title: Pathologic features of rhabdomyosarcoma before and after treatment: a clinicopathologic and immunohistochemical analysis.
abstract: Few studies have analyzed the relationship among pathology, therapy-induced changes, proliferative activity, and outcome for rhabdomyosarcoma (RMS), despite the challenges of histopathologic interpretation of this tumor after treatment. Although cytodifferentiation and decreased mitotic activity after treatment were documented previously, the clinical consequences of these changes are uncertain because of the small number of cases analyzed. We analyzed 16 RMSs with pre- and post-treatment specimens for clinicopathologic features, outcome, and immunohistochemical data on formalin-fixed, paraffin-embedded tissue for vimentin, smooth muscle actin, muscle-specific actin, desmin, myoglobin, p53 protein, topoisomerase II-alpha, and MIB-1 proliferative activity. Four of eight alveolar (ARMS), five of five botryoid (BRMS), and two of three nonbotryoid embryonal (ERMS) RMSs displayed varying degrees of post-therapeutic histologic maturation and expressed one or more myoid markers. The remaining five RMSs had no cytodifferentiation. Myoid marker expression did not change significantly. In BRMS, MIB-1 and topoisomerase II-alpha proliferative activity decreased after therapy and correlated with cytodifferentiation and survival. This relationship was less clear for ERMS and ARMS. Five nonbotryoid RMSs without cytodifferentiation had either unchanged or increased proliferative activity, and four of these patients died of RMS. Six nonbotryoid RMSs with both cytodifferentiation and residual foci of undifferentiated cells had variable outcomes, including longer survival. We conclude that BRMS and ERMS exhibit therapy-induced cytodifferentiation more frequently than does ARMS. Cytodifferentiation and decreased proliferative activity are associated with favorable outcome in BRMS; unchanged or increased post-therapeutic proliferative activity suggests aggressive biologic potential in ERMS and ARMS. Combined patterns of cytodifferentiation and residual undifferentiated foci might be associated with increased, decreased, or unchanged proliferative activity and are difficult to interpret, but the presence of cytodifferentiation might presage an improved survival. Immunohistochemical analysis for proliferation markers might be useful for highlighting foci of less differentiated RMS or cytodifferentiated tumor cells in contrast to non-neoplastic, terminally differentiated muscle cells.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84113, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Coffin
authors.forename: J
authors.initials: J
authors.lastname: Rulon
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Bruggers
authors.forename: F V
authors.initials: FV
authors.lastname: White
mesh_terms: D000199:Actins / Q000032:analysis; D000293:Adolescent; D000951:Antigens, Neoplasm / Q000032:analysis; D034961:Antigens, Nuclear; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins; D003893:Desmin / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007527:Isoenzymes / Q000032:analysis; D019394:Ki-67 Antigen; D008297:Male; D009211:Myoglobin / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000473:pathology* / Q000628:therapy; D016896:Treatment Outcome; D014746:Vimentin / Q000032:analysis
chemical_list: D000199:Actins; D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D015415:Biomarkers; D004268:DNA-Binding Proteins; D003893:Desmin; D007527:Isoenzymes; D019394:Ki-67 Antigen; D009211:Myoglobin; D009687:Nuclear Proteins; D014746:Vimentin; D004250:DNA Topoisomerases, Type II