Musculoskeletal Pathology_2022-3_Assoc. Prof. Belson_compressed.pdf

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1. Assoc. Prof. Belson Rugwizangoga, MD, MMed-Path, PhD
University of Rwanda School of Medicine and Pharmacy
Year 2 General Medicine &
Dental Surgery

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

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

10. Skeletal
System Non-
Tumoral
Diseases
Musculo-Skeletal Pathology
Musculo-Skeletal Pathol_Belson
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11. 11
qImpaired cartilage proliferation in the growth plate; common cause of dwarfism
qDue to an activating mutation in fibroblast growth factor receptor 3 (FGFR3); autosomal dominant
vOverexpression of FGFR3 inhibits growth.
vMost mutations are sporadic and related to increased paternal age
qMental function, life span, and fertility are not affected.
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12. 12
qClinical 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.
Ølntramembranousbone 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
qCongenital defect of bone formation resulting in structurally weak bone
qMost commonly due to an autosomal dominant defect in collagen type I synthesis
qClinical features
vMultiple fractures of bone (can mimic child abuse, but bruising is absent)
vBlue sclera -Thinning of scleral collagen reveals underlying choroidal veins.
vHearing 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
qClinical features include
vBone fractures
vAnemia, thrombocytopenia, and
leukopenia with extramedullary
hematopoiesis -due to bony
replacement of marrow
(myelophthisicprocess, Fig.)
vVision and hearing impairment -due to impingement on cranial nervesvHydrocephalus -due to narrowing of the foramen magnum
vRenal tubular acidosis -seen with carbonic anhydrase II mutationØLack of carbonic anhydrase results in decreased tubular reabsorption of HCO3-, leading to metabolic acidosis.qTreatment is bone marrow transplant; osteoclasts are derived from monocytes
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16. 16
qDefective mineralization of osteoid
vOsteoblasts normally produce osteoid, which is then mineralized with
calcium and phosphate to form bone.
qDue to low levels of vitamin D, which results in low serum calcium and phosphate
vVitamin D is normally derived from the skin upon exposure to sunlight
(85%) and from the diet (15%).
vActivation requires 25-hydroxylation by the liver followed by 1-
alphahydroxylation by the proximal tubule cells of the kidney.
vActive vitamin D raises serum calcium and phosphate by acting on
ØIntestine -increases absorption of calcium and phosphate
ØKidney -increases reabsorption of calcium and phosphate
ØBone -increases resorption of calcium and phosphate
vVitamin 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
qRicketsis 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
qOsteomalaciais 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
qReduction in
trabecular bone mass
qResults in porous
bone with an
increased risk for
fracture
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qRisk 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
qClinical 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
qTreatment 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
qImbalance between osteoclast and
osteoblast function
vUsually seen in late adulthood
(average age > 60 years)
qEtiology is unknown; possibly viral
qLocalized process involving one or
more bones; does not involve the
entire skeleton
qThree 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 of AV shunts in bone
vOsteosarcoma
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26. 26
qInfection of marrow and bonevUsually occurs in children
qMost commonly bacterial; arises via hematogenous spread
vTransient bacteremia (children) seeds metaphysis.
vOpen-wound bacteremia (adults) seeds epiphysis.qClinical 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.
qDiagnosis is made by blood culture.
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27. 27
qCauses include
vStaphylococcus aureus -most common cause (90% of cases)
vN gonorrhoeae -sexually active young adults
vSalmonella-sickle cell disease
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vPseudomonas -diabetics or IV drug abusers
vPasteurella-associated with cat or dog bite/scratches
vMycobacterium 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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31. Bone Tumors
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Musculo-Skeletal Pathology

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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
≥40OsteomaMyeloma;leukemic involvement
chondrosarcoma, osteosarcoma
(Paget's associated), chordoma

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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
qBenign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive bone
qOccurs in young adults < 25 years of age (more common in males)
qArises in cortex of long bones (e.g., femur)
qPresents as bone pain that resolves with aspirin
qImaging reveals a bony mass (< 2 cm) with a radiolucent core (osteoid)
qOsteoblastoma 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
qTumor of bone with an overlying cartilage cap (Fig. right); most common benign tumor of bone
qArises from a lateral projection of the growth plate (metaphysis); bone is continuous with marrow space.
qOverlying cartilage can transform (rarely) to chondrosarcoma
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37. 37
qMalignant proliferation of
osteoblasts
qPeak 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
qPresents as a pathologic fracture
or bone pain with swelling
qImaging reveals a destructive
mass with a 'sunburst'
appearance and lifting of the
periosteum (Codman triangle,
Fig. A).
qBiopsy reveals pleomorphic cells
that produce osteoid (Fig. B)
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39. 39
qTumor comprised of
multinucleated giant cells
and stromal cells
qOccurs in young adults
qArises in the epiphysis of
long bones, usually the
distal femur or proximal tibia
(region of the knee)
q'Soap-bubble' appearance
on x-ray
qLocally aggressive tumor;
may recur
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40. 40
qMalignant proliferation of poorly-differentiated cells derived from neuroectoderm
qArises in diaphysis of long bones; usually in male children(< 15 years)q'Onion-skin' appearance on x-ray
qBiopsy reveals small, round blue cells that resemble lymphocytes (Fig.)vCan be confused with lymphoma or chronic osteomyelitis
vt(11;22) translocation is characteristic.qOften presents with metastasis; responsive to chemotherapy
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41. 41
qBenign tumor of
cartilage
qUsually 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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Musculo-Skeletal Pathology

45. 45
qConnection between 2 bones
qSolid joints are tightly connected to provide structural strength (e.g., cranial sutures).
qSynovial 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
qProgressive degeneration of
articular cartilage; most common
type of arthritis
qMost often due to 'wear and tear'
qMajor risk factor is age (common
after 60 years); additional risk
factors include obesity and trauma.
qAffects 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
qClassic presentation is joint
stiffness in the morning that
worsens during the day.
qPathologic 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
qChronic, systemic autoimmune
disease
vClassically arises in women
of late childbearing age
vAssociated with HLA-DR4
qCharacterized 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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qLaboratory findings
vIgM autoantibody
against Fc portion of
IgG (rheumatoid
factor); marker of
tissue damage and
disease activity
vNeutrophils and high
protein in synovial fluid
qComplications include
anemia of chronic
disease and secondary
amyloidosis

50. 50
qClinical features
vArthritis with morning stiffness
that improves with activity.
ØSymmetric involvement of PIP
joints of the fingers (swan-neck
deformity), wrists (radial
deviation), elbows, ankles, and
knees is characteristic (Fig.);
DIP is usually spared (unlike
osteoarthritis).
ØJoint-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
qGroup of joint disorders
characterized by
vLack of rheumatoid factor
vAxial skeleton involvement
vHLA-B27 association
qAnkylosing spondyloarthritis
involves sacroiliac joints &spine.
vYoung adults, most often male
vPresents with low back pain;
involvement of vertebral bodies
eventually arises, àfusion 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; DIP joints 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
turnover leads to hyperuricemia.
vLesch-Nyhansyndrome -X-
linked deficiency of
hypoxanthine-guanine
phosphoribosyltransferase
(HGPRT); presents with mental
retardation and self-mutilation
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vRenal insufficiency -decreased renal excretion of uric acid
qAcute gout presents as exquisitely painful arthritis of the great toe
(podagra)
vMSU crystals deposit in joint, triggering an acute inflammatory reaction.
vAlcohol or consumption 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).
qLaboratory findings include hyperuricemia;
synovial fluid shows needle-shaped crystals
with negative birefringence under polarized
light (Fig. B).
qPseudogout 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
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Musculo-Skeletal Pathology

59. 59
qInflammatory disorder of skin & skeletal muscle
qUnknown etiology; some cases are associated with carcinoma (e.g., gastric carcinoma).
qClinical 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 (Gottronpapules)
qLaboratory findings
vIncreased creatine kinase
vPositive ANA and anti-Jo-1 antibody
vPerimysialinflammation (CD4+ T cells) with perifascicular atrophy on biopsy (Fig. lower)
qTreatment 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 tissueqDue to defects of dystrophin genevDystrophin 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
qDuchennemuscular dystrophy is due to deletion of dystrophin.
vPresents as proximal muscle weakness at 1 year of age; progresses to involve distal muscles
ØCalf pseudohypertrophy is a characteristic finding.
Ø↑Serum creatine kinase.vDeath results from cardiac or respiratory failure; myocardium is commonly involved.qBecker muscular dystrophy is due to mutated dystrophin; clinically results in milder disease
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63. Neuromuscular
Junction
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64. 64
qAutoantibodies against the postsynaptic acetylcholine receptor at the neuromuscular junctionqMore commonly seen in womenqClinical 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
qAntibodies against presynaptic calcium channels of the neuromuscular junctionqArises as a paraneoplastic syndrome, most commonly due to small cell carcinoma of the lungqLeads to impaired acetylcholine release
vFiring of presynaptic calcium channels is required for acetylcholine release.qClinical 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
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67. 67
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68. 68
qMesenchymal proliferations that occur in the extraskeletal, nonepithelial tissues of the body, excluding the viscera, coverings of the brain, and lymphoreticular system.
qNecessity for a team-approach and clinico-pathological correlationqSoft tissue benign tumors outnumber malignant tumors t 100:1qCause 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 assocwith genetic Sds, the most of which are NF1(neurofibroma, malignant schwannoma), Gardner Sd (fibromatosis), Li-Fraumeni Sd (soft tissue sarcoma), and Osler-Weber-RenduSd (telangiectasia).
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69. 69
qIt 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.
qMany tumors are so undifferentiated that to subclassify
them into their histogenictype is close to impossible,
even with specialized techniques such as EM & IHC
qAfter 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
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Primarytumor(T)T0T1T2
NoevidenceofprimarytumorTumor<5cmTumor>5cm
Lymphnodes(N)N0N1 NoregionalmetastasisRegionalnodemetastasis
Distantmetastasis(M)M0M1 NodistinctmetastasisDistantmetastasis
Histopathologicgrading(G)G1G2G3G4
Welldifferentiated(lowgrade)Moderatelydifferentiated(intermediategrade)Poorlydifferentiated(highgrade)Undifferentiated
Stage
IAG1T1N0M0IBG1T2N0M0IIAG2T1N0M0IIBG2T2N0M0IIIAG3T1N0M0G4T1N0M0IIIBG3T2N0M0G4T2N0M0IVAAnyGAnyTN1M0IVBAnyGAnyTAnyNM1
American
Joint
Committee on
Cancer
(AJCC) of soft
tissue
sarcomas
classification

71. 71
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TumorTranslocation Genes involved in
translocation
Ewing’s Sarcoma/PNETt(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)
Extraskeletalmyxoid
chondrosarcoma
t(9;22)(q22;12)EWS-TEC aka (EWS-CHN)
Myxoid Liposarcomat (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 tissueqMost common benign soft tissue tumor in adults
qAge: Adults (40-60 years); Rare in 1st2 decadesqSex: M > FqMost common site: subcutaneous regions
qEncapsulated, smallqSoft, mobile, and painless (except angiolipoma)
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73. 73
qMalignant tumor of adipose tissueqMost common malignant soft tissue tumor in adults (40’s to 60’s) ; uncommon in childrenqSex: M = FqLipoblast is the characteristic cell.
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74. 74
qBenign smooth muscle tumors,
often arise in the uterus where
they represent the most common
neoplasm in women.
qLeiomyomas 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.
qComposed of fascicles of spindle
cells that tend to intersect each
other at right angles.
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75. 75
q10% to 20% of soft tissue
sarcomas.
qMost develop in the skin and deep
soft tissues of the extremities and
retroperitoneum.
qMicroscopically, the lesion is
composed of interlacing fascicles of
mildly pleomorphic, spindle cells
with blunt-ended nuclei and
eosinophilic cytoplasm.
qAverage mitotic rate was 3 per 10
HPF.
qGeographic areas of necrosis is
present
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qMalignant tumor of skeletal muscle
qMost common malignant soft tissue tumor in childrenqRhabdomyoblastis 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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Distribution of
primary sites
for RMS

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qFibrosarcomasare rare qMay occur anywhere in the body, most commonly in retroperitoneum, thigh, knee, and the distal extremities.
qSigns/Symptoms:vSolitary palpable mass (3.0 to 8.0 cm)
vSlow-growing
v1/3 of cases present with pain
qAge:vAdult type: 30-55 years
vInfantile type: First 2 years of life; Congenital
qSex: M > F
qMorphologyvTypically, unencapsulated, infiltrative, soft, areas of hemorrhage and necrosis.
vHistologic examination: a herringbone pattern of pleomorphic cells, frequent mitoses ±necrosis.
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MPNST on the back,
rapidly growing
qSchwannomav90% of tumors are sporadic
vSigns/Symptoms: Freely mobile, non-painful lesion
vAge:Allages; most common between 20-50 years
vSex: M = FvAnatomic Distribution: Head & neck, flexor surfaces of upper and lower extremities

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qPresent with bleeding, anemia,
abdominal pain.
qMost common in the stomach
(62%), Small intestine (28%),
Colon (10%).
qMetastasize to peritoneum and
liver; later to lung.
qRefractory to standard
systemic chemotherapy.
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qChemoembolization of liver with cisplatin can be palliative.
qCell of origin is the Interstitial cell of Cajal.
qConstitutively expresses c-Kit
q90% of GISTs are c-Kit positive.
qC-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 4thmost common sarcoma.
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Thanks
Questions & comments
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Quiz
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Musculo-Skeletal Pathology

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qA 7-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
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qMatch the small round blue cell tumor with the description
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i. RhabdomyosarcomaA. Most common soft tissue tumor in
adults
ii. Ewing sarcomaB. Usually a biphasic neoplasm, cell of
origin unknown
iii. Poorly differentiated
synovial sarcoma
C. Affectsmedullarypart ofdiaphysisin
children
iv. Paget’s disease of boneD. Morphological types include
embryonal, alveolar and pleomorphic
v. LipomaE. May complicate into an osteogenic
sarcoma