Dedifferentiated liposarcoma ofretroperitoneum and mesentery: Varied growth patterns and histological grades—A clinicopathologic study of 32 cases

Hasegawa, Tadashi; Seki, Kunihiko; Hasegawa, Fumio; Matsuno, Yoshihiro; Shimoda, Tadakazu; Hirose, Takanori; Sendo, Toshiaki; Hirohashi, Setsuo

doi:10.1053/hupa.2000.8222

Cited by 134 publications

(85 citation statements)

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“…21 Although most of the dedifferentiated liposarcomas display extensive areas of high-grade dedifferentiation, some cases have been described as having only Alterations of the RB1 gene in dedifferentiated liposarcoma T Takahira et al areas of low-grade dedifferentiation resembling fibromatosis or well-differentiated fibrosarcoma. 1,2 In this study, one case showed low-grade dedifferentiation. The behavior of dedifferentiated liposarcoma is more aggressive than that of pure welldifferentiated liposarcoma, with a local recurrence rate of 41-75%, a distant metastasis rate of 9-20%, and a disease-related mortality rate of 30-50%, 1,2,22 and low-grade dedifferentiation is not associated with an improved outcome.…”

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confidence: 48%

“…Most of the dedifferentiated liposarcomas display extensive areas of high-grade dedifferentiation resembling malignant fibrous histiocytoma or high-grade fibrosarcoma, whereas some cases contain areas of only low-grade dedifferentiation. 1,2 The behavior of dedifferentiated liposarcoma is more aggressive than that of pure well-differentiated liposarcoma. Dedifferentiation is mostly considered a time-dependent phenomenon, and several reports have suggested an association between dedifferentiation and the altered expression of specific proteins, such as MDM2, P53, H-ras, b-catenin, and retinoblastoma protein (pRB).…”

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Alterations of the RB1 gene in dedifferentiated liposarcoma

et al. 2005

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Dedifferentiated liposarcoma is a malignant adipocytic neoplasm containing a nonlipogenic sarcoma of variable histological grade that arises against the background of a pre-existing well-differentiated liposarcoma. The phenomenon of dedifferentiation is considered to be time-dependent, but the mechanism is not well known. The retinoblastoma protein, encoded by the RB1 gene located at 13q14, is a key regulator of proliferation, development, and differentiation of certain cell types, including adipocytes. In the current study, we investigated the genetic alterations of the RB1 gene, such as mutation (the essential promoter region and the protein-binding pocket domain; exons 20-24) and methylation of the promoter region, in addition to pRB expression and loss of heterozygosity (LOH) status, in two morphologically distinct areas (nonlipogenic dedifferentiated and well-differentiated components) in 27 patients. As a control, 11 undifferentiated high-grade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma samples and 11 well-differentiated liposarcoma samples were also evaluated. Dedifferentiated components showed LOH (15/25; 60%) and abnormal retinoblastoma protein expression (18/27; 66.7%) more frequently than noted in the well-differentiated components (3/24; 12.5% and 9/27; 33.3%, respectively). Five and four out of the 27 dedifferentiated components harbored mutations and promoter methylation, respectively, whereas none of these alterations were seen in the well-differentiated components. These results suggest that retinoblastoma protein has a major role to play in dedifferentiation and that a 'two-hit' mechanism is involved in the altered retinoblastoma protein expression in dedifferentiated liposarcoma.

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confidence: 48%

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Alterations of the RB1 gene in dedifferentiated liposarcoma

et al. 2005

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“…2,3 In spite of its commonly pleomorphic high-grade morphology, several clinicopathological studies have indicated that dedifferentiated liposarcoma behaves less aggressively as compared with other pleomorphic sarcomas of adulthood. 4,5 Some authors considered that the basis for this difference might be related to a comparatively lower metastatic rate, ranging from 1 to 18% depending on series. [1][2][3][4][5][6][7] Nevertheless, two points remained to be cautiously elucidated before drawing such a conclusion.…”

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“…4,5 Some authors considered that the basis for this difference might be related to a comparatively lower metastatic rate, ranging from 1 to 18% depending on series. [1][2][3][4][5][6][7] Nevertheless, two points remained to be cautiously elucidated before drawing such a conclusion. Firstly, most patients with dedifferentiated liposarcoma die of the local effects of their tumor before metastasis become obvious; and secondly, it is difficult to accurately determine what criteria distinguish between local (contiguous) invasion and true metastasis.…”

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“…Dedifferentiated areas in liposarcoma can display a variety of histological patterns, including pleomorphic/storiform malignant fibrous histiocytoma-like, [1][2][3][4][5][6] fibrosarcoma-like, [1][2][3][4][5][6] myxofibrosarcoma-like, 2,4,5,7 and heterologus differentiation, such as myogenic 8,9 or osteogenic or chondro-sarcomatous 8 elements, etc. In addition, the original concept of dedifferentiation in liposarcoma was recently challenged by Henricks et al, 2 who expanded fibrosarcoma or fibromatosis-like appearances.…”

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Distant metastasis in retroperitoneal dedifferentiated liposarcoma is rare and rapidly fatal: a clinicopathological study with emphasis on the low-grade myxofibrosarcoma-like pattern as an early sign of dedifferentiation

et al. 2005

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The metastatic incidence of retroperitoneal dedifferentiated liposarcoma is comparatively lower than other pleomorphic sarcomas, varying widely from 1 to 18%. Low-grade dedifferentiation resembling low-grade fibrosarcoma has been recently accepted as part of the morphologic spectrum of dedifferentiated liposarcoma and was reported to have similar metastatic and survival rates to its high-grade counterpart. We sought to determine the metastatic incidence of retroperitoneal dedifferentiated liposarcoma, the clinicopathological features related to metastasis, and their postmetastatic behavior. Of all 354 retroperitoneal liposarcoma cases diagnosed at Memorial Sloan-Kettering Cancer Center during 1982-2003, we identified seven patients developing distant metastases, occurring in four females and three males, ranging from 35 to 73 years in age at presentation. They were all de novo dedifferentiated, while none of the well-differentiated liposarcoma or secondary dedifferentiated liposarcoma developed distant metastasis. Primary tumor sizes varied from 7.5 to 25 cm. All seven patients developing metastases contained Z50% dedifferentiated elements in the primary tumor, with a predominant morphology resembling myxofibrosarcoma in five cases. The metastatic sites included the lung in four patients, somatic soft tissue in two, and liver in one. The median metastasis-free survival was 48 months, with only two patients experiencing local recurrences before developing metastasis. Six patients died of disease at median follow-up of 53 months after diagnosis and only 5 months after their first metastases. In conclusion, retroperitoneal dedifferentiated liposarcoma have a low metastatic rate, which is strongly related to de novo dedifferentiated histology that usually constitutes a prominent component of the primary tumor. Irrespective of the grade dedifferentiated liposarcoma with myxofibrosarcoma-like features should be closely monitored. Once metastases occur, they tend to follow a rapidly fatal course. Modern Pathology (2005) 18, 976-984.

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Prognostic significance of grading and staging systems using MIB‐1 score in adult patients with soft tissue sarcoma of the extremities and trunk

Hasegawa

Yamamoto

Yokoyama

et al. 2002

Cancer

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BACKGROUND The predictive value of histologic grading and staging systems for overall survival in different types of adult soft tissue sarcoma of the extremities and trunk is unclear. METHODS Histologic slides from 193 patients with primary tumors were reviewed for diagnosis, and Ki‐67 (MIB‐1) immunostaining was performed for grading in all patients. Univariate and multivariate analyses were conducted to analyze the results from patients with soft tissue sarcomas as a group and among the six main histologic categories: malignant fibrous histiocytoma (n = 49 patients), liposarcoma (n = 48 patients), synovial sarcoma (n = 30 patients), spindle cell sarcoma (n = 24 patients), small round cell sarcoma (n = 15 patients), and others (n = 27 patients). The median follow‐up was 50 months. RESULTS Univariate analysis of soft tissue sarcomas showed that tumor size and depth, histologic type, MIB‐1 score, grades based on three criteria (tumor differentiation/histologic type, necrosis, and either mitosis or MIB‐1 score) and disease stage, as assessed by tumor size, depth, and grade, were associated with overall survival. Among these variables, grading and staging systems using the MIB‐1 score had better predictive value compared with the MIB‐1 score and standard grading and staging models in the main histologic categories. Because survival curves for the different tumor grades and stages showed similar trends between the different histologic types, multivariate analysis was conducted adjusting for age, gender, disease site, surgical margin, tumor size and depth, grade, stage, and histologic type. Consequently, Grade 3 emerged as the most significant adverse prognostic factor. Additional adverse prognostic factors were Stage III, Grade 2, a histologic type of spindle cell sarcoma, and patient age > 50 years at the time of presentation. The histologic type liposarcoma was identified as a favorable prognostic factor. CONCLUSIONS The current results indicate that grading and staging systems using the MIB‐1 score are very strong prognostic factors in patients with the main histologic types of soft tissue sarcoma. Specific assessment of histologic type should be carried out before deciding on treatment strategies. Cancer 2002;95:843–51. © 2002 American Cancer Society. DOI 10.1002/cncr.10728

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Dedifferentiated liposarcoma ofretroperitoneum and mesentery: Varied growth patterns and histological grades—A clinicopathologic study of 32 cases

Cited by 134 publications

References 28 publications

Alterations of the RB1 gene in dedifferentiated liposarcoma

Alterations of the RB1 gene in dedifferentiated liposarcoma

Distant metastasis in retroperitoneal dedifferentiated liposarcoma is rare and rapidly fatal: a clinicopathological study with emphasis on the low-grade myxofibrosarcoma-like pattern as an early sign of dedifferentiation

Prognostic significance of grading and staging systems using MIB‐1 score in adult patients with soft tissue sarcoma of the extremities and trunk

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