Acessibilidade / Reportar erro

Updating on Bone and Soft Tissue Sarcomas Staging* * Study performed at Oncologic Orthopedic Group, Orthopedic Service, Santa Izabel Hospital, Santa Casa de Misericórdia da Bahia, Salvador, BA, Brazil, and at the Traumatology and Orthopedics Service, Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Abstract

Bone and soft tissue sarcomas consist of a heterogeneous group of malignant tumors of mesenchymal origin that can affect patients from any age. The precise staging of these lesions determines the best therapeutic strategies and prognosis estimates. Two staging systems are the most frequently used: the system proposed by the University of Florida group, led by Dr. William F. Enneking (1980) and adopted by the Musculoskeletal Tumor Society (MSTS), and the system developed by the American Joint Committee on Cancer (AJCC) (1977), currently in its 8th edition (2017). This paper updates the reader on the staging of bone and soft tissue sarcomas affecting the musculoskeletal system.

Keywords:
neoplasm staging; sarcoma; neoplasms, connective tissue; neoplasms, bone tissue; diagnostic imaging; pathology, surgical

Resumo

Os sarcomas ósseos e das partes moles consistem em grupo heterogêneo de neoplasias malignas de origem mesenquimal que podem ocorrer em qualquer faixa etária. O estadiamento preciso destas lesões determina as melhores estratégias terapêuticas e estimativas de prognóstico. Dois sistemas de estadiamento são os mais frequentemente empregados no manejo destas neoplasias: o sistema proposto pelo grupo da Universidade da Flórida, liderado pelo Dr. William F. Enneking (1980), adotado pela Musculoskeletal Tumor Society (MSTS) e o sistema desenvolvido pela American Joint Committee on Cancer (AJCC) (1977) que se encontra em sua 8a edição (2017). O presente artigo busca atualizar o leitor a respeito do estadiamento dos sarcomas ósseos e das partes moles que acometem o sistema musculoesquelético.

Palavras-chave:
estadiamento de neoplasias; sarcoma; neoplasias de tecido conjuntivo; neoplasias de tecido ósseo; diagnósticoporimagem; patologia cirúrgica

Introduction

Bone and soft tissue sarcomas affect, respectively, 1 and 5 subjects per 100,000 people/year. Together, they account for 1% of all malignancies in humans.11 American Cancer Society. Cancer facts and figures 2017. Atlanta: American Cancer Society. Disponível em: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html. [Acessado em 24 de Julho, 2019]
https://www.cancer.org/research/cancer-f...

Since the most frequent clinical manifestations of bone and soft tissue sarcomas are pain and a mass at the affected segment, respectively, orthopedic surgeons often are thefirst specialists to evaluate affected patients. In case of clinical suspicion, specialized management, through appropriate imaging tests for staging and planning, in addition to a biopsy, will allow accurate and timely diagnosis and fast start of an adequate treatment, which is critical to preserve the affected limb and cure the disease.

By definition, sarcomas potentially develop metastases,22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15 which impact the prognosis.

Staging consists in approaching the patient from the initial examination to the histological diagnosis and definitive classification of a tumor.22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15

For decades, staging has been a critical tool to estimate prognosis, support therapy-related decisions and stratify patients into risk categories for clinical trials.22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15,33 Cates JM. Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma. Am J Surg Pathol 2017;41(03):405–413 The Union for International Cancer Control (UICC) defined the main goals of staging: guide therapeutic planning; estimate prognosis; help evaluate treatment outcomes; make interinstitutional communication effective; and contribute to scientific research.44 Brierley JD, Gospodarowicz MK, Wittekind CW, Eds. International Union Against Cancer: TNM Classification of Malignant Tumors. 8th ed. New Jersey, NY: Wiley-Blackwell; 2017

Cancer staging is considered essential for disease control.55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002 Several systems have been described to stage primary malignant tumors of musculoskeletal system.33 Cates JM. Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma. Am J Surg Pathol 2017;41(03):405–4137 Garcia Filho RJ. Estadiamento de Enneking dos tumores músculoesqueléticos. Rev Bras Ortop 1991;27(08):275–2781212 Stacy GS, Mahal RS, Peabody TD. Staging of bone tumors: a review with illustrative examples. AJR Am J Roentgenol 2006;186(04): 967–976 However, the system proposed by William F. Enneking et al. and adopted by the Musculoskeletal Tumor Society (MSTS)66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120 and the system developed by the American Joint Committee on Cancer (AJCC)88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486,99 Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545 are the most used in the clinical practice. The present paper aims to update the reader on bone and soft tissue sarcomas staging, using the Enneking/MSTS system66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120 and the TNM classification (AJCC), in its 8th edition (2017).88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486,99 Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545

Role of Imaging and Pathology in Evaluating Bone and Soft Tissue Sarcomas

Musculoskeletal tumors are diagnosed in at least one of the following clinical scenarios: pain, bony prominence, palpable soft tissue mass, pathological fracture, or incidental finding on imaging studies.1212 Stacy GS, Mahal RS, Peabody TD. Staging of bone tumors: a review with illustrative examples. AJR Am J Roentgenol 2006;186(04): 967–976

Clinical history and physical examination are often sufficient to raise suspicion on a musculoskeletal tumor, although radiographic examination is the most common test to reveal it.1313 Greenspan A, Jundt G, Remagen W. Differential diagnosis in orthopaedic oncology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006,1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976

Imaging is used for detection, diagnosis and differential diagnosis, as well as evaluation (staging) of primary malignant musculoskeletal tumors.1313 Greenspan A, Jundt G, Remagen W. Differential diagnosis in orthopaedic oncology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006

Conventional, orthogonal radiographs provide information regarding appearance, intraosseous extension, tumor matrix, and margins between the tumor and host bone. Cortical destruction and periosteal reaction are associated with invasive bone tumors.1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976,1515 Peabody TD, Gibbs CP Jr, Simon MA. Evaluation and staging of musculoskeletal neoplasms. J Bone Joint Surg Am 1998;80(08): 1204–1218 In soft tissue tumors, radiographs allow the detection and definition of the mineralization pattern of a lesion, aiding the diagnosis/differential diagnosis with other tumors or pseudotumoral lesions (ossifying myositis, tumor calcinosis, vascular malformations, gout, extraskeletal mesenchymal chondrosarcoma, extraskeletal osteosarcoma, liposarcoma and synovial sarcoma); in addition, they reveal valuable information on tumor density (adipocytic tumors) and possible underlying bone involvement.1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976,1616 Patel DB, Matcuk GR Jr. Imaging of soft tissue sarcomas. Linchuang Zhongliuxue Zazhi 2018;7(04):35

In view of a bone or soft tissue lesion with clinical and radiographic characteristics denoting biological aggressiveness, additional imaging tests are required1212 Stacy GS, Mahal RS, Peabody TD. Staging of bone tumors: a review with illustrative examples. AJR Am J Roentgenol 2006;186(04): 967–976 to determine local extension, distant spread (metastases) and histological diagnosis (►Figure 1).

Local Staging

Local extension of a sarcoma is defined by the involved anatomical spaces. Understanding the relevant topographic anatomy is crucial to define the best therapeutic approach to each clinical situation.1717 Liu PT, Valadez SD, Chivers FS, Roberts CC, Beauchamp CP. Anatomically based guidelines for core needle biopsy of bone tumors: implications for limb-sparing surgery. Radiographics 2007;27(01):189–205, discussion 206

In appendicular segments, joint capsule and cartilage, cortex, periosteum fascial septa, muscle origins and attachments act as natural barriers to tumoral dissemination, defining compartments; a tumor confined to a compartment is considered intracompartmental, which is a stage below to a lesion surpassing such barriers to become extracompartmental. Sarcomas grow centrifugally through lower resistance areas and they are partially contained by a pseudocapsule, in which they can remain confined. Malignant cells, however, tend to extend themselves beyond these limits; if this occurs, but the tumor remains confined to a given anatomical compartment, the lesion is deemed extracapsular and intracompartmental; if the lesion invades an adjacent compartment, it is classified as extracompartmental.1818 Anderson MW, Temple HT, Dussault RG, Kaplan PA. Compartmental anatomy: relevance to staging and biopsy of musculoskeletal tumors. AJR Am J Roentgenol 1999;173(06):1663–1671

The multiplanar assessment and soft tissue enhancement provided by magnetic resonance imaging (MRI) or, if this modality is contraindicated or unavailable,88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486,1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278 computed tomography (CT) with contrast media, made these imaging tests indispensable to local staging1919 Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii; occasionally, MRI and CT can be requested together, as they provide additional information that helps delineating the lesions under study.1717 Liu PT, Valadez SD, Chivers FS, Roberts CC, Beauchamp CP. Anatomically based guidelines for core needle biopsy of bone tumors: implications for limb-sparing surgery. Radiographics 2007;27(01):189–205, discussion 206 It is worth mentioning that these tests must be performed before biopsy to avoid artifacts interfering with image interpretation.2020 Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;(426): 92–96

Magnetic resonance imaging is considered superior to CT for the local staging of bone sarcomas and constitutes the mainstay in imaging evaluation of soft tissue sarcomas.2020 Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;(426): 92–96 Regarding lesion morphology, the main factors for staging are size and local extension,2121 Greene FL, Page DL, Fleming ID, et al. AJCC Manual for Staging of Cancer. 6th ed. Switzerland: Springer; 2002 which are best assessed by gadolinium-enhanced MRI using advanced perfusion and diffusion techniques1919 Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii to determine lesion configuration, location, depth, size and local extension, as well as its relationship with adjacent muscles, muscle compartments, fascial planes, neurovascular structures, joints and organs (►Figures 2 and 3).1515 Peabody TD, Gibbs CP Jr, Simon MA. Evaluation and staging of musculoskeletal neoplasms. J Bone Joint Surg Am 1998;80(08): 1204–1218,1818 Anderson MW, Temple HT, Dussault RG, Kaplan PA. Compartmental anatomy: relevance to staging and biopsy of musculoskeletal tumors. AJR Am J Roentgenol 1999;173(06):1663–1671 It is mandatory to image the entire affected anatomical segment (whole bone) to define intramedullary involvement extension and identify eventual discontinuous bone tumors (skip metastasis), which presence has important prognostic implications.66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120,1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278,1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976,1515 Peabody TD, Gibbs CP Jr, Simon MA. Evaluation and staging of musculoskeletal neoplasms. J Bone Joint Surg Am 1998;80(08): 1204–1218,2020 Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;(426): 92–96

Fig. 1
Algorithm for initial evaluation and imaging staging of suspected bone and soft tissue sarcomas.

The choiceforMRI orCT inbonesarcomaevaluation may be based on radiographic findings. In cases with cortical destruction and extracompartmental tumor, MRI is the preferred modality because it provides excellent soft tissue enhancement and it is better in determining extraosseous tumoral extension compared with CT.1919 Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii Magnetic resonance imaging allows more accurate staging due to its multiplanar (sagittal, coronal, axial and oblique) imaging ability and the lack of CTassociated beam hardening artifacts from cortical bone.1919 Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii Although rarely useful in specific diagnoses, CT is indicated when there is no radiographic evidence of tumor extension to soft tissues, as it improves calcification visualization, periosteal reaction detection, cortical subtle invasion or destruction and intraosseous extension determination.33 Cates JM. Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma. Am J Surg Pathol 2017;41(03):405–413,1919 Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii Computed tomography is also useful to delineate tumors in complex anatomical structures such as the axial skeleton and the pelvic and scapular girdles, in addition to allow a better and more understandable demonstration of surface bone sarcomas, such as parosteal osteosarcoma or juxtacortical chondrosarcoma, through three-dimensional reconstruction.1919 Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii

Systemic Staging

Distant spread is the main prognostic factor for bone and soft tissue sarcomas. Sarcomas have preferential hematogenous diffusion pathways, and the lungs and the skeleton are the most frequent sites for metastatic development. Although less frequent, lymphatic involvement has prognostic importance, andsomehistologicalsubtypesofsoft tissuesarcomas(suchas synovial sarcoma, epithelioid sarcoma, clear cell sarcoma and angiosarcoma) usually affect locoregional lymph nodes.1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976,2222 Ferrari A, Dirksen U, Bielack S. Sarcomas of Soft Tissue and Bone. Prog Tumor Res 2016;43:128–141

Lung evaluation uses chest X-rays in two views, and/or, preferably,88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486 high-resolution chest CT, which is more sensitive for lesion detection.22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15,1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278,1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976

The National Comprehensive Cancer Network (NCCN) recommends abdominal and pelvic CT for staging some soft tissue sarcomas which tend to metastasize to those sites, including myxoid liposarcoma, epithelioid sarcoma, leiomyosarcoma and angiosarcoma.1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976,2323 Maki RG, Moraco N, Antonescu CR, et al. Toward better soft tissue sarcoma staging: building on american joint committee on cancer staging systems versions 6 and 7. Ann Surg Oncol 2013;20(11): 3377–3383,2424 Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 2016;17(05):671–680

Fig. 2
Conventional calcaneal osteosarcoma. (A) Lateral radiography showing calcaneal lytic and sclerotic areas. (B) Sagittal magnetic resonance imaging in T1-weighted sequence showing diffuse hyposignal in the calcaneus with no extracompartmental tumor. (C) Surgical approach for calcaneus resection. Musculoskeletal Tumor Society (MSTS) staging, IA; American Joint Committee on Cancer (AJCC) staging, IIA.
Fig. 3
High-grade pleomorphic sarcoma at the right knee. Proton density sequences with fat suppression in the sagittal plane before treatment (A) showing a heterogeneous lesion in the posterior compartment. Axial dynamic study (B) and color map (C) showing early enhancement in the posterior and superficial portion of the lesion (red line in D). Five months after treatment, a conventional magnetic resonance imaging does not show a significant change in lesion signal intensity (E). However, the dynamic axial study (F) and color map (G) show a change in the pattern of lesion enhancement (red line in H), indicating good therapeutic response. Histological analysis showed more than 90% of tumor necrosis. American Joint Committee on Cancer (AJCC) staging, IIIA.

Bone scintigraphy must be included in bone sarcoma staging to scan the skeleton for similar lesions or metastatic bone disease.22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15,88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486 Bone scanning is not routinely indicated in the initial staging of soft tissue sarcomas.1414 Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976

The routine indication of full body MR,22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15 PET-CT22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15,88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486 or PET-MR22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15 it is still under scrutiny for bone and soft tissue sarcomas staging. However, when necessary, additional imaging modalities can be used to assess suspicious sites since the exact staging of the disease impacts the treatment and clinical outcome.22 Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15

Histological Diagnosis

Biopsy completes the clinical staging process,88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486 confirming the diagnosis and determining the histological grade of the sarcoma through anatomopathological examination, complemented by immunohistochemistry and molecular biology when required.

In patients with suspected sarcoma, biopsy must be performed preferably at a referral center with expertise in treating this tumor.88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486 Imaging evaluation must precede the biopsy.88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486,2020 Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;(426): 92–96

A tumor sample must be obtained through percutaneous biopsy with a core needle guided by the appropriate imaging method (ultrasound, CT, fluoroscopy, etc.), or incisional biopsy. Biopsy location must be carefully planned to allow resection of the entire path along with the surgical specimen at the time of definitive tumor resection.88 Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486

Subtype and histological grade may predict the tumor biological behavior, a variable with greatest impact on the risk for metastatic dissemination and overall survival.1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278 The histological grade correlates with tumor cell proliferation pattern, mitotic activity and metastatic potential.

Histologically, sarcomas are classified as high or lowgrade according to cell atypia, number of mitosis figures, necrosis degree and vascularization.2222 Ferrari A, Dirksen U, Bielack S. Sarcomas of Soft Tissue and Bone. Prog Tumor Res 2016;43:128–141 Low-grade lesions often present lower biological activity, minimal metastatic potential, require less radical surgical treatment, and are not indicated for adjuvant chemotherapy and/or radiotherapy, since these treatments are usually ineffective due to reduced cell proliferation. On the other hand, high-gradelesions often require more radical local and systemic treatment due to their aggressive biological behavior.2222 Ferrari A, Dirksen U, Bielack S. Sarcomas of Soft Tissue and Bone. Prog Tumor Res 2016;43:128–141

Musculoskeletal Tumor Society (MSTS) Staging System

In 1980, the MSTS adopted the surgical staging system for musculoskeletal system sarcomas created in Gainesville, 1977, by the University of Florida group led by Dr. William F. Enneking, from data collected between 1968 and 1976.55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002,66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120 This system is based on the definition of tumor extension in relation to anatomical limits and histological grading, bringing together the most important prognostic factors in a concise classification to estimate survival, guide surgical treatment and indicate potential adjuvant therapies.55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002,66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120 Since it is based on surgical observations, MSTS parameters are intuitive, facilitating operative planning. The MSTS staging system is the most used system by orthopedic oncologists, but it is less employed in soft tissue sarcomas staging, especially by clinical oncologists, oncologic surgeons and other specialists.1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278

This system combines three variables: histopathological grade (I = low grade, II = high grade), local extension beyond the original compartment (A = intracompartmental, B = extracompartmental) and the presence of distant metastases (III) (►Table 1).55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002,66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120 Low-grade (I) lesions correspond to Broder class 1 or 2 (low mitotic rate, low nucleus/ cytoplasm ratio, limited pleomorphism, low risk [<25%] for metastases). High-grade lesions (II) correspond to Broder class 3 and 4 (mitotic figures, prominent nuclei, pleomorphism, higher incidence of metastases). Subcategories A (intracompartmental) and B (extracompartmental) are defined by imaging of the affected segment. Stage III represents any tumor with distant metastasis at imaging modalities.55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002,66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120

Staging determines surgical resection extension, considering the feasibility of obtaining adequate oncological margins. A high-grade lesion usually is more biologically aggressive and, therefore, it is more likely to invade surrounding tissues, increasing the risk for local recurrence and metastasis; in such cases, adjuvant therapies are recommended to eradicate tumor cells that would remain after surgical resection.66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120

The main disadvantages of the MSTS system are: 1. it does not include tumor size, implicated as an important prognostic factor for several subtypes of soft tissue sarcomas (larger lesions tend to have greater metastatic potential and may benefit from neoadjuvant chemotherapy)55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002; 2. it has limited discriminatory prognostic power for the intermediate strata due to its simplified variable dichotomization (histological degree, local and distant extension), tending to group most osteosarcomas and Ewing sarcomas at the same stage; osteosarcomas are usually classified as stage IIB; for Ewing sarcomas, the limitation is more evident because this is a high-grade malignancy and the histological grade is not a variable, preventing their classification as IA1010 Cates JMM. Simple staging system for osteosarcoma performs equivalently to the AJCC and MSTS systems. J Orthop Res 2018;36 (10):2802–2808; 3. skull-originated lesions have different clinical behavior and cannot be classified using this system55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002; 4. it does not consider the presence of a continuous epidural compartment in spinal tumors, a variable with neurological implications (possible spinal cord and spinal roots sacrifice and need for stabilization).55 Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002

American Joint Committee (AJCC) on Cancer Staging System

The staging system proposed by the AJCC for musculoskeletal sarcomas, since its original description as the Manual for Staging of Cancer (MSC) in 1977,2525 Beahrs OH, Carr DT, Rubin P, Eds. AJCC Manual for Staging of Cancer. Chicago, IL: American Joint Committee; 1977 was updated and refined based on the evolution of scientific evidence on the prognosis and survival associated with such tumors.

Primary Malignant Bone Tumors Staging (AJCC)

The MSC, on its 1st edition (1977),2525 Beahrs OH, Carr DT, Rubin P, Eds. AJCC Manual for Staging of Cancer. Chicago, IL: American Joint Committee; 1977 recommended a protocol for primary malignant bone tumors developed by the Task Force On Primary Malignant Bone Tumor to record patient identification, history, clinical data, imaging (radiographs), pathological reports, histological (World Health Organization [WHO] classification of primary bone tumors and pseudotumor lesions) and recurrences or metastases during follow-up. It did not indicate a specific system for sarcoma staging, but it suggested that prospective clinical studies, with a greater number of cases, would allow the creation of a satisfactory clinical classification for staging and outcomes recording in the future.

Starting at its 2nd edition2626 Beahrs OH, Myers MH, Eds. AJCC Manual for Staging of Cancer. 2nd ed. Philadelphia, PA: Lippincott; 1983 (1983), the MSC included a system for staging such tumors based on the TGNM method: tumor size (T), histological grade (G), presence or not of regional lymph node metastasis (N) and presence or not of distant metastasis (M). At this point, stages were already defined (IA, IB, IIA, IIB, III, IVA, IVB), and a prognostic grading was attributed based on the combined evaluation of these variables.

Table 1
Staging system adopted by the Musculoskeletal Tumor Society for malignant musculoskeletal tumors based on the surgical degree, local extension and the presence or not of metastases

Up to its 6th edition (2002),2121 Greene FL, Page DL, Fleming ID, et al. AJCC Manual for Staging of Cancer. 6th ed. Switzerland: Springer; 2002 the MSC defined tumor extension as contained or not in the host bone, like the Enneking/MSTS system. The size of eight centimeters became the cutoff point between the T1 and T2 designations, replacing tumor extension classification as intra- or extracompartmental. The choice was controversial2727 Kim MS, Lee SY, Cho WH, et al. An examination of the efficacy of the 8 cm maximal tumor diameter cutoff for the subdivision of AJCC stage II osteosarcoma patients. J Surg Oncol 2008;98(06): 427–431 because it was based on theliterature regarding Ewing sarcoma, limited to osteosarcoma. Later studies confirmed its value in Ewing sarcoma staging2828 Lee J, Hoang BH, Ziogas A, Zell JA. Analysis of prognostic factors in Ewing sarcoma using a population-based cancer registry. Cancer 2010;116(08):1964–1973 and, to date, the MSC recommends that the size of nine centimeters is the best prognostic indicator for osteosarcoma. The addition of the T3 designation for skip metastasis99 Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545,1616 Patel DB, Matcuk GR Jr. Imaging of soft tissue sarcomas. Linchuang Zhongliuxue Zazhi 2018;7(04):35 was another modification – Wuisman et al.2929 Wuisman P, Enneking WF. Prognosis for patients who have osteosarcoma with skip metastasis. J Bone Joint Surg Am 1990; 72(01):60–68 compared 224 patients without skip metastasis at diagnosis with 23 patients who presented such lesions. Twenty two of these 23 individuals had local recurrence or distant metastasis and died; adjuvant chemotherapy did not improve their prognosis. The 3rd update consisted of differentiating metastases according to location, distinguishing between pulmonary (IVA) and extrapulmonary (IVB) lesions based on evidence that bone sarcomas with pulmonary metastases had better prognostic compared to those with metastases at other sites3030 Ward WG, Mikaelian K, Dorey F, et al. Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases. J Clin Oncol 1994;12(09):1849–1858,3131 Cotterill SJ, Ahrens S, Paulussen M, et al. Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group. J Clin Oncol 2000;18(17):3108–3114–multiple lung metastases were associated with a worse prognosis, although this variable was not included in any staging system.1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278,3030 Ward WG, Mikaelian K, Dorey F, et al. Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases. J Clin Oncol 1994;12(09):1849–1858

In its 7th edition (2010), the MSC3232 Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III. AJCC Manual for Staging of Cancer. 7th ed. New York, NY: Springer; 2010 restricted the definition of stage III only to grade 3 (poorly differentiated) and grade 4 (undifferentiated) tumors. The same staging was employed, regardless of the primary site, for bone and soft tissue sarcomas.

The 8th (current) MSC edition,99 Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545 published in 2017, brought new changes. The main one was the inclusion of defined axial skeleton segments as part of the (T) classification, with three sites for bone sarcomas: (i) appendicular skeleton, trunk, skull and facial bones; (ii) spine and (iii) pelvis. Although it does not affect tumor staging, this inclusion allowed the determination of a structure for future research to improve the system – studies have shown evidence that bone sarcomas with axial location have markedly worse prognosis.3333 Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20(03):776–790

Bone and soft tissue sarcomas have been described separately, according to primary sites, mainly due to differences in prognosis and treatment strategy (►Table 2). The histopathological grade (G) was also changed, from four to three levels, with stage III reserved for G2-G3 (high grade tumors) and eliminating the G4 designation, as recommended by the American College of Pathologists, which uses the system from the Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) to classify soft tissue sarcomas.99 Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545 This change provided uniformity to bone and soft tissue sarcomas classification.1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278

Soft Tissue Sarcoma Staging (AJCC)

The AJCC staging system for soft tissue sarcomas is the most used to stratify prognoses and define the approach to these tumors. It considers additional factors to estimate prognosis and enables better interdisciplinary communication. In contrast to bone sarcomas, which have few histological subtypes, the numerous subtypes of soft tissue sarcomas require a more complex staging.1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278

Since its 1st edition (1977),2525 Beahrs OH, Carr DT, Rubin P, Eds. AJCC Manual for Staging of Cancer. Chicago, IL: American Joint Committee; 1977 the MSC included the TGNM system for staging these tumors; based on the combined assessment of these variables, stages IA, IB, IIA, IIB, IIIA, IIIB, IIIC, IVA and IVB were defined, each with an assigned prognostic score. This classification remained in its 2nd edition (1983)2626 Beahrs OH, Myers MH, Eds. AJCC Manual for Staging of Cancer. 2nd ed. Philadelphia, PA: Lippincott; 1983 and presents gradual changes since the 3rd edition (1988)3434 Beahrs OH, Henson DE, Hutter RVP, Myers MH, Eds. AJCC Manual for Staging of Cancer. 3rd ed. Philadelphia, PA: Lippincott; 1988 to reflect new clinical evidence.

The AJCC manual, in its 6th edition,2121 Greene FL, Page DL, Fleming ID, et al. AJCC Manual for Staging of Cancer. 6th ed. Switzerland: Springer; 2002 considered angiosarcoma and malignant mesenchymoma as exceptions and removed them, while gastrointestinal stromal tumor (GIST) and Ewing soft tissue sarcoma were added. Moreover, G1-2, T2b, N0 M0 tumors were reclassified as stage I instead of stage II.

In its 7th edition, the AJCC manual3232 Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III. AJCC Manual for Staging of Cancer. 7th ed. New York, NY: Springer; 2010 removed fibromatosis, Kaposi sarcoma, infantile fibrosarcoma and GIST from the system. N1 disease was reclassified as stage IIIB instead of stage IV based on level IVevidence – the classic study by Fong et al.3535 Fong Y, Coit DG, Woodruff JM, Brennan MF. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 1993; 217(01):72–77 demonstrated that patients with soft tissue sarcomas and positive lymph nodes have a survival rate similar to those with locally advanced disease, but better than those with distant metastases.3535 Fong Y, Coit DG, Woodruff JM, Brennan MF. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 1993; 217(01):72–7736 Riad S, Griffin AM, Liberman B, et al. Lymph node metastasis in soft tissue sarcoma in an extremity. Clin Orthop Relat Res 2004; (426):129–1343737 Behranwala KA, A’Hern R, Omar AM, Thomas JM. Prognosis of lymph node metastasis in soft tissue sarcoma. Ann Surg Oncol 2004;11(07):714–719 The histological grading system was also changed to three levels, as recommended by the College of American Pathologists, based on level II evidence that the FNCLCC system predicts survival with significant accuracy.3838 Mariani L, Miceli R, Kattan MW, et al. Validation and adaptation of a nomogram for predicting the survival of patients with extremity soft tissue sarcoma using a three-grade system. Cancer 2005; 103(02):402–408 The tumor depth variable was also removed from the classification for staging and prognosis determination1111 Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278; the recommendations for describing tumors as superficial or deep to the fasciawere maintained, but considered irrelevant in staging. Rydholm et al.3939 Rydholm A, Gustafson P. Should tumor depth be included in prognostication of soft tissue sarcoma? BMC Cancer 2003;3:17 showed that depth was a prognostic factor when analyzed regardless of tumor size. Since other studies suggested worse survival with deeper tumors, it remained part of the staging process for soft tissue sarcoma for decades; however, when more detailed analyzes were performed, depth proved to be a variable of confusion, because size is the true independent factor associated with worst prognosis.3333 Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20(03):776–790

Table 2
American Joint Committee on Cancer (AJCC) classification for bone sarcomas. Prognostic stage groups for bone sarcomas in the appendicular skeleton, trunk, skull and facial bones (there are no AJCC prognostic stage groups for spinal and pelvic tumors)
Table 3
American Joint Committee on Cancer classification for soft tissue sarcomas located on the trunk and extremities. Prognostic stage groups

The 8th MSC edition (2017)99 Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545 describes four tumor sites for soft tissue sarcomas: (i) extremities and trunk; (ii) retroperitoneum; (iii) head and neck and (iv) visceral sites. All references to lesion depth were removed66 Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120 due to level II evidence published by Maki et al2323 Maki RG, Moraco N, Antonescu CR, et al. Toward better soft tissue sarcoma staging: building on american joint committee on cancer staging systems versions 6 and 7. Ann Surg Oncol 2013;20(11): 3377–3383 confirming that this variable was not an independent risk factor after multivariate analysis. Another modification was to increase the number of tumor size categories from two (≤5 cm or >5 cm) to four (≤5 cm, >5/≤10 cm, >10/≤15 cm, >15 cm). The decision to group T3 and T4 (>10/≤15 cm and >15 cm) in stage IIIB was corroborated by level II evidence from a study involving 1,091 patients that showed that tumors sized ≤5 cm, > 5/≤10 cm and >15 cm have markedly different mortality rates; this study showed no significant difference in survival between categories >5/≤10 cm and >10/≤154040 Lahat G, Tuvin D, Wei C, et al. New perspectives for staging and prognosis in soft tissue sarcoma. Ann Surg Oncol 2008;15(10): 2739–2748,4141 Tanaka K, Ozaki T. New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol 2019;49(02):103–107; nevertheless, a size categorization in four levels was included according to data published by Maki et al,2323 Maki RG, Moraco N, Antonescu CR, et al. Toward better soft tissue sarcoma staging: building on american joint committee on cancer staging systems versions 6 and 7. Ann Surg Oncol 2013;20(11): 3377–3383 who demonstrated significant differences in local recurrence free global survival between the four groups and a survival plateau in 10 cm tumors. This finding was supported by a recent study, in which nomograms were used to predict overall survival; for any unit change in tumor size >10 cm, there was a markedly lesser effect on survival when compared with the effect on tumor survival <10 cm.2424 Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 2016;17(05):671–680 In this same edition, N1 disease associated with trunk and extremities tumors was reclassified as stage IV, probably because their prognosis is closer to any TN0M1 metastatic disease than any TN0M0; these cases, however, remain as IIIB for tumors located at other sites4141 Tanaka K, Ozaki T. New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol 2019;49(02):103–107 (►Table 3).

Final Considerations

The domain of knowledge about the staging systems for bone and soft tissue sarcomas, as well as imaging, diagnostic methods and histological grading for classifying such tumors, is critical not only for specialists directly involved in the treatment of affected patients, but also for orthopedic surgeons who are often responsible for their first care, which quality has the potential to interfere with the clinical outcome.

References

  • 1
    American Cancer Society. Cancer facts and figures 2017. Atlanta: American Cancer Society. Disponível em: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html. [Acessado em 24 de Julho, 2019]
    » https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html.
  • 2
    Mavrogenis AF, Angelini A, Vottis C, et al. State-of-the-art approach for bone sarcomas. Eur J Orthop Surg Traumatol 2015;25 (01):5–15
  • 3
    Cates JM. Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma. Am J Surg Pathol 2017;41(03):405–413
  • 4
    Brierley JD, Gospodarowicz MK, Wittekind CW, Eds. International Union Against Cancer: TNM Classification of Malignant Tumors. 8th ed. New Jersey, NY: Wiley-Blackwell; 2017
  • 5
    Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 2010;468(07):2000–2002
  • 6
    Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980; (153):106–120
  • 7
    Garcia Filho RJ. Estadiamento de Enneking dos tumores músculoesqueléticos. Rev Bras Ortop 1991;27(08):275–278
  • 8
    Kneisl JS, Rosenberg AE, Anderson PM, Antonescu CR, Bruland OS, Cooper K. Bone. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:469–486
  • 9
    Pollock RE, Maki RG, Brookland RK, Agulnik M, Asare EA, Baldini EH. Soft Tissue Sarcoma. In: Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al, eds. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017:487–545
  • 10
    Cates JMM. Simple staging system for osteosarcoma performs equivalently to the AJCC and MSTS systems. J Orthop Res 2018;36 (10):2802–2808
  • 11
    Steffner RJ, Jang ES. Stagingof Bone and Soft-tissue Sarcomas. J Am Acad Orthop Surg 2018;26(13):e269–e278
  • 12
    Stacy GS, Mahal RS, Peabody TD. Staging of bone tumors: a review with illustrative examples. AJR Am J Roentgenol 2006;186(04): 967–976
  • 13
    Greenspan A, Jundt G, Remagen W. Differential diagnosis in orthopaedic oncology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006
  • 14
    Caracciolo JT, Letson GD. Radiologic Approach to Bone and Soft Tissue Sarcomas. Surg Clin North Am 2016;96(05):963–976
  • 15
    Peabody TD, Gibbs CP Jr, Simon MA. Evaluation and staging of musculoskeletal neoplasms. J Bone Joint Surg Am 1998;80(08): 1204–1218
  • 16
    Patel DB, Matcuk GR Jr. Imaging of soft tissue sarcomas. Linchuang Zhongliuxue Zazhi 2018;7(04):35
  • 17
    Liu PT, Valadez SD, Chivers FS, Roberts CC, Beauchamp CP. Anatomically based guidelines for core needle biopsy of bone tumors: implications for limb-sparing surgery. Radiographics 2007;27(01):189–205, discussion 206
  • 18
    Anderson MW, Temple HT, Dussault RG, Kaplan PA. Compartmental anatomy: relevance to staging and biopsy of musculoskeletal tumors. AJR Am J Roentgenol 1999;173(06):1663–1671
  • 19
    Costa FM, Canella C, Gasparetto E. Advanced magnetic resonance imaging techniques in the evaluation of musculoskeletal tumors. Radiol Clin North Am 2011;49(06):1325–1358, vii–viii vii–viii
  • 20
    Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;(426): 92–96
  • 21
    Greene FL, Page DL, Fleming ID, et al. AJCC Manual for Staging of Cancer. 6th ed. Switzerland: Springer; 2002
  • 22
    Ferrari A, Dirksen U, Bielack S. Sarcomas of Soft Tissue and Bone. Prog Tumor Res 2016;43:128–141
  • 23
    Maki RG, Moraco N, Antonescu CR, et al. Toward better soft tissue sarcoma staging: building on american joint committee on cancer staging systems versions 6 and 7. Ann Surg Oncol 2013;20(11): 3377–3383
  • 24
    Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 2016;17(05):671–680
  • 25
    Beahrs OH, Carr DT, Rubin P, Eds. AJCC Manual for Staging of Cancer. Chicago, IL: American Joint Committee; 1977
  • 26
    Beahrs OH, Myers MH, Eds. AJCC Manual for Staging of Cancer. 2nd ed. Philadelphia, PA: Lippincott; 1983
  • 27
    Kim MS, Lee SY, Cho WH, et al. An examination of the efficacy of the 8 cm maximal tumor diameter cutoff for the subdivision of AJCC stage II osteosarcoma patients. J Surg Oncol 2008;98(06): 427–431
  • 28
    Lee J, Hoang BH, Ziogas A, Zell JA. Analysis of prognostic factors in Ewing sarcoma using a population-based cancer registry. Cancer 2010;116(08):1964–1973
  • 29
    Wuisman P, Enneking WF. Prognosis for patients who have osteosarcoma with skip metastasis. J Bone Joint Surg Am 1990; 72(01):60–68
  • 30
    Ward WG, Mikaelian K, Dorey F, et al. Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases. J Clin Oncol 1994;12(09):1849–1858
  • 31
    Cotterill SJ, Ahrens S, Paulussen M, et al. Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group. J Clin Oncol 2000;18(17):3108–3114
  • 32
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III. AJCC Manual for Staging of Cancer. 7th ed. New York, NY: Springer; 2010
  • 33
    Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20(03):776–790
  • 34
    Beahrs OH, Henson DE, Hutter RVP, Myers MH, Eds. AJCC Manual for Staging of Cancer. 3rd ed. Philadelphia, PA: Lippincott; 1988
  • 35
    Fong Y, Coit DG, Woodruff JM, Brennan MF. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 1993; 217(01):72–77
  • 36
    Riad S, Griffin AM, Liberman B, et al. Lymph node metastasis in soft tissue sarcoma in an extremity. Clin Orthop Relat Res 2004; (426):129–134
  • 37
    Behranwala KA, A’Hern R, Omar AM, Thomas JM. Prognosis of lymph node metastasis in soft tissue sarcoma. Ann Surg Oncol 2004;11(07):714–719
  • 38
    Mariani L, Miceli R, Kattan MW, et al. Validation and adaptation of a nomogram for predicting the survival of patients with extremity soft tissue sarcoma using a three-grade system. Cancer 2005; 103(02):402–408
  • 39
    Rydholm A, Gustafson P. Should tumor depth be included in prognostication of soft tissue sarcoma? BMC Cancer 2003;3:17
  • 40
    Lahat G, Tuvin D, Wei C, et al. New perspectives for staging and prognosis in soft tissue sarcoma. Ann Surg Oncol 2008;15(10): 2739–2748
  • 41
    Tanaka K, Ozaki T. New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol 2019;49(02):103–107

Publication Dates

  • Publication in this collection
    29 Sept 2021
  • Date of issue
    Jul-Aug 2021

History

  • Received
    25 Sept 2019
  • Accepted
    20 Feb 2020
Sociedade Brasileira de Ortopedia e Traumatologia Al. Lorena, 427 14º andar, 01424-000 São Paulo - SP - Brasil, Tel.: 55 11 2137-5400 - São Paulo - SP - Brazil
E-mail: rbo@sbot.org.br