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1. Assoc. Prof. Belson Rugwizangoga, MD, MMed-Path, PhD
University of Rwanda School of Medicine and Pharmacy
Year2GeneralMedicine&
DentalSurgery

2. Skeletal System Non-Tumoral Diseases
Bone Tumors
Joint
Skeletal Muscle
Neuromuscular Junction
Soft Tissue Tumors
2
Musculo-Skeletal
Pathol_Belson

3. 1. Husain A. Sattar. Fundamentals of Pathology:
Medical Course and Step 1 Review, 2021 Edition.
Pathoma LLC: Chicago (Illinois), 2021.
2. Vinay Kumar & Abul K. Abbas & Jon Aster. Robbins
Basic Pathology, 10th Ed. Elsevier: Philadelphia
(Pennsylvania), 2018.
3. John Goldblum, Laura Lamps, Jesse McKenney,
Jeffrey Myers. Rosai and Ackerman's Surgical
Pathology, 11th Ed. Elsevier: Philadelphia
(Pennsylvania), 2017.
4. International Agency for Research on Cancer (IARC).
World Health Organization (WHO) Classification
of Soft Tissue and Bone Tumours, 5th Ed. (Vol. 3)
IARC: Lyon (France), 2020.
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Musculo-Skeletal
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4. Introduction
Musculo-Skeletal Pathology
Musculo-Skeletal Pathol_Belson
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5. 5
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9. 9
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Bone Structure Bone Metabolism

10. Skeletal
System Non-
Tumoral
Diseases
Musculo-Skeletal Pathology
Musculo-Skeletal Pathol_Belson
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11. 11
q Impaired cartilage
proliferation in the growth
plate; common cause of
dwarfism
q Due to an activating
mutation in fibroblast growth
factor receptor 3 (FGFR3);
autosomal dominant
v Overexpression of
FGFR3 inhibits growth.
v Most mutations are
sporadic and related to
increased paternal age
q Mental function, life span,
and fertility are not affected.
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12. 12
q Clinical features
vShort extremities with
normal-sized head and
chest - due to poor
endochondral bone
formation;
intramembranous bone
formation is not
affected.
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ØEndochondral bone formation is characterized by formation of a
cartilage matrix, which is then replaced by bone; it is the
mechanism by which long bones grow.
Ølntramembranous bone formation is characterized by formation
of bone without a preexisting cartilage matrix; it is the
mechanism by which flat bones (e.g., skull and rib cage)
develop.

13. 13
q Congenital defect of bone
formation resulting in
structurally weak bone
q Most commonly due to an
autosomal dominant defect
in collagen type I synthesis
q Clinical features
v Multiple fractures of bone
(can mimic child abuse, but
bruising is absent)
v Blue sclera - Thinning of
scleral collagen reveals
underlying choroidal veins.
v Hearing loss - Bones of the
middle ear easily fracture.
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14. 14
qInherited defect of bone resorption resulting in
abnormally thick, heavy bone that fractures easily
qDue to poor osteoclast function
qMultiple genetic variants exist; carbonic anhydrase
II mutation leads to loss of the acidic
microenvironment required for bone resorption
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15. 15
q Clinical features include
v Bone fractures
v Anemia, thrombocytopenia, and
leukopenia with extramedullary
hematopoiesis - due to bony
replacement of marrow
(myelophthisic process, Fig.)
v Vision and hearing impairment - due to impingement on cranial
nerves
v Hydrocephalus - due to narrowing of the foramen magnum
v Renal tubular acidosis - seen with carbonic anhydrase II mutation
Ø Lack of carbonic anhydrase results in decreased tubular
reabsorption of HCO3
-, leading to metabolic acidosis.
q Treatment is bone marrow transplant; osteoclasts are
derived from monocytes
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16. 16
q Defective mineralization of osteoid
v Osteoblasts normally produce osteoid, which is then mineralized with
calcium and phosphate to form bone.
q Due to low levels of vitamin D, which results in low serum
calcium and phosphate
v Vitamin D is normally derived from the skin upon exposure to sunlight
(85%) and from the diet (15%).
v Activation requires 25-hydroxylation by the liver followed by 1-
alphahydroxylation by the proximal tubule cells of the kidney.
v Active vitamin D raises serum calcium and phosphate by acting on
Ø Intestine - increases absorption of calcium and phosphate
Ø Kidney - increases reabsorption of calcium and phosphate
Ø Bone - increases resorption of calcium and phosphate
v Vitamin D deficiency is seen with decreased sun exposure (e.g.,
northern latitudes), poor diet, malabsorption, liver failure, renal failure.
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17. 17
q Rickets is due to ↓vitamin D
in children, resulting in
abnormal bone mineralization.
vMost commonly arises in
children < 1year of age;
presents with
ØPigeon-breast deformity -
inward bending of the ribs with
anterior protrusion of the
sternum
ØFrontal bossing (enlarged
forehead) - due to osteoid
deposition on the skull
ØRachitic rosary - due to
osteoid deposition at the
costochondral junction
ØBowing of the legs may be
seen in ambulating children.
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18. 18
qOsteomalacia is due to low vitamin D in adults.
vInadequate mineralization results in weak bone with
an increased risk for fracture.
vLaboratory findings include ↓serum calcium, ↓serum
phosphate, ↑PTH, and ↑alkaline phosphatase
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19. 19
q Reduction in
trabecular bone mass
q Results in porous
bone with an
increased risk for
fracture
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q Risk of osteoporosis is based on peak bone mass (attained in
early adulthood) and rate of bone loss that follows thereafter.
vPeak bone mass is achieved by 30 y of age and is based on
(1) genetics (e.g., vit D receptor variants), (2) diet, (3) exercise.
vThereafter, slightly <1% of bone mass is lost each year; bone
mass is lost more quickly with lack of weight-bearing exercise
(e.g., space travel), poor diet, or ↓estrogen (e.g., menopause)

20. 20
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qMost common
forms of
osteoporosis are
senile &
postmenopausal

21. 21
q Clinical features
vBone pain & fractures in
weight-bearing areas such
as vertebrae (àloss of
height & kyphosis), hip, and
distal radius
vBone density is measured
using a DEXA scan.
vSerum calcium, phosphate,
PTH, and alkaline
phosphatase are normal;
labs help to exclude
osteomalacia (which has a
similar clinical presentation).
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22. 22
q Treatment includes
vExercise, vitamin D, and
calcium - limit bone loss
vBisphosphonates - induce
apoptosis of osteoclasts
vEstrogen replacement
therapy is debated
(currently not
recommended).
vGlucocorticoids are
contraindicated (worsen
osteoporosis).
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23. 23
q Imbalance between osteoclast and
osteoblast function
vUsually seen in late adulthood
(average age > 60 years)
q Etiology is unknown; possibly viral
q Localized process involving one or
more bones; does not involve the
entire skeleton
q Three distinct stages are (1)
osteoclastic, (2) mixed osteoblastic-
osteoclastic, and (3) osteoblastic
vEnd result is thick, sclerotic bone
that fractures easily.
vBiopsy reveals a mosaic pattern
of lamellar bone (Fig. lower).
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24. 24
qClinical features
vBone pain - due to
microfractures
vIncreasing hat size-Skull is
commonly affected.
vHearing loss - impingement on
cranial nerve
vLion-like facies - involvement of
craniofacial bones
vIsolated elevated alkaline
phosphatase - most common
cause of isolated elevated
alkaline phosphatase in patients
> 40 years old
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25. 25
qTreatment includes
vCalcitonin - inhibits osteoclast function
vBisphosphonates - induces apoptosis of osteoclasts
qComplications include
vHigh-output cardiac failure - due to formation ofAV shunts in bone
vOsteosarcoma
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26. 26
q Infection of marrow and bone
vUsually occurs in children
q Most commonly bacterial; arises via
hematogenous spread
vTransient bacteremia (children)
seeds metaphysis.
vOpen-wound bacteremia (adults)
seeds epiphysis.
q Clinical features
vBone pain with systemic signs of
infection (e.g., fever and
leukocytosis)
vLytic focus (abscess) surrounded
by sclerosis of bone on x-ray; lytic
focus is called sequestrum, and
sclerosis is called involucrum.
q Diagnosis is made by blood culture.
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27. 27
qCauses include
v Staphylococcus
aureus - most
common cause (90%
of cases)
v N gonorrhoeae -
sexually active young
adults
v Salmonella - sickle
cell disease
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v Pseudomonas - diabetics or IV drug abusers
v Pasteurella - associated with cat or dog bite/scratches
v Mycobacterium tuberculosis - usually involves vertebrae (Pott
disease)
qComplications include squamous cell carcinoma of the
fistulized skin

28. 28
qIschemic necrosis of
bone and bone marrow
qCauses include trauma
or fracture (most
common), steroids,
sickle cell anemia, and
caisson disease.
qOsteoarthritis and
fracture are major
complications.
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29. 29
qHypertrophic
osteoarthropathy
qSoft tissue and
periosteal bone
qEmphysema
qLung cancer
qHeart defects
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30. 30
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31. Bone Tumors
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Musculo-Skeletal Pathology

32. 32
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Bone tumors according to age
Age group
(years)
Most common benign lesions Most common malignant tumors
0 - 10 simple bone cyst
non-ossifying fibroma
Ewing's sarcoma
leukemic involvement
10 - 20 fibrous dysplasia; simple bone cyst;
aneurysmal bone cyst
osteochondroma, osteoid osteoma;
osteoblastoma, chondroblastoma
osteosarcoma,
Ewing's sarcoma,
adamantinoma
20 - 40 Enchondroma
giant cell tumor
chondrosarcoma
metastatic tumors
≥40 Osteoma Myeloma; leukemic involvement
chondrosarcoma, osteosarcoma
(Paget's associated), chordoma

33. 33
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Site of long bone involvement

34. 34
qBenign tumor of bone
qMost commonly arises on the surface of facial
bones (but also seen in other locations)
qAssociated with Gardner syndrome.
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35. 35
q Benign tumor of osteoblasts (that
produce osteoid) surrounded by
a rim of reactive bone
q Occurs in young adults < 25
years of age (more common in
males)
q Arises in cortex of long bones
(e.g., femur)
q Presents as bone pain that
resolves with aspirin
q Imaging reveals a bony mass (<
2 cm) with a radiolucent core
(osteoid)
q Osteoblastoma is similar to
osteoid osteoma but is larger ( >
2 cm), arises in vertebrae, and
presents as bone pain that does
not respond to aspirin.
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36. 36
q Tumor of bone with an overlying cartilage cap (Fig.
right); most common benign tumor of bone
q Arises from a lateral projection of the growth plate
(metaphysis); bone is continuous with marrow space.
q Overlying cartilage can transform (rarely) to
chondrosarcoma
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37. 37
q Malignant proliferation of
osteoblasts
q Peak incidence is seen in
teenagers; less commonly
seen in the elderly
vRisk factors include familial
retinoblastoma, Paget
disease, and radiation
exposure.
vArises in the metaphysis of
long bones, usually the distal
femur or proximal tibia
(region of the knee)
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38. 38
q Presents as a pathologic fracture
or bone pain with swelling
q Imaging reveals a destructive
mass with a 'sunburst'
appearance and lifting of the
periosteum (Codman triangle,
Fig.A).
q Biopsy reveals pleomorphic cells
that produce osteoid (Fig. B)
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39. 39
q Tumor comprised of
multinucleated giant cells
and stromal cells
q Occurs in young adults
q Arises in the epiphysis of
long bones, usually the
distal femur or proximal tibia
(region of the knee)
q 'Soap-bubble' appearance
on x-ray
q Locally aggressive tumor;
may recur
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40. 40
q Malignant proliferation of poorly-differentiated cells derived from
neuroectoderm
q Arises in diaphysis of long bones; usually in male children(< 15 years)
q 'Onion-skin' appearance on x-ray
q Biopsy reveals small, round blue cells that resemble lymphocytes (Fig.)
v Can be confused with lymphoma or chronic osteomyelitis
v t(11;22) translocation is characteristic.
q Often presents with metastasis; responsive to chemotherapy
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41. 41
q Benign tumor of
cartilage
q Usually arises in the
medulla of small
bones of the hands
and feet (Fig.)
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42. 42
qMalignant cartilage-
forming tumor
qArises in medulla of the
pelvis or central skeleton
qUsually ≥40 years of age
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43. 43
qMore common than
primary tumors
qUsually result in
osteolytic (punched-
out) lesions
qProstatic carcinoma
classically produces
osteoblastic lesions.
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44. Joint
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45. 45
q Connection between 2 bones
q Solid joints are tightly
connected to provide structural
strength (e.g., cranial sutures).
q Synovial joints have a joint
space to allow for motion.
vArticular surface of adjoining
bones is made of hyaline
cartilage (type II collagen) that
is surrounded by a joint
capsule.
vSynovium lining the joint
capsule secretes fluid rich in
hyaluronic acid to lubricate the
joint and facilitate smooth
motion.
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46. 46
q Progressive degeneration of
articular cartilage; most common
type of arthritis
q Most often due to 'wear and tear'
q Major risk factor is age (common
after 60 years); additional risk
factors include obesity and trauma.
q Affects a limited number of joints
(oligoarticular); hips, lower lumbar
spine, knees, and the distal
interphalangeal joints (DIP) and
proximal interphalangeal joints
(PIP) of fingers are common sites.
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47. 47
q Classic presentation is joint
stiffness in the morning that
worsens during the day.
q Pathologic features include
vDisruption of the cartilage that lines
the articular surface (Fig.);
fragments of cartilage floating in the
joint space are called 'joint mice.'
vEburnation of the subchondral bone
vOsteophyte formation (reactive
bony outgrowths); classically arises
in the DIP(Heberden nodes) and
PIP(Bouchard nodes) joints of the
fingers
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48. 48
q Chronic, systemic autoimmune
disease
vClassically arises in women
of late childbearing age
vAssociated with HLA-DR4
q Characterized by involvement
of joints
vHallmark is synovitis leading
to formation of a pannus
(inflamed granulation tissue).
vLeads to destruction of
cartilage and ankylosis
(fusion) of joint
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49. 49
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q Laboratory findings
vIgM autoantibody
against Fc portion of
IgG (rheumatoid
factor); marker of
tissue damage and
disease activity
vNeutrophils and high
protein in synovial fluid
q Complications include
anemia of chronic
disease and secondary
amyloidosis

50. 50
qClinical features
vArthritis with morning stiffness
that improves with activity.
Ø Symmetric involvement of PIP
joints of the fingers (swan-neck
deformity), wrists (radial
deviation), elbows, ankles, and
knees is characteristic (Fig.);
DIPis usually spared (unlike
osteoarthritis).
Ø Joint-space narrowing, loss of
cartilage, and osteopenia are
seen on x-ray.
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51. 51
qClinical features (cont’d)
vFever, malaise, weight loss, and
myalgias
vRheumatoid nodules - central
zone of necrosis surrounded by
epithelioid histiocytes; arise in
skin and visceral organs
vVasculitis - Multiple organs may
be involved.
vBaker cyst - swelling of bursa
behind the knee
vPleural effusions,
lymphadenopathy, and interstitial
lung fibrosis
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52. 52
q Group of joint disorders
characterized by
vLack of rheumatoid factor
vAxial skeleton involvement
vHLA-B27 association
q Ankylosing spondyloarthritis
involves sacroiliac joints & spine.
vYoung adults, most often male
vPresents with low back pain;
involvement of vertebral bodies
eventually arises, à fusion of
vertebrae ('bamboo spine').
vExtra-articular manifestations
include uveitis and aortitis
(leading to aortic regurgitation)
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53. 53
qReactive arthritis is
characterized by the triad of
arthritis, urethritis, and
conjunctivitis.
vArises in young adults (usually
males) weeks after a GI or
Chlamydia trachomatis infection
qPsoriatic arthritis is seen in 10%
of cases of psoriasis.
vInvolves axial and peripheral
joints; DIPjoints of the hands
and feet are most commonly
affected, leading to "sausage"
fingers or toes.
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54. 54
qArthritis due to an infectious agent, usually bacterial
qCauses include
vN gonorrhoeae - young adults; most common cause
vS aureus - older children and adults; 2nd most common cause
qClassically involves a single joint, usually the knee
qPresents as a warm joint with limited range of motion; fever,
increased white count, and elevated ESR are often present.
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55. 55
qDeposition of monosodium
urate (MSU) crystals in
tissues, especially the joints
qDue to hyperuricemia;
related to overproduction or
decreased excretion of uric
acid
vUric acid is derived from purine
metabolism and is excreted by
kidney.
qPrimary gout is the most
common form; etiology of
hyperuricemia is unknown.
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56. 56
qSecondary gout is seen with
vLeukemia and myeloproliferative
disorders -Increased cell
turnoverleads to hyperuricemia.
vLesch-Nyhan syndrome -X-
linked deficiency of
hypoxanthine-guanine
phosphoribosyltransferase
(HGPRT); presents with mental
retardation and self-mutilation
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vRenalinsufficiency -decreased renalexcretion of uric acid
q Acute gout presents as exquisitely painful arthritis of the great toe
(podagra)
vMSU crystals deposit in joint, triggering an acute inflammatory reaction.
vAlcohol orconsumption of meat may precipitate arthritis.

57. 57
qChronic gout leads to
vDevelopment of tophi - white, chalky
aggregates of uric acid crystals with
fibrosis and giant cell reaction in soft
tissue and joints (Fig.A)
vRenal failure - Urate crystals may deposit
in kidney tubules (urate nephropathy).
q Laboratory findings include hyperuricemia;
synovial fluid shows needle-shaped crystals
with negative birefringence under polarized
light (Fig. B).
q Pseudogout resembles gout clinically, but is
due to deposition of calcium pyrophosphate
dihydrate (CPPD); synovial fluid shows
rhomboid-shaped crystals with weakly
positive birefringence under polarized light.
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58. Skeletal Muscle
58
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59. 59
q Inflammatory disorder of skin & skeletal
muscle
q Unknown etiology; some cases are associated
with carcinoma (e.g., gastric carcinoma).
q Clinical features
vBilateral proximal muscle weakness; distal
involvement can develop late in disease.
vRash of the upper eyelids (heliotrope rash);
malar rash may also be seen.
vRed papules on the elbows, knuckles, and
knees (Gottron papules)
q Laboratory findings
vIncreased creatine kinase
vPositive ANA and anti-Jo-1 antibody
vPerimysial inflammation (CD4+ T cells) with
perifascicular atrophy on biopsy (Fig. lower)
q Treatment is corticosteroids.
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60. 60
qInflammatory disorder
of skeletal muscle
qResembles
dermatomyositis
clinically, but skin is not
involved; endomysial
inflammation (CD8+ T
cells) with necrotic
muscle fibers is seen
on biopsy
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61. 61
qDegenerative disorder characterized by muscle wasting
and replacement of skeletal muscle by adipose tissue
qDue to defects of dystrophin gene
vDystrophin is important for anchoring the muscle
cytoskeleton to the extracellular matrix.
vMutations are often spontaneous; large gene size
predisposes to high rate of mutation.
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62. 62
q Duchenne muscular dystrophy is due
to deletion of dystrophin.
v Presents as proximal muscle
weakness at 1 year of age; progresses
to involve distal muscles
Ø Calf pseudohypertrophy is a
characteristic finding.
Ø ↑Serum creatine kinase.
v Death results from cardiac or
respiratory failure; myocardium is
commonly involved.
q Becker muscular dystrophy is due to
mutated dystrophin; clinically results in
milder disease
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63. Neuromuscular
Junction
63
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64. 64
q Autoantibodies against the
postsynaptic acetylcholine
receptor at the neuromuscular
junction
q More commonly seen in women
q Clinical features
vMuscle weakness that worsens
with use and improves with rest;
classically involves the eyes,
leading to ptosis and diplopia
vSymptoms improve with
anticholinesterase agents.
vAssociated with thymic
hyperplasia or thymoma;
thymectomy improves symptoms.
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65. 65
q Antibodies against presynaptic calcium
channels of the neuromuscular junction
q Arises as a paraneoplastic syndrome,
most commonly due to small cell
carcinoma of the lung
q Leads to impaired acetylcholine release
vFiring of presynaptic calcium channels is
required for acetylcholine release.
q Clinical features
vProximal muscle weakness that
improves with use; eyes are usually
spared.
vAnticholinesterase agents do not improve
symptoms.
vResolves with resection of the cancer
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66. Soft Tissue
Tumors
66
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67. 67
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68. 68
q Mesenchymal proliferations that occur in the extraskeletal,
nonepithelial tissues of the body, excluding the viscera, coverings
of the brain, and lymphoreticular system.
q Necessity for a team-approach and clinico-pathological correlation
q Soft tissue benign tumors outnumber malignant tumors t 100:1
q Cause unknown in most soft tissue tumors
vRadiation therapy, chemical burns, heat burns, or trauma were
associated with subsequent development of a sarcoma
vKaposi sarcoma in immunosuppressed patients is related to
viruses and defective immunocompetence.
vMost soft tissue tumors occur sporadically, but a small minority
are assoc with genetic Sds, the most of which are NF1
(neurofibroma, malignant schwannoma), Gardner Sd
(fibromatosis), Li-Fraumeni Sd (soft tissue sarcoma), and Osler-
Weber-Rendu Sd (telangiectasia).
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69. 69
q It is very difficult for competent pathologists to agree on
the histogenesis of these tumors. Some sarcomas have
multiple cell types present in different areas of the tumor.
q Many tumors are so undifferentiated that to subclassify
them into their histogenic type is close to impossible,
even with specialized techniques such as EM & IHC
q After the histologic type of soft-tissue sarcoma has been
determined, the tumor is graded 1 to 4, depending on its
degree of differentiation (how similar it is to the original
tissue)
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70. 70
Musculo-Skeletal
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Primary tumor (T)
T0
T1
T2
No evidence of primary tumor
Tumor <5 cm
Tumor >5 cm
Lymph nodes (N)
N0
N1
No regional metastasis
Regional node metastasis
Distant metastasis (M)
M0
M1
No distinct metastasis
Distant metastasis
Histopathologic grading (G)
G1
G2
G3
G4
Well differentiated (low grade)
Moderately differentiated (intermediate grade)
Poorly differentiated (high grade)
Undifferentiated
Stage
IA G1 T1 N0 M0
IB G1 T2 N0 M0
IIA G2 T1 N0 M0
IIB G2 T2 N0 M0
IIIA G3 T1 N0 M0
G4 T1 N0 M0
IIIB G3 T2 N0 M0
G4 T2 N0 M0
IVA Any G Any T N1 M0
IVB Any G Any T Any N M1
American
Joint
Committee on
Cancer
(AJCC) of soft
tissue
sarcomas
classification

71. 71
Musculo-Skeletal
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Tumor Translocation Genes involved in
translocation
Ewing’s Sarcoma/PNET t(11:22)(q 24, q 12) EWS-FLI1
t(21;22)(q22, q12) EWS-ER
t(7;22)(p22;q12) EWS-ETV1
Desmoplastic Small Cell
Tumor
t(12;22)(q13;q12) (EWS-ATF1) aka (EWS-WT1)
Extraskeletal myxoid
chondrosarcoma
t(9;22)(q22;12) EWS-TEC aka (EWS-CHN)
Myxoid Liposarcoma t (12:16) (q13;p11) FUS-CHOP
t (12:22:20) EWS-CHOP
t(X:18)(p11.2;q11.2) SYT-SSX1 and (SYT-SSX2)
Alveolar rhabdomyosarc. t (2:13)(q35;q14) PAX3-FKHR

72. 72
qBenign tumor of adipose
tissue
qMost common benign
soft tissue tumor in
adults
q Age:Adults (40-60 years);
Rare in 1st 2 decades
q Sex: M > F
q Most common site:
subcutaneous regions
q Encapsulated, small
q Soft, mobile, and painless
(except angiolipoma)
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73. 73
q Malignant tumor of
adipose tissue
q Most common
malignant soft
tissue tumor in
adults (40’s to 60’s)
; uncommon in
children
q Sex: M = F
q Lipoblast is the
characteristic cell.
Musculo-Skeletal
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q Benign smooth muscle tumors,
often arise in the uterus where
they represent the most common
neoplasm in women.
q Leiomyomas may also arise in the
skin and subcutis from the arrector
pili muscles found in the skin,
nipples, scrotum, and labia
(genital leiomyomas) and less
frequently develop in the deep soft
tissues.
q Composed of fascicles of spindle
cells that tend to intersect each
other at right angles.
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q 10% to 20% of soft tissue
sarcomas.
q Most develop in the skin and deep
soft tissues of the extremities and
retroperitoneum.
q Microscopically, the lesion is
composed of interlacing fascicles of
mildly pleomorphic, spindle cells
with blunt-ended nuclei and
eosinophilic cytoplasm.
q Average mitotic rate was 3 per 10
HPF.
q Geographic areas of necrosis is
present
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qMalignant tumor of skeletal
muscle
qMost common malignant soft
tissue tumor in children
qRhabdomyoblast is the
characteristic cell; desmin positive
qMost common site: head and
neck; vagina in young girls.
qRMS histological subclassification
vEmbryonal (60%, favorable
prognosis
vAlveolar (20%, unfavorable
prognosis
vPleomorphic (20%, worst
prognosis)
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Musculo-Skeletal
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Distribution of
primary sites
for RMS

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qFibrosarcomas are rare
qMay occuranywhere in the body, most
commonly in retroperitoneum, thigh, knee, and
the distalextremities.
qSigns/Symptoms:
v Solitary palpable mass (3.0 to 8.0 cm)
v Slow-growing
v 1/3 of cases present with pain
qAge:
v Adult type: 30-55 years
v Infantile type: First 2 years of life; Congenital
qSex:M>F
qMorphology
v Typically,unencapsulated,infiltrative,soft,
areasofhemorrhageandnecrosis.
v Histologicexamination:aherringbonepattern
ofpleomorphiccells,frequentmitoses±
necrosis.
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Musculo-Skeletal
Pathol_Belson
MPNST on the back,
rapidly growing
qSchwannoma
v90% of tumors are sporadic
vSigns/Symptoms: Freely mobile, non-painfullesion
vAge:Allages; most common between 20-50 years
vSex: M= F
vAnatomic Distribution: Head & neck, flexorsurfaces of upperand lowerextremities

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q Present with bleeding, anemia,
abdominal pain.
q Most common in the stomach
(62%), Small intestine (28%),
Colon (10%).
q Metastasize to peritoneum and
liver; later to lung.
q Refractory to standard
systemic chemotherapy.
Musculo-Skeletal
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q Chemoembolization of liver with cisplatin can be palliative.
q Cell of origin is the Interstitial cell of Cajal.
q Constitutively expresses c-Kit
q 90% of GISTs are c-Kit positive.
q C-Kit is one of the few tyrosine kinases specifically inhibited by Gleevec.

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qSynovial sarcoma
vSo named because it was
once believed to recapitulate
synovium, but the cell of origin
is still unclear.
vIn addition, although the term
synovial sarcoma implies an
origin from the joint linings,
less than 10% are intra-
articular.
vSynovial sarcomas account for
approximately 10% of all soft
tissue sarcomas and rank as
the 4th most common sarcoma.
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Thanks
Questions & comments
Musculo-Skeletal Pathol_Belson

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Quiz
Musculo-Skeletal Pathol_Belson
Musculo-Skeletal Pathology

84. 84
q A7-year-old girl from Nyanza district is diagnosed with conventional
osteosarcoma. she undergoes neoadjuvant chemotherapy followed by
resection. What is considered a good histologic response to therapy?
A. >70% tumor necrosis
B. >50% tumor necrosis
C. >90% tumor necrosis
D. Any degree of tumor necrosis
E. >20% tumor necrosis
Musculo-Skeletal
Pathol_Belson

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q Match the small round blue cell tumor with the description
Musculo-Skeletal
Pathol_Belson
i. Rhabdomyosarcoma A. Most common soft tissue tumor in
adults
ii. Ewing sarcoma B. Usually a biphasic neoplasm, cell of
origin unknown
iii. Poorly differentiated
synovial sarcoma
C. Affects medullary part of diaphysis in
children
iv. Paget’s disease of bone D. Morphological types include
embryonal, alveolar and pleomorphic
v. Lipoma E. May complicate into an osteogenic
sarcoma