SPIB protein expression in major hematolymphoid neoplasms and human BPDCs. (A) The SPIB protein is overexpressed in BPDC neoplasms and is expressed with variable intensity among B- and T-cell lymphoma types. Cases of BPDC neoplasms show clear-cut nuclear expression of the SPIB protein. However, other cutaneous infiltrates that can mimic this specific tumor type lack SPIB protein expression (a case of acute myelomonocytic leukemia, AMML, is shown for comparison). (B) SPIB is overexpressed in BPDC neoplasms irrespective of the localization of the infiltrate. Cutaneous (i-ii), BM (iii), and lymph node (iv) infiltrates show a similar intensity and distribution of the expression in the neoplastic population. SPIB was found to be negative in all 24 cases of B-cell acute lymphoblastic leukemia tested (v-viii). (C) Heat map showing the distribution of immunohistochemical expression of conventional markers used in the diagnosis of 45 cases of BPDC neoplasms. As depicted, BPDC neoplasms showed significant phenotypic diversity: 29 of 45 (64%) expressed all 4 markers (ie, TCL1, CD123, CD4, and CD56), 11 of 45 (24%) lacked 1 marker (8 cases CD4, 2 cases CD56, 1 case TCL1), 3 of 45 (6%) lacked 2 markers, and 2 of 45 (4%) lacked 3 markers. SPIB continued to be overexpressed in all cases of BPDC neoplasms. Red indicates cases with intense homogeneous expression, yellow indicates cases with partial expression, and green indicates cases that were negative for a given marker. (D) SPIB is overexpressed in all BPDC neoplasms but is negative in all of the tumor types studied (including acute myelomonocytic leukemia, acute myeloid leukemia not otherwise specified, precursor T- and B-lymphoblastic lymphoma/leukemia, nasal type natural killer/T-cell neoplasms, and primary cutaneous T-cell CD4+ lymphoma). (E) SPIB immunohistochemical expression scoring. (i) SPIB mAb positively stains the nuclei of the normal GC B cells. The intensity of these GC B cells is used as the threshold for scoring the neoplastic cases. (ii) DLBCL case with weakly positive SPIB expression. (iii) DLBCL case with moderate intensity SPIB expression. (iv) DLBCL with intense expression of SPIB protein.