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de la Rosa I, Sisó P, Ríos C, Gracia J, Cuevas D, Maiques O, Eritja N, Soria X, Angel-Baldó J, Gatius S, Sanchez-Moral L, Sarrias MR, Matias-Guiu X, Martí RM, Macià A. High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma. Int J Mol Sci 2025; 26:4097. [PMID: 40362334 PMCID: PMC12071846 DOI: 10.3390/ijms26094097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 04/16/2025] [Accepted: 04/19/2025] [Indexed: 05/15/2025] Open
Abstract
Acral lentiginous melanoma (ALM) is a rare melanoma subtype primarily located in acral regions. However, ALMs exhibit a distinctive genetic profile characterized by a high number of copy number variations (CNVs) and limited point mutations. Late diagnosis and restricted therapeutic efficacy contribute to its poor prognosis. The secretome within the tumor microenvironment (TME) influences immune modulation and plays a vital role in melanoma progression. We aim to analyze the role of ALM secretome and CNVs profile with prognosis in primary ALM patients. Here, we demonstrated that high CNV burden (CNVsHigh) was associated with worse clinicopathological characteristics and poor prognosis. Furthermore, our study also revealed that conditioned media (CM) of CNVsHigh genetic profile ALM cell line was associated with pro-tumoral, pro-angiogenic, and immunosuppressive secretome profiles. In addition, CM of CNVsHigh cell lines in vitro promotes macrophage polarization to immunosuppressive phenotype. Moreover, we observed an increased presence of immunosuppressive tumor-associated macrophages (TAMs) at the invasive front (IF) of CNVsHigh ALM biopsies. This research reveals the adverse prognostic impact of CNVsHigh in ALM patients, establishing a novel link with a pro-tumor secretome, offering potential biomarkers for prognosis and personalized treatment to enhanced disease monitoring in ALM patients.
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Affiliation(s)
- Inés de la Rosa
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
| | - Pol Sisó
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
| | - Christopher Ríos
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
| | - Judith Gracia
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
| | - Dolors Cuevas
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain
- Centre of Biomedical Research on Cancer (CIBERONC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Oscar Maiques
- Cytoskeleton and Cancer Metastasis Group, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SM2 5NG, UK;
- Center for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London EC1M 6BQ, UK
| | - Núria Eritja
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
- Centre of Biomedical Research on Cancer (CIBERONC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Xavier Soria
- Department of Dermatology, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (X.S.); (J.A.-B.)
| | - Joan Angel-Baldó
- Department of Dermatology, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (X.S.); (J.A.-B.)
| | - Sonia Gatius
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain
- Centre of Biomedical Research on Cancer (CIBERONC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Lidia Sanchez-Moral
- Innate Immunity Group, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain; (L.S.-M.); (M.-R.S.)
| | - Maria-Rosa Sarrias
- Innate Immunity Group, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain; (L.S.-M.); (M.-R.S.)
- Center for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
| | - Xavier Matias-Guiu
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain
- Centre of Biomedical Research on Cancer (CIBERONC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Rosa M. Martí
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
- Centre of Biomedical Research on Cancer (CIBERONC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
- Department of Dermatology, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (X.S.); (J.A.-B.)
| | - Anna Macià
- Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain; (I.d.l.R.); (P.S.); (C.R.); (J.G.); (D.C.); (N.E.); (S.G.); (X.M.-G.)
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Asato MA, Moares-Neto FA, de Toledo Moraes MP, Ocanha-Xavier JP, Takita LC, Marques MEA, Xavier-Júnior JCC. Depth of invasion analysis to predict acral melanoma outcomes. Ann Diagn Pathol 2024; 71:152305. [PMID: 38640808 DOI: 10.1016/j.anndiagpath.2024.152305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/03/2024] [Accepted: 04/06/2024] [Indexed: 04/21/2024]
Abstract
BACKGROUND Acral melanoma is a subtype with worse outcomes. The Breslow micrometric measurement is the most critical parameter in planning treatment and predicting outcomes. However, for acral lentiginous melanoma, the value of the Breslow thickness is a matter of debate. Depth of Invasion (DOI) is a well-established measure for staging oral squamous cell carcinoma. OBJECTIVE This study compared DOI and Breslow thickness for predicting acral melanoma outcomes. METHODS We performed a retrospective cross-sectional study of 71 acral melanoma lesions subjected to sentinel lymph node biopsy at one Brazilian referral center. RESULTS Cox model univariate analysis showed that both DOI and Breslow thickness predicted melanoma specific survival (HR 1.12; p = 0.0255 and HR 1.144; p = 0.0006, respectively), although Kaplan Meier curve was only significant for Breslow (χ2 = 5.792; p = 0.0161) and not for DOI (χ2 = 0.2556; p = 0.6132). Sentinel lymph node status and presence or absence of ulceration also predicted specific survival in patients with acral melanoma (χ2 = 6.3514; p = 0.0117 and χ2 = 4.2793; p = 0.0386, respectively). Multivariate analysis, however, demonstrated that Breslow depth was the only independent parameter for predicting acral melanoma specific survival (HR 1.144; p = 0.0006). CONCLUSION Even though Breslow thickness remains the main predictor for survival in acral melanoma, it is not a perfect parameter. The introduction of DOI in this context opens new perspectives for predicting acral melanoma outcomes.
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Affiliation(s)
- Marcel Arakaki Asato
- School of Medicine, The Federal University of Mato Grosso do Sul; School of Medicine, São Paulo State University, Botucatu, SP, Brazil.
| | | | | | | | | | | | - José Cândido Caldeira Xavier-Júnior
- School of Medicine, São Paulo State University, Botucatu, SP, Brazil; School of Medicine, Centro Universitário Unisalesiano Auxilium, Araçatuba, SP, Brazil; Pathology Institute of Araçatuba, Araçatuba, SP, Brazil.
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Ismael A, Alsamman MI, Al Laham O, Albrijawy R, Badran A. Progressive Acral Lentiginous Melanoma diagnosed via histopathology and surgically eradicated in a fingernail in a 69-year-old male - A Case Report. Int J Surg Case Rep 2022; 98:107611. [PMID: 36380543 PMCID: PMC9468374 DOI: 10.1016/j.ijscr.2022.107611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/03/2022] [Accepted: 09/04/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction and importance Acral Lentiginous Melanoma (ALM) transpires in a profoundly scarce percentage of the population and is intercalated with a low survival rate. This is partly because such tumors are chiefly diagnosed at an advanced stage. Diagnosis is delayed largely due to the difficulties in recognizing the early histopathological signs and clinical presentations of Acral Melanoma. Case presentation We demonstrate the case of a previously healthy 69-year-old Middle Eastern male patient, who presented to our university hospital's Dermatology clinic with a papule under the right ring fingernail with spontaneous Onycholysis of the entire nail, suggesting a spontaneous malformation in his finger. Clinical discussion ALM is an abundantly rare subtype of melanoma that chiefly originates from the skin of the acral tissues. In this case it arose on the fingernail of a 69-year-old male, who has undergone 2 surgeries to eradicate the tumor with safe margins and as a ramification of successful follow-up for 6 months, has been deemed free of tumor recurrence or metastasis. Conclusion The aim of this article is to highlight the vitality of early detection, diagnosis, prognosis, and treatment of malignant Acral Lentiginous Melanoma in patients of all ages, especially with older patient populations.
Acral Lentiginous Melanoma constitutes approximately 2–3 % of all classes of melanomas. Acral Lentiginous Melanoma is the rarest of the previously mentioned subtypes of melanoma. ALM is usually occurs in white Caucasian populations, but it has a higher affinity to arise in Asian populations. Diagnosis is delayed due to the difficulties in recognizing the histopathological signs and clinical presentations of ALM. The gold standard treatment for malignant melanomas is surgical excision of the lesion along with safety margins.
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Affiliation(s)
- Abrar Ismael
- Dermatology University Hospital, Damascus, Syria; Faculty of Medicine, Damascus University, Damascus, Syria.
| | | | - Omar Al Laham
- Faculty of Medicine, Damascus University, Damascus, Syria.
| | | | - Ayham Badran
- Dermatology University Hospital, Damascus, Syria; Faculty of Medicine, Damascus University, Damascus, Syria.
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Wei X, Wu D, Chen Y, Li H, Zhang R, Yao H, Chi Z, Cui C, Bai X, Mao L, Qi Z, Li K, Lan S, Chen L, Guo R, Yao X, Lian B, Kong Y, Dai J, Tang B, Wang X, Guo J, Si L. Prognostic value of ulceration varies across Breslow thicknesses and clinical stages in acral melanoma: a retrospective study. Br J Dermatol 2022; 186:977-987. [PMID: 35042273 PMCID: PMC9314718 DOI: 10.1111/bjd.21026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/21/2021] [Accepted: 01/11/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Ulceration is regarded as an adverse prognostic factor and is used together with tumour thickness to subcategorize patients with cutaneous melanoma. However, the prognostic impact of ulceration in acral melanoma (AM) is controversial. OBJECTIVES To assess the prognostic impact of ulceration in AM and the variability across different Breslow thicknesses and clinical stages. METHODS A multicentre retrospective study of patients diagnosed with AM between January 2000 and December 2017. Differences in melanoma-specific survival (MSS) between patients with and without ulceration were assessed using the multivariable Cox proportional hazards model and log-rank test. RESULTS Among 1053 enrolled patients, 62.6% had ulceration. After a median follow-up of 61 months, patients with ulceration had a lower median MSS than those without: 66.1 months, 95% confidence interval (CI) 60.0-86.0 vs. not reached; hazard ratio 1.41, 95% CI 1.09-1.82; P = 0.012. Among patients with thin (≤ 1 mm) melanoma, the survival curves of patients with vs. without ulceration clearly separated over time (P < 0.001). No association between ulceration and MSS was observed for melanomas of thickness > 1 mm (subgroups of T2, T3 and T4; all P-values > 0.05) or patients with stage III disease (hazard ratio 1.09, 95% CI 0.71-1.68, P = 0.39). CONCLUSIONS Ulceration is an independent negative prognostic factor for patients with AM, but the impact varies across Breslow thicknesses and clinical stages. Ulceration has a significant effect on prognosis for patients with thin (≤ 1 mm) melanoma, but there was no association between ulceration and survival in intermediate/thick AM or stage III AM. What is already known about this topic? Ulceration status is used together with Breslow tumour thickness to subcategorize patients into different stages according to the America Joint Committee on Cancer melanoma staging system. As one distinctive subtype of cutaneous melanoma, acral melanoma (AM) is characterized by poor survival outcomes due to delayed diagnosis and a high prevalence of negative prognostic and genetic features. The prognostic impact of ulceration in AM is still controversial. What does this study add? This was the first large-scale study to assess the prognostic and staging values of ulceration in patients with AM. Ulceration has a significant effect on prognosis for patients with thin (≤1 mm) melanoma, but no association between ulceration and survival was found in intermediate/thick or stage III AM. These findings should be considered when using ulceration-based staging systems.
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Affiliation(s)
- Xiaoting Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Di Wu
- Cancer CenterThe First Hospital of Jilin UniversityJilinChina
| | - Yu Chen
- Department of Medical OncologyFujian Cancer Hospital & Fujian Medical University Cancer HospitalFujianChina
| | - Hang Li
- Department of DermatologyPeking University First Hospital, National Clinical Research Center for Skin and Immune diseasesBeijingChina
| | - Rui Zhang
- Department of Colorectal SurgeryCancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteLiaoningChina
| | - Hong Yao
- Department of Cancer Biotherapy CenterYunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical UniversityYunnanChina
| | - Zhihong Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Chuanliang Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Xue Bai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Lili Mao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Zhonghui Qi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Ke Li
- Department of Cancer Biotherapy CenterYunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical UniversityYunnanChina
| | - Shijie Lan
- Cancer CenterThe First Hospital of Jilin UniversityJilinChina
| | - Lizhu Chen
- Department of Medical OncologyFujian Cancer Hospital & Fujian Medical University Cancer HospitalFujianChina
| | - Rui Guo
- Department of Colorectal SurgeryCancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteLiaoningChina
| | - Xinyu Yao
- Department of DermatologyPeking University First Hospital, National Clinical Research Center for Skin and Immune diseasesBeijingChina
| | - Bin Lian
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Yan Kong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Jie Dai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Bixia Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Xuan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Jun Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
| | - Lu Si
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and SarcomaPeking University Cancer Hospital & InstituteBeijingChina
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Cheraghlou S, Ugwu N, Girardi M. Sentinel Lymph Node Biopsy Positivity in Patients With Acral Lentiginous and Other Subtypes of Cutaneous Melanoma. JAMA Dermatol 2022; 158:51-58. [PMID: 34878492 PMCID: PMC8655663 DOI: 10.1001/jamadermatol.2021.4812] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 10/05/2021] [Indexed: 12/22/2022]
Abstract
IMPORTANCE Acral lentiginous melanoma (ALM) is a rare subtype of malignant melanoma typically occurring on the palmar and plantar surfaces. Although it has distinctive genetic, prognostic, and behavioral characteristics relative to cutaneous melanomas overall, owing to its rarity, treatment is largely guided by data extrapolated from more common subtypes. Although sentinel lymph node (SLN) status has been shown to be a significant prognostic factor for ALM, the independent effect of ALM-subtype disease on the likelihood of SLN positivity and the stage-specific positivity rates for ALM are not well characterized. OBJECTIVE To evaluate the association of ALM with SLN status as well as to characterize the clinical stage-specific rates of SLN positivity for ALM based on the AJCC Cancer Staging Manual, 8th edition (AJCC-8). DESIGN, SETTING, AND PARTICIPANTS The National Cancer Database (NCDB) includes all reportable cases from Commission on Cancer accredited facilities and represents approximately 50% of all newly diagnosed melanoma cases in the US. This retrospective cohort study included cases of AJCC-8 clinical stage I to II melanomas from the NCDB diagnosed from 2012 to 2015. The analysis took place between April 2021 and September 2021. EXPOSURES Melanoma histopathologic subtype. MAIN OUTCOMES AND MEASURES Sentinel lymph node status. RESULTS We identified 60 148 patients with malignant melanomas, 959 of whom had ALM-subtype disease. Among patients in the cohort, 25 550 (42.5%) were women and the mean (SD) age was 64 (16) years. Multivariable logistic regression controlling for demographic and histopathologic characteristics revealed that ALM was independently associated with the highest risk for SLN positivity among included subtypes (vs superficial spreading melanoma: odds ratio, 1.91; 95% CI, 1.59-2.28). Subgroup analysis by AJCC clinical stage demonstrated that ALM was independently associated with the highest risk for SLN positivity for both stage IB and II disease. The rate of SLN positivity for patients with stage IB and II ALM was 18.39% (95% CI, 13.82%-24.03%) and 39.53% (34.98%-44.26%), respectively. CONCLUSIONS AND RELEVANCE In this cohort study ALM was independently associated with SLN positivity and had relatively high positivity rates at clinical stage IB and II. This suggests that SLNB should be encouraged for all patients with clinical stage IB and II ALM, and such patients should receive appropriate counseling about the higher regional metastatic risk of their cancers. Future work with a larger cohort is required to elucidate the risk of SLN positivity for stage IA ALM.
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Affiliation(s)
- Shayan Cheraghlou
- The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York
| | - Nelson Ugwu
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut
| | - Michael Girardi
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut
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Prognostic significance of acral lentiginous histologic type in T1 melanoma. Mod Pathol 2021; 34:572-583. [PMID: 32759976 DOI: 10.1038/s41379-020-0641-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/20/2020] [Accepted: 07/20/2020] [Indexed: 01/10/2023]
Abstract
Acral lentiginous melanoma (ALM) is a rare type of cutaneous melanoma with a poor prognosis. It is unclear whether the poor outcome of ALM is due to its inherent disease characteristics or advanced stage at initial diagnosis. To address this question, we retrospectively analyzed the clinicopathologic factors of 828 thin (T1; Breslow thickness ≤1.0 mm) melanomas [129 (15.6%) ALMs and 699 (84.4%) non-ALMs] and their nodal and distance metastases and local recurrence rates and determined their relationship with the disease-specific (DSS), overall (OS), and recurrence-free survivals (RFS) at the pathologic stages T1, T1a, and T1b with a median follow-up time of 84.5 months. With the exception of OS at T1b stage, ALM patients showed significantly lower 5- and 10-year DSS, OS, and RFS rates at every pathologic stage when compared with non-ALM. In multivariable analysis, ALM histologic type, SLN positivity, age, and the use of systemic therapy were detected as independent poor prognostic factors associated with significantly lower survival rates. ALM histologic type was associated with lower DSS and OS rates at T1 and T1a stages and lower RFS rates at T1b stage. SLN positivity was associated with lower DSS, OS, and RFS rates at T1, T1a, and T1b stages. Age was associated with lower OS rates at T1 and T1b stages. Whereas the use of systemic therapy was associated with lower DSS rates at T1a stage and RFS rates at T1b stage. In addition, the ALM group showed significantly older median age patients and higher rates of female sex, Hispanic ethnicity, nevoid cytology, non-brisk tumor-infiltrating lymphocytes, nodal metastasis, and local recurrence at every pathologic stage of thin melanoma. Our findings suggest that ALM is inherently more aggressive than other types of cutaneous melanoma. This information may be useful for prognostic stratification of patients with thin melanomas, especially to help guide the clinical decision-making for SLN biopsy and patients entering clinical trials.
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Franke V, Smeets PMG, van der Wal JE, van Akkooi ACJ. Complete response to talimogene laherparepvec in a primary acral lentiginous melanoma. Melanoma Res 2020; 30:548-551. [PMID: 32516238 DOI: 10.1097/cmr.0000000000000673] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Talimogene laherparepvec (T-VEC) is an oncolytic virus, approved for the treatment of stage IIIb-IVM1a melanoma with injectable disease (cutaneous, subcutaneous or lymphatic). It is a modified herpes simplex virus type 1 that induces tumor-specific T-cell responses via reduction of virally mediated suppression of antigen presentation, stimulation of viral pathogenicity and enhancement of tumor-selective replication. Response rates up to 82.6% have been reported for stage III disease. Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with a poor prognosis. Here, we present a case of an elderly and frail patient with primary ALM who refused surgical treatment and consented to receive T-VEC as first-line drug therapy. After 10 courses of treatment, a histopathologically confirmed complete response was achieved. To our knowledge, this is the first case ever reported in which a primary ALM is (successfully) treated with T-VEC.
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Redi U, Marruzzo G, Lovero S, Khokhar HT, Lo Torto F, Ribuffo D. Acral lentiginous melanoma: A retrospective study. J Cosmet Dermatol 2020; 20:1813-1820. [PMID: 32979858 DOI: 10.1111/jocd.13737] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 08/12/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acral lentiginous melanoma (ALM) carries one of the worst prognoses among other subtypes. This malignant tumor is found on the distal limbs and is usually detected at late stages. Hereby, the authors present their experience on this melanoma subtype. METHODS A retrospective study was conducted. Data were extracted from patients' medical records and from phone interviews. RESULTS A total of 43 patients were included in the study. The main signs and symptoms disclosed by the patients were bleeding (41.9%), size greater than 6 mm (41.9%), change in size (37.2%), change in shape (30.2%), rise above the surface of the skin (27.9%), change in color (20.9%), irregular borders (16.3%), and inflammation (16.3%). The first healthcare professional consulted was a general practitioner or a dermatologist in the majority of cases (88.3%). Only 44.2% of the patients were sent by their first physician for a biopsy, whereas 30.3% were sent by the 2nd physician. 14 patients underwent biopsy within 1 month from the first appointment with a physician, while 20 patients within 3 months and 9 patients within 6 months. Only 7 patients sought medical attention in the first 3 months; 21 patients sought medical care between 3 months and one year from the appearance of the lesion, while the remaining 15 patients waited more than a year. CONCLUSIONS One of the major issues found in ALM is represented by the diagnostic delay; this may be due to either the patients or the physicians' failure to recognize warning signs.
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Affiliation(s)
- Ugo Redi
- Department of Surgery "Pietro Valdoni", Plastic Surgery Unit, Sapienza University of Rome, Rome, Italy
| | - Giovanni Marruzzo
- Department of Surgery "Pietro Valdoni", Plastic Surgery Unit, Sapienza University of Rome, Rome, Italy
| | - Stefano Lovero
- Department of Surgery "Pietro Valdoni", Plastic Surgery Unit, Sapienza University of Rome, Rome, Italy
| | | | - Federico Lo Torto
- Department of Surgery "Pietro Valdoni", Plastic Surgery Unit, Sapienza University of Rome, Rome, Italy
| | - Diego Ribuffo
- Department of Surgery "Pietro Valdoni", Plastic Surgery Unit, Sapienza University of Rome, Rome, Italy
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Behbahani S, Malerba S, Samie F. Acral lentiginous melanoma: clinicopathological characteristics and survival outcomes in the
US
National Cancer Database 2004–2016. Br J Dermatol 2020; 183:952-954. [DOI: 10.1111/bjd.19211] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | - S. Malerba
- Rutgers New Jersey Medical School Newark NJ USA
| | - F.H. Samie
- Department of Dermatology Columbia University Irving Medical Center New York NY USA
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10
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Wei X, Wu D, Li H, Zhang R, Chen Y, Yao H, Chi Z, Sheng X, Cui C, Bai X, Qi Z, Li K, Lan S, Chen L, Guo R, Yao X, Mao L, Lian B, Kong Y, Dai J, Tang B, Yan X, Wang X, Li S, Zhou L, Balch CM, Si L, Guo J. The Clinicopathological and Survival Profiles Comparison Across Primary Sites in Acral Melanoma. Ann Surg Oncol 2020; 27:3478-3485. [PMID: 32253677 PMCID: PMC7410855 DOI: 10.1245/s10434-020-08418-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Indexed: 01/10/2023]
Abstract
Background The clinicopathological and survival profiles across primary sites in acral melanoma (AM) are still controversial and unclear. Methods This is a multi-center retrospective study. Clinicopathological data of AM patients diagnosed between 1 January 2000 and 31 December 2017 from 6 large tertiary hospitals in China were extracted. Chi square tests were used to compare basic characteristics between primary sites of sole, palm and nail bed. Melanoma-specific survival (MSS) differences based on primary sites were compared by log-rank tests and multivariate Cox regressions were used to identify prognostic factors for MSS. Results In total, 1157 AM patients were included. The sole group had a more advanced initial stage, deeper Breslow thickness, higher recurrence rate and distant metastases risk (all P < 0.05). The proportion of age < 65 years and ulceration were statistically lower in nail bed and palm groups, respectively. A total of 294 patients underwent sentinel lymph node biopsy and rates of positive SLN status had no statistical difference across primary sites. Among 701 patients with genetic profiles, the mutational frequency of BRAF, C-KIT, and PDGFRA were similar except for NRAS (higher in sole group, P = 0.0102). The median MSS of sole, nail bed and palm patients were 65.0 months, 112.0 months, and not reached, respectively (log-rank P = 0.0053). In multivariate analyses, primary site, initial stage, ulceration and recurrence were the prognostic factors for MSS in overall population, but the statistical significance varied over primary sites. Conclusions Substantial clinicopathological and survival heterogeneities exist across different primary sites in the AM population. Sole melanoma has worse prognosis compared with palm and nail bed subtypes.
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Affiliation(s)
- Xiaoting Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Di Wu
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Hang Li
- Department of Dermatology, National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, China
| | - Rui Zhang
- Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yu Chen
- Department of Medical Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Hong Yao
- Department of Cancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Zhihong Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Xinan Sheng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Chuanliang Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Xue Bai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Zhonghui Qi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Ke Li
- Department of Cancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shijie Lan
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Lizhu Chen
- Department of Medical Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Rui Guo
- Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Xinyu Yao
- Department of Dermatology, National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, China
| | - Lili Mao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Bin Lian
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Yan Kong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Jie Dai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Bixia Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Xieqiao Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Xuan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Siming Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Li Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Charles M Balch
- University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lu Si
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China.
| | - Jun Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China.
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11
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Csányi I, Houshmand N, Szűcs M, Ócsai H, Kemény L, Oláh J, Baltás E. Acral lentiginous melanoma: a single-centre retrospective review of four decades in East-Central Europe. J Eur Acad Dermatol Venereol 2020; 34:2004-2010. [PMID: 31989672 DOI: 10.1111/jdv.16227] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 12/17/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Acral lentiginous melanoma (ALM) occurs on the palms, soles and subungual surface and has poor prognosis. It is uncommon in the Caucasian population and has remained unreported in East-Central Europe. OBJECTIVES Our aim was to collect data from East-Central Europe by analysing the demographic and clinicopathologic features of patients with ALM and comparing data with the reports in literature. METHODS We conducted a single-centre, retrospective review between 1976 and 2016 at one of the largest melanoma referral centres in Hungary. RESULTS We identified 176 patients with ALM (3.83%) from 4593 patients with melanoma (mean age: 66.2 years). The tumours were mainly located on the lower extremities (88.63%). The mean Breslow tumour thickness was 3.861 mm, 37.50% of the tumours were thicker than 4.00 mm, and 71.6% exhibited microscopic ulceration. Nearly one-third of the patients underwent sentinel lymph node (SLN) biopsy, and 60.3% of the biopsies were positive for metastasis. The positive SLN status was associated with significantly thick tumours and reduced survival. Patients with ALM had 5- and 10-year overall survival rates of 60.5% and 41.6%, respectively. The mean delay in diagnosis was 18 months after the discovery of skin tumours. In multivariate analyses, age, tumour thickness and distant metastasis were independent risk factors for poor survival (P < 0.001). CONCLUSIONS Our study, which is the first single-centre report in East-Central Europe focusing on ALM, confirms that patient and tumour characteristics and prognostic factors are similar with previous literature data involving Caucasians; however, tumour thickness and survival suggest even worse prognosis.
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Affiliation(s)
- I Csányi
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
| | - N Houshmand
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
| | - M Szűcs
- Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
| | - H Ócsai
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.,Outpatient Department of Dermato-Oncology, Békés County Central Hospital, Kálmán Pándy Subdivision, Gyula, Hungary
| | - L Kemény
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.,Dermatological Research Group, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary
| | - J Oláh
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.,Department of Oncotherapy, University of Szeged, Szeged, Hungary
| | - E Baltás
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
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12
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Howard M, Xie C, Wee E, Wolfe R, McLean C, Kelly J, Pan Y. Acral lentiginous melanoma: differences in survival compared with other subtypes. Br J Dermatol 2019; 182:1056-1057. [DOI: 10.1111/bjd.18620] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- M.D. Howard
- Victorian Melanoma Service Melbourne Victoria Australia
- School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia
| | - C. Xie
- Department of Dermatology Peter MacCallum Cancer Centre Melbourne Victoria Australia
| | - E. Wee
- Department of Dermatology St Vincent's Hospital Melbourne Victoria Australia
| | - R. Wolfe
- School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia
| | - C.A. McLean
- Victorian Melanoma Service Melbourne Victoria Australia
- Department of Anatomical Pathology Alfred Hospital Melbourne Victoria Australia
| | - J.W. Kelly
- Victorian Melanoma Service Melbourne Victoria Australia
| | - Y. Pan
- Victorian Melanoma Service Melbourne Victoria Australia
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13
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Sentinel Lymph Node Biopsy in Patients With Acral Melanoma: Analysis of 201 Cases From the Brazilian National Cancer Institute. Dermatol Surg 2019; 45:1026-1034. [DOI: 10.1097/dss.0000000000001785] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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14
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Pavri SN, Han G, Khan S, Han D. Does sentinel lymph node status have prognostic significance in patients with acral lentiginous melanoma? J Surg Oncol 2019; 119:1060-1069. [PMID: 30883783 DOI: 10.1002/jso.25445] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 02/20/2019] [Accepted: 02/26/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The prognostic benefit of sentinel lymph node biopsy (SLNB) and factors predictive of survival specifically in patients with acral lentiginous melanoma (ALM) are unknown. METHODS The SEER database was queried for ALM cases that underwent SLNB from 1998 to 2013. Clinicopathological factors were correlated with SLN status, overall survival (OS), and melanoma-specific survival (MSS). RESULTS Median age for the 753 ALM study patients was 65 years, and 48.2% were male. Median thickness was 2 mm with 38.1% of cases having ulceration. SLN metastases were detected in 194 of 753 cases (25.7%). Multivariable analysis showed that thickness, Clark level IV-V, and ulceration significantly predicted for SLN metastasis (P < 0.05). For patients with positive SLN, 5-year OS and MSS were significantly worse at 48.1% and 58.9%, respectively, compared with 78.7% and 88.5%, respectively, for patients with negative SLN (P < 0.0001). On multivariable analyses, older age, male gender, increasing thickness, ulceration, and a positive SLN significantly predicted for worse OS and MSS (all P < 0.05). CONCLUSION This study confirms the important role of SLNB in ALM. SLN metastases are seen in 25.7% of ALM cases, providing significant prognostic information. In addition, thickness, ulceration status, and SLNB status significantly predict survival in patients with ALM.
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Affiliation(s)
- Sabrina N Pavri
- Aesthetic and Reconstructive Surgery Institute, UF Health Cancer Center-Orlando Health, Orlando, Florida
| | - Gang Han
- Department of Epidemiology and Biostatistics, School of Public Health, Texas A&M University, College Station, Texas
| | - Sajid Khan
- Section of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
| | - Dale Han
- Division of Surgical Oncology, Department of Surgery, Oregon Health and Science University, Portland, Oregon
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15
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Acral melanoma: a retrospective cohort from the Brazilian National Cancer Institute (INCA). Melanoma Res 2018; 28:458-464. [DOI: 10.1097/cmr.0000000000000476] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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16
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Häfliger EM, Ramelyte E, Mangana J, Kunz M, Kazakov DV, Dummer R, Cheng PF. Metastatic acral lentiginous melanoma in a tertiary referral center in Switzerland: a systematic analysis. Melanoma Res 2018; 28:442-450. [PMID: 29847461 DOI: 10.1097/cmr.0000000000000465] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Acral lentiginous melanoma (ALM) is a unique histopathological subtype of melanoma with a poorer prognosis than other cutaneous melanomas. This study aims to evaluate the clinicopathological characteristics, metastatic pattern, prognostic factors, response to systemic therapy, and overall survival (OS) of ALM in a White population. This is a retrospective study of patients who were diagnosed and/or treated for ALM at the Department of Dermatology of the University Hospital Zurich, Switzerland, from January 2005 to December 2015. Overall, 172 patients with histologically confirmed ALM were included in the study. In univariate Cox regression, Breslow thickness (P<0.001), age (P=0.003), status of sentinel lymph node (P=0.005), and ulceration (P=0.008) were identified as significant prognostic factors for OS in ALM. In multivariate analysis, only Breslow thickness (P=0.0003) showed statistical significance. The median OS (mOS) was 155.7 months in the entire cohort (n=172) and 11.2 months for stage IV patients (n=36), irrespective of treatment. When first treatment was considered (n=35), mOS for stage IV patients was 8.9, 16.6, 21.7, and 3.7 months, for patients who had received chemotherapy (ChT) (n=17), immunotherapy (n=9), targeted therapy (TT) (n=3), and no therapy (n=6), respectively. The overall response rate was 44% (7/16 patients) to ChT, 100% to TT (3/3), and 25% to ipilimumab (2/8). In our study, Breslow thickness represents the best prognostic factor for OS. In stage IV ALM patients treated with either immunotherapy or TT, there is a trend for extended mOS compared with ChT.
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Affiliation(s)
- Esther M Häfliger
- Department of Dermatology, University Hospital Zurich, Zurich
- Department of Internal Medicine, Zuger Kantonsspital, Baar, Switzerland
| | - Egle Ramelyte
- Department of Dermatology, University Hospital Zurich, Zurich
| | - Joanna Mangana
- Department of Dermatology, University Hospital Zurich, Zurich
| | - Michael Kunz
- Department of Dermatology, University Hospital Zurich, Zurich
| | - Dmitry V Kazakov
- Department of Dermatology, University Hospital Zurich, Zurich
- Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic
| | - Reinhard Dummer
- Department of Dermatology, University Hospital Zurich, Zurich
| | - Phil F Cheng
- Department of Dermatology, University Hospital Zurich, Zurich
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17
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Nunes LF, Mendes GLQ, Koifman RJ. Subungual melanoma: A retrospective cohort of 157 cases from Brazilian National Cancer Institute. J Surg Oncol 2018; 118:1142-1149. [DOI: 10.1002/jso.25242] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 08/27/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Luiz Fernando Nunes
- Brazilian National Cancer Institute; Rio de Janeiro Brazil-Connective Bone Tissue Section
| | - Gélcio L. Q. Mendes
- Brazilian National Cancer Institute; Rio de Janeiro Brazil-Connective Bone Tissue Section
| | - Rosalina J. Koifman
- Department of Epidemiology and Quantitative Methods in Health; National School of Public Health, Oswaldo Cruz Foundation; Rio de Janeiro Brazil
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18
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Desai A, Ugorji R, Khachemoune A. Acral melanoma foot lesions. Part 2: clinical presentation, diagnosis, and management. Clin Exp Dermatol 2018; 43:117-123. [PMID: 29235153 DOI: 10.1111/ced.13323] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2017] [Indexed: 12/28/2022]
Abstract
Acral melanoma (AM) is a rare subtype of cutaneous malignant melanoma found on acral skin, primarily on the soles of the feet. Although rare, it is the most common subtype of melanoma found in patients of African or Asian ethnicity and has a poor prognosis, often because of the more advanced stage of presentation at diagnosis. In the second of this two-part series, we review the clinical presentation, histopathology, diagnosis and management of AM. Clinically, AM presents as a variegated lesion with blue-black pigment and irregular borders on acral skin. A parallel-ridge pattern is a very specific dermoscopic finding for AM. The differential diagnoses of AM include acral naevus, pyoderma gangrenosum, pyogenic granuloma, verrucous carcinoma and peripheral neuropathy-induced foot ulcers. If there is a clinical suspicion of AM, an excisional biopsy should be taken. Once diagnosis is confirmed by histology, surgical excision is the standard treatment. Overall, dermoscopy and histopathology are key tools in the diagnosis of AM. A greater emphasis on melanoma screening and awareness is essential in minority populations to improve survival outcomes in AM.
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Affiliation(s)
- A Desai
- Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, NY, USA
| | - R Ugorji
- Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, NY, USA
| | - A Khachemoune
- Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, NY, USA
- Department of Dermatology, Veterans Health Administration, Brooklyn, NY, USA
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19
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Castaneda CA, Torres-Cabala C, Castillo M, Villegas V, Casavilca S, Cano L, Sanchez J, Dunstan J, Calderon G, De La Cruz M, Cotrina JM, Gomez HL, Galvez R, Abugattas J. Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America. Clin Transl Oncol 2017; 19:1478-1488. [PMID: 28577153 DOI: 10.1007/s12094-017-1685-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 05/24/2017] [Indexed: 10/19/2022]
Abstract
PURPOSE Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. METHODS All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. RESULTS 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). CONCLUSIONS ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.
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Affiliation(s)
- C A Castaneda
- Medical Oncology Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru.
- Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru.
| | - C Torres-Cabala
- Departments of Pathology and Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - M Castillo
- Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - V Villegas
- Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - S Casavilca
- Pathology Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - L Cano
- Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - J Sanchez
- Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - J Dunstan
- Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - G Calderon
- Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - M De La Cruz
- Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - J M Cotrina
- Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - H L Gomez
- Medical Oncology Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - R Galvez
- Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
| | - J Abugattas
- Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru
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20
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Carrera C, Gual A, Díaz A, Puig-Butillé JA, Noguès S, Vilalta A, Conill C, Rull R, Vilana R, Arguis P, Vidal-Sicart S, Alós L, Palou J, Castel T, Malvehy J, Puig S. Prognostic role of the histological subtype of melanoma on the hands and feet in Caucasians. Melanoma Res 2017; 27:315-320. [PMID: 28296711 DOI: 10.1097/cmr.0000000000000340] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Acral melanoma (AM) is associated with a poor prognosis in part because of delayed diagnosis, but probably also because of other intrinsic characteristics of location. The aim of this study was to review the specific characteristics and outcome of AM in Caucasians. This was a cross-sectional retrospective clinical-pathological study of 274 patients identified with AM in the database of a referral unit in Europe from 1986 to 2010. The mean age of the patients was 56.6 (SD 17.7) years. 269 cases could be histologically classified and included in the study. In all, 222 (82.5%) were located on feet. According to melanoma subtype, 165 (61.3%) were acral lentiginous melanoma (ALM), 84 (31.2%) were superficial spreading melanoma (SSM), and 20 (7.5%) were nodular melanoma (NM). SSM patients were characterized by female predominance (77.4%), younger age, and classic melanoma-risk phenotype (fair skin and multiple nevi). Among the 198 invasive cases with a mean follow-up of 56.2 months, the mean (SD) Breslow's thickness was 3.1 (3.6) mm, being 1.4 (1.4) mm in SSM, 3.5 (4.1) mm in ALM and 4.9 (2.9) mm in NM (P<0.001). Ulceration was present in 33.3%, 2.9% in SSM, 38.6% in ALM, and 76.9% in NM (P<0.001). A total of 29.3% relapsed (7.3% of SSM, 35% of ALM and 55% of NM) and 24.2% died because of AM. In multivariate analysis, age at diagnosis, Breslow, and histopathological subtype were independent prognostic factors for both disease-free and AM-specific survival. The ALM and NM subtypes presented poorer outcome after weighting Breslow and age (P=0.02). Histological subtype of AM could have an impact on biological behavior, ALM and NM subtypes presenting a poorer prognosis after adjusting for age and Breslow's thickness.
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Affiliation(s)
- Cristina Carrera
- aMelanoma Unit, Department of Dermatology bMelanoma Unit, Department of Pathology cBiochemical and Molecular Genetics Service, Melanoma Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) dRadiotherapeutic Oncology Service, Melanoma Unit eGeneral Surgery Service, Melanoma Unit fImaging Diagnostic Center, CDI (Radiology and Nuclear Medicine Services), Melanoma Unit, Hospital Clinic gBiomedical Research Center for Rare Diseases, CIBERER. Insituto de Salud Carlos III hMedicine Department, University of Barcelona, Barcelona, Spain
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Asgari M, Shen L, Sokil M, Yeh I, Jorgenson E. Prognostic factors and survival in acral lentiginous melanoma. Br J Dermatol 2017; 177:428-435. [DOI: 10.1111/bjd.15600] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2017] [Indexed: 11/27/2022]
Affiliation(s)
- M.M. Asgari
- Department of Dermatology; Massachusetts General Hospital, and Harvard Medical School; Boston MA U.S.A
- Division of Research; Kaiser Permanente Northern California; Oakland CA U.S.A
| | - L. Shen
- Division of Research; Kaiser Permanente Northern California; Oakland CA U.S.A
| | - M.M. Sokil
- Division of Research; Kaiser Permanente Northern California; Oakland CA U.S.A
| | - I. Yeh
- Departments of Pathology and Dermatology; University of California at San Francisco; San Francisco CA U.S.A
| | - E. Jorgenson
- Division of Research; Kaiser Permanente Northern California; Oakland CA U.S.A
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22
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Criscito MC, Stein JA. Improving the diagnosis and treatment of acral melanocytic lesions. Melanoma Manag 2017; 4:113-123. [PMID: 30190914 DOI: 10.2217/mmt-2016-0017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Accepted: 08/16/2016] [Indexed: 01/15/2023] Open
Abstract
Melanocytic lesions of acral sites are common, with an estimated prevalence of 28-36% in the USA. While the majority of these lesions are benign, differentiation from acral melanoma (AM) is often challenging. AM is a unique subtype of melanoma, with distinct molecular characteristics that are thought to contribute to its high rate of locoregional recurrence and worse prognosis. The advent of dermoscopy has since improved the diagnostic accuracy of AM, resulting in earlier detection and arguably improved survival. Additionally, the identification of unique genomic amplifications in AM invites the potential for future AM-specific targeted therapies. Herein, we discuss the importance of dermoscopy in the diagnosis of acral melanocytic lesions and review the treatment strategies for AM.
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Affiliation(s)
- Maressa C Criscito
- The Ronald O Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
| | - Jennifer A Stein
- The Ronald O Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
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Surgical excision margin for primary acral melanoma. J Surg Oncol 2016; 114:933-939. [DOI: 10.1002/jso.24442] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 09/02/2016] [Indexed: 11/07/2022]
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Han D, Thomas DC, Zager JS, Pockaj B, White RL, Leong SPL. Clinical utilities and biological characteristics of melanoma sentinel lymph nodes. World J Clin Oncol 2016; 7:174-188. [PMID: 27081640 PMCID: PMC4826963 DOI: 10.5306/wjco.v7.i2.174] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 12/05/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.
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Sheen YS, Liao YH, Lin MH, Chiu HC, Jee SH, Liau JY, Chang YL, Chu CY. Insulin-Like Growth Factor II mRNA-Binding Protein 3 Expression Correlates with Poor Prognosis in Acral Lentiginous Melanoma. PLoS One 2016; 11:e0147431. [PMID: 26796627 PMCID: PMC4721868 DOI: 10.1371/journal.pone.0147431] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 01/04/2016] [Indexed: 12/21/2022] Open
Abstract
Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35-9.97, P = 0.011) was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.
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Affiliation(s)
- Yi-Shuan Sheen
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Hua Liao
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Hsien Lin
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hisn-Chu, Taiwan
| | - Hsien-Ching Chiu
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shiou-Hwa Jee
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jau-Yu Liau
- Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yih-Leong Chang
- Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yu Chu
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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Abstract
Acral lentiginous melanoma (ALM) is a rare subtype of melanoma mainly arising on the palms, soles, and nail beds. ALM is the most common subtype of melanoma found in patients of Asian or African descent and tends to more advanced at presentation due to delays in diagnosis. Surgical treatment is difficult owing to the complexity and functional importance of the hands and feet and reconstruction after resection is usually needed. The prognosis for patients with ALM depends on stage of disease and tends to be worse than with other subtypes of melanoma. Newer treatment modalities such as immunotherapies and targeted agents are being tested in patients with advanced ALM with some promising preliminary results.
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Otsuka M, Yamasaki O, Kaji T, Iwatsuki K, Asagoe K. Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute. J Dermatol 2015; 42:954-61. [DOI: 10.1111/1346-8138.12972] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Accepted: 04/29/2015] [Indexed: 11/26/2022]
Affiliation(s)
- Masaki Otsuka
- Department of Dermatology; Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; Okayama Japan
| | - Osamu Yamasaki
- Department of Dermatology; Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; Okayama Japan
| | - Tatsuya Kaji
- Department of Dermatology; Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; Okayama Japan
| | - Keiji Iwatsuki
- Department of Dermatology; Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; Okayama Japan
| | - Kenji Asagoe
- Department of Dermatology; National Hospital Organization Okayama Medical Center; Okayama Japan
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Gumaste PV, Fleming NH, Silva I, Shapiro RL, Berman RS, Zhong J, Osman I, Stein JA. Analysis of recurrence patterns in acral versus nonacral melanoma: should histologic subtype influence treatment guidelines? J Natl Compr Canc Netw 2014; 12:1706-12. [PMID: 25505211 PMCID: PMC4469335 DOI: 10.6004/jnccn.2014.0172] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Current surgical treatment of primary melanoma is uniform for all histosubtypes, although certain types of melanoma, such as acral lentiginous melanoma (ALM), have a worse prognosis. No study has explored the effectiveness of standard melanoma treatment guidelines for managing ALM compared with nonacral melanoma (NAM). Study subjects were identified from a prospectively enrolled database of patients with primary melanoma at New York University. Patients with ALM were matched to those with NAM (1:3) by gender and melanoma stage, including substage (ALM, 61; NAM, 183). All patients received standard-of-care treatment. Recurrence and survival outcomes in both cohorts were compared. ALM histologic subtype was an independent negative predictor of recurrence-free survival (hazard ratio [HR], 2.24; P=.001) and melanoma-specific survival (HR, 2.58; P=.001) compared with NAM. Recurrence was significantly more common in patients with ALM than in those with NAM (49% vs 30%; P=.007). For tumors less than 2 mm in thickness, a significantly higher recurrence rate was seen with ALM versus NAM (P=.048). No significant difference was seen in recurrence for tumors greater than 2 mm (P=.12). Notably, the rate of locoregional recurrence was nearly double for ALM compared with NAM (P=.001). The data presented herein reveal a high rate of locoregional failure in ALM compared with NAM when controlling for AJCC stage. These results raise the question of whether ALM may require more aggressive surgical treatment than nonacral cutaneous melanomas of equal thickness, particularly in tumors less than 2 mm thick. Larger multicenter trials are necessary for further conclusions.
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Affiliation(s)
- Priyanka V. Gumaste
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
| | - Nathaniel H. Fleming
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
| | - Ines Silva
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Richard L. Shapiro
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Department of Surgery, New York University School of Medicine, New York, New York
| | - Russell S. Berman
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Department of Surgery, New York University School of Medicine, New York, New York
| | - Judy Zhong
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
| | - Iman Osman
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Jennifer A. Stein
- Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
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Ito T, Wada M, Nagae K, Nakano-Nakamura M, Nakahara T, Hagihara A, Furue M, Uchi H. Acral lentiginous melanoma: who benefits from sentinel lymph node biopsy? J Am Acad Dermatol 2014; 72:71-7. [PMID: 25455840 DOI: 10.1016/j.jaad.2014.10.008] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 09/16/2014] [Accepted: 10/07/2014] [Indexed: 01/14/2023]
Abstract
BACKGROUND There are significant clinicopathological, genetic, and biological differences between acral lentiginous melanoma (ALM) and other types of melanoma. OBJECTIVE We sought to investigate the use of sentinel lymph node (SLN) biopsy for patients with ALM. METHODS This was a retrospective review of 116 patients with primary ALM. Melanoma-specific and disease-free survival were estimated using the Kaplan-Meier method, together with multivariate analyses using the Cox proportional hazards regression model. RESULTS All patients were Japanese (48 male and 68 female). Metastases in SLN were noted in 13 of 84 patients who underwent SLN biopsy. No patients with thin ALM (≤1 mm) and only 2 patients with nonulcerated ALM had tumor-positive SLN. Patients with positive SLN had significantly shorter melanoma-specific survival (5-year survival rate, 37.5% vs 84.3%; P < .0001) and disease-free survival (5-year survival, 37.5% vs 77.9%; P = .0024). Among patients with thick (>1 mm) ALM, the influence of SLN positivity on melanoma-specific survival was increased (5-year survival, 22.7% vs 80.8%; P = .0005). LIMITATIONS This was a retrospective study and had a small sample size. CONCLUSIONS SLN biopsy should be considered for patients with thick or ulcerated ALM. For patients with thin or nonulcerated ones, it may be of limited importance.
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Affiliation(s)
- Takamichi Ito
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Maiko Wada
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Konosuke Nagae
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Misa Nakano-Nakamura
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Nakahara
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihito Hagihara
- Department of Health Services Management and Policy, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masutaka Furue
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroshi Uchi
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Scanlon P, Tian J, Zhong J, Silva I, Shapiro R, Pavlick A, Berman R, Osman I, Darvishian F. Enhanced immunohistochemical detection of neural infiltration in primary melanoma: is there a clinical value? Hum Pathol 2014; 45:1656-63. [PMID: 24890944 DOI: 10.1016/j.humpath.2014.04.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 03/27/2014] [Accepted: 04/02/2014] [Indexed: 11/17/2022]
Abstract
Neural infiltration in primary melanoma is a histopathologic feature that has been associated with desmoplastic histopathologic subtype and local recurrence in the literature. We tested the hypothesis that improved detection and characterization of neural infiltration into peritumoral or intratumoral location and perineural or intraneural involvement could have a prognostic relevance. We studied 128 primary melanoma cases prospectively accrued and followed at New York University using immunohistochemical detection with antihuman neurofilament protein and routine histology with hematoxylin and eosin. Neural infiltration, defined as the presence of tumor cells involving or immediately surrounding nerve foci, was identified and characterized using both detection methods. Neural infiltration rate of detection was enhanced by immunohistochemistry for neurofilament in matched-pair design (47% by immunohistochemistry versus 25% by routine histology). Immunohistochemical detection of neural infiltration was significantly associated with ulceration (P = .021), desmoplastic and acral lentiginous histologic subtype (P = .008), and head/neck/hands/feet tumor location (P = .037). Routinely detected neural infiltration was significantly associated with local recurrence (P = .010). Immunohistochemistry detected more intratumoral neural infiltration cases compared with routine histology (30% versus 3%, respectively). Peritumoral and intratumoral nerve location had no impact on clinical outcomes. Using a multivariate model controlling for stage, neither routinely detected neural infiltration nor enhanced immunohistochemical characterization of neural infiltration was significantly associated with disease-free or overall survival. Our data demonstrate that routinely detected neural infiltration is associated with local recurrence in all histologic subtypes but that improved detection and characterization of neural infiltration with immunohistochemistry in primary melanoma does not add to prognostic relevance.
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Affiliation(s)
- Patrick Scanlon
- Department of Dermatology, New York University School of Medicine, 10016, New York, NY; The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY
| | - Jaiying Tian
- Department of Dermatology, New York University School of Medicine, 10016, New York, NY; The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY
| | - Judy Zhong
- The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY
| | - Ines Silva
- The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY
| | - Richard Shapiro
- The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY; Department of Surgery, New York University School of Medicine, 10016, New York, NY
| | - Anna Pavlick
- The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY
| | - Russell Berman
- The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY; Department of Surgery, New York University School of Medicine, 10016, New York, NY
| | - Iman Osman
- Department of Dermatology, New York University School of Medicine, 10016, New York, NY; The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY
| | - Farbod Darvishian
- The New York University Interdisciplinary Melanoma Cooperative Group, 10016, New York, NY; Department of Pathology, New York University School of Medicine, 10016, New York, NY.
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31
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Balch CM, Thompson JF, Gershenwald JE, Soong SJ, Ding S, McMasters KM, Coit DG, Eggermont AMM, Gimotty PA, Johnson TM, Kirkwood JM, Leong SP, Ross MI, Byrd DR, Cochran AJ, Mihm MC, Morton DL, Atkins MB, Flaherty KT, Sondak VK. Age as a predictor of sentinel node metastasis among patients with localized melanoma: an inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients. Ann Surg Oncol 2014; 21:1075-81. [PMID: 24531700 DOI: 10.1245/s10434-013-3464-x] [Citation(s) in RCA: 112] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Indexed: 01/21/2023]
Abstract
PURPOSE We have previously reported that older patients with clinical stage I and II primary cutaneous. Melanoma had lower survival rates compared to younger patients. We postulated that the incidence of nodal metastasis would therefore be higher among older melanoma patients. METHODS The expanded American Joint Committee on Cancer melanoma staging database contains a cohort of 7,756 melanoma patients who presented without clinical evidence of regional lymph node or distant metastasis and who underwent a sentinel node biopsy procedure as a component of their staging assessment. RESULTS Although older patients had primary melanoma features associated with more aggressive biology, we paradoxically observed a significant decrease in the incidence of sentinel node metastasis as patient age increased. Overall, the highest incidence of sentinel node metastasis was 25.8 % in patients under 20 years of age, compared to 15.5 % in patients 80 years and older (p < 0.001). In contrast, 5-year mortality rates for clinical stage II patients ranged from a low of 20 % for those 20-40 years of age up to 38 % for those over 70 years of age. Patient age was an independent predictor of sentinel node metastasis in a multifactorial analysis (p < 0.001). CONCLUSIONS Patients with clinical stage I and II melanoma under 20 years of age had a higher incidence of sentinel lymph node metastasis but, paradoxically, a more favorable survival outcome compared to all other age groups. In contrast, patients >70 years had the most aggressive primary melanoma features and a higher mortality rate compared to all other age groups but a lower incidence of sentinel lymph node metastasis.
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Affiliation(s)
- Charles M Balch
- Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA,
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Egger ME, Stepp LO, Callender GG, Quillo AR, Martin RCG, Scoggins CR, Stromberg AJ, McMasters KM. Outcomes and prognostic factors in superficial spreading melanoma. Am J Surg 2013; 206:861-7; discussion 867-8. [PMID: 24124662 DOI: 10.1016/j.amjsurg.2013.09.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 09/04/2013] [Accepted: 09/13/2013] [Indexed: 11/25/2022]
Abstract
BACKGROUND Prognostic factors and risk factors for positive sentinel lymph node (SLN) biopsy results are important to identify in superficial spreading melanoma (SSM). METHODS A single-center database and a prospective clinical trial database were reviewed for all patients with diagnoses of SSM. Logistic regression, Kaplan-Meier survival analysis, and univariate and multivariate Cox models were used. RESULTS A total of 1,643 patients with SSM were identified. Independent risk factors for positive SLN biopsy results were Breslow thickness (BT) ≥2.0 mm, age <60 years, and presence of ulceration. BT ≥2.0 mm, ulceration, lymphovascular invasion, and positive SLN and positive non-SLN biopsy results were independent risk factors for worse disease-free survival. Independent overall survival risk factors included BT ≥2.0 mm, age ≥60 years, ulceration, nonextremity tumor location, lymphovascular invasion, and positive SLN biopsy results. CONCLUSIONS BT, ulceration, lymphovascular invasion, and SLN and non-SLN status are important risk factors for SSM.
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Affiliation(s)
- Michael E Egger
- Hiram C. Polk Jr MD Department of Surgery, University of Louisville, 550 South Jackson Street, Louisville, KY 40202, USA
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Bello DM, Chou JF, Panageas KS, Brady MS, Coit DG, Carvajal RD, Ariyan CE. Prognosis of acral melanoma: a series of 281 patients. Ann Surg Oncol 2013; 20:3618-25. [PMID: 23838913 DOI: 10.1245/s10434-013-3089-0] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2013] [Indexed: 12/26/2022]
Abstract
BACKGROUND Acral melanoma (AM) is an unusual malignancy with poor survival. This study defines a cohort of patients, treated at a single institution, and the factors associated with survival and comparison with nonacral cutaneous melanoma (NACM). METHODS All patients with AM presenting from 1995 to 2010 were identified from a prospectively maintained database. Analysis of clinicopathologic features of AM associated with disease-specific survival (DSS) was performed. A stratified, stage-matched survival analysis compared the outcome of 281 acral to 843 extremity NACM patients. RESULTS A total of 281 AM patients (170 volar, 111 subungual) were identified. Pathologic stage (p < 0.001), ulceration (p < 0.001), Breslow thickness (p < 0.001), and a positive sentinel lymph node (p < 0.001) were found to be poor prognostic indicators associated with DSS. In stage-matched analysis, AM had a worse DSS compared with NACM (hazard ratio 1.8; 95 % CI 1.2-2.7; p < 0.01). CONCLUSIONS This study represents the largest, single-institution series describing the characteristics and outcomes of AM. AM tumors exhibit aggressive histopathologic features associated with a poorer survival outcome. AM patients have an inferior survival than extremity NACM when matched for stage, perhaps reflecting inherent alterations in tumor biology. This warrants further investigation into the differences between acral and cutaneous melanoma.
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Affiliation(s)
- Danielle M Bello
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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