Section 2 -

Non-Neoplastic Orthopaedic Pathology Andrew E. Rosenberg, M.D. Alan L. Schiller, M.D.

Preliminary Terms for Structure, Development, and Maturation of Bone Skeletal System Function Bone as an Organ Topographic terms Cortex-zona compacta Medulla-coarse cancellous bone Epiphysis Metaphysis Diaphysis Epiphyseal plate Marrow-red-hematopoietic yellow-fatty gray-white-fibrous, tumor, infection, etc. Fine cancellous bone Bone as a Tissue Woven bone Lamellar bone Circumferential -> Cortical Interstitial -> Cortical Concentric -> Cortical Trabecular Matrix components Collagen Hydroxyapatite Proteoglycans Cellular components Pleuropotential stem cell Osteoblasts Osteocytes Osteoclasts Embryologic Terms Enchondral ossification Intramembranous ossification Osteoid Growth capacity of bone tissue Interstitial growth Appositional growth Vascular supply of bone Cartilage Types Hyaline Fibrocartilage Elastic Matrix Collagen Proteoglycan Characteristics - growth pattern Development of Bone (as an organ) Primary center of ossification Secondary center of ossification Ring of Ranvier Cylinderization Funnelization Hemispherization Primary spongiosum Cortical development Synovial Chondromatosis 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 loose bodies. 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 neoplasms. 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. Pathology: 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 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 periarticular osteoporosis. 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. Gout Acute Gouty Arthritis Release or urate crystals into joint uptake by PMNs and A cells activation of Hageman factor release of proteases (lysosomal) chemotaxis Associated Factors obesity males diabetes mellitus hyperlipidemia hypertension renal disease (interstitial & collecting system) Chronic Tophaceous Gout = inability to dispose of urate deposits in juxta-articular bone deposits in avascular tissues tendons ear kidney Hyperuracemia Primary (innate) 96% underexcretion 90% overproduction 10% Secondary (due to other disease or drugs) purine synthesis glycogen storage disease (Von Gierke) enzyme deficiency x-linked (Lesch-Nyhan) increased nucleic acid turnover (hematologic neoplasms) decreased renal excretion (diuretics) Treatment colchicine indomethacin phenylbutazone other NbSAIDs Prophylaxis colchicine antihyperuricemic Rx probenecid sulfinpyrazone allopurinol Secondary Hyperuricemia Can be caused by: Myeloproliferative disorders Lymphoproliferative disorders Disseminated carcinoma and sarcoma Sickle cell anemia and other chronic hemolytic diseases Psoriasis ?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 ?Hyperparathyroidism? 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: Pseudogout Pseudorheumatoid arthritis Pseudo osteoarthritis Asymptomatic 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 "pseudogout" acute inflammatory arthritis uptake of crystals by PMNs and A cells Chondrocalcinosis radiographic diagnosis Crystals in articular hyalin and fibrocartilage knee (AC & menisci) wrist (AC & triangular ligament) symphysis pubis hip associated conditions diabetes gout hyperparathyroidism hemochromatosis ochronosis OA Treatment acute attacks joint lavage NSAIDs Steroids chronic NSAIDs 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, weakly positive. General Reference WHO Classification of Tumors Pathology & Genetics Tumours of Soft Tissie and Bone IARC Press, Lyon 2002