Adnexal polyp in a newborn baby.

Birthmarks can frequently be seen in newborn babies, but their etiopathogenesis is often unclear. These lesions can be divided into three groups: vascular birthmarks, pigmented birthmarks, and birthmarks resulting in abnormal development. Some birthmarks may require further analysis and clinical follow-up in order to rule out underlying defects, malignant potential, or correlation with syndromic diseases. Presented here is the case of a newborn baby with two simultaneous birthmarks: an adnexal polyp and a nevus anemicus. Adnexal polyps are considered an uncommon clinical observation

Angles and geometric shapes, but not lines, in melanocytic lesions may be helpful in the clinical diagnosis of melanoma.

BACKGROUND: Geometric shapes have been suggested to be found in malignant melanomas. We have observed a number of melanomas presenting with linear and incomplete angulated figures. OBJECTIVE: To verify the assumption that geometric shapes, a linear border and/or incomplete angulated figures may indicate a potential melanoma. METHODS: Patients with surgically removed melanocytic lesions were admitted to the study. We evaluated the presence of a sharp linear demarcation, the presence of contiguous lines resulting in the formation of angle/s and the presence of complete geometric figure. We distinguished the obtained results into melanoma and benign melanocytic naevi. RESULTS: A total of 471 melanomas and 1979 melanocytic naevi were collected. Linear borders, angles and geometric figures were observed in 42 melanomas and in 75 benign melanocytic naevi. Angles with incomplete geometric configuration were observed in 21 melanomas and in 37 benign naevi (21/471 vs. 37/1979, 4.24% vs. 1.87%; P < 0.0016); complete even if irregular geometrical figures in 12 melanomas and 17 naevi (12/471 vs. 17/1979, 2.54% vs. 0.85%; P < 0.005). The presence of line(s) did not significantly differed in the two considered groups. CONCLUSIONS: Melanocytic lesions with angulated shapes and complete geometrical configurations might indicate a suspect melanoma. Only sharp linear demarcation of the lesion do not seem to be significantly associated with melanoma suspicion.

Clinically and/or histologically pigmented poromas in Caucasian patients.

AIM: Pigmented poromas are rarely reported and considered to be more common in non-white people and on non-acral sites. Objective of the present study was to report our cases of pigmented poromas with particular attention to the presence of clinical and/or microscopic evidence of pigmentation, their characteristics and the diagnostic pitfall with other pathologies. METHODS: All the histologically confirmed poromas observed from January 1994 to July 2012 were considered. Clinic-epidemiological data were collected. The presence of clinical pigmentation was recorded as well as the presence of melanin pigmentation or melanocytes in the histologic specimens. RESULTS: One hundred and one patients with poromas were collected. All the patients were Caucasians. All the lesions were solitary. Only three patients had a clinically visible pigmented poromas. In eight cases the presence of melanin and melanocytes did not produce a clinically visible pigmentation. All the poromas with pigmentation did not occur on palmo-plantar surfaces. CONCLUSION: Pigmented poromas may be observed even in Caucasian patients and their clinical aspect mimic basal cell carcinoma and/or melanoma. The presence of pigment visible at the histology may not be observed in the clinical expression. The absence of pigmentation on palmo-plantar location is confirmed in all the reported cases.

Observational study on the mitotic rate and other prognostic factors in cutaneous primary melanoma arising from naevi and from melanoma de novo.

BACKGROUND: Melanomas can arise from naevi or appear de novo. The frequency or the effect of their origin on prognosis is still debated. Mitotic rate (MR) and ulceration of melanomas have been proposed as further new prognostic indexes. AIM: To determine the different prognostic factors in melanomas de novo and melanomas from pre-existing naevi and whether these two melanoma groups have different MR or presence of ulceration. METHODS: All patients with confirmed primary melanomas observed in our clinic from 1996 to July 2013 were included. The distinction between the two groups of melanomas was histologically based. We compared Breslow's thickness, the number of mitosis/mm(2) and the presence of ulceration between the naevus-associated melanoma and de novo melanoma group. RESULTS: Of the 873 melanomas, 626 (71.8%) have a de novo melanoma, 247 (28.2%) a naevus-associated melanoma. Breslow's thickness was not significantly different in the two groups (0.77 ± 1.47 mm vs. 0.59 ± 1.35 mm). The number of patients with presence of ulceration and MR ≥1 mitosis/mm(2) was not significantly different in the two groups (19.6% vs. 16.3%). In thicker melanomas (Breslow's thickness ≥ 1 mm), the number of patients with ≥6 mitosis/mm(2) was significantly higher (26.6% vs. 7.9%; P < 0.05) in the de novo melanoma group. CONCLUSIONS: When mitosis ≥ 1 mm/mm(2) , the results obtained do not show a better or worse prognosis based on Breslow's thickness, ulceration and MR in melanomas associated with naevus vs. melanomas de novo. When ≥6 mitosis/mm(2) are considered, the number of patients in the de novo melanoma group with thick melanoma is highly more represented. The debate about the cut-off value of mitosis ≥1 mm(2) is open.

Unusual sites for poromas are not very unusual: a survey of 101 cases.

BACKGROUND: Poromas are benign adnexal tumours generally believed to be of eccrine origin, which usually develop on palmoplantar sites. However, it is thought that a percentage of poromas develop on non-palmoplantar or 'unusual' sites. AIM: To review cases of poromas with reference to their clinicoepidemiological characteristics, paying particular attention to the those located on sites other than the palms and soles. METHODS: All histologically confirmed poromas seen at our department between 1994 to 2012 were reviewed. The clinicoepidemiological data recorded included age at diagnosis, gender, location, size, colour, and preoperative and pathological diagnoses. RESULTS: In total, 101 poromas were reviewed, corresponding to 0.0058% of all the epithelial skin tumours biopsied in our department. The mean age was 65.05 years (range 30-100 years), and the male to female ratio was 1.52. All the lesions were solitary and asymptomatic, with no sign of bleeding. The most common presentation was a red or reddish lesion, particularly at palmoplantar sites, where 33 (32.7%) of the 101 poromas were located, Poromas found at other affected sites were more usually skin-coloured, and these lesions included 7 neoplasms located in the armpits and 18 on the head and neck. The correct preoperative diagnosis was made in 12 cases of 33 detected poromas (36%), all of which were localized to the palmoplantar surfaces. CONCLUSIONS: Based on our experience, we consider that there are no 'unusual' sites for poromas, and palmoplantar poromas were in fact in the minority. Furthermore, some localizations suggest derivation of these palmoplantar poromas from the folliculosebaceous apocrine unit.

-308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life.

The relationship between major depression (MD) and dementia in the elderly is still not clear, but it is certain that the immune system and in particular, pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, play a key role in the mechanisms underlying the two neuro-psychiatric disorders. In our experience, the -308(G/A) single nucleotide polymorphism (SNP) in the TNF-alpha gene is associated with earlier age at onset in patients affected by Alzheimer's disease (AD). The aim of this study was to investigate the association between the -308(G/A) SNP and late-life MD in elderly people without dementia. Blood samples were obtained from 50 subjects, after screening with the geriatric depression scale (GDS>or=15) and mini-mental state examination (MMSE>or=24). The -308 (G/A) SNP was genotyped by SSP-PCR amplification. Two-hundred-fourty age-matched healthy volunteers were taken as the control group. We identified different genotype and allele distributions of the SNP in old depressed patients and healthy controls (HC). Our results evidenced a significantly higher percentage of the GG genotype in depressed subjects (84.0% vs. 68.3%; p=0.007) and consequently of the G allele (92.0% vs. 81.9%; p=0.05). The presence of the GG genotype raised the risk of developing MD (odds ratio=OR=2.433, confidence interval=Cl=1.09-5.43). Our findings suggested that the investigated TNF-alpha SNP may: (1) affect MD susceptibility; (2) be involved both in AD and MD development, but probably with a distinct role in the two pathologies.

Seborrheic keratosis with compound nevus, junctional nevus and basal cell carcinoma in the same lesion.

Seborrheic keratosis can be associated with different neoplasms such as basal cell carcinomas, squamous cell carcinomas and melanomas. We describe an unusual case of a man who presented with a brown plaque on his back. The clinical diagnosis was melanoma. Histopathologic examination of the lesion revealed four neoplasms: a compound nevus, a junctional nevus, a superficial basal cell carcinoma and a seborrheic keratosis. Although this association most likely represents a chance phenomenon, we discuss the possibility that the seborrheic keratosis developed from the nevus, and that subsequently the junctional nevus and the basal cell carcinoma developed from the seborrheic keratosis.

17 alpha-O-(aminoalkyl)oxime derivatives of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane as inhibitors of Na(+),K(+)-ATPase at the digitalis receptor.

The synthesis and binding affinities to the digitalis Na(+),K(+)-ATPase receptor of a series of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane derivatives bearing a 17 alpha-(aminoalkoxy)imino chain are reported; some derivatives were also studied for their inotropic activity. Our recently proposed model of interaction of molecules with the digitalis receptor was used to design these compounds. On that basis, the possibility to design novel potent inhibitors of Na(+),K(+)-ATPase without being constrained by the stereochemistry of the classical digitalis skeleton in the D-ring region was predicted. The binding affinities of the most potent compounds in the two series, (EZ)-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-5 beta-androstane-3 beta,14 beta-diol (6f) and (EZ)-3 beta-hydroxy-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-14,15-seco-5 beta-androstan-14-one (24c) are higher than that of the potent natural compound digitoxigenin, despite the unusual alpha-exit of the substituent in position 17 of 6f or the disruption of the D-ring in 24c. These results further support the validity of our recently proposed model of binding at the digitalis receptor. Results of the inotropic tests on guinea pig atrium deserve further investigation on the pharmacological profile of these derivatives.

High sensitivity of human epidermal keratinocytes (HaCaT) to topoisomerase inhibitors.

In the panorama of the numerous established cell lines, the human keratinocyte line HaCaT has a very interesting feature, having a close similarity in functional competence to normal keratinocytes. This cell line has been used in many studies as a paradigm for epidermal cells and therefore we selected HaCaT as a cell model for investigating the activity of three antitopoisomerase drugs (Camptothecin, Doxorubicin, Ciprofloxacin) on in vitro cell growth. The effect was evaluated both by a 24-h cytotoxicity test and by a 7-day antiproliferation assay, in which the cell viability was assessed by an MTT (3-(4,5-dimethyl-2-thiazolyl) 2,5-diphenil-2-H-tetrazolium bromide) test. DNA topoisomerase I was also partially purified from a nuclear extract of HaCaT cells, the level of topo I catalytic activity was measured by a pBR322 DNA relaxation assay and then the in vitro effect of antitopoisomerase drugs on the target enzyme was also assessed. The results indicated that the in vitro sensitivity of human epidermal HaCaT cells to antitopoisomerase drugs is comparable to that of many human tumour cell lines. HaCaT cells express a high level of topoisomerase I activity that is significantly inhibited by both Camptothecin and Doxorubicin and to a minor degree by Ciprofloxacin. A high correlation between the cell sensitivity to the antitopoisomerase I drug measured by the MTT test and the in vitro direct inhibition of HaCaT topoisomerase I was observed, suggesting that HaCaT cells can represent a very interesting model both for studying cellular pharmacokinetics of antineoplastic drugs on keratinocytes and for predicting possible secondary effects, exerted by these drugs on cutaneous cells, during treatment with chemotherapy.

Genetic determinants of alcohol addiction and metabolism: a survey in Italy.

BACKGROUND: Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism. METHODS: We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: No difference was found in the frequency of the CYP2E1 Rsal c2 allele (2.5% among alcoholics and 4.7% among controls) and the DraI C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p = 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics. CONCLUSIONS: Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent patients was observed for the first time.

Benzo(a)pyrene diolepoxide adducts to albumin in workers exposed to polycyclic aromatic hydrocarbons: association with specific CYP1A1, GSTM1, GSTP1 and EHPX genotypes.

We investigated whether the presence of (+)-anti-benzo(a)pyrene diolepoxide adducts to serum albumin (BPDE-SA) among workers exposed to benzo(a)pyrene (BaP) and unexposed reference controls was influenced by genetic polymorphisms of cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (EHPX), glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), all involved in BaP metabolism. Exposed workers had significantly higher levels of adducts (0.124 ± 0.02 fmol BPTmg(-1) SA, mean ± SE) and a higher proportion of detectable adducts (40.3%) than controls (0.051 ± 0.01 fmol BPT mg(-1) SA; 16.1%) (p = 0:014 and p = 0:012). Smoking increased adduct levels only in occupationally exposed workers with the GSTM1 deletion (GSTM1 null) (p = 0:034). Smokers from the exposed group had higher adduct levels when they were CYP1A1 *1/*1 wild-type rather than heterozygous and homozygous for the variant alleles (CYP1A1 *1/*2 plus *2/*2) (p = 0:01). The dependence of BPDE-SA adduct levels and frequency on the CYP1A1 *1/*1 genotype was most pronounced in GSTM1-deficient smokers. Exposed workers with GSTM1 null/GSTP1 variant alleles had fewer detectable adducts than those with the GSTM1 null/GSTP1*A wild-type allele, supporting for the first time the recent in vitro finding that GSTP1 variants may be more effective in the detoxification of BPDE than the wild-type allele. Logistic regression analysis indicated that occupational exposure, wild-type CYP1A1*1/*1 allele and the combination of GSTM1 null genotype+EHPX genotypes associated with predicted low enzyme activity were significant predictors of BPDE-SA adducts. Though our findings should be viewed with caution because of the relatively limited size of the population analysed, the interaction between these polymorphic enzymes and BPDE-SA adducts seems to be specific for high exposure and might have an impact on the quantitative risk estimates for exposure to polycyclic aromatic hydrocarbons.

17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na(+),K(+)-ATPase receptor.

A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na(+),K(+)-ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some interactions are the classical ones already described in the literature; a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

Benzo(a)pyrene diolepoxide-haemoglobin and albumin adducts at low levels of benzo(a)pyrene exposure.

A biomonitoring study was conducted to simultaneously measure individual benzo(a)pyrene (BaP) exposure in 50 office employees, not occupationally exposed to polycyclic aromatic hydrocarbons (PAH), using personal samplers and the formation of (+) r-7, t-8-dihyroxy-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) adducts to haemoglobin (BPDE-Hb) and serum albumin (BPDE-SA). The population enrolled was exposed to an average of 0.58 ± 0.46 ng BaP m(-3) (mean ± SD). The concentration of BaP collected from smokers' samples was double that from non-smokers (P = 0.007). BPDE adducts to Hb and SA were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry. BPDE-Hb adducts were detected in 16% of the population and BPDE-SA adducts in 28%. Smoking did not affect adduct formation. When BaP personal monitoring data were used as the criterion of exposure, no correlation was found with the presence and the levels of BPDE-Hb and BPDE-SA adducts. Undetected sources of PAH, such as the diet, might markedly alter the exposure profile depicted by individual air sampling and affect the frequency and levels of protein biomarkers. This is the first comparative analysis of BPDE-Hb and BPDE-SA adducts, providing reference values for these biomarkers in a general urban population. However it is difficult to establish which biomarkers would be the more relevant in assessing low BaP exposure, due to undetectable factors such as dietary PAHs, that might have influenced the results to some degree.

Eruptive dermatofibromas and immunosuppression.

Multiple and eruptive dermatofibromas are, on the contrary, unusual. Often the patients who show this peculiar cutaneous pattern are referred for immunosuppressive therapy or they have an immunosuppressive disease. We report the case of a woman affected by mycosis fungoides, who developed, in 2 months, 14 dermatofibromas on her legs. The personal history of the patient revealed a previous immunosuppressive treatment with systemic corticosteroids for interstitial pneumonia. Different etiological hypothesis have been proposed to explain the eruptive presence of multiple dermatofibromas and the alteration of the immune response, but the real mechanism is still unclear. Dermatofibromas are benign tumours usually encountered in dermatology.

Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema.

Lymphangiosarcoma is a rare, aggressive, vascular neoplasm arising in chronic congenital or acquired lymphedema. Although it is most frequently associated with post-mastectomy lymphedema (Stewart-Treves's syndrome), lymphangiosarcoma can exceptionally arise in congenital hereditary lymphedema (Milroy's syndrome and Meige's syndrome) and non-hereditary lymphedema (congenital, praecox or forme tarde lymphedemas). We report a case of lymphangiosarcoma of the pubic region, supported by immunohistochemical studies, in a 42-year-old woman affected by congenital, non-hereditary lymphedema of the left genital region and homolateral lower limb. In addition, molecular analysis demonstrated the absence of Kaposi's sarcoma-associated Herpes virus (KSHV) DNA sequences in tumour lesions. To our knowledge, this is the first case of lymphangiosarcoma associated with congenital non-hereditary lymphedema confined to the pubic region. The literature concerning the cases of lymphangiosarcoma arising in congenital hereditary and non-hereditary lymphedema is reviewed. Moreover, we emphasized the importance of regular clinical controls in all patients affected by chronic lymphedema. In fact, although the prognosis of this neoplasm is very poor, a prompt diagnosis and a rapid, ablative surgery associated with radiation therapy can increase the possibility of survival of these patients.

Mometasone furoate decreases adhesion molecule expression in psoriasis.

The topical corticosteroids are widely used in the treatment of moderate psoriasis, because of their usefulness for reducing inflammation and controlling itching. The therapeutic effect of corticosteroids in different cutaneous inflammatory diseases may be partially explained by their varying ability to block in vitro the synthesis of different cytokines, which play a pivotal role in epidermal hyperproliferation and leukocyte recruitment into the skin. The purpose of the present investigation was to further elucidate the mode of action of mometasone furoate, a medium-high potency, topical corticosteroid, on adhesion molecules, cytokines and cytokine receptor expression in psoriatic skin. Using an immunohistochemical assessment, we examined lesional skin biopsies from ten psoriatic patients before treatment and after 1 and 3 weeks of therapy. The overexpression of alpha 2, alpha 3, alpha 6, and beta 1 integrins detected in the spinous layer of untreated psoriatic skin was significantly decreased after therapy in 8 out of 10 cases, characterized by only partial clinical remission. In the remaining patients, a disappearance of the above integrin reactivity paralleling the disappearance of psoriatic lesions was induced by the treatment. With the exception of GM-CSF, no or only marginal effects of mometasone furoate on the cytokine and cytokine receptor system were observed. A significant reduction of the positive immunostaining with anti-ICAM-1 and ICAM-2 monoclonal antibodies on dermal vascular endothelial cells was also seen. Thus, our findings indicate that the therapeutic effects of mometasone furoate in psoriasis are mediated principally by decreasing adhesion molecule expression and to a lesser degree by inhibiting cytokine synthesis.