CD3-and CD20-negative extramedullary non-Hodgkin leukemia/lymphoma: a histopathological study of 118 cases

Histopathological diagnoses are challenging for rare CD3-and CD20-negative extramedullary leukemias/lymphomas. We report 118 cases of CD3- CD20-extramedullary leukemias/lymphomas (2.4% of 4977 cases). CD45 was positive in 68% of cases. Forty-nine (41%) cases were anaplastic large cell lymphomas. Thirty-five (30%) cases were large B-cell lymphomas/plasmablastic lymphomas positive for at least one of the following markers: CD79a, PAX5, CD19, CD138, and MUM1. Nine (8%) cases were peripheral T/NK-cell lymphomas, where at least CD43, CD45RO, or cytotoxic molecules were positive; 4, 3, and 2 cases were extranodal NK/T-cell lymphoma, nasal type, peripheral T-cell lymphoma-not otherwise specified, and adult T-cell leukemia/lymphoma, respectively. The remaining 25 (21%) cases included 11, 8, and 6 cases of myeloid sarcoma, blastic plasmacytoid dendritic cell neoplasm, and B- or NK-cell lymphoblastic leukemia/lymphoma, respectively. For large B-cell lymphoma/plasmablastic lymphoma diagnosis, MUM1 (92%) was the most sensitive marker, followed by CD79a (63%), PAX5 (52%), CD138 (42%), and CD19 (36%). EBER 1 and HHV8 were positive in 32% and 0% of the cases. For peripheral T/NK-cell lymphomas other than ALCL, CD45RO and CD43 were positive in nine cases; however, cytotoxic molecules (TIA1, 86%; granzyme B, 71%) were the most sensitive markers. In conclusion, most cases of the 118 (2.4%) CD3^- CD20^- extramedullary leukemia/lymphoma were represented by anaplastic large cell lymphomas (41%). The second most frequent group of neoplasia, large B-cell lymphoma/plasmablastic lymphoma (30%), characterized a special diagnostic challenge when B-cell markers were not expressed, requiring immunohistochemistry for multiple B-cell markers and molecular analysis in some cases.