Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas.

BACKGROUND: Adnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors. AIM OF THE STUDY: To evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8+ infiltrate, and metastatic evolution. MATERIALS AND METHODS: Eighty-three adnexal carcinomas were included. Immunohistochemistry using anti-PD-L1 monoclonal antibodies (E1L3N and 22C3) and CD8 was performed. PD-L1 expression in tumor and immune cells, and CD8+ tumor-infiltrating lymphocyte (TIL) density were analyzed semi-quantitatively. RESULTS: Among the 60 sweat gland, 18 sebaceous and 5 trichoblastic carcinomas, 11% expressed PD-L1 in ≥ 1% tumor cells, more frequently sweat gland carcinomas (13%, 8/60) including apocrine carcinoma (40%, 2/5) and invasive extramammary Paget disease (57%, 4/7). Immune cells expressed significantly more PD-L1 than tumor cells (p < 0.01). Dense CD8+ TILs were present in 60% trichoblastic, 43% sweat gland, and 39% sebaceous carcinomas. CD8+ TILs were associated with PD-L1 expression by tumor cells (p < 0.01). Thirteen patients out of 47 developed metastases (27%) with a median follow-up of 30.5 months (range 7-36). Expression of PD-L1 by tumor cells was associated with the development of metastasis in univariate analysis (HR 4.0, 95% CI 1.1-15, p = 0.0377) but not in multivariate analysis (HR 4.1, 95% CI 0.6-29, p = 0.15). CONCLUSION: PD-L1 expression is highly heterogeneous among adnexal carcinoma subtypes, higher in apocrine carcinoma and invasive extramammary Paget disease, and associated with CD8+ TILs. Our data suggest the interest of evaluating anti-PD1 immunotherapy in advanced or metastatic cutaneous adnexal carcinoma.

Suppurative keloids: a complication of severe keloid disease.

BACKGROUND: Some keloids show cystic cavities that give rise to acute inflammatory flares and oozing. These suppurative keloids (SK) have rarely been systematically studied. We conducted a retrospective cohort study to evaluate SK frequency and its risk factors. We also reviewed microbiological analyses as well as the histological features of removed SKs. METHODS: Between July 1, 2015, and September 30, 2016, all adult patients attending a specialized keloid clinic were asked to participate. Clinical information and microbiological results were extracted from each patient's file. Histological features were observed and interpreted. RESULTS: In this study, we observed an SK rate of 26% for a mean keloid history of 17.2 years. Male gender, African ancestry, and a family history of keloids were significantly associated with suppuration. Microbiological examination revealed commensal skin flora 7/9 (77.8%), Staphylococcus aureus 1/9 (11.1%), and Enterococcus faecalis 1/9 (11.1%). CONCLUSION: Suppuration is a common complication of keloids occurring in patients with severe keloid disease and may arise from pilosebaceous occlusion and aseptic inflammation.

Prospective association between alcohol intake and hormone-dependent cancer risk: modulation by dietary fiber intake.

BACKGROUND: Alcohol intake is associated with increased circulating concentrations of sex hormones, which in turn may increase hormone-dependent cancer risk. This association may be modulated by dietary fiber intake, which has been shown to decrease steroid hormone bioavailability (decreased blood concentration and increased sex hormone-binding globulin concentration). However, this potential modulation has not been investigated in any prospective cohort. OBJECTIVES: Our objectives were to study the relation between alcohol intake and the risk of hormone-dependent cancers (breast, prostate, ovarian, endometrial, and testicular) and to investigate whether dietary fiber intake modulated these associations. DESIGN: This prospective observational analysis included 3771 women and 2771 men who participated in the Supplémentation en Vitamines et Minéraux Antioxydants study (1994-2007) and completed at least 6 valid 24-h dietary records during the first 2 y of follow-up. After a median follow-up of 12.1 y, 297 incident hormone-dependent cancer cases, including 158 breast and 123 prostate cancers, were diagnosed. Associations were tested via multivariate Cox proportional hazards models. RESULTS: Overall, alcohol intake was directly associated with the risk of hormone-dependent cancers (tertile 3 vs. tertile 1: HR: 1.36; 95% CI: 1.00, 1.84; P-trend = 0.02) and breast cancer (HR: 1.70; 95% CI: 1.11, 2.61; P-trend = 0.04) but not prostate cancer (P-trend = 0.3). In stratified analyses (by sex-specific median of dietary fiber intake), alcohol intake was directly associated with hormone-dependent cancer (tertile 3 vs. tertile 1: HR: 1.76; 95% CI: 1.10, 2.82; P-trend = 0.002), breast cancer (HR: 2.53; 95% CI: 1.30, 4.95; P-trend = 0.02), and prostate cancer (HR: 1.37; 95% CI: 0.65, 2.89; P-trend = 0.02) risk among individuals with low dietary fiber intake but not among their counterparts with higher dietary fiber intake (P-trend = 0.9, 0.8, and 0.6, respectively). The P-interaction between alcohol and dietary fiber intake was statistically significant for prostate cancer (P = 0.01) but not for overall hormone-dependent (P = 0.2) or breast (P = 0.9) cancer. CONCLUSION: In line with mechanistic hypotheses and experimental data, this prospective study suggested that dietary fiber intake might modulate the association between alcohol intake and risk of hormone-dependent cancer. This trial was registered at clinicaltrials.gov as NCT00272428.