Citations

Cumulative evidence demonstrates that most RNAs exhibit specific subcellular distribution. However, the mechanisms regulating this phenomenon and its functional consequences are still under investigation. Here, we reveal that cadherin complexes at the apical zonula adherens (ZA) of epithelial adherens junctions recruit the core components of the RNA-induced silencing complex (RISC) Ago2, GW182, and PABPC1, as well as a set of 522 messenger RNAs (mRNAs) and 28 mature microRNAs (miRNAs or miRs), via PLEKHA7. Top canonical pathways represented by these mRNAs include Wnt/β-catenin, TGF-β, and stem cell signaling. We specifically demonstrate the presence and silencing of MYC, JUN, and SOX2 mRNAs by miR-24 and miR-200c at the ZA. PLEKHA7 knockdown dissociates RISC from the ZA, decreases loading of the ZA-associated mRNAs and miRNAs to Ago2, and results in a corresponding increase of MYC, JUN, and SOX2 protein expression. The present work reveals a mechanism that directly links junction integrity to the silencing of a set of mRNAs that critically affect epithelial homeostasis.

Amicrobial pustulosis of the folds (APF) is a rare disease characterized by aseptic pustular lesions involving cutaneous folds, typically occurring in the context of an autoimmune disorder. We present 4 patients with APF, focusing on clinical and histopathologic characteristics to improve the recognition of this entity. All 4 patients had intertriginous and extra‐intertriginous involvement. Common histopathologic features of skin biopsies in these patients were intracorneal, subcorneal, intraepidermal, perivascular, perifollicular and interstitial neutrophilic inflammation. Pustules overlying adnexal ostium and papillary dermal edema were consistently observed. The pustules were negative for microorganisms on stain testing. In these cases, associated conditions were undifferentiated connective tissue disease, systemic lupus erythematosus, antiphospholipid syndrome, Crohn disease and Hashimoto thyroiditis. The aforementioned clinical and histopathologic characteristics of patients with suspected or diagnosed connective tissue disorders should lead to suspicion for APF.

Background Periodic acid Schiff‐diastase ( PAS ‐D) staining is used routinely in dermatopathology. Conventionally, parakeratosis or intracorneal neutrophils justify use of PAS ‐D stain to identify dermatophytosis. We aimed to investigate the histopathological features of superficial dermatophytosis. Methods Skin biopsies with PAS ‐D stain were retrospectively reviewed by a blinded dermatopathologist. Histopathologic findings in cases with dermatophytosis were compared with those without. Results We studied 110 cases, of which 63 were PAS ‐D positive for dermatophytes. Dermatophytes were identified on hematoxylin and eosin (H&E) staining in 49 (77.8%) of the PAS ‐D‐positive cases. Diffuse compact orthokeratosis (79.37%, p < 0.001) and focal parakeratosis (65.08%, p = 0.03) were significantly more frequent in dermatophytosis. Intracorneal neutrophils and spongiosis were not significant findings. Fungal elements were frequently observed within compact orthokeratosis (62.0%) and parakeratosis (31.8%) but rarely within intracorneal pustules (12.7%). In some dermatophyte cases, intracorneal neutrophils (47.6%) or parakeratosis (17.5%) were absent. Conclusions Compact orthokeratosis or focal parakeratosis justifies PAS ‐D staining, whereas the absence of intracorneal neutrophils or parakeratosis is insufficient to exclude dermatophytosis. Results indicate that having a low threshold to perform PAS‐D stain is justified. PAS‐D stain may be deferred until H&E slides have been evaluated.

Nodular fasciitis (NF) is a clonal self‐limited neoplastic proliferation characterized by rearrangements of the USP6 locus in most examples. To our knowledge well‐documented malignant behavior has never been previously observed in NF. In this report we present an unusual case of NF with classical histologic features that showed a protracted clinical course characterized by multiple recurrences and eventual metastatic behavior over a period of 10 years. Molecular analyses revealed the presence and amplification of the novel PPPR6‐USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of NF. © 2016 Wiley Periodicals, Inc.