Assessment of specificity of dermatopathologic criteria for IgG4-related skin disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Femtosecond electronic structure response to high intensity XFEL pulses probed by iron X-ray emission spectroscopy.

We report the time-resolved femtosecond evolution of the K-shell X-ray emission spectra of iron during high intensity illumination of X-rays in a micron-sized focused hard X-ray free electron laser (XFEL) beam. Detailed pulse length dependent measurements revealed that rapid spectral energy shift and broadening started within the first 10 fs of the X-ray illumination at intensity levels between 1017 and 1018 W cm-2. We attribute these spectral changes to the rapid evolution of high-density photoelectron mediated secondary collisional ionization processes upon the absorption of the incident XFEL radiation. These fast electronic processes, occurring at timescales well within the typical XFEL pulse durations (i.e., tens of fs), set the boundary conditions of the pulse intensity and sample parameters where the widely-accepted 'probe-before-destroy' measurement strategy can be adopted for electronic-structure related XFEL experiments.