Amelanotic primary cervical malignant melanoma:A case report and review of literature

BACKGROUND Primary malignant melanoma of the cervix(PMMC)is an extremely rare disease that originates from primary cervical malignant melanoma and frequently re-presents a challenge in disease diagnosis due to unclarified clinical and histo-logical presentations,particularly those without melanin.CASE SUMMARY Here,we report a case of amelanotic PMMC,with a history of breast cancer and thyroid carcinoma.The patient was finally diagnosed by immunohistochemical staining and staged as IB2 based on the International Federation of Gynecology and Obstetrics with reference to National Comprehensive Cancer Network guide-lines and was treated with radical hysterectomy,bilateral salpingo-oophorectomy and pelvic lymphadenectomy.She then received combination therapy consisting of immunotherapy with tislelizumab and radiofrequency hyperthermia.She has remained free of disease for more than 1 year.CONCLUSION The differential diagnosis process reenforced the notion that immunohisto-chemical staining is the most reliable approach for amelanotic PMMC diagnosis.Due to the lack of established therapeutic guidelines,empirical information from limited available studies does not provide the rationale for treatment-decision making.By integrating'omics'technologies and patient-derived xenografts or mini-patient-derived xenograft models this will help to identify selective thera-peutic window(s)and screen the appropriate therapeutics for targeted therapies,immune checkpoint blockade or combination therapy strategies effectively and precisely that will ultimately improve patient survival.

Primary thoracolumbar intraspinal malignant melanoma:A case report

BACKGROUND Primary intraspinal malignant melanoma is a very rare tumor that most often occurs in the cervical,thoracic,or thoracolumbar segment.CASE SUMMARY A rare case of primary thoracolumbar malignant melanoma is described.A 45-year-old female patient complained of low back pain with numbness and fatigue in both lower limbs.MR revealed an intradural space-occupying lesion at the thoracic 12 to lumbar 1 level.The tumor was partially excised,and a malignant melanoma was confirmed by histopathology.CONCLUSION Primary intraspinal malignant melanoma has rarely been reported,and surgical resection and related characteristics and diagnoses have been discussed.

Intracranial hypertension as the primary symptom of malignant melanoma:A case report

BACKGROUND The etiological diagnosis of intracranial hypertension is quite complicated but important in clinical practice.Some common causes are craniocerebral injury,intracranial space-occupying lesion,subarachnoid hemorrhage,and hydrocephalus.When a patient presents with intracranial hypertension,the common causes are to be considered first so that other causes would be dismissed.With the morbidity lower than 9%,neuromelanin is very rare.Common symp-toms include nerve damage symptoms,epilepsy,psychiatric symptoms,and cognitive disorders.CASE SUMMARY We present a patient with melanoma which manifested with isolated intracranial hypertension without any other neurological signs.A 22-year-old male had repeated nausea and vomiting for 2 mo with Babinski sign(+)on both sides,nuchal rigidity,and subarachnoid hemorrhage.He had been diagnosed with melanoma and was given surgery and whole-brain radiation.Ultimately,the patient died 2 mo later.CONCLUSION Malignant melanoma should be taken into consideration in the differential diagnosis of intracranial hypertension.

Primary Malignant Melanoma of the Larynx:Case Report and Literature Review

Primary malignant melanoma of the larynx is extremely rare.This paper reports a case of a patient with primary malignant melanoma of the larynx.Preoperative laryngoscopy revealed a cauliflower-like mass in the supraglottic region,and a CT scan of the pharynx suggested laryngeal cancer with cervical lymph node metastasis.The patient underwent a total laryngectomy with lymph node dissection,and postoperative pathology confirmed a malignant melanoma in the supraglottic region of the larynx.

Primary pulmonary malignant melanoma diagnosed with percutaneous biopsy tissue:A case report

BACKGROUND Primary malignant melanoma of the lung (PMML) is a rare and highly malignanttumor with a poor prognosis. Here, we report a PMML case diagnosed bycomputed tomography (CT)-guided percutaneous biopsy, describe itspathological features and review relevant literature to improve our understandingof this tumor.CASE SUMMARY A 64-year-old Chinese female presented with productive cough for 7 mo. A chestCT scan showed a large and space-occupying lesion in Lingual lobe. Positronemission tomography-CT revealed multiple nodules located in the superior lobeapicoposterior segment of her left lung. Brain magnetic resonance imagingshowed numerous enhancing nodules, suggesting brain metastasis. AbdominalCT scan did not show any abnormalities. By CT-guided percutaneous biopsy, fourpieces of gray and taupe tissues (1 cm length and 0.1 mm in diameter) wereobtained. After pathologic examination, the tumor was found to consist ofepidermal and nested small round cells, fibrosis and thin-walled blood vessels.The finding was suggestive of malignant melanoma. To confirm the diagnosis,pathological morphology and immunophenotypic features of the biopsyspecimens were observed. The patient denied any history of skin tumors. Noabnormal lesions were detected in other sites of the body. Molecular testing waspositive for wild-type EGFR and KIT gene mutations. Finally, the clinical andpathological findings suggested PMML.CONCLUSION PMML is very rare, and the percutaneous biopsy tissue is limited. Therefore,comprehensive consideration of histology, immunohistochemistry, imaging, andclinical information is important for the diagnosis of PMML.

Laparoscopic abdomino-perineal resection for patients with anorectal malignant melanoma:a report of 4 cases

Anorectal malignant melanoma is a very rare but lethal disease. Patients with anorectal malignant melanoma commonly complain for changes in bowel habits and rectal bleeding. Therefore, anorectal malignant melanoma is often misdiagnosed as hemorrhoids, polyp or rectal cancer. Surgery is the mainstay of treatment for patients with anorectal malignant melanoma. However, whether abdominoperineal resection or wide local excision is the most appropriate surgical approach is still a controversial issue. Recently, with the great development of laparoscopic techniques, more and more operations can be performed by laparoscopic techniques. However, laparoscopic abdominoperineal resection for management of anorectal malignant melanoma has been rarely reported. In this study, we reported 4 patients with anorectal malignant melanoma underwent laparoscopic abdominoperineal resection. The outcomes of these patients were relatively good during a long time follow-up. Meanwhile, we reviewed the relevant studies with particular focus surgical treatment.

Primary malignant melanoma of the liver: A case report

Primary malignant melanoma of the liver is an exceedingly rare tumor. Only 12 cases have been reported in the worldwide literature. We present a case of isolated malignant melanoma of the liver occurring in a 36-year-old Chinese male patient. Comprehensive dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or ocular primary lesion. Other lesions in brain, respiratory tract, lung, gastrointestinal tract and anus, were not demonstrated by serial position emission tomography (PET). Microscopic examination of the resected specimen revealed a malignant melanoma, which was confi rmed by immunohistochemical staining for HMB-45, S-100 protein, melanoma-pan and vimentin. Moreover, electron microscopy demonstrated melanosomes in tumor cell cytoplasm. Our case shows that primary malignant melanoma may occur in the liver and should be considered when the histopathological appearance is not typical for other hepatic neoplasm.

Bsm I(rs1544410) and Fok I(rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.

Up-regulation of Human Leukocyte Antigen G Expression in Primary Cutaneous Malignant Melanoma Associated with Host-vs-tumor Immune Response

Human leukocyte antigen G （HLA-G） is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma （CMM）, a series of 47 skin melanocytic lesions were immunohistochemically evaluated. The correlation between HLA-G expression and CMM clinicohistopahtological data and Bcl-2 expression was also analyzed. HLA-G expression was detected in a variety of cell types. No significant difference in HLA-G expression was observed between malignant and non-malignant melanocytic lesions. HLA-G expression was significantly correlated with the inflammatory infiltration and Bcl-2 expression, whereas no significant correlation with ulceration, tumor thickness, clinical stage, histopathological subtypes were observed. HLA-G expression may be the result of host immune reaction in tumor microenvironment rather than a malignant feature of CMM.

Inhibitory Effect of Live-Attenuated Listeria Monocytogenes-based Vaccines Expressing MIA Gene on Malignant Melanoma

Listeria monocytogenes(LM),a Gram-positive facultative intracellular bacterium,can be used as an effective exogenous antigen expression vector in tumor-target therapy.But for successful clinical application,it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen.In this study,attenuated LM and recombinants of LM expressing melanoma inhibitory activity(MIA) were constructed successfully.The median lethal dose(LD 50) and invasion efficiency of attenuated LM strains were detected.The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma.The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction(PCR) with specific sequence,meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot(ELISPOT) assay.The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM,and attenuated LM expressing MIA,especially the double-genes attenuated LM recombinant,could significantly induce anti-tumor immune response and inhibit tumor growth.This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.

Primary malignant melanoma of lacrimal sac

Dear Sir,We write to present a case report of primary malignant melanoma of the lacrimal sac.Tumors of the lacrimal sac are rare,and most of them are benign and of epithelial origin[1].Malignant melanoma of the lacrimal sac is even rarer accounting for 5%of lacrimal sac tumors and 0.7%of ocular melanoma[2,3].To our knowledge,only 27 cases with complete clinical information have ever been reported worldwide in English literature[4-8].The disease has an insidious onset and masquerades as a chronic

Longest survival with primary intracranial malignant melanoma:A case report and literature review

BACKGROUND Primary intracranial malignant melanoma(PIMM)is rare,and its prognosis is very poor.It is not clear what systematic treatment strategy can achieve long-term survival.This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature.CASE SUMMARY The patient is a 47-year-old Chinese man who suffered from dizziness and gait disturbance.He underwent surgery for right cerebellum melanoma and was subsequently diagnosed by pathology in June 2000.After the surgery,the patient received three cycles of chemotherapy but relapsed locally within 4 mo.Following the second surgery for total tumor resection,the patient received an injection of Newcastle disease virus-modified tumor vaccine,interferon,andβ-elemene treatment.The patient was tumor-free with a normal life for 21 years before the onset of the recurrence of melanoma without any symptoms in July 2021.A third gross-total resection with adjuvant radiotherapy and temozolomide therapy was performed.Brain magnetic resonance imaging showed no residual tumor or recurrence 3 mo after the 3rd operation,and the patient recovered well without neurological dysfunction until the last follow-up in June 2022,which was 22 years following the initial treatment.CONCLUSION It is important for patients with PIMM to receive comprehensive treatment to enable the application of the most appropriate treatment strategies.Long-term survival is not impossible in patients with these malignancies.

Primary malignant melanoma of the esophagus successfully treated with camrelizumab:A case report and literature review

An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.

Targeted therapy for malignant ocular melanomas

In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors,mainly conjunctival and uveal melanoma(UM).Conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous melanomas.Many therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared traits.Existing targeted therapies are for example checkpoint inhibitors like pembrolizumab or nivolumab.As a corollary,due to marked differences in clinics and genetics between UMs and conjunctival melanomas(CMs)or cutaneous melanomas,it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing UMs.Possible novel ways of treating UM are being explored.Fotemustine or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat UM.While CM are treatable using targeted therapies,UM have not been researched enough to find working targeted therapy options.Further research has to be done in order to find acceptable treatment options.

Endoscopic reduction of colocolonic intussusception due to metastatic malignant melanoma:A case report

BACKGROUND Intussusception rarely causes intestinal obstruction in adults.Metastatic malignant melanoma is the main cause of intussusception of the small intestine among adults.However,malignant melanoma rarely causes intussusception of the colorectum.Moreover,emergent surgery is usually performed for such cases.Here,we report a case of a patient with colocolonic intussusception caused by a malignant melanoma,for which endoscopic reduction and elective surgery were performed.CASE SUMMARY The patient was a 64-year-old woman who underwent multiple surgeries and received chemotherapy and immunotherapy for a malignant melanoma.During immunotherapy,she had abdominal pain,diarrhea,and bloody stool.Physical examination and laboratory studies did not reveal any findings that warranted emergent surgery.Computed tomography revealed intussusception in the descending colon without intestinal necrosis and perforation.Intussusception was reduced endoscopically,and elective surgery was performed.CONCLUSION This report suggests that endoscopic reduction and elective surgery constitute a treatment option for colocolonic intussusception of metastatic malignant melanomas.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review

BACKGROUND Primary malignant melanoma of the esophagus(PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.AIM To investigate the clinical features and survival factors in Chinese patients with PMME.METHODS The clinicopathological findings of ten cases with PMME treated at Henan Provincial People’s Hospital were summarized. Moreover, the English-and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.RESULTS A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients(55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients(36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis(LNM) was 51.2%(107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the p T stage [P < 0.001, odds ratio(OR): 2.47, 95% confidence interval(CI): 1.72-3.56] and larger tumor size(P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival(OS) was 11.0 mo(range: 1-204 mo). The multivariate Cox analysis showed both the p T stage [P = 0.005, hazard ratio(HR): 1.70, 95%CI: 1.17-2.47] and LNM(P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival(DFS) was 5.3 mo(range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced p T stage(P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME.CONCLUSION The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and p T stage are independent prognosis factors for OS, and the p T stage is the prognosis factor for DFS in patients with PMME.

Primary malignant melanoma of the esophagus:A case report

BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.

Primary malignant melanoma of the esophagus combined with squamous cell carcinoma:A case report

BACKGROUND Primary malignant melanoma of the esophagus is a rare malignant tumor of the esophagus,and its combination with squamous cell carcinoma is also rare.Here,we report the diagnosis and treatment of a case of primary esophageal malignant melanoma combined with squamous cell carcinoma.CASE SUMMARY A middle-aged man underwent gastroscopy for dysphagia.Gastroscopy revealed multiple bulging esophageal lesions,and after pathologic and immunohistochemical analyses,the patient was finally diagnosed with"malignant melanoma with squamous cell carcinoma".This patient received comprehensive treatment.After one year of follow-up,the patient was in good condition,and the esophageal lesions seen on gastroscopy were controlled,but unfortunately,liver metastasis occurred.CONCLUSION When multiple esophageal lesions are present,the possibility of multiple pathological sources should be considered.This patient was diagnosed with primary esophageal malignant melanoma combined with squamous cell carcinoma.

Treatment of Conjunctival Malignant Melanoma with Topical Interferon Alpha-2a

Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha 2b (INF α 2b). The aim of the study is to present the treatment of a case with CMM using topical Interferon alpha 2a. We present a 38-year-old female with diffuse bulbar dark pigmentation of the conjunctiva that arises from previously primary acquired melanosis (PAM). Biopsy resulted positive for CMM and further investigations were negative for any metastasis. Treatment with topical interferon alpha 2a was started immediately and after three months melanoma disappeared. One year after follow-up there was no sign of recurrence in regional lymph nodes or distant metastasis.

Boron neutron capture therapy for malignant melanoma： first clinical case report in China

A phase Ⅰ/Ⅱ clinical trial for treating malignant melanoma by boron neutron capture therapy（BNCT） was designed to evaluate whether the world＇s first in-hospital neutron irradiator（IHNI） was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography（PET/CT） scan, pathological analysis and gross examination, the patient showed a complete response to BNCT,indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals.