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 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.

Malignant melanoma resection and reconstruction with the first manifestation of lumbar metastasis:A case report

BACKGROUND Malignant melanoma(MM)has shown an increasing incidence worldwide,and a potential to metastasize to almost any part of the body.Clinically,MM with bone metastasis as the initial manifestation is extremely rare.Spinal metastatic MM can cause spinal cord or nerve root compression,resulting in severe pain and paralysis.Currently,the primary clinical treatments for MM are surgical resection in conjunction with chemotherapy,radiotherapy,and immunotherapy.CASE SUMMARY Here,we report the case of a 52-year-old male who presented to the clinic with progressive low back pain and limited nerve function.No primary lesion or spinal cord compression was detected from computed tomography and magnetic resonance imaging of the lumbar vertebrae and positron emission tomography scan.A lumbar puncture biopsy confirmed the diagnosis of lumbar spine metastatic MM.Following surgical resection,the patient’s quality of life improved,symptoms were relieved,and comprehensive treatment was initiated,which prevented recurrence.CONCLUSION Spinal metastatic MM is clinically rare,and may cause neurological symptoms,including paraplegia.Currently,the clinical treatment plan consists of surgical resection in combination with chemotherapy,radiotherapy,and immunotherapy.

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.

Sino-Nasal Malignant Melanoma: A Case Report

Melanoma is a malignant tumor and is commonly found second least in the head and neck region, with approximately 10% - 25% of melanomas followed by ear (8% - 11%). We reported a case of sino-nasal malignant melanoma in a 46-year-old Asian lady who presented with epistaxis and dysphagia. By nasoendoscopy and CT scan imaging, the diagnosis of sino-nasal malignant melanoma was later confirmed by histopathology examination along with immunohistochemistry by using Melan A and S100. Malignant melanoma in the head and neck is rare and has a poor prognosis. There has been an increase in the incidence of 5% per year and mortality at 2% per year. This dictates malignant melanoma has rapidly increased compared to any other cancer except lung cancer in women and has contributed to the third highest number of deaths among all cancers. The mortality rate has also increased, and that is attributed to the negligence of symptoms during the initial period. This usually leads to patients seeking consultation during the advanced stage of the disease. In conclusion, this paper is to report that malignant melanoma may be one of the differentials of sino-nasal masses, and it may mimic nasopharyngeal carcinoma in its presentation.

Plantar Spitz Nevus Resembling Malignant Melanoma: Description of Immunohistochemical Findings

Spitz nevus (SN) is predominantly distributed throughout the lower extremities, while an acral location is rare. Since SN occasionally resembles the clinicopathological presentation of malignant melanoma (MM), it presents a diagnostic challenge, especially on glabrous skin. Past reports suggest that several genetic aberrations are associated with specific clinicopathological subtypes of melanocytic tumors. Immunohistochemistry can provide a clue to the presence or absence of a molecular aberration typical of Spitz tumors. We describe a case of a plantar SN with genetic analysis, including anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), BRAF (V600E) protein, and BRCA1-associated protein-1 (BAP1). However, we were not able to detect a characteristic gene aberration. To the best of our knowledge, no genetic aberrations in plantar SN cases have been reported. A comprehensive understanding of tumor genomics is expected to play an essential role in the classification of melanocytic tumors. Further genetic research on plantar SN is required to establish new criteria for distinguishing between SN and MM.

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.

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.

Primary malignant melanoma of uterine cervix: a suggestion of new scheme of treatment combination

Historically, the lack of melanocytes in the vaginal and cervical mucus membranes has deterred the findings of primary melanomas. Mainly due to its rarity, difficulty to diagnose, and poor prognosis, there has been no absolute agreement on comprehensive treatment so far. In this case report, we present a case of a 46-year-old woman with primary malignant melanoma of uterine cervix. She underwent neo-adjuvant chemotherapy initially followed by a radical hysterectomy. After adjuvant concurrent chemo-radiation, the patient has been followed up for 24 months. So far, she has not shown any symptoms or signs of recurrence. Further studies with more cases based on variable combinations of treatment regimen have been on the way.

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.

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 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

Selective Expression of Progesterone Receptor in Malignant Melanoma Was Inversely Correlated with PCNA

To investigate the role of progesterone receptor （PR） expression in malignant melanoma （MM）, PR and proliferative cell nuclear antigen （PCNA） expression were immunohistochemistrically evaluated in a series of 35 specimens of MM, and the correlation between the immunohistochemistrical findings and clinicopathological data was also analyzed. PR expression was detected in 25.7% （9/35） of the patients with MM. No PR expression was observed in nevi. PR expression was inversely correlated with PCNA expression （r=-0.353, P=-0.026）. PR expression was slightly increased in females, subjects aged under 55 y, those with ulceration, non-acral subtype and diagnosis delay longer than 1 y, but the difference was not statistically significant. Selective expression of progesterone receptor in malignant melanoma might be correlated with inhibited tumor growth.

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.

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.

Metastatic Ovarian Tumor of Vulvar Malignant Melanoma in a 43-Year-Old Woman: A Case Report and Literature Review

An ovarian malignant melanoma sometimes occurs from ovarian teratoma. Ovarian metastatic malignant melanoma is extremely rare. We describe a patient in whom vulvar melanoma (previously resected) metastasized to the ovary, making ovarian metastatic malignant melanoma. A 43-year-old Japanese woman was referred to us because of left ovarian tumor. She had undergone resection for malignant melanoma on the right labia minora with inguinal lymph node metastasis (pT1bN1aM0, stage IIIA, FIGO 2008). Eighteen months after this surgery, CT scans revealed left ovarian tumor and swelled pelvic lymph nodes, with a pelvic examination disclosing a left adnexal solid mass, with normal serum CA125 level (21.7 U/mL). Laparotomy revealed a left solid ovarian tumor measuring 4 cm, which was covered with a smooth grayish capsule. The right ovary, uterus, and pelvic cavity appeared normal. Upon sectioning during the surgery, the cross-sectional surface of the left ovary revealed a dark brown solid tumor. Following an intra-operative frozen-section diagnosis as metastatic melanoma, total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph dissection was performed. Histological examination confirmed the diagnosis as malignant melanoma metastasis to the left ovary and the obturator lymph node: the same laterality (left) as the primary site. The tumor was entirely composed of malignant melanoma cells with no evidence of teratoma. Combined chemotherapy with dabrafenib mesylate and trametinib was planned based on the positive BRAF mutations. This case highlights the importance that physicians should have high index of suspicion for the occurrence of ovarian melanoma metastasis after melanoma surgery. We also made extensive literature review on this issue, of which description may contribute to better understanding of this condition.

In vitro 3D malignant melanoma model for the evaluation of hypericin-loaded oil-in-water microemulsion in photodynamic therapy

Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D culture.These findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.

PRIMARY MALIGNANT MELANOMA OF ESOPHAGUS: REPORT OF FOUR CASES AND REVIEW OF THE LITERATURES

Objective: To investigate the clinical features and prognosis of the primary malignant melanoma of esophagus, to try to find out a rational therapy and to evaluate the value of surgical resection. Methods: Retrospective study was conducted for four cases with Primary malignant melanoma of esophagus hospitalized from May 1975 to April 1999. The relevant literatures of primary malignant melanoma of esophagus in recent years were also reviewed. Results: Four patients received multimodality therapy including surgical resection. The survival time is 16 years, 53 months, 5 months and 6 months, respectively. Conclusion: Primary malignant melanoma of the esophagus has a poor prognosis. Surgical resection plays an important role and is indispensable. The patterns of combination treatment modality need further investigation. Preoperative therapy combined with surgical resection and post-operative therapy may be a better management.

PRIMARY MALIGNANT MELANOMA OF THE VAGINA:CLINICAL, PATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDIES OF 9 CASES

Nine cases of vaginal primary malignant melanoma were diagnosed and treaed in Zhejiang Cancer Hospital from 1964 to 1990. The mean age of patients was 48. 6 years. Abnormal vaginal bleeding was the Incipient symptom in 6 patients. Five cases of malignant melanoma located in the lower one-third of the vagina. Five patients had the tumor in size larger than or equal to 4 cm In diameter. All of them were of the cauliflower-like, nodular configuration grossly. The surface of the mass demonstrated in a variable degree of black or grey- blackish in 7 patients. The htstological appearances were similar to those in the skin. Sections of 4 cases Indicated only few or no melanin under microscope. The covering epithelial changes of 3 vaginal primary malignant melanoma resembled that of malignant melanoma in situ. All sections of 9 cases showed positive reaction to S-100 protein and negative to CEA immunohistochemically. This article laid emphasis on the origin, diagnosis and treatment of this tumor, and make discussion in conjunction with the literature.

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.