Prognostic factors for primary cutaneous anaplastic large cell lymphoma: a multicenter retrospective study from Japan.

BACKGROUND: Clinical implications of DUSP22 rearrangement and the association between DUSP22 rearrangement and lymphoid enhancer-binding factor 1 (LEF1) expression pattern in CD30-positive cutaneous T-cell lymphomas (CTCLs) are unknown.

OBJECTIVES: This study assessed the incidence of DUSP22 rearrangement and its clinical and immunohistochemical implications in primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP), and CD30-positive mycosis fungoides (MF) with large cell transformation (MF-LCT), especially focusing on the association with the prognosis and LEF1 expression pattern. Prognostic factors of pcALCL were also examined.

METHODS: Multicenter retrospective study including patients with pcALCL, LyP, and MF-LCT diagnosed between January 1, 2000 and December 31, 2018 in Japan. Baseline data at diagnosis, treatment course, overall survival (OS), and disease-specific survival (DSS) were collected. Immunohistochemical analysis and fluorescence in situ hybridization to detect DUSP22 and TP63 rearrangement were performed using skin samples at diagnosis. We investigated the association between staining pattern and these gene rearrangements. We also assessed the prognostic implications of clinical status, immunohistochemical results and the presence of gene rearrangements.

RESULTS: DUSP22 rearrangement was detected in 50% of pcALCL cases (11/22), but not in any cases with LyP (0/14) or MF-LCT (0/11). TP63 rearrangement was not detected in any case. Clinically, pcALCL patients with DUSP22 rearrangement did not tend to form ulcers (p = 0.081). There was no significant association between DUSP22 rearrangement status and immunohistochemical results including LEF1 expression pattern. T3 stage and the presence of lower limb lesions were significantly associated with shorter OS (p = 0.012 and 0.021, respectively by log-rank test). Similarly, they were significantly correlated with shorter DSS (p = 0.016 and 0.0001, respectively).

CONCLUSION: DUSP22 rearrangement is relatively specific to pcALCL among CD30-positive CTCLs in Japan. Although LEF1 expression pattern was not related with DUSP22 rearrangement in pcALCL, there was no rearrangement if LEF1 was not expressed. We confirmed that T3 stage and the lower limb involvement were significantly associated with the decreased OS and DSS. Presence or absence of lower limb lesions should better be included in T stage subcategory in the future.