CDX2 and LEF-1 expression in pilomatrical tumors and their utility in the diagnosis of pilomatrical carcinoma

Abstract

Background

The Wnt signaling pathway has been implicated in the pathogenesis of pilomatrical tumors. LEF-1 is a downstream component of this pathway, and CDX2 has been postulated to regulate it, but little is known about expression of these transcription factors in pilomatrical tumors.

Methods

Immunohistochemistry for CDX2, β-catenin, LEF-1, CK19, CK5, SATB2, Cadherin 17, and Androgen receptor was performed on pilomatricomas (PMs) (N=12), pilomatrical carcinomas (PMCAs) (N=12), and non-pilomatrical cutaneous tumors (N=18).

Results

PMs and PMCAs were positive for CDX2 (9/12 PMs, sens=75%,spec=100%;11/12 PMCAs, sens=92%,spec=100%;p<0.01), β-catenin (12/12 PMs, sens=100%, spec=94%;10/12 PMCAs, sens=83%, spec=94%;p<0.01), and LEF-1 (12/12 PMs, sens=100%, spec=56%;12/12 PMCAs, sens=100%, spec=56%;p<0.01 ). CDX2 expression was commonly focal, within a discrete subpopulation of squamoid cells. The LEF-1 expression pattern was different and discernable between pilomatrical tumors (strong, diffuse) and non-pilomatrical tumors (weak, patchy).

Conclusions

This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for pilomatrical carcinoma, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors.

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Cutaneous Intravascular CD30+ T-cell Pseudolymphoma Occurring in a Regressing Keratoacanthoma

Abstract

Cutaneous intravascular CD30+ pseudolymphoma is an uncommon incidental finding that may mimic intravascular or angiotropic lymphoma. We describe a 78-year-old female with a traumatized regressing keratoacanthoma on her left cheek. A shave biopsy was performed which revealed intravascular staining of atypical lymphocytes positive for CD45, CD3 and CD30. Clinical exam revealed no other evidence of lymphoma, the patient denied constitutional symptoms, and routine blood work was normal. The patient is healthy and doing well 28 months after her first visit. CD30+ pseudolymphoma should be distinguished from malignant intravascular lymphoproliferative disorders.

http://ift.tt/2Ge8IFj

#dermpathJC: The First Online Dermatopathology Twitter Journal Club

Twitter, an online social media platform created in the spring of 2006, has now reached approximately 328 million active monthly users¹. It allows for rapid exchange of ideas in 140 character tweets.

http://ift.tt/2rHaGL4

Lichen planopilaris and frontal fibrosing alopecia cannot be differentiated by histopathology

Abstract

Background

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) represent two entities that cause primary cicatricial alopecia. These entities are clinically different; nevertheless the literature suggests that FFA represents a form of LPP. The main argument in support of this hypothesis is that previous studies comparing the histologic findings have not found obvious differences between these diseases.

Methods

Our objective was to more critically compare and contrast 20 histologic findings of these diseases in a large number of patients in order to determine any significant histologic differences between LPP and FFA.

Results

We found three parameters that were statistically different, namely the presence of terminal catagen-telogen hairs (50% FFA versus 23.5% LPP; p = 0.020); a severe perifollicular inflammatory infiltrate (29.4% LPP versus 4.6% FFA; p = 0.010); and a zone of concentric lamellar fibroplasia (85.3% LPP versus 63.6% FFA; p = 0.041).

Conclusions

Although a few histologic features differ between FFA and LPP, we believe these differences are too subtle or non-specific to distinguish between them with confidence. Therefore, clinical correlation is essential to establish the diagnosis.

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Persistent isoflurane-induced hypotension causes hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion

Abstract

Background

Postoperative cognitive dysfunction (POCD) is likely to occur in elderly people, who often suffer from cerebral hypoperfusion and white matter lesions even in the absence of cerebral infarctions.

Methods

Thirty-two adult male rats were randomly assigned to one of four groups: the cerebral normoperfusion + normotension group (n = 8), cerebral normoperfusion + hypotension group (n = 8), chronic cerebral hypoperfusion (CCH) + normotension group (n = 8), and CCH + hypotension group (n = 8). A rat model of CCH was developed via the permanent ligation of the bilateral common carotid arteries, but ligation was avoided in the cerebral normoperfusion groups. Two weeks later, the rats were intubated and mechanically ventilated under isoflurane anesthesia, and their mean arterial blood pressure was maintained over 80 mmHg (normotension) or below 60 mmHg (hypotension) for 2 h. After preparing brain slices, histological cresyl violet staining, ionized calcium binding adaptor molecule 1, a marker of microglial activation, or β amyloid precursor protein, a marker of axonal damage, were performed.

Results and conclusion

CCH per se caused microglial activation and axonal damage, which was not accentuated by hypotension. CCH alone did not cause neuronal damage, but CCH combined with hypotension caused significant neuronal damage in the hippocampal CA1 region. These results suggest that persistent hypotension during general anesthesia might cause neuronal damage in patients with CCH, such as elderly people, and contribute to prevention against POCD.

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The effect of in situ simulation training on the performance of tasks related to patient safety during sedation

Abstract

In many countries, procedural sedation outside of the operating room is performed by pediatricians. We examined if in situ sedation simulation training (SST) of pediatricians improves the performance of tasks related to patient safety during sedation in the Emergency Department (ED). We performed a single-center, quasi-experimental, study evaluating the performance of sedation, before-and-after SST. Sixteen pediatricians were evaluated during sedation as part of their usual practice, using the previously validated Sedation-Performance-Score (SPS). This tool evaluates physician behaviors during sedation that are conducive to safe patient outcomes. Following the sedation, providers completed SST, followed by a structured debriefing. They were then re-evaluated with the SPS during a subsequent patient sedation in the ED. Using multivariate regression, odds ratios were calculated for each SPS component, and were compared before and after the SST. Thirty-two sedations were performed, 16 before and 16 after SST. SPS scores improved from a median of 4 (IQR 2–5) to 6 (IQR 4–7) following SST (p < 0.0009, median difference 2, 95% CI 1–3). SST was associated with improved performance in four SPS components. The findings of this pilot study suggest that sedation simulation training of pediatricians improves several tasks related to patient safety during sedation.

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NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy

Publication date: 20 February 2018
Source:Free Radical Biology and Medicine, Volume 116
Author(s): Kishore Reddy Katikireddy, Tomas L. White, Taiga Miyajima, Shivakumar Vasanth, Duna Raoof, Yuming Chen, Marianne O. Price, Francis W. Price, Ula V. Jurkunas
Fuchs endothelial corneal dystrophy (FECD) is a genetic and oxidative stress disorder of post-mitotic human corneal endothelial cells (HCEnCs), which normally exhibit hexagonal shape and form a compact monolayer compatible with normal corneal functioning and clear vision. FECD is associated with increased DNA damage, which in turn leads to HCEnC loss, resulting in the formation rosettes and aberrant extracellular matrix (ECM) deposition in the form of pro-fibrotic guttae. Since the mechanism of ECM deposition in FECD is currently unknown, we aimed to investigate the role of endothelial-mesenchymal transition (EMT) in FECD using a previously established cellular in vitro model that recapitulates the characteristic rosette formation, by employing menadione (MN)-induced oxidative stress. We demonstrate that MN treatment alone, or a combination of MN and TGF-β1 induces reactive oxygen species (ROS), cell death, and EMT in HCEnCs during rosette formation, resulting in upregulation of EMT- and FECD-associated markers such as Snail1, N-cadherin, ZEB1, and transforming growth factor-beta-induced (TGFβI), respectively. Additionally, FECD ex vivo specimens displayed a loss of organized junctional staining of plasma membrane-bound N-cadherin, with corresponding increase in fibronectin and Snail1 compared to ex vivo controls. Addition of N-acetylcysteine (NAC) downregulated all EMT markers and abolished rosette formation. Loss of NQO1, a metabolizing enzyme of MN, led to greater increase in intracellular ROS levels as well as a significant upregulation of Snail1, fibronectin, and N-cadherin compared to normal cells, indicating that NQO1 regulates Snail1-mediated EMT. This study provides first line evidence that MN-induced oxidative stress leads to EMT in corneal endothelial cells, and the effect of which is further potentiated when redox cycling activity of MN is enhanced by the absence of NQO1. Given that NAC inhibits Snail-mediated EMT, this may be a potential therapeutic intervention for FECD.

Graphical abstract

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