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The increase life expectancy led to an expected increase in skin cancer incidence in older patients. Their treatment can require a complex decision-making process. Limited data are available on characteristics, management and outcome of skin tumours in nonagenarian and centenarian patients. The aim of our study was to describe epidemiology, clinical-pathological features and treatment strategies of skin cancers in a cohort of patients aged ≧95 years. A total of 116 patients ≧95 years of age presented for the evaluation of 225 skin lesions (mean of 1.94 lesions per patient). The mean age was 97.4 years, 57.8% were women. Most patients had an ECOG score of 3 (49.3%) or 4 (32%). Lesions were mainly located on the head and neck area (74.2%), upper (7.1%) and lower (6,2%) limbs. The majority of patients presented with non-melanoma skin cancers (183/225; 81.3%), 25/225 (11.1%) had actinic keratosis, 5 (2.2%) melanoma and 2 (0.9%) atypical fibroxanthoma. Forty-eight lesions (21.3%) were treated with surgery, 58 (25.8%) with radiotherapy. The management of 73 lesion (32.4%) was discussed at the multidisciplinary tumour board meeting. One patient died for the progression of a squamous cell carcinoma; 74 patients died for causes unrelated to skin tumours, 36 are still alive after a mean follow-up of 27.27 months. This cohort study confirms that age is not per se a contraindication for treatment of skin cancers in elderly patients. Our results support the importance of a patient-centred care approach that should take into consideration patient's preferences, comorbidities, compliance and possible adverse events.

Background PReferentially expressed Antigen in Melanoma (PRAME) has been widely investigated in the skin, mainly in melanocytic tumors, and constitutes an aid in differentiating benign from malignant lesions. Very few others studies have been performed on non-melanocytic tumors. Materials We investigated the immunohistochemical expression of PRAME on a series of 11 neurothekeomas, together with three cases of nerve sheath myxoma and one case of plexiform fibrohistiocytic tumor, in order to evaluate the presence and usefulness of this marker in their differential diagnosis. Results PRAME was variably expressed in all cases of NTK, with moderate intensity in three cases, and faint in the remaining cases; on the contrary, cases of NSM and PFT were negative. Conclusions This study expands the entities of cutaneous non-melanocytic tumors expressing PRAME, and confirms that this marker is not restricted to malignant tumors. Expression of PRAME in NTK does not seem to be related to distinctive histopathologic features. This article is protected by copyright. All rights reserved.

Objective Thyroid surgery may lead to postoperative complications. The aim of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged. Design Single-institution retrospective observational study. Methods The clinical records of 786 patients treated at the Otolaryngology Unit of the Azienda USL-IRCCS di Reggio Emilia between January 1990 and December 2015 were reviewed. Patients were divided into two groups according to the surgical treatment received: group TT (637 patients, 81.04%) underwent single-stage total thyroidectomy; Group cT (149 patients, 18.96%) underwent loboisthmusectomy and delayed completion total thyroidectomy. Transient and permanent HPT, assessed after 6 months of follow-up, were the primary endpoints. Risk factors of postoperative HPT were also analysed as secondary outcomes. Results Rates of transient HPT in group TT were higher than those observed in group cT, (P = 0.0057). Analysis of risk factors identified sex as an independent risk factor for transient HPT only for group TT (P = 0.0012) and the number of parathyroid glands remaining in situ (PGRIS) as an independent risk factor for transient and permanent HPT for group TT (P < 0.0001 and P = 0.0002, respectively). Conclusions This study suggests that the risk of transient postoperative HPT is lower in patients that undergo completion thyroidectomy. Further independent risk factors for postoperative HPT are female sex and PGRIS score. In light of the growing use of conservative surgery for thyroid neoplasms, these findings could help to adequately plan surgery in order to reduce endocrine complications.

Background: Papillary thyroid cancers (PTCs) are common, usually indolent malignancies. Still, a small but significant percentage of patients have aggressive tumors and develop distant metastases leading to death. Currently, it is not possible to discriminate aggressive lesions due to lack of prognostic markers. Long noncoding RNAs (lncRNAs), which are selectively expressed in a context-dependent manner, are expected to represent a new landscape to search for molecular discriminants. Transforming growth factor β (TGFβ) is a multifunctional cytokine that fosters epithelial-to-mesenchymal transition and metastatic spreading. In PTCs, it triggers the expression of the metastatic marker Cadherin 6 (CDH6). Here, we investigated the TGFβ-dependent lncRNAs that may cooperate to potentiate PTC aggressiveness. Methods: We used a genome-wide approach to map enhancer (ENH)-associated lncRNAs under TGFβ control. Linc00941 was selected and validated using functional in vitro assays. A combined approach using bioinformatic analyses of the thyroid cancer (THCA) - the cancer genome atlas (TCGA) dataset and RNA-seq analysis was used to identify the processes in which linc00941 was involved in and the genes under its regulation. Correlation with clinical data was performed to evaluate the potential of this lncRNA and its targets as prognostic markers in THCA. Results: Linc00941 was identified as transcribed starting from one of the TGFβ-induced ENHs. Linc00941 expression was significantly higher in aggressive cancer both in the TCGA dataset and in a separate validation cohort from our institution. Loss of function assays for linc00941 showed that it promotes response to stimuli and invasiveness while restraining proliferation in PTC cells, a typical phenotype of metastatic cells. From the integration of TCGA data and linc00941 knockdown RNA-seq profiling, we identified 77 genes under the regulation of this lncRNA. Among these, we found the prometastatic gene CDH6. Linc00941 knockdown partially recapitulates the effects observed upon CDH6 silencing, promoting cell cytoskeleton and membrane adhesions rearrangements and autophagy. The combined expression of CDH6 and linc00941 is a distinctive feature of highly aggressive PTC lesions. Conclusions: Our data provide new insights into the biology driving metastasis in PTCs and highlight how lncRNAs cooperate with coding transcripts to sustain these processes.

Background Anaplastic Thyroid Cancer (ATC) is an undifferentiated and aggressive tumor that often originates from well-Differentiated Thyroid Carcinoma (DTC) through a trans-differentiation process. Epithelial-to-Mesenchymal Transition (EMT) is recognized as one of the major players of this process. OVOL2 is a transcription factor (TF) that promotes epithelial differentiation and restrains EMT during embryonic development. OVOL2 loss in some types of cancers is linked to aggressiveness and poor prognosis. Here, we aim to clarify the unexplored role of OVOL2 in ATC. Methods Gene expression analysis in thyroid cancer patients and cell lines showed that OVOL2 is mainly associated with epithelial features and its expression is deeply impaired in ATC. To assess OVOL2 function, we established an OVOL2-overexpression model in ATC cell lines and evaluated its effects by analyzing gene expression, proliferation, invasion and migration abilities, cell cycle, specific protein localization through immunofluorescence staining. RNA-seq profiling showed that OVOL2 controls a complex network of genes converging on cell cycle and mitosis regulation and Chromatin Immunoprecipitation identified new OVOL2 target genes. Results Coherently with its reported function, OVOL2 re-expression restrained EMT and aggressiveness in ATC cells. Unexpectedly, we observed that it caused G2/M block, a consequent reduction in cell proliferation and an increase in cell death. This phenotype was associated to generalized abnormalities in the mitotic spindle structure and cytoskeletal organization. By RNA-seq experiments, we showed that many pathways related to cytoskeleton and migration, cell cycle and mitosis are profoundly affected by OVOL2 expression, in particular the RHO-GTPase pathway resulted as the most interesting. We demonstrated that RHO GTPase pathway is the central hub of OVOL2-mediated program in ATC and that OVOL2 transcriptionally inhibits RhoU and RhoJ. Silencing of RhoU recapitulated the OVOL2-driven phenotype pointing to this protein as a crucial target of OVOL2 in ATC. Conclusions Collectively, these data describe the role of OVOL2 in ATC and uncover a novel function of this TF in inhibiting the RHO GTPase pathway interlacing its effects on EMT, cytoskeleton dynamics and mitosis.

Anaplastic carcinoma (AC) is a rare but highly aggressive form of thyroid cancer. It mostly arises on a background of pre-existing well-differentiated cancer (WDC); however, whether it evolves directly from a WDC or originates as a second independent neoplasm is still to be defined. To obtain further insights into these mechanisms, we performed morphological, immunohistochemical, and next-generation sequencing analyses to compare AC and its associated WDC in a subset of 13 surgically resected specimens. Histologically, most WDC were of aggressive subtypes. Papillary carcinomas (8 cases; 62%) were tall cell (4/8), columnar (1/8), classic with hobnail features (1/8), classic and follicular variant in the remaining 2 cases; Hürthle cell and follicular carcinomas were present in 5 (38%) and in 1 (8%) patient, respectively. One patient harbored both a PTC, follicular variant, and a Hürthle cell carcinoma. We did not find any correlation between a histotype of WDC and a specific anaplastic growth pattern. Immunohistochemically, ACs retained pankeratin/PAX8 expression but with significantly lower levels than WDCs, and they tended to lose TTF1 expression, as can be expected within a dedifferentiation process. In addition, AC showed a more frequent expression of p63 and/or SMA, a mutated pattern of p53, and an abnormal expression of p16. Genetic analysis showed that the number of mutations was higher in AC than in the associated WDC, confirming a role of the progressive accumulation of genetic damage in this transition. We observed that mutations found in the WDCs were consistently identified in the anaplastic counterparts, further supporting the hypothesis of a developmental link.

NUT carcinoma (NUT-C) is a relatively new malignancy that was recently listed in the 4th edition of the WHO Classification of Head and Neck Tumors in 2017. NUT carcinoma is a rare, aggressive, poorly differentiated carcinoma genetically defined by chromosomal rearrangement of the nuclear protein in testis (NUTM1) gene. The prognosis is extremely poor, with a mean survival

Background: The head and neck are considered one single anatomical unit. No data on clinical, dermoscopic and confocal aspects of neck melanoma are currently available. Objectives: To identify clinical, dermoscopic and confocal diagnostic features of neck melanomas. Methods: Consecutive malignant (cases) and benign (controls) melanocytic skin lesions located on the neck, excised as suspected of being melanoma from March 2011 to February 2018, were retrospectively retrieved. Dermoscopic criteria of the 7-point checklist, integrated by other melanoma features (such as grey colour and irregular hyperpigmented areas) were assessed. Reflectance confocal microscopy (RCM) images were examined when available. Results: 282 lesions located to the head and neck area were biopsied to rule out melanoma. Thirty-one out of 282 (11%) lesions were located on the neck: 21 melanomas and 10 naevi. Melanoma patients were older than patients with naevi (mean age: 60.4 vs. 37.9 years, p < 0.001). Neck melanomas were more frequently located on sun-damaged skin compared to naevi (76.2 vs. 30%, p = 0.02). Dermoscopically, neck melanomas were characterized by irregular dots/globules, grey colour and regression (76.2, 81 and 46.7% of cases) and showed criteria of lentigo maligna melanoma (LMM) in 52.4% of cases. Regression, grey colour, irregular hyperpigmented areas and criteria of LMM typified melanomas on sun-damaged skin, whereas tumours located on non-sun-damaged areas were often characterized by irregular pigmentation (blotches). RCM, implemented to dermoscopy, correctly diagnosed 10/12 melanomas and 3/5 naevi. Conclusion: Neck melanoma has peculiar clinical and dermoscopic aspects that could help clinicians to distinguish it from naevi and to diagnose melanoma earlier.

Objective: The best strategy of care for biphasic malignant pleural mesothelioma (Biph-MPM) is controversial. In this study, a large dataset of Biph-MPM cases was reviewed to identify prognostic factors and to evaluate the role of a multimodal approach, including cancer-directed surgery. Methods: A total of 213 patients with Biph-MPM treated at 4 tertiary centers who experienced MPM from January 2009 to December 2016 were selected, and clinical, pathologic, and surgical information was retrieved. A Cox regression model was used to identify predictors of survival, and the Kaplan–Meier method was used to summarize overall survival. Results: The mean age and the male/female ratio were 68.4 ± 9.5 years and 5:1, respectively. Tumors were assigned to stages I (127, 59.6%), II (3, 1.4%), III (76, 35.4%), and IV (7, 3.3%) according to the Eighth Tumor, Node, Metastasis (TNM) edition. A multimodal treatment including pleurectomy/decortication was performed in 58 patients (27.2%), chemotherapy alone in 99 patients (46.5%), and best supportive care in 56 (26.3%). The median overall survival was 11 months. A univariate analysis revealed that survival was significantly associated with the percentage forced expiratory volume in 1 second (P < .0001), performance status (P = .0002), multimodal treatment including surgery (P < .0001), and TNM stage (P = .011). A multivariable analysis confirmed performance status, percentage forced expiratory volume in 1 second, TNM, and a multimodal approach as independent variables affecting long-term survival. Conclusions: Despite the overall poor prognosis of biphasic histology, a multimodal approach, including cancer-directed surgery, is associated with improved long-term results in very selected patients with Biph-MPM.

Introduction Pulmonary Sarcomatoid Carcinoma (PSC) is a rare subset of NSCLC, associated with worse prognosis and resistant to platinum-based regimens. Recent investigations have shown high levels of PD-L1 expression in PSC, providing a rationale for the potential use of immunotherapy. In this study, we investigated whether the PD-L1 expression was related to clinico-pathologic and molecular characteristics. Materials and methods Fortythree surgically-resected PSCs were selected from 2006 to 2014 and clinical information retrieved. PD-L1 expression was analyzed by immunohistochemistry and correlated with the clinic-pathologic features and driver gene mutations analyzed by Next-Generation-Sequencing. Correlation of clinical, pathological and genetic variants with PD-L1 expression positivity were tested by Fisher’s exact test analysis. Results About 25% of PSCs showed a significant expression of PD-L1 (positive staining defined as staining in ≥10% of tumor cells). PD-L1 expression was associated with aggressive pathological features of PSCs including N2-involvement (PD-L1 positive in 83.3% of N2-PSCs vs in 16.2% of N0/N1-PSCs, p = 0.003) and presence of either local (p = 0.038) and distant metastases (p = 0.022). Furthermore, PD-L1 expression was significantly associated with the overall mutational load of the tumors (PD-L1 positivity only in PSCs with at least one mutational event) and in particular with the presence of KRAS mutation (PD-L1 positive in 44.4% of KRAS-Mut PSCs vs 12.0% in KRAS-Wild PSCs). The correlation between PD-L1 expression and KRAS-mutation were found at univariate analysis (p = 0.031), even considering PD-L1 as a continuous variable (p = 0.018), and confirmed at multivariate analysis (p = 0.035). The mutational status of the other genes explored in the NGS-panel (EGFR, APC, PTEN, PIK3CA, TP53 and STK11) did not correlate with PD-L1 expression. Conclusions PD-L1 expression significantly correlates with overall mutational load and KRAS mutational status in pulmonary sarcomatoid carcinomas.

Background Neck dissection is considered the treatment of choice in patients with lateral neck metastases from well-differentiated thyroid cancer. Methods A multicenter, retrospective review of patients who underwent therapeutic lateral neck dissection for well-differentiated thyroid carcinoma was carried out. Results The study included a total of 405 lateral neck dissections performed in 352 patients; 197 women (56%) and 155 men (44%). When considering ipsilateral neck metastases, levels IIa, IIb, III, IV, Va, Vb, and V (not otherwise specified) were involved in 42%, 6%, 73%, 67%, 11%, 31%, and 35% of cases, respectively. Five-year and 10-year overall survival (OS) were 93% and 81%, respectively. Age >55 years, pathologic T (pT)4 category, tumor diameter >4 cm, aggressive variants of well-differentiated thyroid carcinoma, endovascular invasion, and number of positive nodes >5 turned out to be the most important prognostic factors. Conclusion Neck dissection is a valid treatment option in the presence of neck metastasis from well-differentiated thyroid carcinoma. Levels IIa, III, IV, and Vb should always be removed.

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Methods: Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9±15.4 vs. 46.1±14.8; p

BACKGROUND Frozen histological sections are used for intraoperative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool that offers a promising and faster alternative to frozen histology. OBJECTIVES To evaluate prospectively in a clinical setting the accuracy of FCM vs. frozen sections in margin assessment of basal cell carcinoma (BCC). METHODS Patients with BCC scheduled for Mohs surgery were prospectively enrolled. Freshly excised surgical specimens were examined by FCM and then frozen sections were evaluated. Permanent sections were obtained, in order to validate the sample technique. A blind re-evaluation was also performed for discordant cases. Sensitivity and specificity levels, as well as positive and negative predictive values (PPV and NPV, respectively), were calculated and receiver-operating characteristic curves generated. RESULTS We enrolled 127 BCCs in as many patients (40·2% females). Seven hundred and fifty-three sections were examined. All BCCs were located in the head and neck area. In evaluating the performance of FCM vs. frozen sections, sensitivity was 79·8%, specificity was 95·8%, PPV was 80·5% and NPV was 95·7% [area under the curve 0·88, 95% confidence interval 0·84-0·92 (P < 0·001)]. Forty-nine discordant cases were re-evaluated; 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment. CONCLUSIONS We found high levels of accuracy for FCM vs. frozen section evaluation in intraoperative BCC margin assessment during Mohs surgery. Some technical issues prevent the wide use of this technique, but new devices promise to overcome these limitations.

Background Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. Objective The aim of our study was to describe the dermoscopic and confocal features of SNPF. Methods Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. Results The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. Conclusions The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.

Background Melanomas harboring common genetic mutations might share certain morphological features detectable with dermoscopy and reflectance confocal microscopy (RCM). BRAF mutational status is crucial for the management of metastatic melanoma. Objective To correlate the dermoscopic characteristics of primary cutaneous melanomas with BRAF mutational status. Furthermore, a subset of tumors has been also analyzed for the presence of possible confocal features that might be linked with BRAF status. Methods Retrospectively acquired dermoscopic and confocal images of melanoma patients in tertiary referral academic centers: Skin Cancer Unit in Reggio Emilia and at the Melanoma Unit in Barcelona. Kruskall-Wallis test, logistic regressions, univariate and multivariate analyses have been performed to find dermoscopic and confocal features significantly correlated with BRAF mutational status. Results Dermoscopically the presence of irregular peripheral streaks and ulceration were positive predictor of BRAF mutated melanomas with a statistically significance value while dotted vessels were more represented in wild type melanomas. None of the evaluated RCM features were correlated with genetic profiling. Conclusions Ulceration and irregular peripheral streaks represent dermoscopic feature indicative for BRAF mutated melanoma while dotted vessels are suggestive for wild type melanoma. This article is protected by copyright. All rights reserved.

Introduction Dermoscopic island (DI) is a dermoscopic clue for the diagnosis of thin melanoma (MM). However, its positive predictive value is about 50% and several naevi with DI are unnecessarily excised. Reflectance confocal microscopy (RCM) is a second level non-invasive imaging tool that increases diagnostic accuracy for MM. Objective To evaluate diagnostic RCM features of pigmented lesions typified by the presence of DI and calculate RCM diagnostic accuracy for MM diagnosis. Methods All lesions with DI were retrieved from a database of 1964 cases. RCM diagnoses were given without being aware of the histopathological diagnoses. The number of MMs among lesions presenting with DI and the sensitivity and specificity of RCM for MM were assessed. The frequencies of dermoscopic and RCM features were calculated to evaluate significant differences in naevi and MMs showing DI (Chi-square test). Independently significant RCM criteria for MM were identified by discriminant analysis. Results Sixty-three (3.2%) out of 1964 lesions presented DI. Among them, 30.2% were in situ MMs and 12.7% invasive MMs. Sensitivity and specificity of RCM for the diagnosis of MM in case of DI was 88.9%. Pagetoid cells (Wilks' lambda .804, P < 0.001) and atypical cells at dermo-epidermal junction (Wilks' lambda .762, P < 0.001) were identified to differentiate MM from naevi. Conclusion Our study confirmed that DI could be a sign of early MMs and underlined that RCM could be a good tool to discriminate MMs and naevi in the presence of DI because it can identify the presence of cytological atypia.

Angiosarcoma and anaplastic carcinoma are the most lethal neoplasms of the thyroid worldwide and share some similarities, which have led to a longstanding controversy on their etiopathological relationship. Thyroid angiosarcomas are characterized by vessel formation and an immunophenotype common to endothelial cells, while anaplastic carcinomas are partially or wholly composed of mesenchymal-like cells that have lost the morphologic and functional features of normal thyroid follicular cells. To investigate whether angiosarcomas represent the endothelial extreme of the differentiation spectrum of carcinomas or they are bona fide vascular neoplasms, we studied the clinico-morphologic and genetic characteristics of a series of 10 angiosarcomas and 22 anaplastic carcinomas. Immunohistochemically, among the endothelial markers, CD31 and ERG were the most consistently expressed in angiosarcomas. Among the markers of thyroid origin, PAX8 was the most reliable in anaplastic carcinomas, while TTF-1 reactivity was found in only 5% of anaplastic carcinomas and thyroglobulin was always negative. Pankeratin reacted with most angiosarcomas and anaplastic carcinomas and is therefore not useful in the differential diagnosis. Interestingly a mutated pattern of p53 immunostaining prompted a diagnosis of anaplastic carcinoma. To compare the genetic profile, we used the NGS approach to sequence hotspot regions within a panel of 57 genes. As a result, only a few mutations were found in angiosarcomas and all of them were single events (no TP53 or TERT mutation). On the other hand, anaplastic carcinomas were characterized by a higher number of mutations, and TP53 and TERT promoter mutations were the most frequent genetic alterations. The lack in angiosarcomas of the common mutations identified in anaplastic carcinomas supports a different genetic origin and strongly suggests that, in spite of a shared sarcomatous morphology and a similar clinical aggressiveness, angiosarcomas and anaplastic carcinomas rely on a completely different set of genetic alterations during their evolution.

Merkel cell carcinoma (MCC) is a cutaneous carcinoma with neuroendocrine differentiation. It arises typically on sun-exposed areas of elderly men as an asymptomatic, rapidly growing, red nodule. Although it is usually found as a solitary nodule, in almost one third of cases MCC may be associated with other malignancies such as basal cell or squamous cell carcinomas. Merkel cell carcinoma should be considered as differential diagnosis every time we have a rapidly growing, red nodule, arising in an elderly patient with signs of sun-damage. We report a case of MCC developing in association with a pre-existing Bowen's disease. The association between MCC and Bowen's disease is quite common and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation contributes to the etiology of both the malignancies.

BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles. CONCLUSIONS: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.

Background Nevi of special sites encompass a class of benign lesions characterized by the presence of atypical clinical and histopathologic features that can be difficult to distinguish from melanoma. Dermoscopy and reflectance confocal microscopy may improve the clinical assessment of melanocytic lesions in order to avoid unnecessary excisions. Objectives The aim of this study was to assess the value of specific dermoscopic and confocal criteria in distinguishing melanomas from nevi of the breast area. Methods Dermoscopic and confocal images from consecutive patients with at least 1 clinically and/or dermoscopically equivocal melanocytic skin lesion of the breast area were retrospectively evaluated. In this case-control study, only histopathologically-proven melanomas (cases) and nevi (controls) were included. Spearman's coefficients were first calculated to flag significant correlation; then univariate and multivariate logistic regression analysis were performed to assess which factors were independently associated with the histopathological diagnosis. Finally, a mixed dermoscopic/confocal score was created to distinguish nevi from melanomas on the breast area. Results The study population included 55 skin lesions of the breast area, 34 (61.8%) nevi and 21 (38.2%) melanomas. Among dermoscopic criteria, atypical network and irregular pigmentation resulted independently associated with melanoma diagnosis (OR: 11.1; 95%CI 1.0-119.9; P:.048 and OR: 6.5; 95%CI 1.1-37.5; P:.037, respectively). Furthermore, on RCM examination the presence of pagetoid cells was an independent positive predictor for melanoma (OR: 38.5; 95%CI 3.9-379.6; P:.002). The mixed score showed high levels of sensitivity and specificity, 95.2% and 82.4%, respectively, which were higher than dermoscopic and confocal evaluations alone. Conclusion The combined use of dermoscopy and confocal microscopy in the triage of pigmented lesions of the breast area may help in increasing the diagnostic accuracy and avoiding unnecessary excisions. This article is protected by copyright. All rights reserved.

Background Squamous cell carcinoma (SCC) of the skin is a highly prevalent neoplasm. The management and the prognosis of this tumor is dependent on its invasiveness and its grade of differentiation. Objectives To evaluate whether specific dermoscopic and reflectance confocal microscopy (RCM) criteria can predict the diagnosis of invasive SCC vs in situ SCC and poorly differentiated compared with well- and moderately differentiated SCC. Methods Dermoscopic and RCM images of SCCs were retrospectively evaluated for the presence of predefined criteria. Results Among 143 SCC, 121 cases had a complete set of images and thus were included in the study set. The head and neck area was the most frequently involved body site (74/121; 61.1%) followed by extremities (36/121, 29.7%) and trunk (11/121, 9.1%). Seventy tumors were in situ (57.8%), while 51 were invasive (42.1%), of these 11 were poorly differentiated (21.5%), 16 were moderately differentiated (31.3%), and 24 were well differentiated (47.0%). Chi-squared analysis demonstrated that invasive SCC were characterized by polymorphic vessels, erosion/ulceration, architectural disarrangement, speckled nucleated cells in the dermis, irregularly dilated vessels and absence of hyperkeratosis. Botton-hole vessels, white structureless areas and dotted or glomerular vessels were significantly associated with in situ lesions. Poorly differentiated SCC were typified by red areas, erosion/ulceration and architectural disarrangement. Well or moderately differentiated SCC were associated with white areas and speckled nucleated cells in the epidermis. Conclusion Clinical, dermscopic and RCM images provide useful information that should be integrated in order to achieve the optimal therapeutic management for the patient. This article is protected by copyright. All rights reserved.

Capsular naevi (CNs) in lymph nodes (LNs) are relatively common, occurring in 3-22% of patients who undergo LN surgery for melanoma. Naevus count is one of the principal risk factors for melanoma, as well as a prognostic factor in melanoma patients. However, little is known about the occurrence of CN in melanoma patients on the basis of their naevus count. A case-control study was performed, to look at the naevus count differences between CN-positive and CN-negative melanoma patients. Cases (CN positive) were matched for age, sex and Breslow thickness with controls (CN negative). Total naevus count was recorded at diagnosis and compared between the two groups. This study was conducted in a tertiary referral academic centre for skin cancer. Twenty-two positive CN patients were matched with 22 negative CN patients. The mean Breslow thickness was 2.66 mm (range: 0.6-9). Positive CN patients were significantly associated with an increasing naevus count on their skin (P=0.02). Patients with more than 100 naevi reported an odds ratio of 7.78 on having a CN compared with patients with fewer than 50 naevi on their skin (P=0.02). An increased melanocytic migration to LNs might be the reason for the association between CNs and a high number of melanocitic naevi on the skin. This could shed some light on the physiology of melanocytes and could be an easy way to predict patients at greater risk of having CNs.

Background The latest AJCC classification has included the number of mitoses as a factor for upstaging thin melanomas. Meanwhile, while dermoscopy has often been used to predict melanoma thickness, its value in predicting number of mitoses remains unknown. Objective Our aim is to evaluate the correlation between dermoscopic features and the presence of mitoses in a consecutive cohort of thin melanomas. Methods A case control study has been performed to identify specific dermoscopic parameters that could differentiate thin melanomas with 1 or more mitoses per mm2 from those without mitoses. Results Of 177 melanomas equal to or thinner than 1 mm, 131 (74%) lesions had no mitoses and 46 (36%) lesions had at least 1 mitosis × mm2. Dermoscopic features associated with the presence of 1 or more mitoses were the following: peripheral streaks (OR 4.11; 95% CI 1.94–8.71) and black colour (OR 4.70; 95% CI; 2.28–9.68). In contrast, atypical pigment network (OR (0.30; 95% CI 0.15–0.61)) and brown colour (OR 0.36; 95% CI 0.18–0.75) were associated to melanomas without mitoses. The same variables were also associated to the increasing number of mitoses at linear regression. Conclusion Black colour and peripheral streaks can predict the presence of mitoses in thin melanoma, while atypical pigment network and brown colour are associated to thin melanoma without mitoses.

Syringocystadenoma papilliferum is a benign adnexal neoplasm frequently seen in association with other adnexal tumours. We report the dermoscopic features of three cases of syringocystadenoma papilliferum developing in naevus sebaceus. Clinically the lesions were characterised by exophytic papillary structures. Dermoscopically, polymorphous vessels were the prevalent feature.

BACKGROUND: The management of basal cell carcinoma (BCC) depends, among other factors, on its histopathologic subtype. Although dermoscopic criteria of BCC have been investigated, the possible role of dermoscopy in predicting the tumor subtype remains unclear. OBJECTIVES: We sought to assess the diagnostic accuracy of dermoscopic criteria for differentiating superficial BCC (sBCC) from other BCC subtypes. METHODS: Dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver operating characteristic curves. RESULTS: In all, 77 sBCCs and 258 non-sBCCs were included. Maple leaf-like areas, short fine superficial telangiectasia, multiple small erosions, and shiny white-red structureless areas were potent predictors of sBCC, each making its diagnosis over 5-fold more likely. Conversely, the presence of arborizing vessels, blue-gray ovoid nests, and ulceration gave 11-fold, 15-fold, and 3-fold increased possibility for the diagnosis of non-sBCCs, respectively. Based on the results of the multivariate analysis, we propose a diagnostic algorithm that can predict the diagnosis of sBCC with a sensitivity of 81.9% and a specificity of 81.8%. LIMITATIONS: The retrospective design and the inclusion of only Caucasian patients are limitations. CONCLUSION: Dermoscopy is reliable in differentiating sBCC from other BCC subtypes.

To describe a case of bilateral conjunctival and cervical human papillomavirus (HPV)-related squamous neoplasia. A healthy immunocompetent 55-year-old lady came to our attention for prosecution of care of a right recurrent conjunctival squamous cell carcinoma. Upon examination, she was found disease-free in the right eye but displayed a left conjunctival intraepithelial neoplasia (CIN grade I) and low-grade cervical squamous dysplasia. HPV infection with genotypes 16 (right eye), 11 and 39 (left eye) and 39 (uterine cervix) was also detected. Simultaneous uterine and conjunctival HPV-related squamous neoplasia can occur in immunocompetent individuals. Auto-inoculation and repeated exposure to HPV could explain coexistence of different genotypes.

Summary Background Basosquamous carcinoma (BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathological features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). It is reported to have a nonspecific clinical presentation, which makes naked-eye diagnosis a challenge. Objectives To describe the dermoscopic patterns of BSC, which may facilitate early diagnosis and accurate management. Methods This was a retrospective evaluation of clinical and dermoscopic images of histopathologically proven BSC, collected from skin cancer centres in Australia (Perth), Greece (Thessaloniki) and Italy (Naples, Reggio Emilia). Results Twenty-two tumours were included in the study. Our analysis revealed that the dermoscopic pattern of BSC comprises BCC-related criteria, as well as features that are known to characterize invasive SCC. The most frequently detected criteria were: unfocused (peripheral) arborizing vessels (73%), keratin masses (73%), white structureless areas (73%), superficial scale (68%), ulceration or blood crusts (68%), white structures (64%), blue-grey blotches (59%) and blood spots in keratin masses (55%). Notably, all but one of the tumours exhibited at least one BCC-related plus one SCC-related dermoscopic feature. Conclusions BSC appears to have overlapping dermoscopic features of BCC and invasive SCC, and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. Appreciation of the dermoscopic patterns of BSC might assist in the timely and accurate diagnosis and subsequent optimal management of this unusual and potentially metastatic skin tumour.

The relevance of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) as a negative prognostic factor is a subject of intense debate. This mutation has been associated with several clinicopathological features, but the lack of consistency among data does not support its usefulness as marker of tumor aggressiveness and poorer outcome. Due to the genetic heterogeneity of the tumor, both the occurrence and the allele percentage of the BRAF mutation should be considered to unravel this controversy.We aimed to evaluate the impact of the BRAF V600E mutation occurrence and the allele percentage on the metastatic process in PTCs.The presence and allele percentage of the BRAF mutation were determined by pyrosequencing in 132 cases of well-differentiated PTCs with (n = 37) or without lymph node metastases (LNMs) (n = 95) and in 40 LNMs matched with 35 PTCs.No significant differences were observed in either the occurrence or the allele percentage of V600E mutation between the 2 groups of PTCs with or without LNMs. The LNMs were heterogeneous for the V600E mutation as the primary lesions.In this study, the occurrence and percentage of the BRAF V600E mutated allele was not preferentially associated with the development of metastases and the average mutated allele percentage decreased as the tumor progresses from the primary site to the lymph node metastatic sites. These observations support the need to reevaluate the role of the BRAF V600E mutation as a negative prognostic marker in PTCs.

Objective: In cases of multinodular goiter with negative cytologic result, reasonable management options include surgical treatment, simple follow-up, or more recently introduced conservative therapies such as laser or radiofrequency ablation, and recombinant human thyroid-stimulating hormone-augmented radioiodine. For patients who are eligible for follow-up or nonsurgical treatments. The possibility that they may have an undiagnosed malignancy (false-negative [FN]-fine-needle aspiration cytology [FNAC] result or incidental thyroid cancer [ITC]) should be considered. The aim of our study was to asses. The risk of malignancy in patients known to have presumably benign thyroid disease.Methods: Surgical series of patients who underwent total thyroidectomy for benign disease between 2000 and 2010 at two Italian centers were reviewed. Patients with any preoperative suspicion of malignancy were excluded.Results: Histologic examination revealed that 84 of 970 (8.6%) thyroidectomized patients had malignancy (5% ITC and 3.6% FN-FNAC), with 89.8% of ITCs having a diameter 30 mm. Sixty-seven thyroid malignancy patients (79.8%) had stage I disease (American Joint Committee on Cancer criteria). The risk of FN-FNAC increases with increasing size o. The nodule, whil. The risk of ITC increases as nodule size decreases.Conclusion: The risk of malignancy in presumably benign thyroid disease cannot be overlooked, but can be minimized through skillfully performed ultrasonography (US) examination and FNAC. Once a patient with multinodular goiter is referred for follow-up or nonsurgical therapy, careful US surveillance is mandatory.

Background: The term ‘collision tumor' refers to the association of 2 or more different neoplasms within the same lesion. The association of a benign neoplasm with a malignant neoplasm is of particular significance and warrants diagnostic accuracy. Objective: The purpose of our study was to see if reflectance confocal microscopy (RCM) was a valuable tool when dealing with collision tumors. Methods: We retrospectively evaluated 24 histologically confirmed cases of collision tumors, which were initially assessed using dermoscopy and RCM. Results: The malignancy most commonly detected in association with collision tumors was basal cell carcinoma (BCC) (n = 13), followed by melanoma (n = 5, of which 2 collided with BCC) and squamous cell carcinoma in situ (n = 4). Seborrheic keratoses were the most common benign neoplasms found in association with collision tumors (n = 18), followed by nevi (n = 7). Dermoscopy revealed the malignant component in 14 out of 20 lesions compared to RCM, which revealed a malignant component in 19 out of 20 neoplasms. There was excellent concordance between RCM and histopathology with regard to the identification of a malignant component within a tumor (kappa value >0.9). Conclusion: The dermatoscope and the reflectance confocal microscope, when used in conjunction, are valuable tools aiding in the diagnosis of collision tumors.

Background: Eccrine poroma (EP) belongs to the group of benign adnexal tumors, but cases of eccrine porocarcinoma (EPC) arising on long-standing and untreated EP suggest a certain risk of malignant transformation. Objectives: To describe the clinical, dermoscopic and histopathologic features associated with different extremes in the spectrum of eccrine poroid neoplasms and to review the according literature. Methods: A retrospective analysis of patient characteristics and morphologic features associated with EP, EPC in situ and invasive porocarcinoma patients who attended two skin lesion clinics in Italy and Turkey between 2010 and 2011. Results: A total of 4 cases including 1 EP, 1 EPC in situ and 2 cases of invasive EPC in 4 patients were analyzed. Recent changes including bleeding, ulceration and sudden enlargement of a pre-existing lesion were associated with malignant transformation. Dermoscopically, polymorphous vessels consisting of coiled, hairpin and linear vessels were seen at all stages of progression. Histopathological findings of EPC in situ were limited to the epidermal component and were evident only at higher magnification. Conclusions: Clinicians and pathologists should carefully evaluate EPs with a recent history of change and erosion in order to avoid overlooking the potential development of EPC.

Intralesional (incision) biopsy for melanoma diagnosis can be warranted for large lesions or for those lesions whose in-toto excision leads to cosmetic and/or functional impairment. However, this diagnostic approach carries a risk of underdiagnosis, if a clinicopathologic diagnostic approach is not implemented. As a rule, in large pigmented lesions from special body areas (scalp and acral skin), clinicodermoscopic differential diagnosis of melanoma includes non-melanocytic skin lesions, traumatic skin changes, and nevi. The unique indication to incision biopsy for the differential diagnosis between nevus and melanoma is a relatively small nodular proliferation developing within a medium-large congenital nevus.

Thyroid fine-needle aspiration (FNA) cytology is the primary tool for the diagnostic evaluation of thyroid nodules. BRAF mutation analysis is employed as an ancillary tool in indeterminate cases, as recommended by the American Thyroid Association management guidelines. Hereby, we report the case of a 73-year-old woman who presented an 8-mm-size, ill-defined, left thyroid nodule. FNA resulted "suspicious for papillary thyroid carcinoma". BRAF mutation status was analyzed, and somatic BRAF (V600E) mutation identified. The patient underwent a total thyroidectomy. At histological examination, the nodule was composed of Langerhans cells, admixed with many eosinophils. A final diagnosis of Langerhans cell histiocytosis of the thyroid was made. Our case emphasizes the critical diagnostic pitfalls due to the use of BRAF (V600E) mutation analysis in thyroid FNA. Notably, BRAF (V600E) mutation is common in melanoma, colorectal carcinoma, lung carcinoma, ovarian carcinoma, brain tumors, hairy cell leukemia, multiple myeloma, and histiocytoses. Therefore, in cases of indeterminate FNA with unclassifiable atypical cells BRAF (V600E) mutated, the possibility of a localization of hystiocytosis or a secondary thyroid malignancy should be taken into account.

Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP-array approach, we quantified chromosomal copy number alterations (CNA) across the whole-genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma and, by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity, and lays the basis to define novel strategies for a more precise prognostic stratification of patients. This article is protected by copyright. All rights reserved.

A large number of cases of melanoma exhibit clinical and dermoscopic clues leading to the correct diagnosis; however, sometimes melanoma can mimic benign melanocytic and non-melanocytic lesions. We present a small series of melanomas in which additional clues provided by confocal microscopy increased the index of suspicion and prompted us to perform an excisional biopsy. Practical rules that are useful in difficult-to-diagnose melanomas are discussed.

Papillary thyroid carcinoma (PTC) often presents with two or more anatomically separate foci. A long-standing argument is whether this multifocality is the result of multiple independent tumors ("multicentricity") or of intrathyroidal spread originating from a single tumor mass, presumably through permeation of intrathyroidal lymph vessels. We reexamined this issue with a clonality assay and compared our results with those in the literature. A total of 27 nodules from 11 female patients with bilateral PTC treated with total thyroidectomy were investigated for clonality using the HUMARA assay. Eight of 11 cases were informative (72.7 %). All but one of tumor foci showed a monoclonal population. The outlier sample gave a value indicative of balanced X-inactivation in one nodule. The monoclonality was concordant in three patients, discordant in three, and mixed in two (with both concordant and discordant results). Interestingly, in both of the latter cases (composed of over two samples per case), the contralateral nodules were discordant. Moreover, all four ipsilateral nodules were concordant. The results of our study suggest that some cases of multifocal PTC are the result of true multicentricity, whereas others are the consequence of intrathyroid spread by an originally single tumor mass. These conclusions support those made in the past years on the basis of morphologic considerations. Specifically, the incidental finding of two or more microscopic foci of PTC widely separate from each other was felt to favor multicentricity, whereas the finding of multiple ipsilateral foci of PTC within vascular spaces, often accompanied by multiple lymph node metastases, suggested intrathyroid spread; the most striking manifestation of this phenomenon being seen in the diffuse sclerosing variant of PTC.

Ultrasound (US)-guided percutaneous laser ablation (LA) of benign thyroid nodules may be a potential alternative to surgery in patients with compressive symptoms, at high surgical risk, or in patients who refuse to undergo surgery. We evaluated the morphological effects of LA procedure on 22 patients and compared the cytological findings before and after LA with the histological features on surgical specimens. Twenty-two (4.9%; 19 women, three men, mean age 53.2 years) out of 452 patients treated with LA for benign thyroid nodules in our Hospital underwent surgery after LA procedure, either because nodule regrowth (treatment failure, n = 17) or indeterminate cytology (Thy3) after LA (n = 5). Morphological findings varied according to the time between LA and surgical intervention. Within 2 months, the area was occasionally cavitated and filled in with dark amorphous material. The inflammatory response was abundant and composed of neutrophils, lymphocytes, and macrophages. After 18 months or more since LA, the expected laser-induced histologic changes in thyroid morphology consisted of a well-defined area surrounded by a fibrous capsule and filled in by amorphous material. No significant pathologic features were found in the thyroid tissue adjacent to the treated area. Histological evaluation of thyroid tissues after LA shows that thermal damage is restricted to the ablated area, with no involvement of the nearby parenchyma. Our long-term histopathological findings indicate that LA treatment of benign thyroid nodules is safe, and patients undergoing LA may also be followed up by fine needle aspiration.

Purpose To evaluate the potential use of fluorescence confocal microscopy (FCM) for ex vivo diagnosis and excision margin assessment of conjunctival neoplasms. Design Validity study. Methods setting : Single institution. participants : Consecutive patients with clinically suspicious conjunctival lesions. intervention : Conjunctival lesions were excised in toto using a standard “no-touch technique” by a single surgeon (A.I.). Collected specimens were examined with a commercially available laser scanning fluorescence confocal microscope after immersion in a 0.6 mM solution of acridine orange dye for 10–20 seconds. Specimens were subsequently processed with standard histologic analysis. main outcome measures : FCM diagnosis of the nature and extension of conjunctival lesions. Results Sixteen consecutive patients were included in the study (11 male, 5 female; mean age 58.1 ± 26.1 years, range 10–90 years). The median time needed to process and analyze a sample with FCM was 15 minutes. Eleven of 16 lesions were identified by FCM as squamous (2 benign papillomas, 2 grade 2 conjunctival intraepithelial neoplasias, 7 in situ squamous carcinomas) and 5 as nonsquamous (1 pingueculum, 1 dermolipoma, 2 melanocytic nevi, 1 melanoma). In all cases FCM was able to detect horizontal and vertical extension of the lesion. All FCM findings were confirmed by corresponding subsequent histologic examination. Conclusions FCM provides a fast ex vivo preliminary diagnosis of suspicious conjunctival lesions with good histologic details and margin assessment, and may represent a novel tool for intraoperative and postsurgical management of conjunctival tumors. This is the first study to investigate ex vivo FCM application in ophthalmology.

This is a comparative proteomic study on biopsies from patients with ovarian cancer to identify potential diagnostic/prognostic biomarkers in both healthy and tumor tissue, interstitial fluid (normal interstitial fluid and tumoral interstitial fluid and peritoneal effusion. Protein expression/identification was evaluated by 2-DE and MS analysis: six proteins showed differential expression in tumoral interstitial fluid and tumor tissue compared to normal interstitial fluid and healthy tissue: five were found to be downregulated and identified as galectin 3, glutathione S-transferase A-2, retinol binding protein 1, phosphatidylethanolamine-binding protein and annexin 5, while the calgranulin, was significantly upregulated in all pathological samples, including the ascitic fluid. Validation of S100A8 overexpression in carcinoma tissue was obtained by immunohistochemistry. To our knowledge, this is the first study to report an over-expression of calgranulin by 2-DE associated with MS/MS analysis on surgical biopsy. The reduced expression of galectin 3 and retinol binding protein 1 in cystic fluid and serum of patients with early stage disease is confirmed in this study. The results highlight alterations in proteins that control cell-cycle progression and apoptosis, as well as factors that modulate the activity of signal transduction pathways. Moreover, this study suggests that calgranulin expression may be used as a diagnostic and/or prognostic biomarker.

BACKGROUND AND STUDY AIMS: The study aimed to investigate whether the 25G needle is superior to the 22G needle when used in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of solid lesions. PATIENTS AND METHODS: The study was a single-center randomized clinical trial. The setting was a tertiary referral hospital, where EUS-FNA of solid lesions was assisted by an on-site cytopathologist, who was blinded to the needle size. The main end point was the number of passes performed to obtain adequate samples. Crossover to the other type of needle was allowed after five passes, or when the gastroenterologist experienced difficulties in puncturing the lesions. RESULTS: A total of 129 solid lesions were randomized and data regarding 127 lesions were analyzed. The mean number of passes was 3.7 (± 1.9) in the 22G needle group and 3.8 (± 2) in the 25G needle groups (difference of means: 0.1; 95 %CI: – 0.59 to 0.79). Fifty-eight of 63 (92.1 %) and 60/64 samples (93.7 %) in the 22G and 25G needle groups respectively were adequate (difference: – 1.6 %; 95 %CI: – 12.1 % to 8.9 %). Crossover to the other type of needle was performed in 11/63 (17.5 %) and in 12/64 (18.7 %) lesions in the two groups respectively (difference: – 1.2 %; 95 %CI: – 16.2 % to 13.8 %). A crossover to the 25G needle was successfully performed in four masses in the uncinate process; these lesions were difficult to puncture using the 22G needle. CONCLUSIONS: Our study failed to demonstrate that the 25G is more effective than the 22G needle in EUS-FNA of solid lesions. However, targeting of lesions in the distal duodenum may be simplified by using the 25G needle.

A potential diagnostic pitfall in the management of patients with melanoma is the inability to recognize metastatic melanoma, especially if it shows unusual features. We describe a case of multiple epidermotropic metastatic melanoma, which finally recurred with an extensive chondroid differentiation. To our knowledge, this is the first description of a case of epidermotropic chondroid metastatic melanoma.