Following lentigo maligna may not prevent the development of life-threatening melanoma.

BACKGROUND--Management of lentigo maligna (Hutchinson's melanotic freckle, in situ lentigo maligna melanoma) by regular observation relies on the detection of invasive melanoma before it has developed significant life-threatening potential. Recent studies indicate that lentigo maligna melanoma does not have a better prognosis than other forms of melanoma. OBSERVATIONS--A case is reported of an amelanotic lentigo maligna that evolved from a macular lesion to a deeply invasive, amelanotic, lentigo maligna melanoma within 6 months. The melanoma was Clark level IV and measured 3.0 mm in maximum tumor thickness. CONCLUSIONS--Observation of lentigo maligna at 6-month intervals would not seem to be sufficiently reliable in detecting the development of invasive lentigo maligna melanoma before it becomes a life-threatening disease. Early surgical excision is the treatment of choice.     

Clinicopathologic analysis of malignant melanoma in Taiwan

BACKGROUND: Malignant melanoma is the leading cause of death among skin cancers in western countries. However, the incidence, histologic subtypes, and tumor behaviors are quite different in Asians and people of color. OBJECTIVE: Our purpose was to define the tumor behaviors and possible prognostic predictors of melanomas based on a Taiwanese patient population. METHODS: From the 65 patients diagnosed with melanoma at Veterans General Hospital, Taichung, we analyzed mean age at onset, gender, histologic subtypes, tumor thickness, level of invasion, primary tumor locations, and metastatic sites. Univariate analysis and multivariate analyses for survival, according to clinical and histologic tumor behaviors, were performed by means of Cox proportional hazard model. Survival curves were plotted by Kaplan-Meier method. RESULTS: Fifty-one cutaneous melanomas were identified and analyzed by both clinical behaviors and histology. Acral lentiginous melanoma was the most common type (54.9%), followed by nodular melanoma (29.4%), superficial spreading melanoma, and lentigo maligna melanoma. Univariate analysis for overall survival of melanoma revealed that age at onset older than 55 years, male gender, ulceration of tumor, and thicker tumor have the tendency to poorer prognosis, but without significant differences. The advanced stages (III and IV) and histologic subtypes other than acral lentiginous melanoma predicted a poorer survival with significant differences. Multivariate analysis demonstrated advanced stages, and histologic subtypes were the independent risk factors for poor prognosis. CONCLUSION: We proposed that histologic subtypes other than acral lentiginous melanoma and advanced stages have a poorer prognosis with significant differences.     

Clinical and Pathological Correlation of Malignant Melanoma

We have attempted to review virtually all forms of cutaneous and mucocutaneous melanomas. Superficial spreading, lentigo maligna and nodular melanomas have been more thoroughly investigated and documented in previous studies. Lentigo maligna melanoma appears to have a longer duration and better prognosis than SSM or NM. The overall prognosis probably correlates better with the anatomic level and thickness of invasion than with type (Clark et al. 1975, Breslow 1970, 1975). It appears that certain pitfalls exist in either method of assessing prognosis, and it is recommended that both methods be applied in evaluating a malignant melanocytic lesion when feasible. With regard to in situ melanoma or Level I melanoma, it is our experience that such lesions can achieve a 100% cure rate when completely excised. Hence, we prefer to call such lesions severely atypical melanocytic hyperplasia, and thus avoid labeling these patients with a malignant diagnosis. The most difficult histologic challenge in diagnosing a lesion of malignant melanoma is the Spitz nevus. The pathologist should never be biased by the age of the patient, for a serious mistake can arise. We have seen a case of nodular melanoma in a 13-year-old girl diagnosed as Spitz nevus only to be followed by a lymph node metastasis years later. Other examples of histologic differential diagnoses of malignant melanomas include, for example, halo nevus, soft tissue sarcoma, squamous cell carcinoma with spindle cell proliferation, Paget's disease of metastatic carcinoma, (for example, from the breast). Therefore, the approach to the diagnosis of malignant melanoma necessitates an evaluation of both clinical and pathological features. Histologic study must encompass both the pattern of growth and cellular cytologic detail for successful interpretation.     

Amelanotic lentigo maligna melanoma: a unique case and review of the literature

It has been estimated that 2 percent of all melanomas are clinically amelanotic, with amelanotic lentigo maligna melanoma being an even rarer presentation. These neoplasms have presented clinically as neurodermatitis, eczema, and erythema. Given the lack of clinical markers and subsequent delay in diagnosis of these lesions, they are potentially more dangerous than pigmented lentigo maligna melanomas. We report a case of an amelanotic lentigo maligna melanoma presenting as an ill-defined edematous area on the left cheek of an elderly woman.     

Prognostische Faktoren und operative Strategien bei Melanomen des Gesichts

Background: In treated facial melanomas, the safety margins generally applied in other body sites cannot be achieved for functional and esthetical reasons. To date there are no controlled studies on safety margins for facial melanomas. Clinical parameters and surgical strategies influencing the prognosis of patients with a facial melanoma were evaluated in a retrospective study of melanoma patients in the Department of Dermatology of the University of Tuebingen (1980 – 1999). Patients and Methods: The 368 melanomas of the face comprised 9.3 % of 3960 primary stage I and II melanomas and 63 % of the melanomas in the head and neck area. Results: Multistep procedures, excisional biopsy for histological diagnosis followed by a subsequent resection of a clinical safety margin or re‐excision when the tumor extended to the margin, were associated with a higher probability for recurrence‐free survival (p = 0.0007), but had no statistical influence on overall survival. In a multivariate analysis, level of invasion (p = 0.0049), ulceration (p = 0.011), 3D‐histology (p = 0.027) and defined safety margins (tumor thickness ≤ 1.00 mm: 10 mm; > 1.00 mm 20 mm; lentigo maligna melanoma 5 mm with 3D‐histology) (p = 0,033) were independent significant risk factors for recurrence‐free survival. Level of invasion (p = 0.032), ulceration (p = 0.029), 3D‐histology (p = 0.0047) were identified as independent significant risk factors for overall survival. Multivariate analysis did not show that the histological type of melanoma was of prognostic significance. Conclusion: Reduced safety margins can be employed in melanomas of the face. 3D‐histology allows further reduction of safety margins, detects subclinical tumor strands and is correlated with an improved prognosis in patients with facial melanomas.     

[Translated article] Update on the Diagnosis and Management of Desmoplastic Melanoma

Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.     

Factors associated with a high tumour thickness in patients with melanoma

BACKGROUND: Prognosis of patients with melanoma is strongly associated with tumour thickness at time of diagnosis. Therefore, knowledge of patient characteristics and behaviour associated with a high tumour thickness is essential for the development and improvement of melanoma prevention campaigns. OBJECTIVES: The present study aimed to identify sociodemographic, clinical and behavioural factors associated with high tumour thickness according to Breslow. METHODS: The study population consisted of 217 patients with histologically proven primary invasive cutaneous melanomas seen at the Department of Dermatology and Allergology at the Ludwig-Maximilian-University Munich, Germany, between January 1999 and January 2001. Personal interviews were conducted by two physicians to obtain information on sociodemographic characteristics and on patients' knowledge of melanoma symptoms, sun behaviour, delay in diagnosis and related factors. Multivariate linear and logistic regression analysis with stepwise variable selection was used to identify risk groups with a high tumour thickness. To assess possible effect modifications, interaction terms were included in the regression analysis. RESULTS: The median tumour thickness was 0.8 mm (interquartile range 0.5-1.6). Fifty-seven patients (26%) had tumour thickness >1.5 mm. In a multivariate linear regression analysis, patients living alone and patients with a low educational level showed a significantly greater tumour thickness. The relation of melanoma knowledge to tumour thickness was modified by the melanoma subtype: whereas lack of melanoma knowledge led to an increased tumour thickness for the subtypes superficial spreading melanoma, lentigo maligna melanoma and unspecified malignant melanoma, no significant effect was estimated for the subtypes nodular melanoma (NM) and acrolentiginous melanoma (ALM). Sex, age, self-detection of melanoma, patient delay and professional delay were not significantly associated with the tumour thickness in multivariate linear regression. Similar results were found in multivariate logistic regression. CONCLUSIONS: An increased tumour thickness was found in subjects living alone and having a low educational level. These subjects should be targeted in future prevention campaigns in a more focused way. Further efforts are necessary to improve knowledge and earlier detection of melanoma subtypes NM and ALM.     

Actualización en el diagnóstico y manejo del melanoma desmoplásico

Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.     

Solar radiation and malignant melanoma of the skin

Several observations suggest that a majority of cases of malignant melanoma of the skin are linked to sun exposure. Evidence includes higher occurrence of melanoma on anatomic areas heavily exposed during recreation, development of melanoma more frequently in lightly pigmented persons, and correlation of melanoma incidence and mortality with proximity to the equator. The role of sun exposure in the pathogenesis of melanoma remains unclear, however. Many cases of melanoma may be related to heavy doses of solar radiation received during recreation. Chronic sun exposure is not so clearly linked to the development of melanoma (except in the uncommon lentigo maligna variety). Sunspot cycles have been associated with changes in melanoma incidence; an excess of melanoma cases has been observed every 9 to 12 years after peak sunspot activity. These excess cases may be caused by more intense exposure to solar ultraviolet radiation during sunspot maxima, perhaps related to changes in the stratospheric ozone layer. These epidemiologic and clinical clues suggest that many cases of melanoma are related to sun exposure triggering the appearance of clinically evident melanoma. In this regard, solar radiation behaves as a cocarcinogen or promoter, rather than a dose-dependent carcinogen. These observations also suggest that other factors may be involved in the pathogenesis of melanoma, e.g., nevi, heredity, or exposure to chemical carcinogens.     

Thick melanoma: the problem continues

Background The incidence of melanoma and its associated mortality has stabilized over the recent years, due in part to efforts directed at better prevention and detection of these lesions. We analysed the trends in the distribution of melanomas, mainly according to their thickness. Methods Data from the Dermatology Service of ‘Virgen de la Victoria’ University Hospital in Malaga (Spain) showed a total of 459 cases of melanoma between 1990 and 2005, both inclusive. The lesions were stratified according to year of diagnosis (1990–96 and 1997–2005), sex, age (0–49, ≥ 50), thickness (0–0.99, 1.00–1.99, and ≥ 2 mm) and the histological subtype [lentigo maligna melanoma (LMM), superficial spreading melanoma (SSM), nodular melanoma (NM) and acral lentiginous melanoma (ALM)]. Particular attention was given to the distribution of the groups according to thickness. Results The number of new cases rose by 92% between the two study periods (1990–1996 and 1997–2005). However, the number of new cases of thick melanoma remained almost constant over the two periods, being associated with persons over 50 years of age (65.1% vs. 64.3%), with men having half the cases (48.4% vs. 47%). The proportion of nodular melanomas within the group of thick melanomas was high in both periods (36.5% and 39.3%, respectively). Conclusions This study shows that despite the large increase in new melanomas, the diagnosis of thick melanomas has remained constant, mainly in persons over the age 50 years, with a relative increase in men. New strategies and education programmes are, therefore, required for the early detection of this type of tumour to reduce its incidence in these patients.     

The effect of the sun on expression of beta-catenin, p16 and cyclin d1 proteins in melanocytic lesions

BACKGROUND: The tumour suppressor gene product, p16, is often inactivated during melanoma malignant progression. Although the importance of p16 in melanomas is well documented, its relationship with cyclin D1, beta-catenin and ultraviolet radiation (UVR) remains unclear. AIM: To determine the role of these cell cycle-related proteins and high-risk sun exposure in the biological behaviour of melanocytic lesions. METHODS: We used immunohistochemistry to examine 28 melanocytic naevi (MN; 9 congenital and 19 acquired types) and 24 primary cutaneous malignant melanomas (CMM; 19 nodular melanomas, 3 lentigo maligna melanomas, 1 acral lentiginous melanoma and 1 superficial spreading melanoma) for the presence of p16, cyclin D1 and beta-catenin. The melanocytic lesions were classified into two groups to examine the effects of UVR on these three proteins: high risk of sun exposure (chronically sun damaged; CSD), or low risk of sun exposure (nonchronically sun damaged; non-CSD). We evaluated the relationship between the production of these proteins and the histopathological and clinical characteristics of the lesions. RESULTS: Production of p16 was repressed in most CMM, but not in MN (P < 0.0001). Cyclin D1 was overproduced in CMM but not in MN, and beta-catenin was frequently overproduced both in MN and CMM. Overproduction of beta-catenin was not common in CSD melanocytic lesions, but was more frequent in non-CSD melanocytic lesions (P = 0.027). CONCLUSION: An immunohistochemical panel including melanocytic markers enriched by p16 and cyclin D1 could be used to differentiate some borderline melanocytic lesions. In addition, the Wnt/beta-catenin pathway was more frequently activated in non-CSD than in CSD melanocytic lesions.     

Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients

BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth distinct variant of cutaneous melanoma. The histological diagnosis and prognosis of ALM are still controversial. OBJECTIVES: To review the features of a large series of patients with ALM, and confirm the validity of the histological criteria for this type of melanoma. METHODS: A collection of 2642 patients with cutaneous melanoma was recorded during the period 1986-97, among these 187 were located on acral sites. Histological specimens were reviewed in 112 acral melanomas; the following study is based on this subgroup. RESULTS: Histological examination revealed acral lentiginous melanomas predominantly in palmoplantar and subungual locations (60%), while superficial spreading melanomas (SSM) were found mainly on the dorsal aspects of hands and feet (30%). Nodular melanomas (NM) (9%) occurred in all acral sites. The histological re-examination confirmed the characteristics of ALM as described by Reed in 1976. With increasing tumour thickness nesting of tumour cells and upward migration to the cornified layer was similarly observed. The 5-year survival rate for patients with primary acral melanoma without recognizable metastasis was 82%. ALM differed significantly in survival from SSM (P = 0.001) and lentigo maligna melanoma (P < 0. 001), but survival rates were similar to NM (P = 0.9). CONCLUSIONS: ALM, as diagnosed by current histological criteria, occur on the palms, soles and subungual sites, and have a poor prognosis.     

Nodular melanomas: Analysis of the casistic and relationship with thick melanomas and diagnostic delay

The present study aimed to: (i) define thick melanomas related to nodular melanomas and other melanoma subgroups; and (ii) establish diagnostic delay in relation to the biological behavior of these melanomas and prevention programs. Cutaneous primary melanomas were studied. Nodular melanoma (NM), lentigo maligna melanoma (LMM) and superficial spreading melanoma (SSM) were selected. A further category named vertical growth melanoma (VGM) was also utilized. Analysis for sex, age, different values of thickness (1–2 mm, >2 mm; 1–3 mm, >3 mm; >4 mm), delay to diagnosis and patterns of detection were performed in all of the different subtypes. Eighty‐seven patients with melanomas more than 1 mm of Breslow's thickness out of 506 melanoma were collected. Twenty‐six were nodular cases, 39 SSM, five LMM and 17 VGM. Of those patients with NM, 42% had a thickness of more than 1–2 mm, 34% of 2–4 mm, 23% of more than 4 mm; and 54% with 1–3, 46% with more than 3 mm; and 58% with more than 2 mm. Even considering different values of thickness of more than 1 mm, a delay to diagnosis was significantly lower in NM (4.79 months) than in other subgroups. The value of more than 1 mm of Breslow's thickness may be sufficient to consider a melanoma to be thick. The lower diagnostic delay of NM suggests that they represent faster growing lesions probably with a different biological behavior than other melanoma subtypes. VGM should not be confused with NM, having a longer delay and different clinical features compared with the latter. They represent an area of diagnostic carelessness than potentially be improved.     

Melanoma diagnosis at a specialist dermatology practice without the use of photographic surveillance

Background/Objective

Photographic aides are increasingly used in melanoma surveillance. We report melanoma characteristics detected using traditional surveillance without photographic technologies.

Methods

Retrospective study of melanomas diagnosed by three dermatologists at a private dermatology practice over 7 years. Patients underwent full skin examinations with dermoscopy and suspect lesions were excised or biopsied. Total body photography (TBP) and serial digital dermoscopic imaging (SDDI) were not used. Patient demographics, melanoma subtype and thickness, location, biopsy technique and keratinocyte cancers diagnosed at the same visit were recorded. Ratio of in situ to invasive melanomas was calculated. Melanoma risk factors were recorded for 69 randomly-selected patients.

Results

492 patients were diagnosed with 615 melanomas during 579 visits. 505 (82%) were in situ (in situ to invasive ratio of 4.6:1). Of the invasive melanomas, 85.5% had a Breslow thickness <0.8 mm, 10 (9.1%) 0.8–1 mm and 6 (5.5%) >1 mm. 43.3% of in situ melanomas were lentiginous or lentigo maligna and 41.6% were superficial spreading melanomas (SSM). Of invasive melanomas, 24.3% were lentigo maligna melanoma and 59.5% were SSM. 48.4% of melanomas were diagnosed by shave procedures. Where risk factors were known, 25% were very-high-risk and 43% had a history of melanoma. Keratinocyte carcinoma was diagnosed by biopsy at 26.1% of visits. Studies using TBP and/or SDDI report in situ to invasive ratios of 0.59:1 to 2.17:1.

Conclusion

Tradiational melanoma surveillance with immediate biopsy of suspect lesions results in high in situ to invasive ratios. Studies using photographic surveillance show lower ratios of in situ to invasive disease.     

Melanoma: clinical,evolutive and histopathological characteristics of a series of 136 cases

Background:The incidence of melanoma has been increasing in Brazil and all over the world. Despite improvements in diagnosis and treatment, mortality remains unchanged.Objective:To associate clinical and histopathological aspects with the evolution of 136 cases of cutaneous melanoma.Methods:Retrospective cohort study that analyzed all patients diagnosed with melanoma during the period from 2003 to 2011, with at least 4 years follow up. Archived slides were analyzed to study histopathological variables (Breslow, ulceration, mitoses and histological regression). Medical records were used to retrieve clinical variables (age, sex, localization, time of appearance, diameter) and progression (metastases or death). Association measures were assessed by statistical analysis.Results:There was no statistically significant difference between groups according to age. Superficial spreading subtype showed lower Breslow (0.5mm) than acral lentiginous and nodular subtypes (2 and 4.6mm respectively), less ulceration and metastases (9.4% against 50 and 70.6%). Nodular subtype had higher mitoses’ median (5.0/mm²) than superficial spreading and lentigo maligna (0.0/mm², for both). Regression was more frequent in superficial spreading and lentigo maligna subtypes. There were only deaths by melanoma in the acral group, however, there were deaths for other reasons in groups superficial spreading one, acral lentiginous one and lentigo maligna two.Study limitations:Use of medical records as a source of data to the study.Conclusions:Superficial spreading subtype presents better prognosis indicators. Histological subtype should be considered in follow-up and treatment protocols of patients with cutaneous melanoma.     

Desmoplastic melanoma associated with an intraepidermal lentiginous lesion: case report and literature review

Desmoplastic melanoma tends to present as firm, amelanotic papules. Microscopically, it reveals a proliferation of fusiform cells in the dermis and variable collagen deposition, as well as intraepidermal melanocytic proliferation of lentiginous type in most cases. Biopsy in a 61-year-old white male patient, who had received a diagnosis of lentigo maligna on his face 10 years before, revealed a proliferation of dermal pigmented spindle cells and collagen deposition, reaching the deep reticular dermis, with a lentiginous component. Immunohistochemistry with S-100, Melan-A and WT1 showed positivity, but it was weak with HMB45. Desmoplastic melanoma associated with lentigo maligna was diagnosed. Several authors discuss whether desmoplastic melanoma represents a progression from the lentiginous component or arises "de novo". Desmoplastic melanoma represents a minority of cases of primary cutaneous melanoma (less than 4%). Identification of lentigo maligna indicates that desmoplastic melanoma should be carefully investigated.     

Comparison of Melanoma Subtypes among Korean Patients by Morphologic Features and Ultraviolet Exposure

Background

Genetic alterations have been identified in melanomas according to different levels of sun exposure. Whereas the conventional morphology-based classification provides a clue for tumor growth and prognosis, the new classification by genetic alterations offers a basis for targeted therapy.

Objective

The purpose of this study is to demonstrate the biological behavior of melanoma subtypes and compare the two classifications in the Korean population.

Methods

A retrospective chart review was performed on patients found to have malignant melanoma in Severance Hospital from 2005 to 2012. Age, sex, location of the tumor, histologic subtype, tumor depth, ulceration, lymph node invasion, visceral organ metastasis, and overall survival were evaluated.

Results

Of the 206 cases, the most common type was acral melanoma (n=94, 45.6%), followed by nonchronic sun damage-induced melanoma (n=43, 20.9%), and mucosal melanoma (n=40, 19.4%). Twenty-one patients (10.2%) had the chronic sun-damaged type, whereas eight patients (3.9%) had tumors of unknown primary origin. Lentigo maligna melanoma was newly classified as the chronic sun-damaged type, and acral lentiginous melanoma as the acral type. More than half of the superficial spreading melanomas were newly grouped as nonchronic sun-damaged melanomas, whereas nodular melanoma was rather evenly distributed.

Conclusion

The distribution of melanomas was largely similar in both the morphology-based and sun exposure-based classifications, and in both classifications, mucosal melanoma had the worst 5-year survival owing to its tumor thickness and advanced stage at the time of diagnosis.     

Altersmelanome (LM, LMM) an beiden Wangen Analyse der unterschiedlichen Wachstumsdynamik anhand photokatamnestischer Befunde

The dynamics of tumor growth of malignant melanoma may be reconstructed by evaluation of suitable private photographs of the patient. Photohistorical investigations can greatly aid in following the course of development of malignant melanomas and show impressively the slow and protracted growth of initial melanomas. We report on a 90-year-old patient with an in situ melanoma (lentigo maligna) and an invasive lentigo maligna melanoma in the facial region. We were able to obtain complete series of photographs from this patient, which show the different development of the two melanomas over a period of more than 30 years. The first tumor to appear developed very slowly while the later one showed invasive growth after a short time period. Development of multiple primary melanomas is a well recognized phenomenon. The presence of multiple primary melanomas does not appear to be a negative prognostic factor. However, patients with primary melanoma should be made aware of increased risk of development another primary and physicians should do careful total body skin examinations for new primary melanomas as well as for recurrences of the original melanoma.