Department of Dermatology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Department of Pathology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
J Cutan Pathol. 2024 Feb;51(2):163-169. doi: 10.1111/cup.14548. Epub 2023 Oct 18.
IgG4-related disease (IgG4-RD) represents a recently characterized multisystemic fibroinflammatory condition that can manifest a spectrum of skin findings (IgG4-related skin disease; IgG4-RSD). Histopathologic and immunohistochemical criteria have been proposed; however, the specificity of these criteria merits scrutiny given the potential histopathologic overlap of IgG4-RSD and both neoplastic and inflammatory skin conditions featuring lymphoplasmacytic infiltrates (IgG4-RSD mimics). This study sought to assess the specificity of the criteria by quantifying the frequency by which an expanded spectrum of IgG4-RSD mimics meet proposed thresholds.
Following IRB approval, a total of 69 cases of IgG4-RD mimics, representing 14 different diagnoses featuring plasma cells, were reviewed and analyzed for the following histopathologic and immunohistochemical features: (i) maximum IgG4+ count/high-powered field (hpf) >200; (ii) IgG4/IgG ratio >0.4 averaged over 3 hpfs; (iii) IgG4+ count >10 per hpf.
Screening for IgG4-RSD by histopathologic criteria demonstrated the high frequency of lymphoplasmacytic infiltrates, contrasted with the rarity of storiform fibrosis (only one case of erythema elevatum diutinum [EED]) and obliterative phlebitis (0 cases). By immunohistochemical criteria, the analysis revealed that no cases exceeded 200 IgG4+ cells; 13% (9/69) cases demonstrated an IgG4/IgG ratio of >0.4 averaged over 3 hpfs; and 23% (16/69) cases demonstrated a mean IgG4+ count of >10 per hpf.
Application of proposed IgG4-RSD histopathologic criteria to an expanded spectrum of potential IgG4-RSD mimics (to include cutaneous marginal zone lymphoma, syphilis, necrobiosis lipoidica, lichen sclerosus, ALHE, psoriasis, lymphoplasmacytic plaque, EED, and erosive pustular dermatosis), highlights the relative nonspecificity of lymphoplasmacytic infiltrates contrasted with the stringency of storiform fibrosis and obliterative fibrosis. Furthermore, an IgG4+ cell count of >10 per hpf and an IgG4/IgG ratio of >0.4 are not specific to IgG4-RSD alone. In the appropriate clinical context for IgG4-RSD, histopathologic features still represent the entry threshold for diagnosis consideration, which then allows for further screening by immunohistochemical criteria.
IgG4 相关疾病（IgG4-RD）代表了一种最近被描述的多系统纤维炎症性疾病，它可以表现出一系列皮肤表现（IgG4 相关皮肤病；IgG4-RSD）。已经提出了组织病理学和免疫组织化学标准；然而，鉴于 IgG4-RSD 与具有淋巴浆细胞浸润的肿瘤性和炎症性皮肤病（IgG4-RSD 模拟物）之间存在潜在的组织病理学重叠，这些标准的特异性值得仔细审查。本研究旨在通过量化一系列 IgG4-RSD 模拟物符合提出的阈值的频率来评估这些标准的特异性。
在获得机构审查委员会批准后，总共回顾和分析了 69 例 IgG4-RD 模拟物，这些病例代表了 14 种不同的具有浆细胞的诊断，这些病例的组织病理学和免疫组织化学特征如下：（i）最大 IgG4+计数/高倍视野（hpf）>200；（ii）IgG4/IgG 比值>0.4，在 3 个 hpf 上平均；（iii）每个 hpf 的 IgG4+计数>10。
通过组织病理学标准筛查 IgG4-RSD 显示出淋巴浆细胞浸润的高频率，与硬纤维性纤维化的罕见性形成对比（只有一例硬结性红斑[EED]）和闭塞性静脉炎（0 例）。通过免疫组织化学标准分析显示，没有病例超过 200 个 IgG4+细胞；13%（9/69）的病例 IgG4/IgG 比值>0.4，在 3 个 hpf 上平均；23%（16/69）的病例平均 IgG4+计数>10 个/hpf。
将提出的 IgG4-RSD 组织病理学标准应用于更广泛的潜在 IgG4-RSD 模拟物（包括皮肤边缘区淋巴瘤、梅毒、坏死性脂膜炎、硬皮病、ALHE、银屑病、淋巴浆细胞斑块、EED 和侵蚀性脓疱性皮炎），突出了淋巴浆细胞浸润的相对非特异性，与硬纤维性纤维化和闭塞性纤维化的严格性形成对比。此外，每个 hpf 的 IgG4+细胞计数>10 和 IgG4/IgG 比值>0.4 并不单独针对 IgG4-RD 特异性。在 IgG4-RD 的适当临床背景下，组织病理学特征仍然是诊断考虑的入门阈值，然后可以通过免疫组织化学标准进一步筛选。
