Non neoplastic disorders of bone and joints and Neoplastic disorders of Soft tissue, joint and bone tumors 11/10/2021Osteomyelitis Osteomyelitis is a serious infection of the bone that can be either acute or chronic. All types of organisms, including viruses, parasites, fungi, and bacteria, can produce osteomyelitis, but infections caused by certain pyogenic bacteria and mycobacteria are the most common. Pyogenic osteomyelitis is an inflammatory process involving the bone and its structures caused by pyogenic organisms* Organisms reach bone by “* Hematogenous spread “* Spread from surrounding tissues e.g. from bed sores “+ Direct implantation after compound fractures or orthopedic procedures * In otherwise healthy children, most osteomyelitis is hematogenous in origin and develops in the long bones. * In adults, however, osteomyelitis more often occurs as a complication of open fractures, surgical procedures, and infections of the feet in diabeticsStaphylococcus aureus causes 80-90% of the culture positive cases. S. aureus expresses a collagen-binding adhesin, which permits its attachment to bone cartilage Escherichia coli, Pseudomonas, and Klebsiella are more frequently isolated from individuals with genitourinary tract infections or who are intravenous drug abusers. In the neonatal period, Haemophilus influenzae and group B streptococci are frequent pathogens. In sickle cell disease —salmonella In 50% of the cases no organism can be isolatedPathogenesis Entry of the organisms into bone Slowing of blood flow in vascular loops at the metaphysis in long bones encourages the deposition of microbes and the establishment of infection. The organisms colonize and proliferate in the bone. To contain the disease, phagocytes release enzymes that lyse bone, creating an inflammatory response The bacteria induce a neutrophilic inflammatory reactionThis inflammatory response forms pus (a protein- rich exudate containing dead phagocytes, tissue debris, and microorganisms) and causes increased intramedullary pressure. The inflammatory exudate can rupture through the cortex to the periosteum if left unchecked. Disruption of the periosteum impairs the periosteal blood supply leading to bone ischemia then necrosisThe dead bone is known as a sequestrum. Rupture of the periosteum leads to a soft tissue abscess, which can channel to the skin, creating a draining sinus. Sometimes the sequestrum crumbles, releasing fragments that pass through the sinus tract. Infection may spread to joints causing septic or suppurative arthritis particularly in infants¢ After the first week, chronic inflammatory cells release cytokines that stimulate osteoclastic bone resorption, ingrowth of fibrous tissue, and the deposition of reactive bone at the periphery. * The newly deposited bone can form a shell of living tissue, known as an involucrum, around the segment of devitalized infected bone* The main histopathological finding in acute osteomyelitis are microorganisms, congested or thrombosed blood vessels, and infiltrates of neutrophils. * The hallmark histopathological finding in chronic osteomyelitis is necrotic bone. Also seenis a predominance of mononuclear cells (lymphocytes and plasma cells), replacement of osteoclast resorbed bone by granulation, and fibrous tissue leading to bone loss and the formation of sinus tractsClinical features ¢ Fever, chills, malaise, leukocytosis, pain over the affected region-mainly in cases of Hematogenous spread ¢ In infants- unexplained fever diagnosis * Xray- shows a lytic focus of bone destruction surrounded by a zone of sclerosis * Biopsy and bone cultures Treatment * Combination of antibiotics and surgical drainageClinical course * 5-25% of acute osteomyelitis persist as chronic infections. * This may be due to “Delay in diagnosis “Extensive bone necrosis “Inadequate antibiotic therapy +*Inadequent surgical debridement “Weakened host defensesComplications of acute osteomyelitis include “+ Bacteremia “ Septicemia “ Chronic osteomyelitis Complications of chronic osteomyelitis > Pathologic fractures Secondary amyloidosis Endocarditis Sepsis SCC in the draining sinus tracts Sarcoma in the infected bone Vv VVVVMycobacterial Osteomyelitis * Source of organisms- blood borne or extension from visceral disease *, Bone infections persist for years * Infection is usually solitary except in immunocompromised individuals. ¢ Mycobacterial osteomyelitis tends to be more destructive and resistant to control than pyogenic osteomyelitis Clinical presentation > Low grade fevers, chills » Localized pain >» weight lossHistology “*Caseous necrosis “*Granulomas — epitheliod cells, lymphocytes, multinucleated giant cellsPott disease(Tuberculous spondylitis) * Mycobacterial vertebrae disease * The infection breaks through intervertebral discs to affect multiple vertebrae and extends into the soft tissues. * Destruction of discs and vertebrae frequently results in permanent compression fractures that produce scoliosis or kyphosis and neurologic deficits secondary to spinal cord and nerve compression.Osteoarthritis It is a degenerative joint disease characterized by degeneration of cartilage that result in structural and functional failure of synovial joints. It can be . Primary/idiopathic- appears insidiously without an initiating cause. Age . Secondary- occurs in younger patients and may be due to joint deformity, previous joint injury, underlying systemic disease, infectious arthritis, avascular necrosised Pathogenesis Normally articular cartilage transmits loads to the underlying bone. Cartilage resists compression through the viscoelastic properties of the extracellular matrix (principally type II collagen, proteoglycans, and water) secreted by chondrocytes. Repeated biomechanical stress contributes to development of OA. Genetic factors including genes encoding components of the matrix and signaling molecules, also play a role. This factors predispose to chondrocyte injury and alteration of extracellular matrix. They also lead to inflammation that exacerbates joint destruction* Outgrowths (osteophytes) develop at the margins of the articular surface and are capped by fibrocartilage and hyaline cartilage that gradually ossify * joints commonly involved ; hips, knees, lower lumbar, cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints and first tarsometatarsal jointsClinical presentation >50s or younger with predisposing conditions Joint pains that worsen with use Morning stiffness Crepitus Limitation of range of motion Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression and radicular pain, muscle spasms, muscle atrophy, and neurologic deficits. Heberden nodes, prominent osteophytes at the distal interphalangeal joints. Bouchard’s nodes (posterolateral swellings of PIP joints)Management Pain management NSAIDs to reduce inflammation Intra-articular corticosteroids Activity modification ArthroplastyInfectious arthritis * Joints can become infected from **Hematogenous dissemination **Direct inoculation through the skin, or “*Contiguous spread from a soft tissue abscess “*Osteomyelitis .Suppurative arthritis Usually caused by bacterial infections. H. influenza arthritis predominates in children younger than 2 years of age. S. aureus is the main agent in older children and adults, and gonococcus is prevalent during late adolescence and young adulthood. Individuals with sickle cell disease are prone to infection with Salmonella. Individuals with deficiencies of complement components (C5, C6, C7, or C9) are susceptible to disseminated gonococcal infections and hence arthritisClinical presentation Painful, warm and swollen joint Restricted joint movement Systemic s/s fever, leucocytosis and elevated ESR Common joints involved knee> hip> shoulder>elbow>wrist> sternoclavicular joint Axial joints involved in drug users»~NEOPLASTIC DISORDERSIntroduction Soft tissue neoplasm can arise from any location throughout the human body, and they can affect individuals at the extremes of age. These includes skeletal muscle, adipose tissue, blood, and lymphatics to connective tissue and peripheral nerves. These neoplasms can span a range of clinical presentations from benign lipomas to aggressive metastatic angiosarcomas. Majority of soft tissue sarcomas arise spontaneously. However, germline mutations, radiation and environmental exposure(s) e.g. polyvinyl chloride, arsenic have been causative.Germline mutations Neurofibromatosis Type 1 (NF1) Von Recklinghausen Disease Autosomal dominant (AD) condition caused by mutations in the NF1 gene which codes for a protein called neurofibromin A tumor suppressor of the ras oncogene signaling pathway Mutations in NF1 gene result in multiple cutaneous neurofibromasshutterstock, com + 728968474Li-Fraumeni Syndrome Rare AD disorder caused by mutations in the TP53 gene (17p13.1) which codes for p53 (tumor suppres$or gene) p53 functions to clear damaged cellular DNA This manifests in a wide array of phenotypes and clinical presentations; some patients will develop rhabdomyosarcoma by the age of 4Familial Adenomatous Polyposis (FAP) AD disorder with a mutation in the APC gene (5q21-q22) Tumor suppressor gene, inhibiting localization of B-catenin to the nucleus Mutant protein fails to inhibit this localization which results in unchecked cell cycling and cellular proliferation Clinically this manifests in innumerable colonic polyps with extracolonic manifestations such as epidermoid cysts, osteomas and desmoid tumors Desmoid tumors typically arise approximately 5 years post- prophylactic colectomy and represent a major source of morbidity and mortality; often arising in previous surgical sitesSoft tissue tumors are thought to arise from pluripotent mesenchymal stem cells that then differentiate along various cell lines. Tumor grading is usually based on tumor differentiation, mitotic count and tumor necrosis. Recommended to diagnose with FNA, core biopsy or incisional biopsy so appropriate treatment can be determined in advance Poor prognostic factors Large size Deep seated vs superficial Retroperitoneum vs extremities High grade High stage Positive margins- ass with local recurrenceSMOOTH MUSCLE TUMORSSkeletal muscle tumors * Skeletal muscle neoplasms, in contrast to tumors of other lineages, are almost all malignant. Rhabdomyosarcoma * Primitive malignant soft tissue sarcoma with skeletal muscle phenotype. Subtypes Y Alveolar ¥ Embryonal ¥ Pleomorphic nN° Most common soft tissue sarcoma of childhood/adolescence before age of 20. Alveolar/embryonal Sarcoma botryoides is a variant of embryonal rhabdomyosarcoma that develops in the walls of hollow viscera such as the urinary bladder and vagina. Has the best prognosis Rare in adults who often will have the pleomorphic subtype. The pediatric forms often arise in the sinuses, head and neck, and genitourinary tract.Rhabdomyosarcomas are aggressive neoplasms that are usually treated with surgery and chemotherapy, with or without radiation therapy. The botryoid variant of embryonal rhabdomyosarcoma has the best prognosis, whereas the pleomorphic subtype is often fatal.Smooth muscle tumors Leiomyoma Benign tumor of smooth muscle. Commonly found in the uterus (fibroids) but can arise in any soft tissue site. Soft tissue leiomyomas are usually 1 to 2 cm in size and are composed of fascicles of densely eosinophilic spindle cells that tend to intersect each other at right angles. Tumor cells have blunt-ended, elongated nuclei and show minimal atypia and few mitotic figures. Solitary lesions are cured with surgeryLeiomyosarcoma These are malignant smooth muscle tumors Usually involve the extremities but may arise in the retroperitoneum, mediastinum, breast, large vessels (inferior venacava> saphenous vein. Leiomyosarcomas have complex genotypes that stem from acquired defects that lead to profound genomic instability. They occur in adults and affect women more frequently than men.hy Leiomyosarcomas present as painless firm masses. Retroperitoneal tumors may be large and bulky and cause abdominal symptoms. Mitotic activity and necrosis are common. Treatment depends on tumor size, location, and grade. Superficial leiomyosarcomas are usually small and have a good prognosis, whereas those of the retroperitoneum are difficult to control and cause death by both local extension and metastatic spread, especially to the lungs.Tumors of peripheral nerves Neurofibroma Benign peripheral nerve sheath tumor with classic identifiable features including the presence of a neuronal component comprising transformed Schwann cells and a non-neoplastic fibrous component that includes fibroblasts Occur during the 2"¢ and 3" decades of life © M:F 1:1 Can be sporadic 90% or as part NF type 1 10% Commonly superficial not deepSchwannoma Benign nerve sheath tumor arising from differentiated Schwann cells Biphasic tumor with highly ordered cellular component (Antoni A) that palisades (Verocay bodies) plus myxoid hypocellular component (Antoni B) Usually associated with an identifiable nerve Affects all ages but mainly 20-50yrs 90% are sporadic 3% NF2 More frequently on the limbs with a predilection to the upper limbs, followed by the head and neck area, including the oral cavity, orbit and salivary glands Pain and neurological symptoms are uncommon unless the tumor is largeAustin Publishing Group Massive Facial Neurofibromas: Review of the Literature, New Classification System...Malignant peripheral nerve sheath tumor (MPNST) Also known as malignant schwannoma Bulky deep-seated tumor usually arising from major nerves in neck, forearm, lower leg, buttock 50% associated with neurofibromatosis (NF), 50% arise de novo May be due to radiation; rarely arise from ganglioneuroma Usually adultsTumors of adipose tissue Lipoma * A benign tumor composed of mature adipocytes. * It is the most common soft tissue tumor in adults. * Has no gender predilection. * Usually occur in the trunk, back, shoulder, neck, proximal extremities. * Most are cured by simple excision.Liposarcoma * These are malignant tumors of adipose tissue. * Liposarcoma is one of the most common sarcomas of adulthood. * It occurs mainly in people in their 50s to 60s in the deep soft tissues and retroperitoneum. Types “+ Well differentiated > Myxoid “ Pleomorphic * All types of liposarcoma recur locally and often repeatedly unless adequately excised.Angiosarcoma Malignant tumor arising from the endothelial lining of blood vessels and can arise from essentially any region within the body. They usually occur in the scalp, head, neck (scalp), and viscera and generally occur during the seventh or eighth decade of life Risk factors: chronic lymphedema, PVC, radiation, sun exposure, Thorotrast Nodal metastases in 14%; also metastases to lungs, liver, bone. Histologically they can range from well-differentiated to poorly differentiated. Therapy is aimed at surgical resection with negative marginsJOINT TUMORSbo Synovial cyst Herniation of synovium through joint capsule, usually in joint of extremities. It can also occur in spinal joints (L4-5) May bleed and become a mass-like lesion If it occurs in the popliteal space- Baker cyst. Usually associated with degenerative joint disease e.g. RA/OA. The synovial lining may be hyperplastic and contain inflammatory cells and fibrin.Tumors Tenosynoviatgiant cell tumor o¢ ee This is a benign neoplasm that develops in the synovial lining of joints, tendon sheaths and bursae. 80% occur in the knee. Patients present with pain and may have a palpable mass Rx : surgical excision though may recur Variants Diffuse type- involves large joints Localized- occurs as a discrete nodule attached to a tendon sheath, commonly in the hand. Both types harbour reciprocal somatic chromosomal translocation £172). This results in fusion of the type VI collagen a-3 promoter to the M- CSF gene. Stimulation of macrophage proliferation occursBONE TUMORSIntroduction Primary bone tumors are rare. They can be benign or malignant. Benign tumors are more common and occur within the first 3 decades of life. In older adults , a bone tumor is likely to be malignant. There is predilection of specific types of tumors for certain age groups and particular anatomic sites and this provides important diagnostic clues. Bone tumors may present in a number of ways. The more common benign lesions are often asymptomatic incidental findings. Many tumors, however, produce pain or a slow-growing mass. In some circumstances the first hint of a tumor’s presence is a pathologic fracture. In almost all instances biopsy is necessary for definitive diagnosis* The behaviour of benign bone tumors varies from Y being self-limited and healing spontaneously (eg, nonossifying fibroma, osteoid osteoma), to ¥ inactive but persistent (eg, enchondroma, osteochondroma), ¥ to minimally locally aggressive (eg, aneurysmal bone cyst, chondroblastoma, chondromyxofibroma), ¥ to very locally aggressive (eg, giant cell tumor of bone, osteoblastomaThe treatment of benign bone tumors depends on their growth behavior. Most primary malignant bone tumors should be surgically resected except myeloma and lymphoma of bone. Some patients with malignant bone tumors present with metastasis e.g. osteosarcomaBone tumors arise from the mesenchymal cells normally present in the skeleton. The classification of these tumors is defined by the assumed cell of origin based on the histologic examination. Often it is the matrix of the tumor that indicates the cell type. Therefore, tumors that have a matrix of bone have “osteo” in their name and are believed to have arisen from cells in the osteoblast cell line (eg, osteoid osteoma, osteoblastoma, osteosarcoma). Those with a cartilage matrix have “chondro” in their name and are believed to have arisen from cells in the chondroblast cell line (eg, enchondroma, osteochondroma, chondroblastoma, chondrosarcoma.Those that arise from the fibrous matrix (eg, nonossifying fibroma, fibrosarcoma, malignant fibrous histiocytoma). Those from a vascular origin (eg, hemangioma, hemangioendothelioma, hemangiopericytoma), and Those without a particular matrix (eg, unicameral bone cyst, aneurysmal bone cyst, giant cell tumor of bone, Ewing sarcoma)Osteoid osteoma Small, benign, bone forming tumor associated with pain and limited growth potential Usually less than 2cm in diameter MF 3:1 mainly children, adolescents and young adults. Commonly found on long bones esp femur and tibia (cortex) but can affect any bone. They present with severe nocturnal pain that is relieved by aspirin and other NSAIDs. The pain is probably caused by prostaglandin E2 produced by osteoblasts. Usually, there is a thick rim of reactive cortical bone that may be the only clue radiographically. Rx: radiofrequency ablationOsteoblastoma Benign tumor Largerthan2cm ° Frequently involves the posterior components of the vertebrae(laminae, pedicles). Pain caused is unresponsive to analgesics Malignant transformation can occur Rx: excision or currettageOsteosarcoma A malignant tumor in which the cells synthesize bone. The most common primary malignant solid tumor of bone. It has a bimodal age distribution; 75% of osteosarcomas occur in persons younger than 20 years of age. The smaller second peak occurs in older adults, who frequently suffer from conditions known to predispose to osteosarcoma, such as Paget disease, bone infarcts, and previous radiation. Males more affected. The most common sites in adolescents are the metaphyseal regions of the distal femur and proximal tibia.It presents as a painful, progressively enlarging mass. Sometimes a pathologic fracture is the first indication. X-rays usually show a large, destructive, mixed lytic and sclerotic mass with infiltrative margins The tumor frequently breaks through the cortex and lifts the periosteum, resulting in reactive sub-periosteal bone formation. The triangular shadow between the cortex and raised ends of periosteum, known radiographically as Codman triangle, is indicative of an aggressive tumor, but is not pathognomonic of osteosarcoma.Pathogenesis * Approximately 70% of osteosarcomas nave acquired genetic abnormalities. * Mutations in tumor suppressors genes and oncogenes. * These genes include “* RB gene- germline or somatic “* TP53 “ CDKN2A “* MDM2 * Osteosarcomas peak in incidence around the time of the adolescent growth spurt and occur most frequently in the region of the growth plate in bones with the fastest growth. * The increased proliferation at these sites may predispose to osteosarcoma development.* They are bulky tumors often with areas of hemorrhage and cystic degeneration. * They destroy cortices, infiltrate the medullary canal and replace the marrow. * Rarely they penetrate the epiphyseal plate or enter the joint. Histology * The formation of osteoid matrix or mineralized bone by malignant tumor cells is diagnostic of osteosarcoma. * The tumor cells vary in size and shape (pleomorphic) and frequently have large hyperchromatic nuclei. Bizarre tumor giant cells, vascular invasion, and necrosis are common. Mitotic activity is high, including abnormal forms.Treatment * Neoadjuvant chemotherapy R * Surgery They spread hematogenously to the lungsCartilage forming: * Osteochondroma is an exostosis with a cartilage cap. * Sporadic and syndromic forms arise from mutations in the EXT genes. * Chondromas are benign tumors producing hyaline cartilage, usually arising in the digits. * Chondrosarcomas are malignant tumors of chondroid cells that involve the axial skeleton in adults.Metastatic tumors * Metastatic tumors greatly outnumber primary bone cancers. b * The pathways of tumor spread to bone include (1) direct extension (2) lymphatic or hematogenous dissemination (3) intraspinal seeding (via the Batson plexus of veins). * Any cancer can spread to bone, but in adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. * In children, metastases to bone originate from neuroblastoma, Wilms tumor, and rhabdomyosarcoma.Skeletal metastases are typically multifocal and involve the axial skeleton, especially the vertebral column. The radiographic appearance of metastases may be purely lytic (bone destroying), purely blastic (bone forming), or mixed. The presence of bone metastases carries a poor prognosis. Therapeutic options include systemic chemotherapy, radiation, and bisphosphonates. Surgery may be necessary to stabilize pathologic fractures.