Tumor de células granulares. Estudio clínico de 81 pacientes

IntroductionAlthough a granular cell tumor (GCT) usually develops on the skin or oral mucosa, it has been described in many other organs. GCT typically presents as a solitary tumor, but multiple lesions can occur. It has also been described in association with other diseases.ObjectivesTo describe the clinical characteristics of cutaneous and oral mucosal GCTs and explore potential associations with other diseases.Material and methodsRetrospective study of patients diagnosed with GCT at our hospital between 1995 and 2019. The following information was collected from the patients’ medical records: age, sex, number of GCTs, location, diameter, time to diagnosis, tentative clinical diagnosis, surgical margin status, recurrence, follow-up time, and associated diseases.ResultsWe detected 89 cutaneous or oral mucosal GCTs in 81 patients (43 women, 38 men) with a mean age of 40.21 years. The mean tumor diameter was 1.34 cm. Five of the 81 patients (6.2%) had multiple GCTs, including noncutaneous tumors. Patients with multiple GCTs were on average younger than those with a single tumor (P = .004). There was only a single case of local recurrence and no cases of distant metastasis. None of the patients had associated diseases.ConclusionsMost GCTs are benign and local recurrence is uncommon, even in patients with positive margins. Nevertheless, the possibility of multiple tumors affecting the skin, oral mucosa, or internal organs should be borne in mind, especially in young patients.     

Phenotypic and histologic characteristics of cutaneous melanoma in patients with melanocortin-1 receptor polymorphisms

BackgroundThe melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure.ObjectivesTo analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma.Material and methodsA total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction.ResultsAt least one of the following MC1R variants was present in 58% of the patients: V60L, V92 M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P = .018) and melanomas located on areas with intermittent sun exposure (P = .019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P = .028).ConclusionsThe results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R.     

Estudio descriptivo del patrón de diseminación visceral del melanoma cutáneo

Background and objectivesSome types of cancer tend to spread to certain organs. In the case of melanoma, uveal melanoma spreads almost exclusively to the liver, while cutaneous melanoma spreads to the liver and other organs. Although important advances have been made in our understanding of the molecular mechanisms underlying melanoma, few recent studies have focused on the patterns of visceral metastasis in cutaneous melanoma. The aim of this study was to retrospectively investigate whether clinicopathologic variants of cutaneous melanoma and primary tumor site might be associated with pattern and time of onset of metastasis to visceral sites, including the central nervous system (CNS).Materials and methodsWe included patients diagnosed with cutaneous melanoma between 1988 and 2009 with at least 2 years’ follow-up.ResultsOf the 1083 patients studied, 92 developed visceral metastasis. The CNS was affected in 21 cases, the lungs in 24, the liver in 17, the digestive tract in 7, and multiple organs simultaneously in 23. Metastasis to the lungs, the liver, and the digestive tract occurred within 5 years in most cases, while metastasis to the CNS and multiple organs occurred later (> 5 years in 38% and 43% of cases, respectively).ConclusionsUnlike uveal melanoma, cutaneous melanoma spreads to different organs without any particular predilection. We observed no significant associations between the site of visceral metastasis and either clinicopathologic variant or location of the primary tumor. Metastasis occurred within 5 years of diagnosis in most cases, but it can occur after 10 years.     

Registro nacional de melanoma cutáneo. Características del tumor en el momento del diagnóstico: 15 años de experiencia

Background and objectivesThe Spanish National Cutaneous Melanoma Registry (Registro Nacional de Melanoma Cutáneo [RNMC]) was created in 1997 to record the characteristics of melanoma at diagnosis. In this article, we describe the characteristics of these tumors at diagnosis.Patients and methodsThis was a cross-sectional observational study of prevalent and incident cases of melanoma for which initial biopsy results were available in the population-based RNMC.ResultsThe RNMC contains information on 14,039 patients. We analyzed the characteristics of 13,628 melanomas diagnosed between 1997 and 2011. In total, 56.5% of the patients studied were women and 43.5% were men. The mean age of the group was 57 years (95% CI, 56.4-57 years) while median age was 58 years. The most common tumor site was the trunk (37.1%), followed by the lower limbs (27.3%). The most frequent clinical-pathologic subtype was superficial spreading melanoma (n = 7481, 62.6%), followed by nodular melanoma (n = 2014, 16.8%). Localized disease was observed in 86.2% of cases (n = 10,382), regional metastasis in 9.9% (n = 1188), and distant metastasis in 3.9% (n = 479). Independently of age at diagnosis, men had thicker tumors, more ulceration, higher lactate dehydrogenase levels, and a higher rate of metastasis than women (P < .001).ConclusionsBased on our findings, melanoma prevention campaigns should primarily target men over 50 years old because they tend to develop thicker tumors and therefore have a worse prognosis.     

Características clínicas de los pacientes con melanoma cutáneo en función de las variaciones en el gen del receptor 1 de la melanocortina (MC1R)

IntroductionPatients 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 methodsIn 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.ResultsPatients 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).ConclusionsThe 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.     

Factores de riesgo para el desarrollo de metástasis cutáneas locorregionales como forma única de recaída en los pacientes con melanoma

BackgroundWhile 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 methodsBetween 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.ResultsIn 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).ConclusionPatients who have melanomas with a Breslow thickness of more than 2 mm 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.     

CD10 expression by melanoma cells is associated with aggressive behavior in vitro and predicts rapid metastatic progression in humans

BackgroundNo biological or molecular marker of primary melanoma tumor cells has been shown to predict clinical outcome in melanoma.ObjectiveTo determine whether CD10, CD133, nestin and CD20 may evaluate the prognosis of melanoma.MethodsThe differential expression of these molecules was assessed in pairs of cell lines. We evaluated, by both immunohistochemical staining and RT-qPCR, their expression in a cohort of 32 patients (68 samples) with a history of metastatic melanoma, divided into two groups according to their clinical outcome profile.ResultsCD10 over expression in cancer cell lines was associated with more aggressive behavior in vitro. A CD10-positive staining was more frequent in patients in the “rapidly progressive” group than those in the “long survivor” group (23/35 versus 2/18, p < 10^?4). CD10 expression was associated with a lower median overall survival (1.15 year – IQR: [0.50–2.58] versus 4.27 – IQR: [1.66–6.33]; p = 10^?4). The Odds Ratio of displaying a “rapidly progressive” melanoma when tumor cells expressed CD10 was 15 (95% confidence interval: [3–78]). After adjusting for confounding factors, CD10 expression in melanoma tumor cells remained associated with an increased risk of death and more rapid disease progression (p = 6 × 10^?4; HR = 3.71).ConclusionCD10 may predict clinical outcome in melanoma patients.     

Melanoma subungueal: estudio descriptivo de 34 pacientes

Introduction and objectivesSubungual melanoma constitutes a diagnostic challenge because it often has an atypical clinical presentation. The aims of this study were to revise the clinical and pathologic characteristics of patients with subungual melanoma diagnosed at a tertiary care university hospital and analyze the factors potentially associated with a delayed diagnosis.Material and methodsWe analyzed data for 34 patients diagnosed with subungual melanoma at our hospital over a period of 20 years.ResultsThe study population comprised 18 women and 16 men with a median age at diagnosis of 66 years. Only 5 of the patients had longitudinal melanonychia when examined at the dermatology department. At the time of diagnosis, 19 of the 34 patients had invasive melanoma (median Breslow thickness, 3.70 mm); 16 had ulceration and 8 had regional lymph node involvement. Five patients had subungual melanoma in situ at diagnosis. The median time from appearance of the lesions to consultation at a primary care center was 15 months; the corresponding time from primary care consultation to diagnosis at our hospital was 5.5 months. Lesions located on the toes were more likely to be ulcerated (P = .017) and to be accompanied by regional lymph node involvement at diagnosis (P = .012).ConclusionsThe factors associated with a longer diagnostic delay in patients with subungual melanoma were absence of melanonychia as a presenting feature and involvement of the toes.     

Clinical features associated with the invasive component in lentigo maligna of the head and neck: A retrospective study of 175 cases

BackgroundLentigo maligna (LM) can develop into lentigo maligna melanoma (LMM) with risk of metastatic dissemination. LMM may be underestimated on the basis of the initial biopsy. The invasion may affect both the therapeutic options and the prognosis.ObjectivesTo identify the clinical features associated with invasive forms of LM and factors associated with its recurrence.MethodsA retrospective, single-centre study of consecutive LM and LMM histologically confirmed and treated by surgery between 2009 and 2014.ResultsIn total, 175 patients with LM/LMM were surgically treated in our establishment. In men, lesions were more likely to be in the “peripheral zone” (41.8%), while in women they were seen more often in the “central zone” (P = 0.001). In multivariate analysis, only the peripheral zone was found to be associated with a risk of invasion (P = 0.008). The rate of recurrence was 9% and lesions were more likely to be primary LMM (P = 0.0006) excised with clear margins.ConclusionThe treatment of choice in LM with non-clear margins must be re-excision, especially for lesions situated in the peripheral zone. Close follow-up is recommended due to risk of recurrence, even in the case of clear margins.     

Worse survival of invasive melanoma patients in men and “de novo” lesions

BackgroundThe incidence and mortality of melanoma is increasing in many countries, including Brazil. Survival studies are still scarce in our country, but much needed to know and address this problem better.ObjectiveTo analyze the disease-specific survival of patients with invasive melanoma and to correlate it with clinical and histopathological variables.MethodsRetrospective cohort analysis of 565 cases of invasive melanoma in a tertiary hospital with the objective of testing variables that could be associated with a worse prognosis, such as gender, phototype, thickness, histological type and presence of pre-existing clinical lesion at the site of the tumor.ResultsThe worst survival rates were significantly associated with thicker tumors (p < 0.001), male sex (p = 0.014), high phototype (p = 0.047), nodular melanoma (p = 0.024) and “de novo” lesions (p = 0.005). When all variables were adjusted for melanoma thickness, male patients (p = 0.011) and “de novo” melanomas (p = 0.025) remained associated with worse survival.Study limitationsRetrospective study of a single tertiary hospital.ConclusionsAlthough the causes are still unknown, melanoma-specific survival was statistically worse for males and for “de novo” melanomas even after adjustment of tumor thickness.     

Correlation between clinical, dermatoscopic, and histopathologic variables in atypical melanocytic nevi

IntroductionAtypical melanocytic nevi are acquired melanocytic lesions that were described for the first time by Clark in studies of melanocytic nevi in patients with melanomas. Today, the use of dermatoscopy has made identification of this type of nevus much easier.ObjectiveOur aim was to study the correlation between the clinical, dermatoscopic, and histopathologic findings of melanocytic nevi and compare our findings with those of previous studies. We also aimed to investigate the value of dermatoscopy for identifying atypical melanocytic nevi.Material and methodsIn this cross-sectional, observational study, 200 melanocytic lesions were analyzed in 166 patients examined between January 1, 2005 and December 31, 2005. We recorded the clinical, dermatoscopic, and histopathologic characteristics of each lesion and established the correlation between the different findings on a case-by-case basis. We then determined the agreement between diagnoses and assessed the value of dermatoscopy for identifying atypical melanocytic melanoma.ResultsThe clinical characteristics associated with atypical histology were a macular component (P < .001), irregular borders, and presence of 3 or more colors. Asymmetry, diameter greater than 5 or 6 mm, and progression were not associated with atypical histopathologic characteristics (P > .05). Agreement between clinical and histologic diagnosis was weak (κp = 0.38), whereas the agreement between dermatoscopic and histologic diagnosis was moderate (κp = 0.52). The area under the receiver operating characteristic curve for the model that included dermatoscopy was larger than that for the model that only included clinical data, and this difference was statistically significant.ConclusionsAtypical clinical features were not found to correspond to atypical histology. Dermatoscopy improved the accuracy of clinical diagnosis of atypical melanocytic nevus.     

Prognosis for cutaneous melanoma according to surgical department: comparative study at a tertiary care hospital

IntroductionSurgical treatment of melanoma is performed by dermatologists and general or plastic surgeons. It is not known whether the type of specialist treating the melanoma results in a different prognosis for these patients.Material and methodsA retrospective study was carried out on the epidemiological, clinical/histological and evolutional characteristics of all patients diagnosed with melanoma at Hospital Gregorio Marañón over a 10-year period (1994--2003). The differences by hospital department where the patients were treated (dermatology, general surgery and plastic surgery) were noted.ResultsOver 90 % of the patients with melanoma were treated by the Dermatology Department. The thickness of the tumors and the presence of histologic ulceration were significantly higher in the melanomas treated by general and plastic surgeons (p < 0.05). The differences in overall average survival (105, 55 and 77 months) and disease-free time (88, 24 and 51.3 months) in the melanomas operated on by dermatologists, general surgeons and plastic surgeons, respectively, were significant (p < 0.001).ConclusionsThis study confirms that there are significant differences in the clinical and histological characteristics and the life prognosis of patients with cutaneous melanoma treated by different specialists. The melanomas treated by general or plastic surgeons have usually been developing for a longer time, and therefore are thicker and more often ulcerated than those treated by dermatologists, resulting in a lower survival period. With appropriate medical and surgical training, dermatologists are the most suitable specialists for early diagnosis and treatment.     

Características clínico-patológicas de los melanomas cutáneos diagnosticados en un hospital terciario mediterráneo entre 1990 y 2004: comparación entre sexos,por grupos de edad y evolución a lo largo del tiempo

BackgroundThe incidence of malignant melanoma has increased over recent decades. Early diagnosis continues to be essential for effective treatment. Our objective was to analyze cutaneous malignant melanomas diagnosed over a 15-year period in a tertiary hospital for trends towards earlier diagnosis and to identify subgroups with poorer prognosis.Material and methodsRetrospective analysis of primary cutaneous melanomas analyzed in the pathology department of Hospital La Paz, Madrid, Spain, between 1990 and 2004.ResultsIn total, 526 melanomas were diagnosed. The mean (SD) Breslow thickness was 2.63 (4.84) mm and the median thickness was 0.98 mm (range, 0-65 mm). The mean size (widest point) was 16.59 (12.11) mm. The most common histological type was surface-spreading melanoma and the most common site was the trunk. Melanomas detected in men were generally larger and thicker than in women (P = 0.05). Individuals aged over 60 years consulted for significantly thicker and larger tumors than younger individuals. The incidence of malignant melanomas has increased steadily over the years whereas the mean Breslow thickness and size have decreased.ConclusionsDiagnosis of melanoma in Spain is made increasingly earlier, although locally advanced tumors are still sometimes seen in men and in individuals aged over 60 years.     

The keystone flap and its simplified version for malignant skin tumor defects of the lower limbs: A review of 25 cases

BackgroundSkin tumors commonly occur on the legs and are treated in first line by surgery. Several techniques are available to repair lower limb defects: secondary-intention healing, partial closure, primary closure with or without an s-plasty, or a skin graft. The lack of tissue laxity of the surrounding skin does not allow several local flaps (advancement, rotation, or transposition). Closing large skin defects at this site may be challenging.Patients and methodsWe retrospectively reviewed a series of consecutive patients undergoing malignant tumor wide excision on lower limbs, with a keystone flap or its simplified technique (releasing incision) for closure of a skin defect.ResultsTwenty-five patients, 17 women and 8 men, ranging from 19 to 95 years old (mean age: 70 years) were included. Keystone flap reconstruction on the lower limbs was performed in 19 cases and the simplified technique in 6. The excised tumors were as follows: squamous cell carcinoma (n = 6), basal cell carcinoma (n = 9), melanoma (n = 9) and Bowen's disease (n = 1). Three local complications were observed. No cases of recurrence were observed.ConclusionKeystone flap is a reliable surgical method for reconstruction of lower limb skin defects. Aesthetic results are better than when a skin graft is used, complications are uncommon, and prolonged operative time is avoided.     

Adequacy of surgical margins,re-excision,and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas

BackgroundAchieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC).ObjectivesThe objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC.MethodsThe medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates.ResultsStatistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p = 0.004), tumor size (p = 0.023), tumor location in the H zone of the face (p = 0.005), and aggressive histopathological subtype (p = 0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone.Study limitationsInadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study.ConclusionsOur results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.     

Evaluación de la ecografía cutánea de 15 Mhz en la estimación preoperatoria del espesor tumoral en el melanoma maligno

BackgroundTumor thickness is of great importance in the management of cutaneous malignant melanoma (MM): this variable not only affects prognosis but is also a key factor in planning surgical margins and selecting candidates for sentinel node biopsy. Breslow depth is the standard histologic measure of thickness, but technological advances have provided imaging techniques such as cutaneous ultrasound that can potentially assess tumor thickness and enable prompt initiation of definitive treatment.Objectivesa) To evaluate the utility of ultrasound assessment of tumor thickness in MM, and b) to analyze histologic variables that affect ultrasound assessments of thickness.Materials and methodsRetrospective study of a consecutive series of 79 primary cutaneous MMs in which tumor thickness had been assessed by 15-MHz ultrasound before surgery. We gathered data from histology reports, studying Breslow depth and the presence of ulceration, regression, inflammatory infiltrate, and associated nevi. Correlation coefficients were calculated to evaluate the strength of association between Breslow depth and thickness assessed by ultrasound. We also calculated the sensitivity, specificity, and positive and negative predictive values of ultrasound measurement in the diagnosis of MMs more than 1 mm thick. Associations between histologic variables and the overestimation of thickness by ultrasound were also analyzed.ResultsThe 79 primary MMs studied had a mean (SD) Breslow depth of 0.8 (1.4) mm. There was moderate correlation and agreement between Breslow depth and the ultrasound assessment of thickness (Pearson correlation coefficient, 0.678; intraclass correlation coefficient, 0.78). The tendency of ultrasound to overestimate thickness was nonsignificantly related to the presence of a moderate to intense infiltrate and associated nevi (P > .05). The sensitivity of ultrasound for the diagnosis of MM over 1 mm thick was 82%; specificity was 80%, and positive and negative predictive values were 54% and 94%, respectively.ConclusionsUltrasound imaging quite correctly identifies thin MMs and can be useful for planning adequate surgical margins; however, there are limitations on its usefulness in the diagnosis of thick MMs. Additional studies are required to confirm whether certain histologic characteristics, such as the presence of a moderate to intense inflammatory infiltrate or associated nevi can lead to overestimation of thickness by ultrasound, limiting the clinical utility of this imaging technique in MM management.     

Enfermedad de Paget extramamaria

Background and objectiveExtramammary Paget disease (EMPD) has seldom been studied in Mediterranean populations. We aimed to review the characteristics of our patients with EMPD, the presence of a neoplasm in continuity, and the long-term course of the disease.Patients and methodsRetrospective observational study of 27 patients diagnosed with EMPD between 1990 and 2015. All clinical and pathology findings related to clinical course and outcomes were retrieved for analysis.ResultsTwenty patients were women and 7 were men. Ages ranged from 42 to 88 years (median, 76 years). Lesions were in the following locations: vulva (16 cases), pubis–groin (5), perianal region (4), and axilla (2). Time from onset to diagnosis ranged from 1 to 60 months (median, 12 months) and maximum lesion diameter from 20 to 140 mm (median, 55 mm). In 3 cases (11.1%) EMPD was a secondary condition. None of the lesions developed on a previous cutaneous adnexal adenocarcinoma. Ten of the 24 primary EMPDs (41.7%) invaded the dermis. Eight of the 27 patients (29.6%) experienced local recurrence after the initial surgical treatment.Three patients (11.1%) died as a consequence of metastasis from the EMPD.ConclusionsThe presence of an underlying cutaneous adnexal adenocarcinoma is uncommon, but it is not unusual to find an extracutaneous adenocarcinoma in continuity. Although EMPD is a slow-growing tumor, dermal invasion is frequent and metastasis is not uncommon. Local recurrence is common even after excision with wide margins and may be delated, so long term follow-up is essential.