PATHOLOGY OF

MUSCULOSKELETAL
SYSTEM
I Wayan Juli Sumadi
Department of Anatomical Pathology
Faculty of Medicine
Udayana University
Bali-Indonesia
Introduction
• Congenital diseases : Osteogenesis imperfect, Achondroplasia
• Infection and other inflammatory diseases : Osteomyelitis, Infectious Arthritis,
Gout Arthritis, RA

• Bone diseases associated with endocrine/metabolism disorders and degenerative

bone diseases : Rickettsia and osteomalacea, Osteoporosis, Osteoarthritis (OA),
• Bone and soft tissue neoplasm and tumor like lesions:
– Primary Bone Tumor
– Secondary Bone Tumor (Metastatic bone disease)
– Soft Tissue Tumor
– Tumor like lesions of bone and soft tissue
Infection and other inflammatory
ds
OSTEOMYELITIS
PYOGENIC OSTEOMYELITIS
• The most common pathogens are Staphylococcus sp. (60%–80%). Other
organisms: E. coli, N. gonorrhoeae, H. influenzae and Salmonella sp.

Pathogenesis:
Organisms may reach the bone by:
(1) Hematogenous spread (>> children: H.influenza and group B streptococci)
(2) Extension from a contiguous site,
(3) Direct implantation after compound fractures or orthopedic procedures.
Pathogenesis of hematogenous osteomyelitis

A. The epiphysis, metaphysis and growth plate are normal. A small, septic
microabscess is forming at the capillary loop. B. Expansion of the septic focus
stimulates resorption of adjacent bony trabeculae. Woven bone begins to surround
this focus. The abscess expands into the cartilage and stimulates reactive bone
formation by the periosteum.
C. The abscess, which continues to expand through the cortex into the subperiosteal tissue,
shears off the perforating arteries that supply the cortex with blood, thereby leading to
necrosis of the cortex. D. The extension of this process into the joint space, the epiphysis and
the skin produces a draining sinus. The necrotic bone is called a sequestrum. The viable
bone surrounding a sequestrum is termed the involucrum.
Clinical features: Complications:
• Swelling, erythema and – Septicemia
tenderness over the
involved bone – Acute bacterial
• Fever arthritis
• Leukocytosis, ESR >> – Pathologic fractures
• Radiologic workup: x- – Chronic osteomyelitis
ray, CT, MRI
• Bone biopsy is necessary – Squamous cell
carcinoma
for a definitive diagnosis,
culture and sensitivity
test
Mycobacterial/Tuberculous
osteomyelitis
• Tuberculosis of bone usually originates in the lungs or lymph
nodes
• The mycobacteria spread to the bone hematogenously, direct
spread very rare
• Tuberculous Spondylitis (Pott Disease): The disease affects
vertebral bodies, >>> thoracic vertebrae
• The Histopathologic findings in tuberculous spondylitis is similar to
tuberculosis at other sites: caseous necrosis and granulomas
• Mycobacterial osteomyelitis more destructive and resistant to
control vs pyogenic osteomyelitis.
Infectious Arthritis
• Hematogenous dissemination
• Direct inoculation or from contiguous spread from a soft tissue
abscess or focus of osteomyelitis.

Infectious •Suppurative
arthritis •Mycobacterial
Suppurative Arthritis
• Bacterial infections
• Hematogenous spread.
• In neonates : >> contiguous spread from underlying epiphyseal
osteomyelitis.
• H. influenza : predominates in children < 2 years
• S. aureus : older children and adults
• Gonococcus: late adolescence and young adulthood
Suppurative arthritis
• acutely painful and swollen joint that has a restricted range of
motion (ROM)
• fever, leukocytosis, and elevated ESR
• >>> single joint, most commonly the knee
• Joint aspiration : purulent fluid
• Prompt recognition and effective antimicrobial therapy can
prevent joint destruction.
Mycobacterial Arthritis
• Mycobacterial arthritis is a chronic progressive monoarticular
infection caused by M. tuberculosis
• all age groups, especially adults
• complication of adjoining osteomyelitis or after hematogenous
dissemination from a visceral (usually pulmonary) site of infection.
• Location: the weight-bearing joints (hips, knees, and ankles)
• Pathology: granulomas with central caseous necrosis
Gout Arthritis
• Transient attacks of acute arthritis initiated by urate crystals
deposited within and around joints.
• Morphology:
– Acute arthritis
– Chronic tophaceous arthrtisis
– Tophi in the articular cartilage, ligaments, tendons, and bursae
– Gouty nephropathy
Pathogenesis

Pathogenesis of acute gouty arthritis. Urate crystals are

phagocytosed by macrophages and stimulate the
production of various inflammatory mediators that elicit the
inflammation characteristic of gout. Note that IL-1, one of the
major pro-inflammatory cytokines, in turn stimulates the
production of chemokines and other cytokines from a variety
of tissue cells. LTB4, Leukotriene B4; IL-1β, interleukin 1β.
Gout arthritis

Gouty tophus—an aggregate of dissolved urate

crystals is surrounded by reactive fibroblasts,
mononuclear inflammatory cells, and giant cells.
Degenerative
diseases
Osteoarthritis (OA)
• Degenerative joint disease (DJD)
• Most common type of joint disease
• Slowly progressive destruction of articular cartilage
• Characterized by degeneration of cartilage that results in
structural and functional failure of synovial joints
• Joints commonly affected : proximal and distal interphalangeal
joints, the joints of the arms, knees, hips, cervical and lumbar
spine.
• Primary OA : > 50 y.o
• Symptoms: joint pain that worsens with use, morning stiffness,
crepitus, and limitation of range of movement.
• The joints commonly involved:
– hips, knees, lower lumbar and cervical vertebrae, proximal and distal
interphalangeal joints of the fingers, first carpometacarpal joints, and first
tarsometatarsal joints.
Pathogenesis
Morphology
• Pathology:
– loss of proteoglycans from the
surface of the articular cartilage
– empty lacunae in articular cartilage
 chondrocytes necrosis
– An osteophyte develops, usually in
the lateral portions of the joint:
– the mesenchymal tissue of the
synovium differentiates into
osteoblasts and chondroblasts to
form a mass of cartilage and bone.
 A, Histologic demonstration of the characteristic fibrillation of the
articular cartilage. B, Eburnated articular surface exposing subchondral
bone (1), subchondral cyst (2) and residual articular cartilage (3).
OSTEOPOROSIS
• Osteopenia refers to decreased bone mass
• Osteoporosis: osteopenia that is severe enough to
significantly increase the risk of fracture
• Osteoporosis is a metabolic bone disease in which normally
mineralized bone is decreased in mass to the point that it
no longer provides adequate mechanical support.
• The etiology : menopause, smoking, vitamin D deficiency,
low body mass index, hypogonadism, a sedentary lifestyle
and glucocorticoid therapy.
 Osteoporosis

Primary Secondary
osteoporosis osteoporosis

Type 2 primary Endocrine disorders

Type 1 primary osteoporosis (e.g., hyperthyroidism)
osteoporosis (senile Gastrointestinal
osteoporosis) disorders (e.g.,
malnutrition)
drugs (e.g.,
Corticosteroids)
Elderly people of both sexes Renal insufficiency
Occurs principally in
postmenopausal woman. Reduce physical activity, Cancer.
Calcium status, vit D<
Increase osteoclast activity.
Generally appears after age 70
Estrogen withdrawal.
Reflects decreased osteoblast
function
• Decreased serum
estrogen
• Increased IL-1, IL-
6, TNF levels
• Increased
expression of
RANK, RANKL • Decreased replicative
• Increased activity of osteoprogenitor
osteoclast activity cells
• Decreased synthetic
activity of osteoblasts
• Decreased biologic activity
of matrix-bound growth
factors
• Reduced physical activity
Osteoporosis. A. Femoral head of
an 82-year-old female with
osteoporosis and a femoral neck
fracture (right) compared with a
normal
control cut to the same thickness
(left). B. Microscopically, there is
reduction in the size and thickness
of bone trabeculae and loss of
connectivity.
Bone Tumors
Bone Tumors
• Bone tumors: uncommon but important neoplasms because
many occur in children and young adults and are potentially
lethal.
• Primary bone tumor may arise from any of the cellular elements
of bone.
• Secondary bone tumor: metastasis
• Most neoplasms of bone occur near the metaphyseal area.
• > 80% of primary tumors are found in the distal femur or proximal
tibia.
Primary Bone Tumors
• WHO Classification of Tumors of Bone:
1. Chondrogenic tumrs
2. Osteogenic tumors
3. Fibrogenic tumors
4. Fibrohistiocytic tumors
5. Ewing sarcoma
6. Hematopoietic neoplasms
7. Osteoclastic giant cell-rich tumors
8. Notochordal tumors
9. Vascular tumors
10. Myogenic, lipogenic and epithelial tumors
11. Tumors of undefined neoplastic nature
12. Undifferentiated pleomorphic sarcoma
BONE FORMING TUMORS

• OSTEOID OSTEOMA
• OSTEOSARCOMA
 OSTEOID OSTEOMA
•Size: < 2 cm

•Location: diaphysis of long bones,>femur

•Age: Children and young adults

•Symptoms: Localized pain most severe at night and relieved by NSAIDs

•X-ray: Well-demarcated radiolucency with central mineralization surrounded by

dense sclerosis  Nidus

•Histology:
anastomosing woven bone with prominent osteoblastic rimming, with
intervening fibrovascular stroma
Osteosarcoma
• Malignant, bone-forming tumor in which the neoplastic cells
form bone
• The most common primary (non-hematopoietic) malignancy
of the skeletal system
• Site: >>> metaphysis of long bone
• Bimodal age distribution with 60% occurring before age 25,
and 13% to 30% occurring in individuals older than 40 years

Radiologic Features
• High-grade osteosarcomas usually large, poorly defined,
destructive, mixed lytic, and blastic, and often have a soft
tissue mass, periosteal reaction (+)
Gross specimen of osteosarcoma . The
large tumor is solid tan–white and
hemorrhagic.
Microscopic Findings
• Composed of malignant cells depositing coarse lace-like bone
• Other components include malignant-appearing cartilage and
fibroblastic elements
• The microscopic appearance is variable and depends on the
type of osteosarcoma
osteosarcoma
Osteoblastic OS Chondroblastic OS
CARTILAGENOUS TUMOR

• OSTEOCHONDROMA
• ENCHONDROMA
• CHONDROSARCOMA
Osteochondroma
• An exophytic projection of bone with a cartilage cap that arises
on the surface of bone and with a marrow cavity that is
contiguous with the medulla of the underlying bone
• Age: Peak in second decade of life, M:F ratio = 2:1
• Presentation:
– Metaphysis
– Painless mass, usually of long duration
– May be discovered incidentally on imaging for other conditions
– May present with pain from local pressure effects or fracture
Enchondroma
• Incidence is unknown for
sporadic enchondromas
because most are
asymptomatic
• Up to 15% to 25% of
cartilage tumors
• Male-to-female ratio of 1:1
• Presentation
– Asymptomatic in most large bones
– Small bones may present with firm
mass or pain
– Secondary fracture may also
produce pain
Microscopically:
• lobules of
benign
cartilage
• peripheral
plates of
bone
Chondrosarcoma
• Cartilage formation by the
tumor cells
• 30 – 60 years old
• Mostly in the pelvis, femur, ribs
shoulder girdle, and humerus

The criteria for malignancy :

• cortical destruction
• permeation to the marrow
• plump & multinucleated nuclei
Grade 1 chondrosarcoma shows only mildly increased cellularity and minimal atypia compared with normal
cartilage. The morphology overlaps substantially with enchondroma.
• Grade 2 chondrosarcoma is visible with increased cellularity and cytologic atypia (note nuclear
detail is visible even at intermediate magnification). Permeation of viable lamellar bone is also
present on the right.
Grade 3 chondrosarcoma demonstrates diffuse hypercellularity,
pleomorphic chondrocytes with nuclear hyperchromasia, irregular
nuclear membranes, and necrosis. Mitotic activity is present in this case,
but mitoses may be rare even in grade 3 tumors.
Ewing’s Sarcoma
• primitive sarcomas
composed of small
cells with uniform,
round, hyperchromatic
nuclei
• Usually affects the
meta-diaphyseal
regions of long bones in
children
• periosteal reaction :
onion skin appearance
• Tumor is monomorphous at low
magnification
• No extracellular matrix is present
• Tumor cells are small and contain
round, dark nuclei with scant mitoses
and small nucleoli
• The cytoplasm is fairly scant and
clear to amphophilic with poorly
visualized cell borders
• Aggregates of cells may be arranged
along delicate fibrous septae or
around small blood vessels
• Necrosis is a regular feature, even in
the absence of prior therapy
 CD99 stains the cells in a
characteristic membranous
distribution

Rosettes may be present

Metastatic Bone Disease
• Metastatic tumors are the most common malignant tumors in bone.
• In adults:
– >> carcinomas  prostate, breast, lung, thyroid and kidney.
– The most common location: vertebral column

• In children:
– the most common bone metastases are from rhabdomyosarcoma,
neuroblastoma, Wilms tumor the kidney.
– the appendicular skeleton is the most common site

• Tumor cells usually arrive in the bone via the bloodstream

• X-ray:
– Lytic (e.g., thyroid, gastrointestinal tract, kidney)
– Blastic (prostate)
Tumor like lesions
Ganglion and Synovial Cysts
Ganglion cyst:
• Location : near a joint capsule or
tendon sheath. >>> around the
joints of the wrist
• Presentation: firm, fluctuant,
translucent nodule, small (1–1.5 cm)
• Pathogenesis : as a result of cystic
or myxoid degeneration of
connective tissue; hence the cyst
wall lacks a cell lining.
• Despite the name, the lesion is
unrelated to ganglia of the nervous
system.
Synovial cyst:
• Herniation of synovium through a
joint capsule or massive
enlargement of a bursa may
produce a synovial cyst.
• A well-recognized example is the
synovial cyst that forms in the
popliteal space in the setting of RA
or OA (Baker cyst).
• The synovial lining may be
hyperplastic and contain
inflammatory cells and fibrin.
Ganglion cyst
Fibrous Dysplasia
• A benign intramedullary fibro-osseous lesion that can be mono-ostotic or
polyostotic (fibrocartilaginous dysplasia, generalized fibrocystic disease of bone)
• Most often seen in children and adolescents, although can occur in adults as well
• Males and females are equally affected
• Presentation
– Site of involvement: jaw bones, skull, femoral neck, other long bones, and ribs
– Mostly asymptomatic, although pain and fractures are sometimes seen
– Can be mono-ostotic or polyostotic
– Polyostotic form associated with McCune-Albright syndrome (fibrous dysplasia, skin
pigmentation, and endocrine anomalies)
– Fibrous dysplasia is also associated with Mazabraud syndrome (fibrous dysplasia and
intramuscular myxoma)
• Histology:
• Curvilinear
trabeculae of woven
bone surrounded by
a moderately cellular
fibroblastic
proliferation  C or
comma shaped,
Chinese character
• The trabeculae lack
prominent
osteoblastic rimming
Kumar, V, Abbas, AK. Aster, JC.
Robbins basic pathology. Tenth
edition. Philadelphia, Elsevier. 2018.
Rubin’s pathology : clinicopathologic
foundations of medicine. David S. Strayer,
Emanuel Rubin, Jeffrey E. Saffitz, Alan L.
Schiller, Seventh edition. Philadelphia.
Wolters Kluwer Health. 2015
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