Sarcoma

  • Basics
    • Site of Origin
      • 59% Extremity
      • 19% Trunk, ant abd wall (desmoid), flank
      • 15% Retroperitoneum
      • 9% Head and neck
  • Risk Factors
    • Trauma: burn, scar, chronic tissue irritation, chronic lymphedema
    • Genetics
      • Neurofibromatosis: Von Recklinghausen’s Disease
      • Gardner’s Syndrome
      • Tuberous Sclerosis
      • Li-Fraumeni Syndrome
      • Fap- desmoid
    • Radiation: 10 year latency after radiation therapy or exposure
      • Periphery of radiation (bad)
    • Chemical: polyvinyl chloride, burns
    • Lymphedema: Stewart-Treves Syndrome
  • Classification: Based on soft tissue they resemble
  • Presentation: MC painless lump, slow growing
  • Radiologic Eval
    • Plain Xray: location of bone tumor assoc fractures and cortical disruption
    • CT scan abd & pelvis: always use IV contrast
      • CT scan chest: look for mets
      • Pre op cxr v ct: cxr adequate
        • metadata > 1 cm mets matter
    • MRI: if lesion is >4cm
    • Bone Scan: detects mets, eval cortical and intraosseus extent of bone tumors
    • Angiogram if necessary to assess vascular relationship to tumor
  • Staging TGNM
    • Tumor Size
      • T1 <5cm: a superficial to fascia, b invades
      • T2 >5cm
    • Grade: Extent of differentiation mitotic rate, necrosis
    • Path most imp for grade
      • >25 mitosis for 50 high power fields = high grade = radiation tx
      • Subtype not very imp
      • Histo: Most important prognostic factors
        • Low grade: 5-10% metastic
        • Intermed: 25-30% metastatic
        • High Grade: 50-60% metastatic
    • Mets: MC pulm, retroperitoneal spread to liver first
      • Route of tumor dissemination: hematogenous because they are mesenchymal cell origin
      • Extremity and bone tumors usually spread to lung and then bone
      • Abd, pelvic, and retroperitoneal: go to liver and lung
      • Sarcoma rarely met to LN
        • Primitive tumors: small cell, synovial, clear cell, angiosarcoma, rhabdo, epithelioid
        • Chemo sensitive
        • Pos nodes means complete LND
      • Stage 4: mets or nodes
  • Dx: made by biopsy
    • FNA: not very helpful, small cells lots of fibrosis
    • Core Needle Biopsy: ok but need to tract out in line of incision
    • Excisional: tumor <3cm: ok but don’t enucleate
    • Incisional Biopsy: orient biopsy scar with proposed resection lines
      • Most deep, fixed, within musc
      • Exception: DMFB: firm in SubQ
    • Imaging before doesn’t’ change anything unless worry about neurvasc involvement
  • Tx
    • Complete surgical resection including biopsy sites
      • Radical Surgery: improves local control
      • <10% recurrence if: <5cm tumor, superficial, 1 fascial compartment, margin of 2cm
      • DO NOT SHELL OUT: Wide local excision: 2cm margin preferable
        • Muscle group excision
        • Compartmental excision
        • Drain inline with incision
        • Amputation: reserved for recurrences and tumors that render extremity useless
    • Radiation: Intermed to high grade tumor (high grade or low grade >5cm; high mitosis >10)
      • Improves local control: no survival benefit
      • high grade do respond
      • Inadequate margins: limb preserving procedures, close margins around nerves or vasc structures
      • all op area 5000 cgy and tumor bed 6500: external beam = brachytherapy
      • Pre op vs post op:
        • pre less fibrosis and edema worse wound healing
        • post opposite; high grade in sensitive loc do pre
    • Chemo
      • No survival benefit after complete resection
      • Doxorubicin, dacarbazine, ifosfamide (20-50% respond)
      • Postop beneficial with positive margins and high grade histo
      • DTIC clinical trial: adriamycin; Iphosphomide
        • Adriamycin and ifosfamide demonstrate response rates of 20-30%
          • 80% of skeletal sarc will develop recurrence
          • 50% of pt with high grade sts will recur
      • Neoadjuvant best in osteosarc, ewings, rhabdomyosarc
      • Improves limb sparing, improves overall survival
    • Metastatic Dz = metastectomy
      • 44% occur in lungs: f/u with Chest CT
      • Tx: Surgery should be considered even if multiple and bilateral
        • Stapled metastasectomy with minimal lung removed
      • Not an option if:
        • Primary dz not well controlled
        • other systemic sites involved as well
        • recurrent pulm nodules within 1 year of prior lung resection
  • Recurrence
    • RF: >50 yo, >grade 2, retroperitoneal, tumor depth, size >5cm,  pos margins, path: mfh, angiosarc, rhabdomyosarc
    • Up to 50% of retroperitoneal and intra-abdominal sarcomas will recur after initial resection
      • Retroperitoneal Sarcomas: local recurrence, liver and lung mets
    • Extremity sarcomas: pulmonary metastases
    • Aggressive f/u is life prolonging
    • Follow up imaging q 4 mo
      • Sarcomas that recur usually do so within 5 years
    • Poor prognostic features: liposarc >1cm/mo, large >5cm, short disease free interval
    • Slow growing sarcomas with long dz free interval should consider re-resection
      • R0 resection, resect all prior incision, drain and specimen bed sites
    • Consider neoadjuvant chemo/xrt if lesion is large, fast growing, near critical structures or difficult to achieve limb-spaing approach
    • Resection is preferred treatment for recurrences
      • Amputation
      • Pulmonary metastasectomy: up to 40% 5 year survival
    • Chem and radiation generally palliative at best
  • Subtypes
    • MC: malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma
      • MFH: mc soft tissue sarcoma, lower extremities, 20% of all extremity sarcoma
      • Pleomorphic high grade sarc categorized here as well
      • Liposarcoma: 2nd mc sts, usually lower extremities, 25% of extremity sarcomas and 45% retroperitoneal sarcomas
      • Leiomyosarcoma: 20% of retroperitoneal sarcoma
    • Bone sarcomas are classified according to the matrix they produce
      • Osteosarcoma
        • MC bone tumor
        • Usually teenagers (15)/adolescents: male predominate
        • In pt over 40 yo it is usually assoc with pagets dz or prior bone irradiation
          • Chronic remodeling
        • 80-90% occur in metaphysis of long bones:
          • distal femur > proximal tibia > proximal humerus
        • MCsx: painful soft tissue swelling and tenderness
        • Tx: neoadjuvant chemo followed by limb sparing surgery
      • Chondrosarcoma
        • Usually 40-60yo
        • Commonly occur along pelvis, femur and shoulder girdle
        • Rarely responds to chemo (may be considered in young patient with high grade tumor
      • Ewing’s sarcoma
        • Almost always occur around 20yo, Caucasian
        • 90% assoc with distinct chromosomal translocation 11:22 q24 q12 which results in a chimeric protein EWS/FLI-1
        • Destructive intramedullary lesions that affect the diaphysis
    • Dermatofibrosarcoma: lateral microscopic extensions
      • Check CD34, 30-50
      • Tx/ wide local excision with 4cm
    • GIST: AKA leiomyosarcoma
      • Arise from interstitial cells of cajal: gastric pacemaker cells
      • Expresses CD34 (hematopoetic progenitor cell)
      • Expresses CD 117/c-kit (growth factor receptor)
        • Ckit is an oncogene
      • Can affect any portion of GI tract: stomach most common
      • Sx appear late and are subtle
        • Bleeding and ulceration may occur
        • Obstruction from larger tumor
      • Malignant GIST similar presentation to benign but:
        • Size >5cm
        • High mitotic rate (>10 mitoses/high power field)
        • Necrosis
        • Invasion of other structures
        • Metastases
      • Endoscopy: EUS: shows submucosal tumor: possibly with ulceration
        • Biopsies often nondiagnostic
      • CT scanning of Abd/Pelvis
      • Complete surgical resection best tx if it is possible: 2-4cm margin optimal
        • Survival dependent on size/resectability
        • 75% 5-year survival for smaller resected tumors
        • 20-40% overall for malignant GIST tumors
      • Chemo: C-kit inhibitor: imatinib
        • Indication: metastatic, locally advanced and incompletely resected gist tumor
        • 54% demonstrate tumor reduction: 20% tumor stability
        • ckit oncogene expression: 40% recurrence
        • targets tyrosine kinase inhibitor
      • Recurrence in 40-90% surgically tx pt
        • RF: tumor size, mitotic index, tumor location, tumor rupture during surgery
    • Desmoid: nsaid, sulindac, tamoxifen
    • Retroperioneal Sarcoma:
      • Ddx
        • renal cell, adrenal (primary adrenal coricocarc, pheo)
        • lymphoma (other nodes, b sx, tumor marker ldh)
        • non seminomatous extra gonadal germ cell tumors (Bhcg, afp)
      • Represent 15% of sarcoma
      • Dx delayed d/t lack of sx
        • Usually >10cm at time of presentation
        • 50% are larger then 20cm at diagnosis
      • Liposarc, MFH, and leiomyosarcomas most common
      • Radiologic assessment
        • Chest, abd and pelvic ct scan with IV/PO contrast
        • Assess for liver and lung mets
        • Assess vascular invasion
      • Tx: Complete surgical resection
        • Difficult to achieve tumor free margins
          • on the test you must get 1cm
          • in practice very hard: attempt to get grossly clear margin
        • Achievable in 40-60% of pt
        • Survival 103 mos v 18 mo with incomplete resection
        • Often involves radical extirpative procedures: bowel resection, nephrectomy, pancreatectomy
          • Gluteal tumor: abut the sciatic nerve
          • Fem nerve involvement: lose knee extension
          • Sciatic nerve involvement: lose most leg
          • Local recurrence: chemo and rad pos
      • 5 yr survival 40-50%

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