CHONDROSARCOMAHISTOLOGIC VARIANTS AND

PROGNOSIS

DEPARTMENT OF ORAL PATHOLOGY/MEDICINE

UNIVERSITY OF BENIN TEACHING HOSPITAL

INTRODUCTION

According to the World Health Organization, chondrosarcomas represent a heterogenous group of tumours characterized by their ability of cartilage formation{1}.It is the second most common sarcoma of bone(after osteosarcoma). It rarely occurs in the jaw, about 1-3% of chondrosarcomas occur in the head and neck region.

In the jaws, maxillary lesions are slightly more common than mandibular lesions.Usual presentation is that of a painless, rapidly growing swelling which causes loosening of teeth.Maxillary lesions could be painful, with added features of visual disturbance, epistaxis, nasal obstruction and headache.

HISTOPATHOLOGY

Chondrosarcoma can be classified into 2 types:1. Conventional type2. Variant typei. Mesenchymal chondrosarcomaii. Dedifferentiated chondrosarcomaiii. Clear cell chondrosarcoma

CONVENTIONAL CHONDROSARCOMA

It accounts for more than 90% of all chondrosarcomas{2}. It can further be classified into 3 grades based on i. Cellularity of the neoplasmii. Cytologic atypiaiii. Type of matrixiv. Mitotic figures

GRADE I (LOW GRADE) Low cellularity Limited cytonuclear atypia The nuclei of chondrocytes are round or ovoid, may

show slight degrees of nuclear enlargement and hyperchromasia, and the cytoplasm is abundant and vacuolated or finely granular.

Mainly chondroid matrix Absence of (or rare) mitotic figures. Occasional binucleate cells are present.

GRADE II (INTERMEDIATE GRADE) Moderate cellularity Moderate cytonuclear atypia The nuclei of chondrocytes are roughly twice the

size of non-neoplastic chondrocytes, and are either hyperchromatic or have an open chromatin pattern & irregular contours.

Chondro-myxoid matrix Occasional mitotic figures. Binucleate cells are easily identified; trinucleate

cells are uncommon.

GRADE III (HIGH GRADE) Highly cellular Severe cytonuclear atypia Contain many bizarre multinucleated cells that

demonstrate severe pleomorphism and hyperchromasia.

Mainly myxoid matrix. Significant mitoses.

Approximately 60% of conventional chondrosarcomas are grade I, 35% are grade II and 5% are grade III {2}.In a review of 56 patients with chondrosarcoma of the jaws and facial bones, over 75% were grade I, with the remainder being grade II; no grade III lesions were found{3}.

MESENCHYMAL CHONDROSARCOMA

An aggressive variant type chondrosarcoma; classified as a high-grade lesion. It is composed of sheets of small, round or oval cells and variable amounts of cartilage.The essential histologic features are Sheets of small, round, ovoid or spindle-shaped

cells with hyperchromatic nuclei and scant cytoplasm.

Nodules of mildly to moderately cellular cartilage scattered throughout the tumour.

Mitoses are uncommon There is no significant pleomorphism in either the

small round cells or in the cartilaginous elements{4}.

DEDIFFERENTIATED CHONDROSARCOMA

It is an extremely aggressive variant type of chondrosarcoma, and is classified as a high-grade lesion.It is composed of 2 components: a well differentiated cartilaginous tumour (usually a low-grade conventional chondrosarcoma) next to a high-grade sarcoma, with a remarkably sharp junction between the 2 components.

The 2 components hold identical genetic aberrations and p53 overexpression, with additional genetic changes in the high grade(anaplastic) component, suggesting a common ancestor cell{5}.The high-grade sarcoma is usually a pleomorphic spindle cell sarcoma.

CLEAR CELL CHONDROSARCOMA

It is the least common variant; and is considered to be a low-grade lesion.Microscopically, clear cell chondrosarcoma has a lobular growth pattern, and is composed of sheets of large cells with abundant clear or pink cytoplasm that is rich in glycogen and delineated by well defined cell borders .They also contain areas of conventional low-grade chondrosarcoma.

Moderate to high cellularity Majority of the cells are round to ovoid with

moderate to abundant amounts of clear, frequently vacuolated cytoplasm.

Nuclei of the neoplastic cells are enlarged with a moderately to coarsely granular chromatin and large distinct nucleoli.

Myxoid or Chondromyxoid stroma Multinucleated osteoclast-like giant cells.

PROGNOSIS

The prognosis of chondrosarcoma is directly related to• Histologic grade• Size of tumour at presentation• Adequacy of surgery

Histologic Grade

This is the most important independent prognostic factor. The higher the grade of the lesion, the more aggressive the clinical behaviour, the higher the risk of metastasis, and the poorer the prognosis.Grade I chondrosarcomas generally do not show distant metastases. The incidence of metastatic disease has been shown to be 0%, 10% and 70% for chondrosarcomas of histologic grade I, grade II and grade III respectively{6}.

Size and Location of Tumour

The larger the size of the tumour at presentation, the poorer the prognosis. Lesions greater than 15cm at presentation show a 0% 5yr survival rate.Tumours located in easily accessible sites show a better prognosis. In the orofacial region, mandibular lesions show a better prognosis compared to maxillary lesions.

Adequacy of Surgery

Sensitivity of chondrosarcoma to radiotherapy and chemotherapy is usually poor, hence surgery remains the most important treatment option.Chondrosarcoma usually infiltrates between the marrow spaces for long distances without causing considerable bony expansion. Radiographs therefore may not show the full extent of the lesion.The best form of surgery for chondrosarcoma is a wide local resection with tumour-free margins.When surgery is incomplete, local recurrence rates are very high.

CONCLUSION

Chondrosarcomas are a heterogenous group of tumours that show varying degrees of aggression.They rarely metastasize, but when they do, it is usually to the lungs and bones via the haematogenous route.Chondrosarcomas of the jaws(though rare) usually have a less favourable prognosis compared to extragnathic lesions{7}.The 5yr survival rate for chondrosarcomas of the jaws(15-20%)appears to be poorer than that for chondrosarcomas in other body sites{6}.

Compared to osteosarcoma of the jaws, chondrosarcomas have a poorer prognosis.The most common cause of death due to chondrosarcomas of the jaws is uncontrolled local recurrence and extension into adjacent vital structures{6,8}.As such, surgeons should exhaust all available means at their disposal(e.g Computed Tomography, Frozen sections) to ensure complete removal of the tumour, as this has a direct impact on the long term prognosis.

REFERENCES1. World Health Organization classification of tumours. Pathology

and Genetics. Tumours of soft tiissue and bone. Lyon, France : IARC Press; 2002.pp. 234- 257

2. Silverberg S.G, DeLellis R.A, Frable W.J, LiVolsi V.A, Wick M.R:Silverberg’s principles and practice of surgical pathology and cytopathology. 4th ed, Vol 1, 2006. Chapt 14 pp 715-721.

3. Neville B.W, Damm D.D, Allen C.M, Bouquot J.E.Oral and maxillofacial pathology. 2nd ed, chapt14,pp 578-580.

4. Cawson R.A, Binnie W.H, Eveson J.W. Colour atlas of oral disease. 2nd ed 1993, chapt 7 pp 7.7.

5. Bovee J.V, Cleton-Jansen A.M, Rosenberg C et al. Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis. J Pathol 1999;189(4):454-462.

6. Regezi J.A, Sciubba J.J, Jordan R. Oral pathology, clinical pathologic correlations. 4th ed, chapt 144, pp 328-330.

7. Sapp J.P, Eversole L.R, Wysocki G.P. Contemporary oral and maxillofacial pathology. 2nd ed, 2004. chapt ,pp 129-130.

8. Cawson R.A,Odell E.W. Cawson’s essentials of oral pathology and oral medicine. 7th ed, 2002, chapt 9 pp 144.