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Abstract：
Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.
摘要：
肉芽肿真菌病真菌（GMF）是一种罕见的真菌病（MF），其特征是与肿瘤性淋巴样人群相关的肉芽肿浸润，与常规MF相比，预后较差。T辅助轴(Th)的上调，尤其是Th17，在几种炎性/感染性肉芽肿性皮肤病的发病机制中起重要作用，但其在GMF中的作用至今仍未阐明。在这项研究中,我们评估了Th1（Tbet）的免疫组织化学表达，Th2(GATA-3),Th17（RORγT），T监管（Foxp3），GMF和MF大细胞转化（MFLCT）患者队列中的免疫检查点（IC）（PD-1和PD-L1）标志物。研究了49例患者（28例GMF和21例MFLCT）的皮肤活检。GMF患者与早期临床阶段（p=0.036）和较低水平的乳酸脱氢酶（p=0.042）有关。Tbet阳性的细胞百分比增加（p=0.017），RORγT（p=0.001），在GMF标本中也观察到PD-L1(p=0.011)，而在MFLCT病例中检测到更强的PD-1强度。在这个队列中，LCT,RORγT<10%,Foxp3<10%，年龄,在单因素分析中，晚期与较差的总生存期（OS）相关。GMF显示Th1（细胞反应）和Th17（自身免疫）表型，见于早期MF和肉芽肿过程，分别,这可能与GMF的组织病理学表现和生物学行为有关。需要进行涉及更多病例和更敏感技术的进一步研究。
