Expression of S100 protein in CD4-positive T-cell lymphomas is often associated with T-cell prolymphocytic leukemia

S100 + T-cell lymphomas are infrequent, and except 1 all have been CD4 negative. On the basis of an index case of CD4 + S100 + T-cell prolymphocytic leukemia (T-PLL), we studied S100 protein expression in 19 additional T-PLLs and 56 other T-cell lymphomas that are usually CD4 +, including 15 angioimmunoblastic T-cell lymphomas, 24 anaplastic large cell lymphomas (16 ALK + and 8 ALK -), 7 mycosis fungoides/Sézary syndrome, and 10 peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Two additional S100 + CD4 + PTCL, NOS cases were also reviewed. Thirty percent (6/20) of T-PLLs were S100 + compared with 0/56 other T-cell lymphomas with previously unstudied S100 reactivity (40 CD4 +, 2 CD8 +, 11 CD4 - /CD8 -, 3 unknown) (P=0.0007). There were no significant differences between the S100 + and S100 - T-PLLs with regard to the male:female ratio (2:1 vs. 1:1), age (71.6±7.7 vs. 65.4±9.3), peripheral blood lymphocyte count (67.2±116.6 vs. 101.1±159.7×10 9 /L), or median survival (463 vs. 578 d, where known). The 2 S100 + PTCL, NOS cases occurred in a 7-year-old boy and a 45-year-old woman. Both had involvement of the bone marrow and peripheral blood but were morphologically unlike T-PLL and lacked TCL1 gene rearrangement. These results demonstrate that S100 + T-cell lymphomas include a subset that are CD4 + and most often, but not exclusively, are T-PLL. Although having diagnostic implications, there were no documented clinical differences between the S100 + and S100 - T-PLLs.