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BACKGROUND Prognostic factors for metastasis in soft tissue sarcoma govern decisions regarding adjuvant treatment. However, the significance of initial tumor-related prognostic factors over time is largely unknown. METHODS The current study included 338 patients with malignant fibrous histiocytoma (MFH) of the extremities or the trunk wall whose tumors were reviewed by the Scandinavian Sarcoma Pathology Review Group. Of these 338 patients, 329 (97%) had high-grade tumors. The median follow-up period was 7 years. Metastases occurred in 110 of 338 of patients after a median follow-up period of 14 months, with roughly one-third (32 of 110) occurring after 2 years. The authors investigated the prognostic significance of tumor size, tumor depth, histologic grade, microscopic tumor necrosis, vascular invasion, mitotic rate, and local tumor recurrence at various time intervals using metastases as an endpoint. RESULTS On univariate analysis, all investigated factors were found to be correlated with metastases for the entire follow-up period and also for the first 2 years of follow-up; beyond this time point, only size, tumor depth, and local recurrence were significant. On multivariate analysis, necrosis and local tumor recurrence were significant for the entire follow-up duration and also for the first 2 years of follow-up, whereas only tumor depth and local recurrence were significant beyond 2 years of follow-up. For all initial factors, the annual metastasis risks in the high-risk and low-risk groups converged to < 0.1 after 2 years and to near 0 after 5 years. CONCLUSIONS Prognostic factors for metastasis in MFH were time dependent. The predictive value of the initial prognostic factors was limited to the first 2 years of follow-up. The lack of observed prognostic value beyond 2 years of follow-up probably was attributable to heterogeneity within risk categories as a result of measurement errors and unknown biologic variations. Cancer 2004. © 2004 American Cancer Society.

In this study, we examined the relationship of 19p13 aberrations, usually leading to addition of unknown material (19p+), and ring chromosomes to clinical outcome in patients with malignant fibrous histiocytoma (MFH). Analysis of 69 MFHs revealed 19 tumors with 19p+ and 24 tumors with ring chromosomes. After a median follow-up period of 36 months, 24 patients developed metastases, and 27 patients developed local recurrences. Ten patients had both local recurrences and metastases. Local recurrence was more common in association with 19p+ than without. Metastasis was more common with 19p+ tumors in high-risk patients (tumor size > 5 cm and grade III-IV; n = 48) than those without 19p+. There was a trend suggesting fewer relapses after tumors with ring chromosomes. 19p+ may be an independent marker of unfavorable outcome in MFH.

We have shown that the clinical growth rate of local recurrence from soft-tissue sarcoma could be expressed as a growth-rate index (GRI) which was predictive for metastasis, and which was able to identify 2 equal populations of good (80% 2-year MFS) and poor survivors (33%). We now report the associations between characteristics of the primary and GRI, and combine primary and locally recurrent tumour characteristics in a staging system. We studied 460 adult patients with soft-tissue sarcomas of the extremities and trunk wall who were diagnosed and treated between 1964 and 1990, of whom 134 developed local recurrences and 151 metastases. The association of primary tumour size, histologic malignancy grade, depth, spontaneous necrosis, intratumoral vascular invasion and S-phase fraction with local recurrence, GRI and metastasis were examined. High GRI was associated with primary tumours that were larger, deeper, more malignant, underwent spontaneous tumour necrosis, demonstrated intravascular invasion and had a higher S-phase fraction. The same factors were also strongly associated with the incidence of metastasis. A multivariate analysis found GRI and primary tumour necrosis to be the strongest and most significant prognostic factors. GRI and tumour necrosis were combined in a staging system that identified groups with good survival (79 to 94% 2-year MFS), intermediate survival (61% 2-year MFS) and exceptionally poor survival (6% 2-year MFS). These findings validate our earlier assertion that high GRI reflects highly malignant tumours. A staging system composed of primary tumour necrosis and GRI can identify patients who may be suitable candidates for trials of adjuvant chemotherapy.

A 15-year-old girl had Ewing's sarcoma of the right scapula 1978 and was treated with local radiotherapy and adjuvant chemotherapy. She remained in complete remission until September 1982 when she developed a single pulmonary metastasis in the right lower lobe. She received a high dose of Melphalan twice, always followed by autologous bone-marrow transplantation. A segmental right lower lobectomy revealed haematopoietic bone-marrow tissue emboli within the alveolar capillaries and foreign body granulomatous lesions in the whole surgical specimen. No residual Ewing's sarcoma growth was seen.