Immunotherapy for mucosal melanoma

Mucosal melanoma(MM)is extremely rare in Caucasians,whereas it is the second predominant melanoma subtype in Asian and other non-Caucasian populations.Distinct from cutaneous melanoma in terms of epidemiology,biology,and molecular characteristics,MM is characterized by more aggressive biological behavior,lower mutational burden,more chromosomal structure variants,and poorer prognosis.Because of the rarity of MM,its biological features are not fully understood,and potential novel therapies are less well depicted.Whereas immunotherapy has shown encouraging efficacy for cutaneous melanoma,its efficacy in MM is unclear due to limited sample sizes in clinical trials.Thus,in this review,we describe the epidemiological,clinical,and molecular features of MM and summarize the efficacies of different immunotherapies for MM,including immune checkpoint inhibitors,vaccines,oncolytic virus therapy,adoptive T-cell therapy,and various combination therapies.

Endoscopic ultrasound features of rectal melanoma:A case report and review of literature

BACKGROUND Rectal mucosal melanoma is a rare and highly aggressive disease.Common symptoms include anal pain,an anal mass,or bleeding.As such,the disease is usually detected on rectal examination of patients with other suspected anorectal diseases.However,due to its rarity and nonspecific symptoms,melanoma of the rectal mucosa is easily misdiagnosed.CASE SUMMARY This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months,without any identifiable cause.During colonoscopy,a bulge of approximately 2.2 cm×2.0 cm was identified.Subsequently,the patient underwent endoscopic ultrasound(EUS)to characterize the depth of invasion of the lesions.EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes.Following surgical intervention,the excised tissue samples were examined and confirmed to be rectal malignant melanoma.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

Objective: To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck (HNMM) Methods: From 1984—1994, 35 patients with HNMM were enrolled in this study Among them, 27 cases localized to the nasal cavity or para nasal sinus, 8 to the oral cavity All patients received high dose fraction radiotherapy (6—8 Gy/fraction) with the total dose ranged from 40 to 60 Gy Results: The minimum follow up was 2 years (ranged 2—7 years) The overall 3 and 5 year survival rate was 45 7% and 24%, respectively Conclusion: High dose fraction radiotherapy is effective for local control of HNMM

Difficulties in diagnosing anorectal melanoma: A case report and review of the literature

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 wellrepresented biopsy specimen,and the poor prognosis,even with radical surgery.

Candidate therapeutic agents in a newly established triple wild-typemucosalmelanoma cell line

Background:Mucosalmelanoma has characteristically distinct genetic features and typically poor prognosis.The lack of representativemucosal melanoma models,especially cell lines,has hindered translational research on this melanoma subtype.In this study,we aimed to establish and provide the biological properties,genomic features and the pharmacological profiles of a mucosal melanoma cell line that would contribute to the understanding and treatment optimization of molecularly-defined mucosal melanoma subtype.Methods:The sample was collected from a 67-year-old mucosal melanoma patient and processed into pieces for the establishment of cell line and patientderived xenograft(PDX)model.The proliferation and tumorigenic property of cancer cells from different passageswere evaluated,andwhole-genome sequencing(WGS)was performed on the original tumor,PDX,established cell line,and the matched blood to confirm the establishment and define the genomic features of this cell line.AmpliconArchitect was conducted to depict the architecture of amplified regions detected by WGS.High-throughput drug screening(HTDS)assay including a total of 103 therapeutic agents was implemented on the established cell line,and selected candidate agents were validated in the corresponding PDX model.Results:A mucosal melanoma cell line,MM9H-1,was established which exhibited robust proliferation and tumorigenicity after more than 100 serial passages.Genomic analysis of MM9H-1,corresponding PDX,and the original tumor showed genetic fidelity across genomes,and MM9H-1 was defined as a triple wild-type(TWT)melanoma subtype lacking well-characterized“driver mutations”.Instead,the amplification of several oncogenes,telomerase reverse transcriptase(TERT),v-Rafmurine sarcoma viral oncogene homolog B1(BRAF),melanocyte Inducing transcription factor(MITF)and INO80 complex ATPase subunit(INO80),via large-scale genomic rearrangement potentially contributed to oncogenesis of MM9H-1.Moreover,HTDS identified proteasome inhibitors,especially bortezomib,as promising therapeutic candidates for MM9H-1,which was verified in the corresponding PDX model in vivo.Conclusions:We established and characterized a new mucosal melanoma cell line,MM9H-1,and defined this cell line as a TWT melanoma subtype lacking well-characterized“driver mutations”.The MM9H-1 cell line could be adopted as a unique model for the preclinical investigation of mucosal melanoma.