Hist-O-02 - High PD1 expression H score is associated with Sézary diagnosis: study of 91 patients with erythroderma

Abstract

Erythroderma is a diagnostic challenge for dermatologists and pathologists. We aimed to identify clinical, histological and immunohistochemical markers that can be used to improve erythroderma diagnosis. This single-centre retrospective study included patients with erythroderma. To be included, erythroderma cases needed an accurate final diagnosis, at minimum one year of follow-up, available pictures and available skin biopsies to be reviewed. The demographic, clinical, biological (lactate deshydrogenase, eosinophilia, immunophenotype) and molecular features (T-cell clone in blood and skin) were recorded. All skin biopsies were reviewed for the following features: psoriasiform hyperplasia, parakeratosis, neutrophil microabscess, spongiosis, eosinophil infiltrate, lichenoid lesion, necrotic keratinocytes, epidermotropism, atypical lymphocytes, as well as routine immunostainings (CD3, CD4, CD8). Additional T follicular helper markers (PD1, ICOS and CXCL13), CD7 loss and Ki-67 proliferation index were also studied. For PD1 expression, percentage of positive lymphocytes as well as staining intensity (+ to +++) were recorded, all together combined in the semi-quantitative H score= [0 × (% cells 0) + 1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]. Among 91 patients included with erythroderma, 21 were diagnosed as eczema, 17 as psoriasis, 20 as drug-induced erythroderma (DE), 13 as erythrodermic mycosis fungoides (E-MF) and 20 as Sézary syndrome (SS). Nail alterations, ear involvement and severe scaling were associated with psoriasis (p=0.044). Fever and hypereosinophilia were associated with DE diagnosis (p=0.044 and p=0.0003). Atypical lymphocytes in the skin were more frequent in E-MF and SS (p=0.044), as well as an abnormal blood immunophenotype and identical skin and blood T-cell clone. In SS, PD1 expression by T cells was significantly higher than in other aetiologies, as percentage of positive lymphocytes and intensity. PD1 H-score >50 was associated with SS (p<0.001, Se=75%; Sp=92%), with good reproducibility between observers, kappa coefficient of 0.66 (95% CI 0.33–1.00). CXCL13 expression was also associated with SS (p=0.044); CD7 loss was more frequent in E-MF and SS (p=0.022), and Ki-67 index was higher in SS and DE (p=0.041). In this large series erythroderma, we report the PD1 expression, and specifically the PD1 H-score combining percentage and intensity scoring, as a tool for differential diagnosis between SS and other aetiologies including E-MF. Interdisciplinary expertise combining clinical, pathological, and molecular data remain essential for erythroderma diagnosis. Erythroderma is a diagnostic challenge for dermatologists and pathologists. We aimed to identify clinical, histological and immunohistochemical markers that can be used to improve erythroderma diagnosis. This single-centre retrospective study included patients with erythroderma. To be included, erythroderma cases needed an accurate final diagnosis, at minimum one year of follow-up, available pictures and available skin biopsies to be reviewed. The demographic, clinical, biological (lactate deshydrogenase, eosinophilia, immunophenotype) and molecular features (T-cell clone in blood and skin) were recorded. All skin biopsies were reviewed for the following features: psoriasiform hyperplasia, parakeratosis, neutrophil microabscess, spongiosis, eosinophil infiltrate, lichenoid lesion, necrotic keratinocytes, epidermotropism, atypical lymphocytes, as well as routine immunostainings (CD3, CD4, CD8). Additional T follicular helper markers (PD1, ICOS and CXCL13), CD7 loss and Ki-67 proliferation index were also studied. For PD1 expression, percentage of positive lymphocytes as well as staining intensity (+ to +++) were recorded, all together combined in the semi-quantitative H score= [0 × (% cells 0) + 1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]. Among 91 patients included with erythroderma, 21 were diagnosed as eczema, 17 as psoriasis, 20 as drug-induced erythroderma (DE), 13 as erythrodermic mycosis fungoides (E-MF) and 20 as Sézary syndrome (SS). Nail alterations, ear involvement and severe scaling were associated with psoriasis (p=0.044). Fever and hypereosinophilia were associated with DE diagnosis (p=0.044 and p=0.0003). Atypical lymphocytes in the skin were more frequent in E-MF and SS (p=0.044), as well as an abnormal blood immunophenotype and identical skin and blood T-cell clone. In SS, PD1 expression by T cells was significantly higher than in other aetiologies, as percentage of positive lymphocytes and intensity. PD1 H-score >50 was associated with SS (p<0.001, Se=75%; Sp=92%), with good reproducibility between observers, kappa coefficient of 0.66 (95% CI 0.33–1.00). CXCL13 expression was also associated with SS (p=0.044); CD7 loss was more frequent in E-MF and SS (p=0.022), and Ki-67 index was higher in SS and DE (p=0.041). In this large series erythroderma, we report the PD1 expression, and specifically the PD1 H-score combining percentage and intensity scoring, as a tool for differential diagnosis between SS and other aetiologies including E-MF. Interdisciplinary expertise combining clinical, pathological, and molecular data remain essential for erythroderma diagnosis.