Bone

Bone is a scaffold it bears weight and occasionally gets infected.

Tumours often spread to bone and occasionally arise in bone. Bone tumours are dealt with in the bone tumours article.

Normal bone

Bone anatomy

• Epiphysis = rounded end of the bone.
• Metaphysis = between epiphysis and diaphysis; contains epiphyseal plate - site of growth in childhood.
• Diaphysis = shaft, mid-portion, contains bone marrow.

Image

• 

  Bone. (WC)

Bone histology

Two types (based on arrangement of collagen):

1. Woven bone.
2. Lamellar bone.

Woven bone

• Always abnormal in adults.
• Collagen arranged haphazardly - mechanically weak.

Images:

• Woven bone (ajnr.org).
• Woven bone (brown.edu).

Lamellar bone

• Collagen organized in layers (lamellae).

Woven versus lamellar

• Easiest way to differentiate: polarize; lamellar bone has well-defined layers.

Bone cells

• Osteocytes.
  • Sit in lacunae.
    • Empty lacunae = necrotic bone.
• Osteoblasts.
  • Make bone.
• Osteoclasts.
  • Destroy bone.
  • Multinucleated.

Memory device: 'b' before 'c'.

Bone marrow

Main article: Haematopoiesis

• One of two primary lymphoid organs - the other one is the thymus.
• Fat content (%) ~= age in years.
  • e.g. 60 year old will have 60% fatty replacement.

• One should see three cell lines:
  1. Erythroid (red cells).
  2. Myeloid (white blood cells).
  3. 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.
• Note:
• =Benign variants=
• ==Hyperostosis frontalis interna==
• *No clinical significance -- just has to be recognized as a "nothing".
• =Infections=
• ==Acute osteomyelitis==
• ===General===
• Pathophysiology/entry:
• *Hematogenous - often in children.
• *Direct entry (skin defect) - adults with diabetes.
• ===Microscopic===
• Features:
• *Micro-organisms - esp. cocci.
• ===Stains===
• ==Chronic osteomyelitis==
• ===General===
• Most common organism:
• *Peripheral vascular disease.
• ===Microscopic===
• Features:
• *Plasma cells - '''key feature'''.
• **May be sterile, i.e. no organisms.
• *+/-Fibrosis.
• *+/-Necrotic bone - bone with empty lacunae.
• ===Sign out===
• LOWER LEG, RIGHT, BELOW KNEE AMPUTATION:
• - ACUTE AND CHRONIC OSTEOMYELITIS.
• - MODERATE ATHEROSCLEROSIS.
• - SKIN ULCERATION.
• - SOFT TISSUE SURGICAL MARGIN WITH FAT NECROSIS AND MUSCULAR ATROPHY.
• - NEGATIVE FOR MALIGNANCY.
• =Bone tumours=
• This is a big topic. It is dealt with in a separate article.
• The bone tumour article covers tumour mimics, e.g. brown cell tumour.
• =Fractures=
• This is dealt with in the ''forensic pathology'' article.
• =Others=
• The following is a collection of stuff that doesn't really fit in another category or is just weird.
• ==Osteoarthritis==
• This keeps orthopaedic surgeons busy.
• ==Aneurysmal bone cyst==
• *Abbreviated ''ABC''.
• ===General===
• *Benign.
• **May grow rapidly.
• ===Gross/radiologic===
• *Air-fluid levels (radiology).
• *Usually metaphysis of long bones, but uncommonly the femur.
• *May have an "aggressive" appearance, i.e. erode bone.
• ===Microscopic===
• *Bony trabeculae ''or'' osteoid tissue.
• **Multi-nucleated giant-cells with round randomly arranged nuclei.
• *Benign spindle cells (fibroblasts) - surround bone/adjacent to the giant cells - '''important'''.
• *Blood +/- surrounded by giant cells.
• DDx:
• ====Images====
• 

  ABC - intermed. mag. (WC/Nephron)

• 

  ABC - very high mag. (WC/Nephron)

www:

• ABC - low mag. (webpathology.com).
• ABC - intermed. mag. (webpathology.com).
• ABC - high mag. (webpathology.com).

Myositis ossificans

• AKA fibro-osseous pseudotumour of digits.

General

Epidemiology:

• Young people.
• History of trauma - typically.
• Extremities - digits (fingers, toes).

Notes:

• Histologically "worrisome" (for malignancy) - due to high cellularity.

Microscopic

Features:

• High cellularity.
• Low mitotic activity.
• No atypical mitoses.
• No hyperchromasia.

Other features:

• Low power diagnosis:
  • Lesion is well-circumscribed.
  • Normal muscle is adjacent to the lesion - key feature.

DDx:

• Heterotopic ossification - bone, not cellular, no inflammation.

Images:

• Myositis ossificans (upmc.edu).

Paget disease of the bone

General

• Benign - unlike Paget disease of the breast.
• Afflicts ~ 3% of population > 55 years old.
• Leading cause of secondary osteosarcoma.
• Uncommonly associated with giant cell tumour of bone.
• Diagnosis based on radiology.
• Genetic component - several genes implicated including TNFRSF11A (AKA PDB2) and PDB4.

Clinical

Presentation:

• Fracture.
• Bone pain.
• Bony deformity.
• Deafness.
• Incidental finding - radiologic or biochemical.

Serology:

• Elevated ALP.

Clinical features - mnemonic PANICS:

• Pain (bone).
• Arthralgia and ALP elevated.
• Nerve compression - deafness.
• Increased bone density.
• Cardiac failure (high output) - due to AVM formation in bone.
• Sunburst skull on X-ray.

Stage

Classically divided into three phases:

1. Lytic (predominantly osteoclasts).
2. Mixed lytic (osteoclastic) and blastic (osteoblastic).
3. Sclerotic (burned-out).

Microscopic

Features:

• Bone matrix has jigsaw-puzzle like pattern.
  • Jigsaw-puzzle pieces each ~ 100-500 micrometres in size (largest dimension).
• Increased osteoclast activity.
  • Osteoclast = macrophage that reabsorbs bone matrix.

Images

• 

  Paget disease - bone - high mag. (WC/Nephron)

• 

  Paget disease - bone - intermed. mag. (WC/Nephron)

Fibrous dysplasia

• AKA osteitis fibrosa.

General

Classification:

• Monostotic - one bone involved, ~80% of cases.
• Polyostotic - several bones involved, ~20% of cases.
  • May be associated with McCune-Albright syndrome.

Microscopic

Features:

• Woven bone with odd irregular shapes - key feature.
  • Described as "chinese characters".
• Fibrous tissue around bone.

Notes:

• No osteoblastic rimming.

DDx:

• Desmoplastic fibroma - has lamellar bone.
• Low grade fibrosarcoma.
• Low-grade central osteosarcoma.

Images

• 

  Fibrous dysplasia - low mag. (WC/Nephron)

• 

  Fibrous dysplasia - intermed. mag. (WC/Nephron)

• 

  Fibrous dysplasia - high mag. (WC/Nephron)

www:

• Fibrous dysplasia of bone - high mag. (pathologypics.com).
• Fibrous dysplasia of bone - low mag. (pathologypics.com).

Desmoplastic fibroma

• Not to be confused with desmoplastic fibroblastoma.

General

• Rare.

Microscopic

Features:

• Lamellar bone.
• Fibrotic marrow space with:
  • Collagen.
  • Low cellularity.
  • Spindle cells without significant atypia.

DDx:

• Fibrous dysplasia - has woven bone.
• Low grade fibrosarcoma.

Gaucher disease

Main article: Gaucher disease

General

• May present as a fracture.

Microscopic

• Macrophages in the marrow space with a "crumpled tissue paper" appearance.

Langerhans cell histiocytosis of bone

• AKA eosinophilic granuloma of bone.

Main article: Langerhans cell histiocytosis

General

• Rare.
• Children.

Microscopic

Features:

• Eosinophils.
• Cerebriform and/or reniform macrophages.

Giant cell reparative granuloma

• AKA central giant cell granuloma, abbreviated CGCG.
• AKA solid aneurysmal bone cyst.

General

• Lesion of the mandible and maxilla.

Radiology

• Lytic lesion.

Microscopic

Features:

• Giant cells.
• Fibroblasts.
• Osteoid.
• Hemosiderin-laden macrophages.

DDx:

• Peripheral giant cell granuloma - soft tissue counterpart of CGCG.
• Giant cell tumour of bone.

Images

• 

  CGCG - intermed. mag. (WC/Nephron)

• 

  CGCG - high mag. (WC/Nephron)

Molecular

Recurrent chromosomal translocation:

• t(16;17)(q22;p13).

Osteopetrosis

• AKA marble bone disease.

General

• Rare.
• Genetic - may be autosomal dominant, autosomal recessive or X-linked.
• Pancytopenias - due to oblieration of the marrow space.
• Fractures.
• Radiologic diagnosis.

Gross

• Marbled appearance.
• Thickening with obliteration of the marrow space.
• Patchy (brown) surface due to vascularization/extramedullary hematopoiesis.

Image:

• Osteopetrosis (uaz.edu.mx).

Microscopic

Features:

• Abundant irregular (pink) bony trabeculae with layers of (blue-gray) cartilage.

Image:

• Osteopetrosis (bloodjournal.hematologylibrary.org).

Osteoporosis

General

• Very common.
• Associated with fractures, esp. wrist, hip & vertebra.
• Radiologic diagnosis - bone mineral density.

Etiology:

• Primary (senile).
• Secondary:
  • Endocrine:
    • Hyperparathyroidism.
  • Gastrointestinal:
    • Malabsorption, e.g. celiac disease, cystic fibrosis, Crohn's disease.
    • Starvation.
  • Psychiatric:
    • Anorexia nervosa.
    • Bulimia nervosa.
  • Neoplasia:
    • Multiple myeloma.
  • Drugs:
    • Systemic steroids.

Gross

• Decreased numbers of, abnormally thin, bony spicules.

Images:

• Osteoporosis (sciencephoto.com).
• Osteoporosis (utah.edu).

Microscopic

Features (femoral neck):

• Thinner cortex.
• Decreased trabecular thickness
• Decreased number of trabeculae.

Note:

• One study looking at iliac bone biopsies suggests trabeculae are no different in osteoporosis.

See also

• Cartilage.
• Chondro-osseous tumours.
• Femoral head.
• Hematopathology.
• Soft tissue lesions.
• Small round cell tumours.