Bovine Papillomavirus DNA and S100 Profiles in Sarcoids and Other Cutaneous Spindle Cell Tumors in Horses

Histopathologic differentiation between deep dermal or subcuticular equine sarcoids (ie, nodular sarcoids) and other spindle cell tumors in the dermis and subcutis such as peripheral nerve sheath tumors (PNSTs) can be challenging based on morphologic criteria alone. It has been proposed that polymerase chain reaction (PCR) for bovine papillomavirus (BPV) DNA and S100 immunohistochemistry be used as diagnostic tests to separate equine sarcoids from PNSTs. We reviewed 197 skin-associated spindle cell tumors (ie, soft tissue sarcomas), including PNSTs and sarcoids, received at the University of Florida between 1995 and 2013 and performed BPV PCR and S100 immunohistochemistry on archived paraffin-embedded tissues. We found that BPV DNA was demonstrable in 70% of the sarcoids, 59% of the PNSTs, 37% of the fibrosarcomas, and 22% of other tumors (myxosarcomas, fibromas, and other sarcomas) diagnosed on histomorphologic characteristics. Positive S100 staining was only seen in 12 tumors in the study (5 fibrosarcomas, 3 sarcoids, 2 PNSTs, and 2 other sarcomas). The results demonstrate that BPV is associated with many skin-associated spindle cell soft tissue tumors in horses in addition to sarcoids. S100 was rarely expressed in equine soft tissue sarcomas in the skin but was expressed in many tumor types, including PNSTs and sarcoids. Because 41% of the PNSTs classified by histomorphology in this study were BPV negative and 94% were S100 negative, it is reasonable to classify these as soft tissue sarcomas with nerve sheath tumor histomorphology rather than as either PNSTs or sarcoids.

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Malignant Peripheral Nerve Sheath Tumors

10.1093/med/9780190617127.003.0020 ◽

2018 ◽

Author(s):

Marie-Noëlle Hébert-Blouin

Keyword(s):

Decision Making ◽

Soft Tissue ◽

Peripheral Nerve ◽

Soft Tissue Sarcomas ◽

Nerve Sheath Tumor ◽

Nerve Sheath Tumors ◽

Peripheral Nerve Sheath Tumors ◽

Adjuvant Therapies ◽

Nerve Sheath ◽

Schwann Cell Differentiation

Malignant peripheral nerve sheath tumors (PNSTs) are soft tissue sarcomas arising from a peripheral nerve or a pre-existing benign nerve sheath tumor or are sarcomas with features of Schwann-cell differentiation. Differentiating between benign and malignant PNSTs can be challenging. The chapter begins with a case example and then discusses assessment, investigations (including imaging), and diagnosis of malignant PNSTs, as well as the steps involved in decision-making about management of a malignant PNST. The surgical principles and goals for resection of a malignant PNST, the adjuvant therapies used in treatment, and the complications and outcomes of treatment are presented.

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Pathologic Evaluation of Soft Tissue Sarcoma

10.2310/7800.16097 ◽

2017 ◽

Author(s):

Narasimhan P. Agaram

Keyword(s):

Soft Tissue ◽

Tertiary Care ◽

Soft Tissue Sarcomas ◽

Molecular Diagnostic ◽

Nerve Sheath Tumor ◽

Rare Tumors ◽

Pathologic Evaluation ◽

Nerve Sheath ◽

Different Types ◽

Tertiary Care Centers

Soft tissue sarcomas are rare tumors and are mostly managed in tertiary care centers. They are broadly classified based on their differentiation into multiple different types. They affect patients of all ages and mostly occur in the extremities. Pathologic examination of the biopsy or resection of the tumor is an extremely important aspect in the diagnosis of these tumors and appropriately guiding the clinical team in the management of these rare tumors. This review focuses on the aspects of pathologic evaluation of these tumors and discusses the morphologic aspects of the predominant soft tissue sarcomas based on differentiation. The review also highlights the latest molecular diagnostic studies that are used in the accurate subtyping of these tumors. This review contains 12 figures, 2 tables, and 28 references. Key words: angiosarcoma, fibromatosis, fibrous, liposarcoma, myxoid, nerve sheath tumor, sarcoma, synovial sarcoma

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Pathologic Evaluation of Soft Tissue Sarcoma

10.2310/cgso.16097 ◽

2017 ◽

Author(s):

Narasimhan P. Agaram

Keyword(s):

Soft Tissue ◽

Tertiary Care ◽

Soft Tissue Sarcomas ◽

Molecular Diagnostic ◽

Nerve Sheath Tumor ◽

Rare Tumors ◽

Pathologic Evaluation ◽

Nerve Sheath ◽

Different Types ◽

Tertiary Care Centers

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The Role of Polycomb Repressive Complex in Malignant Peripheral Nerve Sheath Tumor

Genes ◽

10.3390/genes11030287 ◽

2020 ◽

Vol 11 (3) ◽

pp. 287 ◽

Cited By ~ 3

Author(s):

Xiyuan Zhang ◽

Béga Murray ◽

George Mo ◽

Jack F. Shern

Keyword(s):

Peripheral Nerve ◽

Transcriptional Repression ◽

Molecular Mechanisms ◽

Significant Proportion ◽

Soft Tissue Sarcomas ◽

Nerve Sheath Tumor ◽

Polycomb Repressive Complex ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath ◽

Recurrent Mutations

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that can arise most frequently in patients with neurofibromatosis type 1 (NF1). Despite an increasing understanding of the molecular mechanisms that underlie these tumors, there remains limited therapeutic options for this aggressive disease. One potentially critical finding is that a significant proportion of MPNSTs exhibit recurrent mutations in the genes EED or SUZ12, which are key components of the polycomb repressive complex 2 (PRC2). Tumors harboring these genetic lesions lose the marker of transcriptional repression, trimethylation of lysine residue 27 on histone H3 (H3K27me3) and have dysregulated oncogenic signaling. Given the recurrence of PRC2 alterations, intensive research efforts are now underway with a focus on detailing the epigenetic and transcriptomic consequences of PRC2 loss as well as development of novel therapeutic strategies for targeting these lesions. In this review article, we will summarize the recent findings of PRC2 in MPNST tumorigenesis, including highlighting the functions of PRC2 in normal Schwann cell development and nerve injury repair, as well as provide commentary on the potential therapeutic vulnerabilities of a PRC2 deficient tumor cell.

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EWSR1-SMAD3-Positive Fibroblastic Tumor

International Journal of Surgical Pathology ◽

10.1177/1066896920938124 ◽

2020 ◽

pp. 106689692093812

Author(s):

Oliver Foot ◽

Magnus Hallin ◽

Robin L. Jones ◽

Vaiyapuri P. Sumathi ◽

Khin Thway

Keyword(s):

Spindle Cell ◽

Soft Tissue Tumors ◽

Spindle Cell Sarcoma ◽

Correct Identification ◽

Nerve Sheath Tumor ◽

Not Otherwise Specified ◽

Nerve Sheath ◽

Spindle Cells ◽

Subcutaneous Tissues ◽

Malignant Soft Tissue

EWSR1-SMAD3-positive fibroblastic tumor is a recently characterized neoplasm with distinct clinicopathologic features and recurrent EWSR1-SMAD3 gene fusion. ESFT typically presents as a small, painless tumor in extremity subcutaneous tissues. Their behavior is benign, although they are prone to local recurrence. They typically comprise two components: intersecting fascicles of overlapping, uniform plump spindle cells, and less cellular hyalinized areas containing stippled calcifications. Immunohistochemically, the cells consistently show diffuse ERG nuclear expression, while other markers are negative. The morphology of this neoplasm can lead to histologic confusion with both benign and malignant soft tissue tumors, including monophasic synovial sarcoma, malignant peripheral nerve sheath tumor, and spindle cell sarcoma, not otherwise specified. Correct identification of ESFT is critical, most importantly to avoid unnecessary overtreatment as sarcoma.

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Systemic Treatment for Advanced and Metastatic Malignant Peripheral Nerve Sheath Tumors—A Sarcoma Reference Center Experience

Journal of Clinical Medicine ◽

10.3390/jcm9103157 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3157

Author(s):

Paweł Sobczuk ◽

Paweł Teterycz ◽

Anna M. Czarnecka ◽

Tomasz Świtaj ◽

Hanna Koseła-Paterczyk ◽

...

Keyword(s):

Peripheral Nerve ◽

Systemic Treatment ◽

Treatment Options ◽

Soft Tissue Sarcomas ◽

Nerve Sheath Tumor ◽

First Line ◽

Rare Type ◽

Reference Center ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath

Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate the modes and outcomes of systemic treatment of patients with diagnosed MPNST treated in a reference center. In total, 115 patients (56 female and 59 male) diagnosed with MPNST and treated due to unresectable or metastatic disease during 2000–2019 were included in the retrospective analysis. Schemes of systemic therapy and the outcomes—progression-free survival (PFS) and overall survival (OS)—were evaluated. The median PFS in the first line was 3.9 months (95% CI 2.5–5.4). Doxorubicin-based regimens were the most commonly used in the first line (50.4% of patients). There were no significant differences in PFS between chemotherapy regimens most commonly used in the first line (p = 0.111). The median OS was 15.0 months (95% CI 11.0–19.0) and the one-year OS rate was 63%. MPNST are resistant to the majority of systemic therapies, resulting in poor survival in advanced settings. Chemotherapy with doxorubicin and ifosfamide is associated with the best response and longest PFS. Future studies and the development of novel treatment options are necessary for the improvement of treatment outcomes.

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From Genes to -Omics: The Evolving Molecular Landscape of Malignant Peripheral Nerve Sheath Tumor

Genes ◽

10.3390/genes11060691 ◽

2020 ◽

Vol 11 (6) ◽

pp. 691

Author(s):

Kathryn M. Lemberg ◽

Jiawan Wang ◽

Christine A. Pratilas

Keyword(s):

Peripheral Nerve ◽

Soft Tissue Sarcomas ◽

Type I ◽

Nerve Sheath Tumor ◽

Genetic Changes ◽

Genetic Syndrome ◽

Genetic Sequencing ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath ◽

Molecular Landscape

Malignant peripheral nerve sheath tumors (MPNST) are rare, aggressive soft tissue sarcomas that occur with significantly increased incidence in people with the neuro-genetic syndrome neurofibromatosis type I (NF1). These complex karyotype sarcomas are often difficult to resect completely due to the involvement of neurovascular bundles, and are relatively chemotherapy- and radiation-insensitive. The lifetime risk of developing MPNST in the NF1 population has led to great efforts to characterize the genetic changes that drive the development of these tumors and identify mutations that may be used for diagnostic or therapeutic purposes. Advancements in genetic sequencing and genomic technologies have greatly enhanced researchers’ abilities to broadly and deeply investigate aberrations in human MPNST genomes. Here, we review genetic sequencing efforts in human MPNST samples over the past three decades. Particularly for NF1-associated MPNST, these overall sequencing efforts have converged on a set of four common genetic changes that occur in most MPNST, including mutations in neurofibromin 1 (NF1), CDKN2A, TP53, and members of the polycomb repressor complex 2 (PRC2). However, broader genomic studies have also identified recurrent but less prevalent genetic variants in human MPNST that also contribute to the molecular landscape of MPNST and may inform further research. Future studies to further define the molecular landscape of human MPNST should focus on collaborative efforts across multiple institutions in order to maximize information gathered from large numbers of well-annotated MPNST patient samples, both in the NF1 and the sporadic MPNST populations.

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A Rare Malignant Peripheral Nerve Sheath Tumor of the Maxilla Mimicking a Periapical Lesion

Case Reports in Dentistry ◽

10.1155/2016/4101423 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5

Author(s):

José Alcides Arruda ◽

Pamella Álvares ◽

Luciano Silva ◽

Alexandrino Pereira dos Santos Neto ◽

Cleomar Donizeth Rodrigues ◽

...

Keyword(s):

Soft Tissue ◽

Peripheral Nerve ◽

Soft Tissue Sarcomas ◽

Malignant Neoplasm ◽

Surgical Approaches ◽

Type I ◽

Nerve Sheath Tumor ◽

Peripheral Nerve Sheath Tumor ◽

Nerve Sheath ◽

Malignant Soft Tissue Tumor

Malignant peripheral nerve sheath tumor is a malignant neoplasm that is rarely found in the oral cavity. About 50% of this tumor occurs in patients with neurofibromatosis type I and comprises approximately 10% of all soft tissue sarcomas of head and neck region. Intraosseous malignant peripheral nerve sheath tumor of the maxilla is rare. This article is the first to address malignant peripheral nerve sheath tumor of the maxilla presenting as a periapical radiolucency on nonvital endodontically treated teeth in the English medical literature. Surgical approaches to malignant soft tissue tumor vary based on the extent of the disease, age of the patient, and pathological findings. A rare case of intraosseous malignant peripheral nerve sheath tumor is reported in a 16-year-old woman. The patient presented clinically with a pain involving the upper left incisors region and with defined unilocular periapical radiolucency lesion involved between the upper left incisors. An incisional biopsy was made. Histological and immunohistochemical examination were positive for S-100 protein and glial fibrillary acidic protein showed that the lesion was an intraosseous malignant peripheral nerve sheath tumor of the maxilla. Nine years after the surgery, no regional recurrence was observed.

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Role of high-resolution ultrasound in detection and monitoring of peripheral nerve tumor burden in neurofibromatosis in children

Child s Nervous System ◽

10.1007/s00381-020-04718-z ◽

2020 ◽

Vol 36 (10) ◽

pp. 2427-2432

Author(s):

Natalie Winter ◽

Maike F. Dohrn ◽

Julia Wittlinger ◽

Alexander Loizides ◽

Hannes Gruber ◽

...

Keyword(s):

High Resolution ◽

Peripheral Nerve ◽

Malignant Tumors ◽

Diagnostic Procedures ◽

Soft Tissue Tumors ◽

Tumor Burden ◽

Nerve Sheath Tumor ◽

Nerve Sheath Tumors ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath

Abstract Purpose Peripheral nerve sheath tumors are hallmark findings in neurofibromatosis types 1 and 2. With increasing size, they typically lead to neurological symptoms, and NF1 patients have a lifetime risk of 8–13% for developing malignant peripheral nerve sheath tumors. Medical imaging is therefore highly needed for early detection and exact localization of symptomatic or potentially malignant tumors. This review will give an overview of the ultrasound characteristics of peripheral nerve sheath tumors and findings in patients with neurofibromatosis types 1 and 2. Methods A systematic search of electronic databases, reference lists, and unpublished literature was conducted including the keywords “schwannoma,” “neurofibroma,” “neurofibromatosis,” “benign and malignant peripheral nerve sheath tumor.” Results The high-resolution allows a clear analysis of tumor echotexture, definition of margins, and the relation to the parent nerve. The use of color duplex/Doppler and contrast agent adds valuable information for the differentiation of benign and malignant tumors. Conclusion High-resolution ultrasound is a well-established, non-invasive, and easily repeatable first-line tool in diagnostic procedures of soft tissue tumors.

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Diagnostic Pathology of Tumors of Peripheral Nerve

Neurosurgery ◽

10.1093/neuros/nyab021 ◽

2021 ◽

Vol 88 (3) ◽

pp. 443-456

Author(s):

Sarra M Belakhoua ◽

Fausto J Rodriguez

Keyword(s):

Soft Tissue ◽

Peripheral Nerve ◽

Local Level ◽

Plexiform Neurofibroma ◽

Nerve Sheath Tumor ◽

Nerve Sheath Tumors ◽

Peripheral Nerve Sheath Tumors ◽

Nerve Sheath ◽

Biological Potential ◽

Pathologic Features

Abstract Neoplasms of the peripheral nervous system represent a heterogenous group with a wide spectrum of morphological features and biological potential. They range from benign and curable by complete excision (schwannoma and soft tissue perineurioma) to benign but potentially aggressive at the local level (plexiform neurofibroma) to the highly malignant (malignant peripheral nerve sheath tumors [MPNST]). In this review, we discuss the diagnostic and pathologic features of common peripheral nerve sheath tumors, particularly those that may be encountered in the intracranial compartment or in the spine and paraspinal region. The discussion will cover schwannoma, neurofibroma, atypical neurofibromatous neoplasms of uncertain biological potential, intraneural and soft tissue perineurioma, hybrid nerve sheath tumors, MPNST, and the recently renamed enigmatic tumor, malignant melanotic nerve sheath tumor, formerly referred to as melanotic schwannoma. We also discuss the diagnostic relevance of these neoplasms to specific genetic and familial syndromes of nerve, including neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis. In addition, we discuss updates in our understanding of the molecular alterations that represent key drivers of these neoplasms, including neurofibromatosis type 1 and type 2, SMARCB1, LZTR1, and PRKAR1A loss, as well as the acquisition of CDKN2A/B mutations and alterations in the polycomb repressor complex members (SUZ12 and EED) in the malignant progression to MPNST. In summary, this review covers practical aspects of pathologic diagnosis with updates relevant to neurosurgical practice.

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