clear cell chondrosarcoma of the larynx

Case Report

Clear Cell Chondrosarcoma of the LarynxA Case Report of a Rare Histologic Variant in anUncommon Localization

B. Kleist, Ph.D., M. Poetsch, Ph.D., C. Lang, Ph.D., A. Bankau, Ph.D.,G. Lorenz, Ph.D, K. Süess-Fridrich, Ph.D., G. Jundt, Ph.D., andE. Wolf, Ph.D.

The authors describe a clear cell chondrosarcoma of the larynx.The clear cell type is a rare variant of chondrosarcoma that onlytwice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed byimmunohistochemical results, in particular by positive stainingfor S-100 protein and collagen type II, and ultrastructural find-ings. Loss of heterozygosity analysis demonstrated allelic lossat 9p22 and 18q21, but neither in the region of the Rb gene onchromosome 13q nor at the p53 locus on chromosome 17pwhere allelic loss has already been reported in chondrosarco-mas. Furthermore, our molecular genetic investigations re-vealed a methylation of the cell cycle control gene p16, whichis localized on chromosome 9p. This characteristic has beenrecorded previously only in high-grade chondrosarcomas. Mu-tations in the exons of p16, alterations of the putative tumorsuppressor gene MMAC1/PTEN on chromosome 10q, or anamplification of the cyclin D1 gene (CCND1) on 11q13, whichwere found to be changed in other studies of chondrosarcomas,could not be demonstrated here.Key Words: Clear cell chondrosarcoma—Larynx—Immunohistochemistry—Ultrastructure—Molecular genetics.

Am J Surg Pathol 26(3): 386–392, 2002.

Chondrosarcoma of the larynx is a rare tumor com-prising 3% of all chondrosarcomas and <1% of malig-nant laryngeal tumors.5 In a recent review of the litera-ture 250 published laryngeal chondrosarcomas werecompiled.11 Within chondrosarcomas the clear cell type

is an uncommon variant that accounts for about 2% ofthese tumors.10 It was first described as a pathologicentity in 1976.33 The epiphyses of long bones, in par-ticular of the proximal and distal femur, of the proximalhumerus and proximal tibia, are characteristically in-volved. Cases have also been reported in the ulna, rib,small bones of the hand and foot, pelvis, sternum, ver-tebrae, temporal bone, and maxilla.8,10,31 To the best ofour knowledge, clear cell feature in a laryngeal chondro-sarcoma has only twice been recorded previously.21,28

In this article we present a histologic, immunohisto-chemical, ultrastructural, and molecular genetic charac-terization of a further clear cell chondrosarcoma withuncommon localization in the larynx.

CASE REPORT

In November 1997, a 57-year-old man presented withdyspnea. He was admitted to the hospital, where directlaryngoscopy revealed a subglottic neoplasm originatingfrom the left side of cricoid cartilage, extending to thetrachea and having caused two thirds occlusion of theupper tracheal lumen. Magnetic resonance imagingdocumented a mainly exophytic tumor mass that mea-sured 3.0 × 2.5 cm (Fig. 1). The tumor was resectedthrough a laryngeal fissure. Fifteen and 20 months afterthe first diagnosis recurrences occurred and were againlocally removed. Thirteen months after the last surgicalprocedure a third relapse was diagnosed. Magnetic reso-nance imaging showed a 3.0 × 3.0 cm tumor mass origi-nating from the left side of cricoid cartilage and extend-ing to paratracheal tissue. Because of tumor extensionwith airway obstruction and the tendency to recur, a la-ryngectomy was performed in August 2000. A neck dis-section and a left side hemithyroidectomy were included

From the Institute of Pathology (B.K., G.L.), Institute of ForensicMedicine (M.P.), and the Department of Oto-Rhino-Laryngology(C.L., A.B.), Ernst-Moritz-Arndt-University, Greifswald, Germany; theCenter of Bone Tumors of Swiss Society of Pathology (K.S.-F., G.J.),Institute of Pathology, University of Basel, Basel, Switzerland; and theInstitute of Pathology (E.W.), Regional Hospital, Stralsund, Germany.

Address correspondence and reprint requests to Britta Kleist, PhD,Institute of Pathology, Ernst-Moritz-Arndt-University, F.-Loeffler-Strasse 23e, D-17489 Greifswald, Germany; e-mail:[email protected]

The American Journal of Surgical Pathology 26(3): 386–392, 2002 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia

386

because of the presence of clinically suspicious lymphnodes and the close proximity of the tumor to the leftthyroid lobe, which presented clinically a nodular goiter.The patient has been free of disease until now.

MATERIALS AND METHODS

Histology and Histochemistry

For light microscopy examination, the tissue was fixedin 4.5% phosphate-buffered formalin (pH 7), routinelyprocessed, and embedded in paraffin wax using standardmethods. Four-micrometer sections were stained withhematoxylin and eosin, periodic acid–Schiff (PAS) withand without diastase predigestion, and toluidine blue.

The specimens underwent additional independent his-topathologic review in the Center of Bone Tumors ofSwiss Society of Pathology (K.S.-F., G.J.).

Immunohistochemistry

Formalin-fixed, paraffin-embedded tissue was stainedby the streptavidin-biotin-peroxidase method (DakoLSAB [2] system) with 3-amino-9-ethyl-carbazol aschromogen. The antibodies used included vimentin(1:15, Dako, Glostrup, Denmark), S-100 protein (poly-clonal, 1:150, Dako), cytokeratin (clone MNF116, 1:50,Dako), epithelial membrane antigen (1:25, Dako), Ki67antigen (clone MIB-1, 1:10, Dako), proliferating cellnuclear antigen (PCNA) (1:50, Dako), and collagen typeII (1:15, Novocastra Laboratories Ltd, Newcastle uponTyne, UK).

Electron Microscopy

The material for ultrastructural examination was ini-tially formalin fixed. The tissue was subsequently fixedin glutaraldehyde and buffered in sodium cacodylate. Itwas postfixed with osmium tetroxide and stained en blocwith uranyl acetate. Dehydration was performed withgraded solutions of acetone, and infiltration embeddingwas performed with araldite resin 1 �m-sections werestained with thionin and examined by light microscopy.

Representative areas were chosen, sectioned, stainedwith lead citrate, and examined in an EM 910 LEO elec-tron microscope (LEO, Oberkochem, Germany).

Isolation of DNA FromParaffin-Embedded Material

DNA isolation from paraffin-embedded tumor andnon-neoplastic tissue was performed as previouslydescribed23 with the High Pure PCR TemplatePreparation Kit (Roche Molecular Biochemicals,Mannheim, Germany).

Microsatellite Analysis

A panel of nine fluorochrome (6-FAM, HEX, orTAMRA) labeled polymerase chain reaction primer pairsthat amplified informative dinucleotide repeat microsat-ellite loci, located on chromosome 9p22–21 (D9S162,D9S171, D9S197), chromosome 11q25 (D11S910),chromosome 13q12–14 (D13S217, D13S263), chromo-some 17 (D17S513, D17S786), and chromosome 18(D18S58), were obtained from Genome Data Base(http://gdbwww.gdb.org), and cytogenetic locationwas obtained from the genetic location database(ftp://cedar.genetics.soton.ac.uk/publichtml). The poly-merase chain reaction was performed in three multiplexanalyses each comprising three different labeled primersin a final volume of 12.5 �L containing 50–80 ng DNA,0.3 �mol/L of each primer, 200 �mol/L of each dNTP,1.5 �mol/L MgCl2, 15 mmol/L Tris/HCl, 50 mmol/LKCl, and 1 unit AmpliTaq Gold (Applied Biosystems,Weiterstadt, Germany) by denaturing at 95°C for 10 min-utes, followed by 35 cycles of 95°C for 30 seconds, 55°Cfor 90 seconds, 72°C for 120 seconds, and an additional

FIG. 1. Magnetic resonance image demonstrating a tu-mor mass of the larynx (arrow), which caused airwaycompression.

CLEAR CELL CHONDROSARCOMA OF THE LARYNX 387

Am J Surg Pathol, Vol. 26, No. 3, 2002

10 minutes at 72°C with the Trio Thermocycler (Biome-tra, Göttingen, Germany); 1.5 �L polymerase chain re-action product was mixed with 12 �L deionized form-amide and 0.5 �L ROX-labeled internal lane standard,denatured at 90°C for 120 seconds, snap-cooled on ice,and electrophoresed with the ABI 310 DNA sequencer(Applied Biosystems). Loss of heterozygosity was deter-mined as described by Canzian et al.6

Molecular Genetic Analysis

Mutation analysis of the nine exons of thePTEN/MMAC1 gene, mutation analysis of both exons ofp16, and determination of methylation status of p16 werecarried out as described before.24 Analysis of cyclin D1(CCND1) amplification was performed as described byHibberts et al.13

RESULTS

Macroscopic Findings

The recurrent tumors excised in 1997 and 1999 con-sisted of several gray–white and brown firm specimensmeasuring up to 2.5 cm. The completely resected larynxshowed a subglottic firm lobulated tumor mass of 5.0 ×4.5 × 2.5 cm originating from the left cricoid and pro-truding the overlying intact mucosa. The cut surface hada red–brown and gray–white glassy appearance. Theneoplasm had led to obstruction of the laryngeal andtracheal lumina and was situated close to the removedleft thyroid lobe.

Histology and Histochemistry

The findings were similar in resection specimens andtissue of the laryngectomy. The tumor consisted ofdensely packed large tumor cells with distinct boundaries(Fig. 2). The centrally located nuclei were enlarged withmoderate polymorphism and surrounded by abundantclear cytoplasm. PAS/diastase-PAS staining demon-strated small amounts of intracellular glycogen. Binucle-ated cells as well as mitotic figures were extremely rare.Multinucleated osteoclast-like giant cells were fre-quently seen. Scattered throughout the tumor, numeroussmall newly formed irregularly shaped trabeculae of os-teoid and woven bone were present, but neoplastic oste-oid formation was lacking. A few spindle-shaped cellsand a fibrous tissue with ectatic blood vessels were in-terposed between the clear cell areas. Chondroid matrixformation was rare within the clear cell component butabundant in little tumor foci containing medium-sized orwidely spaced chondrocytes with small dense or moder-ately enlarged nuclei, which were consistent with low-grade conventional chondrosarcoma. The tumor wasseparated from thyroid gland tissue and striated musclesby a small fibrotic rim of <1 mm. Invasion of blood orlymphatic vessels and lymph node metastases were ab-sent. The left thyroid lobe was composed of collapsedand cystic distended colloid-containing follicles in anodular configuration without evidence of malignancy.

Immunohistochemistry

The tumor cells were positive for S-100 protein andvimentin. The cytoplasm of a few tumor cells and tinyfoci of interposed chondroid matrix were weakly stainedby collagen type II (Fig. 3). Staining with Ki67 antigen(MIB-1) demonstrated a low proliferative index of <5%of tumor cells. PCNA staining showed a positive rate of48%. Cytokeratin (MNF116) and epithelial membraneantigen were negative.

FIG. 2. (A) Clear cell chondrosarcoma (right part) mergedinto an area of conventional chondrosarcoma (left part) atthe outer margin of the tumor (hematoxylin and eosin,original magnification ×87.5). (B) Proliferation of clearcells with numerous small, irregularly shaped trabeculaeof bone. Multinucleated osteoclast-like giant cells arescattered in the tumor (hematoxylin and eosin, originalmagnification ×175). Inset: Higher magnification showingtumor cells with abundant powdery-to-clear cytoplasmand distinct boundaries (PAS, original magnification×350).

B. KLEIST ET AL.388


Electron Microscopy

The clear cells (Fig. 4A) had an irregularly outlinedcytoplasm. The nuclei were frequently indented and hada finely dispersed chromatin. Furthermore, a few smallmitochondria and rough endoplasmic reticulum cisternaewere seen. Other cells showed more irregular, convo-luted nuclei. Rough endoplasmic reticulum of these cellswas very well developed and presented remarkable dila-tation of the cisternae (Fig. 4B). In a few cells a promi-nent nucleolus occurred.

Microsatellite Analysis

Of the nine loci investigated for this tumor six wereinformative (D9S162, D11S910, D17S513, D17S786,D18S58, and D13S263), whereas the two other loci onchromosome 9p21 and one other locus on chromosome13q12 were not informative. Loss of heterozygositywas found at D9S162 (9p22-p21) and D18S58 (18q21)(Fig. 5).

Molecular Genetic Analysis

All nine exons of the MMAC/PTEN gene and bothexons of the p16 gene could be amplified from tumorDNA, but we could not detect any mutations in the exonsor the sequenced part of the introns. In contrast, we wereable to demonstrate a methylation of the promoter of p16(data not shown). Neither an amplification nor a loss ofheterozygosity could be found for the CCND1 gene (cy-clin D1).

DISCUSSION

Cartilaginous tumors comprise 0.1–0.2% of all laryn-geal neoplasms.4 The first laryngeal chondrosarcomawas described by New in 1935.19 According to Gripp

et al., 254 cases had been reported in the literature until1997.11 Thereafter, 29 laryngeal chondrosarcomas weredocumented: 17 in case reports and 12 in a retrospectivestudy of the Royal National Throat, Nose and EarHospital, London.27 The cricoid cartilage (70–83%) is

FIG. 4. (A) Electron micrograph showing a cell with ir-regularly outlined cytoplasm, little indented nucleus, and anucleolus (original magnification ×15,000). (B) Anothercell with deeply indented nucleus and dilated rough en-doplasmic reticulum cisternae (original magnification×30,000).

FIG. 3. Collagen type II positive staining was present inthe cytoplasm of a few tumor cells (original magnification×100).



reported to be the most common site of involvement,followed by the thyroid cartilage (20%), the arytenoids,vocal cords, and epiglottis.5,27 Most of the laryngealchondrosarcomas considered in the literature are of theuniform conventional type.7,20 The clear cell type wedescribe here is an uncommon and rare variant of chon-drosarcoma, not only in the larynx but also in general. Itaccounts for about 2% of all chondrosarcomas.10 Sincethe first description of this entity in 1976,33 approxi-mately 150 cases have been reported in the literature.8

Clear cell chondrosarcoma is mainly characterized byrounded cells having conspicuous, predominately clearcytoplasm with sparse intervening matrix, and by addi-tional criteria as scattered osteoclast-like giant cells,bone trabeculae, aneurysmal bone cyst-like areas, andalso foci of conventional chondrosarcoma.10,29 Withinthe 16 cases of a recent study of clear cell chondrosar-comas, the portion of the diagnostic clear cell componentvaried between 20% and 80% of the entire tumor area,8

whereas all tumors of an earlier analysis, like the chon-drosarcoma described here, presented predominatelyclear cell features.16

Because of its rarity, the diagnosis of laryngeal clearcell chondrosarcoma has to be confirmed. The light-microscopic appearance and the presence of glycogenand S-100 protein are consistent with this diagnosis butnot specific parameters of a clear cell chondrosarcoma.Additional evidence of cartilaginous differentiation wasprovided by immunohistochemically demonstrated col-lagen type II expression, which could be found only incartilage and in very small amounts in the eye and whichhas already been described as a characteristic for clearcell chondrosarcoma.18 At the electron-microscopic levelthe tumor cells showed an irregularly outlined cyto-plasm, indented nuclei, and large dilated rough endoplas-mic reticulum cisternae. These findings have already

been reported in another ultrastructural study of clear cellchondrosarcoma and were defined there as characteristic,but not specific features because they can occur in de-veloping and aging cartilage as well as in different chon-droid tumors.9 In contrast to our PAS staining presentingintracellular glycogen, there was no certain evidence ofglycogen in our ultrastructural investigation, which couldbe caused by the special processing of initially formalin-fixed tissue for the electron-microscopic examination.

The differential diagnoses of a malignant laryngealneoplasm include squamous cell carcinoma and meta-static clear cell carcinoma. The diagnosis of squamouscell carcinoma was rejected on the basis of histology andthe absence of cytokeratin immunoreactivity. However,there are some variants of squamous cell carcinoma thatmay have associated chondrosarcomatous metaplasticfoci and can thereby be mistaken for chondrosarcoma.The distinction between chondrosarcoma and metastaticclear cell carcinoma, especially renal cell carcinoma, ismore difficult because even immunohistochemical re-sults have to be interpreted with caution, given that abouttwo thirds of renal cell carcinomas express S-100 pro-tein10 and some cases of clear cell chondrosarcoma arefound to be positive for cytokeratins.8 More helpful indistinguishing these entities are collagen type II expres-sion as mentioned above and conventional staining meth-ods such as PAS and Sudan-Red: the cells in clear cellmetastatic lesions contain glycogen and fat, whereasthose of clear cell chondrosarcoma are rich only in gly-cogen.32 Chondroblastic osteosarcoma was also consid-ered as a differential diagnosis but was readily excludedbecause severe nuclear polymorphism and atypical mi-tosis were absent. Furthermore, there was no evidence oftumoral osteoid, which is typical for osteosarcoma. Clearcell feature in an osteosarcoma was described only oncein the literature.25 Chondroblastoma was recently re-ported as a difficult differential diagnosis because itshares several histologic characteristics with clear cellchondrosarcoma.18 However, in the actual case this di-agnosis was considered unlikely in view of the predomi-nating clear cells, which do not occur in such high per-centages in chondroblastoma. In uncertain cases the im-munohistochemical determination of the PCNA indexcould facilitate the differential diagnosis. Recent datasuggest that clear cell chondrosarcoma has a highergrowth activity and thereby a different biologic behaviorcompared with benign chondroblastoma.18 In accordancewith these authors, we could demonstrate a PCNA ex-pression at a relatively high level.

Many important questions concerning the histogenesisof clear cell chondrosarcomas have not been fully inves-tigated and remain controversial. Although clear cellchondrosarcoma is generally considered to be a variantof chondrosarcoma,2,16,33 some reports suggest this tu-mor to be an independent histologic type between chon-

FIG. 5. Electropherogram of the normal DNA(above)/tumor DNA (below) pair. The y-axis representsthe peak height in fluorescence units. The arrows markthe lost allele.

B. KLEIST ET AL.390


droblastoma and chondrosarcoma or an atypical variantof chondroblastoma.17 Other investigators propose itsclassification as an osteoblastic tumor rather than chon-droblastic.3 Cytogenetic analyses or other studies deter-mining gains and losses of chromosomal regions couldprovide more information in this controversial discus-sion. However, the number of cytogenetically analyzedchondrosarcomas is small and, to the best of our knowl-edge, no specific or diagnostic cytogenetic markers havebeen established for the clear cell type. Loss of hetero-zygosity analysis of 22 chondrosarcomas revealed allelicloss at chromosome 13q and 17p in 36% and 25%, re-spectively,34 but the tumor examined here did not showloss of heterozygosity at these chromosomal regions. Incontrast, allelic loss in this actual case of chondrosar-coma could be demonstrated at chromosome 9p22-p21 inthe region harboring the cell cycle control gene p16, aregion in which alterations have also been reported inother chondrosarcomas.14,15 This led us to a methylationstudy of p16 and to the investigation of the exons of p16,which revealed a methylation of the promoter region ofp16 in this tumor but no changes of the genomic struc-ture. A methylation of p16 has already been reported forhigh-grade chondrosarcomas.1 Additional allelic losscould be found at chromosome 18q21 in this investiga-tion, but alterations of this chromosomal region harbor-ing the DCC gene have not been described for chondro-sarcomas so far. Because loss of parts from chromosome1012,26 has been reported in chondrosarcoma, wescreened the putative tumor suppressor geneMMAC1/PTEN on chromosome 10 for alterations butcould not demonstrate any changes of the genomic se-quence. Amplification of cyclin D1 has been demon-strated in many tumors22 and very recently also in chon-drosarcomas of the jaw.30 Therefore, we looked for anamplification of the CCND1 gene on chromosome 11q13but could not show an alteration of this gene in ourcase of chondrosarcoma. A study of larger patient groupswith clear cell chondrosarcoma, especially in head andneck sites, is necessary to determine the biologic signifi-cance of these molecular genetic results. However, in thenear future alterations of the p16 gene could providefurther information concerning the biologic behavior ofchondrosarcoma.

The morphologic findings and the clinical course ofthis case support the general experience that chondrosar-coma of the larynx virtually implies a low grade of ma-lignancy and thus a favorable course of disease as pro-posed by other authors.5,21 Nevertheless, early correctdiagnosis is important to avoid local progressive growthand multiple recurrences. �

AcknowledgmentsThe authors thank S. Uffmann, A. Wolter, S. Balk, S.

Seefeldt, and M. Maschke for excellent technical assistance, M.

Niemeyer for help with the electron microscope, M. Rosenfeldfor preparation of the photographs, and G. Kallwellis for re-viewing the magnetic resonance imaging.

REFERENCES

1. Asp J, Sangiorgi L, Inerot SE, et al. Changes of the p16 gene butnot the p53 gene in human chondrosarcoma tissues. Int J Cancer2000;85:782–6.

2. Bjornsson J, Unni KK, Dahlin DC, et al. Clear cell chondrosar-coma of bone: observations in 47 cases. Am J Surg Pathol 1984;8:223–30.

3. Boss A, Ueda Y, Wuisman P, et al. Histogenesis of clear cellchondrosarcoma: an immunohistochemical study with osteonectin,a noncollagenous structure protein. J Cancer Res Clin Oncol 1991;117:43–9.

4. Brandwein M, Moore S, Som P, et al. Laryngeal chondrosarcomas:a clinicopathologic study of 11 cases, including two ‘dedifferenti-ated’ chondrosarcomas. Laryngoscope 1992;102:858–67.

5. Burggraaf BA, Weinstein GS. Imaging case study of the month:chondrosarcoma of the larynx. Ann Otol Rhinol Laryngol 1992;101:183–4.

6. Canzian F, Salovaara R, Hemminkki A, et al. Semiautomated as-sessment of loss of heterozygosity and replication error in tumors.Cancer Res 1996;56:3331–7.

7. Dorfman HD, Czerniak B. Bone Tumors. St. Louis: Mosby,1997:353–440.

8. Engels C, Werner M, Delling G. Das Klarzellchondrosarkom.Pathologe 2000;21:449–55.

9. Faraggiana T, Sender B, Glicksman P. Light- and electron-microscopic study of clear cell chondrosarcoma. Am J Clin Pathol1981;75:117–21.

10. Fechner RE, Mills SE. Tumors of the Bones and Joints, In: Atlasof Tumor Pathology, 3rd series. Washington, DC: Armed ForcesInstitute of Pathology, 1993:115–8.

11. Gripp S, Pape H, Schmitt G. Chondrosarcoma of the larynx. Therole of radiotherapy revisited: a case report and review of theliterature. Cancer 1998;82:108–15.

12. Gunawan B, Weber M, Bergmann F, et al. Clonal chromosomeabnormalities in enchondromas and chondrosarcomas. CancerGenet Cytogenet 2000;120:127–30.

13. Hibberts NA, Simpson DJ, Bicknell JE, et al. Analysis of CyclinD1 (CCND1) allelic imbalance and overexpression in sporadichuman pituitary tumors. Clin Cancer Res 1999;5:2133–9.

14. Jagasia AA, Block JA, Qureshi A, et al. Chromosome 9 relatedaberrations and deletions of the CDKN2 and MTS2 putative tumorsuppressor genes in human chondrosarcomas. Cancer Lett 1996;105:91–103.

15. Larramendy ML, Tarkkanen M, Valle J, et al. Gains, losses, andamplifications of DNA sequences evaluated by comparative geno-mic hybridization in chondrosarcomas. Am J Pathol 1997;150:685–91.

16. Le Charpentier Y, Forest M, Postel M, et al. Clear-cell chondro-sarcoma. Cancer 1979;44:622–9.

17. Liang-tang W, Tze-chun L. Clear cell chondrosarcoma of bone: areport of three cases with immunohistochemical and affinity his-tochemical observations. Pathol Res Pract 1993;189:411–5.

18. Masui F, Ushigome S, Fujii K. Clear cell chondrosarcoma: apathological and immunohistochemical study. Histopathology1999;34:447–52.

19. New GB. Sarcoma of the larynx: report of two cases. Arch Oto-laryngol 1935;21:648–52.

20. Nicolai P, Ferlito A, Sasaki CT, et al. Laryngeal chondrosarcoma:incidence, pathology, biological behavior, and treatment. Ann OtolRhinol Laryngol 1990;99:515–23.

21. Obenauer S, Kunze E, Fischer U, et al. Unusual chondrosarcoma ofthe larynx: CT findings. Eur Radiol 1999;9:1625–8.

22. Palmero I, Peters G. Perturbation of cell cycle regulators in humancancer. Cancer Surv 1996;27:351–67.

23. Poetsch M, Dittberner T, Woenckhaus C. PTEN/MMAC1 in ma-



lignant melanoma and its importance for tumor progression. Can-cer Genet Cytogenet 2001;125:21–6.

24. Poetsch M, Lorenz G, Kleist B. Detection of new PTEN/MMAC1mutations in head and neck squamous cell carcinomas with loss ofchromosomes 10. Cancer Genet Cytogenet 2001; in press.

25. Povysil C, Matejovsky Z, Zidkova H. Osteosarcoma with a clear-cell component. Virchows Arch A Pathol Anat Histopathol 1988;412:273–9.

26. Raskind WH, Conrad EU, Matsushita M. Frequent loss of hetero-zygosity for markers on chromosome arm 10q in chondrosarco-mas. Genes Chromosomes Cancer 1996;16:138–43.

27. Rinaldo A, Howard DJ, Ferlito A. Laryngeal chondrosarcoma: a24-year experience at the Royal National Throat, Nose and EarHospital. Acta Otolaryngol 2000;120:680–8.

28. Said S, Civantos F, Whiteman M, et al. Clear cell chondrosarcomaof the larynx. Otolaryngol Head Neck Surg 2001;125:107–8.

29. Schajowicz F. International Histological classification of tumours.In: Histological Typing of Bone Tumours, 2nd ed. Berlin: Springer,1993:19–20.

30. Si X, Liu Z. Expression and significance of cell cycle-related pro-teins Cyclin Dl, CDK4, p27, E2F-l and Ets-1 in chondrosarcoma ofthe jaws. Oral Oncol 2001;37:431–6.

31. Slootweg PJ. Clear-cell chondrosarcoma of the maxilla: report of acase. Oral Surg Oral Med Oral Pathol 1980;50:233–7.

32. Taconis WK. Clear cell chondrosarcoma: report of three cases andreview of the literature. Diagn Imag Clin Med 1986;55:219–27.

33. Unni KK, Dahlin DC, Beabout JW, et al. Chondrosarcoma: clearcell variant. A report of sixteen cases. J Bone Joint Surg Am1976;58:676–83.

34. Yamaguchi T, Toguchida J, Wadayama B, et al. Loss of hetero-zygosity and tumor suppressor gene mutations in chondrosarco-mas. Anticancer Res 1996;16:2009–15.

B. KLEIST ET AL.392


clear cell chondrosarcoma of the larynx

Documents