BASIC MUSCULOSKELETAL

TUMOR
QORI
BASI
C
BASIC QUESTIONS
• How do you perform history taking
• How do you perform physical examination
• What additional examination will you ask?
• How do you read plain xray in tumor cases
• Please explain about biopsy. The type and how to do it.
• Please explain the bone tumor staging system
 TERMINOLOGY
IN BONE TUMOR
CLASSIFICATION OF PRIMARY
BONE TUMOR
1)Hematopoietic 6)Notochordal
2)Chondroegenic 7)Vascular
3)Osteogenic 8)Lipogenic
4)Unknown origin 9)Neurogenic
5)Fibrogenic
An osteosarcoma grows in a radial manner, forming a ball-like mass.
When it penetrates the bony cortex, it compresses the surrounding
muscles into a pseudocapsular layer referred to as the “reactive
zone.”

Tumor nodules representing microextensions of the primary mass

invade the reactive zone. These nodules are termed “satellites.”

The entire tumor mass, including the reactive zone (satellites), must
be resected to ensure removal of all gross tumor. Thus, the surgical
margin must be wide.

Tumor nodules growing outside the reactive rim but within the same
bone or across a neighboring joint are termed “skip lesions” and
represent regional intraosseous or transarticular metastases
EXPLAIN THE
GROWTH
PROCESS OF
SARCOMA
 EXPLAIN
METASTATIC
BONE PROCESS
 WHAT IS THE
CAUSE OF PAIN
IN TUMOR
 HOW DO YOU
EVALUATE ONCOLOGY
CASES
- HT
- PE
- LAB INVEST
- RADIOLOGIC INVEST
RADIOLOGIC
QUESTIONS
RADIOGRAPHS FINDING
SEQUENCE INTERPRETATION:
1. Patient Identity
2. Projection
3. Lesion location (metaphyseal region), upper/lower end
4. Lesion type (lytic, blastic or mix)
5. Pattern of the lesion (geographic, moth-eaten, permeative)
6. Ill defined border Secondary Perioestal Reaction:
• Codman’s Triangle
7. Wide transitional zone • Sunburst

8. Periosteal reaction (interrupted, continuous)

9. Soft tissue involvement
MRI FINDINGS (CONTRAST)
SEQUENCE INTERPRETATION:
1. Patient Identity
2. MRI Sequence T1/T2 and slice sagittal, axial and coronal
3. Lesion location (metaphyseal region), upper/lower end
4. Lesion signal (hyperintens signal)
5. Heterogeneity (Homogenic/Heterogenic)
6. Mostly solid mass
7. Extension to the intra-articular, intramedullary and soft tissue
surrounding
8. In axial view evaluate the NV involvement
 LABORATORY
EXAM QUESTIONS
LABORATORY
Serum Alkaline Phosphatase (SAP)
•SAP is metalloproteinase enzyme that separate phosphate from
organophosphate.
•Increase SAP followed by increasing of osteoblast activity.
•As a marker in bone malignancy both primary or metastases bone
disease.
•Decreasing of SAP after chemoterapy and surgical management are the
good indicator that describe decreasing of oesteoblas and
mineralization activity in bone.

Lactate Dehydrogenase (LDH)

Increase LDH showing the high aggressive and activity of tumor.
Tumor cells increase aerobe and anaerobes (mostly) metabolism.
Increase lactate is to maintain production of ATP for glycolysis process.
BIOPSY AND PA
QUESTIONS
E
E
O
O
Non
I
D
UBC
FD
CLASSIFICATION
CLASSIFICATION OF BONE
TUMORS
1. Lichtensein system – Modified by Dahlin  based on type of proliferating cell
(benign/malignant)
2. Intramedullary or Surface of the bone
3. Primary or Secondary
4. Bone tumor grade
5. Enneking system (benign and malignant)
6. American Joint Committee on Cancer (AJCC) (benign and malignant)
CLASSIFICATION OF SOFT
TISSUE TUMOR
TREATMENT
QUESTION
MANAGEMENT
(OSTEOSARCOMA)
1. Systemic Control: Neo-adjuvant chemotherapy
 Three cycles of chemotherapy (8-12 weeks)
 Doxorubicin, High-dose MTX, Cisplatin (Renal toxic), Adriamycin
(cardiotoxic)
2. Local Control: Surgical excision
 Limb salvage / saving
 Limb ablation / amputation
3. Systemic Control: Adjuvant Chemotherapy
Note
Principal Chemotherapy agent High-dose MTX is highly sensitive to
Toxic to tumor cells, but tolerable to osteosarcoma cells, but had a narrow dose
healthy cells between therapetic and toxic, so difficult to
maintain. Complication: Renal toxic
Chemotherapy role in bone
tumor: inhibit
Mitosis & Synthesis Phase
GOAL OF NEO-ADJUVANT
CHEMOTHERAPY
1. To kill micro metastases (include Skip lesion, satellite nodule, reaction zone or
pulmonary metastases)
2. Down-sizing tumor
3. To decrease the inflammation (reactive zone)
4. Can salvage NV because inflammation decreasing
5. Can achieve clear margin when performing surgery (easier to perform limb
salvage surgery)
Chemotherapy Response:
ATYPICAL FEMORAL
FRACTURE
LIMB SALVAGE PRINCIPLE
•No difference between survival rate
(amputation vs limb salvage) if judicious wide
surgical margins are adhered to (higher
functional outcome, higher rate of reoperation,
and lower rate of "disability and handicap",
however)
•4 areas of concern: survival, morbidity,
function, psychosocial benefits
•No delay in adjuvant tx
•Reconstruction should be lasting
•Function should be as good or better than
amputation
PNPK
• Rekurensinya dan survival rate pasien
tidak lebih buruk daripada amputasi
• Prosedur yang dilakukan tidak boleh
menunda terapi adjuvant(PNPK)
• Fungsi ekstremitas harus lebih baik
dari amputasi. Fungsi ekstremitas
pascarekonstruksi harus mencapai
functional outcome yang baik,
mengurangi morbiditas jangka panjang
dan mengurangi/meminimalkan
perlunya pembedahan tambahan.
• Rekonstruksi yang dilakukan tidak
boleh menimbulkan komplikasi yang
membutuhkan pembedahan berikutnya
atau hospitalisasi yang berulang-ulang.
CONTRAINDICATION LLS
(PNPK)
•Ada keterlibatan pembuluh darah ataupun struktur saraf,
•Pathologial Fracture (kontra indikasi relatif)
•Contaminated biopsy
•Infeksi
•Immature skeletal age
•Leg-length discrepancy should not more than 8 cm.
•Ekstensi tumor yang sangat luas ke jaringan lunak.
TOP TESTING
FACTS
 HOW DO YOU
PERFORM ABOVE
KNEE
AMPUTATION
PROGNOSIS
Poor prognostic factor
 Large tumor size
 Skip metastasis
 Pulmonary metastases
 Less than 95% tumor necrosis after chemotherapy
 Pathologic fracture
 Despite improvements in chemotherapy, 20-40% patients ultimately die of osteosarcoma.
OSTEOSARCOMA
QUESTIONS
Explain your findings (clinical , radiologic and histopathology)
How do you classifiy this condition
What is the complete diagnosis
How do you treat this patient
*
GIANT CELL TUMOR
HISTORY TAKING
AND PHYSICAL
EXAM
WHAT ADDITIONAL
EXAMINATION YOU
WILL ASK FOR?
PLEASE EXPLAIN
YOUR RADIOLOGIC
FINDING?
PLEASE EXPLAIN
YOUR
HISTOPATHOLOGY
FINDING?
HOW WILL YOU
TREAT THIS
PATIENT?
OSTEOCHON
DROMA
GIANT CELL TUMOR
PRACTICE
 Case 1
Male, 21 y.o, came to clinic with painful mass at distal femur

1. What is the most likely diagnosis for each of the

predilection sites (A-G) of primary bone tumors ?
 Case 1
Male, 21 y.o, came to clinic with painful mass at distal femur

2. Please describe regarding matrix formation seen in

primary bone tumors !
Please describe matrix formation seen in primary bone tumors ! Matrix formation seen in
primary bone tumours classically includes the following:
Popcorn or punctate calcification. This is seen in cartilage-forming tumours (e.g.
enchondroma, chondrosarcoma) in which calcification can occur around the surface of
tumour lobules

Bone-forming. This is characteristic of osteogenic tumours (i.e. osteosarcomas). New bone

can be mixed with lytic areas within the bone, and is often seen within the associated soft-
tissue mass

Ground glass. This indicates fibrous tissue (e.g. fibrous dysplasia, although the appearances
of fibrous dysplasia are diverse)
 Case 1
Male, 21 y.o, came to clinic with painful mass at distal femur

3. Please describe the periosteium reaction to the presence of

a bone tumor!
Please describe the periosteium reaction to the presence of a bone tumor! The periosteum
reacts to the presence of a tumour by:

Displaying a triangle of reactive bone at the edge of the tumour where the periosteum is
elevated (Codman’s triangle)

Laying down new bone in ‘sunray spicules’

Forming layers of new bone, ‘onion-skinning’, possibly reflecting phases of growth of the
tumour (classically in Ewing’s sarcoma)
 Case 1
Male, 21 y.o, came to clinic with painful mass at distal femur

4. Please describe the mechanism of bone cancer pain !

Cancer cells can generate pain that has nociceptive and neuropathic components
Tumor induced acidosis bone pain (nociceptive) : Cancer cells do not destroy bone directly,
but rather they express the receptor activator of nuclear factor κ-B ligand (RANKL), which
binds to its receptor, RANK, that is expressed by osteoclasts. Activation of the
RANKL/RANK pathway promotes the proliferation of osteoclasts. Osteoclasts resorb bone
by forming a highly acidic resorption that stimulates the transient receptor potential
vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) expressed by nerve
fibers that innervates bone which drive bone cancer pain.
Tumor induced impending /fracture bone pain (nociceptive): Several mechanosensitive ion
channels may be involved in detecting high-threshold mechanical stimuli that occur when
distal processes of sensory nerve fibers are distended from mechanical pressure due to
tumor invasion or as a result of destabilization or fracture of bone. 
Sensory nerve injury (neuropathic): When tumor cells invade the normal tissue, the tumor
appears to first come into contact, injure, and then destroy the very distal processes of
sensory fibers. This tumor-induced injury and destruction of the distal ends of the sensory
nerve fibers that innervate the bone is accompanied by an increase in ongoing and
movement-evoked pain behaviors.

Neuroma formation (neuropathic) by sensory and sympathetic nerve fibers that innervate
the skeleton.

The tumors release factors that sensitize and activate bone nociceptors, injure the
sensory nerve fibers, and release growth factors that drive neuroma formation, all of
which can contribute to bone pain.
 Case 2
Male, 64 y.o, pain on his left hip after slipped on the
floor with history of lung cancer (+).

1. Please desribe “Seed and Soil Hypothesis” !

 Case 2
Male, 64 y.o, pain on his left hip after slipped on the
floor with history of lung cancer (+).

2. Please describe the natural history /process of

metastasis !
 
 Case 2
Male, 64 y.o, pain on his left hip after slipped on the
floor with history of lung cancer (+).

3. Please describe the principal process/method of

dissemination of spinal metastasis !
 
 
The diffusion trough Batson venous system is the principal process of spinal metastasis,
but the dissemination is possible also through arterial and lymphatic system or by
contiguity.

The lung and breast cancers metastasize preferably in the thoracic region because the
venous drainage of the breast through the azygos communicates with the plexus of Batson
in the thoracic region, while lung cancer drains through the pulmonary veins in the left
heart and from there is distributed in the generalized manner in the skeletal;

prostate cancer metastasizes usually to the lumbar-sacral spine and pelvis, because it drains
through the pelvic plexus in the lumbar region. Colon and rectal tumors usually metastasize
through the portal system in the liver and lung, and only late in skeletal.
 Case 2
Male, 64 y.o, pain on his left hip after slipped on the
floor with history of lung cancer (+).

 
4. Please describe the mechanism of biphosphonates
in the treatment of MBD!
 
The overall mechanism of bisphosphonates is to inhibit bone resorption through its
apoptotic effects on osteoclasts after being endocytosed. Uptake causes osteoclast apoptosis
through one of two main mechanisms depending on the class of bisphosphonate.

Endocytosis of non-amino-bisphosphonates (clodronate, tiludronate and etidronate)

results in disruption of ATP supply as osteoclasts metabolize this class into analogues of
ATP and eventually undergo apoptosis

The mechanism by which amino-bisphosphonates (ibantdronate, pamidronate,

alendronate, risedronate and zoledronate) cause apoptosis in osteoclasts is through
inhibition of farnesyl pyrophosphate synthase and the mevalonate pathway.