Bones, Joints, and Soft Tissues

Bones, Joints, and Soft Tissues

The skeletal system provides structural support and protection to the human body and its internal organs, serves as primary home for blood-forming tissues, and stores several vital minerals, above all, calcium. This chapter focuses on alterations of the bony (structural support) part of the skeletal system. Calcium metabolism is also discussed with the endocrine system (chapter 12), and blood-forming tissues are treated separately in the chapter about hematopoietic and lymphatic tissues (chapter 10).

Metabolic Bone Diseases

Metabolic bone diseases include diseases of increased bone resorption, such as osteoporosis, and of calcium metabolism, such as rickets, osteomalacia, hyperparathyroidism, and renal osteodystrophy. Primary osteoporosis is an age-related disorder preferentially affecting women that ultimately may cause a loss of 35% to 50% of cortical or trabecular bone mass. It is related to hormonal influences (e.g., estrogen deficiency), reduced physical activity, and nutritional and genetic factors. Secondary osteoporosis follows a large variety of diseases, including malabsorption or malnutrition, endocrine disorders (e.g., hyperparathyroidism or hypoparathyroidism, hypogonadism, and type 1 diabetes) and neoplastic diseases, such as multiple myeloma and bony metastases. Disorders in calcium homeostasis cause reduced matrix mineralization with osteopenia. Primary and secondary hyperparathyroidism (with the latter related to renal insufficiency) are characterized by increased osteoclastic bone resorption with features of dissecting osteitis and osteitis fibrosa cystica (von Recklinghausen disease of the bone).

Infectious Diseases

Osteomyelitis (OM), an acute or chronic inflammation of the bone marrow cavity and bone, usually has an infectious cause. OM may originate from hematogenous spread of infectious organisms (i.e., secondary to pyemia or septicemia) or from their direct invasion through penetrating wounds (including from orthopaedic procedures) or open fractures. Despite readily available antibiotic drugs, infectious OM still constitutes a serious clinical problem for several reasons: First, OM is rarely a primary disease but more often a complication of an undiagnosed or inadequately treated infection. Second, OM responds poorly to antibiotic treatment (causative organisms may be drug resistant) and may run a chronic course with complications such as amyloidosis. Third, OM may be the source of additional hematogenous spread causing septic shock, hemorrhage, or abscesses in vital organs (brain, myocardium). Therefore, treatment must be radical, combining antibiotic and surgical intervention.

Noninfectious Arthritic Diseases

Osteoarthritis (OA) is an extremely common cause of disability, especially in people aged older than 75 years, 85% of whom show clinical evidence of the disorder. Despite its ubiquity, primary OA is of unknown etiology, although it is thought to result from intrinsic defects of cartilage. Abnormal mechanical forces on the cartilage, decreased water bonding of cartilage, increased stiffness of subcartilaginous bone, and biochemical abnormalities such as decrease in proteoglycans and shortening of glucosaminoglycans have been implicated. The latter decreases cartilaginous water binding in favor of its binding by collagen fibers. Mutations of the collagen type II gene may be involved. Secondary OA occurs in patients with such underlying causes as malformations, trauma, and metabolic diseases with or without crystalline deposits.

Tumors of the Skeletal System

Tumors of the skeletal system comprise a large variety of benign and malignant lesions, including bone cysts. They are classified according to their tissue of origin and are further identified by the age of the patient and the site. Primary tumors of bone are less common than metastatic lesions to the skeletal system, which always should be considered in differential diagnosis (usually, radiographic findings of primary and metastatic lesions are quite characteristic). The extraskeletal malignant neoplasms most likely to metastasize to the skeleton are carcinomas of the prostate, the breast, the lungs, the gastrointestinal tract, the kidneys, and the thyroid. Such metastases may be osteoblastic (e.g., prostate) or osteolytic. Other primary tumors with secondary involvement of the bony skeleton are those of the hematopoietic bone marrow or lymphatic tissues (e.g., plasmacytoma, Hodgkin disease). They are discussed in chapter 10.

Soft Tissue Disorders

Soft tissue refers to the widely distributed interstitial tissue of mesodermal origin filling spaces between ectodermal, endodermal, and skeletal structures. It includes differentiated tissues such as fibrous tissue, fat, and skeletal muscle. Although all pathologic reaction patterns are represented in diseases of soft tissue, including necrosis and degeneration, infection and inflammation, and hyperplasia and neoplasia, only a few examples can be discussed here. We focus on such important disorders as compartment syndrome, collagen-vascular diseases (CVDs), and benign and malignant tumors.

TABLE 11-2


Category Mechanism Causes
Vitamin D deficiencies Decreased synthesis in skin Insufficient sun exposure from 7-dehydrocholesterol
Decreased intestinal absorption Dietary lack, malabsorption syndromes (intestines, pancreas, bile)
Decreased synthesis of 25(OH)-D Liver diseases
Enhanced degradation of 25(OH)-D Various drugs inducing cytochrome and P450 enzymes
Decreased synthesis of 1,25(OH)2-D Advanced renal disease
Phosphate deficiency Increased excretion Renal tubular disorders (e.g., Fanconi syndromes)
Decreased absorption Phosphate-binding drugs (e.g., antacids)
Disturbed reabsorption Tumor associated (e.g., prostate cancer, neurofibromatosis)
Mineralization defects Target organ resistance Congenital lack of receptors (type II rickets)


*1,25(OH)-D indicates 1,25-dihydroxyvitamin-D, active form after second hydroxylation in renal tubule; 25(OH)-D, 25-hydroxyvitamin-D, major circulating metabolite hydroxylated in the liver.

TABLE 11-3


Type of Lesion Ages Usual Location Gross Features
Nonossifying fibroma (fibrous cortical defect) Children Metaphysis, long bones (tibia, fibula) Eccentric cortical lesion with well-demarcated sclerotic margins
Solitary bone cyst Children, adolescents Humerus, femur (adjacent to growth plate) Well-demarcated epidiaphyseal lesion
Aneurysmal bone cyst Children, young adults Long bones, vertebra (essentially everywhere) Rapidly expanding cyst (previous trauma?)
Fibrous dysplasia (monostotic or polyostotic) Adolescents, young adults Long bones Diaphyseal “soap bubble” translucencies
Osteoma (eburneum) (probably not a real neoplasm) Adults Skull, tibia Exophytic solid mass
Osteoid osteoma Children, young adults Tubular bones, lower extremity Diaphyseal cortex “nidus”
Osteoblastoma Children, young adults Vertebra, spinal, transverse process Similar to osteoid osteoma (“nidus”)
Osteochondroma (exostosis) Young adults Long bones Bony exostoses with cartilaginous cap
Chondroma (enchondroma) Adults Tubular bones metacarpi, phalanges Intraosseous, solitary well-circumscribed lesion
Chondroblastoma Children, young adults Long bones femur, tibia, humerus Epiphysis, paraarticular well-circumscribed lesion
Chondromyxoid fibroma Children, young adults Femur, tibia Excentric lucent defect, delicate sclerotic border
Synovial chondromatosis (self-limited) Young adults (men) Large joints Hyaline cartilage nodules and floating free bodies
Villonodular synovitis Pigmented Young adults Knee, hip, ankles, feet, fingers Synovial lining cell proliferation with hemosiderin deposits


TABLE 11-5


Syndrome Autoimmunity* Features
Systemic lupus erythematosus Autoantibodies against native ds-DNA, denatured ss-DNA, histones, and histone complexes T-, NK-cell, and cytokine abnormalities, circulating immune complexes Rashes, arthritis/arthralgia, glomerulonephritis, proteinuria, thrombocytopenia, hemolytic anemia, pleural effusions, pulmonary fibrosis, pericarditis, endocarditis, psychosis, seizures
Vasculitis and thrombosis
Primary systemic sclerosis Autoantibodies against small RNA protein (SS-A/Ro), topoisomerase I (Scl-70), 45K RNA protein (SS-B/La) Hallmark: scleroderma, Raynaud syndrome, proliferative arteritis and fibrosis, capillary malformations such as telangiectasia and bleeding; esophagus and lower GI tract: fibrosis and muscular atrophy with motility problems and dysphagia, interstitial pneumonitis, “shrinking lung disease,” pulmonary hemorrhage; heart: conductive and ventricular dysfunction, renal vasculitis and hypertension
Polymyositis, dermatomyositis tRNA synthetases: Jo-1, PL-7; protein complex (PM-Scl) Muscle weakness: segmental myofiber necrosis with inflammatory infiltrate, fever, myoglobinuria, skin rash, erythema of hands (knuckles), interstitial pneumonitis, approximately 25% associated with malignancies
Rheumatoid arthritis Denatured ss-DNA
Rheumatoid factor, CIC, antikeratin, collagen antibody, T-cell “activation”
Chronic relapsing synovitis, arthritis, small joints of hands, symmetrical, tenosynovitis, soft tissue rheumatic nodules, pleuritis, pericarditis, vasculitis, interstitial pneumonitis, bronchiolitis obliterans, polyneuritis, mononeuritis, Felty syndrome

CIC indicates circulating immune complexes; ds, double-stranded; GI, gastrointestinal; ss, single-stranded.

*Selective antibodies only.

See text for additional microscopy.

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Jun 28, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Bones, Joints, and Soft Tissues

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