ABSTRACT
Dysplastic nevi represent one of the least agreed-upon entities in dermatopathology despite the existence of established criteria. This study explores preferentially expressed antigen in melanoma (PRAME) in dysplastic nevi, an uncharted area. We examined 22 common melanocytic nevi (CMN), 20 cutaneous melanomas (CM), 48 low-grade dysplastic nevi (LG-DN), and 40 high-grade dysplastic nevi (HG-DN). PRAME was immunohistochemically assessed using a five-tiered system (0 to 4 +). Among CMN, 59% scored 0, 32% scored 1 + , and 9% scored 2 + . CM had score 2 + and 4 + in 11% and 89% of cases, respectively. Among LG-DN, 38% presented score 0, 31% score 1 + , 17% score 2 + , 8% score 3 + , and 6% score 4 + . Thirty per cent of HG-DN demonstrated a score 0, 30% with score 1 + , 15% score 2 + , 10% score 3 + , and 15% score 4 + . Compared to CMN and CM, LG-DN and HG-DN showed heterogeneous expression profiles of PRAME. PRAME positivity effectively distinguished HG-DN from CM with 85% specificity and 80% sensitivity (p < 0.0001). Predictive values were 87% (negative) and 76% (positive). Furthermore, a trend of increased PRAME expression from LG-DN to HG-DN was observed. However, the applicability of PRAME in the differential diagnosis of dysplastic lesions remains unclear as can yield conflicting results with morphology, which remains the primary diagnostic tool for melanocytic lesions.
Subject(s)
Antigens, Neoplasm , Biomarkers, Tumor , Dysplastic Nevus Syndrome , Melanoma , Skin Neoplasms , Humans , Dysplastic Nevus Syndrome/pathology , Dysplastic Nevus Syndrome/metabolism , Antigens, Neoplasm/analysis , Antigens, Neoplasm/metabolism , Antigens, Neoplasm/biosynthesis , Skin Neoplasms/pathology , Skin Neoplasms/metabolism , Melanoma/pathology , Melanoma/metabolism , Melanoma/diagnosis , Male , Female , Biomarkers, Tumor/analysis , Middle Aged , Adult , Aged , Nevus, Pigmented/pathology , Nevus, Pigmented/metabolism , Cohort Studies , Immunohistochemistry , Young Adult , Aged, 80 and over , Melanoma, Cutaneous Malignant , Adolescent , Diagnosis, DifferentialABSTRACT
IgG4-Related Disease (IgG4-RD) is a fibroinflammatory condition characterized by a typical histopathological pattern (dense lymphoplasmacytic infiltrate with prevalent IgG4+ plasma cells and storiform fibrosis), which may involve the kidney both directly (IgG4-related kidney disease, IgG4-RKD) or indirectly, as a consequence of post-renal ureteral obstruction due to retroperitoneal fibrosis (IgG4-RD RF). The most frequent presentation of IgG4-RKD is IgG4-related tubulointerstitial nephritis (TIN), but a glomerular disease can be present, in most of the cases a membranous nephropathy. Albeit steroid-responsive, in some cases renal manifestations may lead to progressive and permanent organ damage. In this review we describe four clinical cases representative of typical and less typical renal manifestations of IgG4-RD, emphasizing a potential, subclinical, early involvement of the kidney in the disease.
