BONE TUMORS, INFECTIONS, OSTEONECROSIS Flashcards
Paradigms of Cancer Rehabilitation
Preventive interventions Restorative interventions Supportive interventions Palliative interventions Palliative interventions
Preventive interventions
• lessen the effect of expected disabilities • emphasize patient education. • Improving the patient's physical functioning and general health • Psychological functioning
Restorative interventions
• Goal is to return patients to previous levels of physical, psychological, social, and vocational functioning. • Postoperative ROM exercises for patients undergoing mastectomy and reconstructive surgery for head and neck cancer represent this category of interventions.
Supportive interventions
• Designed to teach patients to accommodate their disabilities • To minimize debilitating changes from ongoing disease. • Supportive efforts include: - teaching patients how to use prosthetic devices after amputation - Adaptive devices - Emotional support
Palliative interventions
• Interventions and goals focus on
minimizing or eliminating complications and providing comfort and support
• Goals include pain control, prevention of contractures and pressure sores, prevention of unnecessary deterioration from inactivity, and psychological support for the patient
Childhood Cancer
• Rare in children • Leading cause of death by disease past infancy among children in the United States • 2014: 15,780 children and adolescents ages 0 to 19 years will be diagnosed with cancer & 1,960 will die of the disease in the United States
Clinical Features • non-specific, therefore a long period of time may elapse until the tumour is diagnosed • Pain, swelling and general discomfort are the cardinal symptoms that lead to the diagnosis of bone tumours. • However, limited mobility and spontaneous fracture may also be important features.
Etiology • Inherited mutation • Genetic mutation • Ionizing radiation • Environmental exposure
Pain
• First and most common symp-tom in
nearly all malignant bone tumours {
• If a spontaneous fracture does not occur, the symp- toms usually
commence slowly.
• Patient has tearing neuralgia-like pain,
which may also be interpreted as
"rheumatic pain".
• Intermittent→ at rest→ distubing→
spreading to adjacent structures
Swelling
• 2nd most important symptom
• May frequently be benign and of long
duration and may not be associated
with other complaints
• Swelling is only observed if there is an
extraosseous part of the tumour or the bone is expanded by the tumourous process.
Limitation of movement
• Mobility may be limited in cases of
lesions close to the joint, in tumours such as osteoblastoma, chrondroblastoma, giant cell tumours and all types of sarco- mas. Occasionally it is not the tumour but reactive synovitis in the joint, especially in chondroblastoma, that causes limita- tion of movement and masks the true diagnosis
Pathologic Fracture
• Fracture is diagnosed early, as it
causes the patient to seek attention
immediately.
• It may occur with no prior symptoms
at all, as is frequently the case in juvenile cysts and in some non- ossifying b one fibromas
• Rare inciting event in primary bone malignancy
Constitutional Symptoms
- Weight loss
- Fever
- Weakness
Diagnosis
• Combining both radiological and
histological criteria is most
appropriate.
• Based on clinical and radiological
signs, one should first diagnose benign lesions for which a subsequent biopsy may not be necessary. Metaphyseal fibrous defect > Fibrous dysplasia, Osteochondrom
Enchondroma, Simple bone cyst,
Vertebral haemangioma
• Age is useful information:
- before age of 5, a malignant tumour is often metastatic neuroblastoma;
- between 5 and 15 years old, osteosarcoma or Ewing sarcoma; a
- after 40 years, metastasis or myeloma.
- Certain tumours are more common inparticular bones. Adamantinoma, usually found in the adult, selectively involves the tibia and fibula.
- The most common epiphyseal tumour in childhood is the chondroblastoma. Tumour size is useful and easy to use.
A tumour less than 6 cm in greatest dimension is likely benign whereas one
bigger than 6 cm may be benign or malignant. The axis of the lesion is also useful to determine
• The next step is to determine the limits of bone tumor
- Patterns of bone destruction indicates the aggressiveness of the tumor
Sarcomas
- Sarcomas are rare (<1% of all
malignancies) mesenchymal neoplasms that arise in bone and soft tissues - Usually of mesodermal origin, although a few are derived from neuroectoderm, and they are biologically distinct from the more common epithelial malignancies.
- Affect all age groups;
- 15% are found in children <15 years of age,
- and 40% occur after age 55 years.
- One of the most common solid tumors
of childhood and are the fifth most common cause of cancer deaths in children. - Sarcomas may be divided into two groups 1) and those 2) soft tissues.
Soft Tissue Sarcomas
• Soft tissues include muscles, tendons,
fat, fibrous tissue, synovial tis-sue,
vessels, and nerves.
• Approximately 60% of soft tissue
sarcomas arise in the extremities, with the lower extremities involved three times as often as the upper extremities.
• MC asymptomatic mass
• Mechanical symptoms referable to
pressure, traction, or entrapment of nerves or muscles may be present
• All new and persistent or growing masses should be biopsied, either by a cutting needle (core-needle biopsy)
• Treatment: Surgery, RT and neoadjuvant chemotherapy
Synovial Sarcoma
• High-grade and soft-tissue sarcoma
that
• Frequently is in the vicinity of joints,
tendons or bursae, although it can also be found in extra-articular location
• Most common cause of soft tissue tumor after rhabdomyosarcoma
• Has embryonic similarity to the synovium
Incidence • Estimated incidence of this tumor in the general population is 2.75 per 100,000 • 4th most common sarcoma after the malignant fibrous histiocytoma, liposarcoma and rhabdomyosarcoma. • Approximately 800 new cases are diagnosed each year in the US • Second only to rhabdomyosarcoma in children
Prevalence
• 1/3rd of synovial sarcomas occur in the
first two decades of life.
• Prevalent in adolescents and adults
between 15 and 40 years of age
• The male:female ratio is 1.2:1, with
males more frequently affected
• Similar incidence in all ethnic groups.
Pathophysiology
• Chromosomal translocation, t(X;18)
(p11;q11)
• SYT-SSX1, SYT-SSX2 or SYT-SS4
- Has been noted in more than 90% of the cases
- SYT-SSX2 and SYT-SSX2 are more common in females
- Fusion of these gene results
to either inhibition of tumor suppressor genes or activation of protooncogenes
Clinical Presentation • Usually occurs in the first three decades of life • Presents as a small nodule that has increased rapidly in size • Mass is generally painful and deep • More commonly found in the knee but is also found in the hands and feet
Anatomic regions a. Trunk-Head, neck, thorax, abdomen and pelvis b. Distal extermity- Hands, feet and ankles c. Proximal extremity- Arms, forearms, thighs and legs
BONE SARCOMAS
• Bone tumors are classified into:
- Primary bone tumors
- Secondary bone tumors
(Metastasis)
- Most are classified according to the normal cell of origin and apparent pattern of differentiation
- Bone sarcomas are rarer than soft tissue sarcomas. Several benign bone lesions have the potential for malignant transformation
- Enchondromas and osteochondromas can transform into chondrosarcoma; fibrous dysplasia, bone infarcts, and Paget’s disease of bone can transform into either UPS or osteosarcoma
Benign tumors
• enchondroma, osteochondroma,
chondroblastoma, and chondromyxoid fibroma, of cartilage origin; osteoid osteoma and osteoblastoma, of bone origin; fibroma and desmoplastic fibroma, of fibrous tissue origin; hem- angioma, of vascular origin; and giant- cell tumor, of unknown origin.
Malignant tumors
• The four most common malignant
nonhematopoietic bone tumors are osteosarcoma, chondrosarcoma, Ewing’s sarcoma, and UPS.
• Rare malignant tumors include chordoma (of notochordal origin), malignant giant-cell tumor and adamantinoma (of unknown origin).
Primary Bone Tumors
Bone-Forming tumors 1. Osteoma 2. Osteoid osteoma and osteoblastoma 3. Osteosarcoma Cartilage-Forming tumors 1. Chondroma (Enchondroma) 2. Osteochondroma 3. Chondrosarcoma
Bone Tumors
• Bone tumors are classified into:
a. Primary bone tumors
b. Secondary bone tumors (Metastasis)
• Most are classified according to the normal cell of origin and apparent pattern of differentiation
Osteoma
• Osteoma are benign lesions of bone
that in many cases represent developmental aberrations or reactive growths rather than true neoplasms.
Malignant Osteoid
Osteoid
• Unmineralized, organic portion of the
bone matrix that forms prior to the maturation of bone tissue. Osteoblastic differentiation of the primitive transformed cells produces malignant osteoid, which result in the formation of the malignant primary bone tumour known as Osteosarcoma
Osteosarcoma
• Is the most common malignant bone tumor
• arise from primitive mesenchymal bone-forming cells, and its histologic hallmark is the production of malignant osteoid
• Pulmonary metastases
• Arises as solitary lesion in the long bones of the femur
LOCATIONS a. Femur (42%, 75% of which are in the distal femur) b. Tibia (19%, 80% of which are in the proximal tibia) c. Humerus (10%, 90% of which are in the proximal humerus) d. Skull and jaw (8%) e. Pelvis (8%) Surgical removal is the mainstay of treatment Chemotherapy is generally given to control the disease progress
Signs and Symptoms • Most common is pain during activity • Swelling may or may not occur • Pathologic fractures are rare • Respiratory symptoms may occur
Treatment
• Neoadjuvant chemotherapy
• Wide resection
• Biopsies
- Open biopsy (preferred to avoid sampling error and to provide adequate tissue for biologic studies)
- Trephine biopsy or core- needle biopsy (preferred for vertebral bodies and many pelvic lesions)
- Fine-needle aspiration (FNA; not recommended)
Osteochondroma
Morphology
• Osteochondromas are mushroom
shaped and range in size from 1 to 20
cm.
• The outer layer of the head of the
osteochondroma is composed of benign hyaline cartilage varying in thickness
• Newly formed bone forms the inner portion of the head and stalk, with the stalk cortex merging with the cortex of the host bone.
Chondrosarcoma • Collective term for a group of tumors that consist predominantly of cartilage • Range from low-grade tumors with low metastatic potential to high- grade, aggressive tumors characterized by early metastasis. See the image below.
Clinical Feature • Deep, dull, achy pain • Pain at night • Nerve dysfunction of the lumbosacral plexus or the sciatic or femoral nerves, with pelvic lesions near a neurovascular bundle • Limitation of joint range of motion and disturbance of joint function • Pathologic fracture • Common sites of predilection • Pelvis and ribs, 45% • Ilium, 20% • Femur, 15% • Humerus, 10% • Others, 10%
Staging
Stage I (low-grade tumor) - Stage I-A, intracompartmental; stage I-B, extracompartmental
Stage II (high-grade tumor) - Stage II-A, intracompartmental; stage II-B, extracompartmental
Stage III (distant metastasis)
- Determines the Chromosomal Translocation
Treatment
Surgery: primary treatment chondrosarcoma
for any
- Complete, wide surgical excision of the chondrosarcoma is the preferred method
Radiotherapy and chemotherapy play limited roles in primary treatment
- An exception is their use as adjuvant therapy or palliative treatment for tumors in surgically inaccessible areas or diffuse metastasis
Work-up: Imaging Studies
o Plain radiographs - Snow storm appearance o Computed tomography - Used to confirm presence of a mass, its size and its location - Non-diagnostic o Magnetic Resonance Imaging - Imaging of choice
Laboratories
Cytogenic analysis
- Determines the Chromosomal Translocation
Treatment • Surgical excision - Cornerstone of treatment of synovial cell sarcoma - Wide excision with negative margins A. Standard surgical procedure is a wide excision with negative margins B. Removing the tumor with a rim of normal tissue around • Tumor free margin of 1-3 cm
Medical Therapy • Adjuvant chemotherapy and neoadjuvant chemotherapy • Chemotherapy remains controversial • Recommended for patients with tumor size larger than 5 cm • Trials: - Doxorubicin and cyclophosphamide-based chemotherapy - Doxorubicin and bolus ifosfamide - Ifosfamide with loposomal daunorubicin - GSF: stimulating the bone marrow
Giant Cell Tumor
• Most challenging benign tumors • This is a neoplasm that contains large numbers of osteoclast like giant cells admixed with mononuclear cells. • Although benign, GCTs show a tendency for: - significant bone destruction, local recurrence, and occasionally metastasis. • Natural history of GCTs varies widely and can range from local bony destruction to local metastasis, metastasis to the lung, metastasis to lymph nodes (rare), or malignant transformation • Lung metastases is rare
Epidemiology
• Female predominance
• 84% of cases occur in patients >19
years
Clinical Presentation • Most are located within the epiphyses of long bones, but they often extend into the metaphysis • Approximately 50% of GCTs are located around the knee. The most common locations are the distal femur, the proximal tibia, and the proximal humerus and distal radius
Work Up
•Radiographic ally, giant cell tumors (GCTs) are lucent and eccentrically located within the bone. These lesions can appear aggressive and are often characterized by extensive local bony destruction, cortical breakthrough, and soft-tissue expansion
- MRI: extent of neoplasm
- CT scan: absence of bone
Treatment
• Surgery
• Denosumab
- Treatment for unresected GCT
Prognosis
• Spontaneous malignant transformation of GCT is not uncommon
• Malignant transformation
- has been defined as a
sarcoma associated with a benign typical GCT at presentation or as a sarcoma arising at the site of a preexisting GCT.
- osteosarcoma, fibrosarcoma, or malignant histiocytoma. (see the images below).
Ewings Sarcoma
Includes:
- Ewing sarcoma, A skin tumor, and peripheral primitive neuroectodermal tumors.
- Ewing sarcoma and the peripheral primitive neuroectodermal: reciprocal translocation between chromosomes 11 and 22
Clinical Features • Localized pain • Back pain, which may indicate a paraspinal, retroperitoneal, or deep pelvic tumor • Palpable mass • Systemic symptoms of fever and weight loss, which often indicate metastatic disease
Physical Examination
• Careful inspection and palpation of
painful sites
- lesions of the long bones can
present with a pathologic
fracture
• Comprehensive neurologic
examination to evaluate asymmetrical weakness, numbness, or pain; tumors close to bone can result in neuropathic pain
• Skin inspection for petechiae or purpura that may be caused by thrombocytopenia due to clinically significant bone marrow metastases
• Pulmonary auscultation for asymmetrical breath sounds, pleural signs, or rales that may indicate lung metastases
Management • Chemotherapy with alternating courses of 2 regimens: (1) vincristine, doxorubicin, and cyclophosphamide; and (2) ifosfamide and etoposide • Neutrophil support • Red blood cell and platelet support • Surgery and/or radiotherapy
Prognosis
• The most significant factor currently known to determine the prognosis in patients with Ewing sarcoma is the presence or absence of metastatic disease.
• Primary site of the tumor also is a prognostic factor, with distal extremities being more favorable than those with central or pelvic sites.
• Age younger than 15 years also seems to be a more favorable prognosis.
• Survival of patients with Ewing
sarcoma depends highly on the initial
manifestation of the disease.
• Approximately 80% of patients present with localized disease, whereas 20% present with clinically detectable metastatic disease, most often to the lungs, bone, and/or bone
marrow
• The overall patient survival rate is
60%; for patients with localized disease, however, the survival rate approaches 70%
• Patients with metastatic disease have a long-term survival rate of less than 25%.
Chemotherapeutic Regimen
- Vincristine - Primarily causes neuropathy, including constipation, myalgias, arthralgias, and cholestasis
- Doxorubicin - Causes myocardial dysfunction and pancytopenia
- Cyclophosphamide - Causes pancytopenia and a dosage- dependent hemorrhagic cystitis
- Ifosfamide - Similar to cyclophosphamide, although it is associated with an increased incidence of hemorrhagic cystitis, which requires the use of mesna; patients near the end of therapy occasionally develop the Fanconi syndrome of electrolyte wasting.
- Etoposide - Can result in pancytopenia, as well as anaphylactic reactions, and it is implicated in the development of second malignancies, particularly acute myelogenous leukemia
- Combination chemotherapy - Results, in general, in alopecia, nausea, vomiting, and occasionally diarrhea; increased risk of infection from immune suppression; the nutritional and psychological status of patients undergoing this therapy must be closely monitored; effects of chemotherapy such as organ damage, infertility, and risk of secondary malignancy
Metastatic Bone Disease
• Cancer that begins in an organ, such as the lungs, breast, or prostate, and then spreads to bone • More than 1.2 million new cancer cases are diagnosed each year. Approximately 50% of these tumors can spread (metastasize) to the skeleton.
Pathophysiology
• Cells from the primary site must,
through the process of neovascularization or through migration to the nearest blood vessel, attach to the basement membrane of the vessel wall and produce proteolytic enzymes that disrupt the basement membrane.
• The cells then migrate through the basement membrane and float away in the bloodstream to a distant site. The process through which these tumor cells are attracted to a specific site in the body is not completely clear, though type I collagen, a byproduct of bone resorption, has been shown to be a chemotactic factor that attracts tumor cells to bone.
Most Common Sites
1. Breast, Lung, Thyroid, Kidney, Prostate
Clinical presentation
• Pain: Most common symptom
• Fractures: Pathologic fracture • Anemia
Metastatic Bone Disease VS Primary Bone Cancer
The diagnosis of metastatic bone disease should not be assumed unless a patient has a known primary cancer that has previously spread to bone.
Treatment
• Radiotherapy
• Spinal surgery
- Decreasing or eliminating pain, decompressing neural elements to protect cord function, and mechanically stabilizing the spine.
- Anterior or posterolateral decompression, combined
with anteroposterior reconstruction, may be used in the following: Diagnostic spinal surgery, Cervical spinal surgery, Thoracic and lumbar spinal surgery
• Monoclonal antibody antineoplastic agents (eg, denosumab)
• Calcium metabolism modifiers/bisphosphonates (eg, pamidronate, ibandronate)
Pathophysiology • Hematogenous spread • Spread from a contiguous site following surgery • secondary infection in the setting of vascular insufficiency or concomitant neuropathy.
Osteomyelitis
• An infection of bone
- can be caused by various micro-organisms that arrive at bone through different routes.
- Spontaneous hematogenous osteomyelitis may occur in otherwise healthy individuals, whereas local microbial spread mainly affects either individuals who have underlying disease (e.g., vascular insufficiency) or patients who have compromised skin or other tissue barriers, with consequent exposure of bone.
• The manifestations of osteomyelitis are different in children and adults. In children circulating microorganisms seed mainly long bones, whereas in adults the vertebral column is the most commonly affected site.
• The most important aim of the management of either type of osteomyelitis is to prevent progression to chronic osteomyelitis by rapid diagnosis and prompt treatment.
• Can be classified by various criteria, including pathogenesis, duration of infection, location of infection, and presence or absence of foreign material.
• Cierny-Mader staging system classifies osteomyelitis according to anatomic site, comorbidity, and radiographic findings, with stratification of long- bone osteomyelitis
Etiology
• The most common primary foci of
infection are the urinary tract, skin/soft
tissue, intravascular catheterization
• Spread from a contiguous source follows either bone trauma or surgical
intervention.
• Wound infection leading to
osteomyelitis typically occurs after cardiovascular intervention involving the sternum, orthopedic repair, or prosthetic joint insertion. Osteomyelitis secondary to vascular insufficiency or peripheral neuropathy most often follows chronic, progressively deep skin and soft tissue infection of the foot.
• The most common underlying condition is diabetes. In diabetes that is poorly controlled, the diabetic foot syndrome is caused by skin, soft tissue, and bone ischemia combined with motor, sensory, and autonomic neuropathy.
Classification: Duration
• Classification of osteomyelitis
according to the duration of infection although ill-defined is useful because the management of acute and chronic osteomyelitis differs.
• Acute hematogenous or contiguous osteomyelitis evolves over a short period.
• Subacute or chronic osteomyelitis lasts for weeks or months before treatment is started.
- Chronic osteomyelitis develops when insufficient therapy leads to persistence or recurrence, most often after sternal, mandibular, or foot infection.
