RESUMEN
ABSTRACT: Most melanocytic tumors are classified as benign or malignant based on clinical morphology, histology, and immunohistochemical (IHC) analysis. A subset of more challenging cases with ambiguous features may require further evaluation with established ancillary diagnostic molecular studies, including fluorescence in situ hybridization and/or single nucleotide polymorphism array, to increase diagnostic certainty. More recently, a diagnostic gene expression-profiling (GEP) assay and an IHC stain for the detection of PRAME (PReferentially expressed Antigen in MElanoma) have been developed. The use of PRAME IHC has been validated in cases of unequivocal and ambiguous melanocytic proliferations via comparing results with fluorescence in situ hybridization and/or single nucleotide polymorphism array. A study comparing performance metrics of PRAME IHC and diagnostic GEP has not been previously published. Herein, we evaluated the use of PRAME IHC in 55 melanocytic tumors with challenging histomorphology by comparing the results with diagnostic GEP and final histomorphologic diagnosis. Intertest agreement occurred in 88% of cases. PRAME IHC supported the final diagnosis in 89% of cases with a sensitivity of 79%, specificity of 95%, and positive predictive value of 88.2%. GEP agreed with the final diagnosis in 88% of cases with a sensitivity of 65%, 97% specificity, and positively predicted melanoma in 91.7% of cases. Because the results of this study align with past publications evaluating the performance metrics of PRAME IHC, showing it to be as sensitive as and more cost effective than all other ancillary molecular tests, we propose the use of PRAME IHC as the optimal first-line diagnostic tool for ambiguous melanocytic proliferations.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Hibridación Fluorescente in Situ , Inmunohistoquímica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Expresión Génica , Antígenos de Neoplasias/genéticaRESUMEN
A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.