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

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) ( 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

Educational Case: Mitochondrial Myopathy.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1

Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90-95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed

Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90-95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed

Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90–95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed

Genetic Events and Signaling Mechanisms Underlying Schwann Cell Fate in Development and Cancer.

In this review, we describe Schwann cell development from embryonic neural crest cells to terminally differentiated myelinated and nonmyelinated mature Schwann cells. We focus on the genetic drivers and signaling mechanisms mediating decisions to proliferate versus differentiate during Schwann cell development, highlighting pathways that overlap with Schwann cell development and are dysregulated in tumorigenesis. We conclude by considering how our knowledge of the events underlying Schwann cell development and mouse models of schwannoma, neurofibroma, and malignant peripheral nerve sheath tumor can inform novel therapeutic strategies for patients with cancers derived from Schwann cell lineages

Sarcomatous Meningioma: Diagnostic Pitfalls and the Utility of Molecular Testing.

Anaplastic meningiomas can have a sarcomatous appearance on histology but true sarcomatous (metaplastic) differentiation is rare. These tumors follow an aggressive clinical course with recurrence and poor clinical outcomes. Due to significant overlap in morphology and immunohistochemical profiles, distinguishing between sarcomatous transformation of a meningioma and a true sarcoma can be challenging. Here, we outline potential diagnostic pitfalls and the utility of ancillary molecular testing in 3 patients diagnosed with sarcomatous meningiomas. We report loss of typical meningothelial markers in sarcomatous meningiomas. Ancillary molecular testing can support the diagnosis of sarcomatous meningioma when a molecular signature consistent with meningioma is seen, such as inactivation of the NF2 gene. Recognition of this rare transformation in meningioma can prevent a misdiagnosis of a primary sarcoma, whether sporadic or radiation-induced from prior treatment of a more classic meningioma