Bone pathology
Osteoblast: bone producing cell derived from marrow residing mesenchymal cells, they have a plump
appearance and often exhibit a perinuclear hallow due to a prominent Golgi zone that give resemblance of
plasma cells, they have high intercytoplasmic contents of alkaline phosphatase. When incorporated into the
bone matrix and housed in the lacunae they are refer to as osteocytes.
Osteoclast: multinucleated giant cells involved in bone resorption they are often found adjacent to dead or
viable bone trabeculae with ragged edges they seen to arise from monocytes macrophages precursors. It
contains abundant of acid phosphates.
Osteoid: is the unmineralized organic precursor matrix of bone .composed of mucopolysacharides and noncollagen protein. it is not a homogenous mass that shows a constant pattern sequence of maturation and
organization.
Bone: formed through mineralization of organic matrix.
Woven bone :fiber bone there is a haphazard arrangement of collagen fibers within matrix which is best
appreciated in polarized light ,seen in fibrous dysplasia ,healing of facture.
Lamellar bone: concentric parallel lamellae.
Acquired metabolic disorders:
Osteoporosis: very common disease affecting 15 million patients in the US with 13 billion $ cost of
treatment every year.
It is characterized by decreased of normal mineralized bone ,lead to increase fragility and susceptibility to
fractures. It develop when an individual is unable to repair and maintain the mass of bone tissues .The main
finding is an increase in amount of resorption but the bone formation level being generally normal.
Pathogenesis: it results when the balance between bone formation and resorption is tilted in the favor of bone
resorption by osteoclasts.
A recent advances in molecular structures revealed that:
A novel member of TNF receptor family are influencing osteoclast functions, this member is RANK
lignd(receptor activator for nuclear factor kB), which binds to a receptor molecule which expressed on
macrophages, this interaction causes differentiation of macrophages into osteoclast, which resorbe bone.
Major factors related to development of the disease are:
1-Genetic factors: men achieve higher bone density than women and white people are more vulnerable than
others.
2-Age :old age group suffer more
3-Hormonal factors: post menopausal women suffer more due to estrogen deficiency.
4-Mechanichal factors: increased weight and reduced physical activity is associated with accelerated bone
loss.
5-Diet: Ca and vitamin D in treatment and prevention.
Osteomalasia and Ricketts: accumulation of unmineralized bone matrix due to diminished rate of
mineralization, caused by wide spectrum of congenital, acquired and metabolic diseases that result in
sufficient decrease in serum calcium, phosphate or both to impair mineralization of the skeleton and epiphysis
growth .The bone matrix is formed but its calcification is incomplete this give rise to uncalcified matrix
around the bone trabeculae.
Osteomylitis: it is inflammation of bone and marrow cavity caused by pyogenic bacteria and
M.tuberculosis.
Pyogenic osteomylitis:
Routes of infection;hematogenus dissemination,direct extension from a focus of acute infection in the
nearest joint or soft tissues.Traumatic implantation after compound fracture or surgical operation.
Causative agents: Staphylococcus aureas.,pneumococci,E-coli,B streptococci especially in neonates and
salmonella in patients with sickle cell anemia.
It can be acute or chronic debilitating illness.
Acute osteomylitis: intense neutrophilic inflammatory infiltrate.
Site of infection: in children metaphysic of long bone due to sluggish blood flow that allow bacteria to settle
in adult vertebral bodies is the commonest site .
Involved bone become necrotic within few days owing to compression of vascular spaces by increased
pressure in the marrow cavity and high concentration of mediator released during inflammatory reaction.
The infection spread through the cortical bone and may reach periosteum sometimes lead to subperiosteal
abscess especially in children . infection may spread to nearby soft tissue and create draining sinuses.
Detachment of periostium in such areas may cut the blood supply to bon resulting in ischemic necrosis.
The residual necrotic bone called sequestrum may be absorbed by osteoclastic activity larger sequesrae are
surrounded by rim of reactive bone called involcrum
Complications of osteomyelitis:
1-draining sinuses opened in the skin.
2-pathological fractures .
3-squamous cell carcinoma
4- amyloidosis .
Tuberculous ostomyelitis: long bones and vertebrae are favored site for hematological spread patients
candidates are AIDS and immunocompramized patients
Congenital and hereditary disorders .
Achondroplasia :
An autosomal dominant disorder caused by mutation in the fibroblast growth factor FGF3 that located on
chromosome 4 lead to arrest of growth at epiphyseal end appears in child with normal parents lead to
dwarfism .affecting all bones that made of cartilage it is diagnosed at birth ,if compatible with life it will
show:
1-normaly developed trunk but the head may be enlarged with depressed bridge of the nose and prominent
forehead
2-disproportionate shortening of proximal extremities .
3-bowing legs .
4-lordotic posture .
mental and sexual development are normal ,in case of homozygusity lead to death soon after birth due to
abnormal development of chest cavity.
Bone tumors:
Bone forming tumors:
Osteoma: it is a benign tumor arise at any age ,presented as bosselated sessile tumor composed of densely
sclerotic well formed bone projecting out from the cortical surface ,most often of skull and facial
bones,oftenly protruded into one of the air sinuses.
Microscopically: mature woven lamellar bone which may be difficult to distinguish from normal bone
It is of little clinical importance not even need to be excised unless for pressure or cosmetic cause.
Osteiod osteoma: also is a benign lesion ,affecting male more than female with age incidence of 10-30 years
,less than 2cm in the greater diameter affecting any bone ,painful ,pain relieved by aspirin
X-ray finding as radiolucent nidus with thickened cortex.
Osteoblastoma: Giant osteoid osteoma
It tends to be larger than osteoid osteoma ,mostly arise in vertebral column, may also cause pain that not
responding to aspirin.Incomplete surgical resection may recur .Occasional conversion into osteosarcoma
Metastatic bone tumors: primary bone tumors are less common than metastatic lesion .The most common
originating site for bone metastasis in descending order of frequency :
Prostates
Breast.
Lung.
Kidney.
G.I.T.
Thyroid.
Metastasis may be destructive (osteolytic) or associated with reactive bone formation
(osteoblastic),appear as pathological fracture
Most metastases as osteolytic process although it is common
for both pattern to be seen in a given lesion.
alkaline phosphetase is elevated reflecting activity of osteoblasts .but in patients with ca
prostate acid phosphatase of prostatic origin also elevated.
Osteogenic sarcoma: (osteosarcoma)
is the most common primary bone tumor after multiple myloma
it is malignant tumor of mesenchymal cells characterized by direct formation of osteoid
or bone by tumor cells some are composed of fibroblast, bone or chondroid
differentiation .
It can be divided into :
Primary osteosarcoma: it occurs in absence of underlying cause affecting young age
group under 20 years.More common in the long bone
Secondary osteosarcoma: occurs in the background of preexisting bone pathology or
previous exposure to some potentially carcinogenic effect:
1-paget's disease of bone
2-multiple osteochondroma.
3-chroni osteomyelitis.
4-fibrous dysplasia.
5-foreign bodies :total hip replacement.
6-truma.
7-viral infection.
8-radiation.
Osteosarcoma is a malignant tumor of osteoblasts ,mostly arise around knee tumor
gradually increase in size causing pain, originate in the medulla close to the metaphyseal
plate and spread and erode through cortical plate and extending into soft tissues.
Usually well advanced at radiological diagnosis, the malignant cells producing amount of
osteoid collagen some of which become mineralized can be demonstrated radiologicaly
especially when the tumor involving the soft tissue .
Clinical course:
-rapidly growing tumor.
-early metastasis via blood stream to lung .
-poor prognosis has generally improved by early surgery with radiotherapy and
chemotherapy.
Microscopic picture : neoplastic osteoblasts secret pink stained osteoid. ranging from
well differentiated to anaplasic lesion with scattered osteoclasts giant cells.
Differential diagnosis
-Callus in pathological fracture due to fibrous dysplasia.
-metastatic carcinoma
Molecular pathology: although the cause of this disease is unknown yet mutations
appear to be important cause of TP53 tumor suppressor gene and over expression of
MDM2 oncogene and mutation in retinoblastoma gene.
Jexta cortical osteosarcoma
It is infrequent slowly growing malignancy affecting old age group, involving metaphysic
of long bones.
Microscopically:disordered pattern of well formed bone ,osteoid ,cartilage and highly
fibrotic stroma
Cartilage forming tumors:
Chondroma:
-Benign tumor.
-Affecting small bones of hands and feet.-may be solitary (solitary enchondroma) or multiple (enchondromatosis)
composed of cartilaginous matrix containing scattered benign chondrocyte
osteochondroma: (exostosis)
-composed of a nodule of protuberant bone covered by a cup of cartilage--mostly affect
humerous,femur and tibia
solitary as sporadic cases in children or multiple as autosomal dominant
condition(Hereditary multiple exostosis).
-X-ray finding as mushroom like shape lesion.
Chondrosarcoma:
-adults usually affected .
-pelvic bone is common site .
-it is slowly growing tumor reaching large size and destructing the surrounding tissues
,slowly metastasis.
macroscopically: glistening white mass that frequently erodes the cortex.
Microscopically: majority is well differentiated similar to benign cartilaginous tumor ,in
high grade pattern poorly differentiated with marked pleomorphism and high number of
mitosis.
Tumors of unknown origin
Ewing sarcoma:
Is a malignant disease of bone ,composed of primitive small round cells resembling those
of malignant lymphoma and other undifferentiated tumors so it is difficult for diagnosis
,it may be neuroectodermal origin with association of chromosomal abnormality in
chromosome 11,22.
-affecting young age group ,with male predominance .
-arises in medullary cavity of long and pelvic causing expantion of bone and elevation of
periosteum and subperiosteal new bone formation giving a characteristic radiological
picture of onion-skin layering
Clinical picture: pain and swelling ,fever ,elevated ESR and WBC count a picture
simulating osteomyelitis.
It is of poor prognosis with early metastasis to lung and other bones may be improved by
chemotherapy.
Giant cell tumor : (Osteoclastoma)
It is potentially malignant or benign but locally destructive tumor .
Affecting young age group(20-40)years old
Affecting epiphysis of long bone and extends to local metaphyseal end and cortex
In X-ray it present as lytic lesion without peripheral bone sclerosis
Microscopically: multinucleated giant cells closely resembling osteoclasts which are the
reactive component ,while the proliferating neoplastic component is a round to spindle
mononuclear cells .
Cysts of bone
Aneurismal bone cyst :
-affecting young adults and children.
-any bone may be affected .
-causing pain and swelling with lytic well defined lesion in the X-ray.
-benign lesion cured by surgery.
Microscopically: composed of anastomosing blood filled spaces ,fibrosis woven bone
and osteoclasts .
Tumor like condition
Fibrous dysplasia: it is a benign disorder of bone which characterized by slow
progressive replacement of a localized area of bone by an abnormal proliferation of
isomorphic fibrous tissue intermixed with poorly formed haphazardly arranged
trabeculae of woven bone .
It is a disordered maturation of bone with arrest at an immature stage of woven bone.
Fibrous cortical defect (Non ossifying fibroma):
They are common non-neoplastic developmental disorder seen chiefly in children almost
always in femur ,tibia and fibula.
Presented as irregular sharply demarcated lobular radiolucent defects in the metaphyseal
cortex leaving intact subperiosteal layer of cortical bone. it is very common lesion may
cause pain predispose to fracture.
It disappear spontaneously in few years.
ARTHRITIS
Osteoarthritis (Degenerative joint disease) is the most common joint disorder. It is a
frequent consequence of aging and is an important cause of physical disability in
individuals over the age of 65. The fundamental feature of osteoarthritis is degeneration
of the articular cartilage.
Pathological features
•• Early changes include proliferation with disorganization of the chondrocytes in the
superficial part of the articular cartilage; subsequent reduction of its elasticity).
•• As the superficial part of the cartilage are degraded vertical and horizontal fibrillation
and cracking of the matrix occur.
•• Small fractures displace pieces of cartilage and subchondral bone into the joint,
forming loose bodies (joint mice).
•• Pathogenesis
•• Regardless of the inciting stimulus (wear & tear of aging, estrogens in females, and
genetic susceptibility), early osteoarthritis is marked by degenerating cartilage
containing more water and less proteoglycan
• Overall, cartilage tensile strength and resilience are reduced. In response to these
degenerative changes, chondrocytes in the deeper layers proliferate and attempt to
compensate.
Gout
This is a disorder caused by the tissue accumulation of excessive amounts of uric acid, an
end product of purine metabolism. It is marked by recurrent episodes of acute arthritis,
sometimes accompanied by the formation of large crystalline aggregates called tophi &
chronic joint deformity.
Not all individuals with hyperuricemia develop gout; this indicates that influences
besides hyperuricemia contribute to the pathogenesis.
.
Pathologic features
The major morphologic manifestations of gout are
1. Acute arthritis
2. Chronic tophaceous arthritis
3. Tophi in various sites, and
4. Gouty nephropathy
Tophi
These are the pathognomonic hallmarks of gout.
• Tophi can appear in the articular cartilage, periarticular ligaments, tendons, and soft
tissues, including the ear lobes. Superficial tophi can lead to large ulcerations of the
overlying skin.
• Microscopically, they are formed by large aggregations of urate crystals surrounded by
an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body
giant cells, attempting to engulf the masses of crystals.
Pathogenesis
• increased levels of uric acid in the blood and other body fluids (e.g., synovium) lead to
the precipitation of monosodium urate crystals. The precipitated crystals are
chemotactic to neutrophils & macrophages through activation of complement
components C3a and C5a fragments. This leads to a local accumulation of neutrophils
and macrophages in the joints and synovial membranes to phagocytize the crystals.
The activated neutrophils liberate destructive lysosomal enzymes. Macrophages
participate in joint injury by secreting a variety of proinflammatory mediators such as
IL-1, IL-6, and TNF. While intensifying the inflammatory response, these cytokines
can also directly activate synovial cells and cartilage cells to release proteases (e.g.,
collagenases) that cause tissue injury.
SKELETAL MUSCLES
Skeletal Muscle Tumors
Rhabdomyosarcoma
Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and
adolescence, usually appearing before age 20. They occur most commonly in the head
and neck or genitourinary tract.
Gross features
• Tumors arising near the mucosal surfaces of the bladder or vagina, can present as soft,
gelatinous, grapelike masses, designated sarcoma botryoides.
•• In other cases they are deceptively demarcated or infiltrative grayish-white to
brownish masses.
Microscopical features
The diagnosis of rhabdomyosarcoma is based on the demonstration of skeletal muscle
differentiation,
SOFT TISSUE TUMORS
Fatty Tumors
. Lipomas are benign tumors of fat, and are the most common soft tissue tumors of
adulthood. Most lipomas are solitary lesions
. Most lipomas are mobile, slowly enlarging, painless masses. Microscopically, they
consist of mature fat cells with no pleomorphism.
Liposarcoma is a malignant neoplasm of adipocytes. These tumors occur most
commonly in the 40 to 60 years of age & mostly in the deep soft tissues (cf. lipoma) or in
visceral sites.
Pathological features (Fig. 12-36)
• Usually they are relatively well-circumscribed large masses.
• Several different histologic subtypes are recognized, including two low-grade variants,
the well-differentiated liposarcoma and the myxoid liposarcoma, the latter
characterized by abundant, mucoid extracellular matrix.
Smooth Muscle Tumors
1. Leiomyomas are common, well-circumscribed neoplasms that can arise from smooth
muscle cells anywhere in the body, but are encountered most commonly in the uterus.
2. Leiomyosarcomas (15% of soft tissue sarcomas). They occur in adults, more
commonly females. Deep soft tissues of the extremities and retroperitoneum are common
sites.
Microscopically, they show spindle cells with cigar-shaped nuclei arranged in
interweaving fascicles.