bone case

“Bone” A Surgical Pathology Case Sec III-A Group 4 October 31, 2006 CASE CASE  An 18 year old male has a 6 month history of progressive pain in his left distal thigh. He had some moderate swelling about his knee. His pain was worse at night. He did not have pain with ambulation. CASE  Radiographs demonstrated a lesion of the distal femur. A mass lesion arising in the metaphysic is seen on gross examination destroying the distal femur and extending through the cortex. The lesion is firm with some hard white areas. CASE  The neoplasm is composed of areas of bone which show calcifications and ossifications of the matrix but these areas are obviously primitive and disorganized. Some areas of the tumor show marked cellularity with pleomorphism, hyperchromatism and mitoses. Chronic pain in left distal thigh Muscle Ligament Joint Bone Vascular X- ray: distal femur Developmental Metabolic Infectious Neoplasm Metaphysis extending Through cortex Benign Malignant Neoplasm Osteoid Osteoma Benign Malignant Rule in •Age 10-30 y/o •Male predominance •Pain worst at night •Appendicular bone involvement •Metaphysis most common site •Involvement of cortex Rule out •Pain increase with ambulation and activity •Tumor regress spontaneously •No malignant potential Neoplasm Osteoid Osteoma Benign Malignant Pleomorphism Hyperchromatic Mitosis Ewing’s Sarcoma Giant Cell Tumor (Osteoclastoma) Osteosarcoma Rule in •80% <20 y/o •M>F •Involves the long bones Rule out •With symptom free interval •X-ray: onion peel appearance Neoplasm Osteoid Osteoma Benign Malignant Ewing’s Sarcoma Giant Cell Tumor (Osteoclastoma) Osteosarcoma Rule in •Arthritic symptoms •Occur as solitary tumor •Located in metaphysis in adolescents •Lower end of femur Rule out •20-40 y/o •Female predominance •(+) hemorrhage in lesion Neoplasm Osteoid Osteoma Benign Malignant Ewing’s Sarcoma Giant Cell Tumor (Osteoclastoma) Osteosarcoma Working Diagnosis: Osteosarcoma Pathophysiology Etiology: unknown(?) Rapid Bone Growth: Adolescent growth spurt Genetic predisposition: Constitutional mutation of the RB gene (germline retinoblastoma); Li-Fraumeni syndrome (germline p53 mutation); Rothmund-Thomson syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts). Environmental factor: Radiation Spindle cell neoplasm producing osteoid (unmineralized bone) Metaphyseal region of the long bones of extremities Distal femur Proximal tibia Proximal humerus tumor destroy surrounding cortices & produce soft tissue masses progressive pain in left distal thigh that worsens at night no joint involvement no pain with ambulation tumor spread extensively in the medullary canal, infiltrating & replacing the marrow surrounding the pre-existing bone trabeculae Radiograph: Lesion of distal femur Gross: firm mass lesion with some hard white areas arising in metaphysic destroying distal femur extending through cortex Histologic: neoplasm composed of area of bone with primitive & disorganized calcification & ossification of matrix; some area showed marked cellularity with pleomorphism, hyperchromatism & mitoses Classification of Osteosarcoma  75% of osteosarcoma fall in the “classic” category, which include osteoblastic, chondroblastic, and fibroblastic osteosarcomas. The remaining 25% are classified as “variants” on the basis of     1.) Clinical characteristics 2.) Morphologic characteristics 3.) Location Epidemiology     accounts for almost 45% of all bone sarcomas, is a spindle cell neoplasm that produces osteoid (unmineralized bone) or bone. It has a predilection for metaphyses of long bones. The most common sites are the femur (42%, 75% of which are distal femur), tibia (19%, 80% of which are proximal tibia), and humerus (10%, 90% of which are proximal humerus). Other significant locations are the skull and jaw (8%) and pelvis (8%). Epidemiology     Frequency: In the United States, incidence is 400 cases per year (4.8 per million population <20 y). Incidence is slightly higher in African Americans than in whites Incidence of osteosarcoma in males is 1.5 to 2 times as often as females About 60% of all osteosarcomas occur in children and adolescents in the second decade of life, and about 10% occur in the third decade of life. Etiology  Unknown  Risk Factors which are apparent for developing osteosarcoma:    Rapid bone growth Environmental factors Genetic predisposition Clinical Manifestations    Symptoms may be present for weeks or months (occasionally longer) The most common presenting symptom of osteosarcoma is pain, There may or may not be a history of swelling, depending on the size of the lesion and its location. Metastases to other sites are extremely rare, and, therefore, other symptoms are unusual. Gross Morphology Gross Morphology  The most common subtype       is arising in the metaphysis of long bones, primary, solitary, intramedullary, poorly differentiated Produces bony matrix          Bulky tumor Gritty Gray white Often contain areas of hemorrhage and cystic degeneration Destroys the surrounding cortices Produces soft tissue masses Spreads extensively to the medullary canal Infiltrates bone marrow Joint invasion   Grows along tendinoligamentous structures Through the attachment site of joint capsule  Tumor extensively involving spine and producing a large soft tissue mass. Histologic Morphology Histologic Morphology  characteristic feature: formation of osteoid or bone (calcified osteoid) Histologic Morphology Normal Osteosarcoma  Coarse, lacelike pattern of neoplastic bone produced by anaplastic malignant tumor cells. Note the mitotic figures. (Robbins 2006). Histologic Morphology Osteoid:  eosinophilicstaining quality  glassy appearance  irregular contours  surrounded a rim of osteoblasts Histologic Morphology  The malignant bone is more basophilic and has more irregular borders than the preexisting bone trabeculae. Other Laboratory Workup Blood Chemistry Imaging Studies (CT Scan, MRI, Bone Scan) Important laboratory studies include tests of the following:    LDH, alkaline phosphatase (prognostic significance LDH, when elevated, confers a worse prognosis, presumably by indicating a more biologically aggressive tumor Patients with elevated alkaline phosphatase values at diagnosis are more likely than others to have pulmonary metastases Important laboratory studies..      CBC, including differential and platelet count Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and albumin levels to assess liver function Electrolyte concentrations: sodium, potassium, chloride, bicarbonate, calcium, magnesium, and phosphorus levels BUN and creatinine  to assess renal function Urinalysis Imaging Studies: CT Scan    helpful locally when the radiographic appearances are confusing, particularly in areas of complex anatomy can depict small amounts of mineralized osseous matrix not seen on radiographs rarely alters the differential diagnosis when it is used to image conventional osteosarcoma CT Scan     helpful in the evaluation of a variety of the osteosarcoma variants helps in delineating the location and extent of the tumor and is critical for surgical plannin most accurate modality for staging of pulmonary metastases details the extent of bony destruction MRI     single most important study for accurate surgical staging of the lesion optimum technique for local staging of osteosarcomas accurately shows soft tissue extension and skip lesions; multi-axial images more sensitive in quantifying the extent of intramedullary involvement This T2 weighted axial FSE MRI scan with fat saturation reveals disruption of the bone cortex along with a mass extending into adjacent soft tissue in the distal femur. Bone Scans (Nuclear Scintigraphy)    The most valuable use for evaluation of osteosarcoma is the detection of metastatic deposits within the skeleton. most useful in excluding multifocal disease more pertinent to staging than for evaluation of the primary lesion Bone scans   Radionuclide bone scanning with technetium99m diphosphonate 18F-Fluoro-deoxy-glucose positron emission tomography or thallium-201 scintigraphy Bone Scan  This bone scan demonstrates a "hot spot" of increased uptake in the distal left femur. Other Tests:   Echocardiography or multiple-gated acquisition (MUGA) scanningCardiac function AudiogramHearing loss is an adverse effect of cisplatin Treatment Treatment for Osteosarcoma  Specific treatment for osteosarcoma will be determined by your physician based on:      patient’s age, overall health, and medical history extent of the disease tolerance for specific medications, procedures, or therapies expectations for the course of the disease your opinion or preference Treatment may include:  Surgery  biopsy, resections, bone/skin grafts, limb salvage procedures, reconstructions   Amputation- for a permanent cure. Chemotherapy Chemotherapy:  Adjuvant chemotherapy  chemotherapy given after surgery  Neoadjuvant chemotherapy  chemotherapy given before surgery to shrink the cancer so that it can be removed during surgery Chemotherapy:       High dose methotrexate with leucovorin Doxorubicin (Adriamycin) Cisplatin Carboplatin (Paraplatin) Cyclophosphamide (Cytoxan) Ifosfamide (Ifex) Others    Radiation therapy Resections of metastases Rehabilitation  physical and occupational therapy, and psychosocial adapting     Prosthesis fitting and training Supportive care (for the side effects of treatment) Antibiotics (to prevent and treat infections ) Continued follow-up care Prognosis Table 1. Histologic Tumor Grading of Osteosarcoma Tumor Grade G1 G2 G3 Tumor Differentiation Well differentiated Moderately differentiated Poorly differentiated G4 Gx Undifferentiated Not assessable Table 2. Clinical Staging of OSteosarcoma Based on Tumor Grade and TNM Tumor Grade G1, G2 G1, G2 G3, G4 G3, G4 Any G Any G TNM T1 N0 M0 T2 N0 M0 T1 N0 M0 T2 N0 M0 Any T, N1, M0 Any T, Any N, M1 Clinical Stage IA IB II A II B IV A IV B Enneking staging    Uses histologic grade and anatomic location of tumor Grade: well differentiated / low grade (tumor cells resemble cells from which they are thought to arise); poorly differentiated / high grade (can barely recognize what normal counterpart of tumor cell would be); also graded as 1-4 (1-2: low grade, 3-4: high grade) Anatomic location: one compartment (confined to bone) or two compartments (tumor has broken through bone into soft tissue) Tumor Staging of the Patient…  Stage IIB  undifferentiated (Grade 4)  high grade lesion (Stage 2)  extramedullary (Substage B) Prognosis for long term survival is 60-70% ( 5 year survival). 