Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas.

Breast adenomyoepitheliomas (AMEs) are rare epithelial-myoepithelial neoplasms that may occasionally produce myxochondroid matrix, akin to pleomorphic adenomas (PAs). Regardless of their anatomic location, PAs often harbor rearrangements involving HMGA2 or PLAG1. We have recently shown that the repertoire of somatic genetic alterations of AMEs varies according to their estrogen receptor (ER) status; whilst the majority of ER-positive AMEs display mutually exclusive PIK3CA or AKT1 hotspot mutations, up to 60% of ER-negative AMEs harbor concurrent HRAS Q61 hotspot mutations and mutations affecting either PIK3CA or PIK3R1. Here, we hypothesized that a subset of AMEs lacking these somatic genetic alterations could be underpinned by oncogenic fusion genes, in particular those involving HMGA2 or PLAG1. Therefore, we subjected 13 AMEs to RNA-sequencing for fusion discovery (n = 5) and/or fluorescence in situ hybridization (FISH) analysis for HMGA2 and PLAG1 rearrangements (n = 13). RNA-sequencing revealed an HMGA2-WIF1 fusion gene in an ER-positive AME lacking HRAS, PIK3CA and AKT1 somatic mutations. This fusion gene, which has been previously described in salivary gland PAs, results in a chimeric transcript composed of exons 1-5 of HMGA2 and exons 3-10 of WIF1. No additional in-frame fusion genes or HMGA2 or PLAG1 rearrangements were identified in the remaining AMEs analyzed. Our results demonstrate that a subset of AMEs lacking mutations affecting HRAS and PI3K pathway-related genes may harbor HMGA2-WIF1 fusion genes, suggesting that a subset of breast AMEs may be genetically related to PAs or that a subset of AMEs may originate in the context of a PA.

Influence of specimen adequacy on the diagnosis of ASCUS.

The impact of specimen adequacy on the diagnosis of cervical cytology is not fully understood. Virtually, the greatest impact of smear quality limitation factors is on the diagnosis of atypical squamous cells of undetermined significance (ASCUS) because this category is more susceptible to interpretation mistake due to its criteria subjectivity. This study aims to evaluate the impact of smear quality impairing factors on the diagnosis of ASCUS. The 1,507 cases of ASCUS studied were obtained from the Cervical Cancer Screening Program of Paraná (CCSPP). The cases were reviewed by expert cytopathologists and the results were correlated to the specimen adequacy. The results showed that the presence of obscuring blood impairs the correct diagnosis and leads the pathologist to overdiagnose negative smears as ASCUS. The presence of adequate endocervical sampling contributes to a higher rate of correct ASCUS diagnoses but did not influence the pathologist to over- or underestimate the cytological findings.