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Background/objectives: Melanoma has become a major public health problem worldwide and its incidence in individuals of Caucasian origin continues to rise. The objective was to determine historical changes in thickness, melanoma proportions and anatomical site of presentation over a 25-year period in our Department., Methods: This was a historical retrospective study (January 1985 to December 2009). Only patients born and living in Italy were considered. The following parameters were evaluated: age, gender, year of diagnosis, site of primitive lesion (head, back, chest, anterior and posterior upper limbs, anterior and posterior lower limb, and acral sites) and Breslow thickness of the lesion., Results: In the 25-year period, 993 cases of melanoma were diagnosed. The total number of cases per year tripled between 1985-1989 and 1995-1999 and more than doubled between 1995-1999 and 2005-2009. Our results also revealed that thicker melanomas were more frequent in elderly patients and on parts of the body that cannot be readily self-inspected., Conclusion: The importance of observation of the posterior parts of the body is stressed, since not only did most melanomas arise in these sites but the diagnosis of lesions in these sites is often delayed., (© 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Various authors have suggested that information from longitudinal observation (follow-up) of dynamic changes in atypical melanocytic pigmented skin lesions (MPSL) could enable identification of early malignant melanoma escaping initial observation due to an absence of specific clinical and dermoscopic features. The aim of our retrospective study was to determine the existence of numerical variables regarding changes in MPSL that could be useful to differentiate early melanomas and atypical nevi. The study was carried out in two Italian dermatology Centres. Digital dermoscopy analyzers (DB-Mips System) were used to evaluate dermoscopic images of 94 equivocal pigmented skin lesions under observation for 6-12 months and then excised because of changes across time (29 melanomas and 65 nevi). The analyzer evaluates 49 parameters grouped into four categories: geometries, colours, textures and islands of colour. The ROC curve designed on the 49 digital dermoscopy analysis parameters showed good accuracy. At sensitivity (SE) = specificity (SP), it correctly classified 89.3% of cases. When objective pigmented skin lesion parameters were considered together with their objective changes over 6-12 months, a decisive increase in discrimination capacity was obtained. At SE = SP accuracy was 96.3%. Analysis of the parameters of our model and statistical analysis enabled us to interpret/identify the most significant factors of modification and differentiation of lesions, providing quantitative insights into the diagnosis of equivocal MPSL and demonstrating the utility of objective/numerical follow-up.

Angiogenesis is critical in melanoma progression and metastasis and relies on the synthesis and release of proangiogenic molecules such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factors (FGFs). S100A13 is a small calcium-binding protein that facilitates the release of FGF-1, the prototype of the FGF family. S100A13 is upregulated in astrocytic gliomas, in which it correlates with VEGF-A expression, microvessel density and tumor grading, and promotes a more aggressive, invasive phenotype in lung cancer-derived cell lines. To investigate the involvement of S100A13 in human cutaneous melanoma, we analyzed a series of 87 cutaneous melanocytic lesions: 14 common acquired melanocytic nevi, 14 atypical, so-called 'dysplastic' nevi, 45 melanomas (17 radial growth phase and 28 vertical growth phase) and 14 melanoma metastases. Main clinical and pathological features, including histotype, Breslow thickness, Clark's level and outcome were recorded. Microvessel density was determined with CD105/endoglin staining. Semiquantitative determination of S100A13, FGF-1 and VEGF-A protein expression was obtained by immunostaining. Quantification of S100A13 mRNA was achieved by real-time PCR. We found that S100A13 was expressed in melanocytic lesions; compared with benign nevi, S100A13 protein expression was significantly upregulated in melanomas (P=0.024), in which it correlated positively with the intensity of VEGF-A staining (P=0.041) and microvessel density (P=0.007). The level of expression of S100A13 mRNA also significantly increased with progression of disease, from radial growth phase (0.7+/-0.7) to vertical growth phase (3.6+/-3.1) to metastases (7.0+/-7.0) (P<0.001). Furthermore, S100A13 mRNA correlated positively with VEGF-A (P=0.023), TNM stage (P=0.05), risk of relapse (P=0.014) and status at follow-up (P=0.024). In conclusion, S100A13 is expressed in melanocytic lesions when the angiogenic switch occurs and it may cooperate with VEGF-A in supporting the formation of new blood vessels, favoring the shift from radial to vertical tumor growth. Therefore, S100A13 may represent a new angiogenic and prognostic marker in melanoma.

Beclin 1 and LC3 autophagic genes are altered in several human cancer types. This study was designed to assess the expression of Beclin 1 and LC3 in cutaneous melanocytic lesions, in which they have not yet been investigated. In melanoma, we correlated their expression with conventional histopathologic prognostic factors. In 149 lesions, including benign nevi, dysplastic nevi, radial growth phase melanomas, vertical growth phase melanomas, and melanoma metastases, proteins were evaluated by immunohistochemistry, and, in representative cases of benign nevi, vertical growth phase melanomas and melanoma metastases were evaluated by Western blotting. In most lesions, messenger RNA level was also assessed by real-time reverse transcriptase polymerase chain reaction. Both genes were expressed in all the investigated conditions. Beclin 1 cytoplasmic protein and messenger RNA, as well as LC3 messenger RNA, significantly decreased with tumor progression (P < .05). The percentage of cases with high cytoplasmic expression of beclin 1 from 100% in benign nevi declined to 86.4% in dysplastic nevi, 54.5% in radial growth phase melanomas, 54.3% in vertical growth phase melanomas, and 26.7% in melanoma metastases. The lowest expression of LC3 II protein was observed in melanoma metastases (53.3% of cases) (P < .05); LC3 II protein overexpression was, however, found in several nonbenign lesions, with the highest percentage (45.5%) in radial growth phase melanomas. LC3 II protein expression was inversely correlated to thickness, ulceration, and mitotic rate. In a multivariate analysis, messenger RNAs for both genes discriminated between nonmalignant (benign and dysplastic nevi) and malignant (radial, vertical growth phase melanomas, and melanoma metastases) lesions. Our results, therefore, indicate that beclin 1 and LC3 II autophagic gene expression is altered also in melanocytic neoplasms., (Copyright 2010 Elsevier Inc.)

The management of unresectable metastatic melanoma is a major clinical challenge because of the lack of reliably effective systemic therapies. Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has recently been proposed as a strategy to enhance cell-mediated immune responses to cancer, and clinical trials have demonstrated that anti-CTLA-4 therapy can produce durable outcomes with different response patterns than cytotoxic chemotherapy. We enrolled eight out of 155 patients with advanced melanoma in a multicentre phase II trial that evaluated the activity and tolerability of ipilimumab, a fully human, anti-CTLA-4 monoclonal antibody ( www.clinicaltrials.gov ; NCT00289627; CA184-008). Here we report our experience with three of these patients, who experienced progressive disease after a variety of previous therapies, including prior immunotherapies, and who achieved good outcomes with ipilimumab. One patient had a partial response ongoing at 17+ months on ipilimumab despite failure with four prior therapies, and the other two patients showed durable stable disease, both still ongoing at 17+ and 20+ months, respectively. The patient achieving a partial response experienced no side effects while receiving ipilimumab. The other two patients developed immune-related adverse events (irAEs) including rash (one case; grade 2) and diarrhoea (both cases; grades 1 and 2, respectively); the histopathology of colon biopsy samples from both was suggestive of colitis, with an abundant CD8+ T-cell infiltrate. Nausea, vomiting and acute pancreatitis were also observed in one patient. In addition, immunohistochemical findings of a dense CD8+, TIA1+ and granzyme B+ lymphoid infiltrate within a biopsied lesion provide indirect evidence of functional T-cell activation induced by treatment. These case reports highlight the potential for anti-CTLA-4-based therapy in previously treated patients with advanced melanoma. Moreover, because the patterns of response to ipilimumab differ from chemotherapy, we need to understand how and when patients may respond to treatment so that appropriate clinical decisions can be made.

Background: Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions., Methods: We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis., Results: Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells., Conclusion: An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma.

Calpains are cysteine proteases comprising members ubiquitously expressed in human tissues and other tissue-specific isoforms. Alterations of calpain 3 (p94), the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and IS2), are strictly associated to the limb-girdle muscular dystrophy type 2A, in which a myonuclear apoptosis has been documented. Our recent demonstration of a proapoptotic role of ubiquitous calpains in drug-induced apoptosis of melanoma cells prompted us to investigate the expression of calpain 3 in human melanoma cell lines undergoing apoptosis and in melanocytic lesions. In melanoma cell lines, we have identified two novel splicing variants of calpain 3 (hMp78 and hMp84): they have an atypical initiation exon and a putative nuclear localization signal, the shorter one lacks IS1 inset and both proteins are extremely unstable. Virtually, both isoforms (prevalently as cleavage forms) are localized in cytoplasm and in nucleoli. In cisplatin-treated preapoptotic cells, an increase of both transcription and autoproteolytic cleavage of the novel variants is observed; the latter event is prevented by the inhibitor of ubiquitous calpains, calpeptin, which is also able to protect from apoptosis. Interestingly, among melanocytic lesions, the expression of these novel variants is significantly downregulated, compared with benign nevi, in the most aggressive ones, i.e. in vertical growth phase melanoma and, even more, in metastatic melanoma cells, characterized by invasiveness properties and usually highly resistant to apoptosis. On the whole, our observations suggest that calpain 3 variants can play a proapoptotic role in melanoma cells and its downregulation, as observed in highly aggressive lesions, could contribute to melanoma progression.

Tumour-infiltrating lymphocytes (TILs) represent the local immune response to cancer, however, their correlation with tumour behaviour is not unanimously considered in the literature. Most studies have not characterized TILs, that are known to comprise distinct subsets, bearing different roles in the complex tumour microenvironment. Characterization of patient lymphocytes has been mainly performed in peripheral blood, that is not always representative of the local immune status. Only few investigations have been performed at the tissue level in cancer, including melanoma. TILs encompass different populations of effector and regulatory T cells (Tregs), and the relevance of the latter in tumour progression is widely accepted. The transcription factor gene product FOXP3 is considered the most reliable marker of Tregs. However, it has not been extensively evaluated in primary cutaneous melanoma. We analyzed 66 vertical growth phase primary cutaneous melanomas, aiming at finding differences in TIL subsets between two groups of cases, that behaved differently in terms of local recurrence. In our study, the percentage of Tregs, as characterized by CD25 and FOXP3 expression, both among tumour cells, inside tumour parenchyma and at its periphery, and among TILs, at the tumour-stroma boundary, was significantly higher in cases that recurred than in those that did not (p=0.00065; p=0.00014; p<0.00001, respectively). TIL characterization by immunohistochemistry in melanoma diagnostic reports, could add further information. The analysis of a larger series of patients and correlation with other clinical parameters, such as distant metastases and/or patient survival, are mandatory for validating its use as a prognostic indicator.

Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in various biological processes. Although MIF's functions in cancer have not been completely elucidated, its expression has usually been correlated with tumour progression and aggressiveness, and it is currently discussed as a new promising target for novel therapies. Recent studies seem to confirm its active role in melanoma pathobiology; however, its expression has not yet been extensively studied in melanocytic tumours. We evaluated MIF protein expression in 126 skin lesions, including benign and atypical nevi, melanoma and melanoma metastases. In 55 cases, we also assessed MIF mRNA expression by real-time RT-PCR. Benign nevi were subdivided into nevocytic and Spitz/blue types; and melanomas into the radial, and vertical growth phase. A strong cytoplasmic MIF positivity was found in most samples, although it was more heterogeneous in malignant tumours; MIF nuclear expression characterized Spitz/blue nevi, atypical nevi, melanomas and metastases. All samples expressed MIF mRNA but it was significantly lower in benign nevi vs atypical nevi, melanomas and metastases (p=0.001; p<0.0001; p=0.002, respectively). Our study shows a widespread distribution of MIF among melanocytic tumours. Whereas we observed a trend towards higher expression levels of mRNA in atypical and malignant tumours, MIF protein was highly expressed in all lesions, although limited to the cytoplasm in most benign nevi. These observations suggest differences in MIF protein storage, subcellular location and properties in most benign nevi vs atypical and malignant tumours that should be confirmed by further investigation and correlation with clinical outcome.

Composite cutaneous haemangioendothelioma is a recently characterized rare tumour of vascular origin. As there are only a few reported cases, the biological behaviour of the tumour and appropriate therapeutic approaches are not yet clear. We report a new case of composite cutaneous haemangioendothelioma and discuss prognostic and therapeutic aspects of this neoplasm.

Background: Striated palmoplantar keratoderma or Brunauer-Fohs-Siemens syndrome is a very rare, focal, nonepidermolytic palmoplantar keratoderma with autosomal inheritance. Unlike other palmoplantar keratodermas, no association with visceral or skin cancer has ever been reported., Objective: We report a case of malignant melanoma arising in the hyperkeratotic lesions on the right heel of a patient with striated palmoplantar keratoderma. The lesion was completely excised; our patient also underwent sentinel lymph node biopsy and then was treated with high-dose interferon adjuvant therapy., Methods: Sentinel lymph node biopsy incision was made in elliptical fashion, long enough to harvest a full-thickness skin graft to cover the wide local excision defect. The skin graft was defatted by sharp dissection. Several perforations were made in graft and it was secured in place with sutures and bolster dressing., Results: At follow-up, the grafted skin showed hyperkeratotic changes but no local or systemic signs of the disease was observed., Conclusion: The association between striated palmoplantar keratoderma and acral melanoma is discussed.

Background: The term 'common mole', often used to describe a subset of benign pigmented skin lesions, is traditionally defined on the basis of morpho-chromatic features. In recent years, certain research groups have developed equipment and methods, such as digital dermoscopy analysis, that enable objective evaluation of pigmented skin lesions., Objective: In this study we use a digital dermoscopy analyser trained for the recognition of pigmented skin lesions to compare the subjective definition of 'common' and the mathematical concept of 'close to the mean of measurements'., Methods: A subset (100) of digital images of flat pigmented lesions, obtained in daily practice, were classified by trained and non-expert clinicians as common moles (60) or clear-cut melanoma (40), and processed with a DB-Mips analyser. The resulting parameters, validated by a classifier, were used to evaluate Hotelling's T2 multivariate distances from the mean., Results: 'Common' moles could not be clearly defined in terms of closeness to the means of objectively evaluated parameters. Their diagnosis indudes many other evaluations and clusters of variables., Conclusion: The clinical semantics of the term 'common' does not conform to any unambiguous mathematical definition.

Background: Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level., Objectives: In this study, 32 melanocytic lesions were analysed by FISH, aiming at investigating possible telomere differences among various benign and malignant lesions and correlation with telomerase activity (TA) level., Methods: FISH was performed on paraffin sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma metastases and nine control samples of normal skin. Telomere mean maximum diameter (Feret max), area and number per nuclear area were calculated by image analysis on fluorescent images elaborated through KS400 and in situ imaging system (ISIS) for FISH analysis programs. Mean TA level was also calculated in all lesions and correlated with telomere parameters., Results: Telomere number per nuclear area was significantly lower in melanomas and metastases than in benign common and Spitz naevi and in control skin (7 small middle dot24 +/- 3.3; 6.11 +/- 3 vs. 14.46 +/- 5.6; 16.92 +/- 7.8; and 12.59 +/- 3.4, respectively; P < 0 .001). No significant differences were found for the other telomere parameters. In common and Spitz naevi, telomere number was positively correlated with Feret max (P = 0.046 and P < 0.0001, respectively). TA was significantly higher in melanomas and metastases than in the other groups (70.18 +/- 25.2; 105.07 +/- 30 vs. 2.16 +/- 2.4; 2 .99 +/- 2.1; 2 +/- 1.2, respectively; P< or = 0. 001) and it was inversely correlated with telomere number per nuclear area in melanomas (P = 0.0041). No other significant correlations were found., Conclusions: Encouraging results have been obtained from quantitative telomere evaluation in the diagnosis of melanocytic lesions, although an analysis of a larger number of cases would be necessary to provide more reliable data. An extreme shortening of some telomeres probably results in the decrease of telomeric signals and the lower mean number of detectable telomeres in melanomas and metastases. In melanomas, telomere number per nuclear area is also inversely correlated with TA levels. Quantitative FISH of melanocytic lesions could give more specific information at the cellular level in telomere and telomerase fields of investigation.

Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.

Telomerase plays a key role in carcinogenesis. It is activated in most immortal cell lines and human cancers, including cutaneous melanoma (CM). Increased cell proliferation and deregulation of the cell cycle occur in human cancers. Links between telomerase activity (TA), cell proliferation, cell death and expression of cell-cycle regulators have not been extensively elucidated in CM. In this study, we investigated TA, mitotic index (MI), apoptotic index (AI), Ki-67 and nuclear positivity of cyclins D1 and A (Ki-67+ N/1,000, cyclin D1+N/1,000, cyclin A+N/1,000) in 42 primary cutaneous melanomas (PCMs). TA was detected in all cases and directly correlated with MI, Ki-67+N/1,000, cyclin D1+N/1,000 and cyclin A+N/1,000 (p < 0.001); it was not correlated with AI. When subdividing PCMs into radial and vertical growth phase melanomas (RGPMs, VGPMs), a correlation was maintained only with MI (p < 0.005) and cyclin D1 +N/1,000 (p < 0.005). Although MI and Ki-67+N/1,000 were highly correlated with cyclin D1+N/1,000 and cyclin A+N/1,000 (p < 0.001) when considering all cases together, a high correlation was found in the RGPM and VGPM groups between cyclin A+N/1,000 and Ki-67+N/1,000 only (p < 0.001), thus suggesting that cyclin A is more closely correlated with cell proliferation than cyclin D1. Our results further support the association between TA, tumor cell proliferation and cyclin D1 and A expression in PCM, though it is possible that links between TA and proliferation, on the one hand, and TA and cyclin D1 expression, on the other, might occur following various pathways.

Telomerase is an enzyme which synthesizes the telomeres, TTAGGG repeats at the end of vertebrate chromosomes. Its activity is suppressed in the majority of somatic cells, whereas it is detectable in most tumor cell lines and human cancers. Telomerase activity has been evaluated in many tumors for diagnostic purposes, and an increase thereof has been found with tumor progression. In our study we used anonisotopic polymerase chain reaction (PCR)-based TRAP (telomeric repeat amplification protocol) method to quantify the level of telomerase activity in a series of cutaneous melanocytic lesions. Thirty-three benign nevi, 8 dysplastic nevi, 38 malignant melanomas, and 4 melanoma metastases were analyzed. Mean relative telomerase activity was low in benign nevi (3.5+/-2.9), and significantly increased in dysplastic nevi (13.1+/-6.8), malignant melanomas (49.8+/-29.6), and metastases (121.2+/-11.2). In addition to the evaluation of telomerase activity as a possible diagnostic tool, its increase with tumor progression also suggest a prognostic role in cutaneous melanoma.

Objectives: To use a digital dermoscopy analyzer with a series of "borderline" pigmentary skin lesions (ie, clinically atypical nevi and early melanoma) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis., Design: A total of 147 pigmentary skin lesions were histologically examined by 3 experienced dermatopathologists and identified as nevi (n = 90) and melanomas (n = 57). The system evaluated 36 variables to be studied as possible discriminant variables, grouped into 4 categories: geometries, colors, textures, and islands of color., Setting: University medical department., Patients: A sample of patients with excised pigmentary skin lesions (nevi and melanomas)., Main Outcome Measures: Sensitivity, specificity, and accuracy of the model for evaluating "borderline" pigmentary skin lesions., Results: After multivariate stepwise discriminant analysis, only 13 variables were selected to compute the canonical discriminant function., Conclusion: The present method made it possible to determine which objective variables are important for distinguishing atypical benign pigmentary skin lesions and early melanoma.

Ninety-six cutaneous melanomas (CMs) were investigated aiming at finding differences, if any, among the main four clinicopathological types, for Bcl-2, c-myc and p53 protein expression, and for tumor cell proliferation and death indices. Proliferation was assessed by calculating the mitotic index (MI, number of mitoses) and the MIB1 labelling index (M-LI, number of MIB1+ nuclei), and tumor cell death by calculating the apoptotic index (AI, number of apoptoses) among 1000 tumor cells. CMs were subdivided into thin (<1 mm) and intermediate thickness (1-4 mm) tumors. Bcl-2 expression did not significantly change among different types. c-myc Expression decreased especially in thicker superficial spreading (SSM) and lentigo maligna melanoma (LMM) types. p53 Expression was higher in nodular melanoma (NM) and in acral lentiginous melanoma(ALM), which also showed the highest degrees of proliferation. AI was significantly higher in thin rather than in intermediate thickness SSMs, LMMs and ALMs (8.4 vs. 2; 6.1 vs. 2.3, and 5.8 vs. 3.6, respectively). AI was low in thin (1.7) and intermediate thickness (1.9) NMs, which also showed high MI (3.9 and 4.5, respectively), and M-LI (16.7 and 2.9, respectively). Thin and intermediate thickness ALMs also showed high MI and M-LI (4.1 vs. 5.2 and 11.3 vs. 14.6, respectively). Bcl-2 is among genes which inhibit apoptotic death, whereas c-myc and p-53 genes promote this process. In CMs, no relation was found between Bcl-2 expression, MI, PI, and AI. All SSMs, LMMs, and ALMs with a high AI showed a high c-myc expression and were negative for p53. c-myc, Although highly expressed, did not promote a significant apoptotic death in NM type. Bc12, c-myc, and p53 were not equally expressed nor equally related to tumor cell turnover in all CMs, suggesting their different influence on the various types and stages, and the role of other factors in CM growth control.

The differential diagnosis between keratoacanthoma (KA) and well differentiated squamous cell carcinoma (WDSCC) is not always easy to perform. Seven cases of KA and seven cases of WDSCC have been here analyzed by morphometry on ultrastructural sections and compared with normal epidermis. Parameters expressing the cohesivity among epithelial cells (numerical and surface density of desmosomes; volume density of intercellular space) were significantly different in KA and WDSCC, so that they may be useful in differential diagnosis. The Authors also questioned the nature of KA, suggesting a continuum between this lesion and WDSCC.