Soft Tissue Sarcoma I: Evaluation

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1 GENERAL SURGERY BOARD REVIEW MANUAL PUBLISHING STAFF PRESIDENT, PUBLISHER Bruce M.White EXECUTIVE EDITOR Debra Dreger SENIOR EDITOR Miranda J. Hughes, PhD ASSISTANT EDITOR Melissa Frederick EDITORIAL ASSISTANT Rita E. Gould SPECIAL PROGRAMS DIRECTOR Barbara T.White, MBA PRODUCTION DIRECTOR Suzanne S. Banish PRODUCTION ASSISTANTS Tish Berchtold Klus Christie Grams Mary Beth Cunney Soft Tissue Sarcoma I: Evaluation Series Editor and Author: Christopher R. McHenry, MD, FACS, FACE Director, Division of Surgery MetroHealth Medical Center Associate Professor of Surgery Case Western Reserve University, Cleveland, OH Contributing Author: Bruce J. Averbook, MD, FACS Assistant Professor, General Surgery and Surgical Oncology MetroHealth Medical Center/Case Western Reserve University Cleveland, OH Table of Contents ADVERTISING/PROJECT MANAGER Patricia Payne Castle Preface ii Introduction NOTE FROM THE PUBLISHER: Etiology This publication has been developed without involvement of or review by the American Soft Tissue Sarcoma of the Extremity Board of Surgery. Pathologic Evaluation and Staging Endorsed by the Diagnostic Workup Association for Hospital Medical Summary Education The Association for Hospital Medical Education References endorses HOSPITAL PHYSICIAN for the purpose of presenting the latest developments in medical education as they affect residency programs and clinical hospital practice. Cover Illustration by Scott M. Holladay Copyright 2000, Turner White Communications, Inc., 125 Strafford Avenue, Suite 220, Wayne, PA , All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of Turner White Communications, Inc. The editors are solely responsible for selecting content. Although great care is taken to ensure accuracy, Turner White Communications, Inc. will not be liable for any errors of omission or inaccuracies in this publication. Opinions expressed are those of the authors and do not necessarily reflect those of Turner White Communications, Inc. General Surgery Volume 6, Part 1 i

2 GENERAL SURGERY BOARD REVIEW MANUAL Preface Hospital Physician s General Surgery Board Review Manual is a study guide intended to help candidates prepare for the written board certification examination. The manual consists of 4 publications focusing on selected topics. Space will not permit an exhaustive review; however, Volume 6 targets several of the more commonly encountered conditions or topics in general surgery. Included in this list are: Part 1 Soft Tissue Sarcoma I: Evaluation Part 2 Soft Tissue Sarcoma II: Management Part 3 Management of Gallstones Part 4 The Parathyroid Glands and Hyperparathyroidism Board examination candidates will find this manual to be a concise review of some of the essential and wellrecognized aspects of these topics. Each manual includes a case study that highlights the clinical presentation, diagnostic evaluation, treatment, and follow-up of a representative patient. The case-based format presents the information in a logical fashion, including important elements of the history and physical examination, etiology, diagnosis, and management. This manual has been developed without the involvement of or review by the American Board of Surgery. It is based on the Series Editor s and Contributing Authors clinical experience, awareness of new developments in the field of general surgery, and knowledge of basic components of education contained in our residency training program. This board review manual program is not comprehensive and should be viewed as a supplement to other preparatory material for board certification. The Editors wish all candidates success on the examination. Christopher R. McHenry, MD, FACS, FACE Director, Division of Surgery MetroHealth Medical Center Associate Professor of Surgery Case Western Reserve University Cleveland, OH ii Hospital Physician Board Review Manual

3 GENERAL SURGERY BOARD REVIEW MANUAL Soft Tissue Sarcoma I: Evaluation Series Editor and Author: Christopher R. McHenry, MD, FACS, FACE Director, Division of Surgery MetroHealth Medical Center Associate Professor of Surgery Case Western Reserve University Cleveland, OH I. INTRODUCTION Contributing Author: Bruce J. Averbook, MD, FACS Assistant Professor General Surgery and Surgical Oncology MetroHealth Medical Center Case Western Reserve University Cleveland, OH Soft tissue sarcoma (STS) is a malignant tumor that develops from connective tissue. Approximately 6000 new cases of STS are reported per year in the United States. More than 50% of patients with STS will die as a result of their tumor. Although sarcomas can arise in any anatomic site, about 50% of STSs occur in the extremities, 35% in the lower extremity and 15% in the upper extremity 1 (Figure 1). The other major areas affected are the viscera, retroperitoneum, and trunk. In general, the keys to improved survival and limitation of morbidity in patients with STS are early recognition, diagnosis, and precise surgical treatment. The principles of management are based on tumor location, stage, and behavior. Combination surgery and radiation are used for limb and corporeal preservation to limit morbidity and optimize patient survival. Chemotherapy has had limited success and is used for treatment of metastatic disease or as part of a clinical trial. This article is the first half (Part 1) of a review on STS. Part 1 of this review ( Soft Tissue Sarcoma I: Evaluation ) focuses on etiology, pathology, and staging of sarcoma and describes how to initiate evaluation of patients with a soft tissue mass. A case patient is also presented to highlight features of managing STS. Part 2 will describe the basic concepts involved in managing patients with STS, including surgical resection, limb-sparing surgery, adjuvant therapy, and follow-up; diagnosis and management of retroperitoneal sarcomas are also discussed. This review is not intended to be comprehensive; additional articles are provided in the reference section. II. ETIOLOGY The cause of STS is unknown. However, genetic mutations in mesenchymal stem cells may predispose these cells to develop malignant clones. The alteration in p53 and RB-1 has been seen in several sarcomas. 2,3 A genetic predisposition to STS has been seen in patients with neurofibromatosis (von Recklinghausen s disease), 4,5 Li-Fraumeni syndrome, 6,7 retinoblastoma, and familial polyposis coli. 8 Cell mutations can result from ionizing radiation. Since 1922, osteogenic sarcoma has been known to result from radiation exposure. 9 Moreover, an increased incidence of malignant fibrous histiocytoma, angiosarcoma, and lymphangiosarcoma appear to occur after external-beam radiation used in cancer treatment. 10 Chemical exposure has also been reported as a potential causal factor in STS. The chemical agents implicated include vinyl chloride, arsenic, chlorophenols, and phenoxyacetic acids. The role of dioxin (Agent Orange) and pesticides in the development of STS remains unclear. 1 General Surgery Volume 6, Part 1 1

4 Lower extremity, 35% 950 Other, 11% Trunk, 10% Upper extremity, 15% Retro/IA, 14% Viscera, 15% Figure 1. Distribution by site of soft tissue sarcomas in 2678 patients aged 16 years and older admitted to Memorial Sloan- Kettering Cancer Center between July 1982 and July Numbers within the chart refer to the number of patients. IA = intra-abdominal; retro = retroperitoneum. Adapted with permission from Brennan MF: The surgeon as a leader in cancer care: lessons learned from the study of soft tissue sarcoma. J Am Coll Surg 1996;182:520. Another known predisposing factor in the development of STS is lymphedema. Lymphangiosarcoma has been well documented in patients who have lymphedema that develops after mastectomy (labeled the Stuart- Treves syndrome). 11 Although most of these patients have been treated with radiation, lymphangiosarcoma is not believed to be induced by radiation because most lymphangiosarcomas develop outside the irradiated field. Trauma does not have a role in the development of STS. However, a patient may first notice a mass after a minor injury, and, as a result, the mass may be attributed to trauma. Unfortunately, the history of trauma can mislead the physician who does not maintain a high index of suspicion, which may lead to inadequate patient follow-up. III. SOFT TISSUE SARCOMA OF THE EXTREMITY CASE PATIENT 1 Presentation Patient 1 is a 72-year-old man referred for evaluation of a large mass in his right thigh, which has been present for about 4 months and is growing. He has no symptoms related to the mass. He denies a history of previous trauma and has no pain, weakness, or sensory loss of his right lower extremity. His medical history reveals insulin-dependent diabetes mellitus, a seizure disorder, chronic obstructive pulmonary disease, psoriasis, and asbestos exposure. He has no history of radiation treatments to his leg and no previous surgeries. Physical examination of patient 1 reveals a cm firm mass involving the anterior surface of the right thigh, extending from just below the inguinal crease to about 10 cm above his patella. There is no associated erythema, tenderness, or inguinal lymphadenopathy. Patient 1 has a normal femoral pulse with no other palpable distal pulses and a normal triphasic Doppler signal of his popliteal, dorsalis pedis, and posterior tibial vessels. He has some asymmetric weakness of his hip flexors on the right. The rest of patient 1 s neuromuscular examination is unremarkable. Workup and Surgery Patient 1 s workup consists of a computed tomographic (CT) scan of the right thigh, which demonstrates a large heterogeneous mass in the anterior fascial compartment of the thigh involving the rectus femoris muscle (Figure 2). The tissue planes around the rectus femoris muscle appear intact with no obvious involvement of surrounding structures. The osseous structures are also intact with no focal abnormalities. The mass does not appear to involve the neurovascular structures of the thigh. Chest radiographs and CT scans of the chest reveal no lung metastases. An incisional biopsy is performed through a vertical incision in the right thigh directly over the palpable mass. The biopsy results show a malignant, fibrous histiocytoma of intermediate grade. Patient 1 undergoes a wide local excision of the mass. Pathologic findings confirm the mass is a malignant fibrous histiocytoma of intermediate grade with a very close deep margin of 0.1 cm. All other margins are free of tumor. Is patient 1 at high risk of recurrence of STS? Initially, what treatment should patient 1 receive? Treatment Patient 1 is at a high risk of recurrence because of the large size and intermediate grade of his tumor. As a result, he should receive external-beam radiation treatment to his right thigh and pelvis. Patient 1 receives external-beam radiation in 25 fractions, for a total dose of 5000 cgy. The radiation treatment has rendered him disease-free 1 year after his surgery. 2 Hospital Physician Board Review Manual

5 Figure 2. Spiral computed tomographic scan of the right thigh of patient 1, demonstrating a large soft tissue mass (arrows) in the rectus femoris muscle. IV. PATHOLOGIC EVALUATION AND STAGING PATHOLOGIC EVALUATION The 3 most common histopathologic subtypes of STS are liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma (MFH) (Figure 3). 1 The most common sarcomas of the extremity are liposarcoma, MFH, fibrosarcoma, and tenosynovial sarcoma. 1 Some sarcomas occur more frequently in certain age groups: fibrosarcoma occurs in patients between 20 and 39 years, MFH in those between 50 and 69 years, and leiomyosarcoma between 40 and 49 and between 60 and 69 years. Liposarcoma is less prevalent in people younger than 30 years and occurs most frequently in those between 50 and 65 years. Extremity sarcoma most frequently metastasizes to lung. (Figure 4). 12 Liposarcomas and leiomyosarcomas account for most retroperitoneal sarcomas. About 50% of all sarcomas occur in children. The most common pediatric sarcomas are small cell sarcomas, including Ewing s sarcoma and embryonal rhabdomyosarcoma. Ewing s sarcoma is part of a spectrum of histopathologic tumors known as primitive neuroectodermal tumors (PNET, small round blue cell tumors). 1 In general, STSs tend to have similar clinical behaviors and natural histories regardless of histologic subtype. However, a few histologic types of STS are highlighted in this review to emphasize specific differences in clinical behavior that affect treatment or follow-up. For example, only about 5% of patients with STS develop lymph node metastases. However, 13% to 17% of patients with rhabdomyosarcoma, epithelioid sarcoma, and synovial cell sarcomas have lymph node metastases. As a result, the lymphatic basins need to be carefully scrutinized in patients with these sarcomas. The differential diagnosis of a soft tissue mass includes various benign and malignant lesions (Table 1). The practitioner should also be aware of unusual presentations of metastatic tumors, melanoma, and lymphoma, which can masquerade as sarcoma. STAGING A comprehensive knowledge of the staging of sarcomas is essential for understanding treatment recommendations and for predicting prognosis (Table 2). 13 The new staging system for sarcomas defined in the fifth edition of the American Joint Committee on Cancer Staging Manual is based on the primary features that affect recurrence and survival. These features are tumor size (T1 5 cm; T2 > 5 cm) and depth (superficial or deep), nodal status (if positive, patient is stage IV), distant metastasis, and histopathologic grade. This is the only American Joint Committee on Cancer General Surgery Volume 6, Part 1 3

6 300 Liposarcoma Leiomyosarcoma MFH Synovial Fibro MPNT Patients, n Lower extremity Upper extremity Retro/IA Viscera Trunk Figure 3. Histopathologic subtypes and location of soft tissue sarcomas in 2678 patients, aged 16 years and older, admitted to Memorial Sloan-Kettering Cancer Center between July 1982 and July Fibro = fibrosarcoma; IA = intra-abdominal; MFH = malignant fibrous histiocytoma; MPNT = malignant peripheral nerve sheath tumor; retro = retroperitoneum. Adapted with permission from Brennan MF, Casper ES, Harrison LB: Soft tissue sarcoma. In Cancer: Principles and Practice of Oncology, 5th ed. DeVita VT Jr, Hellman S, Rosenberg SA, eds. Philadelphia: Lippincott-Raven, 1997:1745. Metastasis, % 100 Lung Liver Other Extremity Viscera Retroperitoneum Figure 4. Primary sites of soft tissue sarcoma (ie, extremity, viscera, and retroperitoneum) correlated with their most common site of metastasis (ie, lung, liver, and other sites) from Memorial Sloan- Kettering Cancer Center, Adapted with permission from Brennan MF:The surgeon as a leader in cancer care: lessons learned from the study of soft tissue sarcoma. J Am Coll Surg 1996;182:520. (AJCC) staging system that incorporates grade. Histologic analysis of grade looks at several features, including mitoses per high-power field and degree of necrosis. Most sarcomas spread hematogenously and not through the lymphatics. As noted in this staging system, depth is an independent prognostic variable and has been validated by studies with large numbers of patients A superficial extremity lesion has no involvement of the superficial investing muscular fascia. A deep extremity lesion is deep to or invasive into the superficial (investing) fascia. This category includes all intraperitoneal visceral lesions or lesions with major vessel invasion, intrathoracic lesions, and most head and neck tumors. 13 The tumor grade is very important both for prognosis and treatment planning (see Section V. Biopsy). The 5-year rates for freedom from local recurrence, disease-free survival, and overall survival are shown in Table 3. The Kaplan-Meier curve in Figure 5 demonstrates the relation between survival and clinical stage of STS for a 12-year period. Both Table 3 and Figure 5 show that patients with STS who have low-grade stage I tumors 4 Hospital Physician Board Review Manual

7 Table 1. Abbreviated Classification of Soft Tissue Tumors Histologic Tumor Category Benign Malignant Fibrous Nodular fasciitis, fibroma Fibrosarcoma Fibrohistiocytic Fibrous histiocytoma, xanthoma Malignant fibrous histiocytoma Lipomatous Lipoma Liposarcoma Smooth muscle Leiomyoma Leiomyosarcoma Skeletal muscle Rhabdomyoma Rhabdomyosarcoma Vascular, lymphatic Hemangioma Angiosarcoma, lymphangiosarcoma, Kaposi s sarcoma Perivascular Glomus tumors Malignant glomus tumor, hemangiopericytomas Mesothelial Multicystic mesothelioma Diffuse mesothelioma Synovial Nodular tenosynovitis Synovial sarcoma, malignant giant cell tumors of tendon sheaths Neural Schwannoma, neurofibroma Malignant schwannoma, neurofibrosarcoma, PNET Paraganglionic Paraganglioma Malignant paraganglioma Extraskeletal cartilaginous, osseous Myositis ossificans Chondrosarcoma, osteosarcoma Pluripotential mesenchymal tumor Mesenchyma Malignant mesenchymoma Miscellaneous Myxoma Alveolar soft part, epithelioid PNET = primitive neuroectodermal tumor. Data from DeVita VT, Hellman S, Rosenberg SE, eds. Cancer: Principles and Practice of Oncology, 5th ed. Philadelphia: Lippincott-Raven, 1997: have a better prognosis and overall long-term survival rate than those with stages II or III tumors. Note that this staging system does not include consideration of the following tumors: Kaposi s sarcoma, dermatofibrosarcoma (protuberans), fibrosarcoma grade I (desmoid tumor), and sarcoma arising from the dura mater, brain, parenchymatous organs, or hollow viscera. 13 V. DIAGNOSTIC WORKUP SIZE An STS is usually large and painless. At presentation, approximately 33% of sarcomas are smaller than 5 cm, 33% are between 5 and 10 cm, and 33% are larger than 10 cm. 1 DIFFERENTIAL DIAGNOSIS A sarcoma should be considered in the differential diagnosis for a patient who presents with a soft tissue mass. The first major clinical concern is to discern whether the lesion is benign or malignant. The second concern is to determine whether surrounding neurovascular structures or bone is involved. This knowledge helps the surgeon to determine whether en bloc resection with limb salvage is possible. Frequently, the physician elicits a history of trauma associated with the onset of a new mass. In general, to exclude the possibility of malignancy, the physician should always follow up a patient who has a soft tissue mass associated with trauma. If the mass has not resolved, an appropriate diagnostic workup is necessary. STS must be differentiated from a lipoma, the most common soft tissue tumor. It can be difficult to differentiate a sarcoma from myositis ossificans, which manifests as a calcified mass in a patient with a history of trauma. Core biopsy or open biopsy of myositis ossificans may lead to substantial hemorrhage. Other lesions that can be difficult to differentiate from STS are the angiomyolipomas, atypical schwannomas, and the angiomyxomas. The pathologist makes the definitive diagnosis. IMAGING CT or magnetic resonance imaging (MRI) is useful for evaluating patients with STS. Radiographic imaging studies of the primary lesion should be done before biopsy of suspicious tumors. If biopsy or resection has already been completed, radiographic imaging should still be performed to evaluate the surgical site and establish a baseline. The purpose of obtaining a CT or MRI is to determine the anatomic extent of the tumor and to determine whether the tumor has invaded neurovascular General Surgery Volume 6, Part 1 5

8 Table 2. Cancer Stage Grouping Stage Histopathologic Grade TNM Status Stage I A (low grade, small, superficial, deep) G1 2 T1a 1b N0 M0 B (low grade, large, superficial) G1 2 T2a N0 M0 Stage II A (low grade, large, deep) G1 2 T2b N0 M0 B (high grade, small, superficial, deep) G3 4 T1a 1b N0 M0 C (high grade, large, superficial) G3 4 T2a N0 M0 Stage III (high grade, large, deep) G3 4 T2b N0 M0 Stage IV (any metastasis) Any G Any T N1 M0 Any G Any T N0 M1 TNM Definitions Primary Tumor (T) Regional Lymph Nodes (N) Distant Metastasis (M) TX = Primary tumor cannot be assessed NX = Regional lymph nodes cannot MX = Distant metastasis cannot be assessed be assessed T0 = No evidence of primary tumor N0 = No regional lymph node metastasis M0 = No distant metastasis T1 = Tumor 5 cm greatest dimension N1 = Regional lymph node metastasis M1 = Distant metastasis T2 = Tumor > 5 cm in greatest dimension Histopathologic Grade (G) Definitions GX = Grade cannot be assessed G1 = Well differentiated G2 = Moderately differentiated G3 = Poorly differentiated G4 = Undifferentiated a = superficial tumor; b = deep tumor; TNM = primary tumor, regional lymph node, distant metastasis. Data from American Joint Committee on Cancer: Soft tissue sarcoma. In AJCC Cancer Staging Manual, 5th ed. Philadelphia: Lippincott-Raven, 1997:152. structures or bone findings that may alter the surgical strategy. The rationale for obtaining an imaging study before biopsy is to evaluate the soft tissue mass with the least amount of soft tissue distortion and to aid the surgeon in determining the optional site for biopsy. An area that appears necrotic on CT or MRI should be avoided as a site for biopsy. Displaced neurovascular structures, which are demonstrated radiographically, may also be avoided. MRI may provide better tumor definition as well as better definition of tissue planes compared with CT. 23 Some clinicians have reported limited or no benefit of MRI over CT. 24 Thus, there is no consensus on what constitutes the best imaging study. Brennan and colleagues 1 suggest that the best imaging studies vary according to the site of the STS. CT may be preferable for evaluation of intra-abdominal STS because of better evaluation of primary tumor and potential metastases. 1 In general, angiography is unnecessary, but occasionally it may be required as part of a research protocol or, in rare cases, may be helpful in determining vascular involvement and tumor resectability. BIOPSY The next step in the diagnostic workup is to biopsy the soft tissue mass and to determine the histology. In a patient with sarcoma, an adequate tissue specimen is necessary for determination of both the histologic type and grade. The tumor grade is important for proper staging and treatment of STS and for determining the prognosis of the patient. Tumor grade influences decisions regarding the use of adjuvant and experimental treatments. Debate on the efficacy of the various methods of biopsy 6 Hospital Physician Board Review Manual

9 Table 3. Five-Year Survival Rates by Stage for Soft Tissue Sarcomas Freedom Diseasefrom Local Free Overall Stage Recurrence, % Survival, % Survival, % I* II III *Low grade < 5 cm deep, or low grade > 5 cm superficial. Low grade > 5 cm deep, high grade < 5 cm, or high grade > 5 cm superficial. High grade > 5 cm deep. Used with permission from the American Joint Committee on Cancer (AJCC), Chicago (IL). Soft tissue sarcoma. In: AJCC Cancer Staging Manual, 5th ed. Philadelphia: Lippincott-Raven; 1997:152. of STS still exists (Table 4); however, an incisional biopsy remains the gold standard. The incisional biopsy should be performed with meticulous hemostasis because, in theory, this prevents hematogenous spread. Poor hemostasis may also delay definitive treatment. An improper biopsy may contaminate surrounding tissue, mandating more extensive definitive surgical resection, increasing the necessity of more complex soft tissue wound closure, and potentially increasing the radiation field. On an extremity, the incision should be made longitudinally over the mass to allow for subsequent definitive en bloc resection and primary wound closure. The use of drains should be avoided. If a drain is deemed necessary, placement should be close to the incision so that the tract is easily excised at the time of definitive surgery. Only closed suction drains should be used. The biopsy site should be excised at the time of definitive resection to avoid leaving tumor behind that may result from potential tumor seeding during biopsy. Excisional biopsy for lesions less than 3 cm in diameter is an acceptable means of establishing a diagnosis; 25 some experts note that this is also acceptable for lesions smaller than 5 cm. 1,26 Fresh biopsy tissue should be sent to pathology to allow assessment for adequate sample (ie, to ensure viable tumor is present) and to enable the pathologist to perform special studies (eg, electron microscopy) as required. Several studies have examined the use of core needle biopsy (Tru-Cut) in the diagnosis of soft tissue masses Table 4 shows data from Memorial Sloan-Kettering Cancer Center (MSKCC) comparing the accuracy of Tru-Cut needle biopsy with that of incisional biopsy. In Proportion of Patients Surviving Low grade < 5 cm (stage I) Low grade > 5 cm deep (stage II) High grade > 5 cm deep (stage III) Time from Admission, mo Figure 5. Kaplan-Meier survival curves for patients with soft tissue sarcoma, showing probability of overall survival by grade. From Memorial Sloan-Kettering Cancer Center, Used with permission from the American Joint Committee on Cancer (AJCC), Chicago (IL). Soft tissue sarcoma. In: AJCC Cancer Staging Manual, 5th ed. Philadelphia: Lippincott-Raven; 1997:153. this study, Tru-Cut biopsy and incisional biopsy results were not statistically different. However, incisional biopsy is considered to be the gold standard and to be the most accurate. Core needle biopsy has pitfalls including sampling error and bleeding. Of note, liposarcoma is not as easily amenable to core biopsy. 27 An important consideration in using core needle biopsy is that an experienced pathologist needs to evaluate the specimen. The pathologist should have specialized techniques available, such as immunohistochemistry and electron microscopy. Enough viable and representative tissue should be obtained. In some centers where the extent of necrosis is used as an important contribution to the grade of the sarcoma, core biopsy may not yield representative tissue. 30 The surgeon should have experience in performing core biopsies and should take precautions during the procedure to limit bleeding and possible tumor spread by not violating larger areas of normal tissue than required. The site should be dressed with an Ace wrap and compression held to avoid bleeding. Fine-needle aspiration (FNA) is primarily valuable for confirming whether recurrence has occurred. It is not recommended for initial diagnosis because FNA does not provide adequate tissue to determine the histologic subtype and grade of the sarcoma. FNA can also miss the diagnosis. Despite arguments to the contrary, FNA is not known to decrease the spread of tumor compared with well-performed biopsy. 27,31 33 Adequate tissue diagnosis General Surgery Volume 6, Part 1 7

10 Table 4. Accuracy of Core Needle (Tru-Cut) Biopsy at Memorial Sloan-Kettering Cancer Center, Accurate Accurate Accurate Biopsy Number Adequate, % Malignancy, % Grade, % Histology, % Tru-Cut Incisional Frozen section* *Because of its inaccuracy, frozen-section biopsy should not be used for the diagnosis of sarcoma. Significant by Fisher s exact test at P < 0.05 when compared with Tru-Cut. Adapted with permission from Heslin M, Lewis J, Woodruff J, Brennan MF: Tru-Cut biopsy is accurate for the extremity mass suspicious for soft tissue sarcoma [Abstract]. Society of Surgical Oncology, March is important for use in institutions testing different modalities of experimental neoadjuvant treatment. Many of these studies for sarcoma are based on grade and type of initial biopsy. Such ongoing programs include analyses of external-beam radiation, brachytherapy, intra-arterial chemotherapy, and systemic chemotherapy. 1,34 Because of its inaccuracy, frozen-section biopsy should not be used for the diagnosis of sarcoma. Frozen section is especially poor in determining the histologic subtype and grade of sarcoma 1 (Table 4). However, frozen section can be used to assess biopsy sample adequacy for pathologic diagnosis. Frozen section may be useful in cases of re-resection, in which clear margins are in question, and may be helpful for assessing the margins of resection in difficult cases. Margin samples should be taken from identifiable areas in the resection bed, labeled, and sent separately for review by the pathologist. VI. SUMMARY Part 1 of this review article has focused on extremity sarcoma but has also discussed how to evaluate patients with a soft tissue mass. Part 2 of this review will discuss how to treat and manage patients with STS and will include diagnosis and management of retroperitoneal sarcoma. STS can arise anywhere. The clinician must have a high index of suspicion to initiate the appropriate workup for soft tissue masses. This workup is especially important to prevent completely missing the diagnosis, which can affect long-term survival and morbidity. In addition, appropriate workup of suspicious tumors larger than 3 to 5 cm is especially important to prevent local tumor contamination of tissue and to avoid hematogenous spread. Pathologic diagnosis depends on obtaining adequate biopsy tissue. Diagnosis by frozen section is unacceptable. Pathologic grading contributes significantly to staging, prognosis, and treatment (as will be discussed in Part 2). In extremity sarcomas, depth is an independent prognostic factor. Retroperitoneal sarcomas are all considered deep and, therefore, depth is ignored as part of their TNM staging. In general, STSs have similar clinical behaviors and spread hematogenously with few exceptions. Extremity sarcomas tend to metastasize to the lungs; retroperitoneal sarcomas metastasize to the lungs and the liver, and true visceral sarcomas metastasize with greater frequency to the liver. A patient is deemed as having stage IV disease if tumor has spread to the lymph nodes. Proper imaging and biopsy of the soft tissue mass are important. CT, MRI, or both are important to assess resectability and to establish a baseline for later followup. Once a diagnosis of STS is made, a CT of the chest is indicated to assure no pulmonary metastases are present and to establish a baseline for future comparison studies. The gold standard for biopsy of sarcomas is an incisional biopsy with the incision oriented longitudinally over the mass. Core biopsies are only acceptable in centers with specific experience. Attention to hemostasis is important in both settings. FNA is not indicated in diagnosis of primary lesions. Retroperitoneal sarcomas should not be biopsied; they should be resected en bloc with adjacent structures or organs, which will be further discussed in Part 2. REFERENCES 1. Brennan MF, Casper ES, Harrison LB: Soft tissue sarcoma. In Cancer: Principles and Practice of Oncology, 5th ed. DeVita VT Jr, Hellman S, Rosenberg SA, eds. Philadelphia: 8 Hospital Physician Board Review Manual

11 Lippincott-Raven, 1997: Latres E, Drobnjak M, Pollack D, et al: Chromosome 17 abnormalities and TP53 mutations in adult soft tissue sarcomas. Am J Pathol 1994;145: Cance WG, Brennan MF, Dudas ME, et al: Altered expression of the retinoblastoma gene product in human sarcomas. N Engl J Med 1990;323: D Agostino AN, Soule EH, Miller RH: Sarcomas of the peripheral nerves and somatic soft tissues associated with multiple neurofibromatosis (von Recklinghausen s disease). Cancer 1963;16: Heard G: Malignant disease in von Recklinghausen s neurofibromatosis. Proc Roy Soc Med 1963;56: Malkin D: The Li-Fraumeni syndrome. In PPO Updates: Principles and Practice of Oncology, vol 7, no 7. Rosenberg SA, ed. Philadelphia: JB Lippincott, Li FP, Fraumeni JF Jr: Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 1969;71: Fraumeni JF Jr, Vogel CL, Easton JM: Sarcomas and multiple polyposis in a kindred. A genetic variety of hereditary polyposis? Arch Intern Med 1968;121: Beck A: Zur frage des Rontgensarkoms, zugleich ein Beitrag zur patholgenese des Sarkoms. Muench med Wochenschr 1922;69: Brady MS, Gaynor JJ, Brennan MF: Radiation-associated sarcoma of bone and soft tissue. Arch Surg 1992;127: Stewart W, Treves N: Lymphangiosarcoma in postmastectomy lymphedema. Cancer 1948; Vezeridis MP, Moore R, Karakousis CP: Metastatic patterns in soft-tissue sarcomas. Arch Surg 1983;118: American Joint Committee on Cancer: Soft tissue sarcoma. In AJCC Cancer Staging Manual, 5th ed. Philadelphia: Lippincott-Raven, 1997: Gaynor JJ, Tan CC, Casper ES, et al: Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults. J Clin Oncol 1992;10: Geer RJ, Woodruff J, Casper ES, Brennan MF: Management of small soft-tissue sarcoma of the extremity in adults. Arch Surg 1992;127: Lewis JJ, Leung D, Casper ES, et al: Multifactorial analysis of long-term follow-up (more than 5 years) of primary extremity sarcoma. Arch Surg 1999;134: Jaques DP, Coit DG, Casper ES, Brennan MF: Hepatic metastases from soft-tissue sarcoma. Ann Surg 1995;221: Pisters PW, Leung DH, Woodruff J, et al: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14: Bevilacqua RG, Rogatko A, Hajdu SI, Brennan MF: Prognostic factors in primary retroperitoneal soft-tissue sarcomas. Arch Surg 1991;126: McGrath PC, Neifeld JP, Lawrence W Jr, et al: Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg 1987;206: Ng EH, Pollock RE, Munsell MF, et al: Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg 1992;215: Olah KS, Dunn JA, Gee H: Leiomyosarcomas have a poorer prognosis than mixed mesodermal tumours when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma. Br J Obstet Gynaecol 1992;99: Demas BE, Heelan RT, Lane J, et al: Soft-tissue sarcomas of the extremities: comparison of MR and CT in determining the extent of disease. AJR Am J Roentgenol 1988; 150: Panicek DM: CT and MR imaging in local staging of malignant musculoskeletal neoplasm. Presented at the Connective Tissue Society; October 31, 1995; Boston, MA. 25. Yang JC, Rosenberg SA, Glatstein EJ, Antman KH: Sarcomas of soft tissues. In Cancer: Principles and Practice of Oncology, 4th ed. DeVita VT Jr, Hellman S, Rosenberg SA, eds. Philadelphia: Lippincott, 1993; Lewis JJ, Brennan MF: Soft tissue sarcomas. Curr Probl Surg 1996;33: Barth RJ Jr, Merino MJ, Solomon D, et al: A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses. Surgery 1992;112: Ball AB, Fisher C, Pittam M, et al: Diagnosis of soft tissue tumors by Tru-Cut biopsy. Br J Surg 1990;77: Kissin MW, Fisher C, Carter RL, et al: Value of Tru-Cut biopsy in the diagnosis of soft tissue tumours. Br J Surg 1986;73: Costa J, Wesley RA, Glatstein E, Rosenberg SA: The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer 1984;53: Kindblom LG: Light and electron microscopic examination of embedded fine-needle aspiration biopsy specimens in the preoperative diagnosis of soft tissue and bone tumors. Cancer 1983;51: Rydholm A: Soft tissue lesions in adults: biopsy yes or no? Ann Oncol 1992;3(suppl 2):S57 S Kissin MW, Fisher C, Webb AJ, Westbury G: Value of fine needle aspiration cytology in the diagnosis of soft tissue tumours: a preliminary study on the excised specimen. Br J Surg 1987;74: Eilber FR, Guiliano AE, Huth J, et al: High-grade soft tissue sarcomas of the extremity: UCLA experience with limb salvage. Prog Clin Biol Res 1985;201: Copyright 2000 by Turner White Communications Inc., Wayne, PA. All rights reserved. General Surgery Volume 6, Part 1 9