Standard melanoma-associated markers do not identify the MM127 metastatic melanoma cell line.
Haridas Parvathi,McGovern Jacqui A,Kashyap Abhishek S,McElwain D L Sean,Simpson Matthew J
Reliable identification of different melanoma cell lines is important for many aspects of melanoma research. Common markers used to identify melanoma cell lines include: S100; HMB-45; and Melan-A. We explore the expression of these three markers in four different melanoma cell lines: WM35; WM793; SK-MEL-28; and MM127. The expression of these markers is examined at both the mRNA and protein level. Our results show that the metastatic cell line, MM127, cannot be detected using any of the commonly used melanoma-associated markers. This implies that it would be very difficult to identify this particular cell line in a heterogeneous sample, and as a result this cell line should be used with care.
Clinicopathological features and prognosis of patients with de novo versus nevus-associated melanoma in Taiwan.
Sheen Yi-Shuan,Liao Yi-Hua,Lin Ming-Hsien,Chen Jau-Shiuh,Liau Jau-Yu,Liang Cher-Wei,Chang Yih-Leong,Chu Chia-Yu
Studies surveying melanomas associated with melanocytic nevi in Asia are rare. In this study, we examined whether nevus-associated melanomas differ from de novo melanomas in terms of their associations with clinical factors, histologic characteristics, and patient survival in Taiwan. Using data on cancer cases obtained from the Department of Pathology archives and the Cancer Registry of National Taiwan University Hospital, we conducted a retrospective analysis of 103 consecutive melanoma patients who were diagnosed between 2010 and 2015 and received follow-up through November 2016. Approximately 17.5% of the melanomas in question were associated with a nevus. In patients under 65 years of age, non-acral lentiginous melanomas were significantly associated with a higher percentage of nevus-associated melanomas. The superficial spreading subtype, younger patient age, thinner tumor, intermittent solar exposure, and early stage were significant predictors of a melanoma being histologically associated with a nevus. The appearance of a nevus associated with a melanoma predicted better recurrence-free survival compared with de novo melanomas. Although acral lentiginous melanomas (70.9%) constituted the most common histologic subtype, only 9.6% of the acral lentiginous melanomas were associated with a nevus. Furthermore, there was no statistically significant difference between the nevus-associated and de novo acral lentiginous melanomas with regard to clinicopathological factors and survival. In conclusion, nevus-associated melanomas were uncommon among acral lentiginous melanomas. Relatedly, because over half of all melanomas in Asians are acral lentiginous melanomas, Asians are less likely than Caucasians to have nevus-associated melanomas.
[Perfil de expresión de Ki67 en lesiones melanocíticas palmoplantares: estudio de casos y controles].
González-Ramírez Roger A,Barboza-Quintana Oralia,Flores-Gutiérrez Juan P,de la Fuente-Villarreal David,Torres-López Ernesto,Ríos-Briones Nidia I
Cirugia y cirujanos
Introducción:El melanoma acral lentiginoso es una neoplasia maligna que afecta a población predominantemente no caucásica. Debido al diagnóstico tardío suele tener mal pronóstico, además de que se considera una neoplasia biológicamente más agresiva, incluso cuando se detecta tempranamente. Objetivo:Determinar la expresión de Ki67 en el melanoma acral lentiginoso invasor y compararla con los nevos acrales. Método:Estudio transversal, descriptivo, observacional. Se realizó inmunohistoquímica con marcador Ki67 en 17 biopsias de melanoma acral lentiginoso invasor (casos) y 17 biopsias de nevos palmoplantares (controles). Se determinó la expresión nuclear de Ki-67 y se comparó entre ambos grupos. Resultados:La media de expresión de Ki67 fue del 8.5% en el grupo control y del 34% en el grupo de melanomas, siendo esta diferencia estadísticamente significativa (p < 0.0001). Discusión:La expresión de Ki67 en los melanomas acrales es considerablemente mayor que en los nevos acrales. El valor pronóstico del marcador Ki67 sigue siendo considerado controversial. Sin embargo, hay estudios en los que en combinación con otros marcadores se refuerza su valor pronóstico. Conclusiones:Por la gran diferencia en inmunorreactividad de Ki67 entre melanomas y nevos, la expresión de Ki67, referida como índice proliferativo, podría ser considerada como factor pronóstico incluso más objetivo que el índice mitótico. Background:Acral lentiginous melanoma is a malignant neoplasm which appears in hands and feet. Acral lentiginous melanoma has an unclear etiology, and usually affects non-Caucasian population. Because it is frequently diagnosed lately, acral melanoma has bad prognosis; however, it is biologically more aggressive than other clinicopathological types of melanoma, even when diagnosed early. Objective:To determine the expression of Ki67 in invasive lentiginous acral melanoma and to compare it with acral nevi. Method:Cross-sectional, descriptive, observational study. Immunohistochemistry with Ki67 marker was performed on 17 biopsies of invasive lentiginous acral melanoma (cases) and 17 biopsies of palmoplantar nevi (controls). Nuclear expression of Ki-67 was determined and both were compared between both groups. Results:The mean expression of Ki67 was 8.5% in the control group, and 34% in the melanoma group, which was statistically significant (p < 0.0001). Discussion:Ki67 expression in acral lentiginous melanomas is higher than in acral nevi. Prognostic value of Ki67 is still considered controversial. However, there are several studies where, in combination with other markers, their prognostic value is reinforced. Conclusions:Due to the wide gap in Ki67 expression between melanomas and nevi showed in this study, Ki67 expression, referred to as a proliferative index, could be considered as a prognostic factor even more objective than the mitotic index.
Progression from Acral Lentiginous Melanoma in situ to Invasive Acral Lentiginous Melanoma.
Bae Jung Min,Kim Hyung Ok,Park Young Min
Annals of dermatology
Acral lentiginous melanoma (ALM) is the most common type of cutaneous melanoma in Asians. The very early stage of ALM demonstrates only a proliferation of a few atypical melanocytes within the epidermis, and has been termed ALM in situ. A 74-year-old male patient presented with a pigmented lesion on the left great toe for 12 years, which had initially showed only a few scattered hyperplastic atypical melanocytes without dermal invasion upon biopsy 5 years ago. This time however, rebiopsy of the lesion confirmed a diagnosis of ALM, stage IIIB. It could be inferred that the lesion had slowly progressed from ALM in situ to invasive ALM over a period of 12 years. Herein we report a case of ALM in situ which progressed to invasive ALM over a long period of time. We expect this report may assist physicians in early recognition and proper management of future cases of ALM in situ.
Acral lentiginous melanoma presents distinct clinical profile with high cancer susceptibility.
Nagore Eduardo,Pereda Carolina,Botella-Estrada Rafael,Requena Celia,Guillén Carlos
Cancer causes & control : CCC
BACKGROUND:Acral lentiginous melanoma (ALM) is a distinct histological variant of cutaneous melanoma that presents a genomic profile different from the other variants. Our aim was to explore the distinctive clinical, pathological, and epidemiological characteristics of ALM. PATIENTS AND METHODS:A series of 978 patients with primary cutaneous melanoma was selected from a single referral center. Among these, 79 were located on acral sites and 46 presented an ALM. This group was compared with a group composed of 932 patients with the remaining three most frequent cutaneous melanoma variants. RESULTS:The ALM differed significantly from other variants: in an older age at diagnosis (65.52 vs. 51.79 years), a lower number of common (88.2 vs. 55.8%) and atypical nevi (95.0 vs. 80.2%), a predisposing genetic trait to cancer (22.2 vs. 7.1% had a personal history of other non-cutaneous malignancies and 58.1 vs. 36.4% had at least one first degree relative with non-cutaneous neoplasia) and lower number of sunburns (88.2 vs. 47.4% remembered none). Also, the tumors were thicker (mean of 2.94 vs. 2.03 mm), more frequently ulcerated (74.2 vs. 23.9%) and with perineural invasion (8.0 vs. 1.5%), had lower degree of inflammatory infiltrate (36.8 vs. 7.5% was absent) and were less frequently associated with a previous melanocytic lesion (8.3 vs. 32.6%). Differences were kept even after age-adjusted analyses. CONCLUSIONS:Our results, from a clinical and epidemiological point of view, support recent data on genetic characterization of melanomas. In comparison with the other frequent variants we have shown that ALM has some important differences which emphasize that it is a distinct entity more probably related to certain cancer susceptibility but unrelated to familial melanoma, tendency to developing nevus or sun exposure.
Acral Lentiginous Melanoma Developing during Long-standing Atypical Melanosis: Usefulness of Dermoscopy for Detection of Early Acral Melanoma.
Oh Tae Seok,Bae Eui Jong,Ro Ki Woong,Seo Soo Hong,Son Sang Wook,Kim Il-Hwan
Annals of dermatology
Clinical guidelines suggest that suspicious pigmented lesions of the plantar or palmar area require biopsy for early detection of acral melanoma. We present here a case of acral lentiginous melanoma in which various melanocytic atypia was observed at each biopsy site, including focal melanocytic proliferation. We suggest that this atypical melanosis is part of a contiguous phase of invasive tumor growth, which is known as the very early stage of melanoma in situ. In addition, noninvasive dermoscopy has been effective for the early discovery of hidden lesions of acral melanoma.
Acral lentiginous melanoma: indolent subtype with long radial growth phase.
Kim Jin Yong,Choi Mira,Jo Seong Jin,Min Hye Sook,Cho Kwang Hyun
The American Journal of dermatopathology
Acral lentiginous melanoma (ALM) is the most common type of cutaneous melanoma in Asian populations. Traditionally, ALM was believed to have a poorer prognosis than other subtypes of cutaneous melanoma because of its aggressive behavior. However, in Asians, there have been several unusual case reports that have shown only subtle melanocytic proliferation despite clinically malignant manifestations. We performed a retrospective study of 13 patients with ALM. We reviewed the clinical histories, histopathologies, and immunohistochemical staining from these patients. Clinically, the lesions were characterized by a brown to black pigmented patch with irregular borders and variegated pigmentation on the sole, heel, or finger. Histopathologically, most specimens revealed only bland scattered proliferation of atypical melanocytes without marked cellular atypia or dermal invasion. However, some of the lesions were suspected to progress to the invasive stage, into the papillary dermis after a long period of time. Although cytological atypia of the melanocytes is not sufficient to ALM in situ, the melanocytic proliferation pattern, dermal inflammation, and correlation with clinical presentation would suffice in making the correct diagnosis of ALM in situ. In these cases, more biopsies of other areas should be recommended for the precise diagnosis and early complete excision in accordance with ALM in situ.
Clinical presentation of acral lentiginous melanoma: a descriptive study.
Pereda C,Traves V,Requena C,Serra-Guillén C,Llombart B,Sanmartín O,Guillén C,Nagore E
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.
Acral lentiginous melanoma of the foot misdiagnosed as a traumatic ulcer. A cautionary case.
Gumaste Priyanka,Penn Lauren,Cohen Nicole,Berman Russell,Pavlick Anna,Polsky David
Journal of the American Podiatric Medical Association
The incidence of cutaneous melanoma is rising faster than that of almost any other cancer in the United States. Acral lentiginous melanoma is a subtype of melanoma that involves the palms, soles, and nail beds. Although it is one of the rarer types of melanoma, it has a poorer prognosis than other more common subtypes. We describe a case of plantar acral melanoma in a 66-year-old woman that was initially misdiagnosed as a traumatic foot ulcer. We highlight this case to emphasize the importance of close observation and biopsy of ulcerative lesions of the foot that have atypical features or are refractory to standard treatment.
Early detection of acral melanoma: A review of clinical, dermoscopic, histopathologic, and molecular characteristics.
Darmawan Claudia C,Jo Gwanghyun,Montenegro Sara E,Kwak Yoonjin,Cheol Lee,Cho Kwang Hyun,Mun Je-Ho
Journal of the American Academy of Dermatology
Acral lentiginous melanoma is a distinct subtype of melanoma on acral skin. Patient presentation at later stages and delayed diagnosis by physicians contribute to a worse associated prognosis and survival rate. Despite our progress in understanding the key features of this disease, the diagnosis of early-stage acral melanoma is still challenging. It is essential to integrate clinical, dermoscopic, and histologic findings in the diagnosis of acral lentiginous melanoma. In addition, molecular studies can be helpful. In this review, we have summarized our current understanding of this disease entity from articles that were published between 1969 and 2018. We have outlined clinical and dermoscopic features as well as pathologic and molecular findings regarding acral melanoma and have presented an algorithm for diagnosis. Understanding and integrating these characteristics may assist clinicians in the early detection of acral melanomas.
Rare cause of non-healing foot wound--acral lentiginous melanoma.
Gerslova Alena,Pokorna Andrea,Stukavcova Alena,Veverkova Lenka
Neuro endocrinology letters
The etiology of skin integrity disorders of the lower extremities can be very diverse. In addition to common diagnoses such as venous ulcers with ischemic etiology, decubitus ulcers and diabetic foot syndrome, ulceration of a malignant etiology must also be considered. Malignant melanoma is one of the most dangerous forms of skin cancer and, although rare, may cause foot lesions. The most frequently encountered type of melanoma on acral parts of the limbs is the rare acral lentiginous variant, which only occurs in 2-10% of all melanoma types. Clinical manifestation ranges from cutaneous surface erosion to ulceration with surrounding hyperkeratosis, which can cause considerable differential diagnostic difficulties in the management of patients with non-healing foot wounds. This paper aims to present a clear case study of a Caucasian female with chronic leg ulceration that resulted in a final diagnosis of malignant acral lentiginous melanoma. Supplemental theoretical information regarding the diagnosis and treatment of malignant melanoma has also been included in the report. Malignant acral lentiginous melanoma is a rare cause of non-healing wounds, but it must be considered in cases with long-term healing complications. Precise diagnostic deliberation is crucial in the management and treatment of all chronic and long-term non-healing lesions, and appropriately performed biopsies are essential to determine whether malignancy is the primary cause.
Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease.
Basurto-Lozada Patricia,Molina-Aguilar Christian,Castaneda-Garcia Carolina,Vázquez-Cruz Martha Estefania,Garcia-Salinas Omar Isaac,Álvarez-Cano Alethia,Martínez-Said Héctor,Roldán-Marín Rodrigo,Adams David J,Possik Patricia A,Robles-Espinoza Carla Daniela
Pigment cell & melanoma research
Acral lentiginous melanoma is a histological subtype of cutaneous melanoma that occurs in the glabrous skin of the palms, soles and the nail unit. Although in some countries, particularly in Latin America, Africa and Asia, it represents the most frequently diagnosed subtype of the disease, it only represents a small proportion of melanoma cases in European-descent populations, which is partially why it has not been studied to the same extent as other forms of melanoma. As a result, its unique genomic drivers remain comparatively poorly explored, as well as its causes, with current evidence supporting a UV-independent path to tumorigenesis. In this review, we discuss current knowledge of the aetiology and diagnostic criteria of acral lentiginous melanoma, as well as its epidemiological and histopathological characteristics. We also describe what is known about the genomic landscape of this disease and review the available biological models to explore potential therapeutic targets.
Acral lentiginous melanoma: Clinicopathologic and survival differences according to tumour location.
Howard Matthew,Xie Charles,Wee Edmund,Wolfe Rory,McLean Catriona,Kelly John W,Pan Yan
The Australasian journal of dermatology
BACKGROUND/OBJECTIVES:Acral lentiginous melanoma (ALM) is a melanoma subtype associated with atypical locations on the hands and feet and advanced disease at diagnosis. There is a limited understanding of whether the survival is similar for nail, non-nail, lower limb and upper limb ALM patients. We therefore explored clinicopathologic characteristics and melanoma-specific survival of ALM patients according to tumour location. METHODS:A prospectively collected cohort study was performed of all primary invasive cutaneous acral lentiginous melanomas with known thickness and tumour location reviewed at a tertiary referral centre over 21 years. RESULTS:A total of 101 ALM patients were reviewed from 1994 until 2016. The majority of cases (82/101) occurred on the feet. Hand ALMs were thicker and more likely to be ulcerated than feet ALMs (P = 0.05 and 0.02, respectively); however, survival was not statistically different between these two groups (univariate HR 0.48 P = 0.11, 95% CI, 0.20-1.17; multivariate HR 0.67 P = 0.40, 95% CI, 0.27-1.69, respectively). Non-nail ALM patients had longer survival when compared to nail ALM on univariate analysis (HR 0.40, 95% CI, 0.17 to 0.90) which was accounted for by Breslow thickness and ulceration (multivariate HR 0.56, 95% CI, 0.24 to 1.34). CONCLUSIONS:The reduced melanoma-specific survival in nail ALM patients was likely due to their greater thickness and ulceration. Although hand ALMs are thicker and more frequently ulcerated, this is likely due to the higher proportion of nail ALMs present in this location.
Acral Lentiginous Melanoma, Indolent Subtype Diagnosed by Excision: A Case Report.
Ohn Jungyoon,Bae Jeong Mo,Lim Ji Soo,Park Jong Seo,Yoon Hyun-Sun,Cho Soyun,Park Hyun-Sun
Annals of dermatology
Nail unit melanoma is a type of acral lentiginous melanoma and requires histopathologic examination for a confirmed diagnosis. However, inadequate biopsy techniques make definitive diagnosis difficult. A 61-year-old man presented with progressive nail pigmentation for 15 years, which was clinically highly suspicious for malignancy. Acral lentiginous melanoma was not detected in punch and longitudinal biopsy specimens, but excision tissue revealed melanoma. Acral lentiginous melanoma is known to have a heterogeneous pathologic manifestation depending on the pigmented region and the time it takes to progress. In this regard, excision can be considered as a first-line biopsy technique to diagnose acral lentiginous melanoma, indolent subtype.
Acral Lentiginous Melanoma of Foot and Ankle: A Clinicopathological Study of 7 Cases.
Hao Xingpei,Yim Joon,Chang Stewart,Schwartz Erika,Rubenstein Seth,Friske Casey,Shamim Sana,Masternick Eric,Mirkin Gene
BACKGROUND/AIM:Acral lentiginous melanoma (ALM) is a rare entity on the foot. This study aimed to reveal its clinical presentations, histopathology and treatment options. MATERIALS AND METHODS:Seven cases of ALM involving foot were treated in our Institute in a 3-year period. RESULTS:The patients' age ranged from 38 to 84 years, with a mean of 65. The ratios of males to females and white to non-white were 4:3 and 5:2, respectively. Clinically, ALM presented as asymmetric, irregular shaped, black-brown, variegatedly discolored, papular, verrucoid, ulcerated or nodular lesions with or without pain. All ALMs were treated with either wide local excision (WLE) or toe amputation. Histologically, ALM was characterized by multiple single and nested atypical melanocytes growing along the dermal-epidermal junction, and extending into dermal layer in nodular growth pattern. CONCLUSION:ALM is a rare, asymmetric, irregularly bordered, variegatedly pigmented lesion. WLE or toe amputation is the standard treatment option.
Acral lentiginous melanoma versus other melanoma: A single-center analysis in Japan.
Wada Maiko,Ito Takamichi,Tsuji Gaku,Nakahara Takeshi,Hagihara Akihito,Furue Masutaka,Uchi Hiroshi
The Journal of dermatology
We summarize herein our 14-year experience of conventional treatment outcomes before the era of molecular-targeted therapy and immunotherapy. Specifically, we conducted a retrospective review of our 252 patients with primary cutaneous melanoma (acral lentiginous melanoma [ALM], n = 121; non-acral lentiginous melanoma [non-ALM], n = 131), and compared the prognostic factors between ALM and non-ALM. Melanoma-specific survival and disease-free survival were estimated using the Kaplan-Meier method. Regarding the results, all patients were Japanese (106 male and 146 female), with a mean age of 60.1 years. Among ALM patients, age was elder and primary tumor size was larger than non-ALM. As for tumor thickness, in situ lesions were more frequently observed in ALM. There was no significant difference in the distribution of tumor thickness between the two groups when excluding the in situ lesions. For treatment of the primary melanoma, 248 patients (98.4%) had undergone curative surgical excision and 120 patients with more than 1 mm or ulcerated melanoma had undergone sentinel lymph node biopsy. Patients with systemic metastasis primarily underwent dacarbazine-based chemotherapy. The Kaplan-Meier survival curves revealed no significant difference in melanoma-specific survival and disease-free survival between those with ALM and non-ALM. The results also showed that both ALM and non-ALM, when they initially metastasize, first affect the regional lymph nodes. Incisional biopsy was not an adverse prognostic factor. These results suggest that ALM does not differ in its biological behavior from non-ALM, so we can consider ALM as being equivalent to non-ALM. The initial treatment for ALM and non-ALM can involve the same strategy.
Histopathological diagnosis of acral lentiginous melanoma in early stages.
Fernandez-Flores Angel,Cassarino David S
Annals of diagnostic pathology
Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma.
National Comprehensive Analysis of Characteristics of Acral Lentiginous Melanoma.
Huayllani Maria T,Restrepo David J,Boczar Daniel,Avila Francisco R,Bagaria Sanjay P,Spaulding Aaron C,Rinker Brian D,Forte Antonio J
BACKGROUND/AIM:Acral lentiginous melanoma (ALM) is the least common subtype of cutaneous melanoma and typically occurs on the palms, soles, and nails. Tumor characteristics and disease severity in the US population are not well understood. Our aim was to analyze the characteristics of ALM of the extremities. PATIENTS AND METHODS:We queried the National Cancer Database to identify patients with the diagnosis of ALM and common malignant melanoma located in the extremities (CMME). We compared demographic, tumor, and treatment characteristics between patients with ALM and those with CMME. Statistical analysis was performed with chi-squared test and multivariate logistic regression models. RESULTS:We identified 5,203 patients with ALM and 118,485 with CMME. When compared with patients with CMME, those with ALM were more likely to be older than 80. years at diagnosis [odds ratio (OR)=2.85, 95% confidence intervaI (CI)=2.12-3.82; p<0.001], have stage III disease (OR=4.22, 95% CI=1.47-12.16; p=0.01), and have ulceration (OR=1.52, 95% CI=1.33-1.74; p<0.001). Moreover, patients with ALM were less likely to have a mitotic count of 1/mm or greater (OR=0.57, 95% CI=0.48-0.67; p<0.001). No statistical difference was found for sex, lymph node involvement, regression, and use of surgery, radiotherapy, and immunotherapy between groups. CONCLUSION:Age, disease stage, ulceration, and mitotic count are independent factors associated with ALM. Knowledge of the disease characteristics may allow for better diagnosis and understanding of disease pathophysiology.