Chondro-osseous tumours

Bone occasionally crosses the desk of the pathologist. Primary bone tumours are rare; the most common bone tumour is metastases.

Normal

• Normal bone has osteocytes.
  • If the osteocytes are missing... the bone is dead.

• Osteoblasts - make bone.
• Osteoclasts - destroy bone.

Memory device: 'b' before 'c'.

Diagnosing bone tumours

• Diagnosis should not be made without radiologic & clinical information.

Bone marrow

• Fat content (%) ~= age (in years)
  • e.g. 60 year old will have 60% fatty replacement.

• Should see three cell lines.
  • The cell lines:
    • Erythroid (red cells),
    • Myeloid (white blood cells),
    • Megakaryocytic (platelets).

Note: Lymphocytes are considered separately and typically spared in bone marrow failure.

Identifying the lines:

1. Megakaryocytes:
   • Big cells ~ 3x the size of a RBC.
2. Normoblasts (RBC precursors):
   • Hyperchromatic, i.e. blue, nucleus.
3. Myeloid line:
   • Granules.
   • Reniform nucleus, i.e. kidney bean shaped nucleus.

Images:

• Myeloid line (WC).

Organization

• Mature hematopoeitic cells at the centre (distant from bone).
• Immature hematopoeitic cells adjacent to the bone.

Infectious

Osteomyelitis

General

• Hematogenous - often in children.
• Direct entry (skin defect) - adults with diabetes.

Micro.

• PMNs.

Chronic osteomyelitis

• Plasma cells.
  • May be sterile, i.e. no organisms.

Bone tumours

General:

• Metastasis:primary bone tumours = >20:1.

Giant cell tumour

General

• Approx. 5% of primary bone tumours.
• Age 20-45 years.

Clinical

• May present with joint pain, immobility.

Micro.

• Mononuclear cells key feature.
• Giant cells.

Chondrosarcoma

Micro

Features:

• Abnormal cartilage.
• Nuclear atypia.
  • Nuclear clearing.
  • Nucleoli.

Ewing sarcoma

General

• AKA EWS/PNET:
  • EWS = Ewing sarcoma.
  • PNET = Primative neuroectodermal tumour.
• EWS and PNET were once thought to be different tumours.

Clinical

• Painful.
• Usually younger than 20 years.

Radiology

Features:

• Long bones, diaphyses.
• Destructive.
• "Onion-skin" periosteal reaction.

Microscopic

Classification:

• Small blue cell tumour.

Features:

• Scant clear cytoplasm (contain glycogen - PAS +ve, PAS-D -ve).
• Lack nucleoli.
• Round small nucleus.

IHC

Features:

• CD99 +ve (plasma membrane staining).
• CD45 -ve.
  • Done to r/o lymphoma.
• +/-Neural markers (NSE, synaptophysin, CD57 (??? CD56 ???), S100).
• +/-Cytokeratins.
• Caveolin-1
  • New kid on the block.

Notes:

• CD99 +ve (plasma membrane) tumours:
  • Lymphoblastic lymphoma/leukemia.
  • Angiomatoid fibrous histiocytoma.
  • Desmoplastic small round cell tumour.

Molecular diagnostics

Common features:

• EWS/FLI-1 fusion gene formation due to translocation: t(11;22)(q24;q12).
  • Often detected by RT-PCR (with EWS 5' and FLI-1 3' primers).

Notes:

• The t(11;22)(q24;q12) is seen in ~90% of EWS/PNET... but also in:
  • Olfactory neuroblastoma.
  • Small cell osteogenic sarcoma.
  • Polyphenotypic tumours.
  • Rhbdomyosarcoma.
  • Neuroblastoma (possibly).
• Several other translocations exist.

Pigmented villonodular synovitis

• Commonly abbreviated: PVNS.
• Course: benign.

Microscopy

Features:

• Subsynovial nodules composed of cells with:
  • Abundant cytoplasm.
  • Pale nuclei.
• Multinucleated giant cells.
• Hemosiderin-laden macrophages.
• Foam cells.

Osteosarcoma

General

• Terry Fox was afflicited by this tumour.

Definition

• Tumour that makes osteoid.
  • Osteoid = (extracellular) organic component of bone, normally produced by osteoblasts (cells which make bone matrix).

Histology

• Spindle cells with malignant features (e.g. nuclear membrane irregularies, marked nuclear

size differences, mitoses) surrounded by delicate strands of osteoid.

• • Osteoid on H&E: pink, homogenous, "glassy".
  • Tumours typically very cellular - when compared to normal bone.
• Large (multinucleated) osteoclast-like giant cells may be seen.

Adamantinoma

General

Features:

• Rare: < 1% of bone tumours.
• 25-35 years old.
• Tibia, fibula.
• Benign, may be locally aggressive.
• Cousin of ameloblastoma.

Radiology

• Intracortical, radiolucent.

Micro.

• Fibrous tumour.

Common malignant

• Osteosarcoma.
• Chondrosarcoma.
• Ewing's sarcoma.
• Multiple myeloma.
• Metastases.
  • Most common tumours metastatic to bone (mnemonic: BLT with Ketchup & Pickles):
    • Breast,
    • Liver,
    • Thyroid,
    • Kidney,
    • Prostate.

Epi.

• Osteosarcoma -> 2nd decade.
• Ewing's ->5-20 yrs.
• Chondrosarcoma -> from enchondroma or osteochrondroma -- patients over 40 yrs.
• Multiple myeloma -> most common primary bone tumour in adults.

Malignant bone tumours by age

Most common by age:

• <1 year old - neuroblastoma.
• 1-10 years old - Ewing's of tubular bones.
• 10-30 years old - osteosarcoma, Ewing's of flat bones.
• 30-40 years old - reticulum cell sarcoma, fibrosarcoma, parosteal osteosarcoma, malignant giant cell tumour, lymphoma.
• >40 years old - mets, multiple myeloma, chondrosarcoma.

Benign aggressive bone tumours

• Giant cell tumours.
• Osteoblastoma.
  • Thought to be related to osteoid osteoma.
  • If in long bones often diaphyseal.

Ref.:

Brown cell tumour

Etiology

• Due to hyperparathyroidism - usually parathyroid adenoma.

Microscopy

• Fibrosis.

Hypercalcemia DDx

Mnemonic GRIMED:

• Granulomatous disease (tuberculosis, sarcoidosis).
• Renal disease.
• Immobility.
• Malignancy (esp. squamous cell carcinoma, plasmacytoma).
• Endocrine (primary hyperparathyroidism - leads to brown cell tumour).
• Drugs (thiazides ... others).

See also

• Hematopathology.