Actinic keratosis and squamous cell carcinoma: clinical and pathological features.

Actinic keratoses (AKs) are the most common keratinocytederived precancerous lesion in humans; they can be observed predominantly in fair-skinned individuals on sun-exposed surfaces. The primary risk factor for AKs is cumulative UV exposure from sunlight and/or tanning salons. AKs may present on a patient as a few detectable lesions. In addition to these, there are subclinical (invisible) AKs that are estimated to occur up to 10 times more often than visible AKs, since unprotected skin receives UV radiation from the sun. Clinical and subclinical AK lesions occurring in photo-damaged skin are called field cancerization. A field of change can be up to 7 cm around the primary lesions, resulting in lesions that are genetically similar. AKs are defined at the histologic level by dysplasia and consist of keratinocytes manifesting atypical nuclei that are enlarged, irregular, and hyperchromatic. The histopathologic changes noted in keratinocytic proliferative lesions involve disturbance of normal surface maturation. The degree and extent of keratinocytic atypia vary in these lesions. The atypical keratinocytes show enlarged nuclei with hyperchromasia, dyskeratosis and mitoses in any layer of the epidermis. In lesions of epidermal dysplasias, surface keratinocytic maturation is present, and a granular cell layer is usually noted. In intraepidermal carcinomas, there is full-thickness involvement of the epidermis by the atypical keratinocytes. While molecular techniques have improved our ability to distinguish squamous cell carcinomas (SCCs) from AKs, they have also reinforced the concept that non-melanoma skin cancers arise through a complex series of aberrations at the molecular level. AKs represent a spectrum along the continuum to invasive cancer. They are the most visible manifestation of field cancerization which creates a population of atypical cells with the potential to progress to invasive malignancy capable of metastasis. As the perilesional epithelium also has abnormalities due to photo exposure, understanding the existence of a "cancerization field" should be explained to the patients, reinforcing the importance of preventive clinical follow-up. The aim of the present review was to emphasize the histopathological aspect of the morphological spectrum in AK, and SCCs, also elucidating the clinicopathology of field canceriziation.

Cutaneous vasculitidis: histology and immunofluorescence.

Cutaneous vasculitis comprises a wide spectrum of diseases that involve predominantly the blood vessels and surrounding tissues of the skin. Few vasculitic syndromes have pathognomonic clinical, radiographic and/or laboratory findings; thus, confident and accurate diagnosis of vasculitis requires histological confirmation. Skin biopsy should be done, optimally within 24 to 48 hours after vasculitic lesions appear. Deep excision biopsy must be preferred. Direct immunofluorescence of lesional skin is helpful in the diagnosis of vasculitides in the light of a proper clinico-pathological setting and diagnostic in some peculiarly forms. Cutaneous histological patterns can be used to generate relevant clinical differential diagnoses, and, when coupled with patient's history, clinical and laboratory data, allow more precise and accurate diagnosis of vasculitic syndromes. This review will focus on histopathological and immunologic pattern of the more common cutaneous vasculitis syndromes, based on the 2012 Revised International CHCC.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease-free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy.

BACKGROUND: Neoplastic T-cell recruitment into the skin is a critical step in the pathogenesis of mycosis fungoides (MF), and the cutaneous T-cell attracting chemokine, CTACK/CCL27, might be involved. OBJECTIVES: To investigate the clinical and prognostic significance of CTACK/CCL27 levels in patients with early-stage MF. METHODS: Serum samples and skin biopsy specimens were collected from 15 patients at the time of diagnosis and after the end of treatment with psoralen plus ultraviolet A/interferon alfa-2b combination therapy. Serum samples were also collected from 20 healthy donors as controls. CTACK/CCL27 serum levels were analysed by enzyme-linked immunosorbent assays. CTACK/CCL27 tissue expression was determined by immunohistochemistry on skin biopsy specimens taken at diagnosis and after therapy. Event-free survival was taken as the primary clinical outcome. RESULTS: In patients with MF at diagnosis, CTACK/CCL27 serum levels were not significantly different from healthy controls, whereas CTACK/CCL27 expression in the skin was increased in 87% of cases compared with normal controls. After therapy, all patients obtained a clinical complete remission, serum levels did not change significantly and tissue expression remained abnormal in 80% of patients, even if complete histological remission was recorded. Serum levels were not significantly different in cases with different intensity of cutaneous immunostaining. Eight patients experienced a relapse: the combination of high CTACK/CCL27 levels both in sera and skin increased the probability of experiencing an event at 51 months from 36% to 83%. CONCLUSIONS: Our data seem to indicate that CTACK/CCL27 levels in skin and sera after therapy might be correlated with risk of recurrence.

Dermatoscopic features of cutaneous atypical fibroxanthoma: three cases.

Atypical fibroxanthoma (AFX) is an uncommon, low-grade, malignant, spindle-cell tumour of fibrohistiocytic histogenesis, which can mimic other malignant skin tumours, such as basal and squamous cell carcinoma (CC), melanoma, and Merkel cell carcinoma (MCC). Three cases of AFX were examined by dermatoscopy, which revealed white areas and an atypical polymorphous vascular pattern characterized by the concurrence of different structures: linear, dotted, hairpin, arborescent and highly tortuous vessels, irregularly distributed over the surface. Seborrhoeic elements and photoageing may be accompanying features depending on the anatomical location of the AFX. AFX may be added to the list of slightly pigmented, reddish, malignant cutaneous tumours, such as SCC, MCC, amelanotic/hypomelanotic melanoma and eccrine porocarcinoma, which display prominent and chaotic dermatoscopic neoangiogenetic features in more advanced stages of proliferation.

Opposed bilateral transposition flap: a simple and effective way to close large defects, especially of the limbs.

BACKGROUND: Excision of large tumours, particularly of the limbs, can be challenging because of problems related to wound repair. This is especially true of the lower legs, where skin is often tight and difficult to mobilize. Closure by flap, which would represent the first choice for defects usually between 12-15 mm to 38-40 mm diameter, is at risk of developing complications, such as end-flap necrosis or dehiscence due to skin tension. For larger defects, usually more than 40 to 45 mm diameter, grafting still remains the only realistic option in the majority of cases, with all the various problems associated with this procedure, such as lengthy healing times and the risk of developing leg ulcers, above all in elderly patients with impaired blood circulation. Second intention healing implies extraordinarily long healing times with often unacceptable delays in normal ambulation and activity. OBJECTIVE: To find an alternative to the usual repair techniques and to try to reduce the risk of complications. CONCLUSIONS: We developed a relatively simple but effective technique for the closure of large wounds resulting from the excision of tumours. Our technique consists of two longitudinal, parallel, transposition flaps obtained from two opposite sides of the wound, with major axes orientated in the cephalic-caudal direction. The two flaps are then rotated around two fulcra placed at two extremes of the wound by approximately 90 degrees . This relatively simple technique has never caused any of the ordinarily associated problems in terms of necrosis or ulcer development. In addition, dehiscence of sutures never occurred, given the fact that suture tension is minimal. Quick healing has resulted in the majority of cases, avoiding all the problems associated with grafting or other traditional flap techniques.

Dermoscopy of lichen planus-like keratosis: a model of inflammatory regression.

BACKGROUND: Lichen planus-like keratosis (LPLK) or benign lichenoid keratosis is an involuting cutaneous entity where regressing features are the histologic hallmark. Most authors consider LPLK as an heterogeneous spectrum of intraepithelial epidermal or melanocytic lesions, mainly pigmented, involuting by inflammatory regression. OBJECTIVE: The authors review the clinico-histologic definition and correlate with the dermoscopic features of LPLK. METHODS: Sixteen LPLK were clinically distributed into three types: plaque-like (PL), flat erythematous (FE) and flat pigmented (FP) type and evaluated with conventional dermoscopy. Dermoscopic features of regression were recorded as the presence of blue-white structures and vascular structures. The predominant distribution, size and colour of pigmented granules were also recorded. All cases were excised and submitted to histopathologic examination and subdivided into three groups according to the early, classic and atrophic subtypes. RESULTS: The FP (44%) and the FE (37%) types are diagnosed more frequently than the PL type (19%). PL type correlates better with the classic type. FE correlates mainly with early/atrophic types, while the FP nearly exclusively with the late atrophic type. Regressive features are present in all but one case with a predominance of blue areas (94%). Localized (55%) and diffuse (37.5%) granular pattern are presenting in all but one case. The diffuse granular pattern correlates with the FP type (5/6 cases), while the localized granular pattern is mainly present (6/9 cases) in the FE type. Vascular structures can be found in half of the cases and white scar-like depigmentation is just present in four cases. BWS and vascular structures present together are observed in four cases (25%). CONCLUSIONS: Our results show a large correlation among clinical, histologic and dermoscopic aspects of LPLK may be interpreted as a spectrum of cutaneous lesions going into inflammatory regression, showing different clinical and dermoscopic patterns according to the involuting stage. The early type of LPLK (FE) shows a localized granular pattern where regression is at the very early stage. The classic dermoscopic features of regressing lesion for LPLK (pigmented granular pattern) apply to the most frequent encountered pigmented atrophic flat type or classic pigmented type, where sometimes regression is advanced or almost complete and no clear diagnosis of a previous benign/malignant - epithelial or melanocytic lesion can often be given. Regressive dermoscopic features must be evaluated in the context of global and clinical pattern of the lesion. Nonetheless dermoscopy can close correlate with clinical incipient or complete regression and must prompt the need for eventual prophylactic surgical removal.

Dermoscopic observation of Bowen's disease.

BACKGROUND: In the literature no specific dermoscopic criteria have been described for the diagnosis of Bowen's disease (BD). OBJECTIVE/AIM: To assess the morphological findings of BD seen under dermoscopic observation. METHODS: Clinical and dermoscopic images of 14 patients affected by BD with various amount of pigmentation were obtained by means of Heine Dermaphot. Dermoscopic images were analysed by experienced observers applying the modified pattern analysis. RESULTS: The most frequently occurring dermoscopic features were found to be: multicomponent pattern (100%); atypical vascular structures (86.6%); absence of pigmented network (64.3%) or presence of pseudo-network (35.7%); irregular diffuse pigmentation or blotches of pigment (64.2%); irregularly distributed dots and globules (64.2%); focal/multifocal hypopigmentation (78.5%), scaly surface (64.2%) and haemorrages (26.6%). CONCLUSIONS: Dermoscopically, BD is mainly characterized by a multicomponent global pattern associated with a prominent vascular pattern (mainly dotted vessels) and a scaly surface. Although no specific dermoscopic criteria can be given for BD, epiluminescence can be a valuable aid in the diagnosis of such a mimicker lesion.

Diffuse scleroderma occurring after the use of paclitaxel for ovarian cancer.

Acase of diffuse scleroderma in a 56-year-old woman who received paclitaxel for the treatment of a metastatic ovarian cancer is presented. The clinical cutaneous alterations, as well as the capillaroscopic and histological findings, were indistinguishable from those encountered in definite systemic sclerosis (SSc). In contrast to SSc, Raynaud's phenomenon and cutaneous calcinosis were absent and antinuclear antibodies were negative. The temporal relationship between the onset of skin involvement and administration of the drug may indicate an effect of paclitaxel.

Concordance between telepathologic diagnosis and conventional histopathologic diagnosis: a multiobserver store-and-forward study on 20 skin specimens.

OBJECTIVE: To study the validity and feasibility of transferring images of cutaneous biopsy specimens via e-mail to remote physicians active in dermatopathology for teleconsultation. DESIGN: Twenty skin specimens previously diagnosed at the Department of Dermatology, University of Graz, Austria, were subsequently sent for teleconsultation using the store-and-forward method. For each case, 3 or 4 images at different magnifications were sent by e-mail to 16 colleagues (11 dermatopathologists and 5 pathologists) in 15 centers in 6 different countries. Six weeks later each observer received the hematoxylin-eosin-stained specimens to render a conventional diagnosis. SETTING: Dermatopathology and pathology units within institutional and private settings. MATERIAL: Twenty small skin biopsy specimens of cutaneous diseases were selected randomly from a study set of 80. MAIN OUTCOME MEASURE: Concordance between telepathologic diagnoses and conventional histopathologic diagnoses of 20 skin specimens. RESULTS: On average, 78% of the telediagnoses were correct (range, 60%-95%), whereas 85% of the conventional diagnoses were correct (range, 60%-95%). A perfect diagnostic concordance was obtained in 7 (35%) of 20 cases, and a significant difference was identified in only 1 case. CONCLUSIONS: Results suggest that telepathology performed by physicians active in dermatopathology may serve as a reliable technique for the diagnosis of cutaneous diseases when experts in dermatopathology are not available locally. Furthermore, teledermatopathology is attractive because it provides an opportunity to obtain timely consultation on difficult cases.

Cutaneous carcinomas and preinvasive neoplastic lesions. Role of MMP-2 and MMP-9 metalloproteinases in neoplastic invasion and their relationship with proliferative activity and p53 expression.

BACKGROUND: Metalloproteinases (MMPs) are thought to be involved in the process of destruction of basement membranes and stromal invasion by neoplastic epithelial cells. AIMS: In order to investigate the role of MMPs in cutaneous oncogenesis we studied the expression of MMP-2 and MMP-9 in 34 cases of epidermal preinvasive neoplastic lesions and invasive carcinomas. We also studied their relationship with the expression of tissue inhibitors of MMPs and with proliferative activity and p53 expression in neoplastic epithelial cells. RESULTS: MMP-9 was found to be focally expressed by neoplastic epithelial cells at the infiltrative edges in microinvasive carcinomas and in dyskeratotic foci in Bowen's disease and widely invasive carcinomas. Gradation of Mib-1 positivity and p53 expression was found with increasing abnormality in the spectrum of malignancy. CONCLUSIONS: Our results seem to suggest the involvement of MMPs in microinvasive carcinomas, which show also low proliferative activity and p53 expression, whether other factors seem to be more important in widely invasive carcinomas.

Calciphylaxis in two patients with end-stage renal disease.

Fatal calciphylaxis (CPX) occurred in two 71-year-old females both requiring haemodialysis for end-stage renal disease. Case 2 also had an associated follicular lymphoplasmocytoid lymphoma. Although laboratory tests disclosed normal coagulation parameters, this woman had a striking cutaneous histological picture of vessel thrombosis and finally died of disseminated intravascular coagulation. CPX is a rare but potentially life-threatening complication of renal failure. The clinical picture is primarily characterized by livedoid purpura with subsequent cutaneous ischaemia and painful ulcerations. Cutaneous ischaemic phenomena are sustained by a progressive process of vascular calcification and thrombosis involving small to medium size arteries of the dermis and subcutis. Although not yet clearly explained, the pathogenetic role of a predisposing hypercoagulability state is currently the most frequently considered hypothesis.

Madura's foot: report of a case caused by Madurella mycetomatis.

We present a case of mycetoma by Madurella mycetomatis on the foot of a Chinese young man, living in Italy for more than ten years. Clinically the lesion closely resembled and was initially misinterpreted as a vascular neoformation. We analyze the histological and morphological features of the Madurella mycetomatis infection through which we managed to type the etiological agent. Our case is worth reporting because of the rarity of this disease in Europe and the unusual clinical presentation. It also offers the opportunity to stress the need for the clinical suspicion of this dermatosis, considering the increase of immigration towards our regions.

Urticaria as a presenting manifestation of adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a rare disorder of unknown aetiology, characterised by high spiking fever, an evanescent, erythematous, maculopapular rash, arthralgia or arthritis, lymphadenopathy, hepatosplenomegaly, sore throat and serositis. It is associated with marked leukocytosis, high erythrocyte sedimentation rate, increased level of serum ferritin and negative rheumatoid factor and antinuclear antibody tests. Here we report a patient in whom an urticaria-like rash was an uncommon presenting clinical feature of AOSD. To our knowledge, this association has only been reported once before.

Low dose interferon-alpha2b combined with PUVA is an effective treatment of early stage mycosis fungoides: results of a multicenter study. Cutaneous-T Cell Lymphoma Multicenter Study Group.

BACKGROUND AND OBJECTIVE: The early stages of mycosis fungoides (MF) can be treated but not cured by photochemotherapy (PUVA) alone; some recent studies of the effect of a combination of human interferon-alpha (IFN(alpha)) and PUVA reported a high degree of response. The aim of our study was to evaluate the activity of a low dose of IFN-alpha2b combined with PUVA. DESIGN AND METHODS: Twenty-five patients were included: 16 men and 9 women aged between 23-80 years; 19 patients ahd stage I and 6 stage II disease. In the induction phase, the dose of IFNalpha was gradually raised over 6-8 weeks to the target dose of 18 MU/week; in the maintenance phase, the combination with PUVA allowed IFNalpha to be reduced to a maximum dose of 6 MU/week; in this way the cumulative administration of IFNalpha and PUVA was considerably lower than in similar combination protocols. Treatment success was analyzed in terms of freedom from treatment failure (FFTF). RESULTS: After the induction phase 9/25 patients (36%) achieved complete remission (CR) and 15/25 (56%) achieved partial remission (PR). One to five months from the beginning of the maintenance phase, a CR was recorded in 19/25 patients (76%) and a PR in 5/25 patients (20%) accounting for an overall response rate of 96%. The median of FFTF was not reached; probability of FFTF was 82% at 12 months and 62% at 24 months. Disease free survival projected to 48 months was 75%. INTERPRETATION AND CONCLUSIONS: Even with low doses of IFNalpha plus PUVA it is possible to achieve excellent clinical responses,many of which are long-lasting, in patients with early MF.