Drug-induced eruptive melanocytic nevi

Introduction: The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown.

Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications.

Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports. Prevalence of this phenomenon is likely to be underestimated, thus reporting should be encouraged in order to better define the actual significance and related clinical implications. The development of multiple melanocytic nevi during immunosuppressive treatments highlights the importance of immune system integrity in the regulation of nevi growth. The observation of eruptive nevi as an unexpected effect of targeted therapies for specific types of cancer, including melanoma, provided intriguing hints to understand the mechanisms underlying this paradoxical event. The synergistic role of additional triggers in the occurrence of drug-induced eruptive nevi has not been explored and may be an interesting area of research.     

Lymphadenopathies in patients with renal cell carcinoma: clinical and pathological predictors of pathologically confirmed lymph node invasion

Introduction

In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI).

Methods

At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status.

Results

Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9–4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1–1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI.

Conclusions

Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology.

     

"Home-brew" FISH assay shows higher efficiency than BCR-ABL dual color, dual fusion probe in detecting microdeletions and complex rearrangements associated with t(9;22) in chronic myeloid leukemia

We carried out fluorescence in situ hybridization (FISH) studies on 18 Ph+ chronic myeloid leukemia (CML) cases with chromosome 22 genomic deletions with the Vysis BCR-ABL dual-color/dual-fusion probe (BCR-ABL DC/DF) to compare the hybridization patterns obtained with this approach to those obtained with the "home brew" BAC/PAC system. Our results are the following: chromosome 22 microdeletions less than 400 kilobases (Kb) were not detected by the BCR DC/DF probe; FISH analysis with the BCR DC/DF probe in cases bearing chromosome 22 microdeletions ranging from 400 to 700 Kb produced a faint signal on the der(9); and the BCR-ABL DC/DF FISH pattern was comparable to the one obtained by the home brew probe in the presence of a 900-Kb chromosome 22 microdeletion. Our home-brew FISH system represents an accurate method for revealing a subset of CML patients with der(9) microdeletions.     

Endometrioid-like yolk sac and Sertoli-Leydig cell tumors in a carrier of a Y heterochromatin insertion into 1qh region: a causal association?

We describe the case of a young woman showing yolk sac tumors (YST) and a Sertoli-Leydig cell tumor (SLCT) in the right ovary, with recurrences in the right adnexum and with hepatic metastasis. To our knowledge, YST and SLCT have never been described as components of the same tumor or reported as associated in the same patient. The patient's karyotype showed the presence of Y chromosome inserted into the 1qh region; the inserted region corresponded to Yq12 heterochromatin. LOH analysis revealed 1p36 paternal allele loss in the proband tumor, thus supporting a germ cell origin for the tumor. The presence of Y heterochromatin in 1qh DNA might induce disturbances in the normal regulation of oncogenes located in 1q.     

Influence of estrogens and antiestrogens on the expression of selected hormone-responsive genes

Estrogen exerts a primary regulatory role on a wide variety of physiological processes in different tissues and organs. Agonistic ad antagonistic compounds are widely used in human health and, therefore, a deep understanding of their mechanisms of action at the molecular level is mandatory. The effect of 17beta-estradiol and three antiestrogenic drugs, comprising two selective estrogen receptor modulator (SERM, 4-OH-tamoxifen, Raloxifene) and the pure antiestrogen ICI 182,780, on genome-wide gene expression levels was evaluated in breast carcinoma cell lines by DNA microarray analysis. Different clusters of genes, showing specific coregulation patterns, were found. First, several groups of genes displaying temporal-specific up- or down-regulation were characterized. Second, clusters of genes responding to different antiestrogenic drugs in either antagonstic or agonistic fashion, were found. Genes responding specifically to antiestrogens, but not to estrogen, were also identified. In addition, each individual compound exhibited a very specific gene regulation. Bioinformatic analysis was applied to the regulatory sequences of different groups of genes and confirmed that specific pathways and secondary responses are activated at each temporal point and in response to different compounds. Our results underline the complexity of genomic responses to estrogen in breast cancer cells and strongly suggest that the molecular characterization of estrogen agonists and antagonists used in human therapy should be carefully studied.     

Composite-to-composite microtensile bond strength in the repair of a microfilled hybrid resin: effect of surface treatment and oxygen inhibition

PURPOSE: To compare the 24-h microtensile bond strength of a microfilled hybrid composite to the same material after mechanical and/or chemical treatment and assess the effect of oxygen inhibition on the composite-composite bond. MATERIALS AND METHODS: Forty composite cylinders of Gradia Direct Anterior (GC) were prepared and stored 24 h prior to the following surface treatments: 50-microm aluminum oxide air abrasion and 37% phosphoric acid etching (group 1); hydrochloric acid and 6.9% hydrofluoric acid etching (group 2); diamond bur roughening and 37% phosphoric acid etching (group 3); diamond bur roughening (group 4). In all groups, Prime & Bond NT (Dentsply De Trey) was applied and light cured in air or under a nitrogen atmosphere, prior to layering a buildup of the repairing resin composite. Microtensile bond strength measurements were performed. Data were statistically analyzed with two-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: The curing atmosphere did not significantly influence the interfacial strength (p < 0.05). Surface treatment significantly affected the composite-composite bond (p > 0.05). Air abrasion, regardless of curing atmosphere, resulted in the strongest bond (p < 0.05). The other treatments were comparable. CONCLUSION: Air abrasion and the application of a bonding agent offer satisfactory bond strengths for composite repair. The oxygen inhibition layer on a light-cured adhesive is not crucial to the success of the 24-h composite-composite bond.     

Effect of operator skill in relation to microleakage of total-etch and self-etch bonding systems

OBJECTIVES: To evaluate the influence of operator skill on microleakage in class V restorations using two-step bonding systems. METHODS: Two standardized box cavities were made on the buccal and lingual surfaces of 54 human bicuspid teeth, with the cervical margin in dentin. The teeth were randomly assigned to two groups according to the operator's skill. Students group: undergraduate students. Expert group: a dentist with 20 years of clinical experience in dental adhesion. The buccal cavities of each tooth were treated with Prime&Bond NT (two-step total-etch system); the lingual cavities were treated with AdheSE (two-step self-etch system). All cavities were restored by a single calibrated operator with one bulk increment of resin composite (InTens; Ivoclar Vivadent). Specimens were thermocycled, immersed in 2% methylene blue and sectioned in a bucco-lingual plane in the middle of the restorations. They were then examined under a stereomicroscope and scored according to microleakage by two operators who were blind to the specimen preparation. The data was subjected to a multilevel statistical model. RESULTS: The microleakage resulting from the self-etch adhesive was similar in the student and in the expert groups. On the other hand, the total-etch adhesive microleakage within the expert group resulted lower than that within the student group. However, the interaction term skill x adhesive resulted statistically significant at the dentin margin (p=0.0474) but not at the enamel margin (p=0.1267). CONCLUSION: While the total-etch adhesive used in this study showed to be skill-sensitive, the self-etch one proved to be less skill-sensitive in obtaining a reliable seal with dentin.     

Myoclonus in mitochondrial disorders

Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of MERRF (myoclonic epilepsy with ragged red fibers). However, its prevalence in mitochondrial diseases is not known. The aims of this study are the evaluation of the prevalence of myoclonus in a big cohort of mitochondrial patients and the clinical characterization of these subjects. Based on the database of the “Nation‐wide Italian Collaborative Network of Mitochondrial Diseases,” we reviewed the clinical and molecular data of mitochondrial patients with myoclonus among their clinical features. Myoclonus is a rather uncommon clinical feature of mitochondrial diseases (3.6% of 1,086 patients registered in our database). It is not strictly linked to a specific genotype or phenotype, and only 1 of 3 patients with MERRF harbors the 8344A>G mutation (frequently labeled as “the MERRF mutation”). Finally, myoclonus is not inextricably linked to epilepsy in MERRF patients, but more to cerebellar ataxia. In a myoclonic patient, evidences of mitochondrial dysfunction must be investigated, even though myoclonus is not a common sign of mitochondriopathy. Clinical, histological, and biochemical data may predict the finding of a mitochondrial or nuclear DNA mutation. Finally, this study reinforces the notion that myoclonus is not inextricably linked to epilepsy in MERRF patients, and therefore the term “myoclonic epilepsy” seems inadequate and potentially misleading. © 2014 International Parkinson and Movement Disorder Society