Chondrosarcoma

Chondrosarcoma
Diagnosis in short
Chondrosarcoma. H&E stain.
LM	"abnormal cartilage": +/-high grade changes - nuclear atypia (nuclear clearing, nucleoli, hyperchromasia), low/intermediate grade changes - bi-nucleation, hypochromatic enlarged nuclei, infiltration of lamellar bone ("invasion"), increased cellularity, irregular spacing of chondrocytes
Subtypes	chondrosarcoma not otherwise specified (NOS), juxtacortical chondrosarcoma, myxoid chondrosarcoma, mesenchymal chondrosarcoma, clear cell chondrosarcoma, dedifferentiated chondrosarcoma
LM DDx	chondroblastic osteosarcoma, enchondroma (esp. for low-grade chondrosarcoma), chordoma, others
Molecular	t(9;22) for extraskeletal myxoid chondrosarcoma
Gross	cartilaginous appearance
Site	hip, shoulder, soft tissue, others
Syndromes	Olier disease, Maffucci syndrome
Clinical history	adults
Signs	mass lesion
Prevalence	uncommon
Prognosis	good ~75% five year survival
Clin. DDx	enchondroma, bone tumours, soft tissue lesions
Treatment	excision

Chondrosarcoma is a malignant tumour of cartilage. It is in the chondro-osseous grouping of tumours and can be lumped into the much large category of the soft tissue lesions.

General

• Usually a good prognosis - 75% five year survival in one large data set.
  • Subtypes vary substantially - chondrosarcoma NOS and myxoid chondrosarcoma have a five year survival of ~70%, but mesenchymal chondrosarcoma only ~50%, and dedifferentiated chondrosarcoma an abysmal ~0%!
• Grade and stage are independent predictors of survival.

Clinical/epidemiologic features:

• Usually arise in a (benign) abnormality of cartilage (e.g. osteochondroma, enchondroma).
• May be associated with a syndrome:
  • Olier disease (multiple enchondromatosis).
  • Maffucci syndrome (multiple enchondromas and hemangiomas).

Subtypes

Several subtypes and their relative prevalence:

• Chondrosarcoma not otherwise specified (NOS) ~83% of cases.
• Juxtacortical chondrosarcoma <1% of cases.
• Myxoid chondrosarcoma ~10% of cases.
• Mesenchymal chondrosarcoma ~4% of cases.
• Clear cell chondrosarcoma <1% of cases
• Dedifferentiated chondrosarcoma ~1% of cases.

Gross

• Appendicular skeleton ~45% of cases.
  • Classically hip.
• Axial skeleton ~30% of cases.
• Soft tissue ~10% of cases.

Note:

• Peripheral chondrosarcoma are very rare.
• Chondrosarcoma is the most common primary malignant chest wall lesion.
  • The classical location is anterior (costochondral arches or sternum), where it is more common than chondroma.

Microscopic

Features:

• "Abnormal cartilage":
  • +/-Nuclear atypia - high grade lesions.
    • High grade lesions:
      • Nuclear clearing.
      • Nucleoli.
      • Hyperchromasia.
    • Low/intermediate grade lesions:
      • Bi-nucleation.
      • Hypochromatic enlarged nuclei.
      • Infiltration of lamellar bone ("invasion") - not common - diagnostic.
  • Increased cellularity.
    • More cellular than cartilage... but relatively paucicellular compared to other sarcomas.
  • Irregular spacing of chondrocytes.

Notes:

• Low grade chondrosarcoma are not cytologically malignant; the diagnosis rests mostly on radiologic findings.
  • The exception is infiltration of lamellar bone -- this is diagnostic of chondrosarcoma.

DDx:

• Chordoma.
• Enchondroma.
• Synovial chondromatosis.
• Osteosarcoma - esp. chondroblastic osteosarcoma - has osteoid, may be focal.

Images

• 

  Chondrosarcoma - low mag. (WC)

• 

  Chondrosarcoma - high mag. (WC)

• 

  Chondrosarcoma - high mag. (WC)

• 

  Grade 2 chondrosarcoma, low power showing bone permeation (SKB)

• 

  Chondrocytic hyperchromasia and atypicality in this photo of a Grade 2 chondrosarcoma. (SKB)

• 

  Lobule of neoplastic Grade 2 cartilage with some bone permeation and calcification at the top of the photo.(SKB)

• 

  Lobule of neoplastic Grade 2 cartilage with atypia and bone permeation. (SKB)

• 

  Grade 3 - very cellular neoplastic cartilage with high grade nuclear atypia. (SKB)

www:

• Chondrosarcoma (upmc.edu).
• Low-grade chondrosarcoma (path.utah.edu).

Variants

Mesenchymal chondrosarcoma

Main article: Mesenchymal chondrosarcoma

Myxoid chondrosarcoma

Microscopic: Features:

• Chordoma-like:
  • Myxoid background.
  • Small cells with eosinophilic cytoplasm.

DDx:

• Chondroid syringoma - These are dermal based, circumscribed and much smaller.
• Parachordoma.
• Chordoma. (???)
• Myxoid liposarcoma.
• Metastatic myxoid carcinoma.

Images:

• 

  Anastomizing chords of small neoplastic cells surround mucin pools.(SKB)

• 

  Chords of neoplastic cells surround mucin pools. (SKB)

• Pathology outlines [1]
• Pathology outlines [2]

Clear cell chondrosarcoma

• Rare variant of chondrosarcoma (1.6%–5.4% of all chondrosarcomas)
• Usually a low-grade malignant tumour
• Younger age than conventional chondrosarcoma
• Teens to 40s; more common in males
• Epiphyses of long tubular bones; proximal femur or humerus
• Rarely head and neck
• Malignant counterpart of chondroblastoma?

Microscopic findings

• Lobules of uniform to polymorphic densely-packed large cells
• Well defined pushing borders
• Clear to intensively acidophilic granular cytoplasm cytoplasm with vacuoles
• Central nuclei with occasional prominent nucleoli
• Low mitotic rate
• Clear cell areas lack production of hyaline chondroid matrix
• Areas with osteoclast-type giant cells mixed with small trabeculae of reactive bone
• May contain conventional low-grade chondrosarcoma
• May have secondary aneurysmal bone cyst changes

• 

  High grade round cells with cytoplasmic clearing. (SKB)

• 

  High grade round cells with cytoplasmic clearing. (SKB)

• 

  Clear cells, giant cells and bone spicules. (SKB)

• 

  Somewhat hemangiopericytomatous vascular pattern with giant cells. (SKB)

• 

  Clear cells, giant cells and bone spicules. (SKB)

• 

  The lesion also had areas of more conventional chondrosarcoma. (SKB)

• Pathology outlines [3]
• Pathology outlines [4]
• Pathology outlines [5]
• Tumor library [6]
• Tumor library [7]

DDX:

• Chondroblastoma
• Giant cell tumour of bone
• Osteoblastic tumours
• Metastatic clear cell renal cell carcinoma

Outside sources: E-immunohistochemistry[8]

Extraskeletal myxoid chondrosarcoma

• Originally thought to be a variant of myxoid chondrosarcoma of bone; however, may not be a chondrosarcoma at all.
• Characteristic chromosomal translocation: t(9;22) CHN-EWS.

DDx:

• Chordoma.
  • S-100 +ve (strong).
  • EMA +ve.
• Myxoid liposarcoma.

Image:

• Extraskeletal myxoid chondrosarcoma (cttr.org).

• 

  Strands of atypical cells suspended in mucin. (SKB)

• 

  Strands of atypical cells suspended in mucin. (SKB)

Dedifferentiated chondrosarcoma

Clinical:

• Abysmal to poor prognosis.
  • In one series (22 patients) 5-year survival ~20%.
  • All dead in two years in another series (25 patients).

Features:

1. Poorly differentiated (mesenchymal) malignancy.
2. Well-differentiated cartilaginous component.

DDx:

• Undifferentiated pleomorphic sarcoma - no cartilaginous component.
• Other dedifferentiated tumours, e.g. dedifferentiated liposarcoma, with a minimal differentiated component.

Images:

• Dedifferentiated chondrosarcoma (upmc.edu).

• 

  A lobule of cartilagenous chondrosarcoma on the left; high grade sarcoma on the right. (SKB)

• 

  High grade sarcoma on the left and upper; malignant cartilage right and lower. (SKB)

Grading

Features:

• Grade I: mild-to-moderate increase of cellularity +/- binucleated cells.
• Grade II: between Grade I and Grade III.
• Grade III: nuclear pleomorphism, mitoses common.

• 

  Grade 1 - Somewhat cellular cartilage with binucleation.(SKB)

• 

  Grade 2 - Very cellular cartilage with obvious hyperchromasia and nuclear atypia. (SKB)

• 

  Grade 3 - Even more cellular neoplastic cartilage with high grade nuclear atypia. (SKB)

IHC

• S-100 positive
• Keratin negative
• Collagen II positive

See also

• Chondro-osseous tumours.