Epithelioid malignant peripheral nerve sheath tumor of the bladder and concomitant urothelial carcinoma: A case report

BACKGROUND Epithelioid malignant peripheral nerve sheath tumor(EMPNST)of the bladder is a rare entity with devastating features.These tumors are thought to originate from malignant transformation of pre-existing schwannomas of pelvic autonomic nerve plexuses,and unlike the conventional malignant peripheral nerve sheath tumor(MPNST),are not associated with neurofibromatosis.The tumor has dis-tinctive morphological,immunohistochemical and molecular features.Addi-tionally,it tends to be more aggressive and have a higher mortality.This is the first case that presents with a synchronous urothelial carcinoma of the bladder and the epithelioid variant of MPNST in the literature.It’s also the second re-ported case of EMPNST originating from the bladder wall.CASE SUMMARY In this case report,we present the detailed clinical course of a 71-year-old patient with EMPNST of the bladder alongside a literature review.CONCLUSION During the management of EMPNST cases,offering aggressive treatment moda-lities to the patient,such as radical cystectomy,is appropriate for the best chance to contain the disease,regardless of the tumor stage and the extent of local disease at initial diagnosis.

Clinicopathological study of malignant peripheral nerve sheath tumors in the head and neck:Case reports and review of literature

BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021.The clinical features,pathological manifestations,treatments,and prognoses were summarized.We also reviewed the literature,focusing on MPNST in the mandible and maxilla.The study population consisted of five women and five men aged 22–75 years(mean age,49 years).Of the 10 patients,7 were initial cases and 3 were recurrent cases.All lesions were sporadic.The most common site was the mandible.The most frequently encountered symptoms were a progressive mass and local swelling.Complete or partial loss of trimethylation at lysine 27 of histone H3(H3K27me3)was evident on staining in four of nine cases(one case was excluded due to lack of tissue for evaluation of loss of H3K27me3).The 2-and 5-year disease-specific survival rates were 86%a nd 43%,respectively.The average survival time was 64 mo.CONCLUSION MPNST is a highly malignant tumor with a poor prognosis,prone to a high risk of recurrence and distant metastasis.Complete surgical resection is the main treatment.

Malignant peripheral nerve sheath tumor with hemophilic syndrome and bone marrow fibrosis:A rare case report

BACKGROUND Malignant schwannoma is a rare tumor in the peripheral nervous system,accounting for approximately 5%to 10%of systemic soft tissue sarcomas.Especially,malignant schwannoma occurring in the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis is extremely rare in clinical practice.Here,we report the first case of an patient diagnosed with malignant peripheral nerve sheath tumor(MPNST)of the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis,and share our reference clinical diagnosis and treatment experience.CASE SUMMARY A patient was diagnosed with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis.She received combination,and repeated imaging revealed further encountered rare complications(hemophilia syndrome and bone marrow fibrosis)after two cycles of chemotherapy.Thereafter,combined treatment with pazopanib,gemcitabine,and dacarbazine was initiated.Unfortunately,the patient succumbed to death at hospital after two weeks.CONCLUSION This report firstly provided reference clinical practice for a patient with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis.Our case raises a reminder about the tolerance and safety of combination therapy,especially in young women.

The prognostic value of C-X-C motif chemokine receptor 4 in patients with sporadic malignant peripheral nerve sheath tumors

Background: Recent studies indicate that C-X-C motif chemokine receptor 4(CXCR4) and its ligand, C-X-C motif chemokine ligand 12(CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor(MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values.Methods: CXCR4, CXCL12, and Cyclin D1 protein expression in samples from 58 Chinese patients with sporadic MPNST was assessed with immunohistochemical staining.Their prognostic values were evaluated with Kaplan-Meier analysis and a log-rank test. Multivariate Cox regression analysis was used to identify independent prognostic factors.Results: High expression of CXCR4, CXCL12, and Cyclin D1 was observed in 19(32.8%), 32(55.2%), and 16(27.6%)samples, respectively. CXCR4 expression was positively correlated with CXCL12 expression(r = 0.334, P = 0.010) and Cyclin D1 expression(r = 0.309, P = 0.018). Patients with high CXCR4 expression showed longer overall survival than those with low CXCR4 expression(χ~2 = 4.642, P = 0.031).Conclusion: High CXCR4 expression may define a specific subtype of sporadic MPNST with favorable prognosis.

Malignant peripheral nerve sheath tumor of proximal third tibia

A 16-year-old man had aswelling over the anterior aspect of the proximal third of the tibia for 1 year, which was peanut size initially and progressively increased to its present size of 10 cm × 8 cm. He underwent fine needle aspiration cytology(FNAC) twice during this period and reported aspindle cell sarcoma. Malignant peripheral nerve sheath tumor(MPNST) is a malignancy of the connective tissue surrounding the nerves. Previously, MPNST was also known as neurofibrosarcoma, malignant schwannoma, andneurogenic sarcoma. We are reporting this case for its rarity and peculiar mode of presentation. FNAC/core biopsy can be used as an effective tool to achievethe correct pathological diagnosis.

Reconstruction using a pedicled upper arm fillet flap after excision of a malignant peripheral nerve sheath tumor: A case report

Non-salvageable extremities have been utilized for harvesting fillet flaps as part of the "spare parts" concept in traumatic and oncologic settings. Here we report on the use of a pedicled fillet flap of the upper arm for chest wall reconstruction after excision of a malignant peripheral nerve sheath tumor in a patient with neurofibromatosis. Pedicled flaps as part of the "spare parts" concept provide the advantage of reduced donor-site morbidity, immediate closure, intact vasculature, and adequate soft tissue coverage of large defects. Malignant peripheral nerve sheath tumor is a rare aggressive tumor with a poor prognosis that may result in large defects post resection. Limited data describes the use of pedicled fillet flaps of the upper extremity. We report the use of a pedicled fillet flap of the upper arm as a viable option that can be successfully used for coverage of soft tissue defects of the shoulder and chest wall post complex resections in an oncologic setting.

Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in malignant peripheral nerve sheath tumor

BACKGROUND： Matrix metalloproteinase-9 （MMP-9） can degrade collagen IV （the main structural ingredient of basilar membrane）, and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 （T1MP-1） can bind with MMP-9 to form 1 ： 1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE： To analyze the relationship of MMP-9 and T1MP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor （MPNST）. DESIGN： An observational comparative experiment. SETTING： Heze Medical College. PARTICIPANTS： Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor （10 cases of nerve sheath tumor and 10 cases of neurofibromatosis） and the normal peripheral nerves （by-products of some surgeries） of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS： The documented paraffin blocks were again prepared to sections of 5 lJ m. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES： Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS： ①Expressions of MMP-9 and TIMP-1 in three tissues： MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor （P 〈 0.05）, while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor （P 〈 0.05）. ②Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST： The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2 - 3 was significantly higher than that in the MPNST patients of grade 1 （P 〈 0.05）, while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 （P 〈 0.05）. The metastatic rate was positively correlated with MMP-9 expression （r =1.696, P 〈 0.05）, but negatively correlated with TIMP-1 expression （r = - 2.125, P 〈 0.05）. CONCLUSION： MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and orognosis of MPNST.

Reconstruction of the chest wall after resection of malignant peripheral nerve sheath tumor:A case report

BACKGROUND Malignant peripheral nerve sheath tumors(MPNSTs)are a group of rare and aggressive sarcomas that often arise from major peripheral nerves and represent a notable challenge to efficacious treatment.MPNSTs can occur in any body surface and visceral organs with nerve fiber distribution.The treatment options for MPNSTs include surgery,chemotherapy,and adjuvant radiotherapy.CASE SUMMARY A 26-year-old female cellist presented with chest pain on her left side when she squatted to lift the cello.One week later,a chest X-ray was performed and revealed fracture of the fourth rib on the left side.Three months later,the patient inadvertently touched a mass on the left side of the chest wall.Chest computed tomography(CT)three-dimensional reconstruction of the ribs revealed bone destruction of the fourth rib on the left side with a soft tissue mass shadow measuring 5.7 cm×3.7 cm.CT-guided puncture biopsy of the tumor showed that heterotypic cells(spindle cells)tended to be nonepithelial tumor lesions.PET-CT demonstrated bone destruction and a soft tissue mass with avid 18F-fluorodeoxyglucose activity(SUVmax7.5)in the left fourth rib.The tumor of the left chest wall was resected under general anesthesia,and reconstruction of the chest wall was performed.The postoperative pathological report exhibited an MPNST.CONCLUSION MPNSTs are relatively chemo-insensitive tumors.The mainstay of treatment for MPNSTs remains resection with tumor-free margins.

Malignant peripheral nerve sheath tumor in an elderly patient with superficial spreading melanoma:A case report

BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a type of spindle cell sarcoma originating from the peripheral nerve,which usually results in the corresponding nerve sign on magnetic resonance imaging(MRI).Patients with MPNST may also have neurofibromatosis type 1.CASE SUMMARY A 78-year-old male was admitted to the hospital due to a tumor in his left knee.He had a previous history of superficial spreading melanoma on the left thigh.Color Doppler ultrasonography showed a hypoechoic mass in the subcutaneous soft tissues of the medial left knee with an abundant rich blood flow.Computed tomography scanning did not show obvious signs of bone destruction,but the skin adjacent to the tumor was slightly thickened.MRI examination revealed that the hypervascular lesion was well-circumscribed,lobulated,invaded the surrounding soft tissues and demonstrated heterogeneous enhancement but lacked an entering and exiting nerve sign.The MRI result indicated the invasiveness of the tumor.The patient underwent a left knee joint mass expanded resection and the first histopathological examination showed a MPNST with positive surgical margins.Therefore,the second extended resection was performed,and the patient had a good outcome in the short term.CONCLUSION MRI is a useful technique for revealing the biological characteristics of MPNST and provides clinical support for evaluation of the surgical area before operation.

Malignant Peripheral Nerve Sheath Tumors of the Scalp: Case Report and Review of Literature

Malignant peripheral nerve sheath tumors of the scalp are rare lesions of the nervous system. ?Only 16 cases have been reported to date. In this report, we present a case of a malignant peripheral nerve sheath tumor (MPNST) of the scalp and retrospectively analyze the clinical features, imaging findings, pathological features, and prognoses of these tumors.

Primary Malignant Peripheral Nerve Sheath Tumor of the Breast—A Case Report

Malignant peripheral nerve sheath tumor is a rare soft tissue sarcoma. Breast is an extremely rare location of this lesion and presentation as a breast lump in the absence of pain or previous benign neural tumor is even rarer. We report such a lesion in a 60 year-old female who presented with hard and painless breast lump for 2 years. Histopathology revealed a malignant spindle cell tumor of low grade potential. It was subsequently confirmed to be malignant peripheral nerve sheath tumor (MPNST) on the basis of immunopositivity for vimentin, neurone specific enolase and S-100.

Malignant Peripheral Nerve Sheath Tumor of the Thigh Invading the Superficial Femoral Artery, with Necrotic Lung Metastases as Presenting Symptoms

A NF1 (neurofibromatosis 1) patient developed multiple necrotic lung metastases from a sciatic malignant peripheral nerve sheath tumor (MPNST) invading the superficial femoral artery. The first diagnosis was metastases of a non-small-cell adenocarcinoma because the right calf MPNST was not clinically noticeable ant that the chest/abdomen PET/CT did not include the region of the legs. When the MPNST was diagnosed, new histological analysis on the metastases changed the diagnosis to that of epithelioid undifferentiated sarcoma. The article deals with the sometimes-delayed diagnosis in those NF1 patients with large palpable masses and chronic pain pre-existing the malignant transformation, and discusses the difficulty of the biopsy of necrotic metastases.

PD-L1 Expression and Tumor Infiltrating Lymphocytes in Neurofibromatosis Type 1-Related Benign Tumors and Malignant Peripheral Nerve Sheath Tumors:An Implication for Immune Checkpoint Inhibition Therapy

Background Neurofibromatosis type 1(NF1)is an autosomal dominant inherited disorder.It can affect multiple systems of the body and cause severe disfigurement and discomfort in these patients.There are two types of neurofibromas,named cutaneous and plexiform neurofibromas.The latter type may transform into malignant peripheral nerve sheath tumors(MPNSTs).Surgical resection is difficult to perform owing to the complex tissue structure of neurofibromas;therefore,it is necessary to develop novel and effec­tive therapies for the treatment of these tumors.Programmed cell death protein 1(PD-1)/programmed cell death-ligand 1(PD-L1)-related immune checkpoint inhibitors have been proven effective for various cancers,and the positive expression of PD-L1 and tumor-infil­trating lymphocytes(TILs)has been recognized as a biomarker for the response to immune checkpoint therapy.Methods We conducted immunohistochemistry(IHC)staining to detect PD-L1 expres­sion in plexiform neurofibroma and MPNST tissue samples.Reverse transcription-poly­merase chain reaction(RT-PCR)and western blotting were performed to detect PD-L1 and PD-1 expression in MPNST cell lines.IHC staining was used to show immune cell infiltra­tion in NF1 and MPNST tissues.Results IHC staining showed PD-L1 positive expression in neurofibromas and MPNST tumor tissues.In addition,qPCR and western blotting showed high expression of PD-L1 in MPNST tumor cells.IHC staining revealed that aberrant T lymphocytes infiltrated the plexiform neurofibroma and MPNST tumor tissues.Conclusion These results indicate that immune checkpoint mechanisms may play a pivotal role in the development of NF1-related tumors,and immune checkpoint inhibitors may be effective for managing neurofibromas and MPNSTs.Combined therapy with other molecular agents may be explored in the future.

Peripheral nerve tumors of the hand: Clinical features, diagnosis, and treatment

The majority of the tumors arising from the peripheral nerves of the hand are relatively benign.However,a tumor diagnosed as malignant peripheral nerve sheath tumor(MPNST)has destructive consequences.Clinical signs and symptoms are usually caused by direct and indirect effects of the tumor,such as nerve invasion or compression and infiltration of surrounding tissues.Definitive diagnosis is made by tumor biopsy.Complete surgical removal with maximum reservation of residual neurologic function is the most appropriate intervention for most symptomatic benign peripheral nerve tumors(PNTs)of the hand;however,MPNSTs require surgical resection with a sufficiently wide margin or even amputation to improve prognosis.In this article,we review the clinical presentation and radiographic features,summarize the evidence for an accurate diagnosis,and discuss the available treatment options for PNTs of the hand.

Malignant Triton Tumor in the Abdominal Wall: A Case Report

Malignant triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyosarcomatous differentiation. We report the case of a 54-year-old male without a history of neurofibromatosis type 1 (NF1) who had a growing abdominal wall tumor diagnosed as MTT. Computed tomography (CT), magnetic resonance imaging (MRI) and 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography/CT (FDG-PET/CT) were performed. The MRI and FDG-PET/CT indicated that the lateral component of the tumor was composed of many proliferative cells, corresponding to the histopathological finding of a cellular proliferation of spindle-shaped cells. In light of this case and previous reports, it is apparent that FDG-PET/CT is a helpful tool for distinguishing MTT from benign peripheral nerve sheath tumor.

坐骨直肠窝恶性外周神经鞘膜瘤1例并文献复习

目的探讨坐骨直肠窝恶性外周神经鞘膜瘤(MPNST)的影像学特点,以提高对该肿瘤的认识。方法回顾性分析1例经病理证实的坐骨直肠窝MPNST病人的CT和MRI表现,并复习相关文献。结果肿瘤为囊实性袋状肿物,部分边界不清,CT平扫呈等-低密度,增强扫描呈不均匀渐进性强化。MRI平扫时T_(1)WI呈等信号、T_(2)WI呈靶状高低混杂信号;扩散加权成像(DWI)呈局部点片状高信号,表观扩散系数(ADC)图呈低信号;增强扫描表现为颗粒状、片絮状,呈不均匀渐进性强化,动态增强曲线为平台型。结论MPNST是坐骨直肠窝的罕见肿瘤,其影像表现具有一定特点,认识特殊征象(不典型“靶征”、“神经出入征”)及动态强化方式有利于诊断。

18号染色体多体在恶性周围神经鞘膜瘤的诊断价值及其与临床病理特征的相关性分析

目的探讨18号染色体多体在恶性周围神经鞘膜瘤(MPNST)的诊断价值及其与临床病理特征的相关性分析。方法收集2010—2024年西京医院病理科诊断的37例MPNST,采用荧光原位杂交(FISH)技术进行检测,并总结其临床病理学特征及免疫表型。结果37例患者中男性22例,女性15例,年龄4~78(平均37)岁。肿瘤平均大小为10.8 cm。MPNST最常见的原发部位为躯干(22/37)。FISH结果示37例患者中10例(27.0%)存在18号染色体多体。统计学结果示18号染色体多体与高核分裂象(P=0.013)和肿瘤分级(P=0.005)呈正相关,且多见于头颈部(P=0.003)。结论在本研究中,FISH显示MPNST中存在18号染色体多体,这可能与肿瘤组织学形态更具侵袭性和分级更高有关,并为其与其他梭形细胞肉瘤的鉴别诊断提供了线索。

萝卜硫素预防Ⅰ型神经纤维瘤病恶性进展的作用机制研究

目的:研究萝卜硫素(SFN)预防Ⅰ型神经纤维瘤(NF-1)进展为恶性周围神经鞘瘤(MPNST)的作用及有关机制。方法:使用CCK-8、克隆形成实验检测细胞增殖能力;尼罗红(Nile Red)染色法检测细胞内脂肪含量;CellTiter-Glo 2.0 Assay试剂盒检测细胞内ATP含量;采用实时荧光定量PCR检测细胞脂肪酸合酶(FASN)、乙酰辅酶A羧化酶1(ACC1)、肉碱棕榈酰转移酶1A(CPT1A)的mRNA水平,免疫印迹实验检测细胞β-catenin、Axin 2、C-Myc、Cyclin D1的蛋白水平。结果:SFN抑制STS26T、ST88-14细胞增殖活性(t=18.70、11.20,均P<0.05),减少细胞克隆数量(t=7.28、3.148,均P<0.05),并减少细胞内脂质积累(t=3.411、5.75,均P<0.05)和ATP的含量(t=14.75、13.53,均P<0.05);与对照组相比,SFN降低STS26T和ST88-14细胞中FASN和CPT1A的mRNA水平(均P<0.05);与对照组相比,15μmol/L SFN可下调STS26T和ST88-14细胞内β-catenin及下游靶基因Axin 2、C-Myc、Cyclin D1的蛋白表达水平(均P<0.05)。结论:SFN能够通过抑制细胞脂肪酸合成及β-氧化和抑制Wnt/β-catenin信号通路来抑制MPNST细胞增殖,具有预防NF-1恶性转化为MPNST的潜力。

Comprehensive clinicopathologic characteristics of intraabdominal neurogenic tumors:Single institution experience

BACKGROUND Neurogenic tumors are rare but represent an important consideration in the differential diagnosis of abdominal mesenchymal tumors.Reports on their incidence,pathological features and clinical characteristics are scarce.AIM To advance the overall knowledge on the histologic,immunohistochemical,clinical and radiologic characteristics of neurogenic tumors through this case series.METHODS An established database of a nationwide tertiary referral center,covering a 15-year period(2005 and 2020),was retrospectively re-evaluated.Diagnoses of neurogenic tumor cases were confirmed by two experts following review of the macroscopic,histological and immunohistochemical records along with findings from analysis of archived tissue sections for each included patient.Tissue microarrays were constructed for cases lacking necessary immunohistochemical studies.Clinical data and follow-up information were collected from the hospital records and the patients themselves,when available.RESULTS The study included 19 cases of intraabdominal neurogenic tumors,representing 12 women and 7 men, between 18 and 86 years of age (median: 51 years). Finalconfirmed diagnoses were 12 schwannomas, 2 diffuse submucosal neurofibromatoses,2 ganglioneuromas, 2 malignant peripheral sheath nerve tumors,and 1 mucosal Schwann cell hamartoma. Sizes of the tumors were variable, with amedian diameter of 4 cm;the two largest (> 10 cm) were schwannomas. Themajority of cases were asymptomatic at presentation, but the most frequentsymptom was abdominal pain. Gastrointestinal tract lesions were detected withendoscopy and extra-luminal lesions were detected with cross-sectional imaging.All cases were S100-positive and CD117-negative;most cases were negative fordesmin, epithelial membrane antigen, smooth muscle actin and CD34. In all but 5cases, the Ki67 proliferation index was ≤ 1%.CONCLUSION Re-evaluation of 19 cases of abdominal neurogenic tumors demonstrated considerablevariability in clinicopathologic characteristics depending on location,dimension and histological features.

A rare case of malignant schwannoma of the brachial plexus

We report a rare case of malignant schwannoma of the brachial plexus treated during a surgical campaign aimed at the poorest communities in the Cuzco region of Peru. A Peruvian 40-year-old-female from a mountain community presented with a mass on the lateral side of her left supraclavicular space. No imaging tools were available during this surgical campaign and so a biopsy of the tumor was carried out. Histopathological examination revealed it to be a low grade malignant schwannoma. A nerve enucleation of the tumor was chosen as neither chemotherapy nor radiotherapy was available.The tumour was a firm mass 4 cm x 3 cm x 2 cm in size. After excision of the lesion the patient presented neurological sequelae(deltoid, bicep, and tricep weakness) but her condition improved over the next 3 years.We report this case of malignant schwannoma of the brachial plexus as its incidence is very rare(the reported incidence is 0.001%) and because of its challenging treatment in poor healthcare conditions.