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In recent years, new drugs have been designed for treating advanced cutaneous malignant melanoma, in particular the metastases. They afford modest benefits despite the fact they are commonly heralded as breakthroughs in the lay press and by some medical opinion leaders. Unfortunately, the use of inflated descriptors of the drug efficacy leads to misunderstandings among the clinicians in charge of patients. Currently, vemurafenib, ipilimumab, pembrolizumab and nivolumab have demonstrated their relative activity in the control of advanced malignant melanoma. The results expected from surrogate markers of efficacy are magnified and idealized regarding the expectations from many patients. The recent therapeutic advance improves the median overall survival for a few months. Some combined treatments could possibly boost the current beneficial effects.

Cutaneous melanoma is the deadliest skin cancer showing an increasingly growing incidence in white populations of Europe and United States. Intensive research in recent years has begun to unlock its molecular pathogenesis. Screening the neoplasm at an early stage remains primordial. Hence, targeting populations at risk is likely efficient. In such an attempt, the regular clinical examination benefits from a series of non invasive procedures such as skin surface biopsies, in vivo confocal microscopy, dermoscopy and specular fluorescent light reflectance.

For aeons, cutaneous sporadic melanoma, exhibiting either a slow or rapid growth rate, is identified using a set of well defined histopathological criteria. Such diagnostic step is greatly appreciated, and it brings a rough estimate of the probable evolution of the cancer. Some additional assessments try to improve the progressive prognosis of cutaneous melanoma. In this scope, fractals and spectral analyses expect to better perceive the individual progressive characteristics of each tumor. The extent in the tumoral germinative compartment and the peritumoral microvascular network are explored and should in a near future make clear the progressive potential of cutaneous melanoma. The posible tumoral regression and the immune reaction should be better perceived.

For the media and the public at large, malignant melanoma is the most dreadful cancer of the skin. This statement is obvious. However, some nuances merit to be considered. The clinical presentations, histopathology and molecular genetics point to the fact that malignant melanoma is not a single monolithic pathological condition. Different types of melanomas are distinguished based on distinct origins and contrasted prognoses. The management and information for the patient should be handled individually.

Cutaneous malignant melanoma represents one of the most dramatic skin cancers because its incidence is steadily growing in White populations. Of note, its metastatic risk and mortality dramatically increase when the primary neoplasm reaches about one millimeter thick. It is believed that angiogenesis and lymphangiogenesis associated with cutaneous melanoma potentially influence the neoplastic progression of the primary tumor and its metastases. In some instances, both the intratumoral and peritumoral microvasculature are correlated to booming of the tumoral growth fraction. In addition, the vascular network serves as a migration path for the intravascular and perivascular neoplastic spread. Hence, the quantification of the microvasculature might help establishing a prognostic factor of evolution. Among the available methods, spectral analysis of immunohistochemical sections highlighting vessels helps defining the microvasculature distribution. The benefit of using spectral analysis is discussed and the modalities of application of this analytical method are scrutinized., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Treating a patient with cutaneous malignant melanoma relies on the recognition of a clever stratification of the distinct stages of the disease. The histoprognostic criteria were recently revisited. In addition, translational research fueled the development of new treatments with at last increased efficacy in the metastatic stage. Such therapeutic advance improves the median overall survival for a few months. Some combined treatments could possibly boost the beneficial effects.

Malignant melanoma (MM) micrometastases are basically seen in three locations inside the peritumoral dermis. They are localized (i) inside the interstitial sector of the dermal stroma; (ii) abutted to the external surface of the microvasculature; and (iii) more rarely present inside vascular channels. Single-cell and paucicellular micrometastases may be disclosed using immunohistochemistry even in the absence of larger microsatellites, which represent micronodular nests of metastatic cells. The presence of microsatellites is frequently tied to markers of MM aggressiveness including thickness and the Ki-67 index. Micrometastases may be present in the same conditions, but even as early as thin MM showing a small growth fraction. Microsatellites as well as micrometastases appear to predict locoregional extension and decreased relapse-free interval, but not distant metastasis and overall survival. These considerations have implications for patient care since patients with microsatellites and micrometastases are now included in the clinical stage III category of the disease. Their implication as a prognostic factor is not fully dependent on or linked to other markers of MM aggressiveness.

Malignant melanoma developed after 60 years of age is not a rare neoplasm. It is mainly but not exclusively represented by the lentigo maligna (LM) and the invasive melanoma developed on LM (LMM). Men are more often affected, and chronic sun exposure is the main cause. The diagnosis relies on the clinical, dermoscopic and dermatopathologic examinations. Surgical excision is recommended but alternative treatments are possible in case of contra-indication.

In a manichean ideal, one expects unreservedly a clear-cut distinction between benign melanocytic neoplasms and the malignant ones. Such a distinction is commonly established by a clinico-pathologic confrontation for the majority of neoplasms. However, the boundaries may be blurred and uncertain for some lesions. We present an exploratory clinicopathologic algorithm of the border area between seemingly benign and seemingly malignant melanocytic neoplasms. The concept of a group of neoplasms called skin melanocytomas shed some light on such quandaries where the risk of misdiagnosis is quite high.

The incidence of skin cancers is still on the rise despite information provided to the public and to cancer screening initiatives. We designed a 3D movie with the support of all Belgian university departments of dermatology. Looking at the impact of ultraviolet light in cells was the objective of this presentation. Several themes of actuality were addressed including genotoxicity of light, the primary prevention of skin cancers, the field actinodermatosis and cancerogenesis, the skin cancer epidemiology, the duality of skin melanomas with contrasted prognoses, and the recognition of melanoma stem cells.

A series of skin cancers are more frequent or show a worse course and outcome in HIV-treated patients. The leading neoplasms correspond to basal and squamous cell carcinomas, some primary cutaneous lymphomas and malignant melanomas. In these patients, early diagnosis and radical treatment on sight should be considered.

The scientific information about melanoma is on the rise. It has a direct impact on the diagnostic acuteness and on the therapeutic management. The most recent aspects of the utmost importance are presented. The concept of the duality between fast-growing (high malignancy) and slow-growing (reduced malignancy) melanoma is stressed. A new international multicentric approach using adjuvant therapy for stage III melanomas involves the clinical oncology department of the CHU of Liège. It concerns a targeted immunotherapy directed to the Mage A3 protein.

Background: In Westernized populations, the number of diagnosed cases of primary cutaneous cancers, particularly malignant melanomas and basal cell carcinomas (BCC), has been previously shown to fluctuate during specific periods of the year., Objective and Method: The aim of the present 6-year study was to explore the seasonality if any in skin cancer detection in Wallonia (south-east Belgium)., Results: For both malignant melanomas and BCC late spring/early summer and mid-autumn were the periods of highest diagnosis prevalence irrespective of gender. The amplitude of this bimodal evolution remained within the range of 2 standard deviations around the monthly means. Similar seasonal variations were also found in non-neoplastic controls consisting of laboratory samplings of onychomycoses and non-infectious onychodystrophies., Conclusion: There is reason to believe that this timing and rhythm is unrelated to any specific cancer chronomics. Rather, the present findings suggest unspecific seasonality in diagnosing skin disorders including malignancies. A variable patient awareness of changing aspects of the skin according to seasons probably represents the major influence of the described space-time clustering of skin cancer diagnosis., (Copyright 2008 S. Karger AG, Basel.)

Skin contains various hormonal receptors, particularly those for estrogens, progesterone and androgens. Steroid hormones of oral contraceptives affect the skin, in particular the control of the cell cycle, DNA replication, apoptosis and other cellular functions. Some estrogen-responsive pathways have the potential to promote tumor development. The question of whether oral contraceptives increase the risk for the development of skin cancer, particularly melanoma, remains an area of concern. There is some evidence that steroid hormones present in oral contraceptives do not significantly increase the risk of developing skin cancer when estrogen exposure is not excessive.

Cutaneous melanoma is a cancer affecting an ever growing proportion of young adults. Currently, the best approach for a prolonged remission or cure relies on early detection of the primary neoplasm and of its first possible metastases. Some therapies can bring much hope at this stage of the disease. The early detection of lymph node metastases is therefore essential in the global management strategy. The excision and the microscopic examination of the sentinel lymph node are important in this evaluation. Echography of the draining lymph nodes is a non invasive procedure which may also prove to be informative. PET-scan brings additional information, particularly when the dissemination risk is beyond the first group of lymph nodes.

In Wallonia, the incidence of cutaneous melanoma has steadily increased over the past decades. Hopefully, the early diagnosis made at the premetastatic stage has benefited from great advances both in the clinical and laboratory fields. Thanks to the "Groupement Oncologique Universitaire Wallonie-Liège" (GOUWL) organization, some efforts are currently made in order to better frame and normalize the management of cancer patients. Some medical staffs involved in prospective clinical research bring by their own experience further practical insights for the benefit to the patients. In this field, Belgium is not destituted. We report a brief review of the contribution of the Mosan Study Group of Pigmentary Tumors (GMETP) at the University Hospital of Liège.

Background: Cells of melanocytic naevi and cutaneous malignant melanomas (MM) are surrounded by a basement membrane (BM)., Aim: To scrutinize any difference between the deposits of alpha1 (IV) and alpha5 (IV) collagen chains in melanocytic naevi and MM., Methods: A total of 27 common melanocytic naevi, 11 dysplastic naevi, 21 atypical naevi (melanocytomas) including Spitz and non-Spitz types, as well as 24 MM were studied. Their phenotypic and functional characteristics defined by immunohistochemistry using a panel of antibodies, including those directed to the alpha1 (IV), alpha3 (IV) and alpha5 (IV) collagen chains., Results: Almost all naevi and half the melanocytomas exhibited a strong positivity for the alpha1 (IV) collagen chain. By contrast, the remaining melanocytomas and MM presented a heterogeneous staining pattern for the alpha1 (IV) collagen chain. One third of the naevi, 23% of the MM without cutaneous micrometastasis and 83% of MM with cutaneous micrometastasis showed discrete cytoplasmic positivity for the alpha5 (IV) collagen chain. All other melanocytic tumours were negative for this antibody. Rare MM cells in transepidermal migration were stained with the anti-alpha1 (IV) or alpha5 (IV) collagen chain antibodies. No immunoreactivity for the alpha3 (IV) collagen chain was disclosed in any of the samples., Conclusion: We report the expression of alpha1 (IV) and alpha5 (IV) collagen chains in naevi and MM. The inconsistent staining pattern for alpha1 (IV) collagen chain in phenotypically atypical melanocytomas and in MM highlight the heterogeneity in both cell differentiation and stroma-tumour interactions. This biological aspect may be related to neoplastic progression and influence metastatic potential.

It is acknowledged that tumour thickness, ulceration and lymph node invasion are the most important prognostic factors for cutaneous melanomas. Other histopathological features may also be informative. The aim of this study was to ascertain whether immunohistochemical methods can improve the detection of satellite micrometastases in primary melanoma patients. In addition, the predictive value of cutaneous satellite micrometastases for sentinel lymph node involvement was evaluated. A total of 265 primary cutaneous melanomas and 68 of the respective sentinel nodes were studied using a panel of seven antibodies directed against melanocyte-related antigens. In 12.4% of the 265 cases, small satellite micrometastases were detected by immunohistochemistry. Sentinel lymph node metastases were found in 14% of the 68 cases. Invasion of the sentinel lymph node correlated with the presence of cutaneous satellite micrometastases. It is concluded that the presence of cutaneous satellite micrometastases may be an indication for the performance of sentinel lymph node biopsy, and this finding calls for a closer follow-up of these patients.

The incidence of primary malignant melanoma (MM) and skin carcinomas, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is progressively raising. As long as their diagnosis and therapeutic managements are initiated early, their prognosis remains favorable. This underlines the importance of early recognition of skin cancers. Furthermore, it has been demonstrated that skin cancer screening programs are efficacious in increasing the population awareness of the early signs of skin cancer and of the dangers of UV - exposure. A skin cancer screening campaign was organised by dermatologists of the German-speaking Community of Belgium in cooperation with the Department of Family, Health, and Social Affairs of the Regional Ministry of the German-speaking Community of Belgium. In order to increase the screening selectivity, two risk populations were targeted; patients presenting 30 or more moles, and patients over 50 years of age presenting recent skin changes of the head and neck area. A media campaign using radio, television and daily press was started to increase the population awareness of the dangers of UV exposure and of the early signs of skin cancer. During 2 screening days, three-hour sessions were organised in 2 health centers located in Eupen and St Vith. A total of 148 patients were examined. A total of 124/148 patients met the selection criteria predefined during the media announcement. The simultaneous presence of 4 dermatologists during the screening sessions allowed a second opinion for warning lesions. Four BBCs as well as 23 patients pesenting dysplastic nevi were clinically diagnosed. During the 2 months following the screening campaign 5 MMs were identified by the same dermatologists in their routine practice. In conclusion, this skin cancer screening campaign led to the diagnosis of 4 carcinomas. The campaign furthermore increased the patient awareness, permitting the diagnosis of 5 MMs during the 2 following months. This figure represents about 30% of all MMs diagnosed yearly in this region of Belgium.

Background: Much is known about the worldwide rising incidence of skin cancers in the white populations. However, contradictory reports have been presented about a gender-linked risk for malignant melanoma (MM)., Objective: To review the recent epidemiological information about primary and metastatic MM in south-east Belgium., Methods: Laboratory records of primary MM according to age and gender were compared per 3-year periods from 1988 to 2002. The numbers of MM per decade of patient age were corrected with regard to the number of citizens in the defined periods of age. This led to the calculation of the rate of estimated prevalence (REP). The same assessments were performed on 187 sentinel lymph node biopsies collected during the last 3-year period., Results: A total of 1,051 primary MM in women and 594 primary MM in men were diagnosed over the 15-year period. The female-to-male ratio rose by 24% over time, with a mean value of 1.77. The most recent years showed a marked increase both in the numbers and REP of primary MM. This situation was present in both genders, although it was most prominent in women of the reproductive age. MM metastases were found in 38/187 sentinel lymph nodes with a female-to-male ratio of 2.17. The age distribution for all sentinel lymph node biopsies copied that of primary MM, but the vast majority of the nodal metastatic MM was found in patients older than 50 years. The ratio between MM metastases and primary MM reached 6.1% (12/198) in men and 6.9% (26/378) in women., Conclusion: A recent increase in primary MM incidence was observed in our laboratory. The most likely cause is ascribed to more sensitive MM detection using the combination of clinical dermoscopy and laboratory immunohistochemistry. During the past 15 years, women were more affected than men by both primary and metastatic MM. The gender difference in incidence of primary MM has progressively widened due to an increased incidence in young and middle-aged women. By contrast, nodal metastatic MM mostly affected postmenopausal women.

Cancers rarely coexist with pregnancy. Cutaneous melanoma, however, is one of the most frequently encountered neoplasms during pregnancy. Gestation may also be a period during which the aspect of some melanocytic naevi can change eventhough the tumor remains benign. Distinction between a benign and a malignant lesion may then be a dilemma. Clinical morphometry, dermoscopy, skin surface biopsy, conventional histology and immunohistochemistry are valuable means that can be used to secure maximum diagnostic confidence.

Sun is at the origin of life. It can also be responsible for death. In the past decades cutaneous melanoma killed more and more young adults. Currently, the disease still progresses in the population, but survival increases hopefully. Sun is pointed out as the main culprit. Hence, protection against harmful effects of ultraviolets is mandatory. However, preventive measures to be taken generate heated scientific argument. Sunlight exposure particularly in moderation is indeed necessary for health through vitamin D3 synthesis and psychological effects on wellbeing. Vitamin D3 provides numerous biological effects, particularly on bone calcification and also by inhibiting proliferation and migration of malignant cells including melanoma cells. Hence, we are facing the dilemma between too much and too little ultraviolet light exposure. Anyway, one cannot advocate that people lie in the sun until they burn or until they turn a rich brown complexion.

A presumed melanoma metastasis is sometimes found without any evidence for the primary neoplasm. Such an orphan metastasis merits a complementary exploration. Searching for the primary melanoma must then be performed using non invasive and clinically oriented methods. Beside a thorough skin examination, otorhinolaryngological, ophtalmic and gynecologic searches are recommended. In addition, paraclinical investigations are conducted according to the metastatic location, the gender and the functional complaints of the patient. The prognosis of these orphan metastases is not more dramatic than when the primary lesion is identified. Therapies are similar to those proposed in the classical presentation of the disease.

Two young adults presented an interdigital intertrigo and a dyschromic nail alteration, respectively. They were adept of intense sport swimming in pools. Lesions had been misdiagnosed as athlete's foot and onychomycosis, respectively. Several antifungal treatments had been tried without success. After many months of inadequate management, the dermatological examination revealed the presence of two malignant melanomas corresponding to the eroded acrolentiginous and nodular subungueal types, respectively.

Background: Radiotracer and blue-dye lymphatic mapping is a recommended combined method to guide sentinel lymphadenectomy and full regional lymph node dissection in selected patients with cutaneous melanoma., Objective: To evaluate the diagnostic accuracy and the prognostic value of gamma-probe-directed lymphatic mapping in cutaneous melanomas., Methods: Sixty-five stage I and II melanoma patients underwent gamma-probe-directed lymphatic mapping. Sentinel lymph nodes were studied by both conventional and immunohistochemical stainings. The median follow-up was 11 months., Results: Sensitivities of preoperative and intraoperative sentinel lymph node detection were 100 and 98%, respectively. Only 1 failure of detection and 1 missed same-basin metastasis were experienced in the axillary and cervical areas, respectively. Eleven patients (16.9%) had sentinel node metastases leading to adjuvant therapy., Conclusion: Gamma-probe-directed lymphatic mapping is useful for staging melanoma. However, in the expectation of a more specific identification of the sentinel lymph node, the standard protocol remains recommended for exploring the axillary and cervical areas. The histological examination supported in some cases by immunohistochemistry remains mandatory in all cases., (Copyright 2002 S. Karger AG, Basel)

Sunbeds used in sun parlours do not garantee a controlled innocuity. By contrast, health hazards are obvious in many instances. Forceful tanning is a transitory aspect behind which the spectrum of many skin changes includes accelerated photoageing, irreversible pigmentary and keratotic changes, and cutaneous malignancies including malignant melanoma. In the absence of protection, the eye is also affected. Even if tanning salon exposure increases the risk for skin cancer by a small amount, it represents a significant potential public health hazard given the number of people attending salons. Digital dermoscopy and ultraviolet light videoscopy are new methods allowing to predict the cutaneous ransom to be paid by the sunbed worshippers.

A man presented with a malignant melanoma of the scalp. The lesion reached a large size before being disclosed. Repetitive sunburns during tennis matches could be responsible for this cancer. Indeed, hair protects only partially the skin from ultraviolet damages.

An epidemiological survey was performed in pupils from primary schools of Liège in order to better identify risk factors for photobiological alterations prone to induce cutaneous melanoma in adult life. Phenotypic and behavioral factors facing up to sun exposure were considered. In a 4-level risk scale, about half of the Liège children showed a high to severe risk at photobiological alterations. Thus melanoma prevention requires a sustained effort in the Mosan region, particularly by health education programs at school.

The development of new therapeutic protocols for malignant melanoma calls for an upgraded assessment of the individual risk to develop metastases. The predictive sentinel lymph node method is best practiced in a multidisciplinary approach. The selective lymphadenectomy of the first draining lymph node is followed by minutely detailed histologic examination combined with immunohistochemistry.

Background: Positron emission tomography (PET scan) using fluorodeoxyglucose (FDG) is increasingly recognized as a reliable diagnostic method to detect metastases of malignant melanoma (MM)., Objective: To compare the diagnostic performance of 18-FDG PET scan to that of conventional imaging., Methods: A total of 28 assessments were conducted in 24 patients at risk of metastatic MM., Results: The diagnostic accuracy was over 80% and similar for PET scan and conventional imaging., Conclusion: Both the specificity and sensitivity of PET scan are high although not perfect. Confrontation of data with anatomical location and clinicopathological findings remains mandatory., (Copyright 2000 S. Karger AG, Basel.)

Progression and metastatic spread of primary cutaneous melanoma (PCM) is largely predicted by the thickness of the primary tumor. However, the accretive or proliferative pattern of growth of PCM is another aspect that might affect the prognosis. We retrieved from our histopathological files 11 superficial spreading PCM which had been documented to show an almost stable size for at least 3 years before excision. The area of the PCM at the skin surface had been measured by planimetry on the excision specimens. Histological sections were used to measure the maximum thickness of the neoplasms. A PCM volume estimate was derived by multiplying the surface area by the thickness of the tumors. In addition, the vessel area was determined beneath and outside the PCM lateral margins on Ulex europaeus agglutinin-1-stained sections using computer-assisted image analysis. Peritumoral vascularity was significantly more developed than at distance of the neoplasms. A significant negative exponential correlation was yielded between the peritumoral vascularity and the PCM volume estimate. Such vascular eclipse might be the cause of clinical PCM dormancy. However, other possible independent mechanisms are not ruled out by the present study.

The Mosan Study Group of Pigmented Neoplasms was founded about 15 years ago. It has collected more than 20,000 cutaneous malignancies including melanomas and basal and squamous cell carcinomas. The incidence of these cancers is on the rise in Wallonia. In particular, malignant melanomas represent a spectrum of emerging cancers characterized by a proteiform biological outcome. They mostly affect young women. The major risk factor appears to be iterative and unwise ultraviolet exposures. The prevention of melanomas is basically founded on such a dogma and accordingly relies on sunscreens. However, controversies about their beneficial effects are rife and fueled by axiomas and contradictory sophisms. At the exception of surgery, the therapeutic options for the diverse types of melanomas do not yet fulfill the scope of evidence-based medicine.

Background: Recent advances in angiogenesis research have led to the introduction of new prognosis factors. Although the vessel count is effective in breast cancer, the prognosis of primary cutaneous melanoma (PCM) does not seems to be directly influenced by this parameter. However, the microscopic examination of PCM suggests variability in the repartition of the microvasculature., Objective and Method: To explore the possibility of extracting information about the vessel distribution by performing a textural analysis on the grey level of histological sections by means of fractal characterization by both Fourier spectrum and multifractal analysis., Results: Three different patterns of vasculature were identified according to the vessel density and distribution., Conclusion: It is possible to differentiate and quantify clearly the differences in the microvessel profile organization using the fractal and multifractal methods.

There is ample evidence for spontaneous antimelanoma immune reactivity mediated by melanocyte-differentiation-antigens (MDAs). Our aim was to determine whether MDA immunoreactivity is associated with increased tumour-infiltrating lymphocytes (TIL) and macrophages (TIM). A retrospective study was conducted in 30 medium and high grade primary cutaneous melanomas (PCM) as identified by CART-analysis. All of the cases had developed clinical evidence for metastasis within 3 years following surgical excision of the PCM. We used immunohistochemistry and computerized image analysis to quantify MDAs positive cells (Melan A/MART-1, gp100/Pmel 17/HMB45, tyrosinase), CD45R0-positive TIL and LI-protein-positive TIM. A stochastic relationship was present between the MDA immuno-reactivities and the densities in TIL and TIM. An inverse relationship was yielded between TIL and TIM. No specific pattern of PCM immunoreactivity for MDAs, TIL and TIM was found to predict metastases.

For years, a wide and deep excision of primary cutaneous melanomas has been recommended to achieve a better care and to decrease the risk of local recurrence of the disease. However, recent studies indicate that removal of peritumoral tissue beyond complete excision of the primary neoplasm does not decrease significantly the risk of local metastases. In addition, it confers no benefit to the patient survival.

The correct staging of potentially metastatic melanoma is essential for an appropriate therapeutic attitude. Current methods include computed tomography, magnetic resonance imaging, ultrasonography and scintigraphy. Another tool is whole-body positron tomography using the radiopharmaceutical 2-fluorine-18-fluoro-2-deoxy-D-glucose as an emitter because it accumulates inside neoplasms, especially melanoma. We report two cases of malignant melanoma in which computed tomography and magnetic resonance imaging suggested visceral metastatic spread. In contrast, whole-body positron emission tomography indicated the absence of metastases, and this was confirmed by histological examination of the organs where metastases were suspected. Whole-body positron emission tomography appears to have high specificity and sensitivity for clinical melanoma staging.

Skin melanoma is one of the rare cancers whose prevalence has increased over the past decades. Its treatment is based on a classification into four anatomoclinical stages. Surgical excision is the mainstay of therapy. However, several protocols of chemotherapy, radiotherapy and immunotherapy also have specific indications in the therapeutic or palliative approach to the disease.

Tumour vascularity has been proposed as a prognostic indicator for a number of solid tumours. In these respects the situation is unclear for cutaneous malignant melanoma (MM). The small number of MM cases studied to date have indicated controversial preliminary conclusions. Hence, tumour thickness remains currently the most reliable prognostic factor for MM. This variable has been shown in previous work to be correlated with both the S-phase fraction and the growth fraction of the MM cells. We studied the relationship between vascularity and growth fraction of 100 thin (< 1 mm) cutaneous MM using immunohistochemistry (Ulex europaeus agglutinin-type 1 (UEA-1) and MIB-1 antibody (Ki-67)) and computerised image analysis. A stochastic relationship was found between intra- and peritumoral vascularity, and between Ki-67 and UEA-1 measures. Approximately 20-40% of PC-MM showing a high Ki-67-positive growth fraction (breakpoint: 30/0.4 mm2) were characterised by a prominent vascularity at the boundary of the neoplasm. In these cases, vessels often exhibited either heterogeneous lumen sizes or a uniform prominent dilated network. The present study shows that the angiogenic phenotype of MM occurs as a stochastic event during neoplastic progression. Its expression is not mandatory for reaching high values in MM growth fraction. It can be hypothesised that the absence of a link between proliferation and vascularity might account for the unusual outcome of some cutaneous MM, including the dormant growth-stunted type and the metastasising thin MM.

Several studies have reported the association of cutaneous malignant melanomas (MM) with carcinomas. Collision malignancies cases from our files were retrieved. Among a series of 78,000 primary cutaneous cancers, 11 were collision tumors of MM with basal cell carcinoma and 106 were basosquamous carcinomas while no association was found between MM and squamous cell carcinomas. It is concluded that coexisting and confluent malignancies of the skin might not always be a random event.

Previous clinical observations have indicated that the metastatic potential for thick malignant melanoma is lower for patients with xeroderma pigmentosum than for other patients. In a prospective study using computerized image analysis to measure the morphometric characteristics of nuclei in these neoplasms, we found that the nuclei of malignant melanoma cells were smaller and more ovoid in patients with xeroderma pigmentosum than in other patients. Objective evaluation and grading of these subtle histopathologic variables could provide a means of establishing prognostic factors unrelated to the thickness of the neoplasm.

We used computerized image analysis, immunohistochemistry, and the incorporation of tritiated thymidine to study the relationship between nuclear size and shape and the proliferation of malignant melanoma cells. A total of 30 nonulcerated primary malignant melanomas and 75 of their cutaneous metastases were considered. We found a positive relationship between (a) the 3H-TdR labeling indices and the thickness of the primary malignant melanoma: (b) the nuclear profile areas of primary lesions and their respective metastases; and (c) the size and regularity of the contours of the nuclei. We failed to find a relationship between 3H-TdR indices and the nuclear size of malignant melanoma cells.

We present a novel approach for improving the management of patients with pigmented neoplasms including malignant melanomas and dysplastic nevi. A cohort of 215 dysplastic nevi and malignant melanomas was studied by cyanoacrylate skin surface stripping (CSSS) and conventional histology. Presence of atypical melanocytes was found in the stratum corneum in more than 95% of malignant melanomas and was always absent in dysplastic nevi. We conclude that this non-invasive technique is rapid, easy to perform, and inexpensive. Its specificity and sensitivity are high enough to be considered by clinicians as an aid for distinguishing dysplastic nevi from malignant melanomas. We recommend this ancillary technique as a screening procedure though not as a substitute for conservative excisional biopsy, when doubt persists in the diagnosis of atypical pigmented neoplasms.