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.

Imaging characteristics of orbital peripheral nerve sheath tumors:Analysis of 34 cases

BACKGROUND Peripheral nerve sheath tumors(PNSTs),a rare group of neoplasms in the orbit,comprise only 4%of all orbital tumors.At present,there are very few studies detailing the features of these tumors identified using imaging technology.AIM To compare the differences in location,morphology,magnetic resonance imaging(MRI)signal intensity/computed tomography(CT)value,and enhancement degree of tumors of different pathological PNSTs types.METHODS Clinical,pathological,CT,and MRI data were analyzed retrospectively in 34 patients with periorbital sheath tumors diagnosed using histopathology from January 2013 to August 2021.RESULTS Among 34 cases of orbital peripheral nerve sheath tumors,21 were schwannomas,12 were neurofibromas,and 1 was a plexiform neurofibroma.Common clinical symptoms presented by patients with these types of tumors include eyelid swelling,exophthalmos,and limited eye movement.Schwannomas mostly occur in the intramuscular space with small tumor volume and rare bone involvement.Neurofibromas develop in the extrapyramidal space with larger tumor volume and more bone involvement.Radiologically,schwannomas and neurofibromas are characterized by regular morphology and uneven density and signal.One case of plexiform neurofibroma showed tortuous and diffuse growth along the nerve,with a worm-like appearance on imaging.CONCLUSION Different pathological types of orbital peripheral nerve sheath tumors have unique imaging characteristics.Comprehensive consideration of the patient's clinical and imaging manifestations is of great value in the diagnosis of orbital peripheral nerve sheath tumors.

Comparative analysis of CT and pathological findings of peripheral nerve sheath tumors

Objective: To improve the qualitative diagnosis of peripheral nerve sheath tumors by computed tomography (CT). Methods: CT findings of 64 cases of pathologically confirmed nerve sheath tumors were compared with the pathological findings of the tumors. Results: Low density of the tumors shown in plain CT images was related to dominating reticular structure in the tumor as found pathologically. Tumors with intact capsule found by pathological findings were shown with smooth margin in CT images. Inhomogeneous density and enhancement of the tumors in CT images was related to tumor necrosis, liquefaction and cystic degeneration, and inhomogeneous enhancement also involved the reticular structure. Conclusion: Nerve sheath tumors are characterized by distribution along the nerves, lower density than that of muscles in plain CT images, and inhomogeneous enhancement in enhanced CT, which can help differentiate nerve sheath tumors from other soft tissue tumors. When nerve sheath tumors lack distinctive CT features, the diagnoses have to depend on their pathological findings.

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.

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.

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.

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.

Clinical Analysis of 73 Cases of Intraspinal Nerve Sheath Tumor

Seventy-three patients with spinal nerve sheath tumor who were surgically treated in our hospital during the years 2004-2010 were retrospectively reviewed with respect to recovery of neurological function, recurrence of the tumor and occurrence of kyphotic deformities. Preoperative clinical manifestations, imaging data, surgical records and follow-up results were comprehensively analyzed. The follow-up duration was 12-60 months with an average of 32.0 months. Out of the 73 cases enrolled, 69 had gradual recovery of sensation, motor and sphincter functions 1 week to 3 months after operation. Forty-six cases had incomplete paralysis, whose American Spinal Injury Association （ASIA） grades, however, were gradually increased during the follow-up period, 4 cases had no significant improvement of the clinical symptoms and no change in ASIA grades during the follow-up period. Two cases had postoperative recurrence of the tumor. There were no deaths, no spinal instability, and no kyphotic malformations fotmd in any cases. Our study indicated that complete removal of the tumor is important for good recovery, and an ideal surgical method may reduce the recurrence of the tumor or the occurrence of complications.

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.

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.

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 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.

Mucosal Schwann cell “Hamartoma”:A new entity?

Schwannoma is a well-described,benign nerve sheath tumor of the soft tissue,but is rare in the gastrointestinal tract.Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions.In this report,we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts.Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein.To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes,it is better to use the designation "mucosal Schwann hamartoma".