Dermatopathology

Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies.

Cutaneous squamous cell carcinoma (cSCC) is an immunogenic malignancy with variable immune infiltration and inconsistent responses to checkpoint blockade. Tumor-infiltrating lymphocytes (TILs) influence tumor progression and therapeutic outcome, yet their phenotypic and functional diversity across disease contexts remains incompletely understood. This review systematically characterizes the TIL landscape in human cSCC. Following PRISMA 2020 guidelines, PubMed and Embase were searched up to May 2025 and restricted to studies evaluating tumor-infiltrating lymphocytes in human cSCC, using the modified Newcatle–Ottawa score to assess risk of bias. Data were synthesized qualitatively given methodological heterogeneity. 48 studies met inclusion criteria. cSCCs exhibited dense CD3⁺ infiltrates composed of cytotoxic (CD8⁺GzmB⁺, Ki-67⁺, CD69⁺) and regulatory (FOXP3⁺, CCR4⁺) subsets. Higher CD8⁺ activity correlated with smaller tumors and longer disease-free survival, whereas FOXP3⁺ enrichment and TGF-β2 signaling promoted immune evasion. Immunosuppressed patients demonstrated diminished CD8⁺ density and clonality. Immune modulation with PD-1/PD-L1 blockade, imiquimod, HPV vaccination, or OX40 stimulation enhanced effector function. The cSCC immune microenvironment reflects a balance between cytotoxic and suppressive factors. Harmonizing multimodal immune profiling and integrating spatial context with systemic immune status may advance both prognostic stratification and therapeutic design.

Accurate diagnosis of melanomas is crucial for proper evaluation and treatment. One immunohistochemical stain frequently utilized is PRAME (PReferentially expressed Antigen in MElanoma), a tumor-associated antigen expressed in most melanomas. This study aims to evaluate the reproducibility of PRAME scoring performed by dermatopathologists at an academic tertiary referral medical center. A blinded survey was designed featuring 21 melanocytic neoplasms stained with PRAME and H&E. For each case, five dermatopathologists provided a PRAME score from 0–4+, percent PRAME positivity, values for H-score, and a descriptive interpretation. Absolute agreement across raters was assessed using a Kappa statistic for PRAME score and intraclass correlations (ICCs) for H-score and PRAME percentage. Statistical analysis indicated poor inter-rater reliability for PRAME score (Kappa = 0.16), percent PRAME positivity (ICC = 0.31), and H-score (ICC = 0.40). Reporting language varied among pathologists. Our study demonstrated that the interpretation of PRAME immunohistochemistry lacks reproducibility, especially for challenging lesions. This suggests that a more rigorous, defined, and reproducible scoring method should be investigated for equivocal cases. Future studies may explore the utility of artificial intelligence software in the interpretation of PRAME for borderline lesions to improve reliability and standardize scoring.