Unusual skin metastasis due to adenocarcinoma of the stomach: a case report

Clinical Findings A 68- year-old man presented with a skin thickening of the anterior neck started few months earlier. Upper respiratory and digestive tract had already been examined which proved normal. On clinical examination a hyper pigmented massively indurated leathery plaque was seen on the anterior and lateral aspect of the neck from the submandibular region down to the jugular fossae. The plaque was firm, well demarcated and measured 15 by 12 cm in diameter. It had a cobblestone like appearance with exaggerated folds, and was non painful. Patient complained of a mild discomfort while swallowing saliva of recent onset, but was otherwise asymptomatic. All his routine blood test was normal. The full skin examination was otherwise unremarkable. Our main differential diagnosis at that stage included a reactive process such as a sclerodermatous process, a neoplastic reaction or a lymph proliferative disease.</br

Actinic Keratosis, a Chronic, Progressive Disease: Understanding Clinical Gaps to Optimise Patient Management

Actinic keratosis (AK) is a chronic, progressive disease of the skin that has undergone long-term sun exposure. The affected areas contain visible and subclinical nonvisible sun damage resulting in epidermal keratinocyte dysplasia, known by many as ‘field cancerisation’ (1), which is prone to AKs and sun-related skin cancer (2). Thus, visible AKs are clinical biomarkers for a photo-damaged field with subclinical damage associated with the unpredictable risk of progression to invasive squamous cell carcinoma (iSCC) (3). The aim of this multiexpert opinion article is to provide a discussion succinctly highlighting the clinical gaps for optimal management of AK: the lack of a universal definition and the need for a standardised grade assessment of AK/field cancerisation that also takes into account individual risk

A Novel Actinic Keratosis Field Assessment Scale For Grading Actinic Keratosis Disease Severity

Actinic keratosis (AK) lesions are surrounded by field cancerization (areas of subclinical, non-visible sun damage). Existing AK grading tools rely on AK counts, which are not reproducible. An Actinic Keratosis Field Assessment Scale (AK-FAS) for grading the severity of AK/field was developed. Standardized photographs of patients representing the full range of AK severity were collected. Six investigators independently rated each photograph according to 3 criteria: AK area (total skin area affected by AK lesions), hyperkeratosis and sun damage. Inter-rater reproducibility was good for all 3 criteria. Validation of the AK-FAS showed good reproducibility for AK area and hyperkeratosis, even for dermatologists untrained on use of the scale. In conclusion, the AK-FAS is objective, easy to use and implement, and reproducible. It incorporates assessment of the entire field affected by AK instead of relying on lesion counts. Use of the AK-FAS may standardize AK diagnosis, making it relevant to routine clinical practice

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

Development and testing of new candidate psoriatic arthritis screening questionnaires combining optimal questions from existing tools

Objective: Several questionnaires have been developed to screen for psoriatic arthritis (PsA), but head-to-head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments.&lt;p&gt;&lt;/p&gt; Methods: Data from the CONTEST study, a head-to-head comparison of 3 existing questionnaires, were used to identify items with a Youden index score of ≥0.1. These were combined using 4 approaches: CONTEST (simple additions of questions), CONTESTw (weighting using logistic regression), CONTESTjt (addition of a joint manikin), and CONTESTtree (additional questions identified by classification and regression tree [CART] analysis). These candidate questionnaires were tested in independent data sets.&lt;p&gt;&lt;/p&gt; Results: Twelve individual questions with a Youden index score of &#8805;0.1 were identified, but 4 of these were excluded due to duplication and redundancy. Weighting for 2 of these questions was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in 6 joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC curve analysis and discarded. The other 3 questionnaires were significant in all data sets, although CONTESTw was slightly inferior to the others in the validation data sets. Potential cut points for referral were also discussed.&lt;p&gt;&lt;/p&gt; Conclusion: Of 4 candidate questionnaires combining existing discriminatory items to identify PsA in people with psoriasis, 3 were found to be significant on ROC curve analysis. Testing in independent data sets identified 2 questionnaires (CONTEST and CONTESTjt) that should be pursued for further prospective testing

Critical analysis of histologic criteria for grading atypical (dysplastic) melanocytic Nevi

Dr Naase collated and processed this unique study of over 300 samples. This has led to a new system of classifying melanocytic Nevi

An atypical presentation of pseudoxanthoma elasticum (PXE) without angioid streaks or peau d’orange

 Pseudoxanthoma Elasticum (PXE) is an inherited multi-system disorder with potentially fatal complications.  Biallelic mutations in the ABCC6 gene, which encodes an ATP-binding cassette transporter, have been identified to underlie this disease.  Patients with pseudoxanthoma elasticum (PXE) classically have angioid streaks and peau d’orange.  In this report, we present the case of a 9-year-old girl with histologically confirmed PXE, who did not have either angioid streaks or peau d’orange in either eye.  Her only ophthalmic finding was the presence of bilateral optic disc drusen.  This atypical presentation of PXE highlights that the presence of optic disc drusen in the absence of other signs should alert the physician to consider PXE