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Bone Histology and benignbonetumors.pptx
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- 3. BONE Bone is aconnective tissue. Composed of cells and extracellular matrix (type I collagen). Total number: 206 (Adult) 270 (At birth) Grouped into: • Axial skeleton (80 bones): Skull, vertebral column, rib cage • Appendicular skeleton (126 bones): Limbs, pectoral and pelvic girdles
- 4. BONE • Major functions •Mechanical support • Determines the body size and shape • Protect vital organs • Metabolic reserves of Calcium and Poshpate
- 5. Bone Shape Examples Longbones Femur, humerus Short bones Carpals, tarsals Flat bones Skull, sternum, ribs Irregular bones Vertebrae, pelvic bones Sesamoid bones Patella
- 7. PARTS OF ALONG BONE
- 9. BONE CELLS • Boneis composed of cells and a predominantly collagenous extracellular matrix (type I collagen) called osteoid. • Osteoid becomes mineralised by the deposition of calcium hydroxyapatite, giving the bone considerable rigidity and strength. • The cells of bone are: 1) Osteoblasts 2) Osteocytes
- 10. CELLS OF BONE Osteoblastsand osteocytes are derived from a primitive mesenchymal (stem) cell called the osteoprogenitor cell. 1) Osteoblasts :- • Synthesize osteoid and mediate its mineralization • Found lined up along bone surfaces (periosteal surface) • Active osteoblasts are large, broad, cuboidal cells with abundant basophilic cytoplasm containing much rough endoplasmic reticulum and a large Golgi apparatus. • Inactive osteoblasts are narrow, attenuated, spindle shaped cells.
- 12. CELLS OF BONE 2)Osteocytes :- • Represent largely inactive osteoblasts incorporated into the matrix of formed bone. • Lie within the lacunae circumferentially around the Haversian canal. • Assist in the nutrition of bone.
- 13. • When nonew bone is being formed on the bone surface, these cells are insignificant flattened cells with spindle-shaped nuclei but, when there is active new bone formation at the periosteal surface, these cells proliferate and increase in size to become osteoblasts.
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- 15. 3) Osteoclasts:- • Multinucleatedphagocytic cells derived from macrophage- monocyte cell line. • Located in depressions resorbed from the bone surface called Howship lacunae. • Function: Resorption of bone in bone remodelling in response to growth or due to changing mechanical stresses upon the skeleton.
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- 17. SUPPORTING STRUCTURES Periosteum: • Denseirregular connective tissue covering exterior of the bone. • Covers full extent of bone except articular cartilages. • Forms outer limiting layer. • Attachment site of tendons.
- 18. SUPPORTING STRUCTURES • Twolayers: • Hard and thick collagenous outer layer • Inner, proliferative (Cambium layer) that lies adjacent to cortical bone and support growth and repair.
- 19. SUPPORTING STRUCTURES Endosteum: • Singlelayer of bone cells covering interior of bone. • Separates medullary cavity from surrounding compact bone. • Lines the Haversian canals in compact bone.
- 21. TYPES OF BONE WovenBone (Primary Bone): • Immature bone found during fetal development or fracture repair. • Characterized by randomly arranged collagen fibers. • More cellular, with numerous osteocytes. • Lower mineral content, mechanically weaker. • Eventually replaced by lamellar bone.
- 22. TYPES OF BONE LamellarBone (Secondary Bone): • Mature bone, seen in adults. • Composed of organized layers (lamellae) of collagen fibers. • Stronger due to parallel alignment of fibers. • Forms both compact and spongy (trabecular/cancellous) bone.
- 25. CORTICAL- COMPACT BONE –Outer,dense, compact, 60% of skeleton. • Provides structural stability. • Has a very dense structure based on an arrangement of cylindrical structures called osteons.
- 26. STRUCTURAL UNIT • Thearea in one concentric unit of lamellae in compact bone is called an osteon or a Haversian unit
- 27. STRUCTURAL UNIT Osteon (HaversianSystem): • Central Haversian canal contains blood vessels and nerves. • Surrounded by concentric lamellae of bone matrix. • Lacunae between lamellae house osteocytes. • Canaliculi connect osteocytes for communication. • Volkmann’s canals run perpendicular, connecting Haversian canals.
- 30. OSTEON • Central spaceis called Haversion canal • Contains blood vessels • Around which are the concentric lamellae Interference contrast
- 31. VOLKMAN’S CANALS • Haversioncanals are connected by means of vascular canals which course perpedicular to the long axis of the bone • Means by which outer cortical and inner cortical circulation anastomose
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- 33. CANCELLOUS BONE • Spongiosa,medulla, spongy region • Makes up 20-25% of the skeleton. 75% marrow and fat and 25 % bone • Bony lamellae are arranged in parallel plates • No concentric arrangement about a central vascular canal. Delicate arrangement consisting of thin partitions (trabeculae) connecting bony plates between which is found the bone marrow
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- 36. CANCELLOUS BONE • Distalfemur • Thin rim of cortical bone • Predominantly cancellous bone
- 38. DIFFERENCE Cortical Bone Cancellous(Trabecular) Bone Compact Spongy/ cancellous Shafts of long bone, anterior surface of flat bones. Ends of long bone, marrow cavity, centre of flat bones, vertebrae. Hard, solid, very strong Spongy & strong Collagen – circumferential lamellae around the haversian canal. Collagen – lamellae are parallel to the surface. Also known as Haversian bone Also known as Non haversian bone
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- 40. INTRODUCTION • Primary tumorsof bone are relatively uncommon. • Bone sarcomas accounts 0.2% of all neoplasms. • Incidence rates of specific bone sarcomas are age related. • Osteosarcoma is the most common malignant primary bone tumors.
- 41. AETIOLOGY • Radiation • Chronicinflammatory states( Chronic Osteomyelitis) • Exposure to • chromium, • nickel, • cobalt, • aluminum, • titanium, • methyl-methacrylate • and polyethyelene • Implanted metallic hardware and joint prostheses
- 42. CLINICAL FEATURES • Pain •Swelling • Limitation of movement • Pathologic fracture • General symptoms • Fever • Exhaustion • Weight loss
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- 45. OSTEOMA • Benign tumorarising on the surface of the bone composed of compact bone • When develops in the medullary cavity – ‘bone island’ Previously Enostosis • M=F • Age= 4th through 6th decade
- 46. ETIOLOGY • Sporadic: Unkown •Syndromic: • Gardner Syndrome(multiple osteomas) • FAP • Multiple bone islands (Osteopoilkilosis)
- 47. OSTEOMA • Sites: • Calvarial,facial and jaw bones i.e typically in bone formed by membranous ossification. • Intramedullary lesions; in the epiphysis and metaphyses of long bones, pelvic and vertebral bones. • Clinical Features: • Slow-growing and asymptomatic. • Pain and headache when obstruction of paranasal sinuses.
- 48. OSTEOMA Radiology: • Round, dense,well-defined ivory- like lesions, which are attached to the underlying bone without cortical invasion • Bone islands are intramedullary lesions typically measuring < 1 cm, although larger lesions can occur.
- 49. OSTEOMA • Macrossopy: • Wellcircumscribed tumors with broad attachment to underlying bone • Bone islands – intramedullary foci of compact bone • < 2 cm
- 50. OSTEOMA • Histopathology • Composedof lamellar/cortical-type bone and broad trabeculae of mature bone within paucicellular fibrous stroma • Subtypes (Compact, Spongious & Mixed) • Cancellous areas – bone lined by active and inactive osteoblasts within a well vascularized and moderately cellular fibrous stroma
- 52. A well-demarcated tumour composedof trabecular bone. Osteoma of the frontal sinus. The tumour is composed of lamellar/cortical-type bone adjacent to sinus epithelium
- 53. Anastomosing bony trabeculae Broad trabeculaeof mature bone
- 54. DIFFERENTIAL DIAGNOSIS • Osteoblastoma •Lamellar bone with prominent osteoblastic rimming • Osteoma may have focal areas of reactive bone with similar features • Parosteal osteosarcoma • Tumor osteoid is arranged in parallel arrays and separated by a hypocellular fibroblastic stroma
- 55. OSTEOID OSTEOMA • Benignbone forming tumor characterized by • small size (< 2 cm), • limited growth potential and • disproportionate pain • M>F • Age: teens and 20s. • Site: appedicular skeleton with 50% in cortex of femur and tibia
- 56. OSTEOID OSTEOMA • Theusual presenting symptom is pain. • Pain at first is intermittent with mild nocturnal exacerbation but later becomes unbearable. • NSAID, even in small doses, completely albeit temporarily relieves the pain.
- 57. OSTEOID OSTEOMA Imaging: • CTis the imaging modality of choice to detect the nidus, an ovoid lucency, < 2 cm, which can have central areas of mineralization. CT scan of the elbow shows lucent lesion centered in the lateral epicondyle of the distal humerus with minimal surrounding reactive bone
- 58. OSTEOID OSTEOMA • Small,round, cortically based red, gritty or granular lesion. • Lesion is surrounded by ivory white sclerotic bone • Size: usually <2cm
- 59. OSTEOID OSTEOMA (MICROSCOPY) •Central portion of the lesion (nidus) contains differentiated plump osteoblasts present as a single layer around trabeculae of unmineralized or mineralized woven bone . • Vascular ized connective tissue, within which there are fibroblast-like stromal cells and cells differentiating into osteoblasts, sepa rates the trabeculae.
- 60. OSTEOID OSTEOMA (MICROSCOPY) •The osteoid may be microscopically disposed in a sheet-like configuration, but it is often organized into microtrabecular arrays.
- 61. Nidus Host lamellar bone Bonytrabeculae Hypocellular fibrovascular CT Osteoblastic rimming
- 62. OSTEOID OSTEOMA Differential Diagnosis •Osteomyelitis and bone abscess • Lack a central nidus • Prominent acute inflammatory cell infiltrate • Osteoblastoma • Tumor size is much greater • Evidence of progressive growth • Lacks peripheral rim of fibrovascular tissue
- 63. OSTEOID OSTEOMA • Osteosarcoma •Lacks fibrovascular stroma and osteoblastic rimming of osteoid osteoma • May exhibit chondroid or fibrous differentiation • Stress fracture • Zonal pattern with central more mature denser bone and peripheral woven bone • Cartilage with endochondral ossification may be present
- 64. OSTEOID OSTEOMA • Molecularpathology • FOS gene rearrangement • Prognosis: • Excellent • Recurrences: uncommon
- 65. OSTEOBLASTOMA • Intermediate, locallyaggressive bone forming tumors morphologically similar to osteoid osteoma but with • Growth potential • Size>2cm in dimension • < 1% of all primary bone tumors • Age: 2nd and 3rd decade. • M:F= 2:1
- 66. OSTEOBLASTOMA Sites: • Posterior spine(laminae and pedicles) >>> > proximal and distal femur, proximal tibia, jaws • Majority: Intraosseous (medullary), occasionally on surface
- 67. OSTEOBLASTOMA Clinical features: • Non-specific,dull aching pain unrelieved by NSAIDs • May have neurological symptoms if nerve compression by the tumor.
- 68. OSTEOBLASTOMA Imaging: • Dense shellof bone surrounding the lesion. +/- central nidus • Bony shell tends to be very thin, with expansion into adjacent soft issues • Cortical expansion and destruction are common
- 69. OSTEOBLASTOMA Macroscopy: • Round tooval with a thinned expanded cortex • Border between tumor and medullary cavity is sharp. • On C/S; Red or red-brown with gritty or sandpaper consistency • Cystic lesion – blood filled spaces simulating ABCs
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- 71. OSTEOBLASTOMA • Identical toosteoid osteoma • Tumor is composed of woven bone spicules or trabeculae that are haphazardly arranged and lined by a single layer osteoblasts • Intertrabecular spaces and vascular and show connetive tissue instead of bone marrow. • Scattered osteoclast like giant cells
- 72. OSTEOBLASTOMA • There maybe osteoid deposition of cartilagenous differentiation. • The borders are usually well defined, often showing peripheral bone maturation in cords, clusters of osteoblasts towards lamellar bone. • No destructive host bone permeation. • No atypical mitoses.
- 73. Osteoclasts like giantcells Bony trabeculae Plumped osteablasts rimming
- 74. Bony lesion surroundedby a sclerotic rim. Interanastomosing trabeculae of woven bone, set within loose edematous fibrovascular stroma, with extravasated erythrocytes
- 75. Epithelioid variant: -Large, plump osteoblasts with a large nucleus and prominent nucleoli, accompanied by mitoses • Pseudomalignant variant: - Osteoblasts with degenerative nuclear atypia - Abscence of mitoses
- 76. OSTEOBLASTOMA Differential Diagnosis • Osteoidosteoma • <2cm • Severe nocturnal pain • No evidence of progressive growth • Giant cell tumor • Sheets of giant cells • Contain mononuclear stromal cell
- 77. OSTEOBLASTOMA Differential Diagnosis •Aneurysmal bonecyst(ABC) •Due to hemorrhagic appearance and presence of reactive new bone formation. •FOS(-)
- 78. OSTEOBLASTOMA • Osteoblastoma-like osteosarcoma •Sheets or aggregates of atypical osteoblasts in contrast to single rim of osteoblasts • Sarcomatoid stroma with cytological atypia and atypical mitosis • Permeation of host bone • Lack of maturation
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- 80. Osteoid osteoma Osteoblastoma Size<2 cm >2 cm Age Teens and 20s Adults Site Appendicular skeleton Spine Clinically Painful lesions, nocturnal, dramatically revlieved by aspirin Painless or if painful-dull and achy and not responsive to salicylates Tumor Actual tumor called NIDUS Absence of reactive bone formation Surrounded by broad zone of sclerosis (reactive bone formation) on X-ray Variants: pseudomalignant osteoblastoma and epithelioid osteoblastoma Treatment NSAIDs Radiofrequency ablation Curratege or Enbloc excision
- 81. REFERENCES WHO Classification ofTumours of Soft Tissue and Bone, 5th edition Wheater’s Functional Histology, 6th EDITION Rosai & Ackerman’s SURGICAL PATHOLOGY, 11TH EDITION Robbins and Cotran Pathologic Basis of Disease 10th edition
Editor's Notes
- #3 Many bones in infants are separate pieces (like the bones of the skull, hip, and spine). As the child grows, these bones gradually fuse into single bones. Fusion reduces the total bone count to 206 in adulthood.
- #8 Epiphysis: rounded end of the bone located at the proximal and distal part, covered by hyaline cartilage., avascular Diaphysis: shaft or central part of long bone. Contained medullary cavity filled with marrow and externally surrounded by periosteum Metaphysis: flared region between epiphysis and diaphysis. Bone growth, presence of epiphyseal growth plate
- #9 Osteoid is the organic, unmineralized portion of the bone matrix that is secreted by osteoblasts during bone formation. It plays a crucial role in bone strength, flexibility, and mineralization. Pale eosinophilic (pink) unmineralized layer adjacent to osteoblasts Lies on the surface of trabecular (spongy) bone or beneath active osteoblasts Von Kossa stain: Differentiates mineralized bone (black) from osteoid (unstained)
- #10 When active, These features reflect a high rate of protein (type I collagen) and proteoglycan synthesis
- #13 FIG. 10.12╇ Periosteum (a) Inactive, H&E (MP) (b) Active, H&E (HP) The outer surface of most bone is covered by a layer of condensed fibrous tissue, the periosteum P, which contains cells capable of converting into osteoprogenitor cells and osteoblasts. Micrograph (a) shows inactive periosteum with barely detectable inactive osteoprogenitor cells Op and mature formed bone containing established osteocytes Oc. Micrograph (b) shows active periosteum with new bone being formed by active periosteal osteoblasts Ob, some of which are being incorporated into newly formed bone to become osteocytes Oc.
- #15 These are important, along with osteoblasts, in the constant turnover and refashioning of bone. The aspect of the osteoclast in apposition to bone is characterised by fine microvilli which form a ruffled border that is readily visible with the electron microscope. The ruffled border secretes several organic acids which dissolve the mineral component, while lysosomal proteolytic enzymes are employed to destroy the organic osteoid matrix. Osteoclastic resorption contributes to bone remodelling in response to growth or due to changing mechanical stresses upon the skeleton. Osteoclasts also participate in the long-term maintenance of blood calcium homeostasis by their response to parathyroid hormone and calcitonin (see Ch. 17). Parathyroid hormone stimulates osteoclastic resorption and so increases the release of calcium ions from bone, whereas calcitonin inhibits osteoclastic activity. Micrographs (a) and (b) are taken from bone showing excessive osteoclastic activity due to the effects of Paget disease of bone, a disorder characterised by continuous disorganised bone resorption and associated new bone formation (see textbox). Micrograph (b) shows uncoordinated new osteoid formation by a row of cuboidal osteoblasts Ob.
- #16 Large multinucleated cells residing in the howships lacunae
- #18 Outer layer: type 1 collagen synthesized by fibroblast, consist of nerves and blood vessels, nourishment to outer surface of bone. Inner layer: osteoprogenitor cells: bone growth and repair.
- #20 Osteiod: organic unmineralised portion of bone matrix secreted by osteoblast during bone formation.
- #22 Lamellae: thin layers or plate of bone matrix seen in both.
- #24 Epiphysis: no medullary cavity Diaphysis with show medullary cavity
- #25 Topographically there are two types of bone that is cortical compact bone and cancellous bone Appendicular skeleton, shafts of long bones
- #26 This image shows the microscopic architecture of compact bone: A single osteon with concentric lamellae A Haversian canal in the center Numerous lacunae with osteocytes Canaliculi connecting the cells This is most likely a ground bone section viewed without decalcification and without typical histological staining like H&E.
- #28 Longitudinal is perforating or volksman canal
- #29 osteocytes are connected via gap junction and nutrition exchange happens between these cells and extracellular fluid in the lacuna and canaliculi
- #30 Best seen in H&E or Goldner’s trichrome Interference contrast microscopy, also known as differential interference contrast (DIC) or Nomarski microscopy, is a technique used to enhance contrast in transparent, unstained samples
- #31 VC – saw tooth configuration- connects 3 HC VC not surrounded by lamellae
- #32 Circumferential lamellae are sheets of bone matrix that run parallel to the bone surface and are found around the perimeter of compact bone, unlike the circular lamellae in osteons. Concentric lamellae are the circular layers of mineralized bone matrix that surround the Haversian canal within an osteon (Haversian system) in compact bone. These lamellae are critical to the strength and resilience of bone.
- #33 Pelvis, vertebrae, epiphyses of long bones.
- #43 Pain: Intermittent aching(B); worsening nonmechanical pain(M) Swelling: (B); When cortex is breached and tumor grows beneath periosteum(M) Pathological fracture: Prev. asymptomatic with fracture through a simple bone cyst(B); Fracture is often caused by minimal force(M)
- #46 Gardner syn: APC, osteomas/enostosis, impacted supernumerary teeth, odontomas, desmoid type fibromatosis and epidermoid cysts. Enostosis, also known as a bone island, is a benign focus of compact (cortical-type) bone located within the medullary cavity of a bone. It is usually discovered incidentally on imaging and is asymptomatic. Thought to represent a hamartomatous lesion (a focal overgrowth of normal bone elements). Synonyms: Bone island, intramedullary osteoma (older term)
- #47 Gardner: epidermoid cyst, desmoidtumor, dental abnodmalities,
- #48 Calvarium: upper part of skull doesnot include facial bone.
- #52 Picture: White arrow cortical bone, Black arrow cancellous bone Osteoblasts and osteocytes are typically inconspicuous, except in frontoethmoidal region where their activity might be more prominent.
- #60 Nidus: growing tumor cells, blood vessels and bone forming cells. Sclerotic margin and relieved by nsaid
- #61 Picture: Sheet like bone matrix entrapping bone forming cells. Color pink to purple depending on state of mineralization.
- #62 FIGURE 25-40 Osteoid osteoma. A, The nidus is formed by an interlacing network of woven bone surrounded by host lamellar bone. B, Anastomosing trabeculae of bone within the nidus rimmed by osteoblasts and embedded in a hypocellular fibrovascular connective tissue stroma.
- #65 FOS gene is a proto-oncogene involved in cell proliferation, differentiation, and survival. Full name: FBJ murine osteosarcoma viral oncogene homolog Regulates: Osteoblast activity Matrix production Bone remodeling
- #74 FIGURE 25-42 Osteoblastoma showing plump osteoblasts rimming trabeculae of woven bone.
- #77 Giant Cell Tumor of Bone (GCTB) is a benign but locally aggressive tumor composed of numerous osteoclast-like multinucleated giant cells uniformly distributed among mononuclear stromal cells, which are the true neoplastic component. Uniform distribution of osteoclast-like giant cells. Mononuclear stromal cells with indistinguishable nuclei from giant cells. No atypia or pleomorphism in typical cases. Mitotic figures may be present, but atypical mitoses are absent. No osteoid production (helps differentiate from osteosarcoma) RANKLPositive (produced by stromal cells)H3F3A (G34W)Positive in most cases (mutation-specific antibody)CD68Positive in giant cells (macrophage lineage marker)VimentinPositive in stromal cells
- #78 Aneurysmal bone cyst (ABC) is a benign, expansile, osteolytic bone lesion composed of blood-filled cystic spaces separated by septa containing giant cells, fibroblasts, and reactive bone. Despite its name, it's not a true cyst because it lacks an epithelial lining. Primary ABC: True neoplasm Associated with USP6 gene rearrangement (e.g., CDH11–USP6 fusion) Secondary ABC: Arises within pre-existing bone lesions: Giant cell tumor Chondroblastoma Osteoblastoma Fibrous dysplasia
- #79 A rare histological variant of conventional osteosarcoma, resembling a benign osteoblastoma but with malignant features, infiltrative growth, and high recurrence/metastatic potential. May show plump osteoblasts like osteoblastoma BUT also shows: Hyperchromatic nuclei Mitotic figures, including atypical Permeation of surrounding bone No peripheral maturation (unlike benign lesions) Atypical mitosis shows irregular, multipolar, or bizarre mitotic spindles, suggesting genetic instability and malignancy.