2ND PRIMARY RHABDOMYOSARCOMAS IN PATIENTS WITH BILATERAL RETINOBLASTOMA - A CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY

We reviewed six cases of rhabdomyosarcoma as a rare second primary mal ignancy in children with bilateral retinoblastoma after irradiation tr eatment. The patients comprised four females and two males (age range 1 year 4 months-7 years 11 months). Second tumors arose in the tempora l muscle inside or close to the previously irradiated fields. All the children were alive and well 24-72 months after diagnosis. Microscopic examination showed proliferation of closely packed, small round cells with scanty cytoplasm, coarse nuclear chromatin, and increased mitoti c activity without a myxoid background nor obvious alveolar architectu re. The most characteristic feature was the presence of rosette-like s tructures in four tumors. Immunoreactivity for many skeletal muscle ma rkers was evident, including desmin (six of six), muscle-specific acti n (HHF35) (six of six), sarcomeric actin (six of six), myogenin (six o f six), vimentin (six of six), and myoglobin (three of six), On revers e transcriptase-polymerase chain reaction examination, three second tu mors lacked specific chimeric transcripts for alveolar rhabdomyosarcom a and Ewing's sarcoma. Unexpectedly, variable reactivity for neurofila ment (150 kd) was identified in six of six second tumors as well as 15 of 20 sporadic primary rhabdomyosarcomas (75%) examined as controls, the result being confirmed by Western blot analysis. In addition, stai ning for retinoblastoma-susceptibility gene protein was negative in al l second tumors, in contrast to positivity in 14 of 17 sporadic primar y tumors (82%). This finding suggests that retinoblastoma-susceptibili ty gene abnormalities could be associated with the development of seco nd primary rhabdomyosarcoma. We consider that knowledge of the occurre nce of rhabdomyosarcoma and appropriate immunohistochemical study are helpful for avoiding a misdiagnosis of recurrent retinoblastoma or Ewi ng's sarcoma when encountering patients with a history of bilateral re tinoblastoma who developed second small round cell neoplasms.