The Laryngoscope
C 2014 The American Laryngological,
V
Rhinological and Otological Society, Inc.
Laryngeal Chondrosarcoma: A Population-Based Analysis
Pariket M. Dubal, BA; Peter F. Svider, MD; Vivek V. Kanumuri, BS; Amit A. Patel, MD;
Soly Baredes, MD, FACS; Jean Anderson Eloy, MD, FACS
Objectives/Hypothesis: Laryngeal chondrosarcoma (LC) is a rare entity, reportedly comprising less than 1% of all
laryngeal tumors. Consequently, the incidence and survival of patients with this slow-growing tumor has been difficult to
study. Our objective was to evaluate incidence, organized by patient demographics, as well as long-term survival trends of
this malignancy using a population-based database.
Study Design: Retrospective analysis of the United States National Cancer Institute’s Surveillance, Epidemiology, and
End Results (SEER) registry.
Methods: The SEER database was searched for patients diagnosed with LC between 1973 and 2010. Data analyzed
included patient demographics, incidence, treatment modality, and survival.
Results: One-hundred and forty-three cases were identified, representing 0.2% of all laryngeal tumors. Median age at
diagnosis was 61.7 years. Men and women constituted 76.2% and 23.8% of patients, respectively. Tumors were locally invasive with 37.7% T4 disease and infrequent regional and distant metastases. The 1-year, 5-year, and 10-year disease-specific
survival for LC was 96.5%, 88.6%, and 84.8%, respectively, compared to 88.3%, 68.2%, and 59.3%, respectively for patients
with all other laryngeal tumors (P values < 0.01). Relative survival was 94.9% at 1 year, 88.5% at 5 years, and 88.4% at 10
years.
Conclusions: This analysis represents the largest LC study sample to date, allowing for evaluation of incidence and
long-term survival. LC occurs infrequently, is locally invasive, but only rarely metastasizes. Prognosis for LC is significantly
better than for other laryngeal malignancies.
Key Words: Laryngeal chondrosarcoma, laryngeal tumors, chondrosarcoma of the larynx, malignancy, SEER,
demographic, incidence, disease-specific survival.
Level of Evidence: 2b.
Laryngoscope, 124:1877–1881, 2014
INTRODUCTION
Chondrosarcoma is rare in the head and neck, comprising only about 0.1% of head and neck neoplasms.1
Chondrosarcoma of the larynx, described in the literature as early as 1816 by Dr. Francis Travers,2,3 is
exceedingly uncommon, reportedly constituting less than
1% of all laryngeal tumors.4,5 Although much time has
passed since Dr. Travers prescribed his laryngeal chondrosarcoma patient “an astringent gargle with an altera-
From the Department of Otolaryngology–Head and Neck Surgery
(P.M.D., V.V.K., A.A.P., S.B., J.A.E.); the Center for Skull Base and Pituitary
Surgery, Neurological Institute of New Jersey (S.B., J.A.E.); the Department of Neurological Surgery (J.A.E.), Rutgers New Jersey Medical
School, Newark, New Jersey; and the Department of Otolaryngology–
Head and Neck Surgery, Wayne State University School of Medicine
(P.F.S.), Detroit, Michigan, U.S.A.
Editor’s Note: This Manuscript was accepted for publication on
January 27, 2014.
Presented as an oral presentation at the 2014 Combined Sections
Meeting of the Triological Society, Miami Beach, Florida, U.S.A., January 10–12, 2014.
The authors have no funding, financial relationships, or conflicts
of interest to disclose.
Send correspondence to Jean Anderson Eloy, MD, FACS, Associate
Professor and Vice Chairman, Director, Rhinology and Sinus Surgery,
Co-Director, Endoscopic Skull Base Surgery Program, Department of
Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical
School, 90 Bergen St., Suite 8100, Newark, NJ 07103.
E-mail: [email protected]
DOI: 10.1002/lary.24618
Laryngoscope 124: August 2014
tive course of calomel,”2 no consensus has yet been
reached regarding optimal treatment for this rare tumor.
Surgical management, including partial and total laryngectomy, has been widely reported in the literature.5,6
The increasing effectiveness of radiotherapy in skeletal
chondrosarcoma, however, has led some to advocate
radiotherapy, with isolated cases of complete remission
reported in the literature.5
Laryngeal chondrosarcoma (LC) originates from
hyaline cartilage, with one case series reporting 75%
arising from the cricoid cartilage.7 Low-grade disease
may be difficult to differentiate from chondroma,
although the former still contains multiple nuclei per
cell and demonstrates invasive behavior that is the hallmark of malignant disease.3,8 Compared to chondrosarcoma located elsewhere in the body, LC tends to be lowgrade, well-differentiated, and less aggressive.3,9 Even
higher grade histologies are relatively indolent in the
larynx, with a low probability for metastasis.10
As LC is an uncommon entity, literature covering
this topic is comprised exclusively of case reports and
small retrospective case series. Additionally, recent analyses have demonstrated that many of these series have
overlapping patient populations,4,6 making a comprehensive analysis of a large patient population potentially
valuable. The Surveillance, Epidemiology, and End
Results (SEER) registry is a valuable tool for evaluating
rare malignancies, and has been effective in extracting
Dubal et al.: Laryngeal Chondrosarcoma
1877
information on many tumors of interest to otolaryngologists.11–16 In the present analysis, we utilize the SEER
database to evaluate the incidence of LC, organized by
patient demographics, treatment modalities, and longterm survival trends.
squamous cell carcinoma (ICD-O-3 8050–8089) and adenocarcinoma (ICD-O-3 8140–8389), which respectively
comprised 95.1% (59,474) and 0.5% (297) of all laryngeal
tumors. Unspecified epithelial neoplasms (ICD-O-3
8010–8049) accounted for 2.5% (1,553) of laryngeal neoplasms, while another 0.9% (558) of laryngeal neoplasms
were completely unspecified (ICD-O-3 8000–8049). The
next most common histology after LC was non-Hodgkin’s
lymphoma of the mature B-cell subtype (0.2%), with 118
reported cases (Table I).
LC has a statistically significant predilection for
whites relative to other laryngeal tumors (P < 0.001)
(Table II). A 3:1 male predominance was noted, although
this predilection did not differ statistically from other
laryngeal tumors (P 5 0.190). The median age at diagnosis was 61.7 years, with a range from 32 to 88 years.
Incidence (adjusted to the standard 2000 U.S. population
as per Census P25–1130) was 0.010 per 100,000. Surgical intervention was utilized in 123 cases; laryngectomy
(partial or total) was more common than local tumor
excision. Whereas other laryngeal tumors were frequently treated with radiotherapy, most LC patients did
not receive radiotherapy (Table III).
MATERIALS AND METHODS
Tumor Characteristics/Staging
SEER 18 was utilized to extract incidence and survival
data for patients diagnosed with LC between 1973 and 2010. The
SEER 18 database consists of data gathered from 18 cancer
registries from various states and metropolitan areas in the
United States. Since the SEER database omits patient identifiers, institutional review board approval was not required. We
queried SEER 18 for malignancies of the larynx (C32.0, C32.1,
C32.2, C32.3, C32.8, and C32.9). The most common malignant
laryngeal histologies were identified for comparative analysis.
Results were filtered using the International Classification of
Diseases and Oncology, Third Edition (ICD-O-3) codes corresponding to chondrosarcoma (9220/ 3–9243/ 3) in order to isolate
data for LC. A combination of collaborative staging codes was
used to gather information on staging based on the American
Joint Committee on Cancer (AJCC) Seventh Edition guidelines.
Average tumor size and the range of tumor sizes
were reported for cases when such information was
available. Staging information based on the AJCC Seventh Edition criteria was available for 54 cases. Tumor
TABLE I.
Most Common Malignant Laryngeal Histologies.
ICD-O-3 Code
Histology
No. of Patients
8050–8089
squamous cell neoplasms
59,474
8010–8049
8000–8009
epithelial neoplasms, NOS
unspecified neoplasms
1,553
558
8140–8389
adenocarcinomas
297
9220–9243
9670–9699
chondrosarcomas
NHL-mature B-cell lymphomas
143
118
8560–8579
complex epithelial neoplasms
71
8120–8139
8430–8439
transitional cell carcinomas
mucoepidermoid neoplasms
48
48
ICD-O-3 5 International Classification of Diseases and Oncology,
Third Edition; NHL 5 non-Hodgkin’s lymphoma; NOS 5 not otherwise
specified.
Statistical Analysis
The SEER*Stat 8.1.2 software (National Cancer Institute,
Bethesda, MD) was used for analysis. Patient data for LC was
compared with that from other laryngeal tumors using two proportion z tests and Fischer exact tests (NCSS Statistical Software, Kaysville, UT). Survival data exported from SEER was
reorganized in Microsoft Excel 2013 (Microsoft Corporation,
Redmond, WA) and then analyzed for disease-specific survival
(DSS) using log-rank analysis in JMP Statistical Discovery 11
(SAS Institute, Cary, NC). Data derived from SEER*Stat 8.1.2
was also used to generate relative survival (RS) data. Statistical
significance was indicated by a probability value (P value)
of < 0.05 for all tests.
RESULTS
TABLE II.
Patient Characteristics.
Total
LC
(N 5 143)
Other
(N 5 62422)
P Value
50,398
109
50,289
0.190
12,167
34
12,133
Race
white
51,743
137
51,606
black
8,573
3
8,570
2,249
3
2,246
61.4
63.3
61.7
32–88
63.0
0–106
Characteristic
Gender
male
female
other/unknown
Age group
mean
median
range
0–29
145
0
145
30–39
40–49
772
5,127
5
13
767
5,114
50–59
15,116
35
15,081
60–69
70–79
20,691
14,904
46
32
20,645
14,872
80 1
5,810
12
5,798
3.630
0.010
3.620
< 0.001
Patient Characteristics
Incidence
(per 100,000)*
One-hundred and forty-three patients with LC were
identified from 1973 to 2010 using SEER 18. LC represented 0.2% of all laryngeal tumors (62,565). LC was the
third most common specified laryngeal malignancy after
*Cases reported from 2000 to 2010, adjusted to the U.S. 2000 population as per Census P25–1130.
LC 5 laryngeal
chondrosarcoma;
other 5 other
laryngeal
malignancies.
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1878
Dubal et al.: Laryngeal Chondrosarcoma
TABLE III.
Treatment Modalities.
Characteristic
LC
(N 5 143)
TABLE IV.
Tumor Characteristics.
Other
(N 5 62422)
Surgery
no surgery†
local excision
16
28
2,6353
10,308
partial laryngectomy
33
2,459
total laryngectomy
laryngectomy, NOS
39
1
6,830
320
pharyngolaryngectomy
3
335
surgery, NOS
unknown
19
4
8,441
7,376
< 0.001*
‡
Radiation
none
radiation
133
8
15,654
44,550
unknown
2
1,773
refused
0
445
Average size (greatest dimension in cm)
3.2
Range of size (greatest dimension in cm)
0.1–7.0
P Value
< 0.001*
*Statistically significant.
†
No tumor-directed surgery
‡
Radiation includes external beam, radioisotopes, combination therapy, and radioactive implants
LC 5 laryngeal chondrosarcoma; NOS 5 not otherwise specified; other 5 other laryngeal malignancies.
extent varied, but T4 tumors were common—comprising
37.7% of cases. There was a complete absence of local
lymph node involvement, and distant metastasis was
extremely uncommon with an incidence of 2.0% (Table IV).
Survival Analysis
DSS and relative survival (RS) were calculated for
LC (Table V). The 1-year, 5-year, and 10-year DSS for
LC was 96.5%, 88.6%, and 84.8%, respectively, compared
to 88.3%, 68.2% and 59.3%, respectively, for patients
with all other laryngeal tumors (P < 0.01) (Fig. 1). RS
(the calculated ratio between observed survival rate and
the expected age-adjusted survival rate) for LC was
94.9% at 1 year, 88.5% at 5 years, and 88.4% at 10
years, respectively, compared to 86.1%, 63.1%, and
50.6%, respectively, for all other laryngeal tumors.
TNM*
No
T1
T2
18
10
DISCUSSION
While changing trends in the management of laryngeal malignancies have been well documented, little is
Laryngoscope 124: August 2014
34.0
18.9
T3
5
9.4
T4
N0
20
50
37.7
100.0
N1
0
0.0
M0
M1
49
1
98.0
2.0
Stage†
No
Percent (%)
I
II
16
9
34.0
19.2
III
5
10.6
IV
17
36.2
*TNM staging is based on American Joint Committee on Cancer
Seventh Edition.
†
Staging is based only on cases with complete TNM information.
TNM 5 tumor, node, metastasis.
known regarding the optimal treatment approach to LC.
Due to its infrequency, literature describing clinical
characteristics of LC is exclusively comprised of case
reports and small case series. The present analysis reinforces LC’s relative infrequency, identifying only 143
patients over the 38 years encompassed by the SEER
database. This database is ideal for evaluating uncommon entities such as LC, as it may be the only resource
with a large enough sample to allow for adequate statistical power.12 Evaluating a single resource containing
this number of cases allows us to address and compare
patient demographic factors. For example, this analysis
suggests that LC has a statistically significant predilection for whites, while at the same time noting an overall
male predominance, although the latter finding did not
TABLE V.
Survival Data.
Therapy
As summarized in Table VI, local tumor excision
had a 100% 5-year DSS. However, total laryngectomy
was the most common treatment for LC, with a 5-year
DSS of 80.3%. Partial laryngectomy, on the other hand,
had a DSS of 100%. Patients treated with laryngectomy
were more likely to die of other unspecified causes than
were patients receiving other treatments. Reliable
outcome-based analysis could not be carried out due to
small sample sizes and a preponderance of unknowns
with respect to cause of death and surgical technique.
Percent (%)
Laryngeal
Other Laryngeal
Chondrosarcoma
Malignancies
(N 5 120)
(N 5 52271)
Survival Measure
P Value
Disease-specific survival
1 year
96.5%
88.3%
< 0.01
5 years
10 years
88.6%
84.8%
68.2%
59.3%
< 0.001
< 0.001
1 year
5 years
94.9%
88.5%
86.1%
63.1%
10 years
88.4%
50.6%
Relatives*
*Relative survival: the ratio between observed survival rate and the
expected age-adjusted survival rate.
Dubal et al.: Laryngeal Chondrosarcoma
1879
Fig. 1. DSS for LC versus other laryngeal tumors. DSS 5 diseasespecific survival; LC 5 laryngeal chondrosarcoma.
reach statistical significance relative to other laryngeal
malignancies (Table II). Reasons for this statistically significant racial predilection, as well as the trend pointing
toward male predominance, are unclear. Further analysis with a prospective design, while ideal for assessing
these characteristics, may be difficult to accomplish due
to the rarity of this lesion.
Patients with LC demonstrated a significantly
greater survival at all time intervals relative to individuals with other laryngeal malignancies (Table IV, Fig. 1).
In evaluating this sample of 143 patients, our analysis
offers an important resource for practitioners seeking
prognostic information regarding this entity. This data
provide patients a clear illustration of this lesion’s excellent prognosis—and allows for a more comprehensive
discussion of the risks, alternatives, and benefits when
deliberating therapeutic approaches than does data
derived from case reports and small case series.
The majority of cases in this retrospective analysis
did not demonstrate metastasis or regional lymph node
involvement, findings that are consistent with LC’s
excellent prognosis (Table VI). These findings are further supported by the literature, which widely reports
LC as a low-grade and well-differentiated entity.4,8,17,18
Despite rare metastasis, LC is locally aggressive, often
only causing symptoms via compression of and local
invasion into adjacent structures.19
Therapeutic management for LC is determined primarily by tumor size and location, with histologic grade
being an ancillary determinant.7 Conservative, functionpreserving surgery is the primary treatment of choice;
however, bulky tumors whose excision may disrupt
laryngeal function require more radical procedures.4,7,10
Successful function-preserving surgery may be achieved
via endoscopic removal, and in certain cases, partial laryngectomy.4 Total laryngectomy, on the other hand, is
usually reserved for large, bulky tumors in which wide
surgical excision could cause destabilization of the cricoid ring.20
Presently, the surgical trend is to perform total laryngectomy in cases in which the neoplasm extends
beyond half the cricoid cartilage.21 In the present analysis, total laryngectomy was associated with a relatively
more unfavorable DSS when compared to local excision
and partial laryngectomy (Table VI). Presumably, the
lower survival in total laryngectomy was due to the
more advanced nature of the tumors.
One-hundred and twenty-three patients in this
analysis underwent surgery, while radiotherapy was
only used in eight individuals (Table III). Interestingly,
radiotherapy has been noted to be a useful adjuvant
therapy in patients suffering from skeletal chondrosarcoma, although some have suggested that higher doses
may be needed in certain tumors.22,23 Regardless, its
infrequent use, coupled with contemporary advances in
radiotherapy techniques, suggests an area for future
evaluation in both laryngeal and extra-laryngeal
chondrosarcomas.
The rate of recurrence for LC is relatively high,
with a reported incidence of 18% to 50%.3,4,9,24,25 Recurrence is usually associated with incomplete removal of
the primary neoplasm, especially in patients whose initial treatment involved partial or local excision.6
Whereas patients who underwent local excision in the
present study had a high survival rate, they may have
been more likely to develop recurrence of LC (Table V).
Unfortunately, data for recurrence was unavailable for a
majority of the patients analyzed in the present study.
Although the SEER database may be ideal for
examining an entity as uncommon as LC, there are several limitations inherent to our analysis. Importantly,
information about individual cases contained limited
details. More comprehensive clinical information detailing specific types of surgical intervention and radiotherapies, as well as details regarding associated
comorbidities, chemotherapy, and prior medical history
would have been invaluable. In addition, there is
TABLE VI.
Survival by Treatment Modality (N 5 117).
Treatment
N
Disease-Specific Deaths
Other Deaths
Total Surviving
5-yr DSS
No surgery
13
1
1
11
92.3%
Excision
22
0
0
22
100.0%
Total laryngectomy
Partial laryngectomy
39
28
6
0
3
2
30
26
80.3%
100.0%
Surgery NOS
15
2
3
10
84.6%
DSS 5 disease-specific survival; NOS 5 not otherwise specified .
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Dubal et al.: Laryngeal Chondrosarcoma
concern over considerable heterogeneity in data collection over a wide geographic area and treatment/therapeutic changes over the long period of time (> 35 years)
studied here.
Nonetheless, this resource contains a geographically
diverse group of patients (i.e., it does not have the limitations of a single-institution study), which allows for
better external validity. Furthermore, it allows for a
large enough sample for adequate statistical power—and
has more standardized and reliable information than
what can be acquired from the scarce case reports and
small case series available in the literature. Consequently, it has been of value in myriad analyses relevant
to head and neck cancers.11,12,14,26–32 It has been extensively used in the study of laryngeal cancer, with notable
advancements in the understanding of squamous cell
carcinoma subtypes, tumors of cartilage and bone, and
the impact of radiotherapy on survival.29,31,33
CONCLUSION
This analysis represents the largest LC study sample to date, allowing for the evaluation of incidence and
long-term survival. LC occurs infrequently, accounting
for 0.2% of all laryngeal tumors. It shows a 3:1 male predilection, with a significant white preponderance. LCs
tend to show extensive local invasion with a significant
proportion of T4 lesions, but they only rarely display
regional or distant metastases. Prognosis for LC is significantly better than for other laryngeal malignancies.
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