Orthopedics

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Staging Systems for Musculoskeletal Neoplasms

Henry A Finn, MD; Michael A Simon, MD

Abstract

ABSTRACT: In the treatment of musculoskeletal neoplasms, preservation of limb function and prolongation of survival have improved over the past decade. With the current emphasis on limb salvage procedures for local control of tumors, and with the addition of adjunctive therapy, the ability to classify and stage these unusual tumors is important in determining prognosis and treatment. In such classifications, a number of prognostic factors are identified and used to define stages. Three recognized staging systems exist for sarcomas of soft tissues and two for sarcomas of bone; there is one system for benign tumors of bone. The prognostic variables used in assigning stages are common to all of these systems, but the relative significance assigned to these variables differs. Documented improvement in survival and preservation of function suggests that current staging systems are significantly affecting outcome in the management of musculoskeletal tumors.

Abstract

ABSTRACT: In the treatment of musculoskeletal neoplasms, preservation of limb function and prolongation of survival have improved over the past decade. With the current emphasis on limb salvage procedures for local control of tumors, and with the addition of adjunctive therapy, the ability to classify and stage these unusual tumors is important in determining prognosis and treatment. In such classifications, a number of prognostic factors are identified and used to define stages. Three recognized staging systems exist for sarcomas of soft tissues and two for sarcomas of bone; there is one system for benign tumors of bone. The prognostic variables used in assigning stages are common to all of these systems, but the relative significance assigned to these variables differs. Documented improvement in survival and preservation of function suggests that current staging systems are significantly affecting outcome in the management of musculoskeletal tumors.

Introduction

The staging of malignant tumors is important to prognosis and in organization of treatment, assignment of treatment priorities, and investigative studies. The first staging system for malignant tumors was that developed for cervical carcinoma by the American Joint Commission on Staging. In this system, designations T, N, and M were used to describe tiie extent of local involvement and of local and distant metastasis: T describes the extent of local tumor involvement, N refers to local or regional lymph node involvement, and M designates metastasis. Eventually, this system was used in developing several methods of staging that are recognized worldwide. Unfortunately, it has been difficult to develop a universally accepted staging system for bone and soft tissue sarcomas of the extremities. Obstacles to the development of such a staging system are probably related to the uncommon occurrence of these tumors, their unique and unpredictable biologic behavior, and a history of unsuccessful treatment.

This report reviews some staging systems in current use, including three systems for adult soft tissue sarcomas and two for sarcomas of bone. Tumors of marrow cell origin are not included, and the staging of benign tumors is mentioned only briefly.

Biologic Behavior of Musculoskeletal Sarcomas

An understanding of the approaches used for staging of musculoskeletal neoplasms requires knowledge of their biologic behavior and natural history. During their early growth, sarcomas of the musculoskeletal system enlarge in a centripetal fashion. A pseudocapsule of fibrous connective tissue or reactive bone is formed as a host reaction by compression and layering of normal tissue cells, inflammatory cells, and newly formed blood vessels at the expanding border of the growing sarcoma. The reactive zone at the periphery of the pseudocapsule usually contains microscopic extensions of the tumor. In addition, satellite colonies of malignant cells may be found at some distance from the tumor.

As their growth continues, sarcomas of the musculoskeletal system are contained in compartments bounded by fascia, cortical bone, synovium, periosteum, and cartilage. Their spread is usually centripetal in a subcutaneous site and longitudinal in a deep muscle or bone compartment. Many sarcomas remain intracompartmental; ie, they are confined within a specific anatomic compartment except in very advanced stages or if they are disrupted by a surgical procedure. Major neurovascular structures are usually displaced rather than invaded.

A sarcoma may arise outside a well defined anatomic compartment. If there is no natural anatomic barrier, such an extracompartmental tumor may spread over considerable distances. Examples are soft tissue sarcomas that involve the popliteal space, groin, or antecubital fossa, or sarcomas of bone that have broken through the cortex into the adjacent soft tissues. Such extracompartmental sarcomas may then spread over great distances along neurovascular planes.

Metastatic spread to the lung by a hematogenous route may be seen at diagnosis in approximately 10% of musculoskeletal neoplasms. Rarely, distant nonpulmonary metastases are found in bone and other soft tissues. Regional lymph node involvement is seen rarely in bone sarcomas and infrequently in adult soft tissue sarcomas except synovial sarcomas.

Principles

For adult soft tissue sarcomas, the three staging systems used at present are those developed by the American Joint Commission, by Enneking, and by Hajdu.1-3 For sarcomas of bone, there are two very similar systems, one of which was developed by Enneking.2 Thé other, a modified version of die same system, was developed by the American Joint Commission.4 Although these staging systems differ in their manner of grouping and assigning relative prognostic significance, there appears to be general agreement about which prognostic variables are important: The grade of the tumor, its location and relative size, and the presence or absence of metastases are the key prognostic factors in any staging system for neoplasms.

Key Prognostic factors

The grade of a tumor is a measure of its aggressiveness or tendency to metastasize. Lesions characterized by cellular atypia, frequent mitoses, extensive necrosis, significant vascularity, and small amounts of immature matrix seem to be aggressive in their behavior, in contrast to tumors that exhibit fewer of these histologic features. Altiiough histologic features are always considered in assigning grade, clinical and radiologic data may also be important in assessing biologic aggressiveness.

Enneking defined only two grades based on histologic, clinical, and radiologic criteria. Odier systems have three or four grades based solely on histologic features. Even among expert pathologists, there is significant difficulty in obtaining agreement in the grading of soft tissue sarcomas, especially in a three- or four-grade system. Despite disagreement about the appropriate number of grades and the manner of assigning them, it is clear that grade should be weighted heavily in any staging system. Ulümately, the assignment of a grade should assist in predicting the likelihood of local recurrence and the risk of distant metastasis.

The location of a tumor as well as its size in relation to the anatomic area it occupies may directly influence the patient's prognosis. The risk of local recurrence and distant metastasis is greater for large than for small tumors. Furthermore, location and size influence the choice of local treatment and assessment regarding adjunctive tíierapy. As already mentioned, a musculoskeletal neoplasm may be intra- or extracompartmental. Intracompartmental tumors are bounded in all dimensions by natural barriers to extension. Extracompartmental tumors are those that have arisen in an extracompartmental location or have extended beyond the natural barriers by either growth or contamination; and their presence may be an indication of invasiveness.

Whereas location has obvious implications for the technical aspects of local control, size may or may not be a significant factor. According to Suit et al, the probability of distant metastasis increases with the size of a soft tissue sarcoma, independent of the histologic type or grade.5 The principal factors governing the extent of the surgical margins and the type of local treatment to be used are the specific compartment or compartments involved and the proximity of the tumor to vital neurovascular structures. Intracompartmental tumors that are smaller than the involved compartment will allow for wider surgical margins of normal tissue and a greater probability of local control.

Concerning depth, Collin et al have shown that approximately 50% of adult soft tissue sarcomas are subcutaneous, and that these generally have a less aggressive biologic behavior than do their deep counterparts.6 This suggests that subcutaneous tumors should be designated as being in a separate intracompartmental site. Or, alternatively, subcutaneous lesions are usually small and may be so designated.

The presence of regional or distant metastases is the most important prognostic variable and needs to be included in any staging system. Musculoskeletal neoplasms infrequently metastasize to regional lymph nodes, but distant metastasis without regional lymph node involvement is possible. According to Enneking, regional and distant metastasis confer an equally poor prognosis.2

Clinical Applications

Most of the current staging systems include the foregoing variables in the assignment of an appropriate stage. Differences among systems involve the assignment of relative prognostic significance and the organization of prognostic variables into a practical and meaningful scheme. Before specific staging systems can be discussed, it is necessary to understand how these variables are defined clinically.

Table

TABLE 1AMERICAN JOINT COMMISSION STAGING PROTOCOL FOR SARCOMA OF SOFT TISSUE9

TABLE 1

AMERICAN JOINT COMMISSION STAGING PROTOCOL FOR SARCOMA OF SOFT TISSUE9

Table

TABLE 2ENNEKING SYSTEM FOR STAGING OF SOFT TISSUE SARCOMA AND SARCOMA OF BONE2

TABLE 2

ENNEKING SYSTEM FOR STAGING OF SOFT TISSUE SARCOMA AND SARCOMA OF BONE2

For clinical application, acquisition of histologic data requires that a biopsy be performed. Preoperatively, information about the biologic behavior of a tumor can be obtained with several imaging techniques. Details about tumor size, location, and proximity to vital neurovascular structures may be determined with radiography, scintigraphy, computed tomography, and magnetic resonance imaging (MRI). In the search for regional and distant metastases, a chest radiograph, a computed tomogram (CT) of tire lungs, and bone scintigraphy are of value. Thus, preoperative staging can be accomplished with an appropriate combination of imaging procedures.7 For staging of both bone and soft tissue sarcomas, conventional radiography of the involved limb and lungs, technetium 99m-phosphonate bone scintigraphy, MRI of the involved limb, and CT of the lungs and involved limb are used routinely. For soft tissue sarcomas, inclusion of gallium 67-citrate scintigraphy may reveal nonpulmonary distant metastases that were not detected in other routine staging studies.8

Staging of Sarcomas of Soft Tissues in Adults

The three systems currently in use for the staging of adult soft tissue sarcomas are summarized in Tables 1 through 3. These systems do not apply to rhabdomyosarcomas in children and adolescents.

The American Joint Cornmission on Cancer System

The recently revised system of the American Joint Commission on Cancer (Table 1) is based on the T, N, M system and the histologic grade (G). 1>5'9 (In this system, T refers to tumor size, N to nodal metastases, and M to distant metastases.) There are four progressive stages: Stages I, II, and III are based primarily on histologic grade (G1, G2, and G^sub 3-4^, respectively), and Stage IV is based on the presence of either regional lymph node metastases (Stage TVA) or distant metastases (Stage IVB). In this system, tumor size is an important factor; each of the first three stages is subdivided into T1 (greatest dimension 5 cm or less) and T2 (greatest dimension greater than 5 cm).

Enneking System

Enneking's alternative system (Table 2) can be applied to both sarcomas of bone and primary sarcomas of soft tissue.2 The stages in this system are based on three factors: surgical grade (G), surgical site (T), and the presence or absence of metastasis (M). The assignment of a surgical grade is determined mainly by histologic criteria; clinical and radiologic data may be incorporated, but this is done more often for bone than for soft tissue sarcomas. The surgical grade, as decided upon by the surgeon and pathologist, is either low (G1: less than 25% risk of metastasis) or high (G2: greater than 25% risk of metastasis).

The surgical site (T) may be either intracompartmental (A) or extracompartmental (B); this information is obtained before surgery by means of conventional staging studies and is confirmed by the operative findings. A tumor is classed as intracompartmental if it is bounded by natural barriers to extension such as bone, fascia, synovium, periosteum, or cartilage. An extracompartmental tumor may be primary (arising in an extracompartmental location) or secondary (an intracompartmental tumor penetrating into an additional compartment by means of natural extension or through surgical contamination).

Table

TABLE 3HAiDU SYSTEM FOR STAGING OF SOFT TISSUE SARCOMA,1

TABLE 3

HAiDU SYSTEM FOR STAGING OF SOFT TISSUE SARCOMA,1

A tumor is assigned to Stage III if metastasis to regional lymph nodes or to distant sites is present (M1). Thus, in Enneking 's system, a tumor may be either in Stage I or Stage II depending on grade, with the stage being further defined as A or B depending on its site; or in Stage III if any metastasis is present.

Hajdu System

The third system, for soft tissue sarcomas only, is that devised by Hajdu (Table 3), in which tumor size, site (depth), and histologic grade are grouped into four major stages.3 The grade is determined only from histologic data, and the site is classified as either above (subcutaneous) or below the superficial fascia. Good prognostic signs include small size (less than 5 cm), subcutaneous location, and low histologic grade. Poor prognostic signs include large size (greater than 5 cm), location deep to the superficial fascia, and high histologic grade. In stage 0, all three prognostic signs are good; in Stage I, two are good and one is poor; in Stage II, one is good and two are poor; and in Stage III all three are poor.

Discussion

Each of the three staging systems for soft tissue sarcomas directly or indirectly incorporates the important prognostic variables of grade, location, size, depth, and lymph node or distant metastasis. It is difficult to devise an adequate three- or four-grade system that will be agreeable to and reproducible by all pathologists. The American Joint Commission gives no detailed guidelines for the four grades in its system, and there may be no practical distinction between the commission's Stages I and II, which are based solely on minor histologic criteria.

The American Joint Commission system and the Hajdu system place a great deal of emphasis on the size of the tumor. Suit and associates are also emphatic about the importance of tumor size.5 Although size may influence prognosis, the proximity of a tumor to neurovascular structures and its size relative to the compartment involved may be considered of more practical importance for surgical strategy. It is obvious that the Enneking system addresses the anatomic site from a more surgical perspective than do the other two, by using the concept of anatomic compartments. However, the Enneking system does not allow for separate consideration of superficial (usually small) tumors, and size is only an indirect variable. Hajdu has incorporated depth as a prognostic variable in his staging system. In the current Enneking staging system, a subcutaneous lesion should perhaps be considered as a third (T) site.

Regional nodal metastases are infrequent in adult soft tissue sarcomas, and the prognosis is similar to that for distant metastases. Therefore, it seems logical to group the two together for simplicity. We believe there is no practical distinction between stage IVA and IVB of the American Joint Commission system. Thus, in all three staging systems for adult soft tissue sarcomas, histologic grade and the presence or absence of metastasis are the most important prognostic variables. There are some differences in the method of assessing histologic or surgical grade. The size, depth, and anatomic site of each tumor are deemed important, but the hierarchy of their importance is unknown, and how they should be weighted in a staging system remains unresolved.

Staging of Sarcomas of Bone

Enneking System

The initial staging system for bone sarcomas was described by Enneking; it is identical to the system that applied to soft tissue sarcomas (Table 2).2 As in the staging of soft tissue sarcomas, both grade and metastasis are included, but the concept of compartments must be clarified further for bone. Intracompartmental bone tumors are those within the confines of the cortex or periosteum (T1), and extracompartmental bone tumors are those that have extended into the soft tissue (T2). The T, designation is also applied to parosteal tumors that have not extended into the underlying cortex.

American Joint Commission System

In 1983 the American Joint Commission recommended a staging system for malignant tumors of bone. At that time, the committee emphasized that its task force on bone tumors was still considering the problem of staging, and that further recommendations would be made in the future. The system described in 1983 has remained unchanged in the third edition of the American Joint Committee's Manual for Staging of Cancer (Table 4).4 In mis system, also, the T, N, M, designation with the addition of grade (G) is used, with G referring to histologic grade, T to the extent of the tumor (confined to or extending beyond the cortex of the bone), N to nodal metastasis, and M to distant metastasis. There are four progressive stages, designated as I to IV. Stages I and II are defined by the histologic grade and modified by cortical involvement (T1, confined within the cortex, and T7, extending beyond the cortex). In this system, Stage 111 remains undefined, and Stage IV is subdivided according to die presence or absence of metastasis. Stage IV is further modified as A, nodal metastasis, or B, distant metastasis.

Table

TABLE 4AMERICAN JOINT COMMISSION STAGING PROTOCOL FOR SARCOMAS OF BONE4

TABLE 4

AMERICAN JOINT COMMISSION STAGING PROTOCOL FOR SARCOMAS OF BONE4

Discussion

For bone sarcomas, if one carefully compares the American Joint Commission system to the Enneking system, it is apparent that the differences are minor. The American Joint Commission system defines four grades based on histologic features but groups them in such a way that, in practice, only two grades exist. For bone, it also seems that only two histologic grades are needed, and that clinical and radiologic criteria should be considered in the determination of grade.

Table

TABLE 5ENNEKING PROTOCOL FOR THE STAGING OF BENIGN MUSCULOSKELETAL NEOPLASMS10

TABLE 5

ENNEKING PROTOCOL FOR THE STAGING OF BENIGN MUSCULOSKELETAL NEOPLASMS10

The anatomic site (T) is essentially identical in the two systems. The only real difference is that the American Joint Commission has a designated, but undefined. Stage III. It appears that the American Joint Commission uses the four-stage system as a standard in staging of any type of tumor, perhaps because it is more acceptable worldwide than is a three-stage system. Furthermore, the American Joint Commission considers nodal and distant metastasis separately. From a practical standpoint, we believe that there is no need to separate nodal from distant metastasis. In essence, the American Joint Commission staging system for bone is an adaptation of the Enneking system.

Biologic Behavior and Staging of Benign Tumors of Bone

Enneking's is the only system for the staging of benign musculoskeletal tumors currently in use (Table 5).10 This system is based on die biologic behavior of these tumors.

Benign tumors of bone are seen most frequently in skeletally immature or growing individuals. They tend to be modestly destructive and either grow slowly or are dormant. Growth occurs in a centripetal fashion, as with their malignant counterparts, and, similarly, with formation of a reactive capsule as the host's response to the tumor. The extent of the reactive capsule reflects the rate of tumor growth: Slowly growing tumors usually have a thick, well defined capsule, whereas the capsule in those that are growing rapidly is poorly defined or barely detectable.

Because they lack histologic uniformity, benign tumors of bone are graded on the basis of clinical and radiologic criteria. Tb distinguish them from the stages of malignant tumors, die stages of benign tumors are designated by Arabic numbers (Table 5).'° This designation, together with the use of T, N, M, and G, makes it possible to combine benign and malignant neoplasms of both bone and soft tissue into a common staging system (Table 6). ,0 In this combined system, which was also proposed by Enneking, G0 designates a histologically benign tumor and T0 specifies an intracapsular location. In benign tumors, distant metastasis is rare, but does occasionally occur. Thus, for both benign and malignant tumors, M0 indicates the absence and M1 the presence of metastasis.

Table

TABLE 6ENNEKING COMBINED STAGING SYSTEM FOR BENIGN AND MALIGNANT MUSCULOSKELETAL TUMORS10

TABLE 6

ENNEKING COMBINED STAGING SYSTEM FOR BENIGN AND MALIGNANT MUSCULOSKELETAL TUMORS10

A Stage 1, latent benign bone tumor is always intracapsular and never metastasizes. Such tumors are usually asymptomatic and are discovered as an incidental radiologic finding. A thick, dense reactive capsule is present on both plain radiographs and CT. The lesion may or may not be inactive on technetium 99m-phosphonate bone scintigrams.

A Stage 2, active benign bone tumor, like a Stage 1 tumor, is intracapsular, and it almost never metastasizes. However, these tumors are actively growing and enlarging and therefore may elicit signs and symptoms. In some cases, destruction of die cortex leads to a pathologic fracture. A Stage 2 tumor demonstrates a thin rim of reactive encapsulation but remains within its confines. In addition, it produces moderate activity on technetium 99m-phosphonate bone scintigraphy, but the activity is usually limited to the area visible on a plain radiograph.

A Stage 3, aggressive benign bone tumor often breaks through the reactive capsule, becoming extracapsular or intracompartmental (T1); occasionally it becomes extracompartmental and extends into soft tissues (T2). Distant metastasis may be seen with up to 5% of these tumors.

Stage 3 lesions are growing at a faster rate than are those in Stage 1 or 2, and they are found both clinically and radiologically to be more aggressive. Pain and tenderness are common, and a mass may be detected on physical examination. Radiographs demonstrate any extension into surrounding tissues, and technetium 99m-phosphonate bone scintigrams demonstrate significant activity that extends beyond the lesion. Malignancy may be suspected in such cases.

Conclusion

The recent emphasis on limb salvage rather than amputation for bone and soft tissue sarcomas of the extremities requires a multimodality therapeutic approach in which limited surgery is combined wim adjuvant or neoadjuvant radiation therapy and chemotherapy. In current studies, attempts are underway to refine and improve these modalities further. An essential aspect of their proper design and application is a fundamental knowledge of the factors that affect patient survival . In the staging systems described above, only tumor-related factors, ie, grade, site, depth, size, and extent of disease, are addressed. It is likely that, over the next decade, some modifications and compromises will be made in the staging of adult soft tissue sarcomas so that a more unified system will evolve. For sarcomas of bone, major changes in the staging systems are less likely in the near future.

It is important to be aware that factors other than those pertaining to the tumor also affect survival. These include patient variables such as age, sex, presence of symptoms (in the case of soft tissue sarcomas), and anatomic site (proximal versus distal); treatment variables such as surgical treatment given, surgical margins, use of adjuvant chemoüierapy or adjuvant radiation therapy, or local treatment failure; and biopsy techniques, as well as many biologic factors that remain undefined at present but are related to the prognosis. The survival of patients with sarcomas of bone and soft tissue is affected by a complex interaction of host, tumor, and treatment parameters.

References

1. Russell WO, Cohen J, Enzinger F, et al. A clinical and pathological staging system for soft tissue sarcomas. Cancer. 1977;40:1562-1570.

2. Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop. 1983;153:106-120.

3. Hajdu SI. Pathology of Soft Tissue Tumors. Philadelphia: Lea & Febiger; 1979;35-47.

4. American Joint Commission on Cancer Bone. In Beahrs OH. Myers MH, eds. Manual for Staging of Cancer, 3rd ed. Philadelphia: JB Lippincott; 1988;123-125.

5. Suit HD, Mankin HJ, Wood WC, et al. Treatment of the patient with stage M0 soft tissue sarcoma. J Clin Oncol, 1988;6:854-862.

6. Collin C, Godbold J, Hajdu S, et al. Localized extremity soft tissue sarcoma: An analysis of factors affecting survival. J Clin Oncol. 1987;5:601-612.

7. Simon MA. Diagnostic and staging strategy for musculoskeletal tumors. In E vans CM. ed. Surgery of the Musculoskeletal System. New York: Churchill Livingstone; I983;4:l 1:16-1 1:24.

8. Finn HA, Marlin WB, Darakjian H, et al. The clinical utility of gallium-67 citrate scintigraphy in the initiai staging of soft tissue sarcomas of the extremities. J Bone Joint Surg. 1987;69A:886-891.

9. American Joint Commission on Cancer. Soft tissues. In Beahrs OH, Myers MH, eds, Manual for Staging of Cancer, 3rd ed. Philadelphia: JB Lippincott; I988;127-I3I.

10. Enneking WF. Staging musculoskeletal tumors. In Enneking WF, ed. Musculoskeletal Tumor Surgery. New York: Churchill Livingstone; 1983;87-88.

TABLE 1

AMERICAN JOINT COMMISSION STAGING PROTOCOL FOR SARCOMA OF SOFT TISSUE9

TABLE 2

ENNEKING SYSTEM FOR STAGING OF SOFT TISSUE SARCOMA AND SARCOMA OF BONE2

TABLE 3

HAiDU SYSTEM FOR STAGING OF SOFT TISSUE SARCOMA,1

TABLE 4

AMERICAN JOINT COMMISSION STAGING PROTOCOL FOR SARCOMAS OF BONE4

TABLE 5

ENNEKING PROTOCOL FOR THE STAGING OF BENIGN MUSCULOSKELETAL NEOPLASMS10

TABLE 6

ENNEKING COMBINED STAGING SYSTEM FOR BENIGN AND MALIGNANT MUSCULOSKELETAL TUMORS10

10.3928/0147-7447-19891001-13

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