Melanoma arising in plaque-type blue nevus and dermal melanocytosis: Diagnostic and prognostic value of BAP1. / Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1.

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques.

Prognostic Value of Vitamin D Serum Levels in Cutaneous Melanoma. / Efecto de los niveles séricos de vitamina D en el pronóstico del melanoma cutáneo.

INTRODUCTION: Vitamin D plays a fundamental role in many metabolic pathways, including those involved in cell proliferation and the immune response. Serum levels of this vitamin have been linked to melanoma risk and prognosis. This study aimed to assess the prognostic value of vitamin D serum level in melanoma. MATERIAL AND METHODS: Retrospective, observational, longitudinal, and analytical study of 286 patients with a histologic diagnosis of melanoma in whom serum levels of vitamin D were measured at the time of diagnosis. We analyzed associations between serum level and epidemiologic and clinical variables and pathology findings; we also analyzed the influence of vitamin D on overall survival. An iterative loop was used to identify a vitamin D serum level to test for its an association with survival. RESULTS: A vitamin D level less than 9.25ng/mL was associated with a histologic finding of ulceration. After a median follow-up period of 39.4 months, 24 patients (8.4%) had died. The cutoff of 9.25ng/mL was associated with lower overall survival according to both the Kaplan-Meier curves and multivariate Cox regression analysis. CONCLUSION: Vitamin D levels less than 9.25ng/mL are associated with ulceration in melanoma and serve as an independent prognostic factor for overall survival in this disease.

Clinical, environmental and histological distribution of BRAF, NRAS and TERT promoter mutations among patients with cutaneous melanoma: a retrospective study of 563 patients.

BACKGROUND: The distinct somatic mutations that define clinical and histopathological heterogeneity in cutaneous melanoma could be dependent on host susceptibility to exogenous factors like ultraviolet radiation. OBJECTIVES: Firstly, to characterize patients with cutaneous melanoma clinically and pathologically based on the mutational status of BRAF, NRAS and TERT promoter. Secondly, to elucidate the modified features due to the presence of TERT promoter mutations over the background of either BRAF or NRAS mutations. METHODS: We performed a retrospective study on 563 patients with melanoma by investigating somatic mutations in BRAF, NRAS and TERT promoter. RESULTS: We observed co-occurrence of TERT promoter mutations with BRAF and NRAS mutations in 26.3% and 6.9% of melanomas, respectively. Multivariate analysis showed an independent association between BRAF mutations and a decreased presence of cutaneous lentigines at the melanoma site, and an increased association with the presence of any MC1R polymorphism. We also observed an independent association between TERT promoter mutations and increased tumour mitotic rate. Co-occurrence of BRAF and TERT promoter mutations was independently associated with occurrence of primary tumours at usually sun-exposed sites, lack of histological chronic sun damage in surrounding unaffected skin at the melanoma site, and increased tumour mitotic rate. Co-occurrence of NRAS and TERT promoter mutations was independently associated with increased tumour mitotic rate. The presence of TERT promoter together with BRAF or NRAS mutations was associated with statistically significantly worse survival. CONCLUSIONS: The presence of TERT promoter mutations discriminates BRAF- and NRAS-mutated tumours and indicates a higher involvement of ultraviolet-induced damage and tumours with worse melanoma-specific survival than those without any mutation. These observations refine classification of patients with melanoma based on mutational status.

Risk factors for the development of a second melanoma in patients with cutaneous melanoma.

BACKGROUND: Cutaneous melanoma patients have an increased risk of developing other neoplasms, especially cutaneous neoplasms and other melanomas. Identifying factors associated with an increased risk might be useful in the development of melanoma guidelines. OBJECTIVES: To identify risk factors related to the development of a second primary melanoma in a series of patients diagnosed with sporadic melanoma and to establish the estimated incidence rate. METHODS: A longitudinal study based on prospective follow-up information of patients diagnosed with sporadic cutaneous melanoma at our centre from 2000 to 2015 was performed. Cumulative incidence was estimated based on competing risk models, and the association of characteristics with the risk of a second melanoma was performed by Cox proportional hazard models. RESULTS: Out of 1447 patients included in the study, after a median follow-up of 61 months, 55 patients (3.8%) developed a second melanoma. Fair hair colour, more than 100 common melanocytic nevi and the presence of more than 50 cherry angiomas were independently associated with the development of a second melanoma. The site and the histological subtype of the first and second melanomas were not consistent. The second melanomas were thinner than the first ones. CONCLUSIONS: Fair-haired and multiple-nevi patients might benefit from more intensive prevention measures. The finding of cherry angiomas as a risk factor suggests that these lesions could be markers of skin sun damage in the setting of certain degree of genetic susceptibility.

Histologic Changes During Treatment With Vismodegib in Locally Advanced Basal Cell Carcinoma: A Series of 19 Cases.

BACKGROUND: There are no large series describing cutaneous histologic changes during treatment with vismodegib in locally advanced basal cell carcinoma (BCC). OBJECTIVE: To analyze histologic changes in skin biopsy specimens from patients with locally advanced BCC treated with vismodegib. METHODS: A descriptive, retrospective study of patients with locally advanced BCC treated with vismodegib between June 2012 and December 2017 at the Instituto Valenciano de Oncología, Spain. Nineteen patients were biopsied before and during the treatment with vismodegib, and we compared histologic changes observed. RESULTS: Seven patients (37%) achieved complete response, which was characterized by replacement of tumor stroma with a hyaline scar, lymphocytic inflammatory infiltrate, keratin formation, and infundibular cysts. Twelve patients (63%) achieved partial response; 5 showed no phenotypic changes, whereas 7 showed histologic changes; 5 cases showed metatypical differentiation; and 2 cases presented squamous differentiation. We observed no cases of squamous cell carcinoma arising at vismodegib treatment sites and no association between initial histologic subtype and clinical response. LIMITATIONS: Many biopsy specimens were obtained by punch biopsy and may not be representative of the full tumors. We studied histologic changes only in complete and partial responses. CONCLUSION: Vismodegib can induce histologic changes toward metatypical or squamous differentiation of BCC in patients with partial response. Keratinizing phenomena were frequent, both in partial and complete response groups.

No association between smoking and sentinel lymph node metastasis and survival in cutaneous melanoma.

BACKGROUND: There is little evidence that smoking is associated with metastasis in patients with cutaneous melanoma. OBJECTIVE: Using a propensity score matching analysis, we assessed whether smoking was associated with a higher rate of sentinel lymph node (SLN) metastasis and worse survival in these patients. METHODS: Retrospective cohort study at a referral hospital for melanoma. We studied 762 patients with known smoking status from the melanoma database of the Instituto Valenciano de Oncología who underwent SLN biopsy between 1 January 2000 and 31 December 2016. The patients were matched by smoking status. The matching procedure was implemented using three logistic regression models featuring never vs. former smokers, never vs. current smokers and former vs. current smokers. The study outcomes were disease-free survival (DFS), melanoma-specific survival (MSS), overall survival (OS) and SLN status. RESULTS: The following groups were formed based on the propensity matching scores: 114 pairs of smokers vs. never smokers, 113 pairs of smokers vs. former smokers and 174 pairs of never smokers vs. former smokers. Smoking status was not associated with SLN metastasis or with DFS, MSS or OS in any of the three groups. CONCLUSION: Smoking does not influence SLN metastasis or survival in patients with cutaneous melanoma.

Is mitotic rate still useful in the management of patients with thin melanoma?

BACKGROUND: T1 melanoma substaging was recently modified by the American Joint Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the most important prognostic factor in melanoma, there is a lack of consensus on whether SLN biopsy should be performed in patients with thin melanoma (≤1 mm). OBJECTIVE: The main aim of this study was to investigate predictors of SLN positivity in patients with thin melanoma, with a special emphasis on mitotic rate. A secondary aim was to evaluate survival in this group of patients. MATERIALS AND METHODS: Retrospective multicenter observational study with analysis of age, sex, tumour location, thickness, mitotic rate, regression and microscopic satellites. Predictive factors were identified using a classification and regression tree (CART) approach. Melanoma-specific survival according to SLN status was estimated using Kaplan-Meier curves. RESULTS: We analysed 203 patients with a melanoma ≤1 mm. Using the new AJCC staging criteria, the CART algorithm identified a 7.5% likelihood of SLN positivity in T1a patients. In the case of T1b melanoma, there was a 14.3% likelihood of SLN positivity in patients with a mitotic rate >1 mitosis/mm2 and a 3.2% likelihood in those with ≤1 mitoses/mm2 . None of the patients with T1b disease who had ≤1 mitoses/mm2 and regression had SLN positivity. In T1b patients, 5-year melanoma-specific survival was 98.7% in the SLN-negative group and 75% in the SLN-positive group (P = 0.05). When stratified by mitotic rate, survival was 100% for patients with a mitotic rate of ≤1 mitoses/mm2 and 91.4% for those with >1 mitosis/mm2 (P = 0.022). There were no deaths in the T1a subgroup. CONCLUSIONS: Sentinel lymph node metastasis was less common in patients with T1b melanoma who had a mitotic rate of ≤1 mitoses/mm2 . Performance of SLN biopsy should be carefully considered in this subgroup of patients, particularly considering the good prognosis.

Cutaneous Angiosarcoma: Clinical and Pathology Study of 16 Cases. / Angiosarcoma cutáneo: estudio clínico-patológico de 16 casos.

INTRODUCTION AND OBJECTIVES: Primary cutaneous angiosarcoma is one of the most aggressive skin tumors and carries a very poor prognosis. Its initially indolent clinical presentation explains the frequently late diagnosis that, together with its typically multifocal pattern and poor delimitation, often makes surgery difficult. The low incidence of primary cutaneous angiosarcoma means that few large single-center series have been published. We review the clinical and pathologic characteristics of cutaneous angiosarcomas treated in our hospital, looking for prognostic factors and for possible diagnostic traits that could facilitate early diagnosis. MATERIAL AND METHODS: This was a retrospective observational study including all patients diagnosed with cutaneous angiosarcoma in Instituto Valenciano de Oncología in Valencia, Spain between January 2000 and December 2015. We recorded 16 clinical parameters, including age, sex, type of angiosarcoma, site, size, and time since diagnosis, and 8 histopathologic parameters. RESULTS: We identified 16 patients (11 women and 5 men) with cutaneous angiosarcoma. Their mean age was 67 years (median, 71 years). The most common site was the trunk (10 cases), followed by the head and neck (5 cases). The mean size of the tumor was 10cm (median, 6.5cm). Fourteen patients underwent surgical excision. Six of the 16 patients were alive at the end of the study, after a mean follow-up period of 42.5 months. CONCLUSIONS: The major determinants of survival among patients with cutaneous angiosarcoma are tumor size and patient age. Other characteristics associated with a poor prognosis were infiltration of deep planes (muscle), a predominantly solid histologic pattern, and a larger number of mitoses.

Use of Lymph Node Ultrasound Prior to Sentinel Lymph Node Biopsy in 384 Patients with Melanoma: A Cost-Effectiveness Analysis. / Valor de la ecografía ganglionar previa a la biopsia del ganglio centinela en 384 pacientes con melanoma: análisis de coste-efectividad.

BACKGROUND AND OBJECTIVES: Locoregional lymph node ultrasound is not typically included in guidelines as part of the staging process prior to sentinel lymph node biopsy (SLNB). The objective of the present study was to make a clinical and economic analysis of lymph node ultrasound prior to SLNB. MATERIALS AND METHODS: We performed a retrospective study of 384 patients with clinical stage I-II primary melanoma who underwent locorregional lymph node ultrasound (with or without ultrasound-guided biopsy) prior to SLNB between 2004 and 2015. We evaluated the reliability and cost-effectiveness of the strategy. RESULTS: Use of locorregional lymph node ultrasound avoided SLNB in 23 patients (6%). Ultrasound had a sensitivity of 46% and specificity of 76% for the detection of metastatic lymph nodes that were not clinically palpable. False negatives were significantly more common in patients aged over 60 years and in tumors with a thickness of less than 2mm. The staging process using SLNB and ultrasound with ultrasound-guided biopsy produced an increase of €16.30 in the unit price. Our cost-effectiveness analysis identified the staging protocol with ultrasound and SLNB as the dominant strategy, with a lower cost-effectiveness ratio than the alternative, consisting of SLNB alone (8,095.24 vs. €28,605.00). CONCLUSIONS: Ultrasound with ultrasound-guided biopsy for the diagnostic staging of melanoma prior to SLNB is a useful and cost-effective tool. This procedure does not substitute SLNB, though it does allow to avoid SLNB in a not insignificant proportion of patients.

Mohs micrographic surgery in dermatofibrosarcoma protuberans allows tumour clearance with smaller margins and greater preservation of healthy tissue compared with conventional surgery: a study of 74 primary cases.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour with aggressive local growth. Whether DFSP should be treated with conventional surgery (CS) or Mohs micrographic surgery (MMS) has long been a topic of debate. OBJECTIVES: To calculate, in a large series of DFSP treated by MMS, the minimum margin that would have been needed to achieve complete clearance by CS. Secondly, to calculate the percentage of healthy tissue that was preserved by MMS rather than CS with 2- and 3-cm margins. METHODS: The minimum margin was calculated by measuring the largest distance from the visible edge of the tumour to the edge of the definitive surgical defect. Tumour and surgical defect areas for hypothetical CS with 2- and 3-cm margins were calculated using AutoCAD for Windows. RESULTS: A mean minimum margin of 1·34 cm was required to achieve complete clearance for the 74 tumours analysed. The mean percentages of skin spared using MMS rather than CS with 2- and 3-cm margins were 49·4% and 67·9%, respectively. CONCLUSIONS: MMS can achieve tumour clearance with smaller margins and greater preservation of healthy tissue than CS.

Predictors of sentinel lymph node status in cutaneous melanoma: a classification and regression tree analysis.

OBJECTIVE: The main aim of this study was to identify predictors of sentinel lymph node (SN) metastasis in cutaneous melanoma. PATIENTS AND METHODS: This was a retrospective cohort study of 818 patients in 2 tertiary-level hospitals. The primary outcome variable was SN involvement. Independent predictors were identified using multiple logistic regression and a classification and regression tree (CART) analysis. RESULTS: Ulceration, tumor thickness, and a high mitotic rate (≥6 mitoses/mm(2)) were independently associated with SN metastasis in the multiple regression analysis. The most important predictor in the CART analysis was Breslow thickness. Absence of an inflammatory infiltrate, patient age, and tumor location were predictive of SN metastasis in patients with tumors thicker than 2mm. In the case of thinner melanomas, the predictors were mitotic rate (>6 mitoses/mm(2)), presence of ulceration, and tumor thickness. Patient age, mitotic rate, and tumor thickness and location were predictive of survival. CONCLUSIONS: A high mitotic rate predicts a higher risk of SN involvement and worse survival. CART analysis improves the prediction of regional metastasis, resulting in better clinical management of melanoma patients. It may also help select suitable candidates for inclusion in clinical trials.

Positive margins in excised dermatofibrosarcoma protuberans: a study of 58 cases treated with slow-Mohs surgery.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is characterized by unpredictable subclinical extension, meaning that positive margins are frequently detected following conventional surgical excision. OBJECTIVE: To study the presence or absence of residual tumour in DFSP with positive margins after conventional surgery and identify possible predictors of residual tumour or clear margins following a single Mohs micrographic surgery (MMS) stage. METHODS: A retrospective study of patients with DFSP and positive margins following conventional excision referred for MMS was performed. We studied gender, age, tumour site, time from presentation to diagnosis, and affected margins. RESULTS: We studied 58 cases, 35 (60.3%) of which had histological evidence of residual tumour. Tumours of the head and neck were significantly associated with the persistence of tumour. A single MMS stage was sufficient to achieve clearance in the majority of cases (n = 46). All tumours with lateral involvement only were resolved with a single Mohs stage. CONCLUSIONS: DFSPs with positive margins after conventional surgical excision should undergo re-excision because the majority have histologic evidence of residual tumour. Re-excision with 1-cm margins beyond the scar could be an option in certain tumour sites, particularly when it is known which margins are involved.

Clinical characteristics of patients with cutaneous melanoma according to variants in the melanocortin 1 receptor gene.

INTRODUCTION: Patients with cutaneous melanoma who are carriers of polymorphisms in the melanocortin 1 receptor gene (MC1R) have distinctive clinical characteristics. The objective of this study was to determine the clinical characteristics associated with differing degrees of functional impairment of the melanocortin 1 receptor, as determined by the number and type (R and r) of MC1R polymorphisms. MATERIAL AND METHODS: In total, 1044 consecutive patients with melanoma diagnosed in our hospital after January 2000 were selected from the melanoma database. These patients were divided into 3 groups according to a score based on nonsynonymous MC1R polymorphisms. The frequencies of epidemiologic, phenotypic, and histologic variables and personal and family history of cancer were compared. RESULTS: Patients with a score of 3 or more were more likely to develop melanoma before the age of 50 years (odds ratio [OR]=1.47), have a tumor on the head or neck (OR=3.04), have a history of basal cell carcinoma or cutaneous squamous cell carcinoma (OR=1.70), have atypical nevi (OR=1.74), and have nevi associated with the melanoma (OR=1.87). CONCLUSIONS: The use of a scoring system for MC1R polymorphisms allowed us to identify associations between the degree of functional impairment of the melanogenesis pathway and the clinical characteristics of the patients and melanoma presentation.

Paraneoplastic dermatomyositis: a study of 12 cases.

INTRODUCTION AND OBJECTIVES: Adult dermatomyositis presents as a paraneoplastic syndrome in up to 25% of cases, but no clinical, histologic, or laboratory markers completely specific for paraneoplastic disease in dermatomyositis have been identified to date. Furthermore, studies on adult dermatomyositis do not usually report the frequency of cutaneous features of dermatomyositis in patients with associated cancer. Our aim was to review the characteristics of paraneoplastic dermatomyositis in patients seen at our hospital. MATERIAL AND METHODS: We studied 12 cases of paraneoplastic dermatomyositis and recorded patient age and sex, associated cancer, time between onset of dermatomyositis and cancer, emergent cutaneous manifestations, muscle involvement, dysphagia, lung disease, and levels of creatine phosphokinase and circulating autoantibodies. RESULTS: The mean age of the patients was 61 years and the 2 most common malignancies were ovarian cancer and bladder cancer. The mean time between the diagnosis of cancer and dermatomyositis was 7 months and in most cases, the cancer was diagnosed first. Seven patients had amyopathic dermatomyositis. The most common cutaneous signs were a violaceous photodistributed rash sparing the interscapular area and a heliotrope rash, followed by Gottron papules and cuticle involvement. Superficial cutaneous necrosis was observed in 3 cases. Myositis-specific autoantibodies were not detected in any of the 6 patients who underwent this test. CONCLUSIONS: Paraneoplastic dermatomyositis is often amyopathic. There are no specific cutaneous markers for malignancy in dermatomyositis. Myositis-specific antibodies are not associated with paraneoplastic dermatomyositis.

Mitotic rate and subcutaneous involvement are prognostic factors for survival after recurrence in patients with only locoregional skin metastasis as the first site of recurrence from cutaneous melanoma.

BACKGROUND: Few reports on literature give detailed figures on prognostic factors of locoregional skin recurrence in cutaneous melanoma. OBJECTIVE: The aim of this study was to evaluate clinical and histological prognostic factors following development of locoregional cutaneous metastasis as the only progression site from melanoma. METHODS: Data from 1327 stage I and II melanoma patients who visited Instituto Valenciano de Oncología and Consorcio Hospital General Universitario de Valencia from 2000 to 2010 were documented in a prospective manner. During follow up, 112 (8.4%) of them developed recurrent disease. A retrospective analysis revealed a subset of 36 patients with locoregional cutaneous metastases as a first event. RESULTS: Significant prognostic factors in the univariate analysis were Breslow thickness, tumor mitotic rate and the presence subcutaneous involvement of the skin metastasis. After multivariate analysis the independent predictive factors for survival after recurrence were tumor mitotic rate (hazard ratio [HR]: 8.6; 95% CI: 1.0-77.2) and subcutaneous involvement of the skin metastasis (HR: 4.3; 95% CI: 1.0-18.5). CONCLUSION: The survival after recurrence of melanoma patients that has relapsed with only locoregional cutaneous metastasis depends on the mitotic rate of the primary tumor and the subcutaneous involvement of the metastasis.

Incipient merkel cell carcinoma: a report of 2 cases.

Merkel cell carcinoma is a malignant skin tumor with a poor prognosis that primarily affects photoexposed areas of elderly patients. Tumor size is a very strong prognostic factor, with much better outcomes associated with small lesions, measuring less than 1cm. However, such lesions are rarely seen in the clinic in view of the rapid growth of this tumor. We report 2 cases of incipient Merkel cell carcinoma. Both cases of incipient Merkel cell carcinoma measured approximately 5mm in diameter. One tumor was confined to the epidermis and papillary dermis on the nose of a 79-year-old man and the other was located in the deep dermis, almost in the hypodermis, on the buttock of an 82-year-old woman. In both cases, the lesions had appeared weeks earlier. The first tumor seemed to originate in the dermoepidermal junction whereas the second originated almost in the hypodermis. Although the lesions were at a similar disease stage and had a similar size, their different locations within the dermis highlight once again the controversy about which cells give rise to Merkel cell carcinoma. The precursor cells could feasibly be Merkel cells in the first case but not in the second.

Risk factors for the development of locoregional cutaneous metastases as the sole form of recurrence in patients with melanoma.

BACKGROUND: While locoregional cutaneous metastases (in transit and satellite) in melanoma have received little attention from researchers to date, they have pathogenic and prognostic features that distinguish them from other forms of locoregional recurrence. Identifying predictors of these metastases would be of great value for their prevention, early diagnosis, and treatment. The aim of this study was to identify the risk factors associated with locoregional cutaneous metastases as the first form of recurrence in the metastatic progression of melanoma. MATERIAL AND METHODS: Between 2000 and 2010, we prospectively collected the data of 1327 patients diagnosed with stage I and II melanoma. During follow up, 112 patients (8.4%) developed metastases. Of these, 36 had exclusively locoregional cutaneous metastases. The clinical and histological characteristics of this subgroup were evaluated. RESULTS: In the univariate analysis, significant predictors were patient age, primary tumor thickness, site, ulceration, mitotic index, and histological type. After multivariate analysis, the independent risk factors were tumor thickness (risk ratio [RR] 5.6; 95% CI: 2.7-11.5) and the location of the primary tumor on the lower limbs (RR 3.4; 95% CI: 1.0-11.5), on the head or neck (RR 4.8; 95% IC: 1.7-13.5), or in acral sites (RR 6.7; 95% IC: 2.2-20.8). CONCLUSION: Patients who have melanomas with a Breslow thickness of more than 2mm located on the lower limbs, head, neck, or acral sites have a higher risk of developing locoregional cutaneous metastases. These findings could be useful in the design of future guidelines for the monitoring and management of melanoma.

Clinical presentation of acral lentiginous melanoma: a descriptive study.

BACKGROUND AND OBJECTIVE: Acral lentiginous melanomas -the melanomas most commonly found on the distal portions of the limbs- have usually reached more advanced stages than other types of melanoma when diagnosed. Our aim was to describe the clinical presentation of these tumors. MATERIALS AND METHODS: Retrospective, descriptive, observational study of cases recorded in the database of the Instituto Valenciano de Oncología. In telephone interviews the patients answered a questionnaire on the presenting features of the lesion, on the presence of signs and symptoms included in the Glasgow 7-point checklist and the ABCDEs of melanoma, and on diagnostic delay attributable to patient or physician. RESULTS: In the interviews with the 23 patients who responded to the questionnaire, we detected a diagnostic delay of more than 1 year attributable to the patient (delay in seeking care) in 30.4% of the cases. Diagnostic delay of more than 1 year attributable to the physician (failure to suspect the diagnosis) was identified in 20%. The most frequent reasons for consulting a physician about a lesion were changes in size, changes in color, bleeding, or failure to heal. In 20% of the cases the evaluating physician did not order histology for over a year. CONCLUSIONS: Diagnostic delay is a significant problem in acral lentiginous melanoma and may be attributable either to patients or to physicians' failure to recognize warning signs. Melanoma prevention campaigns should place more emphasis on the possibility of melanomas appearing on the palms and, particularly, on the soles.