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1
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Sassun R, Sileo A, Ng JC, Ferrari D, McKenna NP, Perry WRG, Larson DW. A 22-year experience of surgical management of anorectal melanoma: risk factors for recurrence and death. Int J Colorectal Dis 2025; 40:99. [PMID: 40263199 PMCID: PMC12014828 DOI: 10.1007/s00384-025-04861-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/08/2025] [Indexed: 04/24/2025]
Abstract
PURPOSE Anorectal melanoma (ARM) poses a significant challenge due to the lack of established guidelines and a 5-year overall survival rate of less than 20%. The only recognized death risk factors are positive lymph nodes and positive surgical margins. This study aimed to identify the risk factors for local/distant recurrences and death in a 22-year multi-institutional experience. METHODS All patients who underwent curative surgical resection or were referred to after resection at the Mayo Clinic for non-metastatic ARM (2002-2024) were included. Risk factors for local/distant recurrences, and deaths were assessed through multivariable Cox regression. RESULTS Eighty-eight patients were included in the study. Seventy-eight percent of patients had anal melanoma and 22% rectal melanoma. Nineteen percent had clinically positive lymph nodes. The surgical margins were positive in 62% of local surgeries, while they were positive in 13% of radical surgery cases. The first recurrence was often a local recurrence (67%), followed by distant metastasis (21%), with an overall comparable overall survival between the two. Radiotherapy administration, radical surgery, and negative margins were associated with less local recurrence. Clinically positive lymph nodes and local recurrences increased the risk of developing distant metastasis over time. Clinically negative lymph nodes, radiotherapy administration, radical surgery, and negative margins all contributed to a reduced death risk. CONCLUSION Local recurrences in ARM may influence distant metastasis and death more than what was previously believed. Positive surgical margins in local surgery were remarkably high, reaching 62%. Protective factors for local recurrence and death included radical surgery, negative surgical margins, and radiotherapy.
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Affiliation(s)
- Richard Sassun
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA.
| | - Annaclara Sileo
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA
| | - Jyi Cheng Ng
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA
| | - Davide Ferrari
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA
| | - Nicholas P McKenna
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA
| | - William R G Perry
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA
| | - David W Larson
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. Southwest, Rochester, MN, 55905, USA
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2
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Jutten E, van Kempen LCLT, Diercks GFH, van Leeuwen BL, Kruijff S, Wevers KP. Real-World Evidence of the Prevalence of Driver Mutations in Anorectal Melanoma. Mol Diagn Ther 2025; 29:229-238. [PMID: 39739287 DOI: 10.1007/s40291-024-00764-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2024] [Indexed: 01/02/2025]
Abstract
INTRODUCTION Anorectal melanoma is a rare neoplasm with an aggressive behavior and poor prognosis. Recently, recurrent gene mutations related to anorectal melanoma have been identified in a small series of cases, and this holds promise for targeted therapies, analogous to cutaneous melanoma. The purpose of this study was to analyze testing rates and prevalence of mutations in anorectal melanoma in the Dutch population. METHODS The Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank were queried for all patients with a diagnosis of anorectal melanoma (2009-2019) and for whom a molecular analysis was performed. The genes that were tested and mutations that were reported were recorded. Mutation status was correlated with clinical characteristics. RESULTS In the period 2009-2019, 121 patients were diagnosed with anorectal melanoma. A molecular analysis was performed for 81 (67%) using single gene testing and various next-generation sequencing panels. Testing rates increased from 53% in 2009-2012 to 73% in 2016-2019. In 29/81 (36%) analyzed tumors, one or more mutations were reported: mutations in KIT (16/70, 23%), CTNNB1 (3/20, 15%), NRAS (6/60, 10%), BRAF non-V600E (4/74, 5%), GNAS (1/19, 5%), KRAS (1/28, 4%), BRAF V600E (1/74, 1%), and SF3B1 (1/1). In this cohort, a positive correlation was found between BRAF mutation status and age. Mutation status did not correlate with sex, date of diagnosis, tumor stage or surgical treatment. Survival was not influenced by any mutation status. CONCLUSION KIT was the most frequently mutated gene in the 81 analyzed anorectal melanomas in the period 2009-2019. With the increasing testing rates and use of next generation sequencing, the molecular landscape of anorectal melanomas is gradually being revealed. Adoption of broad mutation analysis will reveal potentially actionable targets for treatment of patients with anorectal melanoma.
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Affiliation(s)
- E Jutten
- Hospital group Twente, Zilvermeeuw 1, 7609 PP, Almelo, The Netherlands
- University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - L C L T van Kempen
- University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Department of Pathology, University of Antwerp, Antwerp University Hospital, 655 Drie Eikenstraat, 2650, Edegem, Belgium
| | - G F H Diercks
- University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - B L van Leeuwen
- University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - S Kruijff
- University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - K P Wevers
- Comprehensive Cancer Center, University of Maastricht, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.
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3
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Vitzthum LK, Pollom E. A Balancing Act With Adaptive Hypofractionation. Int J Radiat Oncol Biol Phys 2024; 120:930. [PMID: 39424592 DOI: 10.1016/j.ijrobp.2024.08.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 08/12/2024] [Indexed: 10/21/2024]
Affiliation(s)
- Lucas K Vitzthum
- Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California.
| | - Erqi Pollom
- Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California
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4
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Nagarajan P, Yun SJ, Prieto VG. Mucosal melanoma: Review from a pathologist point of view. Clin Dermatol 2024:S0738-081X(24)00177-9. [PMID: 39277090 DOI: 10.1016/j.clindermatol.2024.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Mucosal melanomas (MuM) are rare malignant tumors arising from the epithelia lining the inner mucosal surfaces of the body. Unlike cutaneous melanoma, understanding of MuM is limited among pathologists and clinicians alike, primarily due to rarity of these tumors. MuM are characterized by genetic alterations quite distinct from cutaneous melanomas; however, their causative and promoting factors are unknown. These melanomas are characteristically diagnosed at a later stage due to their occult locations, leading to a worse prognosis. Dedicated staging systems for MuM exist only for sinonasal and conjunctival melanomas. Risk stratification of patients with MuM, particularly those arising from the anogenital area, is challenging. Recent studies have shown that minor modifications of the American Joint Committee on Cancer eighth edition cutaneous melanoma staging system can group patients fairly robustly; however, the proposed T-categorization systems have yet to be validated in larger cohorts. We summarize the demographic, clinical, histopathologic, and molecular features of common subtypes of MuM and highlight the outstanding needs in this field.
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Affiliation(s)
- Priyadharsini Nagarajan
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
| | - Sook Jung Yun
- Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea
| | - Victor G Prieto
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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5
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Fadel MG, Mohamed HS, Weir J, Hayes AJ, Larkin J, Smith MJ. Surgical Management of Primary Anorectal Melanoma: Is Less More? J Gastrointest Cancer 2024; 55:714-722. [PMID: 38180677 PMCID: PMC11186905 DOI: 10.1007/s12029-023-01009-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2023] [Indexed: 01/06/2024]
Abstract
PURPOSE Ano-uro-genital (AUG) Mucosal Melanoma UK guidelines recommended a less radical surgical strategy for anorectal melanoma (ARM) where possible. We report our experience of ARM consistent with that approach including clinical presentation, intervention undertaken and prognosis. METHODS We present a retrospective study of 15 consecutive patients with ARM surgically treated between November 2014 and April 2023. Patients were divided into the two surgery types: wide local excision (WLE, n = 9) and abdominoperineal resection (APR, n = 6). Data on demographics, diagnosis, treatment and oncological outcomes were assessed between the groups. RESULTS The mean age was 65.3 ± 17.4 years and 6 (40.0%) were female patients. Nine patients (60.0%) were diagnosed with stage I and six patients (40.0%) with stage II disease. R0 margins were achieved in all cases. The overall mean length of stay was lower following WLE compared to APR (2.6 ± 2.4 days versus 14.0 ± 9.8 days, p = 0.032). Two complications were observed in the WLE group compared to four complications after APR (p = 0.605). Five patients (55.5%) developed local/distant recurrence in the WLE group compared to three patients (50.0%) in the APR group (p = 0.707), with a median overall survival of 38.5 (12-83) months versus 26.5 (14-48) months, respectively. CONCLUSIONS Achieving clear margins by the least radical fashion may have equivalent oncological outcomes to radical surgery, potentially reducing patient morbidity and preserving function. In our experience, the surgical management of ARM consistent with the 'less is more' approach adhering to AUG guidelines has acceptable outcomes.
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Affiliation(s)
- Michael G Fadel
- The Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital NHS Foundation Trust, London, UK.
- Department of Surgery and Cancer, Imperial College London, London, UK.
| | - Hesham S Mohamed
- The Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital NHS Foundation Trust, London, UK
- The Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust, London, UK
| | - Justin Weir
- Department of Cellular Pathology, The Royal Marsden Hospital NHS Foundation Trust, London, UK
| | - Andrew J Hayes
- The Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital NHS Foundation Trust, London, UK
- The Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust, London, UK
| | - James Larkin
- The Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital NHS Foundation Trust, London, UK
- The Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust, London, UK
- Department of Medical Oncology, The Royal Marsden Hospital NHS Foundation Trust, London, UK
| | - Myles J Smith
- The Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital NHS Foundation Trust, London, UK
- The Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust, London, UK
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Fortuna A, Amaral T. Multidisciplinary approach and treatment of acral and mucosal melanoma. Front Oncol 2024; 14:1340408. [PMID: 38469235 PMCID: PMC10926023 DOI: 10.3389/fonc.2024.1340408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/29/2024] [Indexed: 03/13/2024] Open
Abstract
Acral and mucosal melanoma are uncommon variants of melanoma. Acral melanoma has an age-adjusted incidence of approximately 1.8 cases per million individuals per year, accounting for about 2% to 3% of all melanoma cases. On the other hand, mucosal melanoma, with an incidence of 2.2 cases per million per year, makes up around 1.3% of all melanoma cases. These melanomas, in addition to being biologically and clinically distinct from cutaneous melanoma, share certain clinical and pathologic characteristics. These include a more aggressive nature and a less favorable prognosis. Furthermore, they exhibit a different mutational pattern, with KIT mutations being more prevalent in acral and mucosal melanomas. This divergence in mutational patterns may partially account for the relatively poorer prognosis, particularly to immune checkpoint inhibitors. This review explores various aspects of acral and mucosal melanoma, including their clinical presentation, pathologic features, mutational profiles, current therapeutic approaches, outcomes associated with systemic therapy, and potential strategies to address resistance to existing treatments.
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Affiliation(s)
- Ana Fortuna
- Oncology Department, Centro Hospitalar Universitário do Algarve, Faro, Portugal
| | - Teresa Amaral
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany
- Cluster of Excellence Image-Guided and Functionally Instructed Tumor Therapies (iFIT) (EXC 2180), Tübingen, Germany
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7
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Shimazaki R, Hagiwara M, Tani C, Iwata H, Takahashi H, Fukuyama M, Matsuya T, Imai K, Yuzawa S, Tanino M, Yokoo H. Successful Multidisciplinary Treatment with Laparoscopic Hepatectomy and Adjuvant Therapy for Metachronous Solitary Hepatic Metastasis after Excision of a Primary Anorectal Malignant Melanoma: A Case Report. Curr Oncol 2023; 31:203-210. [PMID: 38248098 PMCID: PMC10813857 DOI: 10.3390/curroncol31010013] [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: 11/24/2023] [Revised: 12/22/2023] [Accepted: 12/27/2023] [Indexed: 01/23/2024] Open
Abstract
Anorectal malignant melanoma (ARMM) is extremely rare and generally lethal, irrespective of the treatment administered. The disease is often diagnosed late, metastases being present in approximately two-thirds of patients at the time of initial diagnosis. Solitary metastasis of ARMM to a distant organ is exceedingly rare. A 76-year-old woman with a history of laparoscopic abdominoperineal resection of an ARMM 13 months previously, was found to have a solitary liver metastasis in the follow-up computed tomography. A preoperative work-up showed no other distant metastases nor contraindication to surgery. It was therefore considered that resection was indicated. The metachronous solitary liver metastasis from an ARMM was treated by laparoscopic wedge hepatectomy of the eighth segment 18 months after excision of her primary ARMM. Adjuvant therapy with pembrolizumab was initiated and continued at 6-week intervals. The patient has not exhibited any immune related Adverse Effects (irAE) during or subsequent to treatment with pembrolizmab and has now completed 12 months of adjuvant pembrolizumab therapy, having survived 33 months from the initial operation for primary ARMM, and remaining recurrence-free 14 months after hepatectomy. ARMM is extremely rare and resection of a metachronous solitary metastasis followed by adjuvant therapy has not previously been reported. We hope this case will be useful for clinicians who might treat similar patients.
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Affiliation(s)
- Ryotaro Shimazaki
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Masahiro Hagiwara
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Chikayoshi Tani
- Division of Gastrointestinal Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Hiroyoshi Iwata
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Hiroyuki Takahashi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Marika Fukuyama
- Department of Dermatology, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan (T.M.)
| | - Taisuke Matsuya
- Department of Dermatology, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan (T.M.)
| | - Koji Imai
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Sayaka Yuzawa
- Department of Diagnostic Pathology, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Mishie Tanino
- Department of Diagnostic Pathology, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
| | - Hideki Yokoo
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
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8
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Alvarez J, Smith JJ. Anorectal mucosal melanoma. SEMINARS IN COLON AND RECTAL SURGERY 2023; 34:100990. [PMID: 38746826 PMCID: PMC11090490 DOI: 10.1016/j.scrs.2023.100990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2024]
Abstract
Anorectal mucosal melanoma accounts for less than 1 % of all anorectal malignant tumors and a tendency for delayed diagnosis leads to advanced disease at presentation.1,2 Due to the rarity of the disease, there are limited prospective trials exploring the optimal treatment strategies. Generally, tumors are surgically excised, with a preference for conservative management with wide local excision. In the past decade, there have been advances with immunotherapy and other targeted therapies. Multiple clinical trials continue exploring neoadjuvant/adjuvant combination treatments in the setting of advanced or unresectable disease.
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Affiliation(s)
- Janet Alvarez
- Research Scholar, Memorial Sloan Kettering Cancer Center, Department of Surgery, 1275 York Avenue | SR-201, New York, NY 10065, USA
| | - J. Joshua Smith
- Associate Member, Associate Attending Surgeon, Memorial Sloan Kettering Cancer Center, Colorectal Service, Department of Surgery, 1275 York Avenue, SR-201, New York, NY 10065, USA
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9
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Sun W, Liu K, Zhou H, Zhao F, Dong Y, Xu Y, Kong Y, Wang M, Cheng X, Chen Y. Whole-exome sequencing reveals mutational profiles of anorectal and gynecological melanoma. Med Oncol 2023; 40:330. [PMID: 37831226 PMCID: PMC10575813 DOI: 10.1007/s12032-023-02192-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 09/11/2023] [Indexed: 10/14/2023]
Abstract
Mucosal melanoma is a rare and highly malignant type of melanoma. Among the sites that mucosal melanoma arises, anorectal and gynecological melanoma has more aggressive behavior and worse prognosis. There was no effective therapy for mucosal melanoma at present. Only a small number of mucosal melanoma patients which harbor mutations in BRAF or KIT benefit from targeted therapy. So it's an urgent need to identify more actionable mutations in mucosal melanoma. To identify more potential therapeutic targets in mucosal melanoma, 48 samples were collected from 44 patients with anorectal or gynecological melanoma and subjected to whole-exome sequencing. The tumor mutation burden was low with a median of 1.75 mutations per Mb. In chromosomal level, 1q, 6p and 8q of mucosal melanoma were significantly amplified while 9p, 10p, 10q, 16p and 16q were significantly deleted. Muc16 was the most frequently mutated oncogene in our samples(25%). The mutation frequency of KIT(20%) was comparable to the "triple-wild" genes-NRAS(20%), NF1(20%), and BRAF(11%). KMT2D mutation was found in 18.18% patients, which is previously unidentified. MAPK signaling pathway and lysine degradation were the most frequently mutated pathways. Moreover, patients with TP53 mutations tend to have worse clinical outcome (median survival time 19 vs. 50 months, log-rank P = 0.006). 2000 ore mutated genes involved in MAPK signaling pathway were identified, which expand the patients potentially benefit from ample MAPK inhibitors. KMT2D could be a potential therapeutic target. Moreover, TP53 could be a potential prognosis marker for mucosal melanoma.
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Affiliation(s)
- Wei Sun
- Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Kunyan Liu
- Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China
| | - Hongyu Zhou
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Gynecological Oncology, Minhang Branch of Fudan University Shanghai Cancer Center, Shanghai, China
| | - Fang Zhao
- Department of Dermatology, University Hospital Essen, Essen, Germany
| | - Yan Dong
- Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China
| | - Yu Xu
- Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yunyi Kong
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Minghe Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xi Cheng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Gynecological Oncology, Minhang Branch of Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yong Chen
- Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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10
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Yan-Quiroz EF, Agreda-Castro FM, Diaz-Lozano L, Tenazoa-Villalobos R, Fernández-Rodríguez LJ. Management of primary anorectal mucosal melanoma during the COVID-19 pandemic. Ecancermedicalscience 2023; 17:1610. [PMID: 38414935 PMCID: PMC10898915 DOI: 10.3332/ecancer.2023.1610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Indexed: 02/29/2024] Open
Abstract
Anorectal melanoma is a rare and difficult-to-diagnose highly malignant cancer with a poor prognosis. The treatment usually involves surgery and often includes adjuvants such as radiation therapy and immunotherapy. We present a case of a 77-year-old Peruvian who was eventually diagnosed with this cancer during the COVID-19 pandemic, which complicated her treatment and allowed the cancer to spread. Her treatment included abdominoperineal resection, bilateral pelvic lymphadenectomy, left internal iliac vein raffia and end colostomy, followed by 3D radiation therapy (50 Gy, 25 sessions) and systemic treatment with nivolumab, all of which were well tolerated. The patient was alive as of 20 August 2023, having survived for more than 3 years since the onset of symptoms.
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Affiliation(s)
- Edgar Fermín Yan-Quiroz
- Hospital de Alta Complejidad Virgen de la Puerta - EsSalud, La Esperanza 13013, Perú
- Faculty of Medicine, Universidad Privada Antenor Orrego, Trujillo 13008, Perú
- https://orcid.org/0000-0002-9128-4760
| | - Folker Mijaíl Agreda-Castro
- Hospital de Alta Complejidad Virgen de la Puerta - EsSalud, La Esperanza 13013, Perú
- Faculty of Medicine, Universidad Privada Antenor Orrego, Trujillo 13008, Perú
- https://orcid.org/0000-0003-4057-6365
| | - Lita Diaz-Lozano
- Faculty of Medicine, Universidad Privada Antenor Orrego, Trujillo 13008, Perú
- Hospital Víctor Lazarte Echegaray - EsSalud, Trujillo 13006, Perú
- https://orcid.org/0000-0003-2842-369X
| | - Richard Tenazoa-Villalobos
- Hospital de Alta Complejidad Virgen de la Puerta - EsSalud, La Esperanza 13013, Perú
- Faculty of Medicine, Universidad Privada Antenor Orrego, Trujillo 13008, Perú
- https://orcid.org/0000-0003-3622-9408
| | - Lissett Jeanette Fernández-Rodríguez
- Faculty of Medicine, Universidad Privada Antenor Orrego, Trujillo 13008, Perú
- Hospital Regional de Lambayeque - Ministerio de Salud, Chiclayo 14012, Perú
- https://orcid.org/0000-0002-4357-4261
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11
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El Homsi M, Golia Pernicka JS, Lall C, Nougaret S, Paspulati RM, Pickhardt PJ, Sheedy SP, Petkovska I. Beyond squamous cell carcinoma: MRI appearance of uncommon anal neoplasms and mimickers. Abdom Radiol (NY) 2023; 48:2898-2912. [PMID: 37027015 PMCID: PMC10775174 DOI: 10.1007/s00261-023-03891-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 03/16/2023] [Accepted: 03/17/2023] [Indexed: 04/08/2023]
Abstract
Anal cancer is an uncommon malignancy. In addition to squamous cell carcinoma, there are a variety of other less common malignancies and benign pathologies that may afflict the anal canal, with which abdominal radiologists should be familiar. Abdominal radiologists should be familiar with the imaging features that can help distinguish different rare anal tumors beyond squamous cell carcinoma and that can aid in diagnosis therefore help steer management. This review discusses these uncommon pathologies with a focus on their imaging appearance, management, and prognosis.
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Affiliation(s)
- Maria El Homsi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Jennifer S Golia Pernicka
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Chandana Lall
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Stephanie Nougaret
- Department of Radiology, Montpellier Cancer Research Institute (IRCM), Montpellier, France
| | - Raj M Paspulati
- Department of Radiology, Moffitt Cancer Center, Tampa, FL, USA
| | - Perry J Pickhardt
- Department of Radiology, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
| | | | - Iva Petkovska
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
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12
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Fastner S, Hieken TJ, McWilliams RR, Hyngstrom J. Anorectal melanoma. J Surg Oncol 2023; 128:635-644. [PMID: 37395165 DOI: 10.1002/jso.27381] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 06/21/2023] [Indexed: 07/04/2023]
Abstract
Anorectal melanoma is an aggressive mucosal melanoma subtype with a poor prognosis. Although recent advancements have been seen for cutaneous melanoma, the optimal treatment paradigm for management of anorectal melanoma is evolving. In this review, we highlight differences in the pathogenesis of mucosal versus cutaneous melanoma, new concepts of staging for mucosal melanoma, updates to surgical management of anorectal melanoma, and current data for adjuvant radiation and systemic therapy in this unique patient population.
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Affiliation(s)
| | - Tina J Hieken
- Department of Surgery, Division of Breast and Melanoma Surgical Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - John Hyngstrom
- Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Surgery, Division of Surgical Oncology, University of Utah, Salt Lake City, Utah, USA
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Akay S, Pollard JH, Saad Eddin A, Alatoum A, Kandemirli S, Gholamrezanezhad A, Menda Y, Graham MM, Shariftabrizi A. PET/CT Imaging in Treatment Planning and Surveillance of Sinonasal Neoplasms. Cancers (Basel) 2023; 15:3759. [PMID: 37568575 PMCID: PMC10417627 DOI: 10.3390/cancers15153759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/20/2023] [Accepted: 07/21/2023] [Indexed: 08/13/2023] Open
Abstract
Sinonasal cancers are uncommon malignancies with a generally unfavorable prognosis, often presenting at an advanced stage. Their high rate of recurrence supports close imaging surveillance and the utilization of functional imaging techniques. Whole-body 18F-FDG PET/CT has very high sensitivity for the diagnosis of sinonasal malignancies and can also be used as a "metabolic biopsy" in the characterization of some of the more common subgroups of these tumors, though due to overlap in uptake, histological confirmation is still needed. For certain tumor types, radiotracers, such as 11C-choline, and radiolabeled somatostatin analogs, including 68Ga-DOTATATE/DOTATOC, have proven useful in treatment planning and surveillance. Although serial scans for posttreatment surveillance allow the detection of subclinical lesions, the optimal schedule and efficacy in terms of survival are yet to be determined. Pitfalls of 18F-FDG, such as post-surgical and post-radiotherapy crusting and inflammation, may cause false-positive hypermetabolism in the absence of relapse.
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Affiliation(s)
- Sinan Akay
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Janet H. Pollard
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Assim Saad Eddin
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Aiah Alatoum
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Sedat Kandemirli
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Ali Gholamrezanezhad
- Department of Radiology, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA 90030, USA
| | - Yusuf Menda
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Michael M. Graham
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Ahmad Shariftabrizi
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
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14
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Ogata D, Tsutsui K, Namikawa K, Moritani K, Nakama K, Jinnai S, Takahashi A, Tsukamoto S, Kanemitsu Y, Yamazaki N. Treatment outcomes and prognostic factors in 47 patients with primary anorectal malignant melanoma in the immune therapy era. J Cancer Res Clin Oncol 2023; 149:749-755. [PMID: 35113236 DOI: 10.1007/s00432-022-03933-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/23/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE Primary anorectal melanoma (ARM) accounts for approximately 1.2% of all melanomas and 16.5% of all mucosal melanomas. ARM is associated with the shortest interval to disease progression and the highest rate of metastasis; however, optimal therapeutic strategies for ARM remain controversial. This study aimed to assess the ideal surgical intervention for ARM and to determine the effect of immune checkpoint inhibitors (ICI). METHODS We included 47 patients with ARM treated at the National Cancer Center Hospital in Japan from 2011 to 2020. We performed a survival analysis for each of these groups: (i) patients with ARM (n = 47); (ii) operable non-stage IV cases at initial presentation (n = 35); and (iii) stage IV cases (n = 32). RESULTS The 5-year overall survival (OS) was 53.6%, and the median OS was 78.7 months in patients with ARM. No statistically significant difference in 5-year OS was found between rectal and anal sites (50.9% vs. 56.7%). In the non-stage IV subgroup, the type of surgery (abdominoperineal resection or wide local excision) did not correlate with OS (HR 1.85; 95% CI 0.46-7.5; p = 0.39). In the stage IV subgroup, the 2-year OS of the ICI treatment group was 61.4%, whereas that of the dacarbazine regimen group was 0% (p = 0.048). CONCLUSION Our ARM prognosis was better than that of previous studies. Our findings suggest that the availability of ICI therapy may improve survival in patients with advanced ARM. However, further research is warranted to identify both the clinical and molecular predictors of response to improve patient selection.
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Affiliation(s)
- Dai Ogata
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan.
| | - Keita Tsutsui
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
- Department of Dermatology, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Kenjiro Namikawa
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Konosuke Moritani
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Kenta Nakama
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Shunichi Jinnai
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Akira Takahashi
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Shunsuke Tsukamoto
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Naoya Yamazaki
- Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
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15
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Bediako-Bowan AA, Gbadamosi H, Ayettey HNG, Kumassah PK, Aperkor N, Dake S, Una UA, Nyamekye-Baidoo J, Dakubo JCB. Anorectal malignant mucosal melanoma. Ghana Med J 2022; 56:331-335. [PMID: 37575632 PMCID: PMC10416284 DOI: 10.4314/gmj.v56i4.12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023] Open
Abstract
Anorectal mucosal melanoma (AMM) is a rare, aggressive malignancy. The symptoms of AMM mimic common benign conditions in the anus, such as haemorrhoids; hence diagnosis is often made late, a third of patients having metastasis at first presentation. Surgical resection remains the standard of treatment, and adjuvant therapy is varied, including immunotherapy, brachytherapy, and chemotherapy. The prognosis is poor, with a 5-year survival of 20%. A 65year old woman presented with a five-year history of symptoms suggestive of haemorrhoids and was diagnosed with a malignant anorectal mucosal melanoma after symptoms worsened and further investigation was performed. She underwent surgical resection and is currently receiving adjuvant therapy. The prognosis of AMM, the lack of consensus on the treatment regimen to date, and the need for a high index of suspicion for early diagnosis are discussed. Funding None declared.
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Affiliation(s)
- Antoinette A Bediako-Bowan
- Department of Surgery, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu Campus, P. O. Box 4236, Accra
- Department of Surgery, Korle Bu Teaching Hospital, P. O. Box 77, Accra
| | - Hafisatu Gbadamosi
- Department of Radiology, Korle Bu Teaching Hospital, P. O. Box 77, Accra
| | - Hannah N G Ayettey
- National Radiotherapy Oncology and Nuclear Medicine Centre, Korle Bu Teaching Hospital, P. O. Box 77, Accra
| | | | - Nicholas Aperkor
- Department of Surgery, Korle Bu Teaching Hospital, P. O. Box 77, Accra
| | - Selorm Dake
- Department of Surgery, Korle Bu Teaching Hospital, P. O. Box 77, Accra
| | - Uduak-Abasi Una
- Department of Surgery, Korle Bu Teaching Hospital, P. O. Box 77, Accra
| | | | - Jonathan C B Dakubo
- Department of Surgery, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu Campus, P. O. Box 4236, Accra
- Department of Surgery, Korle Bu Teaching Hospital, P. O. Box 77, Accra
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16
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Temperley HC, O’Sullivan NJ, Keyes A, Kavanagh DO, Larkin JO, Mehigan BJ, McCormick PH, Kelly ME. Optimal surgical management strategy for treatment of primary anorectal malignant melanoma—a systematic review and meta-analysis. Langenbecks Arch Surg 2022; 407:3193-3200. [DOI: 10.1007/s00423-022-02715-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 10/15/2022] [Indexed: 11/06/2022]
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17
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Songtanin B, Nugent K, Islam S. Prolapsed anorectal malignant melanoma presenting as hemorrhoids. Proc (Bayl Univ Med Cent) 2022; 36:89-90. [PMID: 36578595 PMCID: PMC9762773 DOI: 10.1080/08998280.2022.2119542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Rectal bleeding in a patient with a history of hemorrhoids should not be ignored. It is often benign and resolves spontaneously without treatment. Here we present a case of anorectal malignant melanoma that presented with rectal bleeding and a prolapsed rectal mass.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas,Corresponding author: Busara Songtanin, MD, Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX79430 (e-mail: )
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Sameer Islam
- Division of Gastroenterology, Texas Tech University Health Sciences Center, Lubbock, Texas
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18
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Mitra D, Rao PK, Nagarajan P, Bishop AJ, Farooqi AS, Gershenwald JE, Wargo J, Keung EZ, Fisher SB, Amaria RN, Davies MA, Ross MI, Guadagnolo BA. Outcomes After Sphincter-Sparing Local Therapy for Anorectal Melanoma: 1989 to 2020. Pract Radiat Oncol 2022; 12:437-445. [PMID: 35278716 DOI: 10.1016/j.prro.2022.02.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/08/2022] [Accepted: 02/25/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE The treatment paradigm for patients with anorectal melanoma eligible for sphincter-sparing excision has evolved over time. This study examines outcomes across a 30-year era in this rare disease with poor prognosis. METHODS AND MATERIALS This retrospective cohort study included all patients with pelvis-confined anorectal melanoma undergoing sphincter-sparing local excision and adjuvant radiation therapy (RT) at our institution between 1989 and 2020. Patterns of care and predictors of outcome were evaluated. RESULTS Of the 108 patients included, 92 (85%) presented with clinically uninvolved nodes. For clinically node-negative patients, the sentinel lymph node biopsy rate increased from 18/43 (42%) before 2008 to 38/49 (78%) subsequently and the use of inguinal nodal RT decreased from 33/35 (94%) before 2003 to 1/57 (2%) subsequently. All clinically node-positive patients treated before 2003 received inguinal nodal RT, whereas no node-positive patient treated subsequently received this treatment. Patients treated before 2016 mostly received biochemotherapy, and those treated since 2017 mostly received immune checkpoint inhibitors. With median follow-up of 32 months, 77 patients (71%) recurred. Three-year actuarial outcomes were 84% local control, 64% nodal control, 38% distant metastasis-free survival, 30% disease-free survival, and 51% melanoma-specific survival. Ostomy-free survival at last follow-up was 95%. Factors contributing to outcome were identified. Outcomes for patients treated in the contemporary era (2017+) were not significantly better than those treated earlier. CONCLUSIONS Sphincter-sparing surgery followed by adjuvant RT results in excellent local control and ostomy-free survival for locally resectable anorectal melanoma. Overall oncologic outcomes continue to be poor, reinforcing the need to identify more effective therapies.
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Affiliation(s)
- Devarati Mitra
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer, Houston, Texas.
| | - Pallavi Krishna Rao
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | | | - Andrew J Bishop
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Ahsan S Farooqi
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Jeffrey E Gershenwald
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Jennifer Wargo
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Emily Z Keung
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Sarah B Fisher
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Rodabe N Amaria
- Melanoma Medical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Michael A Davies
- Melanoma Medical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - Merrick I Ross
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
| | - B Ashleigh Guadagnolo
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer, Houston, Texas
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19
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Jung S, Johnson DB. Management of Acral and Mucosal Melanoma: Medical Oncology Perspective. Oncologist 2022; 27:703-710. [PMID: 35640549 PMCID: PMC9355814 DOI: 10.1093/oncolo/oyac091] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/28/2022] [Indexed: 11/13/2022] Open
Abstract
Acral and mucosal melanomas (MM) are rare subtypes of melanoma that are biologically and clinically distinct from cutaneous melanoma. Despite the progress in the treatment of cutaneous melanomas with the development of targeted and immune therapies, the therapeutic options for these less common subtypes remain limited. Difficulties in early diagnosis, the aggressive nature of the disease, and the frequently occult sites of origin have also contributed to the poor prognosis associated with acral and MM, with substantially worse long-term prognosis. The rarity of these subtypes has posed significant barriers to better understanding their biological features and investigating novel therapies. Consequently, establishing standardized treatment guidelines has been a challenge. In this review, we provide a brief overview of the current knowledge regarding acral and MM, focusing on their epidemiology, genetic backgrounds, and unique clinical characteristics. Further discussion centers around the management of primary and advanced disease and the role of emerging targeted and immune therapies for these subtypes, specifically focusing on issues relevant to medical oncologists.
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Affiliation(s)
- Seungyeon Jung
- Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Douglas B Johnson
- Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville TN, USA
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20
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Chiu HT, Pu TW, Yen H, Liu T, Wen CC. Is repeat wide excision plus radiotherapy of localized rectal melanoma another choice before abdominoperineal resection? A case report. World J Clin Cases 2022; 10:5057-5063. [PMID: 35801054 PMCID: PMC9198861 DOI: 10.12998/wjcc.v10.i15.5057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 02/03/2022] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Rectal melanoma is an uncommon neoplasm that accounts for approximately 1 percent of rectal cancer cases. Abdominoperineal resection was regarded as the radical procedure for disease control. Nevertheless, it led to more postoperative complications than sphincter-sparing wide local excision (WLE) and reduced the patient’s quality of life (QOL) owing to creation of colostomy. Therefore, in this study, WLE, radiotherapy (RT), and a second WLE were conducted on a patient who had been diagnosed with localized rectal melanoma.
CASE SUMMARY The patient was a 79-year-old woman who had been experiencing anal pain and bloody stool for 1 mo. Colonoscopy, magnetic resonance imaging, positron emission tomography–computed tomography, and histological analysis of tissue biopsy using the histological markers Melan-A (+), S-100 (+), and Ki-67 (+, 50%) lead to the diagnosis of localized rectal melanoma. The patient had initially undergone WLE to resolve problem of anal bleeding, followed by RT to treat the residual lesion with partial response. Subsequently, the residual lesion was removed with margin-free resection by the second WLE. The patient’s postoperative course was smooth and uneventful. During the 2-year follow-up, no local recurrence was observed. Additionally, a good functional outcome and improved QOL were reported.
CONCLUSION Combining WLE, RT, and repeat WLE is proposed as a viable alternative for treating rectal melanoma accompanied by bleeding symptoms that cannot be completely resected at the beginning.
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Affiliation(s)
- Hao-Tse Chiu
- Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
| | - Ta-Wei Pu
- Division of Colon and Rectal Surgery, Department of Surgery, Songshan Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei 10581, Taiwan
| | - Hao Yen
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
| | - Tung Liu
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
| | - Chia-Cheng Wen
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
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21
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Berhili S, Rezzoug M, Ben Sghier A, Moukhlissi M, Mezouar L. Oral Malignant Melanoma in a Patient With Neurofibromatosis Type 1: An Extremely Rare Association. Cureus 2022; 14:e25331. [PMID: 35761911 PMCID: PMC9232212 DOI: 10.7759/cureus.25331] [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] [Accepted: 05/25/2022] [Indexed: 11/05/2022] Open
Abstract
Neurofibromatosis type 1 (NF1) is a genetic disorder associated with high rates of neural crest-derived tumors, both benign and malignant. Many series have identified cutaneous melanoma as a rare tumor among cancers occurring in individuals with NF1 disease, but the mucosal location has to date never been reported. In this paper, we report an oral melanoma occurring in a patient with NF1 disorder, diagnosed at a locally advanced stage, successfully managed by definitive external beam radiotherapy, along with a comprehensive literature review on the melanoma-NF1 association.
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22
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Schaub SK, Kim EY. Controversy of Adjuvant Locoregional Therapy for Node-Positive Anal Mucosal Melanoma. Int J Radiat Oncol Biol Phys 2022; 112:1071-1072. [PMID: 35286876 DOI: 10.1016/j.ijrobp.2018.07.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 04/28/2018] [Accepted: 07/02/2018] [Indexed: 11/30/2022]
Affiliation(s)
- Stephanie K Schaub
- University of Washington School of Medicine, Department of Radiation Oncology, Seattle, Washington
| | - Edward Y Kim
- University of Washington School of Medicine, Department of Radiation Oncology, Seattle, Washington
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23
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Kim JC, Kim J, Jung J, Kim CW, Yoon YS, Park IJ. Implementation of robot-assisted curative resection for rare anorectal tumours on the basis of individualised treatment. Int J Med Robot 2022; 18:e2348. [PMID: 34741383 DOI: 10.1002/rcs.2348] [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: 08/23/2021] [Revised: 11/01/2021] [Accepted: 11/02/2021] [Indexed: 11/12/2022]
Abstract
PURPOSE To evaluate the validity of robot-assisted curative operation for rare anorectal tumours, characterised by biological heterogeneity and anatomical complexity. METHODS The present study evaluated 16 consecutive patients including three with anorectal squamous cell carcinoma (ARSCC), four with anorectal mucosal melanoma (ARMM), seven with anorectal neuroendocrine tumour (ARNET), and two with other types of anorectal tumours. RESULTS Of the three patients with ARSCC after chemoradiotherapy, two underwent abdominoperineal resection (APR), and one underwent ultralow anterior resection (uLAR)/total intersphincteric resection (ISR), surviving 56-76 months without recurrence. Of the four ARMM patients, APR and uLAR/total ISR were conducted in two patients, respectively, with variable survival outcomes. All seven patients with ARNET were treated with uLAR/ISR and LAR, surviving for 5-106 months to date. CONCLUSIONS Because most anorectal tumours are confined to the dermal and submucosal layers, robotic anorectal function preserving ISR is expected to achieve R0 resection.
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Affiliation(s)
- Jin Cheon Kim
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Jihun Kim
- Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Jay Jung
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Chan Wook Kim
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Yong Sik Yoon
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - In Ja Park
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
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24
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Guadagnolo BA. The Goldilocks Spot for Radiation Therapy in Anorectal Melanoma: Yes to the Primary Site After Local Excision; No to the Groin. Int J Radiat Oncol Biol Phys 2022; 112:1073. [PMID: 35286877 DOI: 10.1016/j.ijrobp.2018.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 05/24/2018] [Accepted: 07/02/2018] [Indexed: 11/28/2022]
Affiliation(s)
- B Ashleigh Guadagnolo
- Department of Radiation Oncology, Department of Health Services Research, MD Anderson Cancer Center, Houston, Texas
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25
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Defer Dissection: Radiation Therapy and Systemic Therapy. Int J Radiat Oncol Biol Phys 2022; 112:1074-1075. [PMID: 35286879 DOI: 10.1016/j.ijrobp.2021.12.169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 12/29/2021] [Indexed: 11/22/2022]
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26
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Mitra D. Locoregional-Directed Therapy Is Still a Cornerstone of Anorectal Melanoma Management. Int J Radiat Oncol Biol Phys 2022; 112:1075. [PMID: 35286880 DOI: 10.1016/j.ijrobp.2021.12.170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 12/29/2021] [Indexed: 10/18/2022]
Affiliation(s)
- Devarati Mitra
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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27
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Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas. Biomedicines 2022; 10:biomedicines10010150. [PMID: 35052829 PMCID: PMC8773579 DOI: 10.3390/biomedicines10010150] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/07/2022] [Accepted: 01/08/2022] [Indexed: 02/05/2023] Open
Abstract
Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.
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28
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Apostu RC, Stefanescu E, Scurtu RR, Kacso G, Drasovean R. Difficulties in diagnosing anorectal melanoma: A case report and review of the literature. World J Clin Cases 2021; 9:11369-11381. [PMID: 35071568 PMCID: PMC8717525 DOI: 10.12998/wjcc.v9.i36.11369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/15/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation. Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established. Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.
CASE SUMMARY A 66-year-old woman presented with intermittent anal bleeding, pain, and tenesmus in the past month, with no associated weight loss. Colonoscopy revealed a cauliflower-like tumour with a diameter of 1.5 cm, with exulcerated areas and an adherent clot but without obstruction. Biopsy results identified an inflammatory rectal polyp with nonspecific chronic rectitis. Tumour markers CA 19-9 and CEA were within the normal range. After 6 mo, due to the persistence of symptoms, a pelvic magnetic resonance imaging scan was performed. A lesion measuring 2.8 cm × 2.7 cm × 2.1 cm was identified at the anorectal junction, along with two adjacent lymphadenopathies. No distant metastases were detected. Immunohistochemistry was performed on the second set of biopsies, and a diagnosis of anorectal melanoma was established. Surgical treatment by abdominoperineal resection was performed. Evolution was marked by the appearance of lung metastases at 1 mo postoperatively, detected on a positron emission tomography-computer tomography scan, and perineal recurrence after 5 mo. After molecular testing, the patient was included in an immunotherapy trial.
CONCLUSION This case highlights the difficulty of establishing a definitive early diagnosis of anorectal melanoma, the importance of performing histological analysis on a well-represented biopsy specimen, and the poor prognosis, even with radical surgery.
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Affiliation(s)
- Raluca Cristina Apostu
- Department of Surgery, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400006, Romania
| | - Elena Stefanescu
- Department of Anesthesia and Intensive Care, Emergency County Clinical Hospital, Cluj-Napoca 400006, Romania
| | - Radu Razvan Scurtu
- Department of Surgery, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, Cluj Napoca 400006, Romania
| | - Gabriel Kacso
- Department of Medical Oncology and Radiotherapy, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca 400006, Romania
| | - Radu Drasovean
- Department of Surgery, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400006, Romania
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29
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Chatterjee A, Rohila J, Kazi M, Sharma V, Desouza A, Ostwal V, Bajpai J, Engineer R, Bal M, Saklani A. Outcomes of radical surgical resections for nonmetastatic anorectal melanomas: Experience from a tertiary care centre. Colorectal Dis 2021; 23:3180-3189. [PMID: 34716986 DOI: 10.1111/codi.15975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 09/19/2021] [Accepted: 10/03/2021] [Indexed: 02/08/2023]
Abstract
AIM The outcome of radical surgery in nonmetastatic anorectal melanoma (AM) patients is studied infrequently. Here, we aimed to explore the stage-wise outcomes and the impact of radical resections in these patients. METHODS In this single-centre retrospective study, data of 154 eligible patients were recorded and analysed. Data were obtained from November 2010 to September 2019 with follow-up until November 2020. Overall survival (OS) and disease-free survival (DFS) was calculated by Kaplan Meir method and univariate analysis of prognostic factors by Cox regression. RESULTS Of 154 patients, 110 were metastatic (stage III) and 44 were nonmetastatic (stage I:22, stage II:22) and underwent curative resections. Median follow-up was 48 months (14-119 months). A total of 39 patients underwent total mesorectal excisions (TME) and five transanal excision (TAE) were performed. Seven patients underwent extended resections. Stage I and II patients had 3- and 5-year OS of 40% and 36%; and DFS of 45% and 33.2%, respectively. Median OS and DFS were 31 and 24 months, respectively. Stage II (node-positive) patients had better median OS compared to stage III (21 vs. 4 months; p = 0.000), and 54.5% patients had recurrences, most commonly both systemic and nodal (45.83%). Median OS of patients without recurrence was 34 months. CONCLUSION In this large surgical series of AMs, outcome in stage I and II patients was significantly better than stage III and patients with stage II disease can have acceptable oncological outcomes. Radical surgical resections with or without lymphadenectomy could be considered in these patients. The role of adjuvant systemic therapy and radiation needs to be explored as part of multimodality treatment.
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Affiliation(s)
- Ambarish Chatterjee
- Unit of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Jitender Rohila
- Unit of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Mufaddal Kazi
- Unit of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Vivekanand Sharma
- Unit of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Ashwin Desouza
- Unit of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Jyoti Bajpai
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Munita Bal
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
| | - Avanish Saklani
- Unit of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Mumbai, India
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30
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Wong DL, Glazer ES, Tsao M, Deneve JL, Fleming MD, Shibata D. Impact of adjuvant therapies following surgery for anal melanoma. Am J Surg 2021; 223:1132-1143. [PMID: 34801225 DOI: 10.1016/j.amjsurg.2021.10.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 10/15/2021] [Accepted: 10/31/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Anal melanoma is rare. Surgery is standard of care for non-metastatic disease. There are limited data supporting adjuvant therapy. We sought to examine the impact of adjuvant radiation, chemotherapy and immunotherapy on survival. METHODS The National Cancer Database was queried. Factors associated with overall survival were examined by Kaplan-Meier and Cox proportional hazards analyses. Patients were grouped by treatment regimen. RESULTS 450 patients had complete treatment data: surgery alone (63.8%), surgery + radiation (14.9%), surgery + chemotherapy (7.6%), surgery + immunotherapy (9.6%) and non-surgical treatment (4.2%). Median survival was 27.2 months. Node-positive patients had worse survival than node-negative (22.4 vs. 36.8 months; p = 0.0002). Non-surgical treatment yielded worse survival than any surgery-inclusive regimen (10.4 vs. 27.8 months; p = 0.0002). No adjuvant modality conferred a survival advantage. By multivariate analysis, increasing age (HR/1 year = 1.02, p = 0.012) and node positivity (HR = 2.10, p = 0.0002) negatively impacted survival. CONCLUSION Adjuvant therapy for non-metastatic anal melanoma does not appear to influence survival.
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Affiliation(s)
- Denise L Wong
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38103, USA
| | - Evan S Glazer
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38103, USA
| | - Miriam Tsao
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38103, USA
| | - Jeremiah L Deneve
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38103, USA
| | - Martin D Fleming
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38103, USA
| | - David Shibata
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38103, USA.
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31
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Kolosov A, Leskauskaitė J, Dulskas A. Primary melanoma of the anorectal region: clinical and histopathological review of 17 cases. A retrospective cohort study. Colorectal Dis 2021; 23:2706-2713. [PMID: 34270837 DOI: 10.1111/codi.15816] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/23/2021] [Accepted: 07/11/2021] [Indexed: 12/24/2022]
Abstract
AIM The aim of our study was to scrutinize diagnostic and treatment factors that may contribute to the low survival rate from anorectal melanoma while adding 17 more cases to the global research database. METHOD We carried out a retrospective analysis of 17 cases of anorectal melanoma treated at a single institution from 2000 to 2020. Data on patient age, sex, complaints, treatment and survival as well as tumour size, resection margins, histological and immunohistochemical features were assessed. RESULTS The median age of patients was 72 ± 12.49 (45-92) years. Most of the patients were women (n = 11, 64.71%). Three (17.65%) patients underwent no radical treatment. Of eight patients treated initially with radical surgery (either total mesorectal excision or abdominoperineal resection), six (75%) were found to have positive lymph nodes. Mean survival was 20 ± 23.46 (1-84) months. The average diameter of the resected tumours was 5.43 ± 3.02 cm (1.3-10 cm). Most tumours had epithelioid or spindle cell morphology and were positive for one or more melanocytic markers (S100, HMB-45 or MITF). More than half of the tumours contained no or very little melanin pigment. None of the tumours had significant lymphocytic infiltration. Three tumours showed positivity for keratins (PANCK or CAM5.2) and one tumour showed positivity for C-KIT stain. CONCLUSION An aggressive surgical approach may have an effect on survival in most early stages while more advanced disease benefits from a more conservative approach. Attention to sentinel lymph nodes and further systemic research into therapy is required. For now, treatment and diagnostic modalities seem to be inconsistent, requiring further investigation to elucidate common points.
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Affiliation(s)
- Andrej Kolosov
- Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania.,Faculty of Mechanics, Department of Biomechanical Engineering, Vilnius Gediminas Technical University (Vilnius Tech, Vilnius, Lithuania.,Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Jurgita Leskauskaitė
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania.,National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Audrius Dulskas
- Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania.,Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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Abstract
Noncutaneous melanomas are rare subtypes of melanoma with high rates of metastatic disease and poor overall survival. One-third to one-half of cases are amelanotic, which may contribute to a delay in diagnosis. Immunohistochemistry staining with typical melanoma markers helps confirm the diagnosis. There is no standard staging system across mucosal melanomas. Elective nodal dissection is not recommended and there is a paucity of data to support use of sentinel lymph node biopsy. Mutational analysis should be routinely performed. Systemic therapy options include targeted inhibitors, immunotherapy, and cytotoxic chemotherapy, although further studies are needed to confirm their efficacy.
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Affiliation(s)
- Ann Y Lee
- Department of Surgery, NYU Langone Health, 550 1st Avenue, NBV 15N1, New York, NY 10016, USA.
| | - Russell S Berman
- Department of Surgery, NYU Langone Health, 550 1st Avenue, NBV 15N1, New York, NY 10016, USA. https://twitter.com/bermar01
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33
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Nigam JS, Kumar T, Singh A, Tewari P, Pandey JK. Anorectal Melanoma-Brownish Black Mass Not Always a Hemorrhoid. J Gastrointest Cancer 2021; 53:825-829. [PMID: 34347246 DOI: 10.1007/s12029-021-00678-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2021] [Indexed: 11/26/2022]
Abstract
The non-specific clinical symptoms of anorectal brownish-black mass do not help to differentiate colorectal cancer, hemorrhoids, rectal ulcers which result in a delayed diagnosis or lead to inadequate management of lethal anorectal melanoma. Primary malignant melanoma of the anorectal region is an uncommon tumor, constituting approximately 1% of anal canal tumors which may be misdiagnosed clinically as hemorrhoids. Because of aggressive behavior and poor prognosis, efficient and prompt diagnosis is required in these cases. We report 2 cases of this rare tumor.
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Affiliation(s)
- Jitendra Singh Nigam
- Department of Pathology and Lab Medicine, All India Institute of Medical Science, Bibinagar, Telangana, India.
| | - Tarun Kumar
- Department of Pathology / Lab Medicine, All India Institute of Medical Science, Patna, Bihar, India
| | - Avinash Singh
- Department of Pathology / Lab Medicine, All India Institute of Medical Science, Patna, Bihar, India
| | - Prerna Tewari
- Department of Pathology / Lab Medicine, All India Institute of Medical Science, Patna, Bihar, India
| | - Jagjit Kumar Pandey
- Department of Surgical Oncology, All India Institute of Medical Science, Patna, Bihar, India
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34
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Nagarajan P. Mucosal Melanomas of the Anogenital Tract: Clinical and Pathologic Predictors of Patient Survival. Surg Pathol Clin 2021; 14:225-235. [PMID: 34023102 DOI: 10.1016/j.path.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Primary anogenital mucosal melanomas (AGMs) are rare aggressive malignancies that are typically diagnosed at an advanced stage. Ulceration is a common feature in AGMs and may not correlate with outcome. Therefore, staging of AGMs similar to primary cutaneous melanomas, based on tumor thickness and ulceration, may not robustly predict outcome. Derivation of site-specific staging systems is essential for prognostication and optimal management of these patients. To this end, recent retrospective studies have revealed tumor thickness (TT) and mitotic rate (MR) as features of most prognostic significance as follows: in anorectal (TT only) and vulvar (TT and MR) melanomas.
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Affiliation(s)
- Priyadharsini Nagarajan
- Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, B3-4621, Unit 85, Houston, TX 77030, USA.
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35
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Kahl AR, Gao X, Chioreso C, Goffredo P, Hassan I, Charlton ME, Lin C. Presentation, Management, and Prognosis of Primary Gastrointestinal Melanoma: A Population-Based Study. J Surg Res 2021; 260:46-55. [PMID: 33316759 PMCID: PMC7946707 DOI: 10.1016/j.jss.2020.11.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 09/19/2020] [Accepted: 11/01/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary gastrointestinal (GI) melanomas, compared with cutaneous melanomas, have a much lower incidence. As a result, there is a paucity of data regarding their presentation, treatment, and prognosis. The aim of this study was to analyze the incidence, patient characteristics, treatment patterns, and survival of primary GI melanomas in comparison with cutaneous melanomas using a population-based cohort. METHODS Patients diagnosed with primary GI and cutaneous melanomas were identified from Surveillance, Epidemiology, and End Results 1973-2016 data. RESULTS A total of 872 primary GI melanomas and 319,327 cutaneous melanomas were identified. GI melanoma incidence increased by an annual percent change of 1.82 (P < 0.05) during the study period. The most common sites for GI melanoma were the anus (50%) and rectum (34%). Compared to cutaneous melanoma, patients diagnosed with GI melanomas were older, women (58% versus 45%), non-White (16% versus 6%), and presented with a higher stage (36% versus 4% distant stage, all P < 0.001). GI melanomas had significantly worse cancer-specific survival (CSS) than cutaneous melanoma. Despite the poor prognosis, the CSS has increased in recent years. Among patients with anorectal melanomas, local excision with chemotherapy and/or radiation had a similar CSS compared with those with major surgery only. CONCLUSIONS Despite a steady increasing incidence since 1975, GI melanomas are rare, present with advanced stages, and have worse outcomes than cutaneous melanomas. The improved prognosis of these tumors in recent years might reflect the impact of novel targeted treatments and the more common use of local tumor excision over major resections.
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Affiliation(s)
| | - Xiang Gao
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Catherine Chioreso
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
| | - Paolo Goffredo
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Imran Hassan
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Mary E Charlton
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
| | - Chi Lin
- University of Nebraska Medical Center
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36
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Bleicher J, Cohan JN, Huang LC, Peche W, Pickron TB, Scaife CL, Bowles TL, Hyngstrom JR, Asare EA. Trends in the management of anorectal melanoma: A multi-institutional retrospective study and review of the world literature. World J Gastroenterol 2021; 27:267-280. [PMID: 33519141 PMCID: PMC7814367 DOI: 10.3748/wjg.v27.i3.267] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 12/28/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Anorectal melanoma (ARM) is a rare disease with a poor prognosis. Evidence on optimal treatment is limited and surgical management varies widely. We hypothesized that the frequency of abdominoperineal resection used as primary treatment of ARM has decreased over the past several decades.
AIM To update our understanding of outcomes for patients with ARM and analyze management trends around the world.
METHODS This is a multi-institutional, retrospective study of patients treated for ARM at 7 hospitals. Hospitals included both large, academic, tertiary care centers and smaller, general community hospitals. Using prospectively maintained institutional tumor registries, we identified 24 patients diagnosed with ARM between January 2000 and May 2019. We analyzed factors prognostic for recurrence and survival. We then used Cox regression to measure overall survival (OS) and melanoma-specific survival. We also performed a literature review to assess trends in surgical management and outcomes.
RESULTS Of the 24 patients diagnosed with ARM, 12 (50.0%) had local, 8 (33.3%) regional, and 4 (16.7%) distant disease at diagnosis. Median time to recurrence was 10.4 mo [interquartile range (IQR) 7.5-17.2] with only 2 patients (9.3%) not developing recurrence following surgical resection. Median OS was 18.8 mo (IQR 13.5-33.9). One patient is still alive without recurrence at 21.4 mo from diagnosis; no other patient survived 5 years. Primary surgical management with abdominoperineal resection (APR) vs wide excision (WE) did not lead to differences in OS [hazard ratio = 1.4 (95%CI: 0.3-6.8)]. Review of the literature revealed geographic differences in surgical management of ARM, with increased use of WE in the United States and Europe over time and more frequent use of APR in Asia and India. There was no significant improvement in survival over time.
CONCLUSION There is wide variation in the management of ARM and survival outcomes remain poor regardless of approach. Surgical management should aim to minimize morbidity.
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Affiliation(s)
- Josh Bleicher
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
| | - Jessica N Cohan
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
| | - Lyen C Huang
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
| | - William Peche
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
- Department of Surgery, George E Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84114, United States
| | - T Bartley Pickron
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
| | - Courtney L Scaife
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
| | - Tawnya L Bowles
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
- Department of Surgery, Intermountain Medical Center, Murray, UT 84107, United States
| | - John R Hyngstrom
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
- Department of Surgery, George E Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84114, United States
| | - Elliot A Asare
- Department of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84114, United States
- Department of Surgery, Intermountain Medical Center, Murray, UT 84107, United States
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Chacón M, Pfluger Y, Angel M, Waisberg F, Enrico D. Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives. Cancers (Basel) 2020; 12:E2362. [PMID: 32825562 PMCID: PMC7565756 DOI: 10.3390/cancers12092362] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/25/2020] [Accepted: 07/29/2020] [Indexed: 12/26/2022] Open
Abstract
Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs-not associated with classical V600E/K BRAF mutations-malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.
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Affiliation(s)
- Matías Chacón
- Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires 1426, Argentina; (Y.P.); (M.A.); (F.W.); (D.E.)
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38
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Smith HG, Bagwan I, Board RE, Capper S, Coupland SE, Glen J, Lalondrelle S, Mayberry A, Muneer A, Nugent K, Pathiraja P, Payne M, Peach H, Smith J, Westwell S, Wilson E, Rodwell S, Gore M, Turnbull N, Smith MJF. Ano-uro-genital mucosal melanoma UK national guidelines. Eur J Cancer 2020; 135:22-30. [PMID: 32531566 DOI: 10.1016/j.ejca.2020.04.030] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 01/22/2020] [Accepted: 04/08/2020] [Indexed: 02/03/2023]
Abstract
Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE). A summary of the key recommendations is presented. The full documents are available on the Melanoma Focus website.
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Affiliation(s)
| | - Izhar Bagwan
- Royal Surrey County Hospital NHS Foundation Trust, UK
| | - Ruth E Board
- Lancashire Teaching Hospitals NHS Foundation Trust, UK
| | | | | | | | | | | | - Asif Muneer
- NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust and Division of Surgery and Interventional Science University College London, UK
| | - Karen Nugent
- University Hospital Southampton NHS Foundation Trust, UK
| | | | - Miranda Payne
- Oxford University Hospitals NHS Foundation Trust, UK
| | - Howard Peach
- Leeds Teaching Hospitals NHS Foundation Trust, UK
| | | | - Sarah Westwell
- Brighton and Sussex University Hospitals NHS Foundation Trust, UK
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Nonaka K, Kudou K, Sasaki S, Jogo T, Hirose K, Kasagi Y, Hu Q, Tsuda Y, Hisamatsu Y, Ando K, Nakashima Y, Saeki H, Oki E, Kamori M, Mori M. Primary anorectal malignant melanoma with laparoscopic abdominoperineal resection: a case study and review of the relevant literature. Int Cancer Conf J 2020; 9:116-122. [PMID: 32582514 PMCID: PMC7297936 DOI: 10.1007/s13691-020-00401-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 02/13/2020] [Indexed: 12/18/2022] Open
Abstract
ARMM is a disease with a poor prognosis. ARMM is often diagnosed at an advanced stage, and the 5-year survival rate of ARMM is < 20%. Although the number of case reports on ARMM is gradually increasing, the optimal treatment strategy for ARMM remains controversial. We report the case of an 81-year-old woman who had experienced bloody stool for 6 months before her diagnosis and who had been initially diagnosed with hemorrhoids. The pathological diagnosis of a biopsy specimen was malignant melanoma. Other examinations showed no evidence of lymph node or distant metastasis. Based on these results, laparoscopic abdominoperineal resection was performed. Three months later on her first follow-up examination, distant metastasis to the lung and liver was detected. Immunotherapy using Nivolumab was initiated to treat the recurrent disease. We reviewed the characteristics of a total of 1834 ARMM patients described in previous reports on ARMM for which the full text was available on PubMed. We experienced a case of ARMM. The prognosis of ARMM is still poor, regardless of the surgical procedure. Previous studies and our case report suggest that systemic therapy, such as immunotherapy using an anti-PD-1 ligand may be more important than reinforcement of local control for improving the prognosis of ARMM patients.
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Affiliation(s)
- Kentaro Nonaka
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kensuke Kudou
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Endoscopy and Endoscopic Surgery, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, Fukuoka 814-0193 Japan
| | - Shun Sasaki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoko Jogo
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kosuke Hirose
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuta Kasagi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Qingjiang Hu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuo Tsuda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuichi Hisamatsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koji Ando
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroshi Saeki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mitsuo Kamori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Kamori Clinic, Fukuoka, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Smith HG, Glen J, Turnbull N, Peach H, Board R, Payne M, Gore M, Nugent K, Smith MJF. Less is more: A systematic review and meta-analysis of the outcomes of radical versus conservative primary resection in anorectal melanoma. Eur J Cancer 2020; 135:113-120. [PMID: 32563895 DOI: 10.1016/j.ejca.2020.04.041] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 04/19/2020] [Accepted: 04/28/2020] [Indexed: 01/18/2023]
Abstract
INTRODUCTION Anorectal melanoma (ARM) is a rare disease with a poor prognosis. There is no consensus as to the optimal primary surgical treatment for ARM, with advocates for both radical (abdominoperineal resection [APR]) and conservative strategies (wide local excision [WLE]). Here, we report a systematic review of studies comparing outcomes between these strategies. METHODS Studies comparing APR with WLE in patients with ARM were included, and a systematic review using the Grading of Recommendations, Assessment, Development and Evaluation methodology was performed. Outcomes deemed critical included overall survival, disease-free survival, local recurrence and quality of life. RESULTS Forty studies were identified, of which 27 were suitable for inclusion. Twenty-three studies compared overall survival between WLE and APR, with no difference in outcomes noted (risk ratio [RR]: 0.80, 95% confidence interval [CI]: 0.60-1.07, p = 0.13). Seven studies compared disease-free survival, with no difference in outcomes noted (RR: 1.08, 95% CI: 0.61-1.91, p = 0.79). A total of 19 studies compared local recurrence rates, with again no significant difference in outcomes noted (RR: 0.71, 95% CI: 0.44-1.14, p = 0.16). None of the studies identified reported quality of life-related outcomes. CONCLUSION There is no evidence to suggest that a radical primary surgical strategy improves outcomes in ARM. Therefore, given the well-documented morbidity associated with APR, WLE with regular surveillance for local recurrence should be the primary strategy in most patients.
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Affiliation(s)
- Henry G Smith
- The Skin Unit, The Royal Marsden Hospital NHS Foundation Trust, London, England, UK; Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Jessica Glen
- National Guideline Centre, Royal College of Physicians, London, England, UK; The Health Research Council of New Zealand, Auckland, New Zealand
| | | | - Howard Peach
- Leeds Teaching Hospitals NHS Foundation Trust, UK
| | - Ruth Board
- Lancashire Teaching Hospitals NHS Foundation Trust, UK
| | - Miranda Payne
- Oxford University Hospitals NHS Foundation Trust, UK
| | - Martin Gore
- The Skin Unit, The Royal Marsden Hospital NHS Foundation Trust, London, England, UK
| | - Karen Nugent
- University Hospital Southampton NHS Foundation Trust, UK
| | - Myles J F Smith
- The Skin Unit, The Royal Marsden Hospital NHS Foundation Trust, London, England, UK.
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Anal Melanoma: A Rare Perianal Tumor With a Poor Prognosis. Dis Colon Rectum 2020; 63:573-576. [PMID: 32271217 DOI: 10.1097/dcr.0000000000001672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
A 69-year-old woman with a nonrelevant past medical history was referred to an outpatient colorectal clinic because of the incidental finding of an anal pigmented lesion during a routine gynecological examination. Anal inspection and proctoscopy indicated possible anal melanoma ( and ).
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Nassar KW, Tan AC. The mutational landscape of mucosal melanoma. Semin Cancer Biol 2020; 61:139-148. [PMID: 31655118 PMCID: PMC7078020 DOI: 10.1016/j.semcancer.2019.09.013] [Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 09/13/2019] [Accepted: 09/19/2019] [Indexed: 12/27/2022]
Abstract
Mucosal melanoma is a rare and aggressive subtype of melanoma that has a less favorable prognosis due to the lack of understanding and identification of oncogenic drivers. Recently, whole genome and whole exome sequencing have unveiled the molecular landscape and potential oncogenic drivers of mucosal melanoma, which remains distinct from cutaneous melanoma. In this review, we provide an overview of the genomic landscape of mucosal melanoma, with a focus on molecular studies identifying potential oncogenic drivers allowing for a better mechanistic understanding of the biology of mucosal melanoma. We summarized the published genomics and clinical data supporting the observations that mucosal melanoma harbors distinct genetic alterations and oncogenic drivers from cutaneous melanoma, and thus should be treated accordingly. The common drivers (BRAF and NRAS) found in cutaneous melanoma have lower mutation rate in mucosal melanoma. In contrast, SF3B1 and KIT have higher mutation rate in mucosal melanoma as compared to cutaneous melanoma. From the meta-analysis, we also observed that the mutational profiles are slightly different between the "upper" and "lower" regions of mucosal melanoma, providing new insights and therapeutic options for the mucosal melanoma patients. Mutations identified in mucosal melanoma should be incorporated into routine clinical testing, as there are targeted therapies already developed for treating patients with these mutations in the precision medicine era.
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Affiliation(s)
- Kelsey W Nassar
- Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80111, USA; Cancer Biology Training Program, Graduate School, University of Colorado Anschutz Medical Campus, Aurora, CO 80111, USA
| | - Aik Choon Tan
- Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80111, USA; Cancer Biology Training Program, Graduate School, University of Colorado Anschutz Medical Campus, Aurora, CO 80111, USA; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612 USA.
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Prognostic model for patient survival in primary anorectal mucosal melanoma: stage at presentation determines relevance of histopathologic features. Mod Pathol 2020; 33:496-513. [PMID: 31383963 DOI: 10.1038/s41379-019-0340-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 07/06/2019] [Accepted: 07/07/2019] [Indexed: 02/03/2023]
Abstract
Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients.
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Menon H, Patel RR, Cushman TR, Amini A, Seyedin SN, Adams AC, Lin C, Verma V. Management and outcomes of primary anorectal melanoma in the United States. Future Oncol 2020; 16:329-338. [DOI: 10.2217/fon-2019-0715] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aims: To analyze outcomes in primary anorectal melanoma, a rare disease with limited data and treatment guidelines. Materials & methods: We analyzed 305 subjects in the National Cancer Database from 2004 to 2015. The primary end point was overall survival (OS). Results: Surgery was predictive of OS (median 2.24 vs 1.18 years; p = 0.009) with no survival difference between local and transabdominal approaches (p = 0.77). No OS benefit was seen with chemotherapy (p = 0.16), radiotherapy (p = 0.31) or adjuvant therapy post surgery (p > 0.05 for all groups). Targeted therapy trended toward higher survival in metastatic patients (1.33 vs 0.55 years; p = 0.06). Conclusion: In nonmetastatic patients, surgery of any method is associated with a survival benefit. The trend for improved survival following targeted therapy in metastatic patients merits further exploration.
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Affiliation(s)
- Hari Menon
- Department of Radiation Oncology, University of Arizona College of Medicine – Phoenix, Phoenix, AZ 85004, USA
| | - Roshal R Patel
- Department of Radiation Oncology, Albany Medical College, Albany, NY 12208, USA
| | - Taylor R Cushman
- Department of Radiation Oncology, University of Arizona College of Medicine – Phoenix, Phoenix, AZ 85004, USA
| | - Arya Amini
- Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Steven N Seyedin
- Department of Radiation Oncology, University of Iowa Hospital & Clinics, Iowa City, IA 52242, USA
| | - Anngela C Adams
- Department of Radiation Oncology, University of Arizona College of Medicine – Phoenix, Phoenix, AZ 85004, USA
| | - Chi Lin
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Vivek Verma
- Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA 15212, USA
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Merichal Resina M, Cerdan Santacruz C, Sierra Grañón E, Tarragona Foradada JA, Olsina Kissler JJ. Anal melanoma, a radically different pathology from cutaneous melanoma with a tragic prognosis. Cir Esp 2019; 98:491-493. [PMID: 31898949 DOI: 10.1016/j.ciresp.2019.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 11/25/2019] [Accepted: 11/27/2019] [Indexed: 11/17/2022]
Affiliation(s)
- Mireia Merichal Resina
- Cirugía General y del Aparato Digestivo, Hospital Universitario Arnau de Vilanova, Lleida, España.
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Affiliation(s)
- Shaheer Khan
- Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
| | - Richard D. Carvajal
- Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
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Naqvi J, Lee A, Lederman A, Kavi A, Osborn VW, Schreiber D. Patterns of Care and Survival Outcomes in the Treatment of Anal Melanoma. J Gastrointest Cancer 2019; 51:211-216. [PMID: 30982929 DOI: 10.1007/s12029-019-00238-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE Anal mucosal melanoma is an uncommon malignancy of the anal canal, with few large studies available to establish clear trends in the treatment modalities presently available. The primary goal of this study was to identify the patterns of care in the treatment of anal melanoma and secondarily to determine outcomes. METHODS This was a retrospective study performed utilizing the National Cancer Database (NCDB). A total of 787 patients diagnosed with anal melanoma between 2004 and 2014 were selected, of which 398 had staging information. The four treatment groups analyzed were surgical excision alone, surgical excision and radiation therapy, surgical excision and immunotherapy/chemotherapy, and radiation therapy plus minus immunotherapy/chemotherapy. Treatment was grouped by extent of disease; the Kaplan-Meier method was used to analyze overall survival and multivariate Cox proportional model was used to identify factors associated with overall survival. RESULTS The majority of patients presented with either node-positive (39.4%) or metastatic disease (37.4%). Patients with surgical excision and radiation therapy had the highest median survival at 32.3 months. This is in contrast with those receiving surgical excision alone (22.9 months), surgery and immunotherapy/chemotherapy (18.4 months), and radiation without surgery (5.1 months) (p < 0.0001). CONCLUSIONS Treatment with surgical excision was the most common initial treatment with no single modality superior over another in this rare entity.
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Affiliation(s)
- Jaffer Naqvi
- Department of Radiation Oncology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Mail Stop #1211, Brooklyn, NY, 11203, USA
| | - Anna Lee
- Department of Radiation Oncology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Mail Stop #1211, Brooklyn, NY, 11203, USA.
- Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA.
| | - Ariel Lederman
- Department of Radiation Oncology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Mail Stop #1211, Brooklyn, NY, 11203, USA
- Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA
| | - Ami Kavi
- Department of Radiation Oncology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Mail Stop #1211, Brooklyn, NY, 11203, USA
- Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA
| | - Virginia W Osborn
- Department of Radiation Oncology, Elmhurst Hospital Center, Queens, NY, USA
| | - David Schreiber
- Department of Radiation Oncology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Mail Stop #1211, Brooklyn, NY, 11203, USA
- Summit Medical Group, Berkeley Heights, NJ, USA
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Primary anorectal melanoma: clinical, immunohistology and DNA analysis of 43 cases. Pathology 2018; 51:39-45. [PMID: 30497801 DOI: 10.1016/j.pathol.2018.09.060] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 08/30/2018] [Accepted: 09/09/2018] [Indexed: 12/31/2022]
Abstract
Primary melanoma involving the anorectal region is rare, accounting for <1% of all melanomas in most Western countries. It characteristically presents at an advanced clinical stage and is associated with poor clinical outcomes. Preliminary reports suggest that response rates to immunotherapies in patients with advanced stage mucosal melanoma are much lower than in cutaneous (or acral) melanoma patients but reasons for this are unclear. Comprehensive characterisation of the immune microenvironment in anorectal melanoma has not previously been performed. A single-institution cohort of 43 primary anorectal melanoma patients was examined to describe clinicopathological features and characterise the immune microenvironment to provide insights into the behaviour of this rare melanoma subtype. The tumours displayed multiple adverse prognostic attributes including deep thickness (median 11.5 mm), ulceration (81%) and high mitotic rate (median 12/mm2). The median overall survival was 24 months and the median recurrence-free survival was 9 months. Tumour-infiltrating lymphocytes (TILs) were absent or mild in most tumours (75%); PD-L1 positive staining (>1% of tumour cells) was present in 44% of cases, however in 86% of positive tumours the percentage of positive cells was ≤10%. Four tumours underwent whole genome sequencing; no ultraviolet signature was identified, and there was a lower mutational load but higher structural chromosomal variant load compared with cutaneous melanomas. Poor responses of anorectal melanomas to immunotherapy may be caused by lower immunogenicity of these tumours as characterised by low mutation burden (and therefore low neoantigenicity), low TILs infiltrates and low PD-L1 expression. Further investigation is required to determine whether TILs and PD-L1 expression predict response to immunotherapy in patients with mucosal melanoma.
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Atak I. Anorectal Malignant Melanoma: Retrospective Analysis of Six Patients and Review of the Literature. Prague Med Rep 2018; 119:97-106. [DOI: 10.14712/23362936.2018.9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
Abstract
Malignant melanomas are rare aggressive tumours originating from the pigment-producing melanocytes. In our study, a review of the literature and a retrospective analysis of patients undergoing surgery at our clinic due to anorectal malignant melanoma were performed. The information of 6 patients undergoing surgery in our clinic due to anorectal malignant melanoma between January 2010 and January 2018 was retrieved retrospectively. The patients were assessed regarding demographic data, physical examination and imaging findings, the surgical method performed, postoperative complication, histopathological findings, oncological treatment and follow-up results. Four of the patients were female and 2 were male and the mean age was 61.6 (46–83) years. Two patients (33%) had liver metastases at the time of initial presentation. Abdominoperineal resection (APR) was performed in all patients 3 with laparoscopic method. The mean length of hospital stay was recorded to be 6.5 ± 1 days (5–12 days). Adjuvant chemotherapy and radiotherapy were administered in all patients. Also, interferon treatment was administered in one patient additionally. During the follow-up, 4 patients died due to extensive metastatic disease determined approximately in the 13th month. Two patients with regular follow-up are well and free of disease and their mean postoperative lifetime has been determined to be 12.5 months (6–26 months). Anorectal malignant melanomas (ARMM) are rare but aggressive tumours. The treatment should be focused on minimizing morbidity and maximizing the quality of life and function while removing the gross tumour.
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50
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Tyrrell H, Payne M. Combatting mucosal melanoma: recent advances and future perspectives. Melanoma Manag 2018; 5:MMT11. [PMID: 30459941 PMCID: PMC6240847 DOI: 10.2217/mmt-2018-0003] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 08/03/2018] [Indexed: 12/20/2022] Open
Abstract
Mucosal melanomas are a rare subtype of melanoma and are associated with a particularly poor prognosis. Due to the rarity of the diagnosis, and the pace with which the management of cutaneous melanoma has evolved over recent years, there is little good evidence to guide management and evidence-based clinical guidelines are still in development in the UK. In this review we provide an overview of the management of mucosal melanoma, highlighting the critical differences between cutaneous and mucosal melanomas, before examining recent advances in the systemic treatment of this disease and likely future directions.
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Affiliation(s)
- Helen Tyrrell
- Oxford Cancer Centre, Oxford University Hospitals NHS Foundation Trust Oxford, Oxford, United Kingdom of Great Britain & Northern Ireland
| | - Miranda Payne
- Oxford Cancer Centre, Oxford University Hospitals NHS Foundation Trust Oxford, Oxford, United Kingdom of Great Britain & Northern Ireland
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