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Biomedical subjects

B Giannotti

Publications and source records attributed to B Giannotti.

At least 37 records · Page 2Linked to original sources

The role of pattern analysis and the ABCD rule of dermoscopy in the detection of histological atypia in melanocytic naevi.

BACKGROUND: Clinical features of melanocytic naevi correlate poorly with the presence, histopathologically, of architectural disorder and cytological atypia, making the detection of histological atypia by means of macroscopic appearance unreliable. OBJECTIVES: The aim of this study was to investigate the diagnostic effectiveness of dermoscopy in the non-invasive detection of histological atypia in naevi. METHODS: Observers blinded for histological diagnosis classified a series of 168 melanocytic naevi as common or atypical on the basis of their clinical features and on their dermoscopic profile. The diagnostic performance of both methods compared with the true (histopathological) diagnosis was assessed. RESULTS: Dermoscopy using pattern analysis showed better results than clinical examination in the non-invasive detection of naevi with architectural disorder with or without cytological atypia (diagnostic accuracy 45% vs. 28%). A statistically significant difference in the frequency of dermoscopic parameters between atypical and common naevi was found for atypical pigment network (39% vs. 17%, P = 0.001) and dermoscopic regression structures (13% vs. 2%, P = 0.008). Dermoscopic features, which best predicted histological atypia in naevi, were regression structures (white scar-like areas or peppering), irregular vascular pattern and grey-blue areas (positive predictive values 83%, 83% and 73%, respectively). In contrast, no statistically significant difference in the mean values of the ABCD score between common and atypical naevi was found. The best diagnostic performance of dermoscopy by means of the ABCD rule (cut-off point of 4.0 of total dermoscopy score) was not dissimilar to that of clinical diagnosis (diagnostic accuracy 30%). CONCLUSIONS: Dermoscopy by means of pattern analysis enhances the diagnostic accuracy of dermatologists in the prediction of histological atypia in melanocytic naevi as compared with clinical examination alone.

Diagnosis, Differential↗

Dermatoscopy in the diagnosis of pigmented skin lesions: a new semiology for the dermatologist.

Dermatoscopy or epiluminescence microscopy (ELM), is a noninvasive method that enables clinicians to evaluate fully--by means of a magnified oil immersion diascopy--numerous morphological features, not visible with the naked eye, which enhance the diagnosis of nearly all pigmented skin lesions. In recent years, a burst of research activity in this topic has been carried out, dealing with different aspects, and new frontiers, of this technique. First, a continuous refinement of dermatoscopic terminology is undertaken, paying particular attention to the diagnostic performance of dermatoscopy at peculiar anatomical sites and to the building of different dermatoscopic algorithms aimed at a simplified diagnosis of melanoma, even for less experienced observers. Another point of interest concerns the possible role of dermatoscopy in the pre-operative assessment of melanoma thickness. Finally, promising data about the role of digital equipment in the follow up of melanocytic skin lesions as well as in the automated diagnosis of pigmented skin lesions have been recently reported. This paper should enable readers to become familiar with the procedure and terminology of ELM in the diagnosis of pigmented skin lesions encouraging a greater understanding of different methods (pattern analysis, algorithms) in the diagnosis of melanoma using ELM.

Algorithms↗

Preoperative assessment of melanoma thickness by ABCD score of dermatoscopy.

BACKGROUND: Epiluminescence microscopy is a useful tool for the noninvasive diagnosis of malignant melanoma based on criteria that have been correlated with specific histologic characteristics. Previous studies have also shown a good correlation between the frequency of some dermatoscopic criteria based on pattern analysis (pigment network, blue-gray areas, vascular pattern) and tumor thickness. This technique could be useful in the preoperative assessment of tumor thickness as an indication for sentinel node biopsy. OBJECTIVE: Our purpose was to evaluate the possible role of the total dermatoscopy score (TDS) assigned to a series of lesions in accordance with the ABCD rule of dermatoscopy as a preoperative predictor of melanoma thickness. METHODS: For 84 cutaneous melanomas (17 were in situ melanomas; 67 invasive cases with mean thickness 0. 93 mm; range, 0.2-3.9 mm; standard deviation, 0.63) consecutively excised at the Department of Dermatology of Florence, TDS was established by two observers blinded as to the tumor thickness. The performance of different cut-off points of TDS in the diagnosis of melanoma with Breslow's thickness more than 0.75 or 1.00 mm was investigated by receiver operating characteristic (ROC) analysis. Accuracy of classification was evaluated in terms of sensitivity, specificity, and area under ROC curves (AUC). RESULTS: The TDS assigned to cutaneous melanomas by the ABCD rule increased with the thickness of the lesions from in situ melanomas to melanomas of intermediate thickness (0.75-1.50 mm). As a preoperative method for the detection of melanomas with a Breslow thickness greater than 0. 75 mm, a TDS cut-off point of 6.80 showed 80% sensitivity, 84% specificity, and 82% diagnostic accuracy (AUC value, 0.90). TDS performed better in the diagnosis of a thickness threshold of 0.75 than 1.00 mm (higher AUC value). CONCLUSION: The TDS calculated by the ABCD rule of dermatoscopy-a simplified approach to dermatoscopic diagnosis of melanoma-provides useful information for the preoperative assessment of melanoma thickness greater than 0.75 mm.

Humans↗

CD30-CD30 ligand interaction in primary cutaneous CD30(+) T-cell lymphomas: A clue to the pathophysiology of clinical regression.

Primary CD30(+) cutaneous T-cell lymphomas (CTCLs) represent a spectrum of non-Hodgkin's lymphomas (NHLs) that have been well defined at the clinical, histologic, and immunologic level. This group, which includes 2 main entities (large cell lymphoma and lymphomatoid papulosis [LyP]) and borderline cases, is characterized by the expression of CD30 antigen by neoplastic large cells at presentation, possible spontaneous regression of the skin lesions, and generally favorable clinical course. Although the functional relevance of CD30 and its natural ligand (CD30L) expression in most cases of NHL is presently undefined, previous studies indicate that CD30L is likely to mediate reduction of proliferation in CD30(+) anaplastic large-cell NHL. No information is currently available concerning the expression of CD30L in primary CD30(+) CTCLs. In this study, we investigated the immunophenotypic and genotypic expression of CD30 and CD30L in different developmental phases of skin lesions (growing v spontaneously regressing). By immunohistochemistry, CD30L expression was detected in regressing lesions only; by molecular analysis, the expression of CD30L was clearly higher in regressing lesions than in growing ones. CD30L, while expressed by some small lymphocytes, was most often coexpressed by CD30(+) neoplastic large cells, as demonstrated by 2-color immunofluorescence and by immunohistochemistry on paraffin sections. Taken together, these data suggest that CD30-CD30L interaction may play a role in the pathobiology of primary cutaneous CD30(+) lymphoproliferative disorders. In particular, CD30L (over)expression might have a major role in the mechanism of self-regression of skin lesions, the most distinctive clinical feature of this cutaneous lymphoma subtype.

Adult↗

Cutaneous melanoma histologically associated with a nevus and melanoma de novo have a different profile of risk: results from a case-control study.

BACKGROUND: Histopathologic association between melanocytic nevus and melanoma has been reported in approximately 10% to more than 50% of melanoma cases. Whether melanomas in contiguity with a nevus have a different natural history and pathogenesis from melanomas without a nevus is still to be determined. OBJECTIVE: The present study was undertaken to clarify whether melanocytic nevus-associated melanomas (MN[+]) have a different risk factor profile from cases without histopathologic evidence of melanocytic nevus association (MN[-]). METHODS: The study population consisted of 131 invasive melanoma cases with a thickness of 4.00 mm or less and 174 control cases without melanomas. The whole series was evaluated for the following risk factors: phenotypic traits; the number of common, atypical, and congenital nevus-like nevi; and freckling and history of sunburns. Melanoma cases were revised for the presence of associated melanocytic nevi. The analysis of risk factors was performed by a case-control approach comparing cases, classified by histologic association with nevus, to the group of controls. Possible differences in risk factor distribution between MN(+) cases and MN(-) cases were evaluated with a polychotomous logistic regression model and a likelihood ratio test for heterogeneity. RESULTS: Histopathologic association between melanocytic nevus and melanoma was found in 27 cases (20.6%). Phenotypic traits were shown to be more powerful predictors of risk for MN(-) than for MN(+) cases (blond/red hair; odds ratio, 7.4 and 1.2, respectively; likelihood ratio test for heterogeneity, 4.13; P < .05). Conversely, history of frequent sunburn was a risk factor only in MN(+) cases (more than 5 sunburns; odds ratio, 6.7; 95% confidence interval, 1.3-33.7), but not in MN(-) cases (odds ratio, 1.2; 95% confidence interval, 0.3-4.0; likelihood ratio test for heterogeneity, 4.2; P < .05). Where melanocytic nevi are concerned, an increased number of common nevi was a predictor of melanoma risk in both MN(+) and MN(-) cases, but with a different magnitude of risk, higher for MN(+) cases (number of common nevi, 10-30; odds ratio, 14.4 and 4.7, respectively; likelihood ratio test for heterogeneity, 3.7; P = .055). CONCLUSION: This study showed that, although MN(+) and MN(-) melanomas share many risk factors, there is a different strength of association between the 2 groups. The effect of a history of sunburn as a predictor of risk was found only for nevus-associated melanomas, suggesting a possible role of sunburns in the neoplastic transformation of nevi.

Adult↗

Characterization of [3H]substance P binding sites in human skin.

Radioligand binding experiments were performed with crude homogenates from normal human skin in order to investigate substance P receptor density. Binding of [3H]substance P ([3H]SP) reached equilibrium after 20 min and was saturable analysis of saturation curves gave a significantly better fit using two-site binding compared to the single-site model. Competition studies employing some selective agonists for NK1, NK2 and NK3 receptors have demonstrated that only the NK1 selective agonist, [Sar9, Met(O2)11]-SP, was a competitor for [3H]SP binding. In addition, the non-hydrolyzable guanosine 5'-0-(3-thiotriphosphate) altered the dissociation of SP from NK1 receptors by increasing the number of low-affinity sites. These data show that in the skin [3H]SP binds to a single population of substance P high-affinity sites, which represent NK1-type receptors.

Aged↗

Skin melanoma in Italy: a population-based study on survival and prognostic factors.

Survival and prognostic factors of invasive cutaneous melanoma patients diagnosed in the province of Florence, Italy, were studied using a regression analysis of relative survival rates. The case series consisted of 428 patients reported by the Tuscany Cancer Registry between 1985 and 1989. The effect of gender, age, anatomical site, histological type and microstaging parameters upon relative survival were evaluated using an extension of the Cox proportional hazard model. Five-year relative survival was 70%; 8-year relative survival, referring to a subset of patients, was 67%. In univariate analysis, the following variables were significantly associated with better prognosis: female gender, age younger than 60 years, superficial spreading melanoma (SSM) compared with nodular melanoma (NM), location on the limbs, a thinner lesion according to Breslow, a shallower Clark level. Females had a clear-cut prognostic advantage over males in each category of the variables considered above. After simultaneous adjustment for all other variables, three factors continued to show an independent prognostic effect: age, gender and microstaging parameters (Breslow thickness and Clark level, separately fitted in the model). In the multivariate analysis, the prognostic advantage of females over males was specifically seen for lesions located on the trunk and for both SSM and NM histotype.

Adolescent↗

Sun exposure and large numbers of common and atypical melanocytic naevi: an analytical study in a southern European population.

The study analysed the relationship between high counts of common naevi and numbers of atypical naevi (AN) in sites differing in exposure to the sun. A series of 90 subjects with 100 or more common naevi (cases) and 92 controls was investigated by means of a case-control study. A striking association between high numbers of common naevi and prevalence of AN (whole body) was found. The adjustment for phenotype and phototype did not obscure this association. Similar findings were obtained after exclusion of subjects with familiarity for melanoma. Cases had more AN than controls in all the body sites, except for the buttocks, where sun exposure can be considered minimal or absent: in this site, an excess of common naevi but not of AN was found. The present study suggests that subjects with high common naevi counts show a higher prevalence of AN independently of their complexion, sunburn history and family history of melanoma. Phenotypic expression of AN seems to be enhanced by direct sun exposure.

Adult↗

Immunophenotypic analysis of normal human dendritic cells isolated from epidermis and dermis.

BACKGROUND: The skin immune system comprises two types of dendritic cells, i.e. CD1a-positive Langerhans cells in the epidermis and CD36-positive dendritic macrophages in the dermis. Dendritic cells can migrate from skin explants into a culture medium. METHODS: We have examined the morphology and immunophenotype of the dendritic cells migrating from epidermal and dermal sheets in vitro. The epidermis and dermis of keratomes of normal human skin were separated with dispase and cultured for 72 h. At this time, the non-adherent cells in the medium were removed, enriched on a metrizamide or Lymphoprep gradient, counted, prepared by cytospin, and labeled for CD1a, CD36, and HLADr. RESULTS: Cells migrating from the epidermis and dermis show many thin projections or a few veils from the cell surface. Approximately four times more cells migrate from epidermal than dermal sheets from the same keratome. CONCLUSIONS: Using methods to separate the epidermis from the dermis, both CD1a-positive Langerhans cells and CD36-positive dendritic macrophages can be obtained from both tissues, although in different numbers.

Antibodies, Monoclonal↗

Hormonal contraception and the skin.

The use of hormonal contraception is of great interest in dermatological therapy because of the effectiveness of hormonal contraception with its antiandrogenic properties in the treatment of androgen-dependent dermatological disease and because of the need for a pregnancy prevention strategy in dermatological treatments with teratogenic potential (retinoids, thalidomide, methotrexate). We discuss here the main indications for the use of hormonal contraception in dermatology.

Abnormalities, Drug-Induced↗

In situ expression of transforming growth factor beta is associated with melanoma progression and correlates with Ki67, HLA-DR and beta 3 integrin expression.

Transforming growth factor-beta (TGF beta), which is secreted by cultured melanoma cells constitutively, inhibits the proliferation of normal melanocytes and of most melanoma cells in vitro, but some melanoma cells from advanced stages of the disease develop resistance to TGF beta-dependent growth inhibition, without developing any change in TGF beta cell surface binding. In vitro TGF beta also downregulates the expression of HLA-DR molecules on melanoma cells, and upregulates the expression of the beta 3 integrin subunit on some cell lines. Immunohistochemical analysis of 53 melanocytic lesions (12 naevi, 30 primary melanomas and 11 metastases) revealed a trend of increasing expression of TGF beta and TGF beta receptor type III with tumour progression, and a significantly higher expression of both TGF beta (P < 0.0001) and the receptor (P < 0.05) in metastatic and thick (> 1 mm) primary melanomas compared with thin (< 1 mm) primary melanomas. The expression of TGF beta correlated with expression of a marker of proliferation, Ki67, and with HLA-DR and beta 3 integrin subunit expression. Coexpression of the four molecules was observed in all metastases and in most thick primary melanomas. These findings argue against an inhibitory effect of TGF beta on cell proliferation or HLA-DR antigen expression in melanoma, and suggest the upregulation of the beta 3 subunit. TGF beta protein appears to be a biological marker of melanoma progression in situ.

Adult↗

Epidemiology of atypical melanocytic naevi: an analytical study in a Mediterranean population.

Atypical naevi are markers for increased risk of malignant melanoma, providing additional information about melanoma risk beyond that given by common melanocytic naevi. Little is known about the epidemiology of atypical naevi (AN), and available data are limited to predominantly fair-skinned populations. By using a case-control study that included 705 subjects with atypical naevi and 1,782 controls, we have analysed the aetiology of AN in a Mediterranean population, paying particular attention to the role of sunburn. After adjusting for age, sex and years of formal education, the presence of atypical naevi was significantly related to frequent sunburn before the age of 20 (odds ratio, OR, = 1.8; 95% CI, 1.3-2.5). Although less evident, this relationship was maintained by also taking into account the sun sensitivity, expressed as phototype, as a cofounder (OR = 1.5; 95% CI, 1.0-2.0). Concerning phenotypical features, an increased risk of having atypical naevi was found for all the parameters included in so-called 'fair complexion', i.e. blue eyes, blond or red hair, fair skin, phototype I-II, and a tendency to freckle. The greatest difference between subjects with and without atypical naevi related to the number of common melanocytic naevi: more than 30 common naevi were found in 41.5% of cases, but only in 9% of controls (OR = 8.0; 95% CI, 6.3-10.3). Overall, the six variables entered in the multivariate model that best predicted the risk of atypical naevi, were: young age, male sex, high educational level, presence of a large number of common naevi, phototype I-II, and a history of painful sunburn. In conclusion, the variables predicting the risk of developing atypical naevi in Mediterranean people are identical to those observed in predominantly fair-skinned populations. The aetiologic role of sunlight has been pointed out and shows a statistically significant relationship between frequent sunburn and the development of atypical naevi also after controlling for the subject's phototype.

Adolescent↗

Malignant melanoma in Italy: risks associated with common and clinically atypical melanocytic nevi.

BACKGROUND: Most epidemiologic studies on risk factors for cutaneous melanoma have been performed in predominantly fair-skinned populations. OBJECTIVE: Our purpose was to assess by means of a case-control study the importance of common melanocytic nevi (CMN) and clinically atypical nevi (CAN) as risk factors for cutaneous melanoma in a Mediterranean population. METHODS: One hundred six patients with invasive cutaneous melanoma and 109 population control subjects were included in the study. All subjects were younger than 70 years of age and were residents of the Florence area. RESULTS: The adjusted odds ratios obtained by exact conditional analysis, accounting for age, sex, place of birth, and residence, were 2.6 (95 confidence interval [CI], 1.0 to 6.7) for 10 to 30 CMN, and 22.3 (CI, 4.8 to 215) for more than 30 CMN (chi 2 for trend, 25.41; p < 0.001), 2.9 (CI, 1.2 to 7.5) for large nevi, and 8.4 (CI, 2.2 to 31.4) for CAN. Tendency to freckle resulted in a twofold increase in risk (odds ratio, 2.2) (CI, 1.0 to 5.2). The relative risk associated with a large number of CMN was statistically significant after adjustment for all other variables. When adjusted for the number of CMN, none of the other variables showed a statistically significant increased risk. CONCLUSION: A large number of CMN represents the most important risk factor for cutaneous melanoma in the Italian population. The presence of large nevi and CAN did not result in an increased risk when the number of CMN was considered.

Adult↗

Squamous cell carcinoma arising in vulval lichen sclerosus: a longitudinal cohort study.

Histological changes of lichen sclerosus (LS)--a chronic inflammatory disease--are frequently found in association with squamous cell carcinoma (SCC) of the vulva, suggesting that women with this disorder are at increased risk. However, follow-up studies have been less convincing, showing that the vast majority of these patients do not go on to develop cancer. In this study, a series of 211 women affected by histologically demonstrated vulval LS were treated with topical therapy (testosterone, clobetasol) and followed prospectively by repetitive vulval examination. Three patients developed SCC of the vulva (two invasive, one in situ) at the sites affected by LS during an average follow-up period of 1 year and 8 months. Compared with the reference population, the number of cases of invasive SCC detected significantly exceeded the number estimated to occur in a comparable age-matched group. The standardized incidence rate of vulval SCC in the LS cohort was 317 (95% CI 35.7-1146.2). Cumulative risk was 14.8% (0.06% in the general female population), with a relative risk of 246.6. In conclusion, these data support the view that LS is a precursor of SCC, although characterized by slight tendency to evolve to carcinoma. Medical treatment of LS, although useful in the control of severity of disease, did not seem to be able to prevent the evolution to malignancy.

Administration, Topical↗

Incidence of cutaneous melanoma in the centre of Italy: anatomic site distribution, histologic types and thickness of tumour invasion in a registry-based study.

The majority of epidemiological data on cutaneous melanoma (CM) derives from studies carried out in a predominantly fair-skinned population. On the contrary, little is known of the epidemiological figures (including incidence data) in mediterranean populations. The aim of this study was to investigate the incidence rates of CM in a geographically-defined area of the centre of Italy, with particular attention to anatomic site distribution, histologic types and thickness of tumour invasion. After revision of the data base of the Tuscany Cancer Registry concerning the period 1985 to 1987, 282 incident cases of invasive CM (135 males, 147 females) were found in a resident population of 1,174,121 inhabitants. The mean annual age-standardized rates were 6.7/100,000 for males and 7.0/100,000 for females. Site-specific incidence rates showed an almost three-fold higher incidence of CM of the trunk in males than females (3.7/100,000 vs 1.4/100,000). Conversely, a four-fold higher incidence in females than in males was observed for the lesions of lower limb (2.1/100,000 vs 0.5/100,000). A statistically significant difference of incidence rates was also observed for the thigh (females 1.1/100,000, males 0.2/100,000), a normally sun-exposed area. Concerning histologic types of CM, the incidence of the nodular type was higher in males than in females (1.8/100,000 vs 1.3/100,000), even if the difference was not statistically significant in any class of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dendritic cells in cutaneous lupus erythematosus: a clue to the pathogenesis of lesions.

In view of the critical role of dendritic cells in immune mediated skin diseases, we have investigated the membrane antigen patterns and ultrastructure of cutaneous dendritic cells in eight patients with chronic discoid lupus erythematosus and five with subacute cutaneous lupus erythematosus. In the lesional epidermis, the expression of HLA-DR antigens by epidermal dendritic cells was reduced, as compared with perilesional, clinically normal skin. In addition, only few CD1a+ dendritic cells (Langerhans' cells), along with some CD11c+ and CD14+ cells (presumable precursors of Langerhans' cells), were found in atrophic areas of lesional epidermis. In contrast, the number of Langerhans' cells in non-atrophic areas of lesional epidermis was similar to that in perilesional skin. On electronmicroscopy, epidermal Langerhans' cells appeared depleted of organelles and dendrites and contained tubuloreticular inclusions. In the lesional dermis, both CD1a+ and CD36+ dendritic cells were found, associated with CD4+ and CD8+ T-cells, respectively. Moreover, CD11c+ and CD14+ cells were found around capillaries in the papillary dermis on electronmicroscopy. Indeterminate cells (dendritic cells with features of Langerhans' cell lineage, but apparently without Birbeck granules) and dendritic macrophages were found, associated with lymphocytes and mast cells. No cells with intermediate/transitional features between these two dendritic cell types were found. Conversely, peculiar dendritic cells--with short and blunt dendrites and cytoplasm containing many flat, rough cisternae, moderately well developed Golgi apparatus and no lysosomes--were found in the same location as the CD11c+ and CD14+ cells identified by light microscopy. These findings might be interpreted as follows: 1 the alterations in cytological differentiation and expression of functionally meaningful molecules by epidermal Langerhans' cells in cutaneous lupus erythematosus lesions suggest an impairment of their immunological efficiency; 2 in the lesional dermis of cutaneous lupus erythematosus, a CD4+ T-cell/CD1a+ dendritic cell-based, delayed-type immune response is possibly modulated by a suppressor T-cell circuit in which CD36+ dendritic cells may act as accessory cells; 3 CD11c+ and CD14+ cells with peculiar ultrastructure are possible precursors of both CD1a+ indeterminate cells and CD36+ dermal dendrocytes in the dermis.

Adolescent↗