Liposarcoma of the spermatic cord: The state of art and our experience.

Liposarcoma of the spermatic cord is a malignant neoformation so rare that less than 200 cases are reported in the world. It is a tumor that originates from adipose tissue and when it is found in the spermatic cord it can deceptively simulate an inguinal hernia and not be easily identified. The present work describes the case of a 37-year-old man with liposarcoma of the spermatic cord who arrives at our institution with painless swelling of the left testicle. Physical examination revealed a painless swelling in the scrotal sac. The scrotal ultrasound examination revealed a mass, measuring 8 cm (cranio-caudal) × 5.4 cm (latero-lateral) × 8 cm (antero-posterior) and characterized later with a basal CT examination of the abdomen. The patient was subsequently surgically treated with excision of the tumor, plus hernial plastic with plug and mesh. Histological examination revealed a mature adipocyte neoplasm whose morphological and molecular characteristics (amplification of the MDM2 gene) are consistent with the diagnosis of dediferrentiated liposarcoma variety CO-MINGLED, G2 (sec. FNCLCC). The patient is currently under cancer surveillance with no signs of loco-regional recurrence. Spermatic cord liposarcoma is an extremely rare malignancy. It's not easy to identify as it can simulate an inguinal hernia, hydrocele, lipoma, funicular cyst, or testicular tumor. Diagnosis is usually established postsurgery, however, relapses are common and the role of chemo-radiotherapy remains to be defined.

Genetically Driven CD39 Expression Affects Sezary Cell Viability and IL-2 Production and Detects Two Patient Subsets with Distinct Prognosis.

Sézary syndrome (SS) is a rare and aggressive variant of cutaneous T-cell lymphoma. It is characterized by the copresence of CD4+ neoplastic lymphocytes, named Sezary cells, mainly in the blood, lymph nodes, and skin where they induce chronic inflammation that in turn impairs the patient's QOL and fuels neoplastic cells. SS is not readily cured, but immunotherapy is becoming an effective option for this lymphoma. In this study, we investigated, in a large cohort of patients with SS, the expression and function of the immune checkpoint molecule CD39, which degrades proinflammatory extracellular adenosine triphosphate. We showed that the SNP rs10748643 A/G within the ENTPD1 gene coding for the CD39 protein controls its expression level. Patients carrying the A/G‒G/G genotype showed a significantly higher frequency of clonal CD4+CD39+ SS cells than those carrying the A/A genotype. Different from other cancers, high CD39 expression correlates with a better prognosis. Comparing primary G/G with A/A lymphoma cells, we observed that G/G SS cells have a higher ability to degrade adenosine triphosphate, increased apoptotic susceptibility, and upon activation, reduced IL-2 production. Accordingly, CD39 enzymatic inhibition enhances SS cell viability and IL-2 production on activation. These results strongly suggest a special caution for SS treatment with therapeutic inhibitors of CD39.

Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.

Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-ß and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-ß were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found.

Eosin treatment for psoriasis reduces skin leukocyte infiltration and secretion of inflammatory chemokines and angiogenic factors.

BACKGROUND: Eosin has been traditionally employed as a topical treatment for psoriasis, but the biological mechanism of its therapeutic action has not been fully elucidated. OBJECTIVES: To analyse eosin effects on psoriatic skin in vivo and keratinocytes and endothelial cells in vitro. MATERIALS & METHODS: Skin biopsies were taken from psoriatic plaques before and after a three-day eosin treatment and processed for histological analysis. Cultured human psoriatic keratinocytes and dermal endothelial cells were treated with eosin, and release of inflammatory chemokines was analysed by multiplexed bead-based immunoassay and ELISA. RESULTS: In patients, the three-day eosin treatment significantly reduced the number of infiltrating T lymphocytes, neutrophilic granulocytes, and dermal dendritic cells. A reduction in VEGF-A expression was also observed. In vitro, eosin treatment significantly decreased the release of CCL2, CCL5, and VEGF-A by keratinocytes and angiopoietin-2 by endothelial cells. CONCLUSIONS: Eosin treatment impacts on psoriatic inflammatory infiltrates and dampens the release of proinflammatory chemokines and angiogenic factors.

The protective effect of coffee consumption on cutaneous melanoma risk and the role of GSTM1 and GSTT1 polymorphisms.

PURPOSES: The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals. RESULTS: High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54). CONCLUSIONS: Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.

Effect of written emotional disclosure interventions in persons with psoriasis undergoing narrow band ultraviolet B phototherapy.

The beneficial health effects of emotional writing disclosure (ED) on several chronic diseases have been reported. The aim of this pilot study was to investigate the effects of two ED techniques on psoriatic patients treated with ultraviolet B (UVB) therapy. Forty patients were randomly assigned to two different ED treatments (according to Pennebaker [PW], writing about stressful events, to King [KW], writing about major life goals), or to a control group (CG). Disease severity and quality of life (QoL) were assessed at baseline, halfway through and at the end of UVB treatment, and 4 months after ED. Outcome measures were the PASI and SAPASI scores, the Skindex-29, and the GHQ-12, to assess disease severity, health-related QoL and psychological wellbeing, respectively. Increases in SAPASI scores were recorded between end of therapy and the final assessment in KW (p: 0.07) and CG individuals (p: <0.05), whereas no differences were found in PW patients. Significant differences in Skindex-29 values between PW and the other groups were reported.Patients allocated to the PW group had a longer period of remission after phototherapy. This provides preliminary evidence that such a simple and inexpensive tool may play a role in enhancing treatment efficacy and QoL.

The role of 9-O-acetylated ganglioside D3 (CD60) and {alpha}4{beta}1 (CD49d) expression in predicting the survival of patients with Sezary syndrome.

BACKGROUND: Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4(+) T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×10(9)/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described. DESIGN AND METHODS: We used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vß repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4(+) T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan-Meier product-limit estimates and hazard ratios from the Cox proportional hazards model. RESULTS: We found that both higher number of CD60(+) and lower number of CD49d(+) cells within circulating CD4(+) T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4(+)CD60(+) cells (≥ 0.5×10(9)/L) and low proportion of CD4(+)CD49d(+) cells (<0.5×10(9)/L) (hazard ratio = 12.303, 95% confidence interval 1.5-95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vß subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vß 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vß 12 and 13.1. CONCLUSIONS: In this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4(+) T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome.

Identifying individuals at high risk of melanoma: a simple tool.

Simple and reliable tools for identifying patients at high risk for melanoma with preventive measures have important public health implications. An individual risk score for cutaneous melanoma was constructed and externally validated. With the summary coefficients of the risk factors for cutaneous melanoma, derived from a meta-analysis, a melanoma risk score was tested in an Italian population and externally validated in a Brazilian population. Common nevi, skin and hair color, freckles, and sunburns in childhood were the variables included in the final predictive model. The discriminatory ability of the models was assessed by the receiver operating characteristic (ROC) curve. The performance of the model was also evaluated by conducting an external validation. The area under the curve (AUC) of the candidate model was 0.79 (95% confidence interval: 0.75-0.82). The same model, when applied in the Brazilian population, presented an AUC of 0.79 (95% confidence interval: 0.70-0.86). At the cut-off level of 3 and more, 89 and 80% of the melanoma cases were correctly classified as 'at risk for melanoma' in the Italian and in the Brazilian populations, respectively. The risk model is a simple tool that identifies patients for preventive measures and may be used with reasonable confidence in different populations. The risk model may help family doctors in referring patients to dermatological clinics and thus improve early diagnosis.

The association between residential pesticide use and cutaneous melanoma.

Occupational pesticide exposure has been linked to cutaneous melanoma in epidemiological studies. We studied the association between cutaneous melanoma and the residential use of pesticides. This is a case-control study of cutaneous melanoma (287 incident cases; 299 controls). Data on pesticide use was obtained with a standardised interview. An increased risk of melanoma was found for high use (4 times annually) of indoor pesticides (odds ratio (OR)=2.18; 95% confidence intervals (CI) 1.07-4.43) compared to low use (1 times annually), after adjustment for sex, age, education, sun exposure and pigmentary characteristics. Subjects exposed for 10 years or more had two and a half times the risk (OR=2.46; 95% CI 1.23-4.94) of those exposed for less than 10 years. A dose response was observed for the intensity of pesticides use (p(trend)=0.027). The results indicate that residential pesticide exposure may be an independent risk factor for cutaneous melanoma.