Chondrosarcoma (primary, secondary, periosteal)

Bone & joints

Chondrosarcoma

Authors: Akif K. Guney, M.D., Shadi Qasem, M.D.

Resident / Fellow Advisory Board: Erna Forgó, M.D.

Editorial Board Member: Jose G. Mantilla, M.D.

Topic Completed: 22 April 2021

Minor changes: 22 April 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed search: chondrosarcoma [title] bone [title] review[ptyp]

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Table of Contents

Cite this page: Guney AK, Qasem S. Chondrosarcoma (primary, secondary, periosteal). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonechondrosarcoma.html. Accessed May 17th, 2021.

Definition / general

Locally aggressive or malignant group of tumors characterized by formation of cartilaginous matrix
Primary: arising without a benign precursor
Secondary:
- Central: arising in preexisting enchondroma
- Peripheral: arising in preexisting cartilaginous cap of an osteochondroma
Periosteal chondrosarcoma: occurs on the surface of the bone in association with the periosteum

Essential features

Locally aggressive or malignant group of tumors characterized by formation of cartilaginous matrix and chondrocytes embedded in lacunae
Histologic grade, extracompartmental spread and local recurrence are important prognostic factors
Radiology is essential, especially for low grade lesions
Change in the size or clinical symptoms might be an indicator of malignant transformation in enchondromas and osteochondromas
IDH1 and IDH2 mutations in approximately 50% of cases

Terminology

Atypical cartilaginous tumor = tumors resembling grade 1 chondrosarcoma arising in the appendicular skeleton
Periosteal chondrosarcoma = juxtacortical chondrosarcoma
Conventional chondrosarcoma = primary, secondary and periosteal chondrosarcomas
For low grade tumors, the term low grade cartilaginous neoplasm can be used

ICD coding

ICD-O: 9220/3 - chondrosarcoma, NOS
ICD-O: 9221/3 - periosteal chondrosarcoma

Epidemiology

Accounts for ~20% of all malignant bone tumors
Second most common primary malignant bone tumor after osteosarcoma (Cancer 1995;75:203)
Middle aged to older adults (secondary and periosteal chondrosarcoma are seen in younger patients)
M > F

Sites

Most common sites are the pelvic bones, femur and humerus (Cancer Imaging 2003;4:36)
Other sites are the trunk, skull and facial bones
Involvement of the hands and feet is rare
Periosteal chondrosarcoma involves the metaphysis of long bones, usually distal femur and humerus
Conventional type chondrosarcoma is also the most common sarcoma arising in the larynx (Am J Surg Pathol 2002;26:836, Head Neck Pathol 2020;14:707)

Etiology

Unknown etiology for primary chondrosarcoma
Malignant transformation from benign precursors in secondary chondrosarcomas (J Am Acad Orthop Surg 2010;18:608)
Increased risk of secondary chondrosarcoma in patients with Ollier disease and Maffucci syndrome (Oncologist 2011;16:1771)

Clinical features

Pain, local swelling and enlarging mass are the most common presenting symptoms (Semin Diagn Pathol 2014;31:10)
Neurological symptoms in skull base tumors (StatPearls: Chondrosarcoma [Accessed 9 March 2021])
Change in the size and clinical symptoms might be an indicator of malignant transformation in enchondromas and osteochondromas

Diagnosis

Diagnosis of chondrosarcoma can be made on imaging studies (Xray, CT scan, MRI) in combination with biopsy specimen (Skeletal Radiol 2013;42:611)
Radiology is essential, especially in low grade lesions

Radiology description

Xray: popcorn-like calcifications (punctate and ring-like opacities), lytic lesions, endosteal scalloping, thickened cortex, cortical erosion or destruction, soft tissue involvement (Curr Probl Diagn Radiol 2019;48:262)
Cortical destruction and soft tissue extension of pre-existing enchondromas might be indicators of secondary central chondrosarcoma
Thick cartilaginous cap > 1.5 - 2 cm in secondary peripheral chondrosarcoma (Radiologe 2016;56:476)
Multilobular appearance in periosteal chondrosarcoma
CT scan and MRI: helpful in showing the extent of the tumor

Radiology images

Contributed by Shadi Qasem, M.D.

Soft tissue extension

Corresponding MRI for previous image

Finger tumor

Pelvic tumor

Secondary tumor

Prognostic factors

Histologic grade, extracompartmental spread and local recurrence are important prognostic factors (J Bone Joint Surg Br 2002;84:93)
Atypical cartilaginous tumor / grade I chondrosarcomas are locally aggressive and have a good prognosis (~85% 5 year survival rate)
Grade II / III chondrosarcomas have a worse prognosis (~50% 5 year survival rate)
Local recurrence is related to tumor size and adequacy of surgical margins

Case reports

30 year old woman with periosteal chondrosarcoma and bone metastasis (World J Surg Oncol 2015;13:121)
35 year old man with postradiation chondrosarcoma (Int J Biol Markers 2014;29:e440)
36 year old man presenting with sciatica (J Orthop Case Rep 2020;10:53)
43 year old woman presenting with dyspareunia (Rom J Morphol Embryol 2018;59:927)
54 year old man with pain and swelling in the left preauricular area (Med Oral Patol Oral Cir Bucal 2009 Jan;14:E39)

Treatment

Wide surgical resection is the mainstay of treatment
Low grade chondrosarcomas are often surgically cured
Chondrosarcomas are in general resistant to chemotherapy and radiotherapy (Curr Opin Oncol 2016;28:314)
Chondrogenic tumors require a high dose of radiation (Oncologist 2008;13:320)
Resection with adjuvant radiotherapy yields the best outcome for high grade chondrosarcomas (Neurosurgery 2017;81:520)

Gross description

Neoplastic hyaline cartilage has a lobular, gray-tan cut surface
Cystic changes with myxoid or mucoid material
Mineralization appears as chalky calcium deposits
Cortical erosion and soft tissue extension can be seen
Thick cartilage cap (1.5 - 2 cm) with cystic cavities in secondary peripheral chondrosarcoma
Periosteal chondrosarcoma appears as a large, lobular mass attached to the surface of bone (Am J Surg Pathol 1985;9:666)

Gross images

Contributed by Shadi Qasem, M.D.

Femoral tumor

Pelvic tumor

Frozen section description

Nodules of hyaline cartilage with variable atypia (Sarcoma 2014;2014:902104)
For low grade tumors, the term low grade cartilaginous neoplasm can be used

Frozen section images

Contributed by Shadi Qasem, M.D.

Frozen section

Microscopic (histologic) description

Abundant cartilaginous matrix with chondrocytes embedded in lacunae
Lobular or diffuse growth (depending on grade)
Permeation of intertrabecular spaces
Varying degrees of increased cellularity, nuclear atypia and mitotic activity
- Grade I: minimally increased cellularity, nodular growth and occasional binucleate nuclei
- Grade II: moderate cellularity and diffuse growth
- Grade III: high cellularity, marked atypical cells, pleomorphic appearance and easily identifiable mitotic figures
Myxoid changes, chondroid matrix liquefaction and necrosis can be seen
Formation of nodules and cystic cavities can be seen in secondary peripheral chondrosarcoma (generally low grade tumors)
Periosteal chondrosarcoma:
- Grade I or II tumors seen on the external surface of the bone
- Cortical invasion, soft tissue extension and size (> 5 cm) can be helpful in distinguishing from periosteal chondroma (AJR Am J Roentgenol 2001;177:1183)

Microscopic (histologic) images

Contributed by Shadi Qasem, M.D.

Grade I

Myxoid degeneration

Grade II

Grade III

Bone permeation

Virtual slides

Images hosted on other servers:

Grade I

Grade II

Grade III

Cytology description

Abundance of extracellular matrix material, which is best appreciated on air dried, Giemsa based stained material
Recognizable lacunae, often containing binucleated or multinucleated chondrocytes
Atypical cartilaginous tumor / grade I chondrosarcoma is cytomorphologically indistinguishable from an enchondroma
Grade II / III chondrosarcomas are more cellular, more atypical with more myxoid matrix
Cytology is more reliable in metastatic than primary tumors (Diagn Cytopathol 2006;34:413)

Cytology images

Contributed by Shadi Qasem, M.D.

Magenta color matrix

Multinucleation

Positive stains

Stains are not necessary in the majority of cases
S100: uniformly strongly positive but in grade III it can be focally negative in less differentiated areas
D2-40 (Appl Immunohistochem Mol Morphol 2009;17:131)

Negative stains

Cytokeratin

Molecular / cytogenetics description

IDH1 and IDH2 mutations in approximately 50% of cases
Aneuploidy is seen with increasing histologic grade
TP53 mutations and affected active signaling pathways (RB1, CDKN2A, CDK) are identified particularly in high grade chondrosarcomas (J Cell Mol Med 2009;13:2843)

Videos

Chondrosarcoma versus enchondroma

Sample pathology report

Tibia, biopsy:
- Low grade cartilaginous neoplasm (see comment)
- Comment: The differential diagnosis includes enchondroma and low grade chondrosarcoma. Clinical and radiologic correlation is recommended.
Femur, resection:
- Chondrosarcoma, grade II (see comment)
- Surgical margins are negative
- See synoptic report below
- Comment: The diagnosis is made in conjunction with radiologic findings.

Differential diagnosis

Chondroblastic osteosarcoma:
- If there is significant osteoid formation, then it is osteosarcoma
- Clinical and radiological correlation is helpful (typically younger patients)
Enchondroma:
- No aggressive features radiologically
- Cytologically almost indistinguishable from low grade chondrosarcoma
- Less cellular, uniform hyaline, abundant matrix calcification
- Small, uniform, round nuclei with homogenous chromatin
Fracture callus:
- Sometimes can contain abundant proliferating cartilage looking like cartilaginous neoplasia
- Chondroid matrix is less mineralized and dark blue in color
- Clinical and radiological correlation is helpful
Chondromyxoid fibroma:
- Clinically and radiologically not aggressive
- Stellate cells
- More myxoid and less chondroid background
- SMA positive

Additional references

Surg Pathol Clin 2017;10:537, Arch Pathol Lab Med 2020;144:71

Board review style question #1

A 54 year old man had an 8 cm mass in the femur, which was resected. Which of the following is the best assessment?

Radiotherapy is the mainstay of treatment
Skull is the most common site
The most likely genetic abnormalities are IDH1 and IDH2 mutations
The tumor is sensitive to chemotherapy
There is a female predominance

Board review style answer #1

C. The most likely genetic abnormalities are IDH1 and IDH2 mutations

Comment Here

Reference: Chondrosarcoma (primary, secondary, periosteal)

Board review style question #2

A 45 year old man had a biopsy from a 7 cm mass in the proximal humerus demonstrating a low grade cartilaginous lesion. Which of the following is true?

Correlation with radiologic findings is essential
Fingers and toes are common sites for this neoplasm
Molecular testing is important for diagnosis
The tumor cells strongly stain with cytokeratin
This tumor is common in pediatric population

Board review style answer #2

A. Correlation with radiologic findings is essential

Comment Here

Reference: Chondrosarcoma (primary, secondary, periosteal)