Aggresive Lymphoma—Leukemia Presenting As a Solitary Bone Tumor and Mimicking Ewing's Sarcoma

Background. Lymphomas and leukemias may rarely present as bone tumors and may mimick Ewing's Sarcoma.

Methods.Within a cohort of 493 lymphoma-leukemia cases diagnosed and treated between 1990-2012, in the Istanbul University, Oncology Institute (which is a referral center for bone tumors), five cases presented as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma.

Cases. Five children, two male and three female, with a median age of 10 years (range, 6-15 years) presented with extremity pain without significant constitutional symptoms. In all cases, on radiographic evaluation, osteolytic lesions were observed, in the tibia in two cases, in the humerus in the two cases and in the femur in the other case. In all five cases, the initial pathology of the biopsy specimens were reported as "Ewing's sarcoma" or "consistent with Ewing's sarcoma" and immunohistochemical stains showed that the neoplastic cells expressed CD99 (MIC2 gene product). However, further immunophenotyping revealed that these cases were leukemia/lymphoma. One presented with anemia (hemoglobin 6.5 g/dl) and bone marrow aspiration and biopsy revealed hemophagocytosis which regressed after the first course of chemotherapy, there were no atypical cells. In a 6 year old girl with a lesion in the humerus, bone marrow evaluation showed atypical lymphocytes, immunophenotypic analysis by flow cytometry showed precursor B lymphoblastic leukemia, malignant cells were positive for CD 10, CD 19. Real time RT-PCR revealed positive BCR/ABL arrangement. So, she was diagnosed as high risk leukemia with t(9,22). She had no matched family donor. She recieved BFM-high risk protocol with imatinib mesylate between high risk courses and is in remission for 9 years from diagnosis. Three cases were diagnosed as large cell lymphoma (LCL) expressing ALK-1 in two, all recieved BFM B cell lymphoma protocols and are with no evidence of disease (NED) for five years, 13 years and 19 years from diagnosis. One case had precursor B cell lymphoblastic lymphoma (pBLL). She was treated by the BFM lymphoblastic lymphoma protocol and is with NED 4 years from diagnosis. Bone marrow aspiration and biopsy were evaluated as normal in the last three cases. In the lymphoma cases there was complete metabolic response on PET-CT (in two cases), whereas the radiological response was slower in MRI or CT.

Conclusion. Lymphomas and leukemia should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because most lymphomas and leukemias are curable in the pediatric age group with appropriate therapy. For bone lesions, metabolic response on PET-CT seems to be quicker than anatomic response in CT or MRI, suggesting not to alter treatment if there is good metabolic response but slow anatomic response.