HYPERPLASIA, METAPLASIA, ANAPLASIA

NEOPLASIA, TNM CLASSIFICATION AND ITS

ORTHOPAEDIC APPLICATIONS, SURGICAL
CLASSIFICATION, HISTOLOGIC
CLASSIFICATION AND PRINCIPLES OF LIMB
SALVAGE SURGERY

Dr. Sushil Paudel

 NEOPLASIA
 A neoplasm is an
abnormal mass of
tissue, growth of
which exceeds & is
uncoordinated with
that of the normal
tissues **

**Willis RA; The spread of tumours in the human body.

London, Butterworth & Co, 1952
 HYPERPLASIA
 Increase in the number of cells in an organ
or tissue
Physiological hyperplasia
Pathological hyperplasia
 METAPLASIA
 Reversible change in which one cell type
(epithelial or mesenchymal) is replaced by
another
Epithelial metaplasia
Connective tissue metaplasia
Eg; Myositis ossificans
 DIFFERENTIATION AND
ANAPLASIA

 Anaplasia is loss of Differentiation

Pleomorphism
Altered N:C ratio
Atypical mitoses
Tumor giant cells
 DYSPLASIA
 Disordered growth
 Loss in the uniformity of individual cells as
well as loss in architectural orientation
CLASSIFICATION OF BONE
TUMORS
 HISTORY
 Dates back to 1920, origin of Bone Sarcoma
Registry by Dr Codman
 Dr Codman along with James Ewing and
Bloodgod drew up in 1922, the first classification
of the Registry
 Efforts of many pathologists and oncologists has
given shape to Revised WHO Histologic
Classification of Bone tumours in 1993**

**Schajowicz etal,Cancer 1995 Mar

 TNM CLASSIFICATION
Primary tumour (T) TX: primary tumour cannot be assessed
T0: no evidence of primary tumour
T1: tumour 􀀩 8 cm in greatest dimension
T2: tumour > 8 cm in greatest dimension
T3: discontinuous tumours in the primary bone site
Regional lymph nodes (N) NX: regional lymph nodes cannot be assessed
N0: no regional lymph node metastasis
N1: regional lymph node metastasis
Note: Regional node involvement is rare and cases in which nodal status is not
assessed either
clinically or pathologically could be considered N0 instead of NX or pNX.
Distant metastasis (M) MX: distant metastasis cannot be assessed
M0: no distant metastasis
M1: distant metastasis
M1a: lung
M1b: other distant sites
 HISTOPATHOLOGICAL GRADING
Translation table for ‘three’ and ‘four grade’ to ‘two grade’ (low vs. high grade)
system
TNM two grade system Three grade systems Four grade systems
Low grade Grade 1 Grade 1
Grade 2
High grade Grade 2
Grade 3 Grade 3
Grade 4
Note: Ewing sarcoma is classified as high grade.
Stage IA T1 N0,NX M0 Low grade
Stage IB T2 N0,NX M0 Low grade
Stage IIA T1 N0,NX M0 High grade
Stage IIB T2 N0,NX M0 High grade
Stage III T3 N0,NX M0 Any grade
Stage IVA Any T N0,NX M1a Any grade
Stage IVB Any T N1 Any M Any grade
Any T Any N M1b Any grade
 ENNEKING STAGING
Benign Malignant

 Latent
 Stage IA-Low grade,
intracompartmental
 Active  Stage IB-Low grade,
extracompartmental
 Aggressive
 Stage IIA-High grade,
intracompartmental
 Stage IIB-High
grade,extracompartmental
 Stage III - Metastatic
 WHO HISTOLOGICAL
CLASSIFICATION
 Osteogenic tumours
 Cartilage tumours
 Fibrogenic tumours
 Round cell lesions
 Giant cell tumour of bone
 Notochordal tumours
 Vascular tumours
 Smooth muscle tumours
 Lipogenic tumours
 Neural tumours
 Miscellaneous tumours
 Joint lesions
Each class is further divided into benign and malignant
 BONE FORMING (Osteogenic)
LESIONS
BENIGN LESIONS
 Osteoma

 Enostoses (Bone island)

 Osteoid osteoma

 Osteoblastoma
 MALIGNANT LESIONS

 OSTEOSARCOMAS
share the ability to form osteoid from the
neoplastic cells

MODIFIED WHO CLASSIFICATION

 Takes into account etiology, localisation,

bone specific topography and histology
PRIMARY OSTEOSARCOMAS


INTRAOSSEOUS OSTEOSARCOMA

 INTRACORTICAL OSTEOSARCOMA

 SURFACE OSTEOSARCOMA

 EXTRASKELETAL OSTEOSARCOMA
 INTRAOSSEOUS OSTEOSARCOMA
1. INTRAMEDULLARY
Osteoblastic
Chondroblastic
Fibrogenic
Epithelioid
 IMAGING

Medullary and cortical bone destruction , aggressive periosteal reaction of the velvet
and sunburst types, soft tissue mass contains tumor bone.
 HISTOPATHOLOGY

Markedly pleomorphic tumor cells are separated by lace-like osteoid

2.MALIGNANT FIBROUS HISTIOCYTOMA
LIKE (Fibrohistiocytic) OSTEOSARCOMA

3.GIANT CELL RICH OSTEOSARCOMA

4.SMALL CELL OSTEOSARCOMA

5.LOW GRADE CENTRAL

OSTEOSARCOMA
6.TELANGIECTATIC OSTEOSARCOMA
Malignant bone aneurysm
Aggressive and
poor prognosis
7.GNATHIC OSTEOSARCOMA

8.MULTIFOCAL OSTEOSARCOMA

9. OSTEOSARCOMAS WITH UNUSUAL

CLINICAL PRESENTATIONS
Werner syndrome, Li fraumeni syndrome,
Blooms syndrome, Retinoblastoma
syndrome
SECONDARY OSTEOSARCOMAS
PAGET SARCOMA
FIBROUS DYSPLASIA
BONE INFARCT ?
POST IRRADIATION
 CARTILAGENOUS LESIONS
BENIGN LESIONS
 CHONDROMA

Enchondroma
Periosteal chondroma
Enchondromatosis –
Olliers disease, Mafucci syndrome
Soft tissue chondroma
 OSTEOCHONDROMA

Multiple hereditary
osteochondromata
 CHONDROBLASTOMA
( Codman tumor )
Preferred site– epiphysis

 CHONDROMYXOID FIBROMA

 SYNOVIAL
OSTEOCHONDROMATOSIS
MALIGNANT TUMOURS
 CHONDROSARCOMA
PRIMARY CHONDROSARCOMAS
CONVENTIONAL MEDULLARY
CHONDROSARCOMA

Destructive lesion in the medulla with

annular and comma shaped calcifications and
periosteal new bone formation
 CLEAR CELL CHONDROSARCOMA

 MESENCHYMAL CHONDROSARCOMA

 MYXOID CHONDROSARCOMA

 DEDIFFERENTIATED CHONDROSARCOMA

 PERIOSTEAL CHONDROSARCOMA

 SYNOVIAL CHONDROSARCOMA

 EXTRASKELETAL CHONDROSARCOMA
SECONDARY CHONDROSARCOMAS
ENCHONDROMA

OSTEOCHONDROMA

PAGETIC BONE

SYNOVIAL CHONDROMATOSIS

RADIATION INDUCED
 FIBROGENIC, FIBROOSSEOUS AND
FIBROHISTIOCYTIC LESIONS

BENIGN LESIONS
FIBROUS CORTICAL DEFECT
AND NON OSSIFYING FIBROMA

BENIGN FIBROUS HISTIOCYTOMA

PERIOSTEAL DERMOID

FIBROUS DYSPLASIA

POLYOSTOTIC
MONOSTOTIC MC CUNE ALBRIGHT SYNDROME
MAZABRAUD SYNDROME
OSTEOFIBROUS DYSPLASIA
(KEMPSON CAMPANACCI LESION)
Decided preference for Tibia

DESMOPLASTIC FIBROMA
 FIBROSARCOMA AND
MALIGNANT FIBROUS HISTIOCYTOMA

PRIMARY SECONDARY

Pagets disease
Fibrous dysplasia
Bone infarct
Chronic sinuses of osteomyelitis
 ROUND CELL LESIONS

BENIGN LESIONS

LANGERHANS CELL
HISTIOCYTOSIS
Eusinophilic granuloma
Hand Schullers Christian disease
Letterer Siwe disease

Vertebra plana
MALIGNANT LESIONS
 EWINGS SARCOMA

Diaphysis of long bones

 MALIGNANT LYMPHOMA
Non hodgkins lymphoma
Hodgkins lymphoma

permeative bone destruction

with an aggressive periosteal reaction
 TYPES

 MYELOMA
(Plasmacytoma)
Most common
primary malignant
tumour
VASCULAR LESIONS

BENIGN LESIONS

INTRAOSSEOUS HEMANGIOMA

SYNOVIAL HEMANGIOMA

CYSTIC ANGIOMATOSIS

LYMPHANGIOMA

GLOMUS TUMOUR
MALIGNANT LESIONS

EPITHELOID HEMANGIOENDOTHELIOMA

ANGIOSARCOMA

HEMANGIOPERICYTOMA
 UNCLASSIFIED LESIONS

GIANT CELL TUMOUR

BENIGN
20-40 yr, F>M
Epiphyseal region of

long bones

MALIGNANT

Radiolucent, eccentric, expansive,

absence of reactive sclerosis
MISCELLANEOUS TUMORS AND
TUMOR LIKE LESIONS
BENIGN
 SIMPLE BONE CYST

Metaphyseal, central, lack of periosteal reaction

 ANEURYSMAL BONE
CYST
<20 yr, F>M
Metaphysis of long bones

 SOLID VARIANT OF
ANEURSYMAL BONE
CYST

Giant cell reparative

granuloma
Radiolucent, eccentric, expansive,
butress of periosteal reaction
MALIGNANT LESIONS

 ADAMANTINOMA

 CHORDOMA

 LEIOMYOSARCOMA OF BONE
 OSSEOUS METASTASES

SOLITARY
r
MULTIPLE CORTICAL
PRINCIPLES OF LIMB SALVAGE
SURGERY
 DEFINITION
A set of surgical procedures designed to accomplish
removal of a malignant tumor and reconstruction of
the limb with an acceptable oncologic, functional, and
cosmetic result**

** HENRY DEGROOT et al, LIMB SALVAGE FOR EXTREMITY SARCOMAS

 HISTORY AND CHANGING
TREND
 Eiselberg in 1897
 Lexer  1st successful series of 6 patients
 Lexer  concept of using allografts in tumor surgery
(1907)
 Major changes since 1970 with the advent of advanced
imaging, chemotherapy and radiotherapy, improved
surgical techniques

 Limb salvage possible in up to 85% cases**.

**Bacci G, Picci 2, Pignatti G,etal
 INDICATION
 Every patient with tumor of the extremity
should be considered for limb salvage if
the tumor can be removed with an
adequate margin and the resulting limb is
worth saving
 No justification for limiting the limb salvage
process based only on the prognosis
 BARRIERS TO LIMB
SALVAGE
 Poorly placed biopsy incisions
 Major Neurovascular involvement
 Displaced pathologic fracture
 Fungating and infected tumors
 Recurrence of malignant tumors
 Inability to afford chemotherapy
 Vascular involvement is not an absolute
contraindication for limb salvage surgery
as vascular homografts can be used for
reconstruction (bypass surgery) **

 In selected cases limb salvage can be

combined with metastatectomy
**Faenza A et al, Transplant Proc 2005:37(6):2692-3
 THREE STRIKE RULE
 Bone
 Nerves
 Vessels
 Soft tissue envelope

If three of these key components are

involved, the limb salvage is probably
not worth considering
 GOAL
 Painless limb

 Functional, tumor free limb

 Good psychological outcome

 SUCCESS
Early Management and Referral

Work up – Multidisciplinary

Staging

Patient Education

Surgical resection and Reconstruction

 STAGING
 The most important step in formulating a
treatment plan

Histogenic type of tumor

Local extent
Possibility of metastasis

Radiological staging Surgical staging

 RADIOLOGICAL STAGING
 Probable diagnosis

 Define the anatomic extent of the lesion

 Metastasis
 RADIOGRAPHY
 Site and number of lesions
 Location in bone
 Type of destruction
 Soft tissue mass
 Matrix of tumour
 CT SCAN

 Evaluation of cortical penetration

 Osseous details
 Detecting pulmonary metastasis
 MRI
 Evaluation of the intra-medullary extent of

the tumor
 Soft tissue component
 Relationship to neurovascular
structures
 Skip lesions
 Plan the surgical margins
 ANGIOGRAPHY

 Difficult anatomic location

 Limb salvage surgery where some
neurovascular bundle must be sacrificed and
reconstructed
 Micro vascular surgery
 Intra-arterial chemotherapy
 Pre operative Embolisation
 SCINTIGRAPHY
Tech 99m MDP
 Estimate the local intramedullary extent
 Screen for other skeletal areas of
involvement
TL- 201 and DMSAV
 Differentiation of primary & metastatic
lesions, benign & malignant cartilage lesions
 PET SCAN
 Effect of
chemotherapy
(Necrosis of tumor
mass)
 Investigation of
choice for metastatic
lesions with unknown
primary lesion
 Residual tumor
 Recurrence of tumor
 SURGICAL STAGING
 BIOPSY
Accurate diagnosis
Histological grade
 FNAC or Needle biopsy

 Core biopsy
 Incisional biopsy
 Excisional biopsy
 PRINCIPLES OF BIOPSY

Total excision of the tract Longitudinal incision

Work through muscle not anatomical plane

Oval window
Drain in the line of incision
 RESTAGING AFTER PRE OP
ADJUVANT THERAPY
Indicators for favorable response
 ↓ tumor volume

 ↓ in angiographic vascularity

 Changes in plain X-ray/CT and/or MRI patterns

of matrix appearance

PET scans are better than MRI & CT for depicting

residual or recurrent tumor after treatment
 PRINCIPLES
 Resection of tumor

 Skeletal reconstruction

 Soft tissue & muscle transfer

 RESECTION

SURGICAL MARGINS(As described by Enneking)

 Intralesional

 Marginal

 Wide resection

 Radical resection
 Exactly what constitutes an adequate
margin in any particular case remains
controversial
 For high grade sarcomas, a wide margin is
considered adequate
 In low grade tumors or in high grade
tumors where preoperative radiation
therapy has been given, a marginal
margin may be adequate.
 Tumor resection Margin Curetting of the tumor site

Burring of the resected tumor site Lavaging with Adjuvants & curetting
 SURGICAL ADJUVANTS
 Local physical or chemical agents
Cryosurgery
Methacrylate augmentation
Nitrogen mustard, Merthiolate, Hypertonic
saline
Carbolic acid
High concentration ethanol
Bisphosphonates in Giant cell tumor of bone
 Chemotherapy – Neoadjuvant or Adjuvant
 Radiotherapy
 Immunotherapy
Specific – Active and Passive
Nonspecific – IFN and CSF’s
 RECONSTRUCTION

 Arthrodesis
 Osteoarticular allograft
 Endoprosthetic replacement
 Allograft Prosthetic composite
 Rotationplasty
 Autoclaved tumor bone
 ARTHRODESIS
 With acute docking and shortening
 With bone grafting
 Allograft
 Autograft (fibula,iliac crest,ribs)
 Autoclaved bone tumour graft

FIXATION
EXTERNAL
INTERNAL
Ilizarov
Long ILN
External fixator
Plating
Charnleys clamp
ALLOGRAFT
 Advantages:
 Length can be adjusted
 Biological soft tissue
healing
 Avoid the risks and
complications of
intramedullary fixation of
endoprosthesis.
 Direct attachment of
remaining musculature.
 Disadvantages:
 Long healing time
 Potential for transfer of
disease and infection
 Immune rejection
 Necessity of articular surface
size matching
 Fracture
 Infection
 Non-union
AUTOGRAFT
VASCULARISED FIBULAR GRAFT
 Can heal in hostile environment (Irradiated
tissue and active infection)

 Addresses the complications such as host

allograft nonunion and allograft fracture**

**The Journal of Bone and Joint Surgery (American). 2008;90:93-100.

 ENDOPROSTHESIS
MEGAPROSTHESIS
 Large metallic device designed to replace

the excised length of bone and the

adjacent joint

 Modified hinge design

Proximal femoral prosthesis Saddle prosthesis
Proximal humeral Proximal tibial prosthesis Distal femoral
prosthesis prosthesis
AUTOCLAVED AUTOGRAFT
 ALLOGRAFT PROSTHETIC
COMPOSITE
 Allograft provides a
source of bone stock
& site for tendon
insertions, while the
prosthesis provides a
reliable & stable
articulation & some
support for allograft
 ROTATIONPLASTY
 Amputation of the leg
above the knee, lower
leg and foot are rotated
180 degrees, tibia is
then fused to the
proximal femur. The
ankle now functions in
place of the knee joint
 LIMB SALVAGE IN UPPER
EXTREMITY
 HAND
 WRIST – Arthrodesis or Reconstruction
 ELBOW – Reconstruction
 HUMERUS – Arthrodesis or
Reconstruction
 SCAPULA - Scapulectomy or
Reconstruction
 LIMB SALVAGE IN LOWER
EXTREMITY
 ANKLE – Arthrodesis or Reconstruction
 KNEE - Arthrodesis or Reconstruction
 FEMUR – Arthrodesis or Reconstruction
 PELVIS – Resection and Arthrodesis or
Reconstruction
 LIMB SALVAGE IN CHIDREN
 Rotationplasty
 Tibial turn up
( Turno plasty)
 Modular Expandable
prosthesis**

**Michael D Neel etal, Cancer control Aug 2001

 CONCLUSION
 Limb salvage has become accepted standard
care of the patients with malignant bone tumors
 Success depends on prompt and early referral
by primary care doctor and on careful and
coordinated sequencing of events.
 Achieving a surgical margin that will ensure a
low rate of local recurrence is paramount.
 Multidisciplinary approach is required