The Journal of Dermatology | 2021
Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder with high Ki‐67 proliferation index
Abstract
Dear Editor, Primary cutaneous CD4+ small/medium Tcell lymphoma has been reclassified as primary cutaneous CD4+ small/medium Tcell lymphoproliferative disorder (PCSMLPD) in the latest revision of the World Health Organization (WHO) classification,1 due to its indolent clinical behavior and uncertain malignant potential. PCSMLPD is characterized by a predominance of small to mediumsized CD4+ pleomorphic T cells expressing follicular helper Tcell markers, presentation with a solitary skin lesion in most cases, and no evidence of the patches/plaques typical of mycosis fungoides. The Ki67 proliferation index is low (mostly ≤20– 30%).1,2 We report a case of PCSMLPD with high proliferation index. A 33yearold woman presented with a 2month history of a topical corticosteroidresistant nodule in her right preauricular region. Physical examination revealed a solitary erythematous nodule with a diameter of 18 mm in the right preauricular region (Figure 1a). There was no other cutaneous lesion or lymphadenopathy. Serum antibody to human Tcell leukemia virus type 1 was negative. The skin biopsy specimen showed nonepidermotropic, dense, diffuse dermal infiltrates mainly consisting of small to mediumsized pleomorphic lymphocytes with mild nuclear atypia, admixed with a small number of large lymphocytes and histiocytes (Figure 1b,c). Mitoses were rare (1 in 10 consecutive highmagnification fields [×400]). The infiltrates showed a predominance of CD3+, CD4+, and CD7− T cells (Figure 1d– f). There was a considerable admixture of CD20+ B cells, small reactive CD8+ T cells, and CD68+ histiocytes (Figure 1g– i). Atypical T cells expressed follicular helper Tcell markers, programmed cell death 1 (PD1), BCL6, and CXCL13 (Figure 1jl), but not CD10. Clusters of PD1+ cells were evident. CD30 or cytotoxic proteins were not expressed. The Ki67 proliferation index was 40% (Figure 1m). Clonal TRB or IGH gene rearrangement was not detected by Southern blot analyses. The lesion regressed completely 4 weeks after the biopsy (Figure 1n). During the 1year followup period, there was no recurrence of the lesion. Although our case showed typical clinical presentation and course, histopathological features, and immunophenotype of PCSMLPD except for the high Ki67 proliferation index, we could not demonstrate Tcell clonality. Therefore, the lesion might be alternatively diagnosed as nodular Tcell pseudolymphoma. In a recent multicenter study, however, a Tcell clone was not detected in 31% of PCSMLPD cases even by sensitive polymerase chain reaction analyses.2 PCSMLPD and nodular Tcell pseudolymphoma are considered to be the same process, but we made a diagnosis of PCSMLPD primarily based on the characteristic clustering of PD1+ cells.2 Early studies of primary cutaneous CD4+ small/medium Tcell lymphoma included cases with aggressive clinical behavior.3,4 Aggressive cases were characterized by widespread skin lesions, large rapidly growing tumors, more than 30% large pleomorphic T cells, fewer reactive CD8+ cells, and/or high Ki67 proliferation index. Such cases are classified as peripheral Tcell lymphoma, not otherwise specified according to the current WHO classification.1 Our case indicates that clinical behavior cannot be predicted only by the high Ki67 proliferation index, and PCSMLPD should not be excluded based on this single criterion alone, as suggested also by a recent study.5 As with other lymphoid neoplasms, PCSMLPD should be diagnosed comprehensively based on all available information including clinical features, morphology, immunophenotype, and genetic data.