Pregnancy as a driver for melanoma.

Whether or not pregnancy favours the occurrence and growth of melanoma is a source of controversy in the literature. Several case reports have shown dramatic courses of diseases in pregnancy. We present a case of a 36-year-old woman with multiple naevi with one melanoma detected in 2009 in the first trimester and a second primary melanoma in 2010 in the third trimester of her pregnancy. Both lesions have been present for at least 5 years and have been interpreted as dysplastic naevi. Because of their growth during pregnancy they were removed. No metastatic disease has been found between 2010 and early 2017. This case shows the difficulty of detecting melanomas in pregnancy, particularly when they mimic dysplastic naevi in women with multiple naevi, who are at higher risk. Therefore, we suggest that pregnant women with numerous naevi should be precautious of any changes of their naevi in size, shape and colour. Every suspicious lesion should be either excised or documented/monitored carefully, for example with sequential digital dermoscopy imaging.

Guidelines on the use of extracorporeal photopheresis.

BACKGROUND: After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease. MATERIALS AND METHODS: In order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. RESULTS AND CONCLUSION: These guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.

Patient acceptance and diagnostic utility of automated digital image analysis of pigmented skin lesions.

BACKGROUND: Computerized analysis of pigmented skin lesions may help to increase diagnostic accuracy for melanoma, help to avoid unnecessary procedures and reduce health care costs. OBJECTIVES: We evaluated both the patient acceptance and diagnostic utility of such an analysis tool in a real clinical setting. METHODS: Two hundred nine consecutive patients (median age: 34 years, range: 2-73 years), who were concerned about a pigmented skin lesion, answered a questionnaire about their attitude towards computerized analysis and their confidence in the resulting findings. Using a dermoscopy analyser, their skin lesions (n = 219) were then grouped into the categories, benign, suspicious and malignant, and results were compared with those obtained by in-person examination of dermato-oncologic experts. RESULTS: More than half of the patients (n = 114) would accept the use of computer analysis for melanoma screening; although 16 (14.0%) patients would accept this method solely, 98 (86.0%) patients would prefer an additional in-person examination by a dermatologist. Of the 219 pigmented skin lesions, the dermoscopic experts rated 171 (78.1%) as benign, 36 (16.4%) as suspicious and 12 (5.5%) as malignant, whereas computer analysis revealed 102 (46.6%) benign, 78 (35.6%) suspicious and 39 (17.8%) malignant lesions. At the expense of specificity (48.8%), the sensitivity of computerized analysis was excellent (100%) and equal to that of in-person examination. CONCLUSIONS: Most patients would accept computer analysis for melanoma screening, some of them even without reservations. However, due to a high rate of false positive computer assessments, it cannot be recommended as a screening tool at this time.

[Skin infections after transplantation]. / Hautinfektionen nach Transplantation.

Skin infections after transplantation are frequent and of special importance because they may be quite severe. The spectrum of dermatologic infections in transplant recipients includes bacterial, mycotic and viral diseases. Pyoderma, herpes virus 6/7, herpes simplex virus, varicella-zoster virus, cytomegalovirus and candida infections predominate. Rare pathogens must be also considered. Cutaneous infections can be divided into three phases following transplantation. Diagnosis and adequate early therapy together with specific prophylaxis and follow-up of transplant patients should be strived for to avoid life-threatening complications.

Frequency, clinical and dermoscopic features of benign papillomatous melanocytic naevi (Unna type).

BACKGROUND: Most previous studies on melanocytic naevi have not distinguished between the different types of naevi, except for some studies trying to define atypical naevi. No large, population-based studies on papillomatous or Unna-type melanocytic naevi have been performed. OBJECTIVES: To investigate the dermoscopic and clinical features of papillomatous naevi and to study some of the factors which could potentially influence their development. METHODS: Seven hundred and seven caucasians aged 1-82 years participated in a screening campaign at open-air recreation facilities in Austria. The volunteers underwent a total body examination by experienced dermatologists and answered a questionnaire. Clinical and dermoscopic images of one representative papillomatous naevus per person were taken. RESULTS: Twenty-nine per cent of the volunteers exhibited papillomatous naevi, the highest frequency being found in young adults. No correlation between the frequency of papillomatous naevi and gender, skin type, sunburns, sunbed use or hormonal factors was found. Most lesions were brown papules (median diameter 5.0 mm), located on the trunk. Dermoscopy showed a predominance of homogeneous and globular pattern, multifocal hypo/hyperpigmentation and comma vessels. Of the papillomatous naevi, 9.8% showed suspicious scores with dermoscopic algorithms. CONCLUSIONS: The lack of exogenous influencing factors and the predominance of globular dermoscopic pattern strengthen the hypothesis that papillomatous naevi belong to the same spectrum as small congenital melanocytic naevi. As the role of papillomatous naevi as precursors of melanoma remains unclear and they are frequently not recognized by the patients, one should perform dermoscopy of papillomatous naevi during skin cancer screening.

Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study.

BACKGROUND: Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level. OBJECTIVES: To assess cytomorphological and architectural RCM features of facial LM/LMM. METHODS: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. The histopathological diagnosis of LM was made in 15 areas; the other two were diagnosed as early LMM. RESULTS: A focal increase of atypical melanocytes and nests surrounding adnexal openings, sheets of mainly dendritic melanocytes, cord-like rete ridges at the dermoepidermal junction (DEJ) and an infiltration of adnexal structures by atypical melanocytes were found to be characteristic RCM features of facial LM/LMM. Areas with a focal increase of atypical melanocytes and nests surrounding adnexal openings were observed at the basal layer in three cases. The remaining cases displayed these changes at suprabasal layers above sheets of mainly dendritic melanocytes. Cord-like rete ridges at the DEJ and an infiltration of adnexal structures by atypical melanocytes were observed in all cases. Previously described criteria for RCM diagnosis of melanoma, such as epidermal disarray, pleomorphism of melanocytes and pagetoid spreading of atypical melanocytes, were additionally observed. CONCLUSIONS: We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.

Dermoscopic classification of atypical melanocytic nevi (Clark nevi).

OBJECTIVES: To create a dermoscopic classification of atypical melanocytic nevi (Clark nevi) and to investigate whether individuals bear a predominant type. DESIGN: Digital dermoscopic images of Clark nevi were classified according to structural features, ie, reticular, globular, or homogeneous patterns or combinations of these types. The nevi were also characterized as central hypopigmented or hyperpigmented, eccentric peripheral hypopigmented or hyperpigmented, or multifocal hypopigmented or hyperpigmented. SETTING: Two pigmented skin lesion clinics. PATIENTS: We examined 829 Clark nevi on 23 individuals. MAIN OUTCOME MEASURE: A reliable dermoscopic classification of Clark nevi and frequency of different dermoscopic types. RESULTS: Using the dermoscopic classification, the 829 Clark nevi were classified as follows: 221 (26.7%) as reticular, 167 (20.1%) as reticular-homogeneous, 148 (17.9%) as globular-homogeneous, 112 (13.5%) as reticular-globular, 89 (10.7%) as homogeneous, 84 (10.1%) as globular, and 8 (1.0%) as unclassified. Most individuals were prone to a predominant type of Clark nevus. Seven individuals (30%) showed a single type of Clark nevus in more than 50% of their nevi and 5 (22%) in more than 40% of their nevi. CONCLUSIONS: The proposed dermoscopic classification of Clark nevi is easily applicable and allows a detailed characterization of the different dermoscopic types of Clark nevi. Knowledge of these dermoscopic types should reduce unnecessary surgery for benign melanocytic lesions. Exact classification of the different types of Clark nevi is a necessary prerequisite for further clinical, dermoscopic, and histopathologic studies, which will give new insights in the biology of acquired melanocytic nevi.

Ultraviolet radiation of melanocytic nevi: a dermoscopic study.

BACKGROUND: UV radiation can lead to clinical, histological, and ultrastructural changes in melanocytic nevi. In this study, we investigated whether exposure to 2 minimal erythema doses of UV radiation induces changes in the dermoscopic image of acquired melanocytic nevi. OBSERVATIONS: Fifteen melanocytic nevi were exposed to 2 minimal erythema doses of UV radiation. Differences in dermoscopic parameters (asymmetry, border, erythema, and telangiectasias in the nevus; pigmentation; hypopigmented areas; presence, regularity, and sharpness of pigment network; and brown-black globules) in digital dermoscopic images taken before and 3, 7, 14, and 28 days after UV irradiation were scored. Three days after UV irradiation, the borders of nevi were more faded (P<.02), the nevi were darker brown (P<.02), the hypopigmented areas were smaller (P<.02), and the pigment network structures were more faded (P<.007) and less prominent (P<.02) than before UV irradiation. Seven days after UV irradiation, pigmented globules have also grown (P<.05). After 28 days, all parameters, except hypopigmented areas, were essentially the same as before UV irradiation. CONCLUSION: UV irradiation of melanocytic nevi with 2 minimal erythema doses induces transient changes in their dermoscopic appearance that are sometimes suggestive of malignant melanoma.

Face-to-face diagnosis vs telediagnosis of pigmented skin tumors: a teledermoscopic study.

BACKGROUND: Teledermoscopy uses telecommunication technologies to transfer images of pigmented skin lesions, including clinical and anamnestic data, via e-mail to specialized centers for teleconsultation. DESIGN: Sixty-six pigmented skin lesions examined on a face-to-face basis in a skin lesion clinic in L'Aquila, Italy, were sent via e-mail on a standard-resolution color monitor for consultation at a university dermatology department in Graz, Austria. INTERVENTION: Digital photographs of the clinical and dermoscopic images of all pigmented tumors were taken with a stereomicroscope connected to a high-resolution video camera in Truevision advanced graphic array (Targa) format file and converted successively into a Joint Photographic Expert Group (PEG) format file. All lesions were excised surgically and diagnosed histopathologically. MAIN OUTCOME MEASURE: Diagnostic concordance between face-to-face diagnosis and telediagnosis. RESULTS: The diagnostic concordance was 60 (91%) of 66 cases. The number of correct telediagnoses was lower, but the difference was not statistically significant (Wilcoxon test, P = .10). The accuracy of the telediagnoses was not related to the quality of the images, but highly depended on the level of diagnostic difficulty of a given pigmented skin tumor (Spearman correlation, P= .01). CONCLUSION: Teleconsultation of clinical and dermoscopic images of skin tumors via e-mail provides a similar degree of diagnostic accuracy as face-to-face diagnosis.

Sensitivity in the clinical diagnosis of malignant melanoma.

Accurate clinical diagnosis of malignant melanoma is of great importance for early detection and further treatment. The purpose of this retrospective study was to evaluate the accuracy of clinical diagnosis by using different clinical and histopathological parameters. Calculations are based on a total of 44,258 histopathologically examined skin neoplasms, including 529 melanomas, which were recorded in the histological database of the Department of Dermatology, University of Graz during a 2 year period. The clinical diagnosis of the referring physicians was compared statistically with the final histopathological interpretation. Clinical diagnosis of melanoma showed a sensitivity of 70.1%, a specificity of 99.4%, and a positive predictive value of 60.7%. One hundred and fifty eight melanomas (29.9%) could not be diagnosed clinically. The age-dependent sensitivity was 47.6% in patients <40 years, whereas for patients >80 years the value was 90.2%. Remarkably, the sensitivity in melanomas >4 mm thickness (64.8%) was lower than in 'melanoma in situ' (72.6%). Our findings underline the importance of further development of clinical examination techniques such as dermoscopy and digital epiluminescence microscopy.

Clinicopathological correlation of pigmented skin lesions using dermoscopy.

Dermoscopy (dermatoscopy, epiluminescence microscopy) is an additional measure for making the diagnosis of pigmented skin lesions more accurate. It enables the clinician to visualize features not discernible by the naked eye. By applying enhanced digital dermoscopy and a standardized gross pathology protocol to pigmented skin lesions, a precise clinicopathological correlation of relevant dermoscopic features can be made. Histological specimens of four pigmented skin lesions (melanoma in situ, Clark's nevus, Reed's nevus, seborrheic keratosis) were processed using a standardized gross pathology protocol and viewed along with the clinical photographs and digital dermoscopic images that were magnified and enhanced to better visualize the corresponding dermoscopic structures. Furthermore, measurements of dermoscopic structures using digital equipment were correlated with histometric findings. Our understanding of dermoscopic features, especially the broadened pigment network - a specific dermoscopic criterion for melanoma - was refined by this detailed case-by-case correlation. In addition, some not yet fully characterized dermoscopic features, such as black lamella, radial streaks, and exophytic papillary structures, were described in detail dermoscopically and histopathologically. Moreover, measurements of these dermoscopic features and the underlying histological structures were found to be similar. Linking dermoscopy more closely with cutaneous pathology may help refine the definitions and diagnostic criteria of pigmented skin lesions for dermatologists as well as dermatopathologists.

Ancient melanocytic nevus.

Ancient melanocytic nevus is an example of a simulator of malignant melanoma, designated ancient because it shares numerous features with ancient schwannoma. Knowledge of the histopathologic characteristics of this benign melanocytic neoplasm should enable pathologists to avoid overdiagnosis of it as melanoma arising in the intradermal portion of a nevus. Ancient nevi are found most commonly on the face of older persons. The neoplasm is usually a dome-shaped, skin-colored or reddish brown papule, usually with features of a Miescher's nevus. Histopathologically, ancient nevi are exoendophytic, mostly intradermal proliferations of two populations of melanocytes: one with large pleomorphic nuclei and the other with small monomorphous ones. The large melanocytes may resemble those of the epithelioid type of Spitz's nevus. A few mitotic figures may be present in a particular section. The epidermis usually is uninvolved, but sometimes there may be a junctional component. Other important findings are degenerative changes that include thrombi, zones of hemorrhage, pseudoangiomatous changes, thick rims of sclerosis around dilated venules, fibrosis, and mucin. Ancient nevi frequently are misdiagnosed as melanoma arising in an intradermal nevus.

Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi.

BACKGROUND: Based on the dermoscopic classification of acquired melanocytic naevi, six different dermoscopic types can be distinguished by morphology (globular, globular-reticular, globular-homogeneous, reticular, reticular-homogeneous, homogeneous) and by pigment distribution (uniform, central hyperpigmentation, central hypopigmentation, peripheral hyperpigmentation, peripheral hypopigmentation, multifocal hyper/hypopigmentation). It has been suggested that most individuals harbour one predominant dermoscopic type among their naevi. OBJECTIVES: To evaluate whether the age of the patient influences the predominant naevus pattern observed in individuals with multiple acquired melanocytic naevi. METHODS: Individuals were recruited from the pigmented skin lesion clinic in Graz between July 2000 and February 2001. Individuals with at least 10 melanocytic naevi were selected consecutively until a total of 10 individuals in each of five age groups was obtained. Age groups were: 0-15 years, 16-30 years, 31-45 years, 46-60 years and > 60 years. Digitized images of acquired melanocytic naevi, defined as benign melanocytic proliferations having a diameter of at least 5 mm with a macular component and which were not apparent within the first year of life, were evaluated by dermoscopic criteria. The associations of dermoscopic features as a function of patient age were analysed. We calculated absolute numbers and frequencies, given as percentages, as well as predominance of the dermoscopic types of naevi in the different age groups. RESULTS: Analysis of 1268 naevi revealed that the globular pattern predominated in the youngest age group. By contrast, the reticular and/or homogeneous patterns were increasingly exhibited in naevi from older individuals (older than 15 years). Uniform pigmentation was most common in melanocytic naevi in the youngest age group, while central hyperpigmentation was predominantly seen in the group of individuals aged 16-30 years. CONCLUSIONS: The predominance of dermoscopic types of melanocytic naevi varies according to the individual's age. Awareness of the age-related dermoscopic predominance of melanocytic naevi might allow more accurate recognition of dermoscopic patterns of melanocytic skin lesions that are unusual with respect to the individual's age. This observation may help in the early recognition of some 'banal'-appearing melanomas. Furthermore, the observations made in this study raise interesting questions regarding naevus evolution.

Renogram evaluation using an equation of balance for clearance and transit time determination.

A method of [123I]hippuran (OIH) renogram evaluation is proposed, which delivers transition rates for total and split renal clearance. It is based on the reconstruction of the true kidney input, using an equation of balance and a two-compartment model assumption of OIH kinetics. Results are compared with clearance determinations using whole body principles and transit time determination by deconvolution. It is shown that the reconstructed true input corresponds to the plasma activity while the vascular volume of distribution corresponds to the blood.

Determination of total, divided and regional tubular clearance and excretion by compartmental analysis of camera renograms.

A method to analyze the camera renogram is described in a mathematical manner. It is based on a 6-compartment model, which simulates the hippurate in vivo kinetics. Results are transfer rate constants from which the tubular clearance (by multiplying with the plasma volume) and additionally excretory parameters can be derived. The method is quick and simple and needs a gamma-camera and a small data processing system only, but no special equipment and no blood sampling.

[Reticular lentigo]. / Retikuläre Lentigo.

We studied the clinical and histopathologic features in five patients with reticulated lentigo. This peculiar pigmented skin lesions has previously been described under the designations "acquired reticulated lentigo", ink spot lentigo, "reticulated melanotic macule" or "reticulated lentigo". Each of the 4 males and 1 females in our study (age range: 16 to 57 years; mean age: 34 years) had a single, 4-6 mm large, black macule with irregular, fingerlike extensions at the periphery. All lesions were situated on the upper back and surrounded by numerous sun-induced freckles. Dermatoscopic examination revealed irregularly formed "meshes" and confirmed the reticulated pattern seen clinically. Reticulated lentigo presented mostly in individuals with skin type 1, red to blond hair, and blue eyes. The clinical diagnosis in 4 out of 5 cases was melanoma in situ. Histopathologically, reticulated lentigo was mainly characterized by a sharply circumscribed hyperpigmentation of the lower epidermis with accentuation at the tips of elongated and clubbed rete ridges. In addition, a normal or slightly increased melanocyte number in the basal layer and an infiltrate of melanophages in the upper dermis was noted. Reticulated lentigo shows histopathologic features similar to those of melanotic macules on volar skin and mucous membranes. Because of its characteristic clinical, dermatoscopic and histopathologic features reticulated lentigo can be regarded as a distinctive clinicopathologic entity.

Proliferating pilomatricoma. A histopathologic simulator of matrical carcinoma.

We report on 9 patients with pilomatricomas that showed unusual histopathologic features. Our patients were mainly elderly individuals (age range 42 to 88 years; mean age 70.1 years) who presented solitary cutaneous nodules situated on the head and neck (7 neoplasms), upper arm (1 neoplasm), and back (1 neoplasm). All the lesions were treated by simple excision. Follow-up data available in 7 of the 9 patients (mean follow-up, 17 months) revealed local recurrences in 1 patient whose lesion recurred 3 times. No lymph node involvement or distant metastases were recorded in any of our cases. Histopathologically, most neoplasms were characterized by a relatively large lesion in the dermis that in some cases showed extension to the subcutis. Each lesion was predominantly composed of a lobular proliferation of basaloid cells in association with adjacent focal areas containing eosinophilic, cornified material with shadow cells. In some cases, relatively large areas of shadow cells were present, whereas, in others only small foci of shadows cells were observed. Cytomorphologically, the basaloid cells showed features of matrical and supramatrical cells of a normal hair follicle and exhibited variable nuclear atypia and mitotic figures. The overall architectural pattern of the neoplasms was different from that of large fully developed stereotypical pilomatricomas that maintain a cystic character with basaloid cells predominantly aligned at the periphery. Based on the histopathologic findings, namely the presence of a large, lobular proliferation of basaloid cells in association with small to large foci of shadow cells, we interpreted these neoplasms to be a distinctive proliferative variant of pilomatricoma and propose the designation "proliferating pilomatricoma." Proliferating pilomatricomas should be differentiated from the recently described matricoma, basal-cell carcinoma with matrical differentiation, and matrical carcinoma (pilomatrical carcinoma).

Comparison of different methods of clearance determination.

Clearance determination by compartmental analysis of hippurate renograms was compared in 30 cases to the conventional PAH and to the partly shielded whole body counting technique. Good correlations between compartmental analysis and PAH method (r = 0.96) as well as the whole body technique (r = 0.94) were found. Correlation between PAH and whole body method was not always satisfactory (r = 0.85). In an additional study influence of greater count rates become obvious: correlation coefficients increase from 0.89 (131I-hippurate, n = 97) to 0.95 (123I-hippurate, n = 38). Determination of the divided clearance correlates well (r = 0.95). Using 123I-hippurate all the information available by radioisotopic kidney investigations can be obtained in a one-step procedure.