Anorectal Malignant Melanoma: Morphologic and Immunohistochemical Features

Chute, Deborah J.; Cousar, John B.; Mills, Stacey E.

doi:10.1309/dvwl-tv8f-fkc3-l80h

Cited by 48 publications

(95 citation statements)

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“…Their study did not include any mucosal melanomas, but no other information as to tumor location and/or sun-exposure was specified. The junctional and the in situ component of all melanomas showed strong KIT staining, 21 identified KIT expression in 12 of 16 cases tested, with a diffuse staining pattern in 38% of tumors. However no mutational analysis was provided in these KIT positive primary tumors.…”

Section: Discussionmentioning

confidence: 88%

L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition

Antonescu

Busam

Francone

et al. 2007

Intl Journal of Cancer

228

188

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Activating mutations in either BRAF or NRAS are seen in a significant number of malignant melanomas, but their incidence appears to be dependent to ultraviolet light exposure. Thus, BRAF mutations have the highest incidence in non-chronic sun damaged (CSD), and are uncommon in acral, mucosal and CSD melanomas. More recently, activating KIT mutations have been described in rare cases of metastatic melanoma, without further reference to their clinical phenotypes. This finding is intriguing since KIT expression is downregulated in most melanomas progressing to more aggressive lesions. In this study, we investigated a group of anal melanomas for the presence of BRAF, NRAS, KIT and PDGFRA mutations. A heterozygous KIT exon 11 L576P substitution was identified in 3 of 20 cases tested. The 3 KIT mutation-carrying tumors were strongly immunopositive for KIT protein. No KIT mutations were identified in tumors with less than 41 KIT immunostaining. NRAS mutation was identified in one tumor. No BRAF or PDGFRA mutations were identified in either KIT positive or negative anal melanomas. In vitro drug testing of stable transformant Ba/F3 KIT L576P mutant cells showed sensitivity for dasatinib (previously known as BMS-354825), a dual SRC/ABL kinase inhibitor, and imatinib. However, compared to an imatinib-sensitive KIT mutant, dasatinib was potent at lower doses than imatinib in the KIT L576P mutant. These results suggest that a subset of anal melanomas show activating KIT mutations, which are susceptible for therapy with specific kinase inhibitors. ' 2007 Wiley-Liss, Inc.Key words: melanoma; anal; mucosal; KIT; NRAS; BRAF mutations The KIT receptor tyrosine kinase plays a critical role in the normal development and function of the melanocytes during embryonic stage and in the postnatal organism.1,2 Loss-of-function mutations in KIT and its ligand result in white spotting phenotype in mice and humans. [3][4][5] In contrast, activating KIT mutations have been implicated in the pathogenesis of certain human malignancies, such as gastrointestinal stromal tumors, seminomas, mastocytomas, but were not reported until recently in patients with malignant melanoma. Furthermore, KIT expression, typically found in normal melanocytes, benign nevi and in situ melanoma, appears to be downregulated in invasive and metastatic melanomas.6 This progressive decrease in KIT immunopositivity is associated with increasing dermal invasiveness of the tumor. One hypothesis is that KIT signaling may be important in regulating cell differentiation and tissue morphogenesis, and therefore loss of its expression may be a required step in the course of tumor progression. 7 In this context, isolated reports of activating KIT mutations in melanoma patients, 8,9 are intriguing and suggest an alternative mechanism, in which constitutive activation of KIT through oncogenic mutations positively regulate mitogenesis and induces neoplastic transformation.The genetic alterations identified in melanomas at different sites and with different levels of sun exposure indi...

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Section: Discussionmentioning

confidence: 88%

L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition

Antonescu

Busam

Francone

et al. 2007

Intl Journal of Cancer

228

188

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“…Obvious melanin pigmentation is present in about 20% of patients. 9,11,12,14 The tumour is located usually in or close to pectinate line, and may grow towards rectal ampulla. It may extend along the submucosa proximally towards rectum, simulating a primarily rectal tumour.…”

Section: Discussionmentioning

confidence: 99%

Spindle anorectal melanotic melanoma in a 70 year old woman

Afsar

Abid

Khan³

et al. 2015

Int J Sci Rep

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<p class="abstract">A 70 year old lady presented with symptoms of changed bowel movements and rectal bleeding. She was operated and the resected specimen of intestine was brought to Department of pathology for histopathological examination. The specimen was fixed in 10% formal saline. Tissue bits were taken from the representative areas in the mass for further fixation and processing. Sections were stained with hematoxylin and eosin and thoroughly examined under microscope for establishing the diagnosis of Spindle variant of melanotic melanoma. Anorectal melanomas are rare malignancies and an infrequent occurrence in the seventh decade of life. The aim was to evaluate a pigmented anorectal mass and establish its diagnosis in a 70 year old woman by thorough histopathological examination.</p>

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“…AMM'ler, oldukça nadir görülen; fakat agresif seyreden mukozal tümörlerdir [5]. Mukozal melanomlar; tüm melanomların %1.2'sini oluşturmakla birlikte, bu oranın ¼'ünü AMM meydana getirmektedir [6].…”

Section: Tartışma Ve Sonuçunclassified

“…Primer rektum mukozasındaki melanositlerden köken alan MM ise çok enderdir [11]. Kitlenin anal girimden uzaklığı, hastalaın %90'ında 2 cm olarak bildirilmekle birlikte çalışmamızdaki kitleler 2.5-4 cm arasındaki mesafede saptanmıştır [2,5,6]. Brady ve ark.nın yayınladıkları 85 olguluk en geniş seride AMM olgularının 7'sinin (%8) rektal, 78'inin (%92) ise anal kanal veya sınırda yerleştiği bildirilmiştir [12].…”

Section: Tartışma Ve Sonuçunclassified

Approach to Malign Melanoma in Anorectal Area

2016

Ann Clin Anal Med

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ÖzetAmaç: Anorektal malign melanomlar, tüm malign melanomların %0.2-1'ini oluştururlar. Son derecede agresif seyirlidirler. Çoğu hasta, tedavi edilemeyen sistemik hastalık nedeniyle kaybedilmektedir. Çalışmamızda anorektal malign melanom nedeni ile opere ettiğimiz hastalarımızın cerrahi ve onkolojik takip sonuçlarını değerlendirmeyi amaçladık. Gereç ve Yöntem: Ekim 2008-Nisan 2013 arası anorektal malign melanom nedeni ile opere ettiğimiz 4 hasta analiz edildi. Hastalar, demografik veriler, şikayet ve süresi, fizik muayene ve görüntüleme bulguları, tedavi prosedürü, lokal nüks veya metastaz varlığı ve takip sonuçları ile analiz edildi. Bulgular: Çalışma grubu; 2 erkek, 2 kadın olmak üzere toplam 4 hastadan oluştu. Ortalama yaş 64.2 idi. Başlıca yakınma rektal kanama olup; ortalama şikayet süresi 7.5 aydı. Fizik muayene ve görüntüleme tetkikleri sonrası tüm hastalarda anorektal kitle saptandı. Kitleden yapılan biyopsiler, malign melanom ile uyumlu olarak raporlandı. İleri tetkiklerde bir hastada karaciğerde metastaz saptandı. Bir hastaya geniş lokal eksizyon sonrası, 3 hastaya ise ilk başvuru sırasında abdominoperineal rezeksiyon uygulandı. Postoperatif komplikasyonlar konservatif olarak tedavi edildi. Ortalama takip süremiz 19.2 ay olup, ortalama tümör çapı 3.9 cm idi. Bir hastada iliak bölgedeki nüks nedeniyle lenf nodu diseksiyonu uygulandı. Postoperatif problem gelişmeyen hastaların ortalama hastanede kalış süresi 9.7 gündü. Takip süresinde 3 hasta yaygın metastaz nedeni ile kaybedildi. Düzenli takibi yapılan 1 hastamız, postoperatif 22. ayında halen hastalıksız yaşamını sürdürmektedir. Tartışma: Anorektal malign melanom; nadir görülen, prognozu kötü olan ve klinik semptomlar açısından anorektal bölge-de sık rastlanan benign hastalıklara benzerlik gösterdiğinden dolayı geç tanı alan bir antitedir. Hastalığın prognozunu düzeltmek için, erken tanı sonrası en kısa sürede uygun cerrahi ve adjuvan tedavi planlanmalıdır. Anahtar KelimelerAnal Kanal; Malign Melanom; Rektum; Cerrahi Abstract Aim: Anorectal malign melanoma comprise 0.2-1 % of all malign melanoma. They are extremely aggressive. Most patients are lost beacuse of incurable systemic illness. In our study, we aim to evaluate the results of surgical and oncological follow-up of our patients that we operated because of anorectal malign melanoma. Material and Method: Our 4 patients operated because of anorectal malign melanoma between October 2008 and April 2013 were analysed. The patients were analysed in terms of demographic datas, complaint and its time, physical examination and imaging findings, treatment procedure, local recurrence or presence of metastasis and follow-up results. Results: Our study group comprised 4 people (2 men and 2 women) with the mean age of 64,2 years. The main complaint was rectal bleeding. The avarage complaint duration was 7.5 months. In all patients, anorectal mass was detected after physical examination and imaging studies. Biopsies of the mass were reported to be consistent with malign melanoma. With the further studies, one p...

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Anorectal Malignant Melanoma: Morphologic and Immunohistochemical Features

Cited by 48 publications

References 0 publications

L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition

L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition

Spindle anorectal melanotic melanoma in a 70 year old woman

Approach to Malign Melanoma in Anorectal Area

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