Getting Your Laboratory on Track With Neurotrophic Receptor Tyrosine Kinase.

Context.—: Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration-approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making.

Mast cell sarcoma: clinicopathologic and molecular analysis of 10 new cases and review of literature.

Mast cell sarcoma (MCS) is an exceedingly rare form of mastocytosis characterized by invasive malignant mast cell growth and metastatic potential. Diagnosis of MCS is very challenging due to its marked morphologic variations and significant immunophenotypic overlap with other neoplasms. In this study, we undertook an extensive study of 10 cases of MCS from our series, with review of additional 24 cases from the literature, to better clarify the clinicopathologic and molecular features of MCS.

Clinicopathologic Features of Lymphoproliferative Neoplasms Involving the Liver.

: Primary hepatic lymphoproliferative neoplasms (PHL) are uncommon. This retrospective study is aimed to present the clinicopathological characteristics of PHL and compare to secondary hepatic lymphoproliferative neoplasms (SHL). : Patients who were diagnosed with lymphoproliferative neoplasms involving the liver between January 2004 and December 2018 at a tertiary medical center in central Taiwan were included.

Case Report: Phenotypic Switch in High-Grade B-Cell Lymphoma With and Rearrangements: A Potential Mechanism of Therapeutic Resistance in Lymphoma?

Lineage switch between myeloid and lymphoid in acute leukemia is well established as a mechanism for leukemic cells to escape chemotherapy. Cross-lineage transformation is also recognized in some solid tumors on targeted therapy, such as adenocarcinomas of the lung and prostate that transforms to neuroendocrine carcinoma on targeted therapy. Now lineage plasticity is increasingly recognized in mature lymphomas, such as small B-cell lymphomas transforming to histiocytic/dendritic cell sarcoma.

Mutational profiling of myeloid neoplasms associated genes may aid the diagnosis of acute myeloid leukemia with myelodysplasia-related changes.

AML with myelodysplasia-related changes (AML-MRC) is a subtype of AML known to have adverse prognosis. The karyotype abnormalities in AML-MRC have been well established; however, relatively little has been known about the role of gene mutation profiles by next generation sequencing. 177 AML patients (72 AML-MRC and 105 non-MRC AML) were analyzed by NGS panel covering 53 AML related genes.

Adverse Impact of DNA Methylation Regulatory Gene Mutations on the Prognosis of AML Patients in the 2017 ELN Favorable Risk Group, Particularly Those Defined by Mutation.

The 2017 ELN risk stratification has been widely adopted, but some studies have suggested the outcomes are heterogenous within the ELN risk groups and may be affected by other co-existing genetic mutations. This study evaluated the impact of DNA methylation regulatory gene (, , , ) mutations (DMRGM) evaluated by NGS in the outcome of AML patients in each ELN risk group. A total of 114 patients were analyzed with a median follow-up of 12 months.

Local ALK-Positive Histiocytosis With Unusual Morphology and Novel Gene Fusion.

ALK-positive histiocytosis was first described in 2008 as a systemic histiocytic disorder involving young infants and neonates. Subsequently, cases of local ALK-positive histiocytosis as well as clinical presentation in adult patients have been increasingly reported in the literature. The current case documented the hitherto largest local ALK-positive histiocytosis lesion involving the mesentery of a 20-year-old female patient, a clinical presentation that has not been previously reported in the medical literature.

Prognostic Value of KRAS Mutation Subtypes and PD-L1 Expression in Patients With Lung Adenocarcinoma.

Background: The prognostic value of different KRAS (Kirsten rat sarcoma viral oncogene) mutation subtypes and their association with programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma (LADC) remain unclear. We examined the association of KRAS mutation subtypes with clinical outcomes and PD-L1 expression status.

Patients And Methods: Patients diagnosed with KRAS-mutated LADC were evaluated for PD-L1 expression, cancer staging, overall survival (OS), and relapse-free survival.

Leukemic Non-nodal Mantle Cell Lymphoma: Diagnosis and Treatment.

Mantle cell lymphoma (MCL) encompasses nearly 6% of all the non-Hodgkin lymphomas. It is considered an incurable neoplastic process arising from B cells. The cytogenetic abnormality t(11;14) (q13; q32) leading to cyclin D1 overexpression is the sentinel genetic event and provides an exceptional marker for diagnosis.

Rosai-Dorfman Disease of the Breast With Variable IgG4+ Plasma Cells: A Diagnostic Mimicker of Other Malignant and Reactive Entities.

Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis.

Superficial and Deep Cutaneous Involvement by RAS-Associated Autoimmunne Leukoproliferative Disease (RALD Cutis): A Histologic Mimicker of Histiocytoid Sweet Syndrome.

RAS-associated autoimmune leukoproliferative disease (RALD) is a recently described noninfectious and nonmalignant clinical syndrome characterized by autoimmune disorders, massive splenomegaly, modest lymphadenopathy, and monocytosis. On the molecular level, RALD is defined by somatic mutations of either NRAS or KRAS gene in a subset of hematopoietic cells. To date, there is a dearth of well-documented histopathologic description of cutaneous involvement by RALD in the literature.

Prognostic Significance of the Dynamic Change of Programmed Death-ligand 1 Expression in Patients with Multiple Myeloma.

Background The inhibition of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway has been shown to be an effective targeted therapy in fighting both solid organ cancers and hematological malignancies. PD-L1 expression also serves as a prognostic marker in various cancers. However, the expression of PD-L1 and its prognostic significance in multiple myeloma remains largely unknown.

A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood: A single tertiary care pediatric institution experience in North America.

Background: Systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T-cell lymphoma (S-EBV-TCL), and systemic chronic active EBV infection (S-CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities.

An analysis of blastic plasmacytoid dendritic cell neoplasm with translocations involving the MYC locus identifies t(6;8)(p21;q24) as a recurrent cytogenetic abnormality.

Aims: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm with leukaemic features and frequent skin involvement. Translocations involving the MYC locus have been recently identified as recurrent cytogenetic abnormalities in this entity. The aim of this study was to assess the clinicopathological, immunophenotypic and genetic features in MYC-rearranged BPDCN cases.

A theorem proving approach for automatically synthesizing visualizations of flow cytometry data.

Background: Polychromatic flow cytometry is a popular technique that has wide usage in the medical sciences, especially for studying phenotypic properties of cells. The high-dimensionality of data generated by flow cytometry usually makes it difficult to visualize. The naive solution of simply plotting two-dimensional graphs for every combination of observables becomes impractical as the number of dimensions increases.

Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.

Context: - Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various cancers and reveal a new era of cancer immunotherapy.

Objective: - To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression.

Acute mast cell leukemia associated with t(4;5)(q21;q33).

To the best of our knowledge, this manuscript describes clinical and pathologic findings of the first case of acute mast cell leukemia harboring t(4;5)(q21;q33), compatible with fusion of the PDGFRB gene to a rare partner, PRKG2. Translocation involving the PDGFRB gene is confirmed by fluorescence in situ hybridization study. This case presented a relatively fulminant clinical course with acute mast cell leukemia and "C" findings (cytopenia, hepatosplenomegaly, and weight loss), mast cell sarcoma, and severe basophilia.

Detection of BRAF mutation in the cytocentrifugation supernatant fluid from fine-needle aspiration of thyroid lesions may enhance the diagnostic yield.

Objective: BRAF mutations using cellular DNA from fine-needle aspiration (FNA) specimens are commonly used to support the diagnosis of papillary thyroid carcinoma (PTC). The goal of this study was to preliminarily evaluate the diagnostic utility of detecting BRAF mutations in the routinely discarded FNA specimen supernatant fluid.

Materials And Methods: Seventy-eight FNAs of thyroid lesions were evaluated for BRAF mutations using both cellular and supernatant DNA.

Mutated genes and driver pathways involved in myelodysplastic syndromes—a transcriptome sequencing based approach.

Myelodysplastic syndromes are a heterogeneous group of clonal disorders of hematopoietic progenitors and have potentiality to progress into acute myelogenous leukemia. Development of effective treatments has been impeded by limited insight into pathogenic pathways. In this study, we applied RNA-seq technology to study the transcriptome on 20 MDS patients and 5 age-matched controls, and developed a pipeline for analyzing this data.

SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II.

Multiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite extensive research efforts. This is due, in part, to frequent disease recurrences associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs through genetic or biochemical alterations.

De novo CD3 negative hepatosplenic T-cell lymphoma: diagnostic challenges and pitfalls.

Hepatosplenic T-cell lymphoma is a rare and aggressive peripheral T-cell malignancy that is distinctively characterized by sinusoidal infiltration of mature medium-sized T lymphocytes in the spleen and liver. The neoplastic cells are classically surface CD3(+), CD2(+), CD5(-), CD4(-), and CD8(+/-) and manifest variable expression of markers associated with natural killer (NK) cells such as CD16 and CD56. In this article, we report the first case to date of a newly diagnosed de novo surface CD3(-) hepatosplenic T-cell lymphoma with circulating blastlike neoplastic cells expressing NK-cell-associated markers.

High throughput quantitative reverse transcription PCR assays revealing over-expression of cancer testis antigen genes in multiple myeloma stem cell-like side population cells.

Multiple myeloma (MM) stem cells, proposed to be responsible for the tumourigenesis, drug resistance and recurrence of this disease, are enriched in the cancer stem cell-like side population (SP). Cancer testis antigens (CTA) are attractive targets for immunotherapy because they are widely expressed in cancers but only in limited types of normal tissues. We designed a high throughput assay, which allowed simultaneous relative quantifying expression of 90 CTA genes associated with MM.