Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: A report of the CHAMP study group

Abstract

With the aim of identifying objective cytogenetic‐morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, 1 as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three‐grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high‐grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic‐morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear‐cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups. Genes Chromosomes Cancer 22:16–25, 1998. © 1998 Wiley‐Liss, Inc.

Distinct chromosomal imbalances in pleomorphic and in high‐grade dedifferentiated liposarcomas

“…In contrast to the highly complex and inconsistent karyotypes obtained by chromosomal banding analysis 6,13 and to one recurrent chromosomal abnormality detected with CGH in a small number of pleomorphic LS analyzed by Parente et al, 22 we identified in our series of pleomorphic LS analyzed by CGH a considerable number of recurrent chromosomal imbalances. Moreover, our data show that the DNA copy number changes detected in pleomorphic LS differ essentially from those in the cytomorphologically similar high-grade areas of dedifferentiated LS and from those in well-differentiated LS/ALT described in the literature.…”

“…6,13 Except for the presence of definite evidence of adipocytic differentiation, pleomorphic LS are histomorphologically often similar to pleomorphic malignant fibrous histiocytomas (MFH) or MFH-like pleomorphic tumors with different lines of cellular differentiation; additionally, an epithelioid variant of pleomorphic LS focally resembling a solid carcinoma has been described. 2 Although the high-grade component of dedifferentiated LS, which may be predominating especially in tumor recurrences, is frequently MFHlike, dedifferentiated LS differ irrespective of the grade of the non-lipogenic component from pleomorphic LS by a less aggressive biological behavior.…”

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

“…Most reported karyotypes are complex, contain a high number of chromosomal changes, and show marked heterogeneity within this group of sarcomas. [14][15][16][17][18][19] Comparative genomic hybridization (CGH) studies have also shown multiple and complex changes, suggesting a genetically advanced disease. So far, CGH has been used to identify gains and losses of DNA copy number changes in less than 200 cases of leiomyosarcoma.…”

44th Maude Abbott Lecture

“…One might also hope that each of the pleomorphic sarcomas would harbor a unique cytogenetic abnormalities that would allow each to be studied and understood more mechanistically, as has occurred with many of the nonpleomorphic sarcomas, such as myxoid liposarcoma, Ewing's sarcoma, alveolar rhabdomyosarcoma, and clear cell sarcoma. To date, no recurring specific differences have been noted among pleomorphic sarcomas (41). All are characterized by numerous and complex genetic alterations (Fig.…”

“…All are characterized by numerous and complex genetic alterations (Fig. 19), although there appears to be a correlation between the degree of complexity and the grade (41). One exception is the dedifferentiated liposarcoma, which retains giant marker and/or ring chromosomes as a vestige of its origin from a welldifferentiated liposarcoma (42) (Fig.…”