The LaryngoscopeVC 2014 The American Laryngological,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 alllaryngeal tumors. Consequently, the incidence and survival of patients with this slow-growing tumor has been difficult tostudy. Our objective was to evaluate incidence, organized by patient demographics, as well as long-term survival trends ofthis malignancy using a population-based database.

Study Design: Retrospective analysis of the United States National Cancer Institute’s Surveillance, Epidemiology, andEnd Results (SEER) registry.

Methods: The SEER database was searched for patients diagnosed with LC between 1973 and 2010. Data analyzedincluded 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 atdiagnosis was 61.7 years. Men and women constituted 76.2% and 23.8% of patients, respectively. Tumors were locally inva-sive with 37.7% T4 disease and infrequent regional and distant metastases. The 1-year, 5-year, and 10-year disease-specificsurvival for LC was 96.5%, 88.6%, and 84.8%, respectively, compared to 88.3%, 68.2%, and 59.3%, respectively for patientswith 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 10years.

Conclusions: This analysis represents the largest LC study sample to date, allowing for evaluation of incidence andlong-term survival. LC occurs infrequently, is locally invasive, but only rarely metastasizes. Prognosis for LC is significantlybetter 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

INTRODUCTIONChondrosarcoma is rare in the head and neck, com-

prising only about 0.1% of head and neck neoplasms.1

Chondrosarcoma of the larynx, described in the litera-ture as early as 1816 by Dr. Francis Travers,2,3 isexceedingly uncommon, reportedly constituting less than1% of all laryngeal tumors.4,5 Although much time haspassed since Dr. Travers prescribed his laryngeal chon-drosarcoma patient “an astringent gargle with an altera-

tive course of calomel,”2 no consensus has yet beenreached regarding optimal treatment for this rare tumor.Surgical management, including partial and total laryn-gectomy, has been widely reported in the literature.5,6

The increasing effectiveness of radiotherapy in skeletalchondrosarcoma, however, has led some to advocateradiotherapy, with isolated cases of complete remissionreported in the literature.5

Laryngeal chondrosarcoma (LC) originates fromhyaline cartilage, with one case series reporting 75%arising from the cricoid cartilage.7 Low-grade diseasemay be difficult to differentiate from chondroma,although the former still contains multiple nuclei percell and demonstrates invasive behavior that is the hall-mark of malignant disease.3,8 Compared to chondrosar-coma located elsewhere in the body, LC tends to be low-grade, well-differentiated, and less aggressive.3,9 Evenhigher grade histologies are relatively indolent in thelarynx, with a low probability for metastasis.10

As LC is an uncommon entity, literature coveringthis topic is comprised exclusively of case reports andsmall retrospective case series. Additionally, recent anal-yses have demonstrated that many of these series haveoverlapping patient populations,4,6 making a comprehen-sive analysis of a large patient population potentiallyvaluable. The Surveillance, Epidemiology, and EndResults (SEER) registry is a valuable tool for evaluatingrare malignancies, and has been effective in extracting

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 PituitarySurgery, Neurological Institute of New Jersey (S.B., J.A.E.); the Depart-ment of Neurological Surgery (J.A.E.), Rutgers New Jersey MedicalSchool, 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 onJanuary 27, 2014.

Presented as an oral presentation at the 2014 Combined SectionsMeeting of the Triological Society, Miami Beach, Florida, U.S.A., Janu-ary 10–12, 2014.

The authors have no funding, financial relationships, or conflictsof interest to disclose.

Send correspondence to Jean Anderson Eloy, MD, FACS, AssociateProfessor and Vice Chairman, Director, Rhinology and Sinus Surgery,Co-Director, Endoscopic Skull Base Surgery Program, Department ofOtolaryngology–Head and Neck Surgery, Rutgers New Jersey MedicalSchool, 90 Bergen St., Suite 8100, Newark, NJ 07103.E-mail: jean.anderson.eloy@gmail.com

DOI: 10.1002/lary.24618

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information on many tumors of interest to otolaryngolo-gists.11–16 In the present analysis, we utilize the SEERdatabase to evaluate the incidence of LC, organized bypatient demographics, treatment modalities, and long-term survival trends.

MATERIALS AND METHODSSEER 18 was utilized to extract incidence and survival

data for patients diagnosed with LC between 1973 and 2010. TheSEER 18 database consists of data gathered from 18 cancerregistries from various states and metropolitan areas in theUnited States. Since the SEER database omits patient identi-fiers, institutional review board approval was not required. Wequeried SEER 18 for malignancies of the larynx (C32.0, C32.1,C32.2, C32.3, C32.8, and C32.9). The most common malignantlaryngeal histologies were identified for comparative analysis.Results were filtered using the International Classification ofDiseases and Oncology, Third Edition (ICD-O-3) codes corre-sponding to chondrosarcoma (9220/ 3–9243/ 3) in order to isolatedata for LC. A combination of collaborative staging codes wasused to gather information on staging based on the AmericanJoint Committee on Cancer (AJCC) Seventh Edition guidelines.

Statistical AnalysisThe SEER*Stat 8.1.2 software (National Cancer Institute,

Bethesda, MD) was used for analysis. Patient data for LC wascompared with that from other laryngeal tumors using two pro-portion z tests and Fischer exact tests (NCSS Statistical Soft-ware, Kaysville, UT). Survival data exported from SEER wasreorganized 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 8.1.2was also used to generate relative survival (RS) data. Statisticalsignificance was indicated by a probability value (P value)of<0.05 for all tests.

RESULTS

Patient CharacteristicsOne-hundred and forty-three patients with LC were

identified from 1973 to 2010 using SEER 18. LC repre-sented 0.2% of all laryngeal tumors (62,565). LC was thethird most common specified laryngeal malignancy after

squamous cell carcinoma (ICD-O-3 8050–8089) and ade-nocarcinoma (ICD-O-3 8140–8389), which respectivelycomprised 95.1% (59,474) and 0.5% (297) of all laryngealtumors. Unspecified epithelial neoplasms (ICD-O-38010–8049) accounted for 2.5% (1,553) of laryngeal neo-plasms, while another 0.9% (558) of laryngeal neoplasmswere completely unspecified (ICD-O-3 8000–8049). Thenext most common histology after LC was non-Hodgkin’slymphoma of the mature B-cell subtype (0.2%), with 118reported cases (Table I).

LC has a statistically significant predilection forwhites relative to other laryngeal tumors (P<0.001)(Table II). A 3:1 male predominance was noted, althoughthis predilection did not differ statistically from otherlaryngeal tumors (P 5 0.190). The median age at diagno-sis was 61.7 years, with a range from 32 to 88 years.Incidence (adjusted to the standard 2000 U.S. populationas per Census P25–1130) was 0.010 per 100,000. Surgi-cal intervention was utilized in 123 cases; laryngectomy(partial or total) was more common than local tumorexcision. Whereas other laryngeal tumors were fre-quently treated with radiotherapy, most LC patients didnot receive radiotherapy (Table III).

Tumor Characteristics/StagingAverage tumor size and the range of tumor sizes

were reported for cases when such information wasavailable. Staging information based on the AJCC Sev-enth 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 epithelial neoplasms, NOS 1,553

8000–8009 unspecified neoplasms 558

8140–8389 adenocarcinomas 297

9220–9243 chondrosarcomas 143

9670–9699 NHL-mature B-cell lymphomas 118

8560–8579 complex epithelial neoplasms 71

8120–8139 transitional cell carcinomas 48

8430–8439 mucoepidermoid neoplasms 48

ICD-O-3 5 International Classification of Diseases and Oncology,Third Edition; NHL 5 non-Hodgkin’s lymphoma; NOS 5 not otherwisespecified.

TABLE II.Patient Characteristics.

Characteristic TotalLC

(N 5 143)Other

(N 5 62422) P Value

Gender

male 50,398 109 50,289 0.190

female 12,167 34 12,133

Race

white 51,743 137 51,606 < 0.001

black 8,573 3 8,570

other/unknown 2,249 3 2,246

Age group

mean 61.4 63.3

median 61.7 63.0

range 32–88 0–106

0–29 145 0 145

30–39 772 5 767

40–49 5,127 13 5,114

50–59 15,116 35 15,081

60–69 20,691 46 20,645

70–79 14,904 32 14,872

80 1 5,810 12 5,798

Incidence(per 100,000)*

3.630 0.010 3.620

*Cases reported from 2000 to 2010, adjusted to the U.S. 2000 popu-lation as per Census P25–1130.

LC 5 laryngeal chondrosarcoma; other 5 other laryngealmalignancies.

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extent varied, but T4 tumors were common—comprising37.7% of cases. There was a complete absence of locallymph node involvement, and distant metastasis wasextremely uncommon with an incidence of 2.0% (Table IV).

Survival AnalysisDSS and relative survival (RS) were calculated for

LC (Table V). The 1-year, 5-year, and 10-year DSS forLC was 96.5%, 88.6%, and 84.8%, respectively, comparedto 88.3%, 68.2% and 59.3%, respectively, for patientswith all other laryngeal tumors (P< 0.01) (Fig. 1). RS(the calculated ratio between observed survival rate andthe expected age-adjusted survival rate) for LC was94.9% at 1 year, 88.5% at 5 years, and 88.4% at 10years, respectively, compared to 86.1%, 63.1%, and50.6%, respectively, for all other laryngeal tumors.

TherapyAs summarized in Table VI, local tumor excision

had a 100% 5-year DSS. However, total laryngectomywas the most common treatment for LC, with a 5-yearDSS of 80.3%. Partial laryngectomy, on the other hand,had a DSS of 100%. Patients treated with laryngectomywere more likely to die of other unspecified causes thanwere patients receiving other treatments. Reliableoutcome-based analysis could not be carried out due tosmall sample sizes and a preponderance of unknownswith respect to cause of death and surgical technique.

DISCUSSIONWhile changing trends in the management of laryn-

geal malignancies have been well documented, little is

known regarding the optimal treatment approach to LC.Due to its infrequency, literature describing clinicalcharacteristics of LC is exclusively comprised of casereports and small case series. The present analysis rein-forces LC’s relative infrequency, identifying only 143patients over the 38 years encompassed by the SEERdatabase. This database is ideal for evaluating uncom-mon entities such as LC, as it may be the only resourcewith a large enough sample to allow for adequate statis-tical power.12 Evaluating a single resource containingthis number of cases allows us to address and comparepatient demographic factors. For example, this analysissuggests that LC has a statistically significant predilec-tion for whites, while at the same time noting an overallmale predominance, although the latter finding did not

TABLE III.Treatment Modalities.

CharacteristicLC

(N 5 143)Other

(N 5 62422) P Value

Surgery

no surgery† 16 2,6353 < 0.001*

local excision 28 10,308

partial laryngectomy 33 2,459

total laryngectomy 39 6,830

laryngectomy, NOS 1 320

pharyngolaryngectomy 3 335

surgery, NOS 19 8,441

unknown 4 7,376

Radiation‡

none 133 15,654 < 0.001*

radiation 8 44,550

unknown 2 1,773

refused 0 445

*Statistically significant.†No tumor-directed surgery‡Radiation includes external beam, radioisotopes, combination ther-

apy, and radioactive implantsLC 5 laryngeal chondrosarcoma; NOS 5 not otherwise specified; oth-

er 5 other laryngeal malignancies.

TABLE IV.Tumor Characteristics.

Average size (greatest dimension in cm) 3.2

Range of size (greatest dimension in cm) 0.1–7.0

TNM* No Percent (%)

T1 18 34.0

T2 10 18.9

T3 5 9.4

T4 20 37.7

N0 50 100.0

N1 0 0.0

M0 49 98.0

M1 1 2.0

Stage† No Percent (%)

I 16 34.0

II 9 19.2

III 5 10.6

IV 17 36.2

*TNM staging is based on American Joint Committee on CancerSeventh Edition.

†Staging is based only on cases with complete TNM information.TNM 5 tumor, node, metastasis.

TABLE V.Survival Data.

Survival Measure

Laryngeal Other Laryngeal

P ValueChondrosarcoma Malignancies

(N 5 120) (N 5 52271)

Disease-specific survival

1 year 96.5% 88.3% < 0.01

5 years 88.6% 68.2% < 0.001

10 years 84.8% 59.3% < 0.001

Relatives*

1 year 94.9% 86.1%

5 years 88.5% 63.1%

10 years 88.4% 50.6%

*Relative survival: the ratio between observed survival rate and theexpected age-adjusted survival rate.

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reach statistical significance relative to other laryngealmalignancies (Table II). Reasons for this statistically sig-nificant racial predilection, as well as the trend pointingtoward male predominance, are unclear. Further analy-sis with a prospective design, while ideal for assessingthese characteristics, may be difficult to accomplish dueto the rarity of this lesion.

Patients with LC demonstrated a significantlygreater survival at all time intervals relative to individu-als with other laryngeal malignancies (Table IV, Fig. 1).In evaluating this sample of 143 patients, our analysisoffers an important resource for practitioners seekingprognostic information regarding this entity. This dataprovide patients a clear illustration of this lesion’s excel-lent prognosis—and allows for a more comprehensivediscussion of the risks, alternatives, and benefits whendeliberating therapeutic approaches than does dataderived from case reports and small case series.

The majority of cases in this retrospective analysisdid not demonstrate metastasis or regional lymph nodeinvolvement, findings that are consistent with LC’sexcellent prognosis (Table VI). These findings are fur-ther supported by the literature, which widely reportsLC as a low-grade and well-differentiated entity.4,8,17,18

Despite rare metastasis, LC is locally aggressive, oftenonly causing symptoms via compression of and localinvasion into adjacent structures.19

Therapeutic management for LC is determined pri-marily by tumor size and location, with histologic grade

being an ancillary determinant.7 Conservative, function-preserving surgery is the primary treatment of choice;however, bulky tumors whose excision may disruptlaryngeal function require more radical procedures.4,7,10

Successful function-preserving surgery may be achievedvia endoscopic removal, and in certain cases, partial lar-yngectomy.4 Total laryngectomy, on the other hand, isusually reserved for large, bulky tumors in which widesurgical excision could cause destabilization of the cri-coid ring.20

Presently, the surgical trend is to perform total lar-yngectomy in cases in which the neoplasm extendsbeyond half the cricoid cartilage.21 In the present analy-sis, total laryngectomy was associated with a relativelymore unfavorable DSS when compared to local excisionand partial laryngectomy (Table VI). Presumably, thelower survival in total laryngectomy was due to themore advanced nature of the tumors.

One-hundred and twenty-three patients in thisanalysis underwent surgery, while radiotherapy wasonly used in eight individuals (Table III). Interestingly,radiotherapy has been noted to be a useful adjuvanttherapy in patients suffering from skeletal chondrosar-coma, although some have suggested that higher dosesmay be needed in certain tumors.22,23 Regardless, itsinfrequent use, coupled with contemporary advances inradiotherapy techniques, suggests an area for futureevaluation in both laryngeal and extra-laryngealchondrosarcomas.

The rate of recurrence for LC is relatively high,with a reported incidence of 18% to 50%.3,4,9,24,25 Recur-rence is usually associated with incomplete removal ofthe primary neoplasm, especially in patients whose ini-tial treatment involved partial or local excision.6

Whereas patients who underwent local excision in thepresent study had a high survival rate, they may havebeen more likely to develop recurrence of LC (Table V).Unfortunately, data for recurrence was unavailable for amajority of the patients analyzed in the present study.

Although the SEER database may be ideal forexamining an entity as uncommon as LC, there are sev-eral limitations inherent to our analysis. Importantly,information about individual cases contained limiteddetails. More comprehensive clinical information detail-ing specific types of surgical intervention and radio-therapies, as well as details regarding associatedcomorbidities, chemotherapy, and prior medical historywould have been invaluable. In addition, there is

Fig. 1. DSS for LC versus other laryngeal tumors. DSS 5 disease-specific survival; LC 5 laryngeal chondrosarcoma.

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 39 6 3 30 80.3%

Partial laryngectomy 28 0 2 26 100.0%

Surgery NOS 15 2 3 10 84.6%

DSS 5 disease-specific survival; NOS 5 not otherwise specified .

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concern over considerable heterogeneity in data collec-tion over a wide geographic area and treatment/thera-peutic changes over the long period of time (> 35 years)studied here.

Nonetheless, this resource contains a geographicallydiverse group of patients (i.e., it does not have the limi-tations of a single-institution study), which allows forbetter external validity. Furthermore, it allows for alarge enough sample for adequate statistical power—andhas more standardized and reliable information thanwhat can be acquired from the scarce case reports andsmall case series available in the literature. Conse-quently, it has been of value in myriad analyses relevantto head and neck cancers.11,12,14,26–32 It has been exten-sively used in the study of laryngeal cancer, with notableadvancements in the understanding of squamous cellcarcinoma subtypes, tumors of cartilage and bone, andthe impact of radiotherapy on survival.29,31,33

CONCLUSIONThis analysis represents the largest LC study sam-

ple to date, allowing for the evaluation of incidence andlong-term survival. LC occurs infrequently, accountingfor 0.2% of all laryngeal tumors. It shows a 3:1 male pred-ilection, with a significant white preponderance. LCstend to show extensive local invasion with a significantproportion of T4 lesions, but they only rarely displayregional or distant metastases. Prognosis for LC is signifi-cantly better than for other laryngeal malignancies.

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