Laryngeal mucous membrane plasmacytosis with 15 year follow-up: Case report and literature review.

Mucous membrane plasmacytosis (MMP) is an uncommon variant of mucositis represented by a polyclonal plasma cell infiltration of mucosal tissue. Various clinical presentations in the upper airway have been reported ranging from erythematous mucosa to fungating masses. Histologic features include mucosal epithelial hyperplasia or psoriasiform changes with a dense submucosal infiltrate of polytypic plasma cells.

Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool.

Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis.

Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in Chromophobe Renal Cell Carcinoma: A Potential Role in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma.

Overlapping morphologic, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS).

Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice.

The p53 tumor suppressor acts as a guardian of the genome by preventing the propagation of DNA damage-induced breaks and mutations to subsequent generations of cells. We have previously shown that phosphorylation of the Mdm2 oncoprotein at Ser394 by the ATM kinase is required for robust p53 stabilization and activation in cells treated with ionizing radiation, and that loss of Mdm2 Ser394 phosphorylation leads to spontaneous tumorigenesis and radioresistance in Mdm2 mice. Previous in vitro data indicate that the c-Abl kinase phosphorylates Mdm2 at the neighboring residue (Tyr393) in response to DNA damage to regulate p53-dependent apoptosis.

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1.

Immunohistochemical loss of 5-hydroxymethylcytosine expression in acute myeloid leukaemia: relationship to somatic gene mutations affecting epigenetic pathways.

Aims: Genes affecting epigenetic pathways are frequently mutated in myeloid malignancies, including acute myeloid leukaemia (AML). The genes encoding TET2, IDH1 and IDH2 are among the most commonly mutated genes, and cause defective conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), impairing demethylation of DNA, and presumably serving as driver mutations in leukaemogenesis. The aim of this study was to correlate 5hmC immunohistochemical loss with the mutation status of genes involved in epigenetic pathways in AML.

Role of Tetrasomy for the Diagnosis of Urothelial Carcinoma Using UroVysion Fluorescent In Situ Hybridization.

Context: -UroVysion fluorescent in situ hybridization (FISH) is routinely used to detect urothelial carcinoma (UC). A positive threshold is defined as chromosome polysomy in 4 or more cells, which also includes tetrasomy, a natural product of cell division.

Objectives: -To evaluate tetrasomy for UC detection and explore the relation to the surgical diagnosis or patient history.

Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A).

We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis.

MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice.

Objectives: Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice.

Methods: We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review.

Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare.

IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma.

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated.

Oncofetal protein IMP3, a new cancer biomarker.

IMP3 is a member of a family of RNA-binding proteins that consists of IMP1, IMP2 and IMP3. These proteins contain 2 RNA recognition motifs and 4 K-homology domains that allow them to bind RNAs strongly and specifically. IMP3 is an oncofetal protein involved in embryogenesis and its expression is associated with a number of malignant neoplasms.

MYC protein expression is detected in plasma cell myeloma but not in monoclonal gammopathy of undetermined significance (MGUS).

It has been recognized that monoclonal gammopathy of undetermined significance (MGUS) precedes a diagnosis of plasma cell myeloma in most patients. Recent gene expression array analysis has revealed that an MYC activation signature is detected in plasma cell myeloma but not in MGUS. In this study, we performed immunohistochemical studies using membrane CD138 and nuclear MYC double staining on bone marrow biopsies from patients who met the diagnostic criteria of plasma cell myeloma or MGUS.

Five important advances in hematopathology.

Context: Hematopathology is a dynamic field that has always been on the frontier of clinical research within the scope of pathology. Several recent developments in hematopathology will likely affect its practice clinically.

Objective: To review 5 important recent advances in hematopathology: (1) detection and prognostic implication of MYC in diffuse large B-cell lymphomas, (2) determining origin and prognosis through immunoglobulin gene usage in mature B-cell neoplasms, (3)detecting minimal residual disease in multiple myeloma, (4) using genome-wide analysis in myelodysplastic syndromes, and (5) employing whole-genome sequencing in acute myeloid leukemias.

Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors.

DNA methylation is the most well-studied epigenetic modification in cancer biology. 5-hydroxymethylcytosine is an epigenetic mark that can be converted from 5-methylcytosine by the ten-eleven translocation gene family. We recently reported the loss of 5-hydroxymethylcytosine in melanoma compared with benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis.

Advances in understanding the pathogenesis of HLH.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule-dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies.

Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.

DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications.

ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice.

DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage.

Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations.

Post transplant lymphoproliferative disorder (PTLD) is a heterogeneous disease that may occur in recipients of solid organ transplants (SOT) and hematopoietic stem cell transplant. The risk of lymphoma is increased 20-120% compared with the general population with risk dependent in part on level of immune suppression. In addition, recent data have emerged, including HLA and cytokine gene polymorphisms, regarding genetic susceptibility to PTLD.

IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer.

The expression of IMP3, an oncofetal protein, has been strongly associated with aggressive cancers. In this study, we investigated whether IMP3 can serve as a biomarker to predict invasive squamous cell carcinoma (SCC) in patients with cervical intraepithelial neoplasia (CIN) II and III. A total of 1249 patients with no dysplasia, CINs, or invasive SCC were studied for IMP3 expression.

The oncofetal protein IMP3: a novel molecular marker to predict aggressive meningioma.

Context: One of the major clinical challenges is to predict recurrence of meningioma. Recently, we have found that IMP3, an oncofetal RNA-binding protein, is a biomarker to predict aggressive tumors.

Objective: To investigate whether IMP3 can be used as a new biomarker to predict the recurrence and overall survival of patients with meningiomas.

Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation.

The distinction of malignant mesothelioma from reactive mesothelial proliferation remains to be a major challenge for surgical pathologists. In this study, we investigated whether insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), an oncofetal protein, can be used as a biomarker to distinguish between malignant and reactive mesothelial cells. A total of 109 cases (mesothelioma, n=45; reactive mesothelial proliferation, n=64) were examined by immunohistochemistry for IMP3 expression.