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© 2001 American Society for Clinical Oncology Clinicopathologic Re-Evaluation of 100 Malignant Fibrous Histiocytomas: Prognostic Relevance of SubclassificationFrom the Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; and Departments of Orthopedics and Pathology and Cytology, University Hospital, Lund, Sweden. Address reprint requests to Pelle Gustafson, MD, PhD, Department of Orthopedics, University Hospital, SE-221 85 Lund, Sweden; email: pelle.gustafson{at}ort.lu.se
PURPOSE: Malignant fibrous histiocytoma (MFH) has been regarded as the most common soft tissue sarcoma (STS) in adults. Yet its true nature and the validity of this diagnostic concept have increasingly been questioned. Available data suggest that most patients with MFH can be subclassified into specific STS types, but the clinical relevance of such categorization has been argued. In a retrospective study, we reclassified 100 tumors of the extremity and trunk wall primarily diagnosed as MFH and analyzed the outcome. PATIENTS AND METHODS: Patients were adults (median age, 70 years; range, 32 to 94 years). The median tumor size was 8 cm (range, 1 to 30 cm), and the thigh was the most common tumor location (n = 31). Median follow-up was 8 years (range, 3 to 16 years). The overall 5-year metastasis-free survival rate was 0.64. The tumors were reanalyzed histologically, immunohistochemically, and, where available, ultrastructurally, and were classified according to strict diagnostic criteria. Patients were staged according to the American Joint Committee on Cancer system, and prognoses were compared among different groups of the reclassified diagnoses, paying special attention to myogenic tumors. RESULTS: In 84 of 100 tumors, a specific line of differentiation was either proved or strongly suggested. The most common diagnoses were myxofibrosarcoma (n = 22) and leiomyosarcoma (n = 20). Overall, 30 tumors could be grouped as some form of myogenic sarcoma. These tumors had a worse prognosis, even within the same American Joint Committee on Cancer stage, and a shorter time to metastasis than nonmyogenic tumors. CONCLUSION: This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.
MALIGNANT FIBROUS histiocytoma (MFH) was first described in the early 1960s.1-3 After publication of an article entitled "Fibroxanthosarcoma of the soft tissues: A type of malignant fibrous histiocytoma" by Kempson and Kyriakos in 1972,4 MFH became widely accepted as a specific soft tissue sarcoma (STS) type.5-7 The light-microscopic description provided was universally accepted as the prototype for storiform-pleomorphic MFH. Four other variants of MFH, myxoid, giant cell, inflammatory, and angiomatoid, with the latter three being rare, were described and morphologically defined between 1972 and 1979. Thereafter, MFH was generally accepted as the most common type of STS.8-12 Several large series focusing on prognosis have been published.13-16 However, for many years, there has been discussion about the histogenesis, or line of differentiation, shown by MFH.17-19 Various theories have been proposed, most notably those of a fibroblastic or dual fibroblastic-histiocytic tumor, or origin from primitive mesenchymal cells capable of showing variable differentiation. None has been universally accepted despite extensive application of various diagnostic methods, including electron microscopy, histochemistry, immunohistochemistry, and cytogenetics. These findings have led pathologists to question MFH as a discrete entity. It was proposed that MFH, especially the most common type (the storiform-pleomorphic), could represent a common morphologic appearance shared by various poorly differentiated STS as well as other tumor types. This hypothesis was based on tumors that showed areas of well-defined types of STS adjacent to so-called pleomorphic MFH.20,21 It was suggested that MFH represented a final common pathway of tumor progression. Fletcher19 then reappraised a large series of pleomorphic sarcomas and claimed that it was possible to find a specific line of differentiation in most of the tumors investigated. In a later review,22 the various subtypes of MFH were reanalyzed, and it was concluded that the only variants that could be regarded as specific and reproducible entities were myxoid MFH and angiomatoid MFH; it was also proposed that the term myxoid MFH be changed back to the original term myxofibrosarcoma, as had been first proposed by Angervall et al.23 The other types of MFH were considered to represent a morphologic manifestation of progression shared by various STS, as well as other neoplasms including carcinoma and malignant lymphoma. In a recent series of pleomorphic sarcomas studied by Schurch et al,24 most were found to express a myogenic line of differentiation (pleomorphic leiomyosarcoma or pleomorphic rhabdomyosarcoma), and these authors concluded that these pleomorphic myogenic tumors often exhibited histomorphologic similarities to storiform-pleomorphic MFH, and that accurate diagnosis demanded the use of ancillary techniques. Arguments commonly raised against the subclassification of pleomorphic STS, which are often lumped together as MFH, have included issues of reproducibility and, more importantly, the lack of clear evidence that such categorization has any clinical utility. We have therefore retrospectively analyzed 100 consecutive patients with MFH of various subtypes, diagnosed as such after 1990, to see if specific lines of differentiation could be demonstrated. Furthermore, we determined whether the patient outcome differed according to the line of differentiation identified, with special focus on tumors with myogenic differentiation.
Patients The population-based database at the Musculoskeletal Tumor Center in Lund, Sweden, holds details of 700 patients with STS of extremity and trunk wall diagnosed between 1964 and 1997. Patients have been identified via the Regional Tumor Registry. The database therefore comprises all patients in the Southern Swedish Health Care Region (1.6 million inhabitants), irrespective of whether the patients have been treated at the University Hospital in Lund or at local hospitals in the region. Criteria for inclusion in the database as well as classification of histopathology (including malignancy grading) and treatment have previously been described.8 From this database, 101 patients with MFH treated between 1980 and 1995 with primary surgery in Lund and with all paraffin-embedded samples available for recutting were selected. In 1989 to 1990, all patients diagnosed between 1964 and 1990 had been re-evaluated for our previous report on MFH13; therefore, all MFH diagnoses were made according to criteria in use after 1989. In the present series, one tumor was reclassified from myxoid MFH to nodular fasciitis, and thus 100 patients remained for analysis. The 100 patients, 55 of whom were men, had a median age of 70 years (range, 32 to 94 years) and a median tumor size of 8 cm (range, 1 to 30 cm). Five patients had metastasis at diagnosis (four pulmonary and one skeletal). The thigh was the most common primary site. Thirty-one tumors were subcutaneous. According to the Enzinger and Weiss classification of subtype, 61 tumors had been diagnosed as pleomorphic-storiform MFH, and 39 tumors were myxoid MFH.11 Two tumors were grade I, six tumors were grade II, 16 tumors were grade III, and 76 tumors were grade IV. According to the American Joint Committee on Cancer staging system (5th edition),25 seven patients were stage I (six IA and one IB), 32 patients were stage II (one IIA, 21 IIB, and 10 IIC), 56 patients were stage III, and five patients were stage IV. All patients were surgically treated, 11 with marginal excision without radiotherapy and 89 with marginal excision with radiotherapy or wide or radical excision. A total of 96 of the patients underwent limb-sparing surgery. Five patients received chemotherapy, all of them postoperatively. No patient was lost to follow-up. The median follow-up time for the 45 patients alive at last follow-up was 8 years (range, 3 to 16 years). Twenty-seven patients developed local recurrence. At the latest follow-up, 37 patients had developed metastasis, giving a 5-year metastasis-free survival rate (MFSR) of 0.64. Of the 55 patients who were dead at last follow-up, 35 had died as a result of tumor, four patients had tumor but died as a result of other causes, and 16 patients were without tumor but died as a result of other causes. The total follow-up period was 513 person-years. Compared with all 288 MFH in our population-based database, the 100 patients were a representative in terms of age, sex, localization of disease, and MFH subtype. This series differed in terms of grade IV tumors, which were more common (76% v 65%), and the median tumor size was larger (8 cm v 7 cm). There was also a trend in this series for tumors being more often deep-seated (69% v 62%). These findings likely reflect the fact that large, high-grade, deep-seated tumors are more often referred to the specialist center in Lund, and hence the accessibility of their pathology materials for review.
Histopathologic Re-Examination Pleomorphic liposarcoma was a high-grade malignant pleomorphic or spindle-cell tumor that, in the absence of any other evident specific differentiation, contained multivacuolated lipoblasts. Dedifferentiated liposarcoma was a high-grade nonlipogenic spindle-cell neoplasm with a variably pleomorphic or myxoid matrix that, in the absence of any other specific differentiation, developed in association with (or as a recurrence of, although this was not the case in this series) an atypical lipomatous tumor (well-differentiated liposarcoma). The latter was defined by the presence of adipocytic atypia and bizarre stromal cells, with or without lipoblasts, in an otherwise well-differentiated lipomatous neoplasm. Leiomyosarcoma was a tumor that at least focally showed the presence of eosinophilic spindle cells with vesicular blunt-ended nuclei arranged in a fascicular pattern. Such foci always accounted for at least 5% to 10% of the surface area examined. The tumors with these characteristics were required also to show extensive positivity for smooth-muscle actin (SMA); desmin was also strongly, if only focally, positive in most specimens. Pan-muscle actin (HHF-35) showed extensive positivity in all specimens. Fast myosin and myoglobin were always negative. Pleomorphic rhabdomyosarcoma was a high-grade pleomorphic spindle-cell sarcoma often containing large polygonal cells that usually demonstrated copious brightly eosinophilic cytoplasm. The tumor cells were strongly positive for desmin in all cases and always coexpressed either fast myosin or myoglobin. HHF-35 was usually diffusely positive, but SMA was either negative or else stained cells only rarely. Cytoplasmic cross-striations were not a required feature. Pleomorphic myogenic sarcoma was a high-grade pleomorphic spindle-cell tumor, expressing either desmin or SMA in many cells, but failing to fulfill morphologic or additional immunophenotypic features for either leiomyosarcoma or rhabdomyosarcoma. Possibly myogenic pleomorphic sarcoma comprised pleomorphic spindle-cell sarcomas, often containing cells with prominent eosinophilic cytoplasm, but that showed only HHF-35 positivity and that were negative for SMA, desmin, fast myosin, or myoglobin. Myxofibrosarcoma (myxoid MFH) was characterized by the presence, at least focally, of distinctive nodular myxoid areas with atypical, hyperchromatic spindled or multinucleate cells, mucin-containing, finely vacuolated cells, and distinctive curvilinear vessels. This component of the tumor showed no evidence of specific differentiation by immunohistochemistry. Tumors could display low, intermediate, or high-grade malignancy, depending on cellularity and the presence of a variably prominent, solid, pleomorphic, and spindle-cell component.27 Focal actin positivity (HHF-35 or SMA) was quite common in the nonmyxoid areas, but desmin was always negative. Myofibroblastic sarcoma was a pleomorphic spindle-cell sarcoma with either storiform or fascicular growth patterns composed mainly of cells with pale or moderately eosinophilic cytoplasm (without sharply defined cell borders) and pointed, tapering, or somewhat wavy hyperchromatic nuclei. In undoubted cases, there was always widespread positivity for HHF-35 or SMA but not for desmin, and the nuclear features were not convincing for leiomyosarcoma (see above). In those specimens listed as possibly myofibroblastic sarcoma, the staining for actins was more limited in extent, although usually there was staining in at least 20% of tumor cells. Soft tissue osteosarcoma comprised pleomorphic spindle-cell neoplasms that, in the absence of other specific differentiation, showed bone or osteoid production in connection with cytologically malignant cells. Malignant mesenchymoma comprised tumors that showed two separate and distinct lines of specific malignant mesenchymal differentiation, proven either morphologically or immunohistochemically. The following patterns were not accepted: undifferentiated sarcoma, fibrosarcoma, myxofibrosarcoma, pleomorphic MFH-like sarcoma, and hemangiopericytoma. Specific dedifferentiated sarcomas were also excluded, as were malignant peripheral nerve sheath tumors showing heterologous differentiation. Finally, pleomorphic sarcoma not otherwise specified (NOS) comprised all pleomorphic spindle-cell sarcomas that did not show evidence of specific differentiation by the criteria outlined above. These tumors were also negative for epithelial, melanocytic, and hematopoietic markers.
Electron Microscopy
Staging and Statistics
Histopathologic Classification In 84 of the 100 tumors, a specific line of differentiation was either found or suggested. The most common diagnosis was high-grade myxofibrosarcoma (n = 23), then high-grade leiomyosarcoma (n = 20) (Table 1).
In the original classification, 39 tumors had been classified as myxoid MFH. Twenty-two of these were reclassified as myxofibrosarcoma, three as leiomyosarcoma, three as liposarcoma, three as pleomorphic sarcoma NOS, two as malignant peripheral nerve sheath tumor, three as myofibroblastic sarcoma, and one each as fibromyxoid sarcoma, dermatofibrosarcoma protuberans with fibrosarcomatous change, and spindle-cell and myxoid sarcoma NOS. Of the 61 tumors originally classified as storiform-pleomorphic MFH, 17 were reclassified as leiomyosarcoma, 11 as pleomorphic sarcoma NOS, seven as myofibroblastic sarcoma, eight as pleomorphic myogenic sarcoma, six as high-grade myxofibrosarcoma, three as soft tissue osteosarcoma, two as malignant mesenchymoma, two as spindle-cell sarcoma NOS, and one each as pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, pleomorphic-myxoid sarcoma, myogenic spindle-cell sarcoma, and sarcomatoid carcinoma. For the purposes of survival analyses (below), leiomyosarcoma, rhabdomyosarcoma, pleomorphic myogenic sarcoma, and myogenic spindle-cell sarcoma were grouped together as one category showing myogenic differentiation (n = 30).
Clinical Characteristics
Outcome In the 88 patients with stage II or stage III tumors according to the American Joint Committee on Cancer system, 26 patients with myogenic tumors had a worse 5-year MFSR (0.45) than 62 patients with tumors without myogenic differentiation (0.73) (P = .006) (Fig 1). The difference was most pronounced in stage III tumors. Four of the five patients in stage IV (metastases at diagnosis of the primary tumor) had tumors with myogenic differentiation.
For most of the past 25 years, MFH, particularly in its storiform-pleomorphic and myxoid forms, has been regarded as the single most common type of STS. As a consequence, it has featured prominently in many outcome or grading studies. Despite this fact, many pathologists harbored doubts regarding the validity of this diagnostic concept that essentially took the field of sarcomas by storm in the 1970s and 1980s. By 1990, MFH had also been described in virtually every organ in the body and there were more than 1,000 indexed publications on this tumor type. Yet there were no defined criteria by which to make this diagnosis, and some clinicians became increasingly concerned that this was a default term for almost any morphologically pleomorphic and spindle-cell neoplasm. We (and other clinicians) also noticed that the spectrum of clinical behavior in MFH (treatment sensitivity including time to metastasis and pattern of metastasis), as well as ultimate outcome, was remarkably variable, and this did not always correlate reliably with histologic grade. The advent of immunohistochemistry in the 1980s led many authors to try to validate the originally proposed histiocytic nature of MFH. This was in vain. It was increasingly believed that these lesions were composed of either primitive mesenchymal cells or of fibroblasts that had the capacity to manifest a broad spectrum of differentiation.17 The problem with this conclusion was that it left only the rather subjective morphology as assessed via hematoxylin and eosin–stained sections as a diagnostic criterion. It became abundantly clear, as studies of differentiation became more numerous and sophisticated, that the morphologic appearance known as pleomorphic MFH could be shared by many different tumor types. A major retrospective study published in 199219 demonstrated that most pleomorphic sarcomas could be definably subclassified into specific sarcoma types with reproducible criteria (eg, liposarcoma and leiomyosarcoma). Furthermore, by taking the trouble to identify the line of differentiation in these lesions, one could also identify a subset of cases that represented misclassified metastatic carcinomas, melanomas, and sarcomatoid lymphomas. Since then, the credibility of MFH as a diagnostic concept has progressively diminished, and at the least, there has been general consensus among soft tissue pathologists that every effort should be made to identify the nonsarcoma tumors previously subsumed under this diagnostic heading. However, some have clung to the MFH concept, citing two principal reasons: first, in these cost-conscious times, there is no evidence that subclassification has any influence on therapy; and second, there is as yet no convincing evidence that subclassification has any prognostic value. It goes without saying that any differences in treatment sensitivity or prognosis between subsets of so-called MFH could not be identified at all without histologic subclassification. There is no question that the reliable identification of tumors in this category with a more aggressive clinical course would provide a more rational basis for trials of new or more intensive chemotherapeutic regimens; conversely such data might also assist in the recognition of prognostic subsets with a low risk of metastasis and affected patients might thus be spared aggressive therapies. There already exist preliminary data that support the notion of divergent outcomes among pleomorphic sarcomas; for example, dedifferentiated liposarcomas have a metastatic risk of less than 25%,28,29 the metastatic risk in high-grade myxofibrosarcoma (at least in the first 5 years) is 35% to 40%,27,30 and most patients with pleomorphic rhabdomyosarcoma develop metastases within 2 years.31 Yet it is an indisputable fact that most tumors in each of these diagnostic categories have often been labeled simply as MFH. The purpose of the current study was to retrospectively reclassify a large series of lesions diagnosed as MFH and to see whether further histopathologic classification could be performed and whether this further classification was of clinical importance, especially in terms of demonstration of myogenic differentiation. The tumors were carefully reanalyzed initially by one of us (C.D.M.F.) in the absence of any outcome data, and a consensus diagnosis was then reached with the original study pathologists. No diagnostic differences were noted when the listed criteria were used. The newly agreed diagnoses were afterward correlated with outcome by the surgeons (who, in fact, initiated this study). The results confirm not only the relatively better prognosis of myxofibrosarcoma27 but, perhaps more importantly, demonstrate convincingly for the first time that pleomorphic sarcomas showing myogenic differentiation as a whole (ie, leiomyosarcoma, rhabdomyosarcoma, and myogenic sarcoma NOS) have a substantially higher metastatic rate and a shorter mean time to metastasis compared with other pleomorphic sarcomas. We believe that our findings provide evidence that the subclassification of so-called MFH is worthwhile. Rather than being simply an academic exercise (or controversy) among pathologists, it is of clinical relevance. In fact, if this principle is applied to larger series in a nonspecialist environment, one might expect to see even clearer discrimination into prognostic categories. The basis for this claim is the presence of an additional, almost unavoidable bias in our study: the collection of the reanalyzed tumors in a specialist center means that the original pathologic diagnoses were rendered by experienced soft tissue pathologists. As such, their threshold for recognizing uncommon STS subtypes would be lower than that for nonspecialists, and furthermore, they were well aware of (and progressively more responsive to) doubts concerning the diagnosis of MFH. Hence, they had made increasingly greater efforts to subclassify pleomorphic sarcomas in the latter part of the time that the patients were collected, thus leaving a greater proportion of unclassifiable or difficult-to-categorize lesions in this diagnostic category. It could be argued that this then raises doubts concerning the ability of pathologists consistently (or equally) to subclassify pleomorphic sarcomas. It is for this reason that we adopted defined diagnostic criteria (laid out in detail in Patients and Methods); all the study pathologists readily agreed to these, and we believe they can be widely applied. In summary, we believe that these data, combined with the prevailing doubts concerning the validity of MFH as a specific entity, provide evidence to suggest that those interested in the diagnosis and management of patients with STS should seek to minimize use of the term MFH (reserving it, if absolutely necessary, for unclassifiable pleomorphic sarcomas). Instead, effort should be concentrated on the establishment of reproducible histologic subclassification of such tumors and to develop (and tailor) clinical trials that will take account of the undoubted heterogeneity in prognosis (even within same stages as defined by the American Joint Committee on Cancer system) and treatment response that has long been diffused within this tumor category. In particular, it is clear that new and more intensive therapeutic strategies should be developed specifically for the group of pleomorphic myogenic sarcomas.
We thank Catherine Quigley, FIBMS, for her assistance with immunohistochemistry and Birgitta Carlén, PhD, for her help with electron microscopy.
1. Kauffman SL, Stout AP: Histiocytic tumors (fibrous xanthoma and histiocytoma) in children. Cancer 14: 469-482, 1961 2. Ozzello L, Stout AP, Murray MR: Cultural characteristics of malignant histiocytomas and fibrous xanthomas. Cancer 16: 331-344, 1963 3. O’Brien JE, Stout AP: Malignant fibrous xanthomas. Cancer 17: 1445-1455, 1964[Medline] 4. Kempson RL, Kyriakos M: Fibroxanthosarcoma of the soft tissues: A type of malignant fibrous histiocytoma. Cancer 29: 961-976, 1972[Medline] 5. Weiss SW, Enzinger FM: Malignant fibrous histiocytoma: An analysis of 200 cases. Cancer 41: 2250-2266, 1978[Medline] 6. Weiss SW, Enzinger FM: Myxoid variant of malignant fibrous histiocytoma. Cancer 39: 1672-1685, 1977[Medline] 7. Weiss SW: Malignant fibrous histiocytoma: A reaffirmation. Am J Surg Pathol 6: 773-784, 1982[Medline] 8. Gustafson P: Soft tissue sarcoma: Epidemiology and prognosis in 508 patients. Acta Orthop Scand 65: 1-31, 1994 (suppl 259)[Medline] 9. Singer S, Corson JM, Gonin R, et al: Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg 219: 165-173, 1994[Medline] 10. Tanabe KK, Pollock RE, Ellis LM, et al: Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer 73: 1652-1659, 1994[Medline] 11. Enzinger FM, Weiss SW: Soft Tissue Tumors (ed 3). St Louis MO: Mosby, 1995
12.
Coindre JM, Terrier P, Bui NB, et al: Prognostic factors in adult patients with locally controlled soft tissue sarcoma: A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 14: 869-877, 1996 13. Rööser B, Willén H, Gustafson P, et al: Malignant fibrous histiocytoma of soft tissue: A population-based epidemiologic and prognostic study of 137 patients. Cancer 67: 499-505, 1991[Medline] 14. Becker RL, Venzon D, Lack EE, et al: Cytometry and morphometry of malignant fibrous histiocytoma of the extremities. Am J Surg Pathol 15: 957-964, 1991[Medline] 15. Pezzi CM, Rawlings MS, Esgro JJ, et al: Prognostic factors in 227 patients with malignant fibrous histiocytoma. Cancer 69: 2098-2103, 1992[Medline] 16. Le Doussal V, Coindre JM, Leroux A, et al: Prognostic factors for patients with localized primary malignant fibrous histiocytoma: A multicenter study of 216 patients with multivariate analysis. Cancer 77: 1823-1830, 1996[Medline] 17. Fletcher CDM: Malignant fibrous histiocytoma? Histopathology 11: 433-437, 1987[Medline] 18. Dehner LP: Malignant fibrous histiocytoma: Nonspecific morphologic pattern, specific pathologic entity or both? Arch Pathol Lab Med 112: 236-237, 1988[Medline] 19. Fletcher CDM: Pleomorphic malignant fibrous histiocytoma: Fact or fiction? A critical reappraisal based on 159 tumors diagnosed as pleomorphic sarcoma. Am J Surg Pathol 16: 213-228, 1992[Medline] 20. Brooks JJ: The significance of double phenotypic patterns and markers in human sarcomas: A new model of mesenchymal differentiation. Am J Pathol 125: 113-123, 1986[Abstract] 21. Hashimoto H, Daimaru Y, Tsuneyoshi M, et al: Soft tissue sarcoma with additional anaplastic components: A clinicopathologic and immunohistochemical study of 27 cases. Cancer 66: 1578-1589, 1990[Medline] 22. Hollowood K, Fletcher CDM: Malignant fibrous histiocytoma: Morphologic pattern or pathologic entity? Semin Diagn Pathol 12: 210-220, 1995[Medline] 23. Angervall L, Kindblom L-G, Merck C: Myxofibrosarcoma: A study of 30 cases. APMIS 85A: 127-140, 1977 24. Schurch W, Begin LR, Seemayer TA, et al: Pleomorphic soft tissue myogenic sarcomas of adulthood: A reappraisal in the mid-1990s. Am J Surg Pathol 20: 131-147, 1996[Medline] 25. American Joint Committee on Cancer: AJCC Cancer Staging Manual (ed 5). In: Fleming ID, Cooper JS, Henson DE, et al (eds). Philadelphia, PA: Lippincott-Raven, 1997 26. Mertens F, Fletcher CDM, Dal Cin P, et al: Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: A report of the CHAMP study group. Genes Chromosomes Cancer 22: 16-25, 1998[Medline] 27. Mentzel T, Calonje E, Wadden C, et al: Myxofibrosarcoma: Clinicopathologic analysis of 75 cases with emphasis on the low grade variant. Am J Surg Pathol 20: 391-405, 1996[Medline] 28. McCormick D, Mentzel T, Beham A, et al: Dedifferentiated liposarcoma: Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among the pleomorphic sarcomas. Am J Surg Pathol 18: 1213-1223, 1994[Medline] 29. Henricks WH, Chu YC, Goldblum JR, et al: Dedifferentiated liposarcoma: A clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol 21: 271-281, 1997[Medline] 30. Merck C, Angervall L, Kindblom L-G, et al: Myxofibrosarcoma: A malignant soft tissue tumor of fibroblastic-histiocytic origin—A clinicopathologic and prognostic study of 110 cases using multivariate analysis. APMIS 91A: 1-40, 1983 (suppl 282) 31. Gaffney EA, Dervan PA, Fletcher CDM: Pleomorphic rhabdomyosarcoma in adulthood: Analysis of 11 cases with definition of diagnostic criteria. Am J Surg Pathol 17: 601-609, 1993[Medline] Submitted December 28, 1999; accepted March 16, 2001.
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 test. Clinicopathologic factors were univariately analyzed for influence on metastasis rate by Kaplan-Meier methods and the generalized Wilcoxon test. P < .05 was considered significant. 
