Peripheral nerve sheath malignancy with multiple metastasis: a rare clinical case

Background. Tumours of peripheral nervous system are represented by benign and malignant neoplasms with different clinical and biological traits. Malignant peripheral nerve sheath tumours of paraspinal localisation with the involvement of nerve structures are extremely rare and may occur isolated or comorbid with congenital neurofibromatosis. Current literature contains a few bioptic and selected autopsy clinical reports. Herewith, we present an own sectional observation of a rare malignant peripheral nerve sheath tumour with multiple metastasis supplemented with morphological and immunohistochemical descriptions.Clinical Case Description. An autopsy was performed on a 30-yo man’s cadaver. A tumour infiltrate was observed along Th5—Th9 of the spinal column intimately associated with thoracic vertebral bodies. Metastases were detected in the right lung, myocardium, peripancreatic and perirenal adipose tissue. Histological tumour examination revealed heterogeneous solid and rosette-like structures. Tumour immunophenotype: vimentin+, pancytokeratin-, CD45-, S-100+, NSE+, GFAP-, proliferative activity index (Ki-67 = 75-80%). This profile is descriptive of peripheral nerve sheath malignancy of high grade with multiple organic metastases.Conclusion. The sectional observation presented illustrates the difficulty to in vivo diagnose rare peripheral nerve sheath malignancies due to their infiltrative growth into spinal bone marrow and metastasis to organs (lungs, myocardium, peripancreatic and perirenal adipose tissue).

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Malignant peripheral nerve sheath tumor in the maxilla. Clinical сase

Head and neck tumors (HNT) ◽

10.17650/2222-1468-2019-9-3-72-76 ◽

2019 ◽

Vol 9 (3) ◽

pp. 72-76

Author(s):

V. V. Baryshev ◽

F. Е. Sevryukov ◽

V. V. Polkin ◽

Е. А. Khanenya ◽

Т. А. Аgababyan ◽

...

Keyword(s):

Peripheral Nerve ◽

Clinical Case ◽

Malignant Potential ◽

Nerve Sheath Tumor ◽

Term Outcome ◽

Long Term Outcome ◽

Peripheral Nerve Sheath Tumor ◽

Nerve Sheath ◽

Precise Diagnosis

A clinical case of the malignant peripheral nerve sheath tumor is presented. It is a rare tumor in the head and neck area. The tumor arises from Schwann cells, its malignant potential is unclear. This low-growing tumor is presenting as a solitary nodule. To make a precise diagnosis immunohistochemistry assay is used. Surgical approach provides good long-term outcome.

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RADT-20. HISTOPATHOLOGIC FINDINGS IN MALIGNANT PERIPHERAL NERVE SHEATH TUMOR ARE BOTH PROGNOSTIC FOR OVERALL SURVIVAL AND PREDICTIVE FOR RESPONSE TO RADIATION THERAPY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.773 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii185-ii186

Author(s):

Harish N Vasudevan ◽

Calixto-Hope G Lucas ◽

William Chen ◽

Stephen Magill ◽

Steve Braunstein ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Peripheral Nerve ◽

Hierarchical Clustering ◽

Nerve Sheath Tumor ◽

Ki 67 ◽

Peripheral Nerve Sheath Tumor ◽

Prognostic Features ◽

Nerve Sheath ◽

Egfr Expression

Abstract BACKGROUND Malignant peripheral nerve sheath tumor (MPNST) is an aggressive neoplasm associated with neurofibromatosis type 1 (NF1). Despite multimodal therapy, clinical outcomes remain poor. To elucidate markers of MPNST treatment response, we retrospectively reviewed the medical records of MPNST patients at a single institution and performed histopathological and immunohistochemical (IHC) analysis for predictive and prognostic features. METHODS We identified 54 consecutive patients treated at University of California San Francisco between 1990 and 2018 that met diagnostic criteria for MPNST on pathologic review with sufficient tissue available for histology and immunohistochemistry (IHC) assays. IHC was performed for Ki-67, EGFR, p53, H3K27me3, neurofibromin, S100, p75NTR, SOX10, p16, and SOX2. Overall survival (OS), metastasis free survival (MFS), and locoregional failure free rate (LFFR), were estimated using the Kaplan-Meier method. Log-rank test, Cox Proportional Hazards regression, and hierarchical clustering were performed in R. RESULTS With a median follow up of 19.2 months, the 5-year OS, MFS, and LFFR were 58%, 68%, and 66%, respectively, with no significant differences between NF1 associated (n=32) and sporadic tumors (n=22). Radiation therapy significantly improved 5-year LFFR (80% versus 49%, p=0.05), but not OS or MFS. Tumor grade was associated with worse OS by Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) grading (p=0.02). Furthermore, elevated Ki-67 index was associated with worse 5-year OS (39% versus 73% for Ki-67 index ³ 60 and Ki-67 index < 60, p=0.01). Finally, hierarchical clustering of IHC data identified a predictive signature defined by elevated Ki-67 and EGFR expression associated with improved responses to radiation therapy (5-year OS 86% versus 10%, p=0.004). CONCLUSIONS Our data provide insights into the diagnosis and treatment of MPNST. Additional investigation is needed to understand the biologic mechanisms and generalizability of the signatures uncovered in our analysis.

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Immunohistochemical Markers for Schwannomas, Neurofibromas and Malignant Peripheral Nerve Sheath Tumors—What Can the Recent Literature Tell Us?

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0038-1667180 ◽

2018 ◽

Vol 37 (02) ◽

pp. 105-112 ◽

Cited By ~ 2

Author(s):

José Guedes-Corrêa ◽

Rodrigo Cardoso

Keyword(s):

Peripheral Nerve ◽

Recent Literature ◽

Case Reports ◽

Ki 67 ◽

Nerve Sheath Tumors ◽

Peripheral Nerve Sheath Tumors ◽

Immunohistochemical Markers ◽

Nerve Sheath ◽

Diagnostic Potential ◽

Different Types

Introduction Schwannomas and neurofibromas are the two most common benign neoplasms of the peripheral nerve sheath, and although they are generally easy to distinguish, in some cases, they can closely resemble one another. Furthermore, malignant peripheral nerve sheath tumors (MPNSTs), another example of peripheral nerve sheath neoplasm, may likewise constitute, due to their morphology and lack of specific immunohistochemical markers, a challenging diagnostic. Objective To bring attention to new and promising biomarkers for schwannomas, neurofibromas and MPNSTs and to outline, based on the recent literature, a immunohistochemical profile for each neoplasm at hand, as well as to emphasize the need for further studies that could help us understand their diagnostic potential and disrupt our dependence of limited and nonspecific biomarkers. Methods An overview of the recent literature published in English on both the classical promising immunohistochemical markers of schwannomas, neurofibromas and MPNSTs was performed. We discarded case reports. Conclusions There is still a lack of specific biomarkers for peripheral nerve tumors. However, plenty of new immunohistochemical markers have been coming to light with presumed higher specificity and more diverse helpful uses than the classical ones. For example, Sox10 is a good biomarker for differentiating schwannomas and neurofibromas from sarcomas, calretinin schwannomas from neurofibromas, TLE1 and HMGA2 MPNSTs from sarcomas, and nestin, EGFR, p16 and Ki-67 MPNSTs from different types of schwannomas and neurofibromas. There is still need for further studies; however, the potential of some of these promising markers, among others, should not be disregarded.

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Aberrations of TBX2-CHK2-p53 Signaling Pathway and its Role in Malignant Peripheral Nerve Sheath Tumors

Journal of Surgical Oncology ◽

10.31487/j.jso.2020.02.09 ◽

2020 ◽

pp. 1-10

Author(s):

Jilong Yang ◽

Chao Zhang ◽

Fangyuan Chang ◽

Hongji Dai ◽

Jilong Yang ◽

...

Keyword(s):

Peripheral Nerve ◽

Signaling Pathway ◽

Nerve Sheath Tumor ◽

Ki 67 ◽

P53 Expression ◽

Genetic Aberrations ◽

Peripheral Nerve Sheath Tumors ◽

P53 Signaling ◽

Nerve Sheath ◽

P53 Signaling Pathway

Background and Objectives: The dismal outcome of malignant peripheral nerve sheath tumor (MPNST) highlights the necessity of identifying new biomarkers and pathogenesis for this aggressive sarcoma. Therefore, it is necessary to detect the aberrations of the TBX2-CHK2-p53 pathway and investigate its biological role in MPNST. Methods: Genetic aberrations of TBX2, CHK2 and p53 were detected by next generation sequencing (NGS) in 10 MPNST samples. Protein expression of TBX2, CHK2, p53, Ki-67 and cyclin D1 were assessed by immunohistochemistry (IHC) in 63 MPNST samples. Results: Our present data demonstrated that there were gene mutations of TBX2, CHK2 and p53 in MPNST samples. TBX2 expression was correlated with American Joint Committee on Cancer (AJCC) stage, recurrence and metastasis. Correlation analysis found that TBX2 was positively correlated with CHK2 (p=0.045) and CHK2 was positively correlated with p53 (p=0.006). Furthermore, both CHK2 and p53 were positively correlated with Ki-67 (p<0.05), which is related to tumor differentiation, metastasis and prognosis. As for survival analyses, patients with high TBX2, CHK2 and p53 expression exhibited shorter disease-free survival (DFS) and overall survival (OS), respectively (p<0.05) and TBX2 and CHK2 were independent prognostic factors for MPNST patients (p<0.05). Conclusion: There are genetic aberrations of the TBX2-CHK2-p53 signaling pathway in MPNST, which might promote the progression of MPNST by increasing Ki-67 expression. Thus, TBX2 and CHK2 might be useful markers for MPNST.

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Carcinosarcoma of the Urinary Bladder—An Aggressive Tumor With Diverse Histogenesis

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-1172-cotuba ◽

2000 ◽

Vol 124 (8) ◽

pp. 1172-1178 ◽

Cited By ~ 7

Author(s):

Dmitry Y. Baschinsky ◽

Janny H. Chen ◽

Manjunath S. Vadmal ◽

Joel G. Lucas ◽

Robert R. Bahnson ◽

...

Keyword(s):

Urinary Bladder ◽

Peripheral Nerve ◽

Urothelial Carcinoma ◽

Malignant Neoplasms ◽

Nerve Sheath Tumor ◽

Clinicopathologic Features ◽

Bladder Tumors ◽

Peripheral Nerve Sheath Tumor ◽

Nerve Sheath ◽

Aggressive Tumor

Abstract Objective.—Carcinosarcomas of urinary bladder are rare malignant neoplasms. Seventy-eight cases have been previously described. The histologic composition of these tumors is variable, but diagnosis requires the presence of both epithelial and mesenchymal malignant components. We report 4 additional cases, with an emphasis on unusual histologic features. Methods.—Histologic and immunohistochemical examinations were performed on bladder tumors from 4 patients. Clinicopathologic features of previously reported and current cases were reviewed and summarized. Results.—Four patients (3 men, 1 woman) age 54 to 77 years were found to have polypoid masses in the urinary bladder. In all cases, histologic examination showed biphasic neoplasms with distinct mesenchymal and epithelial components. The morphologic and immunohistochemical characteristics of the tumors varied. One of the cases was remarkable for the presence of liposarcoma, malignant peripheral nerve sheath tumor, and micropapillary urothelial carcinoma. Two of the patients died 2 years after diagnosis, which is consistent with the previously reported aggressive nature of urinary bladder carcinosarcomas. Conclusions.—Carcinosarcomas of the urinary bladder are rare, aggressive malignant neoplasms. To our knowledge, a liposarcomatous component has been reported in only 1 case previously, and components of micropapillary urothelial carcinoma and malignant peripheral nerve sheath tumor have not been reported previously in carcinosarcomas of the urinary bladder. Because of the aggressive biologic behavior of these tumors, they should be identified promptly and treated appropriately.

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Malignant peripheral nerve sheath tumors

Neurosurgical FOCUS ◽

10.3171/foc.2007.22.6.13 ◽

2007 ◽

Vol 22 (6) ◽

pp. 1-8 ◽

Cited By ~ 62

Author(s):

Gaurav Gupta ◽

Allen Maniker

Keyword(s):

Peripheral Nerve ◽

Soft Tissue Sarcomas ◽

Nerve Fibers ◽

World Health ◽

Malignant Schwannoma ◽

Malignant Neoplasms ◽

Cell Of Origin ◽

Nerve Sheath Tumors ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas of ectomesenchymal origin. The World Health Organization coined the term MPNST to replace previous heterogeneous and often confusing terminology, such as “malignant schwannoma,” “malignant neurilemmoma,” “neurogenic sarcoma,” and “neurofibrosarcoma.” Malignant peripheral nerve sheath tumors arise from major or minor peripheral nerve branches or sheaths of peripheral nerve fibers, and are derived from Schwann cells or pluripotent cells of neural crest origin. The Schwann cell is thought to be the major contributor to the formation of benign as well as malignant neoplasms of the nerve sheath. While this fact remains essentially true, the identity of cell of origin of the MPNST remains elusive, and has not yet been conclusively identified. It has been suggested that these tumors may have multiple cell line origins. In this review, the authors discuss the epidemiology, diagnosis, management, and treatment of MPNSTs.

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p53 and Ki-67 Proliferating Cell Nuclear Antigen in Benign and Malignant Peripheral Nerve Sheath Tumors in Children

Pediatric and Developmental Pathology ◽

10.1007/s100249900138 ◽

1999 ◽

Vol 2 (4) ◽

pp. 377-384 ◽

Cited By ~ 31

Author(s):

Helen Liapis ◽

Edith F. Marley ◽

Yuan Lin ◽

Louis P. Dehner

Keyword(s):

Soft Tissue ◽

Peripheral Nerve ◽

Plexiform Neurofibroma ◽

Soft Tissue Sarcomas ◽

Nuclear Antigen ◽

Ki 67 ◽

Nerve Sheath Tumors ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath ◽

Pathologic Features

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon soft tissue tumors. In children with neurofibromatosis 1 (NF1), a MPNST often arises in a preexisting neurofibroma, or may represent an initial manifestation without other obvious stigmata of the disease. The development of MPNSTs may be associated with instability of the p53 tumor suppressor gene since it is the most frequent genetic abnormality in soft tissue sarcomas. To assess the presence of p53 accumulation in MPNSTs and its correlation with clinical and pathologic features, we studied 12 neurofibromas (NFs), including 4 tumors with cellular features (one congenital) and 10 MPNSTs. Six MPNSTs were associated with NF1, all of which developed within a plexiform neurofibroma. Cell proliferation evaluated with an antibody to Ki-67 and nuclear p53 staining were both detected by immunohistochemistry We found p53 positivity in 60% of MPNSTs. All NFs except the congenital tumor were p53 immunonegative ( P < 0.01). Rare p53-positive nuclei were detected in the transitional zone in two of six MPNSTs arising in plexiform NFs. Ki-67 distinguished the NFs from MPNSTs ( P < 0.005). Half of the NF1 patients with p53-positive MPNSTs developed recurrence or metastases or developed a second malignancy within 2 years of diagnosis, whereas patients with p53-positive sporadic MPNSTs were free of disease 1 to 7 years later. We found p53 accumulation more frequently in NF1-associated MPNSTs. p53 mutations may be an additional biologic factor to account for the poor prognosis in these tumors.

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Histopathologic findings in malignant peripheral nerve sheath tumor predict response to radiotherapy and overall survival

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa131 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Calixto-Hope G Lucas ◽

Harish N Vasudevan ◽

William C Chen ◽

Stephen T Magill ◽

Steve E Braunstein ◽

...

Keyword(s):

Overall Survival ◽

Peripheral Nerve ◽

San Francisco ◽

Strong Predictor ◽

Malignant Neoplasm ◽

Nerve Sheath Tumor ◽

Ki 67 ◽

Peripheral Nerve Sheath Tumor ◽

Locoregional Failure ◽

Nerve Sheath

Abstract Background Malignant peripheral nerve sheath tumor (MPNST) is an aggressive and poorly understood malignant neoplasm. Even in the setting of multimodal therapy, the clinical course of MPNST is frequently marked by metastatic conversion and poor overall prognosis, with optimal treatment paradigms for this rare tumor unknown. Methods We reviewed the medical records and histopathology of 54 consecutive patients who were treated at University of California San Francisco between 1990 and 2018. Results Our cohort consisted of 24 male and 30 female patients (median age 38 years). Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) sarcoma grading criteria segregated patients into groups with differences in overall survival (OS) (P = .02). Increasing Ki-67 labeling index was associated with poor OS (hazard ratio [HR] 1.36 per 10%, P = .0002). Unsupervised hierarchical clustering-based immunohistochemical staining patterns identified 2 subgroups of tumors with differences in H3K27me3, Neurofibromin, S100, SOX10, p16, and EGFR immunoreactivity. In our cohort, cluster status was associated with improved locoregional failure-free rate (P = .004) in response to radiation. Conclusions Our results lend support to the FNCLCC sarcoma grading criteria as a prognostic scheme for MPNST, although few cases of grade 1 were included. Further, we identify increased Ki-67 labeling as a strong predictor of poor OS from MPNST. Finally, we identify a subset of MPNSTs with a predictive immunohistochemical profile that has improved local control with adjuvant radiotherapy. These data provide insights into the grading and therapy for patients with MPNST, although further studies are needed for independent validation.

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