Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease that can be life-threatening. Recently, it has been reported that familial GPP is caused by homozygous or compound heterozygous mutations of IL36RN. However, the majority of GPP cases are sporadic and it is controversial whether IL36RN mutations are a causative/predisposing factor for sporadic GPP. We searched for IL36RN mutations in two groups of GPP patients in the Japanese population in this study: GPP without psoriasis vulgaris (PV), and GPP with PV. Eleven cases of GPP without PV (GPP alone) and 20 cases of GPP accompanied by PV (GPP with PV) were analyzed. Surprisingly, 9 out of 11 cases of GPP alone had homozygous or compound heterozygous mutations in IL36RN. In contrast, only 2 of 20 cases of GPP with PV had compound heterozygous mutations in IL36RN. The two cases of GPP with PV who had compound heterozygous mutations in IL36RN are siblings, and both cases had PV-susceptible HLA-A*0206. We determined that GPP alone is a distinct subtype of GPP and is etiologically distinguished from GPP with PV, and that the majority of GPP alone is caused by deficiency of the interleukin-36 receptor antagonist due to IL36RN mutations.

Immunohistochemical evaluation of PD-L1 expression in tumour and non-malignant HRS-like large cells may be useful for assessing either immune escape or immunodeficiency in their pathogenesis.

BackgroundPrimary intestinal diffuse large B‐cell lymphoma (iDLBCL) is rare. In this study, we investigated the clinicopathological features of this disease to further understand the prognostic value of CD5, programmed cell death ligand 1 (PD‐L1), and Epstein‐Barr virus (EBV) on tumor cells.MethodsTumor specimens from 62 patients consecutively diagnosed with primary iDLBCL at a single institution were analyzed.ResultsOur series consisted of EBV‐positive (EBV+) iDLBCL (n = 10), de novo CD5+ iDLBCL (n = 4), and DLBCL, not otherwise specified (DLBCL‐NOS; n = 48). Notably, seven of 10 EBV+ cases had treated lymphoma‐associated (n = 4) or iatrogenic immunodeficiency (n = 3). Two of 10 EBV+ cases expressed PD‐L1 on tumor cells, whereas the remaining eight were positive for PD‐L1 on microenvironment immune cells. Only one DLBCL‐NOS case had neoplastic PD‐L1 expression with a giant cell‐rich appearance. Both EBV‐harboring and PD‐L1 expression on tumor cells, but not CD5, were associated with worse overall survival (OS) in iDLBCL patients receiving rituximab‐containing chemotherapy (P = 0.0354, P = 0.0092, and P = 0.1097, respectively). Multivariate analysis identified PD‐L1 positivity on tumor cells (P = 0.0106), PD‐L1 negativity on microenvironment immune cells (P = 0.0193), and EBV positivity (P = 0.0324) as poor independent prognostic factors for OS. Among iDLBCL cases without any EBV association, CD5 positivity, or neoplastic PD‐L1 expression, high PD‐L1 expression (≥40%) on microenvironment immune cells predicted an extremely favorable outcome.ConclusionEBV+ iDLBCL mainly comprised immunodeficiency‐associated patients, which may highlight the specificity of the intestine. PD‐L1 expression on tumor cells or microenvironment immune cells was found to have an opposite prognostic impact in iDLBCL.

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