Risk of mycosis fungoides in psoriatic patients: a critical review.

Psoriasis has been controversially associated with risk of non-Hodgkin lymphoma (NHL) and mycosis fungoides (MF). Also patients who developed MF after systemic treatment for psoriasis have been reported, and some authors suggested that the association between MF and psoriasis is not infrequent. We performed an extensive literature review in order to examine the risk of developing MF in psoriatic patients with a systematic search of the English-language databases. An increased risk for lymphoma overall in psoriatic patients has been found only by three out of seven studies. The risk of developing MF in psoriatic patients has been investigated by different studies in different populations and with different methodologies presenting bias and limitations, and it seems reasonable that misclassification between psoriasis and MF may explain the association reported. In contrast to the large number of psoriatic patients treated with biologicals, only 27 case reports of MF after biological therapy for psoriasis have been reported, and in 10 cases, the initial psoriasis diagnoses were then revised as MF. A true association between MF and psoriasis is possible, but the real incidence and prevalence are still unknown. The reported higher risk of developing MF in psoriatic patients should be reconsidered in the light of the bias of misclassification and the low magnitude reported in previous studies. There is not enough evidence to support a causal relation among biological therapies and MF in psoriatic patients.

Reflectance confocal microscopy analysis of equivocal melanocytic lesions with severe regression.

BACKGROUND: The differential diagnosis between regressing nevi and melanoma might be challenging; regressing areas can represent a confounding factor for the diagnosis and the histology still remain mandatory to rule out melanoma. Reflectance confocal microscopy may add valuable information by revealing features suggestive of the nature of the melanocytic proliferation. OBJECTIVE: To assess the impact of confocal microscopy in the management of regressive melanocytic lesions. METHODS: The dermoscopic analysis of 92 melanocytic lesions showing that more than 30% of regressions have been retrospectively considered, among them, 32 melanocytic lesions with a 7 check point list ≥3 they were assessed at the rcm and subsequently excised. For each selected lesion, dermoscopic features of regression (white scar-like areas, blue areas, blue white areas), distribution of regressing areas (central, peripheral, or both) and the percentage of regression have been examined by an expert in dermoscopy, blinded to the histological and confocal diagnosis. Subsequently, two experts in confocal microscopy revaluated, blinded from histology, RCM images. RESULTS: Of the 32 lesions analyzed, 23 (71.5%) were diagnosed histologically as nevi, and 9 (28.5%) as melanomas. 26 of 32 lesions (81.5%) exhibited regression >50% of the overall. On RCM, 11 lesions have been interpreted as malignant and 21 as benign. On RCM the majority of nevi exhibited regular architecture without cytological atypia. Epidermal disarray, pagetoid infiltration, disarranged dermo-epidermal junction architecture and atypical nests were considered as suspicious for malignancy. Good concordance between confocal readers has been detected. CONCLUSION: A combined dermoscopic/confocal approach can be used for the management of lesions exhibiting dermoscopic features of regression in order to provide a more conclusive pre-histological diagnosis avoiding a high number of unnecessary excisions. Limits of this study were represented by the relatively small number of lesions and the retrospective approach. Further, prospective studies on a larger number of cases, will be necessary in order to compare the efficacy of dermoscopy alone versus dermoscopy in combination with RCM for the evaluation of regression, suspected pigmented lesions.

Cannabis and alcohol use, and the developing brain.

Sex hormones and white (and grey) matter in the limbic system, cortex and other brain regions undergo changes during adolescence. Some of these changes include ongoing white matter myelination and sexually dimorphic features in grey and white matter. Adolescence is also a period of vulnerability when many are first exposed to alcohol and cannabis, which appear to influence the developing brain. Neuropsychological studies have provided considerable understanding of the effects of alcohol and cannabis on the brain. Advances in neuroimaging have allowed examination of neuroanatomic changes, metabolic and neurotransmitter activity, and neuronal activation during adolescent brain development and substance use. In this review, we examine major differences in brain development between users and non-users, and recent findings on the influence of cannabis and alcohol on the adolescent brain. We also discuss associations that appear to resolve following short-term abstinence, and attentional deficits that appear to persist. These findings can be useful in guiding earlier educational interventions for adolescents, and clarifying the neural sequelae of early alcohol and cannabis use to the general public.

Age-related prevalence and morphological appearance of facial skin tumours: a prospective, cross-sectional, observational, multicentre study with special emphasis on melanocytic tumours.

BACKGROUND: The clinical and histopathological diagnosis of skin tumours arising on the face may be challenging. OBJECTIVE: An improved knowledge about the age-related patterns of facial skin tumours may aid the correct diagnosis and management. METHODS: We conducted a prospective, cross-sectional morphological study to investigate the age-related frequency and morphological variability in facial skin tumours in a cohort of consecutive subjects attending two skin lesion clinics in Italy between June and September 2011. A total of 454 consecutive subjects (249 women; 55.5%) presenting with a total of 1866 facial tumours were enrolled in the study. Of the entire cohort, 54 (11.9%) subjects had no facial lesion. RESULTS: Total body naevus count correlated significantly with the mean number of facial lesions (ρ = 0.289, P < 0.001). The majority of flat lesions were pigmented (1056; 75.70%), compared to palpable (233; 17.40%) and raised lesions (93; 6.90%), the association being statistically significant (Pearson's chi square, P < 0.001. Considering melanocytic tumours only, the frequency of flat lesions significantly decreased with increasing age, while the number of palpable and raised lesions increased with increasing age (chi-square, P < 0.001). This trend was mainly due to naevi, whereby pigmented melanocytic naevi decreased with increasing age. Conversely, the percentage of non- pigmented naevi increased with increasing age (chi-square, P < 0.001). LIMITATIONS: The study was conducted in skin lesion clinics in Italy, thus any general conclusions with respect to common traits or features based on the phenotypic and genetic diversity within the European population cannot be stated. CONCLUSIONS AND RELEVANCE: Our study suggests that a high number of facial naevi could predict a high total naevus count. Moreover, naevi present a different morphological appearance during lifetime being initially flat, small and pigmented and becoming later raised, large and hypopigmented. Instead, lentigo maligna is an intraepidermal proliferation that typically presents as flat, large pigmented macule. A given histopathological diagnosis of a junctional naevus of a flat, facial pigmented macule of an elderly should be critically reviewed and treated with caution.

Vitiligo: characterization of melanocytes in repigmented skin after punch grafting.

BACKGROUND: Punch grafting is a surgical technique mainly applied in therapy-resistant, stable and circumscribed vitiligo. OBJECTIVE: (i) To characterize in detail the features of the repigmented skin among punch grafts; and (ii) to correlate the ex vivo results with clinical data and punch grafting outcome. METHODS: We evaluated by immunohistochemistry and image analysis the expression of a panel of specific melanocyte markers including HMB45, MITF, c-kit, MART-1 and TRP1, the proliferation marker Ki67 and the cell-cell adhesion molecule E-cadherin in tissue samples collected from nine patients after punch grafting. RESULTS: Cells positive for MITF, c-kit, MART-1 and TRP1 were detected in the repigmented skin of all biopsies, whereas no reactivity was observed for HMB45. Melanocytes were identified along the entire length of the sections, and their mature state was assessed by the immuno-reactivity for the differentiation marker MART-1, the absence of cells positively stained for Ki67 and by the co-expression of c-kit and TRP1, a marker of a differentiated and pigmented state. Clinically, smaller punch grafts aimed at repigmenting lesional areas on the face gave the faster clinical results with no side-effects. Patients subjected to bigger punch grafts on the knee exhibited a longer repigmentation time and presented cobble stoning. CONCLUSION: Our results suggest that the repigmentation observed in the areas between the grafts is due to the activation of the melanocytes located in the donor sites. These cells start to horizontally migrate towards the lesional skin thanks to successively the enlargement of intercellular spaces in relation to a decrease of E-cadherin reactivity and the up-modulation of pro-melanogenic mediators. Production and transfer of melanin in the surrounding keratinocytes and their persistence were assessed by the reactivity for MITF, c-kit, MART-1 and TRP1 but not for the pre-melanosome marker (HMB45).

Dermoscopy and reflectance confocal microscopy of pigmented actinic keratoses: a morphological study.

BACKGROUND: Actinic keratoses (AKs) are very common lesions on sun damaged skin and, when pigmented, represent a challenge in the differential diagnosis with early melanoma. Non-invasive diagnostic methods, such as dermoscopy and reflectance confocal microscopy (RCM) have been shown to improve the diagnostic accuracy of melanoma and non-melanoma skin cancer, however, only one case report described confocal findings of pigmented AKs up to now. OBJECTIVES: The aim of our retrospective morphological study was to analyse dermoscopic and confocal images of a series of histopathologically proven pigmented AKs, located on the face and other body sites, to define peculiar features of these "difficult to diagnose" lesions. METHODS: Clinical, dermoscopic and RCM images of 17 histopathologically confirmed pigmented AKs were retrospectively collected from the databases of four skin lesion clinics in Italy and USA. Dermoscopic and RCM images were analysed for prevalent morphological features. RESULTS: The majority of the lesions were located on the face (n = 8); followed by scalp (n = 4) and trunk (n = 4); and one lesion was located on the lower limbs. On dermoscopy the majority of lesions were characterized by grey dots/globules/granularity and structureless brown pigmentation. The main RCM feature of pigmented AKs was as follows: (i) the presence of epidermal changes (atypical keratinocytes, parakeratosis, scaling); (ii) increased epidermal thickness; (iii) bright, small, dermal papillae with enlarged interpapillary space; and (iv) intraepidermal dendritic cells referrable to Langherans cells. Features suggestive of melanocytic lesions, such as nesting, meshwork pattern or atypical cells infiltrating the junction, were never detected in our case series at the dermal epidermal junction (DEJ) level. CONCLUSION: Larger case series with adequate control population are warranted to validate these findings and to test their value in clinical setting.

Morphological features of naevoid melanoma: results of a multicentre study of the International Dermoscopy Society.

BACKGROUND: Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. OBJECTIVES: To describe the clinical and dermoscopic features associated with NeM. METHODS: Lesions with a histopathological diagnosis of NeM were collected via an e-mail request sent to all members of the International Dermoscopy Society. All lesions were histopathologically reviewed and only lesions fulfilling a set of predefined histopathological criteria were included in the study and analysed for their clinical and dermoscopic features. RESULTS: Twenty-seven of 58 cases (47%) fulfilled the predefined histopathological criteria for NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular. Analysis of the global dermoscopic pattern identified three types of NeM. The first were naevus-like tumours (n = 13, 48%), typified by a papillomatous surface resembling a dermal naevus. In these lesions local dermoscopic features included irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical vascular structures (46%). The second type were amelanotic tumours (n = 8, 30%), typified by an atypical vascular pattern (75%). The third type consisted of tumours displaying a multicomponent pattern (n = 4, 15%), characterized by classical local melanoma-specific criteria. Two lesions (7%) were classified as mixed-pattern tumours as they did not manifest any of the aforementioned patterns. CONCLUSIONS: While NeMs may be clinically difficult to differentiate from naevi, any papillomatous lesion displaying dermoscopically atypical vessels and/or irregular dots/globules should prompt consideration for the possible diagnosis of NeM.

Inflammasome activation and vitiligo/nonsegmental vitiligo progression.

BACKGROUND: Polymorphisms of NLR (nucleotide-binding domain and leucine rich repeat containing) family, pyrin domain containing protein 1 (NLRP1) have been found in patients with vitiligo/nonsegmental vitiligo (NSV), and increased NLRP1 expression has been detected in the leading edge of lesional skin biopsies. OBJECTIVES: To evaluate the presence and intensity of NLRP1 immunostaining in lesional and perilesional skin of patients with vitiligo/NSV and to search for possible correlations between NLRP1 and interleukin (IL)-1ß expression, lymphocytic infiltrates and disease activity. METHODS: Of 14 consecutive vitiligo/NSV patients, eight had active disease [Vitiligo European Task Force (VETF) spreading score +1 to +5], one patient had stable disease and five patients had regressive disease (VETF spreading score -1 to -3). We performed immunostaining for NLRP1, B and T lymphocytes, IL-1ß and kallikrein 7 on lesional and perilesional vitiligo skin. RESULTS: NLRP1 and IL-1ß immunostaining in perilesional vitiligo/NSV skin was significantly associated with progressive disease (P = 0·009 and 0·04, respectively) and performed better than the simple detection of lymphocytic infiltrates. CONCLUSIONS: Our findings suggest that markers of the NLRP1 inflammasome could be a useful test for assessing disease activity in addition to the detection of inflammatory infiltrates in the progressing margins of vitiligo/NSV lesions.

Real-time, non-invasive microscopic confirmation of clinical diagnosis of bullous pemphigoid using in vivo reflectance confocal microscopy.

BACKGROUND: Bullous pemphigoid is an autoimmune disease affecting prevalently the elder. In vivo reflectance confocal microscopy is a non-invasive technique for real-time imaging of the skin with cellular-level resolution. No previous data has been reported about confocal microscopy of bullous pemphigoid. Aim of this preliminary study is the evaluation of the potential of in vivo reflectance confocal microscopy for real-time, microscopical confirmation of clinical bullous pemphigoid diagnosis. METHODS: A total of nine lesions from patients affected by pemphigoid underwent in vivo reflectance confocal microscopy before histological examination. RESULTS: In our preliminary study, confocal microscopy showed high grade of correspondence to histopathology. In particular, presence of sub-epidermal cleft and variable amount of oedema of the upper dermis associated with inflammatory cells infiltration were seen as prevalent confocal features in the bullous lesions considered. Differently, in urticarial lesions, no specific features could be appreciated at confocal analysis beside the presence of signs of spongiosis and perivascular inflammation. CONCLUSION: Confocal microscopy seems to be useful for in vivo, microscopical confirmation of the clinical suspect of bullous pemphigoid and for biopsy site selection in urticarial lesions to obtain a more significant specimen for histopathological examination.

hMena: altered expression in psoriatic skin.

Psoriasis is a chronic inflammatory skin disease, characterized by an enhanced proliferation and a deregulated differentiation of keratinocytes. hMena is an actin regulatory protein involved in the control of cell motility and adhesion. hMena results up-modulated in several human tumors with respect to normal tissues and its expression has been positively correlated to proliferation rate, tumor size and aggressiveness in response to mitogenic stimuli, such as epidermal growth factor. The hyperproliferation of keratinocytes observed in psoriasis prompted us to evaluate hMena expression on biopsies collected from involved and uninvolved skin of 12 patients with active plaque-type psoriasis with respect to healthy skin. We analyzed the expression of hMena at transcript and protein levels by quantitative RT-PCR and immunohistochemistry. We correlated the expression of hMena to Ki67 proliferation index and to keratin 10 (K10) and keratin 16 (K16) used as markers of keratinocyte differentiation and activation. We demonstrated the expression of hMena in a hyperproliferative skin condition not related to neoplastic transformation. Interestingly, we observed that hMena is not expressed in healthy skin, but it becomes detectable in non-lesional areas and it is even more expressed in lesional psoriatic skin. In addition, we found that hMena expression is correlated to the rate of keratinocyte proliferation and activation. Hence, our observations indicate hMena as a new possible player, involved in the development and/or maintenance of the hyperproliferative state of psoriatic keratinocytes.

Visceral leishmaniasis revealed by a squamous cell carcinoma in an HIV-1 infected patient.

We present a case of visceral leishmaniasis confirmed after the histological investigation of an ulcerate lesion of the scalp in an HIV-1-infected patient receiving highly active antiretroviral therapy (HAART). Histological examination of the skin lesion revealed a squamous cell carcinoma superinfected by amastigotes of Leishmania infantum from the bloodstream. Because HIV-1-infected individuals can harbour parasitic infections in normal and neoplastic tissue, it is necessary to examine carefully any skin lesions, particularly those with uncommon aspects or a worsening course, to exclude superinfections by unsuspected pathogens.

Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal-dominant disorder characterized by the association of sebaceous tumors or keratoacanthomas with an early onset visceral cancer in the spectrum of Lynch syndrome. OBSERVATIONS: A total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of six patients with MTS were analysed. Two main clinico-dermoscopic features were observed: (1) clinically pink to white papules/nodules with a central crater, dermoscopically characterized by radially arranged, elongated crown vessels surrounding opaque structureless yellow areas at times covered by blood crusts (n = 13) and (2), clinically pink to yellow papules/nodules without a central crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like globules and branching arborizing vessels (n = 7). Confocal microscopy was available in three sebaceous adenomas and revealed a good histopathologic correlation; sebaceous lobules were composed by clusters of ovoid cells with dark nuclei and bright, highly refractile glistening cytoplasm. They were delimited by a rim of epithelial cells, corresponding to basaloid cells. CONCLUSIONS: A better characterization of clinical, dermoscopic and confocal microscopy features of sebaceous tumors may improve their recognition and consequently, aid to rise the suspect for MTS.

Lichen sclerosus and the risk of malignant progression: a case series of 159 patients.

AIM AND METHODS: We analyzed 159 stored specimens of Lichen Sclerosus (LS) collected in the period 1999-2011 from 159 patients, in order to evaluate the histological patterns, clinical outcomes and possible associations with malignancies. The histopathologic analysis revealed 145 cases (males and females) with LS alone, 7 in whom penile LS was associated with spinocellular carcinoma (SCC), and 7 in whom LS was associated with a pseudocarcinomatous-hyperplasia (PCH). Extragenital LS was found in 20% (17/85) of the males and 78% (58/74) of the females. In the cases of SCC, immunohistochemical analyses was performed. RESULTS AND CONCLUSION: The results showed very low positivity to p16INK4A and Ki-67; biomolecular PCR was positive in only two cases, and in both cases the non-oncogenic genotype HPV 100 was detected. No important additional risk factors for malignancies were found (e.g., hormones, infections, other autoimmune diseases).