Positive predictive value of ERBB2 copy number gain by tissue or circulating tumor DNA next-generation sequencing across advanced cancers

BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood. MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing. RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast ( CONCLUSIONS: ERBB2 CNG by NGS is detected in numerous malignancies for which HER2 testing is not standard. Detection of ERBB2 CNG by tissue NGS and ctDNA has a high PPV for true HER2-positivity by standard IHC and/or FISH testing in breast cancer

Distinguishing histopathologic features of acantholytic dermatoses and the pattern of acantholytic hypergranulosis

Background: Acantholysis can be seen in multiple skin diseases. Adnexal acantholysis has been regarded as a distinguishing feature of pemphigus vulgaris (PV) from other acantholytic conditions. Methods: A retrospective review of the histopathologic features of diseases with acantholysis including PV, pemphigus foliaceus (PF), Hailey-Hailey disease (HHD), Darier disease (DD), Grover's disease, and pityriasis rubra pilaris (PRP) was performed. Results: Biopsies of PV (n = 49), HHD (n = 27), DD (n = 25), Grover's disease (n = 65), and PRP (n = 33) showed suprabasilar acantholysis. Acantholysis was limited to the lower epidermis in PV and PRP, and involved all epidermal layers in HHD, DD, and Grover's disease. Acantholysis in PF (n = 38) mainly involved the upper epidermis. Follicular acantholysis occurred more frequently in PV and PF (P < 0.0001). Eccrine acantholysis was found in PV (42%), HHD (18%), PF (13%), and DD (4%). Grover, DD, and HHD had greater dyskeratosis (P < 0.0001). Neutrophils were more common in PV, PF, and HHD, while eosinophils were more common in Grover's and DD. A pattern termed acantholytic hypergranulosis occurred predominantly in PF. Conclusion: Adnexal acantholysis does not reliably distinguish PV from PF. The level of acantholysis, degree of dyskeratosis, and acantholytic hypergranulosis are distinguishing features between the two types of pemphigus and other acantholytic disorders