Malignant Bone Tumors---Musculoskeletal---Week 2

Monday, August 08, 2011

Dr. Templeton & ONeil

CASE 1: OSTEOSARCOMA
o 13 year old male who first noted onset of pain in his left proximal tibial metaphysis 4 months prior to X-rays. No history of trauma o X-rays: Destructive process within L. proximal tibial fo metaphysis. o Tc99 bone scan revealed uptake in same general area. o CT of the chest was normal. o Labs Normal o Diagnosis: Osteosarcoma Most common primary malignant bone tumor Bimodal age distribution (75% occur in pts < 20 yo) Mutations in the genes encoding p53 and RB o Pts with hereditary retinoblastomas at 1,000x more likely to develop osteosarcoma Bone infarcts, chronic osteomyelitis, Paget disease, radiation, also associated with a bone neoplasia Develop at sites of greatest bone growth (metaphysis)

 CASE 2: CHONDROSARCOMA
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72 year old black female with aching discomfort in her right shoulder, worse at night. Duration of approximately six months. X-ray: expansile lesion replacing the head of the right humerus, with characteristic punctate calcifications. Bone scan shows intense uptake in region of tumor. Lab: no abnormal values Diagnosis: Chondrosarcoma 40 years or older Central skeleton pelvis, shoulder, ribs Malignant hyaline and myxoid cartilage

CASE 3: EWINGS SARCOMA

o 7 year old female presented with one month history of right shoulder pain. She noted an acute exacerbation while trying to climb a fence on the day prior to being seen in the office. She had been running low-grade fevers for approximately a month without chills. X-ray: Permeative lesion involving diaphysis of humerus. Bone scan positive only in area of involved bone. MRI showed extensive marrow involvement with possible involvement of the proximal growth plate and a surrounding soft tissue mass. Diagnosis: Ewings sarcoma small/round blue cell tumor Most patients are < 20 years old Pain, fever, leukocytosis (import differential is osteomyelitis) Diaphysis of long bones Sheets of small cells with inconspicuous cytoplasm Ddx: Metastatic neuroblastoma, metastatic rhabdomyosarcoma, lymphoma Ewings Sarcoma/PNET (peripheral neuroendocrine tumor) Similar phenotype, identical translocation SAME TUMOR differing by degree of neural differentiation 2nd most common bone tumor in children (2nd to osteosarcoma) More common in Caucasians, slightly more common in boys Genetics o 85% t (11;22) o 5-10% t(21;22) o 1% t(7;22) o In ALL cases there is fusion of the EWS gene on chromosome 22 to a member of the ETS family of transcription factors, most commonly FLI1 o EWS-FLI1 fusion gene acts as a dominant oncogene constitutively active transcription factor that stimulates cell proliferation Treatment o Chemotherapy and surgical excision +/- radiation o 75% 5-yr survival, 50% long-term cure

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CASE 4: MULTIPLE MYELOMA

o o o o 62 year old male presented to family practice physician complaining of back pain, fatigue and headache Pain is worse at night and not relieved with aspirin/Ibuprofen He also notes he has lost 20 pounds in the last 6 months Labs - pancytopenia, proteinuria X-ray Numerous lytic lesions in skull and spine

Multiple Myeloma Summary: o 50-60 year olds o More common in blacks than whites o Excess IgGk o Bone pain due punched out lytic lesions Production of osteoblast inhibitor Release IL-1 (osteoclast activating factor) o Ribs, vertebrae, skull, pelvis

CASE 5: METASTATIC RENAL CELL CARCINOMA

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46 year old male with a Hx of renal cell carcinoma Presents w/ right hip pain, 10 pound weight loss X-ray: large lesion in right proximal femur that is worrisome for a fracture 1.2 million patients present with cancer each year in the United States. Of these, approximately 600,000 persons have metastases to bone. In contrast, 2,700 patients per year develop primary bone sarcoma. The age range of patients with sarcoma is different from that of individuals with carcinoma of bone; most metastatic bone lesions occur in adults older than 50 years Most sarcomas occur in adolescents or young adults (< 30 y) A bone-occupying mass in an adult is much more likely to be a focus of metastatic carcinoma than to be a primary sarcoma of bone Females: Breast and Lung Male: Prostate and Lung Others: Thyroid and Renal cell carcinoma

Hip Lesion

More on Metastatic Carcinoma: Tumor cells up-regulate osteoclasts through production of RANK ligand potent stimulator of osteoclastic activity RANK ligand 1) recruits & 2) activates osteoclasts which degrade bone, producing pockets or holes in bone for tumor cells to grow Parathyroid hormone related peptide (PTHrP) Breast carcinoma cells small cell carcinoma of the lung Potent stimulant of osteoclasts