Pleomorphic and dedifferentiated leiomyosarcoma: clinicopathologic and immunohistochemical study of 41 cases

Summary

In this article, we supplement the few published articles by describing the clinical and pathologic features of pleomorphic and dedifferentiated leiomyosarcoma from 41 patients (27 women and 14 men) with an age range of 25 to 75 years (mean, 56.5 years), representing the largest cohort reported to date. The typical leiomyosarcoma component accounted for <5% to 60% (mean, 15%) of the tumor. The pleomorphic sarcoma component was composed of polygonal cells in 57% of cases, spindle cells in 21%, a combination of polygonal, epithelioid, rhabdoid, and/or spindle cells in 18%, and predominantly epithelioid cells in 3%. The classical leiomyosarcoma component was positive for at least one myogenic immunohistochemical marker in 29 tumors tested; smooth muscle actin in 100% (27/27), calponin in 90% (9/10), muscle-specific actin in 90% (10/11), desmin in 86% (23/27), smooth muscle myosin heavy chain (SMMS-1) in 67% (4/6), and caldesmon in 57% (4/7). The pleomorphic sarcoma component was reactive for at least one muscle marker in 77% (23/30) of cases; smooth muscle actin in 63% (17/27), calponin in 60% (6/10), SMMS-1 in 60% (3/5), desmin in 59% (16/27), muscle-specific actin in 40% (4/10), and caldesmon in 29% (2/7). The classical leiomyosarcoma component was often strongly positive for myogenic markers, and the pleomorphic sarcoma component usually showed focal and less intense immunoreactivity. Based on staining for muscle markers in the pleomorphic component, twenty-three cases were designated as pleomorphic leiomyosarcoma, and 7 cases were designated as dedifferentiated leiomyosarcoma (negative for all muscle markers used). Eleven cases, in which tissue was not available for immunhistochemical stains, the question of pleomorphic versus dedifferentiated leiomyosarcoma could not be answered. The incidence of metastasis was 89% (32/36) and the mortality rate was 50% (18/36) at last follow-up (3-104 months; mean, 27.5 months).

Introduction

Typical or classic leiomyosarcoma is a tumor with recognizable areas of blunt-ended spindle cells forming fascicles that resemble smooth muscle tissue. It is not unusual to have small foci of pleomorphic cells in an otherwise classic leiomyosarcoma. The coexistence of a large pleomorphic component has led to the concept that this mixture represents a variant of leiomyosarcoma, which has been aptly designated as pleomorphic leiomyosarcoma [1]. The pleomorphic component is usually a high-grade sarcoma indistinguishable from the so-called pleomorphic malignant fibrous histiocytoma (undifferentiated high-grade pleomorphic sarcoma) or giant cell malignant fibrous histiocytoma [1], [2], [3], [4]. The pleomorphic sarcoma component of pleomorphic leiomyosarcoma variably expresses smooth muscle markers, while that of dedifferentiated leiomyosarcoma does not express any smooth muscle markers. Based on our experience and the published cases of pleomorphic leiomyosarcoma, these tumors often follow an aggressive clinical course [1], [2], [3], [4], [5]. A metastasis rate of 48% (11/23) and mortality rate of 65% (15/23) was reported by Oda et al [1].

Further pathologic and clinical characterization of these tumors has been hampered by their rarity and possible misclassification [1], [4], [5], [6]. The largest cohort published in the literature to date had 28 cases; the remainder are case reports or series with a small number of patients [1], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. In the series of Oda et al [1], pleomorphic leiomyosarcoma accounted for 8.6% of all leiomyosarcomas. The true incidence, however, may be higher, since the inherent pleomorphic histomorphology of many of these tumors may have led them to be misclassified as malignant fibrous histiocytoma (MFH) or one of the other pleomorphic sarcomas [1], [2], [3], [4], [5], [6].

In this study, we report 41 cases of pleomorphic and dedifferentiated leiomyosarcomas seen at MD Anderson Cancer Center between 1986 and 2006 and discuss the pathologic and clinical features, issues in the diagnosis, and the natural history of these uncommon sarcomas.