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* Context.--Pemphigus is an autoimmune blister disease that causes blisters on the skin and mucosal surfaces. Direct immunofluorescence (DIF) testing is critical for the clinical diagnosis of pemphigus. However, it is limited to fresh tissue specimens and fluorescence microscopy. Objective.--To assess the value of C3d immunohistochemistry (IHC) on paraffin-embedded skin tissue for the diagnosis of pemphigus by comparing C3d-IHC results to DIF and enzyme-linked immunosorbent assay testing in pemphigus and other blister-related skin diseases. Design.--C3d-IHC assays were retrospectively performed on paraffin-embedded skin tissue sections from 115 patients (63 with pemphigus and 52 controls). Both the case group and the control group underwent the same protocol, and cases with C3d position in the peripheral spinous layer were considered as positive samples. Results.--C3d-IHC and DIF testing had similar performance for pemphigus diagnosis, with a sensitivity of 71.0% (95% CI, 51.8%-85.1 %) and 77.4% (95% CI, 58.5%-89.7%), specificity of 96.4% (95% CI, 79.8%-99.8%) and 100% (95% CI, 85.0%-100%), positive predictive value of 95.7% (95% CI, 76.0%-99.8%) and 100% (95% CI, 82.8%-100%), and a negative predictive value of 75.0% (95% CI, 57.5%-87.3%) and 80.0% (95% CI, 62.5%-90.9%), respectively. Conclusions.--Our study indicated that C3d-IHC results for paraffin-fixed tissues were not significantly different from DIF results for the diagnosis of pemphigus. The C3dIHC assay has the potential for routine diagnosis of pemphigus, especially in the absence of fresh-frozen tissue. (Arch Pathol Lab Med. 2024;148:1022-1027; doi: 10.5858/arpa.2023-0274-OA), Pemphigus is an autoimmune blister disease that causes blisters on the skin and mucosal surfaces (1) and is characterized by autoantibodies against desmoglein (Dsg)1 or Dsg3. (2-4) There are 2 [...]

Background: Tumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive aggregates, which have been reported to be associated with better prognosis in various tumors. However, their exact characteristics and prognostic value in extramammary Paget's disease (EMPD) remain unknown. Objective: To explore the features of TLSs in EMPD and their association with clinicopathological characteristics. Methods: In total, 171 EMPD patients from 2015 to 2023, retrospective, single center cohort were collected to assess the presence, maturation status, and location of TLSs by immunohistochemistry. Then, their clinicopathologic association and prognostic significance were further examined. Results: TLSs were detected in 97 cases (57%) of 171 EMPD patients, including high-density TLSs in 88 cases (91%), peritumoral TLSs (pTLSs) in 89 cases (92%), TLSs around appendages (aTLSs) in 23 cases (24%), and mature TLSs in 16 cases (16%). Secondary EMPD was more likely to produce TLS (Secondary: 16/21 [76%]; Primary: 81/150 [54%]; P = 0.06), and more likely to produce Mature TLS (Secondary: 5/10 [50%]; Primary: 11/80 [14%]; P = 0.02). The subjective symptoms of EMPD patients did not seem to correlate with the presence of TLS. EMPD patients with tumor invasion were more likely to form mature TLS (Invasion: 8/32 [25%]; In situ : 8/65 [12%]; P = 0.06), recurrent EMPD patients were more likely to form TLS (Recurrent: 34/50 [68%]; Initial: 63/121 [52%]; P = 0.06) especially mature TLS (Recurrent: 8/34 [24%]; Initial: 8/63 [13%]; P = 0.04). The depth of tumor invasion in EMPD patients with mature TLS was mostly less than or equal to 4mm (mature TLS+: 7/8 [88%]; TLS-: 6/17 [35%]; P = 0.05), aTLS were less common in EMPD patients with skin appendage invasion (aTLS+: 4/23 [17%]; aTLS-: 32/74 [43%]; P = 0.03). The same EMPD patients relapse after, the existence of TLS increased [TLS+ (initial): 9/17 (53%); TLS+ (recurrence):14/17 (82%); P =.07]. Limitations: Retrospective study design. Conclusions: Mature TLS is a positive prognostic factor for invasive EMPD and may serve as a new biomarker and therapeutic target for EMPD. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo. [ABSTRACT FROM AUTHOR]

Background: Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear., Objective: This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma., Methods: Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS., Results: The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy., Conclusion: These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: Conflicts of interest the authors declare no conflicts of interest. H.Z. and P.X. share first authorship.