, for both males and females, in their early 20s. The ASIR for males was higher than the ASIR for females, with the gap increasing between ages 40 and 79. Incidence of malignant tumors peaked for both males and females in their late 70s and decreased thereafter. In contrast to malignant tumors, benign tumors were lowest in childhood and adolescence and increased with increasing age. ASIRs for benign tumors were consistently higher among females for all age groups except ages 10–14 (Fig. 1).

Fig. 1.

Fig. 1

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Age-specific incidence rates (ASIR) of first primary benign and malignant brain and other nervous system tumors by sex, California, 2001–2005

In Fig. 2, incidence of malignant tumors was highest for non-Hispanic white males, followed by Hispanic males (7.8 and 5.7 per 100,000, respectively), and lowest for Asian/Pacific Islander and non-Hispanic black females (3.0 and 3.1 per 100,000, respectively). Incidence of benign tumors was highest for all females, with rates for non-Hispanic black, non-Hispanic white, and Hispanic females being very close (10.5, 10.2 and 9.8 per 100,000, respectively).

Fig. 2.

Fig. 2

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Age-adjusted incidence rates (AAIR) of first primary central nervous system tumors by race/ethnicity, behavior and sex, California, 2001–2005

In Table 2 we see that malignant PCNST were primarily glioblastoma (45.3%), followed distantly by lymphoma (7.5%) and anaplastic astrocytoma (7.0%). The vast majority of benign tumors consisted of meningiomas (51.6%), pituitary tumors (24.1%), and nerve sheath tumors (18.0%). Tumors of uncertain behavior were distributed similarly to benign tumors, with the largest proportion being meningiomas (26.0%), followed by craniopharyngiomas (16.6%), which are tumors of the sellar region like those of the pituitary gland. These two groups were followed by hemangioblastoma (13.3%), which are considered tumors of the meninges.

As shown in Table 3, the highest incident histologies were glioblastoma (2.6 per 100,000) for malignant and meningioma (4.5 per 100,000) for benign PCNST. The AAIR for glioblastomas was 1.7 times greater in males compared to females, while the rate of meningiomas was 2.3 times greater in females compared to males. Non-Hispanic white males had the highest AAIR of glioblastoma (3.9 per 100,000), which was significantly higher than all other race/ethnic groups by sex. Non-Hispanic white males had significantly higher AAIRs than other race/ethnic groups; a higher incidence of anaplastic astrocytoma, except for Hispanic males; and a higher incidence of nerve sheath tumors, except for Asian/Pacific Islander males. The AAIRs for astrocytoma, NOS, and pilocytic astrocytoma were significantly higher for non-Hispanic white males compared to Asian/Pacific Islander males. Among females, non-Hispanic white females had the highest rate of glioblastoma (2.4 per 100,000), regardless of race/ethnicity. Non-Hispanic white females had a significantly higher AAIR compared to other race/ethnic groups for nerve sheath tumors, except for Asian/Pacific Islander females.

Table 3.

Age-Adjusted Incidence Rates (AAIR)* of selected first primary malignant and benign central nervous system tumors by histology and sex, California, 2001–2005

Behavior Histology Sex Total NH White NH Black Hispanic API
AAIR 95% CI AAIR 95% CI AAIR 95% CI AAIR 95% CI AAIR 95% CI
Malignant Astrocytoma, anaplastic Total 0.4 0.3, 0.4 0.5 0.4, 0.5 0.1 0.1, 0.2 0.3 0.3, 0.4 0.2 0.2, 0.3
Male 0.4 0.4, 0.5 0.6 0.5, 0.6 0.1 0.0, 0.2 0.4 0.3, 0.5 0.3 0.2, 0.4
Female 0.3 0.3, 0.4 0.4 0.3, 0.5 0.2 0.1, 0.3 0.3 0.2, 0.4 0.2 0.1, 0.3
Astrocytoma, NOS Total 0.3 0.3, 0.4 0.4 0.4, 0.5 0.2 0.2, 0.4 0.3 0.3, 0.4 0.2 0.1, 0.2
Male 0.4 0.3, 0.4 0.5 0.4, 0.5 0.4 0.2, 0.6 0.4 0.3, 0.5 0.2 0.1, 0.3
Female 0.3 0.3, 0.3 0.3 0.3, 0.4 0.1 0.1, 0.3 0.3 0.2, 0.4 0.2 0.1, 0.3
Glioblastoma Total 2.6 2.5, 2.7 3.1 3.0, 3.2 1.5 1.3, 1.8 2.3 2.1, 2.5 1.2 1.1, 1.4
Male 3.3 3.1, 3.4 3.9 3.7, 4.1 2.0 1.6, 2.5 2.8 2.5, 3.1 1.6 1.3, 1.9
Female 2.0 1.9, 2.1 2.4 2.3, 2.5 1.1 0.9, 1.5 1.9 1.7, 2.2 0.9 0.7, 1.1
Oligodendroglioma Total 0.3 0.2, 0.3 0.3 0.3, 0.4 0.1 0.0, 0.2 0.2 0.2, 0.2 0.2 0.1, 0.2
Male 0.3 0.3, 0.3 0.4 0.3, 0.5 0.1 0.0, 0.3 0.2 0.1, 0.3 0.2 0.1, 0.3
Female 0.2 0.2, 0.2 0.3 0.2, 0.3 0.1 0.0, 0.2 0.2 0.1, 0.3 0.1 0.1, 0.2
Anaplastic oligodendroglioma Total 0.1 0.1, 0.1 0.2 0.1, 0.2 0.0 0.0, 0.1 0.1 0.1, 0.1 0.1 0.1, 0.1
Male 0.1 0.1, 0.1 0.1 0.1, 0.2 0.1 0.0, 0.2 0.1 0.1, 0.2 0.1 0.1, 0.2
Female 0.1 0.1, 0.1 0.2 0.1, 0.2 0.0 0.0, 0.1 0.1 0.0, 0.1 0.1 0.0, 0.1
Ependymomas, anaplastic Total 0.2 0.2, 0.3 0.3 0.2, 0.3 0.2 0.1, 0.3 0.2 0.2, 0.3 0.2 0.1, 0.2
Male 0.2 0.2, 0.3 0.3 0.2, 0.3 0.2 0.1, 0.4 0.2 0.2, 0.3 0.1 0.1, 0.2
Female 0.2 0.2, 0.3 0.3 0.2, 0.3 0.2 0.1, 0.3 0.2 0.2, 0.3 0.2 0.1, 0.3
Mixed glioma Total 0.2 0.2, 0.2 0.2 0.2, 0.3 0.1 0.0, 0.2 0.1 0.1, 0.2 0.2 0.1, 0.2
Male 0.2 0.2, 0.2 0.3 0.2, 0.3 0.1 0.0, 0.2 0.1 0.1, 0.2 0.2 0.1, 0.3
Female 0.2 0.1, 0.2 0.2 0.1, 0.2 0.1 0.0, 0.3 0.1 0.1, 0.2 0.2 0.1, 0.2
Glioma malignant, NOS Total 0.3 0.3, 0.3 0.3 0.3, 0.4 0.3 0.2, 0.4 0.3 0.2, 0.3 0.2 0.2, 0.3
Male 0.3 0.3, 0.4 0.4 0.3, 0.4 0.3 0.1, 0.5 0.3 0.2, 0.4 0.3 0.2, 0.4
Female 0.3 0.2, 0.3 0.3 0.2, 0.4 0.3 0.2, 0.5 0.3 0.2, 0.4 0.2 0.1, 0.3
PNET/Meduloblastoma Total 0.2 0.2, 0.2 0.2 0.2, 0.3 0.1 0.1, 0.2 0.2 0.2, 0.3 0.2 0.1, 0.2
Male 0.3 0.2, 0.3 0.3 0.2, 0.4 0.1 0.0, 0.2 0.3 0.2, 0.4 0.1 0.1, 0.2
Female 0.2 0.1, 0.2 0.2 0.1, 0.2 0.1 0.0, 0.2 0.2 0.1, 0.2 0.2 0.1, 0.3
Lymphomas Total 0.4 0.4, 0.5 0.4 0.4, 0.5 0.4 0.3, 0.5 0.4 0.3, 0.5 0.5 0.4, 0.6
Male 0.5 0.5, 0.6 0.5 0.4, 0.6 0.4 0.3, 0.6 0.5 0.4, 0.6 0.6 0.4, 0.7
Female 0.3 0.3, 0.4 0.3 0.3, 0.4 0.3 0.2, 0.5 0.3 0.2, 0.4 0.4 0.3, 0.5
Benign Pilocytic astrocytoma Total 0.3 0.2, 0.3 0.4 0.3, 0.4 0.2 0.2, 0.3 0.2 0.2, 0.2 0.1 0.1, 0.2
Male 0.3 0.2, 0.3 0.4 0.3, 0.4 0.2 0.1, 0.4 0.2 0.2, 0.3 0.1 0.1, 0.2
Female 0.3 0.2, 0.3 0.4 0.3, 0.5 0.2 0.1, 0.4 0.2 0.2, 0.3 0.2 0.1, 0.3
Nerve sheath Total 1.5 1.4, 1.6 1.8 1.7, 1.8 0.7 0.5, 0.9 1.0 0.9, 1.1 1.5 1.3, 1.7
Male 1.6 1.5, 1.7 1.9 1.7, 2.0 0.8 0.5, 1.0 0.9 0.8, 1.1 1.6 1.4, 1.9
Female 1.4 1.4, 1.5 1.7 1.5, 1.8 0.6 0.4, 0.9 1.0 0.9, 1.2 1.4 1.2, 1.6
Meningioma Total 4.5 4.4, 4.6 4.7 4.5, 4.8 5.0 4.5, 5.5 4.0 3.7, 4.2 4.2 3.9, 4.5
Male 2.7 2.5, 2.8 2.9 2.7, 3.1 3.2 2.6, 3.8 2.0 1.7, 2.2 2.3 2.0, 2.7
Female 6.1 5.9, 6.3 6.3 6.1, 6.5 6.5 5.8, 7.2 5.7 5.3, 6.1 5.8 5.3, 6.2
Pituitary tumors Total 2.0 1.9, 2.1 1.7 1.6, 1.8 3.2 2.9, 3.6 2.5 2.3, 2.7 1.8 1.6, 2.0
Male 2.1 2.0. 2.2 1.8 1.7, 2.0 3.8 3.2, 4.5 2.5 2.3, 2.8 1.8 1.5, 2.1
Female 2.0 1.9, 2.1 1.6 1.5, 1.7 3.0 2.5, 3.5 2.6 2.4, 2.8 1.8 1.6, 2.1
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* Age-adjusted incidence rates are per 100,000 population. Rates are standardized to the 2000 US population

PNET primitive neuroectodermal tumors

Non-Hispanic black males had significantly higher AAIR for pituitary tumors (3.8 per 100,000) compared to all other race/ethnic groups by sex and a significantly higher AAIR for meningiomas compared to Hispanic males. Non-Hispanic black females had a significantly higher AAIR for pituitary tumors compared to males and females in other race/ethnic groups, except non-Hispanic black males and Hispanic males and females.

Table 4 shows that malignant tumors occurred most often among adults, 20–64 years old. The exception was PNET/medulloblastoma (71.9%) which occurred mostly among children, adolescents and teens, 0–19 years old. Adults aged 65 years and older had higher proportions of glioblastomas (44.3%) and lymphomas (40.6%). Malignant tumors occurred chiefly among males with the exception of glioma and pilocytic astrocytoma, which occurred slightly more often among females. Hispanics had higher proportions of PNET/medulloblastoma (47.4%) and ependymoma/anaplastic ependymoma (33.5%). A higher proportion of lymphoma (13.5%) was seen among Asian/Pacific Islanders compared to other histologies. Most cases lived in areas of high SES, except for PNET/medulloblastoma, where 41.9% of the cases were of the lowest SES group.

Table 4.

Number of cases and percent of selected first primary malignant and benign central nervous system tumors by demographics and histology, California, 2001–2005

Malignant
Demographic characteristics Anaplastic astrocytoma Glioblastoma Ependymoma/anaplastic ependymoma Glioma, NOS PNET/medullo-blastoma Lymphoma Other Total
n % n % n % n % n % n % n % n %
Age group (years)
    0–19 52 8.1 53 1.3 128 30.6 166 33.4 287 71.9 18 2.6 410 17.1 1,114 12.1
    20–64 443 68.8 2,277 54.5 253 60.5 183 36.8 110 27.6 394 56.8 1,542 64.1 5,202 56.3
    65+ 149 23.1 1,850 44.3 37 8.9 148 29.8 <5 0.5 282 40.6 452 18.8 2,920 31.6
Sex
    Male 363 56.4 2,441 58.4  212 50.7 247 49.7 248 62.2 398 57.3 1,323 55.0 5,232 56.6
    Female 281 43.6 1,739 41.6 206 49.3 250 50.3 151 37.8 296 42.7 1,081 45.0 4,004 43.4
Race/ethnicity
    Non-Hispanic White 423 65.7 3,059 73.2 219 52.4 276 55.5 164 41.1 400 57.6 1,424 59.2 5,965 64.6
    Non-Hispanic Black 16 2.5 143 3.4 23 5.5 29 5.8 13 3.3 38 5.5 116 4.8 378 4.1
    Hispanic 152 23.6 724 17.3 140 33.5 140 28.2 189 47.4 156 22.5 621 25.8 2,122 23.0
    Asian-Pacific Islander 50 7.8 242 5.8 34 8.1 47 9.5 31 7.8 94 13.5 228 9.5 726 7.9
    Other/unknown <5 0.5 12 0.3 <5 0.5 5 1.0 <5 0.5 6 0.9 15 0.6 45 0.5
Socioeconomic status
    Low 218 33.9 1,218 29.1 157 37.6 184 37.0 167 41.9 245 35.3 831 34.6 3,020 32.7
    Medium 131 20.3 875 20.9 69 16.5 105 21.1 77 19.3 141 20.3 509 21.2 1,907 20.6
    High 295 45.8 2,087 49.9 192 45.9 208 41.9 155 38.8 308 44.4 1,064 44.3 4,309 46.7
Level of urbanization 
    Rural 52 8.1 305 7.3 26 6.2 34 6.8 19 4.8 47 6.8 148 6.2 631 6.8
    Urban 592 91.9 3,875 92.7 392 93.8 463 93.2 380 95.2 647 93.2 2,256 93.8 8,605 93.2
Total 644 4,180 418 497 399 694 2,404 9,236
Benign
Pilocytic astrocytoma Nerve sheath tumors Meningioma Pituitary tumors Other Total
n % n % n % n % n % n %
Age group (years)
    0–19 371 76.0 48 1.9 30 0.4 143 4.2 106 27.1 698 5.0
    20–64 111 22.7 2,037 80.3 3,863 53.2 2,444 72.2 221 56.5 8,676 61.7
    65+ 6 1.2 452 17.8 3,364 46.4 797 23.6 64 16.4 4,683 33.3
Sex
    Male 240 49.2 1,290 50.8 1,923 26.5 1,634 48.3 190 48.6 5,277 37.5
    Female 248 50.8 1,247 49.2 5,334 73.5 1,750 51.7 201 51.4 8,780 62.5
Race/ethnicity
    Non-Hispanic White 250 51.2 1,639 64.6 4,626 63.7 1,528 45.2 223 57.0 8,266 58.8
    Non-Hispanic Black 31 6.4 74 2.9 460 6.3 322 9.5 15 3.8 902 6.4
    Hispanic 168 34.4 423 16.7 1,273 17.5 1,116 33.0 112 28.6 3,092 22.0
    Asian-Pacific Islander 30 6.1 326 12.8 829 11.4 385 11.4 35 9.0 1,605 11.4
    Other/unknown 9 1.8 75 3.0 69 1.0 33 1.0 6 1.5 192 1.4
Socioeconomic status
    Low 191 39.1 630 24.8 2,323 32.0 1,299 38.4 130 33.2 4,573 32.5
    Medium 94 19.3 488 19.2 1,537 21.2 689 20.4 101 25.8 2,909 20.7
    High 203 41.6 1,419 55.9 3,397 46.8 1,396 41.3 160 40.9 6,575 46.8
Level of urbanization 
    Rural 35 7.2 165 6.5 469 6.5 159 4.7 31 7.9 859 6.1
    Urban 453 92.8 2,372 93.5 6,788 93.5 3,225 95.3 360 92.1 13,198 93.9
Total 488 2,537 7,257 3,384 391 14,057
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NOS not otherwise specified, PNET primitive neuroectodermal tumors

Patients with benign tumors were more similar demographically across histology groups than those with malignant tumors. Unlike malignant tumors, benign tumors occurred chiefly among females (62.5%). Benign PCNST occurred most often among adults, 20–64 years old (61.7%); non-Hispanic whites (58.8%) followed by Hispanics (22.0%); those in the higher SES groups (46.8%) followed by those in the lowest (32.5%); and urban residents (93.9%) at time of diagnosis. Meningiomas were highest among females (73.5%). Pilocytic astrocytoma (76.0%) occurred mostly among children, adolescents and teens, 0–19 years old. Among Hispanics and non-Hispanic blacks, tumors of the pituitary gland occurred more often than other anatomic sites (33% and 9.5%, respectively).

Discussion

Thirty-seven percent of California’s PCNST were found to be malignant and 56% benign. The AAIR of malignant PCNST in California was 5.8 cases per 100,000 persons, and benign PCNST was 8.5 cases per 100,000 persons.

Consistent with findings of other studies, the incidence of malignant tumors increased with increasing age except for the youngest (0–14 years) and oldest (>65 years) members of our study population [11, 17, 18]. A similar, but more monotonic age-related pattern was found for benign tumors. The highest incidence for both malignant and benign PCNST was among adults, 20–64 years old. Median age at diagnosis ranged widely by sex, race/ethnicity, SES, and the level of urbanization of patient residence. Significant differences were found in median age at diagnosis by sex for malignant but not for benign PCNST. Non-Hispanic whites were the oldest (57 years old) while Hispanics were the youngest (41 years old). Those in the lowest SES level and those who lived in rural California were significantly younger at the time of diagnosis. Disparities in median age at diagnosis could indicate etiologic differences in PCNST or disparities in healthcare utilization, access and diagnostics among these groups.

The incidence of malignant PCNST was highest among non-Hispanic white males, followed by Hispanic males [17, 19, 20]. Benign PCNST in California occurred more often among females. The AAIRs were similar across all race/ethnic groups, lead slightly by non-Hispanic black females (10.5 per 100,000). In our race/ethnicity analyses, we found significantly higher AAIRs for glioblastoma, pilocytic astrocytoma, anaplastic astrocytoma, oligodendroglioma, and nerve sheath tumors among non-Hispanic white males and females. In comparison, non-Hispanic black males and females had significantly higher rates of meningiomas and pituitary tumors [21–28]. We found higher incidence rates of nerve sheath tumors among Asian/Pacific Islanders. Unlike other studies, we found that the AAIR of pituitary tumors among Asian/Pacific Islanders was nearly the same rate as reported for non-Hispanic whites [29–32].

Overall PCNST proportional incidence, regardless of tumor behavior, was highest for the highest SES group, followed by the lowest SES group [28, 33]. Inskip et al. (2003) found similar results for gliomas and meningiomas, in which the incidence was highest among those with more education, greater income, and private insurance. The incidence among those with public insurance was also somewhat higher, possibly betraying a reporting bias linked to population healthcare coverage [33, 34]. Differential tumor detection and reporting between those with and without health insurance may account for some of the observed differences.

As in other studies, glioblastoma was the dominant histologic category for malignant PCNST (43%) in California [35, 36]. Although the proportion of cases we found in California was exceedingly higher than that found by others [11, 37], California’s AAIR (2.6 per 100,000 cases) was lower than those recorded elsewhere, which range from 3.1 to 4.8/100,000 [11, 38, 39]. The AAIR of lymphoma (0.4 per 100,000) was similar in California to that reported elsewhere [11, 38–40], despite changes in their histological classification and their effect over time [41].

The dominant histologic categories for benign PCNST were meningiomas (53.5%), tumors of the pituitary gland (24.9%), and tumors of the nerve sheath (18.7%), collectively representing 97% of California’s benign tumor cases. The AAIRs for meningiomas, tumors of the pituitary gland, and tumors of the nerve sheath were 4.5, 2.0, and 1.5 per 100,000, respectively. Californian rates for meningiomas were similar to those reported by some other studies [11, 35, 38, 39, 42] but not all [43]. The rate of pituitary tumors in California was higher than that reported by CBTRUS, 1.37 per 100,000 [11], while the incidence rate for tumors of the nerve sheath was the same as that reported for the nation.

Cancer incidence is difficult to compare across geographical areas, time-periods and information sources. Data used in national and international incidence studies can differ in diagnostic and neuropathological assessment, case ascertainment practices [44–47]. Some studies are single institution or if population-based may lack a sufficient case population to calculate incidence rates or if rates can be calculated, the use of the world standard population for incidence rates standardization rather than the U.S. standard population [48, 49].

Among U.S. CNS tumor incidence studies, counts and rates can vary by data collection sources and tumor classifications systems. All national CNS tumor incidence statistics derived cases from one of four centralized data collection sources: the NPCR from the CDC; the North American Association of Central Cancer Registries (NAACCR); SEER and CBTRUS. Both NPCR and NAACCR are population-based and cover more than 95% of the U.S. population [8, 50], while SEER, a non-random sample of central cancer registries, represents 26% of the population [9]. CBTRUS differs from these agencies since it is a voluntary repository for CNS tumor data. In 1999, CBTRUS was estimated to cover 15% of the U.S. population with contributions from 16 state registries (excluding California) [11, 51]. All of these cancer data collection agencies use the ICD-O tumor classification system [7]; whereas neuropathologists use the WHO grading system, which is specific to classifying CNS tumors [52]. Both of these tumor malignancy scales were created by the World Health Organization and can differ substantially, one essential difference is in tumor behavior categories. The ICD-O category of uncertain tumor behavior applies to CNS tumors, whereas the WHO grading scheme does not have an option for coding tumors of uncertain behavior. Coding discrepancies can occur at the individual pathology report level. This issue is further complicated by the application of data collection agency specific coding rules. Pilocytic astrocytoma is considered benign using the WHO grading system and ICD-O-3, but it is classified as malignant for reporting purposes by NAACCR and SEER and thus all North American central tumor registries. Given that pilocytic astrocytoma is a high-incidence histology, its inclusion or exclusion could significantly sway pediatric PCNST statistics. On the other hand, some statistical sources choose not to partition histologies by tumor behavior, thus the incidence of CNS tumors calculated by these sources can appear higher than from other sources [11].

Other differences in CNS tumor incidence statistics can arise from the inclusion of all CNS tumors from a single case, regardless of tumor sequence (first primary tumors versus all primary tumors) and the organization of tumor histology codes. The CCR as well as all member central cancer registries of NPCR and NAACCR, use the SEER program’s incidence site recode system that standardizes ICD-O histology subgroups [7, 9]. When comparing the incidence of pituitary gland tumors between sources, we found wide variation in the ICD-O-3 histology codes used by CBTRUS and SEER. These code subgroup differences may explain a nearly two-fold difference in reported incidence in California compared to the nation, as reported by CBTRUS [11].

This is the first study to examine both malignant and benign PCNST in California. California is a large, heavily populated state with a diverse ethnic, cultural, and socioeconomic population. This diversity is reflected in the CCR, and we were able to conduct robust analyses and make comparisons that few others can perform. The CCR’s epidemiologic value stems from the 1988 state-mandated comprehensive reporting of cancer cases from all physicians, hospitals, clinics, treatment facilities and pathology laboratories. Because a single standard is used for statewide data collection, quality assurance, and training and education for cancer registration, we acquire optimal case ascertainment and a high level of accuracy for many data items.

Our study and data source are not without limitations. This study was conducted solely using the CCR and was not supplemented with other data. The CCR data are collected for the purpose of surveillance and can be less detailed than those derived from medical records to support the design of a specific research study. Population-based cancer registry data are derived from many sources, thus, the quality of some variables may vary. Individual-level social indicators are not available to the CCR. Our SES measure is a composite of census-derived data and is more efficient for data analysis, and it avoids biases inherent in the use of individual component indicators. Another potential source of error is the misclassification of cases. Despite a rigorous data review and cleaning process, cases could have been misclassified based on tumor behavior, histology, and/or anatomical site.

Cancer surveillance identifies populations at greatest risk and which of their specific population attributes are associated with disease, providing valuable insights into disease etiology and prevention. This study of California PCNST establishes a foundation for future studies to examine age-group differences (i.e., children and seniors), specific histologies (i.e., glioblastoma and pituitary tumors), risk factors, and incidence trends over time.

Acknowledgement

The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Sect. 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N01-PC-54404 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement 1U58DP00807-01 awarded to the Public Health Institute. The authors would like to thank Mark Allen, Research Scientist II, Winny Roshala, CTR, Quality Control Specialist II and Jennifer Dodge, MS, Research Scientist I, of the California Cancer Registry for their technical support and Dr. Erica Whitney of the University of California, Davis and Cynthia Klutznick for their editorial guidance.

Disclaimer The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred.

Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Contributor Information

Monica Brown, Phone: +916-779-2687, FAX: +916-779-0264, Email: MBrown@ccr.ca.gov, Email: MonBrown@ucdavis.edu.

Rudolph Schrot, Email: Rudolph.Schrot@ucdmc.ucdavis.edu.

Katrina Bauer, Email: KBauer@ccr.ca.gov.

Deanna LeTendre, Email: DLeTendre@ccr.ca.gov.

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