Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas

Ottaviano, Margaret; Giunta, Emilio Francesco; Marandino, Laura; Tortora, Marianna; Attademo, Laura; Bosso, Davide; Cardalesi, Cinzia; Fabbrocini, Antonietta; Rosanova, Mario; Silvestri, Antonia; Montella, Liliana; Tammaro, Pasquale; Marra, Ester; Trojaniello, Claudia; Vitale, Maria Grazia; Simeone, Ester; Troiani, Teresa; Daniele, Bruno; Ascierto, Paolo A.

doi:10.3390/biomedicines10010150

Cited by 12 publications

(6 citation statements)

References 164 publications

(257 reference statements)

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“…The results are consistent with the poor prognosis for the individuals suffering from melanoma with DMKN mutations and those having MM with NRAS/KRAS mutations, respectively [7]. In a personalized oncology model, the different results of the various studies may be explained by low mutation rates for individual signaling components [40,41]. Regarding the present study, an association was observed between high DMKN levels with tumor invasion, as well as a higher incidence of BRAFV600E and NRASP29S mutation metastasis.…”

Section: Discussionsupporting

confidence: 87%

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Imani

et al. 2022

Preprint

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In the present study, the vulnerability associated with dermokine (DMKN), as a new trigger for the Epithelial-Mesenchymal Transition (EMT)-driven melanoma, was assessed based on a genome-wide genetic screening using transgenic. The results suggested a significantly higher DMKN expression in human Malignant Melanoma (MM), which was correlated with poor overall survival among melanoma patients, especially BRAF-mutated MM samples. Additionally, an in vitro knockdown of DMKN inhibited the cell proliferation, invasion, and apoptosis of MM cancer cells by activating ERK/MAPK signaling pathways and regulating STAT3 in downstream molecules. The interrogation of in vitro melanoma dataset and characterization of advanced melanoma samples revealed that DMKN downregulated the EMT-like transcriptional program through disrupting MET/EMT cortical actin, enhanced the expression of epithelial markers, and decreased that of mesenchymal markers. Whole-exome sequencing was presented with p.E69D and p.V91A DMKN mutations as novel somatic loss-of-function mutations. Further, the purposeful proof-of-principle modeled the interaction of ERK with p.E69D and p.V91A DMKN mutations in the ERK-MAPK kinase signaling that may be naturally associated with the EMT triggering during the melanomagenesis. These results provided preclinical evidence for the role of DMKN in shaping the EMT-like melanoma phenotype and introduced DMKN as a new exceptional responder to personalized MM therapy.

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Section: Discussionsupporting

confidence: 87%

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Imani

et al. 2022

Preprint

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“…Mucosal MM is rare, representing less than 2% of all MM. 28 Vaginal (Va) and VuMM constitute between 1% and 3% of MM diagnosed in women, while PeMM accounts for 1.4% of primary penile cancers, and less than 0.1% of primary MM. 29 , 30 , 31 …”

Section: Discussionmentioning

confidence: 99%

Genital lichen sclerosus and melanoma; a systematic review

Sim

Dear

Mastoraki

et al. 2022

Skin Health and Disease

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Background Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe) squamous carcinoma (SCC) is now well established but melanoma (MM) has only rarely been reported complicating GLSc. Methods We have performed a systematic literature review of GLSc in patients with genital melanoma (GMM). Only articles that mentioned both GMM and LSc affecting either the penis or vulva were included. Results Twelve studies with a total of 20 patients were included. Our review shows that an association of GLSc with GMM has been more frequently reported in women and female children than men viz, 17 cases compared with three. It is notable that five of the cases (27.8%) concerned female children aged under twelve. Discussion These data suggest a rare association between GLSc and GMM. If proven, there arise intriguing questions about pathogenesis and consequences for counselling of patients and follow‐up.

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“…The appropriateness of which treatment modalities, in which combination, is determined by a multidisciplinary team. Factors considered are the aspects of a patient's tumour location and presence of metastasis coupled with their individual personal preferences and baseline health status 5 …”

Section: Figmentioning

confidence: 99%

“…Factors considered are the aspects of a patient's tumour location and presence of metastasis coupled with their individual personal preferences and baseline health status. 5 The intricacies of managing this patient were further complicated by her age and comorbidities. This case is unique in that should the patient have been younger at the time of diagnosis and alternative surgical plan of abdominoperineal resection AEchemotherapy or immunotherapy may have been offered to her and potentially altered her outcomes.…”

mentioning

confidence: 99%

Primary amelanotic malignant melanoma of the rectum

Hamilton

2022

ANZ Journal of Surgery

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An 82 year old Caucasian female underwent colonoscopy for investigation of per rectal bleeding and iron deficiency anaemia with faecal occult blood test 3 of 3 positive. She was found to have a large malignant appearing anorectal mass 1-2 cm from the anal verge (Fig. 1). Biopsies confirmed an ulcerated cellular malignant tumour with features consistent with melanoma. The patient has a distant past history of melanoma in situ on the right forearm which was completely excised with no evidence of recurrence or metastasis so this rectal tumour was provisionally diagnosed as a primary amelanotic malignant melanoma of the rectum.MRI rectum demonstrated a 23 mm diffuse thickening of the posterior wall of the rectum (Fig. 2) but no extension into the mesorectal fascia, no extramural vascular invasion and no lymph node involvement (Fig. 3). CT staging scans showed some scattered intrahepatic cysts but no definitive lesions concerning for metastasis. The tumour was intensely fluorodeoxyglucose (FDG) avid on PET scan, showing a 30 mm rectal tumour but no FDG avid lymphadenopathy, thus excluding FDG avid distant or locoregional metastatic disease, confirming the diagnosis of primary amelanotic melanoma arising from the rectum. This case was extensively discussed at both the colorectal and melanoma multidisciplinary team meetings to determine the best treatment modality. Given her age and comorbidities, including heart failure, recurrent unprovoked venous thromboembolism and previous breast cancer, the patient was deemed unsuitable for abdominoperineal resection (APR) or chemotherapy and given the MRI findings local resection was advised with adjuvant radiation treatment.

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Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas

Cited by 12 publications

References 164 publications

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

Genital lichen sclerosus and melanoma; a systematic review

Primary amelanotic malignant melanoma of the rectum

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