Rhabdoid Features in Leiomyosarcoma of Soft Tissue: With Special Reference to Aggressive Behavior Yumi Oshiro, M.D., Hideki Shiratsuchi, M.D., Yoshinao Oda, M.D., Satoshi Toyoshima, M.D., Masazumi Tsuneyoshi, M.D. Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University soft tissue with rhabdoid cells showed a tendency The presence of rhabdoid cells has been reported in for poorer prognoses than cases without rhabdoid various types of malignant neoplasms and has been features. On the contrary, retroperitoneal cases did determined to be a predictor of aggressive behavior not. This study indicates that rhabdoid features are of neoplasms regardless of tumor histogenesis. One associated with aggressive biological behavior in hundred and thirteen cases of leiomyosarcoma, se- leiomyosarcoma of the external soft tissue. lected from 1800 soft tissue sarcomas, were re- viewed on hematoxylin and eosin sections, and im- KEY WORDS: Leiomyosarcoma; rhabdoid cells. munohistochemical staining when available, and Mod Pathol 2000;13(11):1211–1218 seven cases with rhabdoid features were retrieved. Clinicopathologic differences were analyzed to Leiomyosarcoma is a relatively rare soft-tissue sar- compare between cases with rhabdoid features and coma, accounting for between 5 and 10% of soft- those without rhabdoid features. In the seven cases tissue sarcomas. They can be divided into groups as with rhabdoid features, two were intra-abdominal, follows: 1) leiomyosarcoma of retroperitoneum and and the others arose in external soft tissues includ- other intra-abdominal sites; 2) leiomyosarcoma of ing muscle, subcutis, and cutis. Patient age ranged deep soft tissue, other than at abdominal sites; 3) from 33 to 84 years, three were female, and four leiomyosarcoma of cutaneous or subcutaneous tis- were male. Tumor size ranged from 3 to 22 cm. sue; 4) leiomyosarcoma of vascular origin. The lo- Clinical evidence showed no differences from those cation is important because it is accurately re- cases without rhabdoid features. Histologically, one flected in the outcome for the patient. Tumor size is of the abdominal cases was epithelioid leiomyosar- also known to be an important prognostic factor. coma. Two of the 7 cases were better subclassified as Histological features of leiomyosarcoma, case by pleomorphic leiomyosarcoma, in which rhabdoid case, show a great variety of patterns and are not cells are diffusely scattered. In cases other than yet recognized as prognostic factors (1–3). those with pleomorphic leiomyosarcomas, foci of Malignant rhabdoid tumor of the kidney is a dis- anaplastic areas were observed, and collections of tinctive clinicopathological entity that is recognized rhabdoid cells were present in those areas. Immu- as a highly aggressive renal tumor of childhood nohistochemical examination of the cases con- (4–6). Extrarenal malignant rhabdoid tumors have firmed myogenic differentiation, and showed rhab- been proposed to exist at several sites, including doid cells being positive for vimentin and desmin in soft parts. However, there have been doubts as to the inclusion bodies, and diffusely so for muscle the existence of such an entity, because of the lack actin in the cytoplasm. After dividing all the cases of of clinicopathologic uniformity among the cases leiomyosarcoma by their location, prognostic anal- (7–23). Furthermore, the presence of rhabdoid cells ysis was performed. Leiomyosarcoma of external has been reported in various types of specific ma- lignant neoplasms, either mesenchymal or epithe- lial (24–37). Despite the degree of differentiation of Copyright © 2000 by The United States and Canadian Academy of tumors with a rhabdoid phenotype, these are now Pathology, Inc. VOL. 13, NO. 11, P. 1211, 2000 Printed in the U.S.A. recognized as highly aggressive neoplasms. Only a Date of acceptance: June 13, 2000. few examples of leiomyosarcomas have been re- This work was supported in part by a Grant-in-Aid for Cancer Research from the Fukuoka Cancer Society, Fukuoka and a Grant-in-Aid for Gen- ported to show rhabdoid features in the reviews of eral Scientific Research from the Ministry of Education, Science, Sports and Culture (09470052), Tokyo, Japan. malignant rhabdoid tumors of soft tissue (8, 9). In Address reprint requests to: Masazumi Tsuneyoshi, M.D., Department of the current study, we describe seven cases of Anatomic Pathology, Graduate School of Medical Science, Kyushu Uni- versity, 3–1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan; e-mail: leiomyosarcoma with rhabdoid features and show a [email protected]; fax: 81-92-642-5968. relationship to aggressive biological behavior, espe- 1211 cially in cases of leiomyosarcoma arising in an ex- ranged from 11 to 89 years (mean, 57) in all cases, ternal soft tissue site. 24 to 84 (mean, 58) in retroperitoneal cases, 11 to 89 (mean, 54) in external soft tissue cases, and showed no significant differences. Male-to-female ratio was MATERIALS AND METHODS 53:78 (unknown, 2), 36:49 in retroperitoneal cases, One hundred and thirty-three cases of leiomyo- and 17:29 in external soft tissue cases. Tumor sizes sarcoma were reviewed, taken from the 1800 cases ranged from 5 to 35 cm (mean, 13.8) in retroperi- of soft-tissue sarcoma in the files of the Department toneal cases and 1 to 25 (mean, 5.8) in external soft of Anatomic Pathology at Kyushu University, Japan. tissue cases including superficial cases (mean, 3.8) Leiomyosarcomas originating in the perineal re- and deep external soft tissue cases (mean, 9.2). gion, vessels, or intestinal wall were excluded from Significant differences were observed between the this study. Cases containing significant extent of tumor sizes of abdominal cases and those of super- tumor cells with rhabdoid features, despite rela- ficial cases (P Ͻ 0.001), and also between deep tively low total fraction of cells or only focal collec- external soft tissue cases and superficial cases (P ϭ tions, are recognized as cases with rhabdoid fea- 0.002557). ture. Cases containing only a few rhabdoid-like Seven cases showed rhabdoid features. A sum- cells are not included in the cases. Seven cases with mary of the clinicopathological data of the cases rhabdoid features were retrieved from the files. with rhabdoid features is listed in Table 2. In these Representative sections from the available cases cases, patient age ranged from 33 to 84 years, three were selected for immunohistochemistry. The im- were female, and four were male. Tumor size munoperoxidase staining was done using the ranged from 3 to 22 cm. Patient ages and tumor streptavidin biotin-peroxidase method (Histofine sizes showed no differences between cases with SAB-PO Kit, Nichirei Co, Tokyo, Japan). The anti- rhabdoid features and those without rhabdoid fea- bodies used shown in Table 1. tures, regardless of the tumor site. In 91 of these cases, including six with rhabdoid features, follow-up data was available for analysis. The length of survival was tested by Kaplan-Meier Therapy analysis with both Gehan-Wilcoxon and Peto log- The summary of the therapy in patients with rank tests. rhabdoid features is listed also in Table 2. In patient 1, with an intra-abdominal mass, the tumor was easily resected from the omentum. The other with RESULTS an intra-abdominal mass, patient 2, showed no in- Clinical Findings vasion to the surrounding organs and was treated by excision. Patient 3, with a subcutaneous tumor, Clinical data of all 133 cases of leiomyosarcoma underwent excision with a required wide surgical were analyzed to compare between cases with rhab- margin. In patient 4, a subcutaneous tumor was doid features and those without rhabdoid features. also excised with a wide margin. Patient 5 had an The cases of leiomyosarcoma constituted 86 cases intramuscular tumor that was easily movable and in retroperitoneum, mesentery or other intra- was excised with the required wide surgical margin abdominal sites (defined as retroperitoneal cases), after preoperative chemotherapy with vincristine, and 47 cases in nonretroperitoneal external soft actinomycin-D, and cyclophosphamide. In patient tissue sites. External soft tissue cases are composed 6, with a tumor arising in the thigh, pulmonary of 34 cases with depth clarified (21 in superficial metastasis was found at presentation and the pa- sites such as subcutis or cutis and 13 in deeper site tient underwent preoperative radiation and chemo- such as fascia and muscle of extremities) and 13 therapy with adriamycin, vincristine, and cyclo- with unknown depths. Details of the location of phosphamide, followed by the excision of the external soft tissue were as follows: 22 cases in tumor arising in the sartorius muscle. In the re- lower extremities, 8 each in upper extremities, limb maining case, of a tumor arising in the buttocks, the girdle, and trunk, and one of the head. Patient age tumor was excised but details are not known. TABLE 1. Monochronal antibodies used Histological Findings Clone Source Dilution The seven cases with rhabdoid features showed a Vimentin V9 DAKO 1:25 great variety of histological features compared with ␣SMA 1A4 SIGMA 1:5000 Muscle actin HHF35 Biomeda 1:200 leiomyosarcomas without rhabdoid features. Three Desmin D33 DAKO 1:100 cases showed well to moderately differentiated Cytokeratin CAM5.2 Becton Dickinson 1:20 leiomyosarcoma, displaying interlacing bundles of SMA, smooth muscle actin. elongated spindle cells with abundant eosinophilic 1212 Modern Pathology TABLE 2. List of cases with rhabdoid features Patient Age Sex Site Size (cm) Therapy Prognosis Histologic finding 1 55 F Abdominal cavity 18 ϫ 9.5 Marginal excision 85 mo. Alive Epithelioid leiomyosarcoma 2 62 F Omentum 13 ϫ 10 Marginal excision Unknown Moderately differentiated 3 53 F Thigh, subcutis 8 ϫ 6 Wide excision 19 mo. DOD Moderately differentiated 4 76 M Buttock, subcutis 6 ϫ 5 Wide excision 27 mo. Alive Pleomorphic, myxoid MFH like area 5 33 M Thigh muscle 5 ϫ 6 Wide excision after chemotherapy 45 mo.