Dr Mohammad.ali Department of Orthopedics TUMOR Dr Mohammad.ali Department of Orthopedics

PATHOLOGY of NEOPLASM Abnormal mass of tissue Growth is autonomous, exceeds normal, & persist after cessation of stimuli Benign vs. Malignant Differentiation & Anaplasia Growth rate Local invasion Ability to metastasize

HISTOPATHOLOGY Anaplasia Hallmark of malignancy Pleomorphism Hyperchromatism Nuclear cytoplasmic ratio of 1:1 Abundant mitoses Tumor giant cells

MALIGNANT (SARCOMAS) are rare Differentiation of the lesion BENIGN more common MALIGNANT (SARCOMAS) are rare Differentiation of the lesion Fibrous tissue Fibrohistiocytic Adipose tissue Muscle tissue Lymph vessels Synovial tissue Peripheral nerves Cartilage and Bone Forming tissue Pluripotential Mesenchyme Blood Vessels Uncertain Histogenesis

DIAGNOSTIC CLUES Size A mass that is small (< 5 cm in its greatest dimension) is unlikely to be malignant, while a mass that is > 5 cm has at least a 20% chance of being a soft tissue sarcoma Determined by physical examination if the lesion is subcutaneous and easily palpable, or by ultrasound, CT or MRI

DIAGNOSTIC CLUES Superficial or deep? Superficial lesions are more likely to be benign and, when malignant, may have a better prognosis than deep lesions The depth is best determined by physical exam, ultrasound or MRI The thigh and buttocks are the 2 most common sites of sarcomas. Any large deep mass in the thigh or buttocks should be considered at high risk for being a malignant lesion

DIAGNOSTIC CLUES Cystic or solid Most cystic lesions are inflammatory or benign lesions, such as ganglion cysts or soft tissue abscesses If the lesion is solid, it could represent either a benign or malignant neoplasm Attempt Transillumination If deep, ultrasound or MR scan will determine this

DIAGNOSTIC CLUES Length of symptoms Rapidly increased in size over 2 months is more likely to be a sarcoma than the lesion that has slowly enlarged over a 20-year period A mass that increases and decreases in size is usually a cystic lesion Caution should be taken with masses that have been present for a long time. Soft tissue sarcomas occasionally present with a history of many years duration up to 30 years

TUMOUR WORKUP History (age, sex, site and past history) Clinical examination Thyroid Breasts Chest Liver Kidney Rectal (prostate & rectal tumors) Bloods FBC (leukaemic cells etc) & ESR (often elevated) Biochemistry (Ca++, PO4, liver enzymes and Alkaline Phosphatase) -> mets Acid Phosphatase (prostate and increased with metastatic deposits) Thyroid function tests PSA Serum Protein Electrophoresis (Myeloma)

TUMOUR WORKUP (cont) Urinalysis Urine Bence-Jones (myeloma) CXR Abdominal ultrasound Bone scan -> other sites MRI -> soft tissue extent and association with nerves and vessels CT of lesion and chest (-> staging) Angiography -> tumor blood supply and relationship to major vessels Biopsy

IMAGING OF SOFT TISSUE TUMOR Plain radiograph Soft tissue shadow, isodense with muscle Specific features Phlebolith within a hemangioma Cartilaginous juxta-articular masses in synovial osteochondromatosis Mature peripheral calcification in myositis ossificans Central calcification in extraosseous osteosarcoma Amorphous calcium deposit in tumoral calcinosis Bony involvement

IMAGING OF SOFT TISSUE TUMOR Ultrasound Rapid inexpensive test Differentiate solid from cystic Determine size Can suggest sarcoma features As many soft tissue sarcoma present as hypoechoic mass than the echogenic pattern seen in benign lesion, with exception of liposarcoma Delineate areas of distinctly solid portion of a a mass, a great help for biopsy Aid in percutaneous needle biopsy Study of vascular supply by Color Doppler

IMAGING OF SOFT TISSUE TUMOR CT scan Detecting calcification or ossification within the lesion Evaluate lung metastases CT guided needle biopsy Arteriography Less frequently used Mapping of lesions in difficult anatomy location Identifying normal anatomic variants before surgery Preoperatively, to embolize hypervascular lesions

IMAGING OF SOFT TISSUE TUMOR Bone scan Technetium Tc 99m bone scan Detects area of rapid bone turnover Sensitive but not very specific, abnormal scan should be further studied with plain radiograph, CT and MRI Part of staging

IMAGING OF SOFT TISSUE TUMOR MRI Replace role of CT and arteriography Advantages superior soft tissue contrast multiplanar imaging no ionizing radiation & the need for iodinated contrast agent no artifact problem General Roles Accurate preoperative staging Restriction of differential diagnosis Assistance with biopsy placement Monitoring response to neoadjuvant chemotherapy or radiotherapy Identification of residual or recurrent tumor during postoperative period

IMAGING OF SOFT TISSUE TUMOR MRI (cont) Conventional T1 weighted and T2 weighted T1 weighted differentiate the hyperintense fatty tissue with hypointense tumor T2 weighted with or without fat suppression is the most appropriate sequence; tumor will be hyperintense

STAGING SYSTEM Prognostic variables Histologic grade Tumor size Tumor depth Compartment status Metastases

STAGING SYSTEM SURGICAL STAGING SYSTEM (SSS) Enneking staging system American Joint Committee on Cancer (AJCC) Cancer Staging Manual 5th Edition Memorial Sloan Kettering Cancer Center (MSK)

STAGING SYSTEM SURGICAL STAGING SYSTEM (Enneking) Stage Stage Description Prognostic Factors IA Low Grade Intracompartmental G1 T1 M0 G1 Low Grade G2 High Grade T1 Intracompartmental T2 Extracompartmental M1 Any regional or systemic metastasis IB Low Grade Extracompartmental G1 T2 M0 IIA High Grade G2 T1 M0 IIB High Grade G2 T2 M0 III Any Metastases Any G, Any T, M1

Prognostic Factors Histologic Grade (assessment of biological aggressiveness) G0    Histological benign Well differentiated and low cell to matrix ratio G1    Low grade malignant Few mitoses, moderate differentiation and local spread only Have low risk of metastases G2    High grade malignancy Frequent mitoses, poorly differentiated High risk of metastases Features of aggressive tumors: Cellular atypia Frequent mitoses Extensive necrosis Significant vascularity Small amounts of immature matrix

Prognostic Factors Low Grade High Grade Myxoid Liposarcoma Lipoma-like Liposarcoma Angiomatoid Malignant Fibrous Histiocytoma Malignant Fibrous Histiocytoma Pleomorphic Liposarcoma Synovial Sarcoma Rhabdomyosarcoma

Prognostic Factors Site (anatomic setting of the lesion) T0 Intracapsular  T1 Intracompartmental (e.g. cortical bone, joint capsule or fascia) T2 Extracompartmental (spreads beyond 'fascial' plane without longitudinal containment)

Prognostic Factors Intracompartment Extracompartment Intraosseous Intraarticular Intrafascial compartments Ray of Hand or Foot Posterior or Anterior Leg Ant, Med, Post Thigh Buttocks Volar or Dorsal Forearm Ant or Post Arm Pericapsular Soft Tissue Extension Deep Fascial Extension Extrafascial Planes/Spaces (Neurovascular containing spaces) Mid & Hind Foot Mid Hand Popliteal Fossa Groin-Femoral Triangle Intra Pelvic Antecubital Fossa Axilla Paraspinal

BIOPSY OF TUMORS Simple ? Low Risk Procedure ? The planning of the biopsy is technically demanding All Biopsy carry extreme risk to patient’s limb and potentially to the patient’s life Poorly planned biopsy can affect diagnostic accuracy and result in delay in diagnosis and treatment

BIOPSY OF TUMORS Planning the biopsy Basic understanding of diseases/tumors and an ability to generate differential diagnosis The differential diagnosis determines the indications for biopsy Knowledge of appropriate placement of limb salvage incisions for resection and reconstruction Access to experienced musculoskeletal pathologist

BIOPSY OF TUMORS Type of Biopsy Closed Biopsy (Core Needle) Open Biopsy Incisional Biopsy Excisional Biopsy Primary Wide Excision

BIOPSY OF TUMORS Closed Open Accuracy of 85% Attributed to small size of biopsy leading to sampling error Insufficient for electron microscopic, immunohistochemical, and molecular genetic testing Non diagnostic needle biopsy results in delay in diagnosis and the need for subsequent formal open biopsy Accuracy of 96% Further minimizes risk of misdirected treatment and its associated morbidity

BIOPSY OF TUMORS Closed Open Less invasive Invasive Requires only LA outside formal OT Requires Formal Anesthetics Support and OT Less soft tissue contamination Needle tract contamination Inappropriate incision placement & soft tissue contamination that cannot be incorporated into a limb salvage or amputation plan Leading to increase likelihood of the need for soft tissue coverage and a higher risk for amputation Lower risk of complication Higher risk of perioperative complication; infection, haematoma and pathological # Useful in areas of difficult access, like spine and pelvis without risking significant contamination

Biopsy Technique Incisional Biopsy Excisional Biopsy Directly cutting into tumor to remove a sample without excising lesion The entire field is excised en bloc with the major tumor mass at the time of definitive resection Excisional Biopsy Removing the entire lesion at the time of biopsy Marginal excision Primary Wide Excision Entire lesion is excised while cutting through normal healthy tissue and leaving a margin of surrounding healthy tissue against the lesion

Biopsy Technique Excisional Biopsy Indication To obtain a large sample size For benign non aggressive diagnosis, is the treatment of the lesion in single stage Carry higher risk of extensive soft tissue & important structures contamination Not for lesion which is suspiciously malignant or at high risk anatomical region

Biopsy Technique Primary Wide Excision Biopsy Indication High suspicious of malignancy When the risk of contaminating major important structures with another form of biopsy outweighs the risks and functional and cosmetic deficits of excising the lesions primarily

Biopsy Procedure Longitudinal Incision Limb Salvage or Amputation incision Surgical Instrument handling Anybody fingers should not be placed directly into the wound Soiled sponges The surgical field should not be in continuity with other surgical field Tourniquet, no exsanguinations

Biopsy Procedure (cont) Direct approach, contaminating only one compartment, not through planes Hemostasis Vessels, nerves and tendons should not be exposed Blunt retractors draping Biopsies the peripheral portion with ellipse shaped cut Cultures Volume of 1 to 2 cm3 Post biopsy hemostasis Closure in layers Small bite suturing Light pressure bandaging Immobilization and protection of weight bearing

OPTION OF DEFINITIVE MANAGEMENT CLINICAL AND RADIOLOGICAL DIAGNOSIS BIOPSY OBSERVE STAGING STUDIES ELIMINATION OF PRIMARY TUMOR NON SURGERY SURGERY RADIOTHERAPY CHEMOTHERAPY GENETIC IMMUNOLOGIC PROTEIN BASED COMBINATION OF SURGERY AND NON SURGERY

PRINCIPLES OF TUMOR SURGERY INTRALESIONAL Incomplete excisions, either gross or microscopic tumor remains ( MARGIN? ) MARGINAL EXCISION Resection at border between the tumor & the immediate adjacent tissues, leaving no tumor, as verified by both gross and microscopic inspection ( SATELLITE LESION? ) WIDE EXCISION Excision through normal tissue that is not reactive or edematous, as judged by preoperative MRI, intraoperative gross inspection and microscopic sections ( SKIP LESION? ) RADICAL EXCISION Wide excision based on anatomic barriers to tumor infiltration ( METASTATIC LESION?) ? COMPLETE REMOVAL AND RECURRANCE RATE

PRINCIPLES OF TUMOR SURGERY TUMOR RESECTION STRATEGIES COMPLETE RESECTION for CURE INCOMPLETE RESECTION with CURE obtained from LOCAL ADJUVANT THERAPIES PARTIAL RESECTION without the expectation of achieving cure (DEBULKING) CURE means when no local or distant viable tumor cells remain after surgical resection Tumor debulking is to eliminate a majority of the tumor with minimum of morbidity to prolong quality of life and to reduce or eliminate pain

PRINCIPLES OF TUMOR SURGERY Meticulous attention to the isolation of clean and contaminated fields, instruments, and personnel Minimize perioperative exposure to pathogens IV antibiotic, antibiotic cement, antibiotic in irrigation medium Allograft and Prosthetic components

PRINCIPLES OF TUMOR SURGERY HIGH GRADE SARCOMA The goal is to remove as much tumor to achieve cure while removing the least amount of healthy tissue as possible to preserve function AMPUTATION versus Limb Salvage Surgery No Significant Statistical Advantage in term of Local Recurrence Following amputation 1 to 3% Following limb salvage surgery <8% Functional loss can be extreme in amputation group Revision surgery rates for complications and revisions are considerably lower for amputation group

PRINCIPLES OF TUMOR SURGERY HIGH GRADE SARCOMA Superficial sarcoma of the trunk have better prognosis than deep axially located tumor Deep axially located tumor like around the spine and pelvis Usually present late and often large by the time the diagnosis is made Do not routinely permit large volumes of normal surrounding tissue to be removed with the tumor

PRINCIPLES OF TUMOR SURGERY HIGH GRADE SARCOMA The more inflammatory, fast growing, & infiltrative the tumor, the wider the margin should be, & the more strongly preoperative radiation or chemotherapy is indicated Final consideration is the patient’s personal wishes.

PRINCIPLES OF TUMOR SURGERY LOW GRADE SARCOMA Generally treated similar to the high grade Margins are typically smaller as they show; Smaller or absent reactive zone of inflammation Limited infiltration However a wider margin of excision might be preferable it if would eliminate the need for radiation therapy Cure is achieved through a carefully planned surgical excision without adjuvant therapy

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION The second part of surgical resection Planned preoperatively Liaison with plastic surgeon Principles for Pure Soft Tissue Defect Recon Preserve Limb Viability Restore Function Achieve Skin Closure

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION Principles of Wound Closure To have the most rapid biologic reconstitution of a viable skin barrier, between the deep tissue and outside world Minimize ‘dead’ space in the deep tissue layer which can harbor bacterial inoculum Radiation and Chemotherapy impair wound healing

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION Dynamic Reconstruction Space Filling Reconstruction Skin Barrier Reconstruction

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION Dynamic Reconstruction Dynamic function include stability, power, blood transport or nerve conduction Refers to the implant or transfer of tissues Ligaments deficit in knee replaced with autograft, allograft or artificial replacement Vessels Reconstruction to restore blood flow Nerve Grafting for protective sensation and motor function Tendon or Muscle Transfer restore lost motor power

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION Space Filling Reconstruction To fills defects created by surgery Not to restore function but to relieve tension on the wound, obliterate dead space and place healthy tissue in areas that will promote rapid healing and reduce infection risk Muscle or Myocutaneous Local, Free and Vascularized Flap

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION Skin Barrier Reconstruction Precise wound closure is critical Wound breakdown can result in deep infection & subsequent limb loss, might prevent or delay the use of chemotherapy or local radiation therapy Skin and subcutaneous fascial layer should be closed in layers, with precise matching of the anatomic layers Non braided suture & short tail to minimize foreign body Small skin staplers with Antibiotic Ointment applied Early & often changing of dressing If skin closure with minimal tension cannot be achieved SSG of flap

PRINCIPLES OF TUMOR SURGERY DEFECT RECONSTRUCTION Surgical drains Eliminate dead space-preventing accumulating of fluid pockets Divert drainage from the skin incision Prevent formation and spread of haematoma along fascial planes-might carry tumor cells Drain tracks Should not traversed uninvolved anatomic areas Should exit the skin in line with the incision Critical drains can be sutured to skin but keep the suture sites close by for easy excision with drain track if needed

PRINCIPLES OF TUMOR SURGERY INTRAOPERATIVE ADJUVANT THERAPIES Tumor killing potential H2O2 - tumoricidal ability Thermal kill Tissue Heating with diathermy, heat gun, cryosurgery using liquid nitrogen Produce necrosis of 1 to 10mm Lasers Intraoperative Radiation Advantage; Precise & Direct to tumor bed, & not associated with wound healing difficulty seen with preop, high dose radiation therapy Brachytherapy Deliver local radiation through catheters implanted surgically after tumor excision

PRINCIPLES OF TUMOR SURGERY THE YOUNG CHILD Remarkable adaptive capabilities to anatomic loss either by tumor itself or amputation Preserving epiphyses through very closed resection margins a few mm away from metaphyseal tumor If the child survive from the sarcoma, the extremely long life span ahead raises the lifetime risk of developing Secondary radiation induced sarcomas and other radiation associated morbidities Secondary chemotherapy induced cancers

PRINCIPLES OF TUMOR SURGERY THE VERY OLD Most common; malignant fibrous histiocytoma Problem; less cardiac reserve and overall poorer physiologic function Adjuvant chemotherapy and high dose radiation therapy will cause more risk than benefit More radical resection with much wider margin Senile and Demented Patients, Medical disease which complicate wound healing Aim for NO TREATMENT or PALLIATIVE

PRINCIPLES OF TUMOR SURGERY METASTATIC SARCOMA AT PRESENTATION Poor prognosis Survival depends on removal of primary tumor & eradication of metastatic disease through either surgical or chemotherapeutic modalities or combination of both CHEMOTHERAPY IS ESSENTIAL to eliminate the micrometastases Any surgical complication that can delay or prevent perioperative chemotherapy must be avoided Limb salvage has NO ROLE

PRINCIPLES OF TUMOR SURGERY ‘UNRESECTABLE’ TUMOR Tumor involves major vessels, nerves or other critical structures Means unacceptable morbidity Truly unresectable situation is death as result. In cases with unacceptable morbidity like resection of tumor including the sciatic nerve, producing insensate lower limb Amputation is better choice OR Limb Salvage surgery with the idea of tiring and skill demanding nerve grafting or reconstruction, in mind OR if complication arises, amputation at a very high level is unavoidable Excellent candidate for preoperative chemotherapy, radiation therapy or more aggressive techniques like isolated limb perfusion to gain tumor size regression.

PRINCIPLES OF CHEMOTHERAPY Action of Chemo Agents Damage DNA Alkylating agents, platinum compounds, anthracyclines, epipodophyllotoxins Deplete the cellular building blocks required for replication Antifolates, 5-fluoropyrimidines, cytidine analogs Interfere with microtubule function required for mitosis Vinca alkaloids, taxanes

PRINCIPLES OF CHEMOTHERAPY Chemo Agents are cytotoxic to tumor cells through induction of apoptosis Selectivity is due to the fact that rapidly dividing tumor did not have sufficient time to repair the chemotherapy induced damage Combination chemotherapy Antitumor effect will be cumulative whereas the toxicity will not Avoid resistant Effective for different phases of cell cycle

PRINCIPLES OF CHEMOTHERAPY Indication Induction chemotherapy (Neoadjuvant or Preoperative) Decrease tumor size In tumor that are capable of metastases (Standard of care for osteosarcoma and Ewing’s sarcoma) Malignant musculoskeletal tumor with systemic metastases Chemosensitive neoplasm Osteosarcoma Ewing’s sarcoma Rhabdomyosarcoma Synovial sarcoma Malignant Fibrous Histiocytoma For chemosensitive benign tumors which is multiply recurrent or impinge on vital structures

PRINCIPLES OF CHEMOTHERAPY Chemoresistant tumors Gastrointestinal stromal tumors Chondrosarcoma Alveolar soft part sarcoma

PRINCIPLES OF CHEMOTHERAPY Side Effects Stunting of growth Osteoporosis AVN Cisplatinum -> Nephrotoxicity and hearing loss Adriamycin -> Cardiotoxicity Vincristine -> Neurotoxicity Chemotherapeutic induced malignancy usually blood forming eg leukaemias but also may -> Ca bladder or skin (particularly associated with cyclophosphamide)

PRINCIPLES OF RADIOTHERAPY Radioactive focused local treatment Using high energy photon beam produced by a linear accelerator Others; gamma rays, electron beams, radiation from brachytherapy, beams from heavy particle like protons and neutrons Mechanism of action Oxygenation of water molecules within the cells, producing free radicals that interact with DNA to cause strand break, eventually results in cell death

PRINCIPLES OF RADIOTHERAPY Radiation units Grays (Gy), a unit of absorbed dose (1Gy=1J/kg) In the past; rads 1 rad = 1 centigray (cGy) or 1/100 of a Gy Radiotherapy is delivered in small doses or fractions over many days Allows a large total dose of radiation to be delivered without exceeding the tolerance levels of surrounding normal tissue Standard fractionation; 180 to 200 cGy daily, 5 days per week

PRINCIPLES OF RADIOTHERAPY Indication in soft tissue sarcoma Radiosensitive sarcoma, theoretically, well oxygenated tumors Rhabdomyosarcoma PNET (extraosseous Ewing’s sarcoma) (definitive primary radiotherapy local control rate for the above type of tumor is 80%) (mandatory treatment for all patient) Other unresectable soft tissue tumor local control rate is in the range of 25 to 30% Current standard for high grade resectable extremity soft tissue sarcomas is limb salvage surgery, when possible, in conjunction with radiotherapy

PRINCIPLES OF RADIOTHERAPY Indication in soft tissue sarcoma Postoperative radiotherapy Decrease risk of local relapse for both high grade and certain high risk low grade sarcoma. For low grade sarcoma, consider if having microscopic positive margin or of large tumor size (>5cm) Preoperative radiotherapy Shrink tumor size Decrease risk of tumor contamination Intact well oxygenated tumor respond better than hypoxic tumor bed Disadvantages Delay in surgery Possible wound healing complication Less information on tumor extent and pathology

PRINCIPLES OF RADIOTHERAPY Indication in soft tissue sarcoma Brachytherapy Insertion of radiation sources into tissues after tumor resection before closure Radioactive source (usually cesium or iodine) placed inside the catheters on post op D5 Excellent postoperative treatment for extremity soft tissue sarcoma (adjuvant brachytherapy local control rate for high grade lesion is 89%) Intraoperative Radiotherapy Electron or orthovoltage beam 74% local control rate for primary retroperitoneal sarcomas when combined with external beam radiotherapy

PRINCIPLES OF RADIOTHERAPY Timing of radiotherapy Definitive radiotherapy for rhabdomyosarcoma and Ewing’s sarcoma is generally integrated into the middle of a chemotherapy program Postoperatively, as soon as adequate wound healing is achieved, usually 3 to 6 weeks

PRINCIPLES OF RADIOTHERAPY Side Effects Acute side effects depend on the total dose of radiation and overall treatment time Late side effects depend on fraction size

PRINCIPLES OF RADIOTHERAPY Acute Side Effects begins after first 2 weeks and increase as the treatment continues Most common is fatigue Majority develop erythema, and temporary desquamation Uncommon; wound dehiscence, suppresses blood counts and other complications pertaining to anatomic site involved At least one clinic visit per week to see radiation oncologist to assess and manage potential side effects

PRINCIPLES OF RADIOTHERAPY Late Side Effects Months to years after receiving radiotherapy Muscle fibrosis; stretching exercise Weaken Bones and cause Joint Dysfunction Edema distal to irradiated site; full circumference of limb should never be treated to a high dose More then 20 years after radiation Secondary malignancy esp. in children Rate of secondary bone cancer after radiation treatment for all childhood cancers was less than 1% For those treated for Ewing’s sarcoma, the risk was 5.4% Others; bone growth arrest and iatrogenic scoliosis in children

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