Enrico Pegolo

Hormone receptor and human epidermal growth factor receptor 2 status evaluation on ThinPrep specimens from breast carcinoma: correlation with histologic sections determination.

Fine‐needle aspiration cytology (FNAC) is a well‐accepted procedure for the diagnosis and biological characterization of breast carcinoma. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status have a strong prognostic and predictive value in invasive breast carcinoma (IBC). ThinPrep (TP) cytology, which uses an alcohol‐based fixative, is increasingly being used for immunocytochemistry. In this study, the authors compared the immunocytochemical evaluation of hormone receptors (HR) and HER2 on TP‐processed FNAC with the immunohistochemical analysis performed on the corresponding formalin‐fixed paraffin‐embedded (FFPE) breast tumor specimens, which are considered the gold standard.

Molecular Differences Between Human Thyroid Follicular Adenoma and Carcinoma Revealed by Analysis of a Murine Model of Thyroid Cancer

Mouse models can provide useful information to understand molecular mechanisms of human tumorigenesis. In this study, the conditional thyroid mutagenesis of Pten and Ras genes in the mouse, which induces very aggressive follicular carcinomas (FTCs), has been used to identify genes differentially expressed among human normal thyroid tissue (NT), follicular adenoma (FA), and FTC. Global gene expression of mouse FTC was compared with that of mouse normal thyroids: 911 genes were found deregulated ± 2-fold in FTC samples. Then the expression of 45 deregulated genes in mouse tumors was investigated by quantitative RT-PCR in a first cohort of human NT, FA, and FTC (discovery group). Five genes were found significantly down-regulated in FA and FTC compared with NT. However, 17 genes were found differentially expressed between FA and FTC: 5 and 12 genes were overexpressed and underexpressed in FTC vs FA, respectively. Finally, 7 gene products, selected from results obtained in the discovery group, were investigated in a second cohort of human tumors (validation group) by immunohistochemistry. Four proteins showed significant differences between FA and FTC (peroxisomal proliferator-activated receptor-γ, serum deprivation response protein, osteoglycin, and dipeptidase 1). Altogether our data indicate that the establishment of an enriched panel of molecular biomarkers using data coming from mouse thyroid tumors and validated in human specimens may help to set up a more valid platform to further improve diagnosis and prognosis of thyroid malignancies.

One-step nucleic acid amplification (OSNA) for intraoperative evaluation of sentinel lymph node status in breast cancer: a comparative study between CK19 protein expression and CK19 mRNA level in primary tumors and lymph node metastasis

The one-step nucleic acid amplification (OSNA) method is an increasingly used procedure for intraoperative analysis of sentinel lymph node (SLN) status in breast cancer patients. It measures cytokeratin19 (CK19) mRNA copy numbers in homogenized samples of SLN; CK19 has been chosen for identifying node metastasis because most breast cancers express this molecule. However, to avoid false-negative OSNA results, testing the preoperative needle core biopsy (NCB) of breast carcinomas for CK19 by immunohistochemistry (IHC) has been recommended. This procedure relies on the assumption that protein expression is strictly related to mRNA expression. We developed this study to evaluate if IHC gives similar result to the molecular assay. In a series of breast cancer patients with axillary metastasis, corresponding surgically resected tumor and metastatic lymph node specimens have been tested for CK19 protein by IHC and for CK19 mRNA by real-time PCR; furthermore, CK19 immunostaining has been performed in NCBs when available. Statistical analysis revealed that (1) the immunohistochemical evaluation of CK19 in NCB is a reliable test, reflecting protein expression in the whole tumor and in the metastatic lymph node; (2) there is no correlation between CK19 protein expression and CK19 RNA level neither within the primary breast cancer nor within the metastatic node; moreover, no correlation as well has been found between protein expression in NCB and mRNA level in metastatic lymph nodes. Thus, our results suggest that there is no evidence-based reason to stain every NCB for CK19 before performing OSNA in patients with breast cancer.

Dermoscopy of Grover's disease: Variability according to histological subtype

Distinguishing Grovers disease from other papular dermatoses is often a troublesome task. According to two relatively recent case reports, dermoscopy may be useful in assisting the diagnosis of such a disorder by showing a peculiar pattern. The aim of this study was to evaluate the dermoscopic features of Grovers disease in a larger series of patients and correlate dermoscopy with histopathological findings. Seven patients with histopathologically confirmed Grovers disease were included in the study, with three of them displaying a Darier‐like histology and the remaining four cases having a spongiotic histological pattern. The results of our study suggest that Grovers disease may display different features according to the histological subtype, with a central star‐shaped/branched polygonal/roundish‐oval brownish area surrounded by a whitish halo being characteristic of the Darier‐like histological subtype and whitish scales over a reddish‐yellowish background being characteristic of the spongiotic histological subtype.

Dermoscopy: a useful auxiliary tool in the diagnosis of type 1 segmental Darier's disease.

Type 1 segmental Darier’s disease is a blaschkolinear variant of Darier’s disease resulting from a postzygotic mosaicism. Since it usually lacks diagnostic clues typical of the generalized form, including positive family history of the disease, nail and mucosal abnormalities, and/or acral involvement, its distinction from other acquired inflammatory blaschkolinear dermatoses may often be quite challenging, thus requiring histopathological examination to reach a definitive diagnosis. We report a case of type 1 segmental Darier’s disease with its dermoscopic findings in order to show the usefulness of dermoscopy in assisting the noninvasive identification of this condition.

An NF-κB signature predicts low-grade glioma prognosis: a precision medicine approach based on patient-derived stem cells

Background While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and representative of the glioma microenvironment. Methods By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery. Gene set enrichment and pathway enrichment analyses were applied. The prognostic role of a nuclear factor-kappaB (NF-κB) signature derived from GASC-BAD was tested in 530 newly diagnosed diffuse LGG patients comprised within The Cancer Genome Atlas (TCGA) database. The prognostic value of the GASC upstream regulator p65 NF-κB was assessed, by univariate and multivariate Cox analyses, in a single center case study, including 146 grade II LGGs. Results The key elements differentiating the transcriptome of GASC isolated from LGG with different prognoses were mostly related to hallmarks of cancer (eg, inflammatory/immune process, NF-κB activation). Consistently, the NF-κB signature extrapolated from the GASC study was prognostic in the dataset of TCGA. Finally, the nuclear expression of the NF-kB-p65 protein, assessed using an inexpensive immunohistochemical method, was an independent predictor of both overall survival and malignant progression-free survival in 146 grade II LGGs. Conclusion This study demonstrates for the first time the independent prognostic role of NF-kB activation in LGG and outlines the role of patient-based stem cell models as a tool for precision medicine approaches.

Dermoscopy as a Supportive Instrument in the Early Recognition of Erosive Adenomatosis of the Nipple and Mammary Paget's Disease

Vol. 29, No. 3, 2017 365 Received May 12, 2016, Revised June 11, 2016, Accepted for publication June 15, 2016 Corresponding author: Enzo Errichetti, Institute of Dermatology, “Santa Maria della Misericordia” University Hospital, Piazzale Santa Maria della Misericordia, 15. 33100-Udine, Italy. Tel: 39-0432559820, Fax: 39-0432559892, E-mail: enzoerri@yahoo.it This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright

Dermoscopy as an auxiliary tool in the early differential diagnosis of acute generalized exanthematous pustulosis (AGEP) and exanthematous (morbilliform) drug eruption.

CLINICAL PRESENTATION Two men, aged 77 years (case 1) and aged 68 years (case 2), presented with a 2and a 3-day history, respectively, of a moderately febrile, widespread, pruritic rash occurring some days after taking a nonsteroidal anti-inflammatory agent. In both patients, clinical examination showed multiple, partially confluent, 3to 5-mm diameter, erythematous macules and papules on the arms and trunk (Fig 1).

Acquired lymphangioma of the penis in a patient with severe phimosis

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Atypical fibroxanthoma arising in a scar of discoid lupus erythematosus.

Background: Malignant change in the scars of discoid lupus erythematosus (DLE) is a well-known event. In most cases, tumors are of epithelial origin, particularly squamous cell carcinomas and, less frequently, basal cell carcinomas and keratoacanthomas. The onset of soft tissue sarcomas in a DLE scar is a very rare event, however, because only one case of malignant fibrous histiocytoma has been described in the literature. Objective: We describe the first documented report of atypical fibroxanthoma (AFX) arising in an old scar of DLE. Results: Although we cannot exclude an accidental association between AFX and DLE, our case emphasizes that patients with DLE may develop AFX in the context of an old scar. Conclusion: Our finding further underlines the importance of strict and long-term surveillance of people with DLE to identify and remove eventual tumors at an early stage.