Preliminary Terms for Structure, Development, and Maturation of Bone
Bone as an Organ
- Topographic terms
- Cortex-zona compacta
- Medulla-coarse cancellous bone
- Epiphyseal plate
- gray-white-fibrous, tumor, infection, etc.
- Fine cancellous bone
Bone as a Tissue
- Woven bone
- Lamellar bone
- Circumferential -> Cortical
- Interstitial -> Cortical
- Concentric -> Cortical
- Matrix components
- Cellular components
- Pleuropotential stem cell
- Embryologic Terms
- Enchondral ossification
- Intramembranous ossification
- Growth capacity of bone tissue
- Interstitial growth
- Appositional growth
- Vascular supply of bone
- Characteristics - growth pattern
Development of Bone (as an organ)
- Primary center of ossification
- Secondary center of ossification
- Ring of Ranvier
- Primary spongiosum
- Cortical development
An uncommon benign synovial lesion of unknown etiology characterized by synthesis of hyaline cartilage
nodules within the synovial lining. If enchondralossification occurs, the
entity is termed synovial osteochondromatosis. These nodules often break loose and float in the joint
cavity simulating joint mice and must be distinguished from them pathologically. Treatment consists of
removal of the free-floating nodules and in scone cases, synovectomy.
Age and Sex: Twice as common in young males than females. The temporal mandibular joint is
more common involved in women. Hand and feet, equal involvement of sexes, usually elderly.
Location: Large, diarthrodial joints, especially knee (50% of cases). Next most common sites
are hip, elbow, shoulder and ankle. In 10% of cases bilateral involvement.
Diagnosis : Pain, joint swelling, stiffness and locking of joint; related to the numerous
X-ray : Many nodules may be calcified and seen as loose bodies. Bone erosion may occur by
direct pressure of the nodules. If a tendon sheath of a digit is involved, a linear arrangement of
calcified nodules may be seen.
Pathology: A thickened synovium studded with numerous cartilage/bone nodules (0.1-0.5cm). In
addition, numerous cartilage free-floating nodules, often larger (1-2cm) than the tissue embedded arms.
Microscopic findings of a gradual transition or blending between synovium and cartilage foci are
characteristic. The cartilage nodules lack a tidemark distinguishing them from joint mice. Often,
enchondral ossification is present within the synovium. Usually the adjacent synovium is normal.
There are clonal chromosomal abnormalities reported in 6 cases from the knee. They were near-diploid
or pseudodiploid karyotypes and three had structural chromosomal rearrangements.
Pigmented Villonodular Synovitis (Diffuse-Type Giant Cell Tumor)
Pigmented villonodular synovitis (Diffuse-type giant cell tumor) and pigmented villonodular
tenosynovitis (giant cell tumor of tendon sheath) are believed to be closely related, if not identical,
lesions. Type A (histiocytic) and Type B (fibrocytic) synovial cells, according to many authors
contribute to the development of the lesion- Jaffe suggested that the basic, proliferating, polyhedral or
roundish cell arose "through hyperplasia of undifferentiated (especially perivascular) connective tissue
cells." Soule considered the lesion a benign fibrous xanthoma (fibrous histiocytoma) and Enzinger
preferred the designation of giant cell tumor of tendon sheath and of synovium. Today the WHO
classification considers diffuse and nodular forms and we believe these lesions to be true benign
Tenosynovial tumors are mostly in peripheral joints or tendon sheaths whereas synovial lesions are
mostly encountered in the knee joint- synovial lesions are more difficult to treat and recurrence is much
more common than the tenosynovial lesions. Diffuse tumors, may destroy adjacent bone. In such advanced
cases, the histopathological changes are usually characteristic and the diagnosis is easily made. Early
diffuse lesions, particularly in the knee joint, may be difficult to differentiate from the synovial
reaction to repeated hemorrhage as seen in the hemophiliac patient or in the patient subject to repeated
trauma. A few instances of malignant degeneration have been reported, but they are rare, and have the
pattern of giant cell sarcoma.
Grossly PVNS is soft friable villonodular red-brown to yellow masses of tissue diffusely covering the
articular cartilage. These masses may be small or large and extend into the soft tissue or bone marrow.
Giant cell tumor of tendon sheath is often a lobulated rubbery tan yellow mass, which easily separates
from the adjacent tissue. Microscopically, the neoplastic synovial living cell invades into the synovial
tissue as mononuclear oval or polygonal cells. Multinucleate osteoclast-type giant cells, foam cells,
and hemosiderin-laden macrophages are admixed or focally nested amongst the mononuclear cells. Often,
particularly in giant cell tumor of tendon sheath, prominent collagenous septae traverse the tumor and
may be mistaken for bone formation. Mitotic activity may be present in the mononuclear cells but
atypical forms are usually not seen.
The immunopathology of PVNS has macrophage markers from the mononuclear cells as well as CD68. The
osteoclast-type giant cells are also positive for CD68 and CD45. Some cells are also desmin positive.
Chromosome abnormalities include pseudodiploid karyotypes and gene rearrangements and only in PVNS,
trisomies of 5 and 7 are found, whereas in giant cell tumor of tendon sheath such variances are not seen.
Gout may be divided into three clinical stages: acute gouty arthritis, intercritical
or intermediate, and the chronic stage in which tophaceous deposits may be seen.
Acute gout is usually monoarticular and predilects the lower extremities.
On the X-ray, the characteristic appearance is sharp, punched-out juxta-articular lesions, with
little reactive sclerosis, and no regional osteoporosis, in contrast to rheumatoid arthritis, which has
Synovial fluid in gout has an inflammatory exudate, which may resemble and be confused with
infection. Examination of the fluid under polarized light, using a first order red filter has crystals
that are strongly negatively birefringent and needle shaped. The urate crystals are found
intra-cellular. Processing of the crystals for study requires the use of alcohol fixation, as routine
formalin processing is water based and the crystals dissolve.
The microscopic appearance of gouty tissues is unusual; superimposed upon ordinary chronic
inflammation are large fields of amorphous pink-staining areas representing the urate deposits with the
crystals dissolved. Sometimes, granuloma formation is seen.
- Acute Gouty Arthritis
- Release or urate crystals into joint
- uptake by PMNs and A cells
- activation of Hageman factor
- release of proteases (lysosomal)
- Associated Factors
- diabetes mellitus
- renal disease (interstitial & collecting system)
- Chronic Tophaceous Gout = inability to dispose of urate
- deposits in juxta-articular bone
- deposits in avascular tissues
- Primary (innate) 96%
- underexcretion 90%
- overproduction 10%
- Secondary (due to other disease or drugs)
- purine synthesis
- glycogen storage disease (Von
- enzyme deficiency x-linked
- increased nucleic acid turnover (hematologic neoplasms)
- decreased renal excretion (diuretics)
- other NbSAIDs
- antihyperuricemic Rx
Can be caused by:
- Myeloproliferative disorders
- Lymphoproliferative disorders
- Disseminated carcinoma and sarcoma
- Sickle cell anemia and other chronic hemolytic diseases
- ?Paget's disease?
- Administration of cytotoxic drugs
- Competition of diuretics in kidney with uric acid
- Decreased Renal Clearance of Uric Acid
- Intrinsic disease of the kidneys
- Chronic renal insufficiency
- Sickle cell disease
Saturnine gout: the interesting Hogarthian epidemic in 18th century England where gout was prevalent
amongst the upper classes that had homes with lead plumbing. The lead ingested (or imbibed) caused a
tubular nephropathy leading to a hyperuricemia. The Romans had a similar problem including (but lead
encephalopathy. Both drank fruits lead vessels as well. Pewter formerly contained lead- (Saturn is the
alchemist's symbol for lead.)
Calcium Pyrophosphate Crystal Deposition Disease (CPPD)
According to McCarthy, CPPD may be classified clinically as:
- Pseudorheumatoid arthritis
- Pseudo osteoarthritis
- Pseudoneurotrophic joints
- Pseudo ankylosing spondylitis
Formerly called "chondrocalcinosis," calcium pyrophosphate dehydrate deposition disease has only
recently been recognized. Since the first recognized manifestation, pseudogout, several other syndromes
have been described, listed below. The disease is sometimes associated with sane other metabolic
condition such as hyperparathyroidism, hemochromatosis, Wilson's disease, ochronosis, or hypothyroidism.
About 50% of patients present with progressive degeneration of several joints, in order of
involvement; knees, ankles, wrists, elbows, hips, and shoulders. Appearance is usually in the third or
fourth decade. Another 15% have an acute gout-like picture with an acute onset with marked inflammation
and swelling. Frequently, however, its severity is less than gout, and there are cluster attacks with
first a single joint affected, then satellite joints.
On X-ray there are punctate or linear calcifications in fibrocartilage or hyaline cartilage.
Grossly, there are chalky white deposits. Microscopically the deposits are crystalline or amorphous,
surrounded by a chronic inflammation and giant cell reaction but without classic granuloma formation.
Usually there is no reaction to the crystals when embedded in cartilage.
- Intrasynovial release of calcium pyrophosphate dehydrate
- acute inflammatory arthritis
- uptake of crystals by PMNs and A cells
- radiographic diagnosis
- Crystals in articular hyalin and fibrocartilage
- knee (AC & menisci)
- wrist (AC & triangular
- symphysis pubis
- associated conditions
- acute attacks
- joint lavage
Polarized Light Crystal Examination
This is performed using two polarizing lenses placed as shown. Either of the polarizing discs is
rotated until the field is nearly dark-just light enough to identify the leukocytes- Crystals will show
up as brightly birefringent needles (gout) or more pleomorphic rectangular crystals (pseudogout).
More positive identification is rarely necessary and requires a first-order red filter. When the red
plate is rotated so that the crystal is parallel to the axis line of the filter, sodium urate crystals
are bright yellow. Rotating the filter 90 degrees (perpendicular to the axis of the crystal) changes the
color of the crystal to bright blue; this is negative birefringence.
When the axis of the red plate is aligned with the long axis of the calcium pyrophosphate crystal,
the crystal is a weak blue color, when perpendicular, pale yellow. This is positive birefringence.
Intensity is implied by the terms "strong" and "weak". Urate crystals are strongly negative, CPPD,
WHO Classification of Tumors
Pathology & Genetics
Tumours of Soft Tissie and Bone
IARC Press, Lyon 2002