Low-molecular-weight fucoidan inhibits the proliferation of melanoma via Bcl-2 phosphorylation and PTEN/AKT pathway

Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-Helicobacter pylori properties.However,the effects of low-molecular-weight fucoidan(LMW-F)on melanoma cell lines and three dimensional(3D)cell culture models are not well understood.This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma.Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F.MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D-printed collagen scaffold.The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan.Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56,which was associated with the prevention of anti-apoptotic activity of cancer cells.Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.

Biological characteristics and clinical management of uveal and conjunctival melanoma

Uveal and conjunctival melanomas are relatively rare tumors;nonetheless,they pose a significant risk of mortality for a large number of affected individuals.The pathogenesis of melanoma at different sites is very similar,however,the prognosis for patients with ocular melanoma remains unfavourable,primarily due to its distinctive genetic profile and tumor microenvironment.Regardless of considerable advances in understanding the genetic characteristics and biological behaviour,the treatment of uveal and conjunctival melanoma remains a formidable challenge.To enhance the prospect of success,collaborative efforts involving medical professionals and researchers in thefields of ocular biology and oncology are essential.Current data show a lack of well-designed randomized clinical trials and limited benefits in current forms of treatment for these tumors.Despite advancements in the development of effective melanoma therapeutic strategies,all current treatments for uveal melanoma(UM)and conjunctival melanoma(CoM)remain unsatisfactory,resulting in a poor long-term prognosis.Ongoing trials offer hope for positive outcomes in advanced and metastatic tumors.A more comprehensive understanding of the genetic and molecular abnormalities involved in the development and progression of ocular melanomas opens the way for the development of personalized therapy,with various potential therapeutic targets currently under consideration.Increased comprehension of the molecular pathogenesis of UM and CoM and their specificities may aid in the development of new and more effective systemic therapeutic agents,with the hope of improving the prognosis for patients with metastatic disease.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

BET inhibitors potentiate melanoma ferroptosis and immunotherapy through AKR1C2 inhibition

Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.

Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

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 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.

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.

Malignant melanoma:An important differential diagnosis for clear cell sarcoma of the gastrointestinal tract

A case report by Liu et al describes the characteristics of metastatic clear cell sarcoma(CCS)of the pancreas and provides valuable therapeutic insights for this rare malignancy.This case is interesting because of its rarity,suggesting that the pancreas may be a potential target organ for CCS,either primary or metastatic.At the same time,the authors also emphasize the importance of regular postoperative follow-up for timely detection of recurrent lesions,as CCS is characterized by a high degree of malignancy and a high rate of recurrent metastases.Considering that CCS of the gastrointestinal tract is easily confused with malignant melanoma(MM)of the gastrointestinal tract,here we compare the clinical features,histopathological and immunohistochemical characteristics,diagnosis,treatment,and prognosis of CCS and MM of the gastrointestinal tract,hoping to provide a reference for clinical work.

Uveal melanoma:Recent advances in immunotherapy

Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

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.

Acalypha australis L.extract inhibits B16 melanoma cell metastasis through PI3K/AKT signaling pathway

Background:Melanoma is a deadly skin tumor resulting from the malignant transformation of melanocytes.It is highly malignant and invasive,with the highest mortality rate among skin cancers.Acalypha australis L.(AAL),a plant with dual medicinal and culinary purposes,is commonly regarded as an edible wild vegetable in southern China.Additionally,AAL has a long history of medicinal use in China,often employed for its hemostatic,anti-diarrheal,and anti-inflammatory properties.Modern pharmacology has demonstrated that AAL possesses functions such as weight loss,antimicrobial activity,antiviral effects,and treatment for ulcerative colitis.However,there is currently no research available regarding its effectiveness and mechanisms of action on melanoma.Methods:In this investigation,we used methyl thiazolyl tetrazolium assay to detect cell viability,transwell assay to detect cell migration and invasion ability,and Western blot assay to detect relevant signaling pathways.Results:The present study reveals that 2 mg/mL AAL effectively suppresses the metastasis of B16 cells,while simultaneously triggering the expression of key apoptosis-related proteins,including Bcl-2,Bax,and cleaved caspased 3.Subsequent investigations demonstrate that AAL exerts this inhibitory effect via the PI3K/AKT signal transduction pathway,as evidenced by the observed deficits in Ras,AKT,p-AKT,and PI3K expression levels.Conclusion:These findings indicated that AAL could be a valuable therapeutic option for reducing the metastatic potential of B16 melanoma cells.

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.

Expression of A, G and B melanoma antigen genes in human hepatocellular carcinoma

Objective: To observe the expression of the A melano- ma antigen (MAGE), G melanoma antigen (GAGE) and B melanoma antigen (BAGE) genes in human hepatocellular carcinoma cell lines. Methods: The MAGE-1, MAGE-3, GAGE1-8, GAGE1-2 and BAGE mRNA lever in hepatocellular carcinoma cell lines SMMC-7721, QQY-7701, BEL- 7402 were studied by reverse transcription polymer- ase chain reaction and were compared with biopsied liver tissues. Results: MAGE-1 and BAGE mRNA were expressed in SMMC-7721, MAGE-3 and BAGE in QGY-7701, MAGE-1 and GAGE1-2 in BEL-7402. None of these genes was expressed in biopsied liver tissues. Conclusions: MAGE-1, MAGE-3, GAGE1-8, GAGE1-2 and BAGE were expressed in hepatocellu- lar carcinoma cell lines, respectively. These tumor- specific antigens can be used as molecular markers and possible targets of immunotherapy for patients with hepatocellular carcinoma.

Trends in the management of anorectal melanoma:A multiinstitutional retrospective study and review of the world literature

BACKGROUND Anorectal melanoma(ARM)is a rare disease with a poor prognosis.Evidence on optimal treatment is limited and surgical management varies widely.We hypothesized that the frequency of abdominoperineal resection used as primary treatment of ARM has decreased over the past several decades.AIM To update our understanding of outcomes for patients with ARM and analyze management trends around the world.METHODS This is a multi-institutional,retrospective study of patients treated for ARM at 7 hospitals.Hospitals included both large,academic,tertiary care centers and smaller,general community hospitals.Using prospectively maintained institutional tumor registries,we identified 24 patients diagnosed with ARM between January 2000 and May 2019.We analyzed factors prognostic for recurrence and survival.We then used Cox regression to measure overall survival(OS)and melanoma-specific survival.We also performed a literature review to assess trends in surgical management and outcomes.RESULTS Of the 24 patients diagnosed with ARM,12(50.0%)had local,8(33.3%)regional,and 4(16.7%)distant disease at diagnosis.Median time to recurrence was 10.4 mo[interquartile range(IQR)7.5-17.2]with only 2 patients(9.3%)not developing recurrence following surgical resection.Median OS was 18.8 mo(IQR 13.5-33.9).One patient is still alive without recurrence at 21.4 mo from diagnosis;no other patient survived 5 years.Primary surgical management with abdominoperineal resection(APR)vs wide excision(WE)did not lead to differences in OS[hazard ratio=1.4(95%CI:0.3-6.8)].Review of the literature revealed geographic differences in surgical management of ARM,with increased use of WE in the United States and Europe over time and more frequent use of APR in Asia and India.There was no significant improvement in survival over time.CONCLUSION There is wide variation in the management of ARM and survival outcomes remain poor regardless of approach.Surgical management should aim to minimize morbidity.

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transforma-tion of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-Raf V600 E and N-RasQ 61 R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor(EGFR), stem cell-like factor(SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor-4(CXCR4) and vascular endothelial growth factor(VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition(EMT)-associated molecules, including phosphatidylinositol 3'-kinase(PI3K)/Akt/ molecular target of rapamycin(mT OR), nuclear factor-kappaB(NF-κB), macrophage inhibitory cytokine-1(MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.

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.

Immunohistochemical evaluation of vitamin D receptor(VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.

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.