Dermoscopy of non‐skin cancer nail disorders

Nail dermoscopy is becoming more and more frequently utilized for the diagnosis of nail disorders. It can be performed with handy dermoscope or with a video dermoscope, which allows magnifications of up to 200. Nail dermoscopy requires a good knowledge of nail anatomy and physiology and the pathogenesis of nail diseases: we have to know which part of the nail we have to look at! The nail is in fact not visible as a whole at one time, but its different parts should be observed, moving the lens back and forth and transversally. All nail disorders can be observed by dermoscopy. However, except for some diseases in which the technique really adds a lot to clinical examination, in most of the cases, nail dermoscopy only permits a better visualization of symptoms already evident to the naked eye. Dermoscopic features of nail signs are always very interesting and surprising, and may help in our understanding of nails.     

Involvement of non‐melanocytic skin cells in vitiligo

Despite melanocytes are the key players in vitiligo, a continuous cross‐talk between epidermal and dermal cells may strictly affect their functionality, in both lesional skin and non‐lesional skin. Focusing on this interplay, we have reviewed existing literature supporting evidence on cellular and functional alterations of surrounding epidermal keratinocytes, extracellular matrix (ECM) proteins and fibroblasts in the underlying dermal compartment that may contribute to melanocyte disappearance in vitiligo. We have also examined some clinical and therapeutic aspects of the disease to sustain the non‐exclusive involvement of melanocytes within vitiligo. As a result, a different and more complex scenario has appeared that may enable to provide better understanding about origins and progress of vitiligo and that should be considered in the evaluation of new treatment approaches.     

Highly pigmented Tg(Grm1) mouse melanoma develops non‐pigmented melanoma cells in distant metastases

Murine model systems are critically required tools for the investigation of unknown mechanisms of melanoma development and metastasis and for developing more efficient therapies. The Tg(Grm1)EPv melanoma mouse model is characterized by spontaneous development of pigmented cutaneous melanomas at hairless skin regions, with a short latency and 100% penetrance. Local metastasis was described in initial analyses; however, melanoma cells were not observed in distant organs. Here, we demonstrate that the established Tg(Grm1)EPv melanoma mouse model exhibits more extensive metastasis into distant organs than previously described. Disseminated cells undergo phenotypic changes, as we observed high numbers of non‐pigmented Grm1‐expressing melanoma cells within distant organs. As such changes during metastasis are common in human melanoma, our findings demonstrate that this mouse model represents an even more useful tool to study unknown mechanisms of metastasis in human melanoma than previously assumed.     

CASH algorithm versus 3‐point checklist and its modified version in evaluation of melanocytic pigmented skin lesions: The 4‐point checklist

Dermoscopy, in expert hands, increases accuracy, sensitivity and specificity in diagnosis of pigmented skin lesions of a single operator, compared with clinical examination. Simplified algorithmic methods have been developed to help less expert dermoscopists in diagnosis of melanocytic lesions. This study included 125 melanocytic skin lesions divided into melanocytic nevi, dysplastic nevi and thin melanomas (<1 mm). We compared the 3‐point checklist and CASH algorithm to analyze different pigmented skin lesions. Based on preliminary results, we proposed a new modified algorithm, called the 4‐point checklist, whose accuracy is similar to the CASH algorithm and whose simplicity is similar to the 3‐point checklist.     

Occupational exposure to non‐artificial UV‐light and non‐melanocytic skin cancer – a systematic review concerning a new occupational disease

Background: Although UV exposure is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), a systematic review analyzing the risk of occupational UV exposure is missing. Methods: Based on a systematic literature search in PubMed (until 05/2009) supplemented by hand search, the association between occupational UV exposure and SCC and BCC was analyzed. Literature search and data abstraction was done independently by 2 reviewers. The association between occupational UV exposure and cancer risk is presented as odds ratios (OR). Results: We identified 25 relevant epidemiologic studies (5 cohort studies, 17 case‐control studies, 3 cross‐sectional studies). 12 studies described a positive association between occupational UV exposure and risk of SCC with OR > 3 in 6 studies and OR 1.5–2.0 in another 6 studies. 3 studies did not find a relevant association (OR: 1.0–1.4). A significant positive association between occupational UV exposure and BCC was reported in 5 studies; 11 studies did not find a significant association. Conclusions: The association between occupational UV exposure and SCC is well and consistently documented epidemiologically (approximately 2‐fold increased risk), so that the criteria for a new occupational disease are fulfilled. The association with BCC is unclear due to significant methodological limitations in the published studies.     

BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumors

Although discussed using variable terminology, cutaneous BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumor (BIMT) has been considered a discrete diagnostic entity since 2011. Here, we review the initial genomic studies that identified these distinct melanocytic tumors and the clinical and histopathological features that define these tumors. These epithelioid, predominantly dermal, and melanocytic tumors present as erythematous nodules and histopathologically have features that may overlap with Spitz nevi and nevoid melanoma. There is no sex predilection, and cutaneous BIMTs can appear at any age; however, in most familial (germline mutant) cases patients have multiple cutaneous tumors with a first diagnosis in the second or third decade of life; ocular melanoma and other tumors are increasingly identified in these kindreds with germline BAP1 mutation. These tumors have been described with a myriad of terms including: Wiesner nevus, nevoid melanoma‐like melanocytic proliferation (NEMMP), BAP1 mutant Spitz nevus, BAP1 mutant nevoid melanoma, cutaneous BAPoma, and most recently cutaneous BIMT.     

Meta‐analysis of digital dermoscopy follow‐up of melanocytic skin lesions: a study on behalf of the International Dermoscopy Society

It has been demonstrated that dermoscopic monitoring of melanocytic lesions allows for the recognition of melanoma in early stages while minimizing the excision of benign lesions. However, it is still pending to determine the real impact of digital follow‐up in the clinical management of pigmented lesions. To assess the evidence of follow‐up of melanocytic skin lesions with digital dermoscopy in the management of individuals at risk for melanoma by performing a meta‐analysis. Medline database was screened, no limits in terms of date or language were applied. Original studies were selected when the following criteria were met: performed in clinical setting with clinical and dermoscopic evaluation made by physicians, data regarding population characteristics included, follow‐up strategy used described. Fourteen of 145 retrieved references were retained. Included studies account for a total of 5787 patients (mean 445 per study) and 52 739 lesions monitored (mean per study 4057; range 272–11 396) with a mean of 12 lesions monitored per patient; a total of 4388 lesions (8.3%) were excised. The mean length of follow‐up was 30 months. A mean of <1 lesion was excised per patient along the surveillance period. The number needed to monitor (NNM) ranged from 31 to 1008 (mean: 348) among eligible studies. For every additional month of monitoring, 1additional melanoma was detected. Using digital dermoscopy follow‐up, the proportion of in situ melanoma and thin melanomas are higher than expected in general population. Chances to detect a melanoma during surveillance increase as the length of follow‐up extends.     

Hypofractionated radiotherapy in older patients with non‐melanoma skin cancer: Less is better

Radiotherapy is a non‐surgical option for patients with non‐melanoma skin cancer. Lesions in middle‐aged to older patients with good performance status are typically prescribed 4–5 weeks of outpatient weekday treatment. Daily radiotherapy fraction sizes of 2–3 Gy are recommended to decrease the late cutaneous consequences such as in‐field hypopigmentation and telangiectasia. In elderly, often unwell patients, these concerns are less of an issue and larger fraction sizes (5–7 Gy), referred to as hypofractionation, can be delivered over a shorter time yet still achieve excellent in‐field control and improve a patient's quality of life and avoid the need for surgery. The three case studies presented illustrate this approach along with a review of the evidence to support this.     

Modified dermoscopic algorithm for the differentiation between melanocytic and nonmelanocytic skin tumors

BACKGROUND: The use of dermoscopy (dermatoscopy, epiluminescence microscopy, surface microscopy) improves the clinical diagnostic accuracy of skin tumors by applying different algorithms or scores. The first step in the dermoscopic evaluation is the differentiation between melanocytic and nonmelanocytic skin tumors. OBJECTIVE: To evaluate the diagnostic accuracy of the established dermoscopic algorithm (EDA) and the modified dermoscopic algorithm (MDA) for melanocytic versus nonmelanocytic skin tumors. METHODS: Two hundred forty-nine patients with melanocytic and nonmelanocytic skin lesions were included. Dermoscopic images of the tumors were taken with 10-fold magnification, followed by surgery and histopathology at the departments of Dermatology at the universities of Tuebingen, in Germany, and Naples, in Italy. Each lesion was classified using the EDA and MDA. In the MDA, accessory nipples and dermatofibromas were considered in particular. RESULTS: With the EDA, 225 of 249 (90.4%) skin tumors were correctly classified in one of the six groups. With the MDA, 237 of 249 (95.2%) were correctly classified. Improvement was achieved in 12 (4.8%) better classified skin tumors. In both algorithms, no melanoma was classified as a nonmalignant melanocytic tumor. All melanomas were classified in the group of melanocytic tumors and one melanoma was classified in the group of basal cell carcinomas. CONCLUSION: Both dermoscopic algorithms for the differentiation between melanocytic and nonmelanocytic skin tumors were simple and effective when applied step by step. The MDA is an improvement on the EDA with the classification of accessory nipples and dermatofibromas.     

PTH‐independent hypercalcaemia and non‐melanoma skin cancer

Background Recently, it became more evident that skin is a target for neuroendocrine signals. Aims (1) To evaluate the relationship between tumour aggressiveness and hypercalcaemia in patients with non‐melanoma skin cancer; (2) to identify clinical, functional, biological alterations caused by this setting; (3) calcium redistribution from extracellular fluids to intracellular compartments; (4) to describe several molecular aspects of hypercalcaemia development. Materials and methods This study was conducted between January 2000 and May 2009 in Dermatoveneorological Center, Bucharest. From the 1232 cases that were investigated, there were 32 patients with keratoachantoma, 468 patients with basal cell carcinoma, 412 patients with squamous cell carcinoma and 320 healthy volunteers. All the patients were screened by clinical and paraclinical examinations (haematology, biochemistry, immunology). After biochemical confirmation of hypercalcaemia, patients had endocrine tests, electrocardiography and imagistic approaches. Total serum calcium was measured in extracellular fluids (serum, urine) by spectrophotometric methods. Ionized calcium was calculated depending on total serum calcium and total proteins. Corrected serum total calcium (cTCa) levels were calculated using albumin and total serum calcium levels. In tumour tissues and intact skin, calcium was assayed by physical methods of analysis: Instrumental Neutron Activation Analysis (INAA), Proton‐Induced X‐ray Emission (PIXE). Intact PTH was measured by ELISA. Results PTH‐independent hypercalcaemia prevalence is low in SCC patients (1.21%). Hypercalcaemia manifestations are multiple including: digestive, renal, neuromuscular, and cardiovascular abnormalities. In these patients, intact PTH (iPTH) is normal, urinary calcium is decreased, serum albumin is reduced, and calcium concentration in tumour tissue is significantly increased compared to healthy tissue. Conclusions PTH‐independent hypercalcaemia has a low prevalence in SCC patients. Hypercalcaemia is correlated with susceptibility to develop metastases in SCC. A possible mechanism is PTHrp hypersecretion by malignant keratinocytes.     

Melanotic pigmentation in excision scars of melanocytic and non-melanocytic skin tumors

The appearance of pigmented lesions in melanoma surgical scars is a frequent finding that in some instances may cause confusion with a melanoma persistence. Nevertheless, only a few papers have dealt with this subject in the dermatologic literature. The melanoma surgical scars of 60 consecutive patients were reviewed with special attention to the presence of pigmentation and its clinical characteristics. Simultaneously, the scars of 60 consecutive patients who had been subjected to excision of a non-melanoma skin tumor were also studied. Biopsies were performed in representative clinical cases of pigmented lesions arising on the scars of both groups, as well as in non-pigmented scars, and processed for hematoxylin-eosin and immunohistochemistry. Pigmented lesions were present in a similar percentage in both groups (30% in melanoma scars (18/60) and 25% in non-melanoma scars (15/60)). Clinically, three types of clinical pigmentation were observed: lentigine-like lesions; pigmented streaks in scars after direct closure; and diffuse pigmentation in grafts. Histologically, two patterns emerged: one with lentiginous epidermal hyperplasia, hyperpigmentation, and a normal or moderately increased number of melanocytes; and a second one characterized by melanocytic hyperplasia of a variable degree. The scar process itself, irrespective of the tumor excised, seems to be responsible for the pigmentation. We suggest the existence of an induction process of scar tissue acting on melanocytes of the overlying epidermis.