Abstract
PURPOSE: Histopathological, immunohistochemistry- and molecular pathology-based diagnostics to distinguish metastasis of retinoblastoma from subsequent primary malignancy in patients with heritable retinoblastoma. OBSERVATIONS: An eight year-old girl presented with tibial pain and bone lesion five years after multimodal treatment of bilateral retinoblastoma, initially clinically suspicious of osteomyelitis. Histopathological examination of bone biopsy specimen revealed a highly proliferative small blue round cell tumor mimicking Ewing's sarcoma of bone. Immunohistochemistry confirmed the diagnosis of a distant metastasis of the previous retinoblastoma. Other subsequent primary malignancies presenting as small blue round cell tumors, such as sarcomas or leukemia, were excluded by immunohistochemistry and molecular methods. CONCLUSIONS AND IMPORTANCE: In countries with early diagnosis of retinoblastoma, distant metastases of retinoblastoma are extremely rare, whereas subsequent primary malignancies are common in survivors of heritable retinoblastoma. Immunohistochemistry and molecular pathology are essential components of diagnostic pathway. In retinoblastoma patients, distant metastases including osseous lesions should be included in the differential diagnosis of small blue round cell tumors.