Lawrence M Weiss

Although about 90% of the world's population is infected by EBV only a small subset of the related infections result in neoplastic transformation. EBV is a versatile oncogenic agent involved in a multitude of hematopoietic, epithelial, and mesenchymal neoplasms, but the precise role of EBV in the pathogenesis of many of the associated lymphoid/hist...

Epstein-Barr virus (EBV)is associated with many neoplastic hematologic conditions, but scattered EBV-positive cells can be detected in lymph nodes of healthy individuals and they usually represent latently infected lymphocytes. The incidence of EBV detection in normal bone marrow samples has not been studied and is largely unknown. The lack of know...

Targeting of the PD1/PD-L1 immune checkpoint pathway has rapidly gained acceptance as a therapeutic strategy for a growing number of malignancies. Testing for expression of PD-L1 in tumor cells and immune cells has been used as a companion or complementary test for drugs targeting the PD1/PD-L1 pathway. We evaluated the results of PD-L1 testing in...

Epstein-Barr virus (EBV) has been linked to many human neoplasms including hematopoietic, epithelial, and mesenchymal tumors. Since our original review of EBV-associated lymphoproliferative disorders in 2007 (1), many advances and developments have been reported. In this review, we will examine the recent advances in EBV-associated lymphoid/ histio...

Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe arra...

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to defin...

Peripheral T-cell lymphoma (PTCL) is rare in children. Expression of cytotoxic molecules (CM) in nodal PTCL has unique clinicopathologic features, including an Epstein-Barr virus (EBV) association. However, CM+, EBV-associated PTCL is extremely rare in the childhood, with only 1 study having been reported to date, including both pediatric and adult...

Piwi-interacting RNAs (piRNAs) are a distinct group of small non-coding RNAs (sncRNAs) that silence transposable genetic elements to protect genome integrity. Due to their limited expression in gonads and sequence diversity, piRNAs remain the most mysterious class of small RNAs. Studies have shown piRNAs are present in somatic cells and dysregulate...

Context Diffuse large B-cell lymphoma is the most commonly diagnosed subtype of lymphoma worldwide. The current World Health Organization (WHO) classification includes several subtypes, based on a combination of clinical, immunohistochemical, and genetic differences. Immunohistochemical staining is essential in evaluating diffuse large B-cell lymph...

The cytotoxic T-cell and natural killer (NK)-cell lymphomas and related disorders are important but relatively rare lymphoid neoplasms that frequently are a challenge for practicing pathologists. This selective review, based on a meeting of the International Lymphoma Study Group, briefly reviews T-cell and NK-cell development and addresses question...

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent...

Classical Hodgkin lymphoma can be diagnosed with confidence in the majority of cases, but there is a significant subset that remains a diagnostic challenge. The authors have investigated the utility of a novel hyperplexing technology, MultiOmyx™, which may be applied to stain with >60 antibodies on single tissue sections from formalin-fixed paraffi...

Human immunodeficiency virus (HIV) infection substantially elevates diffuse large B-cell lymphoma (DLBCL) risk, but its impact on the distinct DLBCL subtypes defined by cell of origin is unclear. We compared DLBCL molecular characteristics and prognosis in 51 HIV-infected and 116 HIV-uninfected cases diagnosed during 1977–2003. Using immunohistoche...

Rare cases of Merkel cell carcinoma have been encountered in lymph nodes with unknown extranodal primary, which exhibit similar morphologic and immunophenotypic features to those in primary cutaneous Merkel cell carcinomas. However, it is uncertain whether the nodal Merkel cell carcinoma is a primary tumor of the lymph node or represents a metastas...

Classical Hodgkin lymphoma has a characteristic immunophenotype in most cases, with expression of CD30, CD15, and PAX-5, and absence of CD45 and T-lineage markers. However, in a significant subset of cases, atypical staining patterns may be seen for one or more antigens, particularly negative staining for CD15 or staining for one or more B-lineage...

Background/Introduction The diagnosis of classical Hodgkin lymphoma is often difficult to establish due to the rarity of the neoplastic component and the necessity to perform immunostains on serial sections. We have developed a fluorescent multiplexed methodology in formalin-fixed, paraffin-embedded sections which enables assessment of multiple ant...

Background Recent genome wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified several associations at both HLA and non-HLA loci. However, much of HL heritability remains unexplained. Methods To identify novel risk loci, we performed a meta-analysis of 3 HL GWAS including a total of 1,810 cases and 7,879 controls. Results were r...

Mast cells are often increased in AML with t(8;21). We analyzed characteristics of mast cells to elucidate their relationship with leukemic blasts. In 31 cases in which the results of KIT mutation analysis were available, five cases showed mutations. None of the cases positive for KIT mutation showed increased mast cells. In five cases with increas...

T-cell lymphomas (TCLs) are a heterogenous group of diseases that show histologic and immunophenotypic features overlapping with reactive lymphoid proliferations and often require the use of ancillary testing for accurate diagnosis. The oncoprotein, bcl-2, is expressed in various types of lymphoma. At present, expression of this protein is useful f...

2097 Background: GBM is the most common brain tumor in humans and has a dismal prognosis. Although antiangiogenic therapy (bevacizumab) is an option for GBM, there is still unmet need to understand tumor pathophysiology and predictive biomarkers. We built a tissue based multiplexed immunofluorescent assays and developed algorithms to identify and q...

e19536 Background: Routine diagnosis of classical Hodgkin lymphoma is performed with a panel of immunohistochemistry markers to evaluate the biomarker expression profile of the relatively rare Hodgkin cells. One of the key challenges of this technique is that serial immunostains are used and hence it can be difficult or impossible to locate the sam...

Epstein-Barr encoding region (EBER) in situ hybridization is the methodology of choice for the detection of the Epstein-Barr virus (EBV) in tissue sections. Because of the large numbers of copies of EBERs present in latently infected cells, non-isotopic methods can be used. Positive studies show staining in the nuclei of the EBV-infected cells, acc...

Metastatic tumors with an uncertain primary site can be a difficult clinical problem. In tens of thousands of patients every year, no confident diagnosis is ever issued, making standard-of-care treatment impossible. Gene expression profiling (GEP) tests currently available to analyze these difficult-to-diagnose tumors have never been directly compa...

Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morpholog...

Follicular dendritic cells (FDCs) are a specialized type of antigen-presenting dendritic cells that are largely restricted to lymphoid follicles. They form dense three-dimensional meshwork patterns within benign follicles, which maintain the follicular architecture. The FDC function is to bind and retain antigens by linking to complement and immune...

Benign lymphadenopathy is a common biopsy finding, and may often be confused with malignant lymphoma. It may be separated into major morphologic patterns, each with its own differential diagnosis with certain types of lymphoma. Most cases of reactive follicular hyperplasia is easy to diagnosis, but some cases may be confused with follicular lymphom...

Accurate tumor classification is fundamental to inform predictive biomarker testing and optimize therapy. Gene expression-based tests are proposed as diagnostic aids in cases with uncertain diagnoses. This study directly compared the diagnostic accuracy of IHC analysis versus molecular classification using a 92-gene RT-PCR assay for determination o...

Mast cell diseases comprise a spectrum of disorders including cutaneous mastocytosis, indolent or aggressive systemic variants including leukemia, and unifocal tumor formations such as benign extracutaneous mastocytoma or aggressive mast cell sarcoma (MCS). Many mast cell diseases are associated with aberrancy of c-KIT proto-oncogene resulting in t...

STAT3 plays a crucial role in promoting progression of human cancers, including several types of B-cell lymphoma. However, as a transcription factor lacking its own enzymatic activity, STAT3 remains difficult to target with small-molecule drugs in the clinic. Here we demonstrate that persistent activated STAT3 colocalizes with elevated expression o...

Introduction: HIV-infected patients are at elevated risk of non-Hodgkin lymphoma (NHL), especially diffuse large B-cell lymphoma (DLBCL), compared with the general population. Because DLBCL is a molecularly and clinically heterogeneous disease, we compared frequencies and prognostic significance of molecular characteristics in HIV+ and HIV- DLBCLs....

e21019 Background: Metastatic tumors of uncertain or unknown origin pose diagnostic and therapeutic challenges. Accurate tumor classification is fundamental to inform predictive biomarker testing and optimize therapy. Standard of care employs IHC analysis for tumor classification that is varied in approach and interpretation. More recently, gene ex...

Renal cell carcinoma (RCC) metastasis portends a poor prognosis and cannot be reliably predicted. Early determination of the metastatic potential of RCC may help guide proper treatment. We analyzed microRNA (miRNA) expression in clear cell RCC (ccRCC) for the purpose of developing a miRNA expression signature to determine the risk of metastasis and...

Patients’ Information. (DOC)

Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymo...

IgG4-related sclerosing disease encompasses a family of disorders associated with increased numbers of IgG4 plasma cells and mass forming lesions in various tissues. Lymphadenopathy is a common finding, seen in up to 80% of cases. In the largest series of cases to date, we describe histologic, immunohistochemical, special stain and flow cytometric...

Mucinous adenocarcinomas (MAs) of various origins may have a similar histologic appearance and frequently metastasize to distant sites, which often causes diagnostic problems in surgical pathology practice. The immunohistochemical profiles of MAs of various origins have not been well studied. We investigated the expression of 10 immunohistochemical...

Indeterminate cell tumor is an extremely rare neoplasm that mainly occurs in the skin. We report a case of indeterminate cell tumor arising from the spleen, a previously unreported site for indeterminate cell tumor. Histologically, the tumor showed nests, nodules, and sheets of large polygonal cells with mostly oval nuclei; open chromatin; variable...

Breast cancer accounts for approximately one quarter of all cancers in females. Estrogen and progesterone receptor testing has become an essential part of the clinical evaluation of breast carcinoma patients, and accurate results are critical in identifying patients who may benefit from hormone therapy. The present study had the aim of investigatin...

Indeterminate cells are considered by many to be pre-Langerhans cells as they mimic Langerhans cells in certain morphologic and immunophenotypic aspects. Indeterminate cells express CD1a and S-100 but lack Langerin expression (Langerin is used as an immunohistochemical substitute for electron microscopy for the detection of Birbeck granules). Migra...

We describe two cases of acute myeloid leukemia with an unusual histological pattern mimicking metastatic non-hematopoietic neoplasm, leading to diagnostic difficulties. Both patients presented with pancytopenia and absence of circulating blasts. Bone marrow aspirations were not successful. Bone marrow core biopsies contained neoplastic cells arran...

Since many biomarkers of both the tumor and its microenvironment are expected to involve differential expression of divalent proteins capable of protein or peptide ligand interaction, we are developing multivalent nanodevices for the identification of biomarkers in prostate cancer. We compared a multivalent thioredoxin-targeted nanodevice with mono...

Persistent STAT3 signaling contributes to malignant progression in many diverse types of human cancer. STAT3 is constitutively active in activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL), a class of nongerminal center derived DLBCL cells for which existing therapy is weakly effective. In this report, we provide a preclinical proof...

Persistent STAT3 signaling contributes to malignant progression in many diverse human tumors. STAT3 has been found to be constitutively active in activated B cell (ABC)-like diffuse large B cell lymphomas (DLBCL). We investigated the effect of STAT3 silencing in human DLBCL Ly3 cells both in vitro and in vivo. For this purpose, we established stabl...

To determine the recurring DNA copy number alterations (CNA) in classical Hodgkin lymphoma (HL) by microarray-based comparative genomic hybridization (aCGH) using laser capture microdissected CD30(+) Hodgkin and Reed-Sternberg (HRS) cells. Archived tissues from 27 CD30(+) HL plus control samples were analyzed by DNA microarrays. The HL molecular ka...

Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.

Introduction: MicroRNA (miRNA) is a group of small non-coding regulating RNA and has shown altered expression in cancer. With great advantages in test specificity and capability to detect novel (unknown) miRNA and other small RNA targets, the next-generation deep sequencing technology is replacing microarray platforms, at least in the discovery pha...

Introduction: Clear cell renal cell carcinoma (ccRCC) represents the most common renal cancer histology. In the setting of metastatic disease, few patients achieve a durable remission with currently available therapies. Early determination of metastatic potential may help guide therapy and improve clinical outcome. MicroRNA (miRNA) is a group of sm...

This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented fro...

The need for bilateral pediatric bone marrow biopsies for cytogenetic and fluorescent in situ hybridization (FISH) studies has not been clearly delineated. We retrospectively identified 166 pediatric bilateral bone marrow biopsy specimens obtained from patients with a variety of clinical diagnoses, including solid tumors, lymphoma, leukemia, and ot...

2686 Nodular sclerosis Hodgkin lymphoma (NSHL) is epidemiologically and pathologically distinct from other Hodgkin lymphoma subtypes. It is highly heritable and is the most common form of HL in young adults. In a combined analysis of results from two genome-wide association scans (one undertaken at the University of Southern California using the Il...

Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL...

Myopericytoma is a rare, histologically distinctive tumor that shows evidence of differentiation toward perivascular myoid cells. Myopericytoma is largely considered a neoplasm of skin and soft tissues, with examples of this lesion involving visceral sites being extremely limited. We present the clinical and pathologic details of an unusual case of...

Breast cancer accounts for approximately one quarter of all cancers in females. HER2 gene amplification or HER2 protein overexpression, detected in about 20% of breast carcinomas, predicts a more aggressive clinical course and determines eligibility for targeted therapy with trastuzumab. HER2 testing has become an essential part of the clinical eva...

Renal cell carcinoma (RCC) is one of the leading causes of cancer mortality. Characterization of microRNA (miRNA) expression of RCC will help disclose new pathogenic pathways in tumourigenesis and progression and may lead to the development of molecular biomarkers and target-specific therapies for diagnosis, prognostication and treatment. With limi...

Langerhans cell histiocytosis (LCH), also known as histiocytosis X, is a rare human disorder characterized by an abnormal accumulation and/or clonal proliferation of Langerhans cells (LCs) in various body organs. The cellular origin of LCs has been a subject of considerable debate since their discovery. As specialized dendritic cells strategically...

In the current study, we investigated C/EBPA gene mutations and promoter hypermethylation in a series of 53 patients with CN-AML. In addition, we also analyzed two other frequent mutations (FLT3/ITD and NPM1) in these patients and correlated them with C/EBPA gene alterations. 13/53 patients were FLT3/ITD+/NPM1-, 11/53 patients were FLT3/ITD+/NPM1+,...

The identification of monotypic light chains is an important adjunct to the diagnosis of B-cell lymphoma, yet to reliably perform it on formalin-fixed paraffin sections is often difficult. We have evaluated a new set of monoclonal antibodies to kappa and lambda light chains that are reactive in paraffin sections. In reactive lymphoid tissues, polyt...

Immunohistochemical evaluation of CD30 expression is commonly performed in the assessment of hematopoietic disorders and germ cell tumors. A new monoclonal antibody, CON6D/B5, directed against the CD30 antigen has become commercially available for use in formalin-fixed paraffin-embedded tissue samples. The performance characteristics of CON6D/B5 we...

We immunohistochemically studied TCL1 protein expression in different histologic types of 63 testicular germ cell tumors: 23 seminomas, 14 embryonal carcinomas, 4 teratomas, 2 yolk sac tumors, and 20 mixed germ cell tumors. The 20 mixed germ cell tumors contained components of seminoma (n = 10), embryonal carcinoma (n = 18), teratoma (n = 16), yolk...

The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has b...

Adrenal neoplasms composed of more than one cell type and demonstrating a mixed histologic appearance are exceedingly rare. We report the clinical and pathologic features of a morphologically distinctive tumor of the adrenal gland composed of cortical, chromaffin, and neural cells. Histologically, the tumor consisted of intermixed areas of prolifer...

MUM1/IRF4 protein is a member of the interferon regulatory factor (IRF) family of transcriptional factors initially described as downstream regulators of interferon signaling. The quantity of this factor varies within the hematopoietic system in a lineage and stage-specific way. It is considered to be a key regulator of several steps in lymphoid, m...

1570 Poster Board I-594 Acute myeloid leukemia with normal cytogenetics (CN-AML) represents approximately 40-50% of de novo AML cases and constitutes the single largest cytogenetic group of AML. CN-AML is composed of a heterogeneous group of AML considered to be more or less in the intermediate prognostic category. Stratified prognostic determinant...

Diffuse large B-cell lymphoma (DLBCL) is a very infrequent neoplasm in the pediatric age group; therefore there are very few studies on the immunophenotype or genetics of these cases. We studied a series of 16 patients with nodal DLBCL occurring in patients between 10 and 18 years of age. The cases were classified according to the 2008 World Health...

Mantle cell lymphoma (MCL) characteristically express CD20, CD5, and cyclin-D1, carries the translocation t(11;14) (q13;q32) and typically has no expression of germinal center cell markers. So-called aberrant phenotypes such as CD5 negative and cyclin-D1-negative MCL have been described. Also few cases with CD10 and/or BCL-6 protein expression have...

Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/or early recurrence. Herein we present a method for detecting microins...

No detection of mosaicism in a “gene pool” analysis of the EGFR 15/18 bp deletions in 6,400 individuals. The possibility of somatic mosaicism in 6400 control individuals was tested in leukocyte DNA. Sixteen pools, each containing DNA from 400 individuals at an aggregated concentration of 200 ng/µl, were analyzed by MAP for the EGFR 15/18 bp deletio...

No detection of the EGFR 15 bp deletion in human lung by MAP in 4 normal lung samples and mushroom control. The common EGFR 15 bp deletion (sample ID1-4) was not found in normal lung from 1×107 copies (0.5×106 copies/tube ×20) of human lung tissues. The first two lanes in every sample and mushroom DNA are positive controls spiked with 10 and 4 copi...

Real-Time MAP shows a linear relationship in case-5 (also see Table 2). DNA from Patient #5 (see Table 2) with a p53 gene mutation (c.216_217insC) was analyzed by real-time PCR on the BioRad RQ5 instrument. Real-time MAP shows a linear relationship between MAP cycle number and the log of the starting quantity (from 1 to ∼10,000 copies) (R2 = 0.992)...

Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in approximately 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its as...

Primary Hodgkin's lymphoma (HL) of the stomach is an extremely rare entity. Most cases of gastric involvement by HL are observed in the setting of disseminated disease. The nonspecific nature of the symptoms and endoscopic findings, which include a large malignant-looking ulcer and mass or wall thickening, together with the considerable histologica...

The pattern of adolescent/young adult Hodgkin lymphoma (YAHL) suggests causation by a relatively late infection with a common childhood virus, but no causal virus has been found. Susceptibility is heritable and linked to lower interleukin 12 (IL12) levels, which can also result from fewer fecal-oral microbial exposures early in life. We studied twi...

We report a mucinous borderline tumor arising from a mixed epithelial and stromal tumor of left kidney (MESTK). The patient was an 82-year-old woman who presented with gross hematuria and recurrent urinary tract infection for years. The patient had a cytoscopy with a retrograde pyelogram, which indicated a dilated left kidney with a central mass le...

Dedifferentiated liposarcoma (DDL), occurring in up to 10% of well differentiated liposarcoma cases, has similar histologic features to that of undifferentiated high-grade pleomorphic sarcoma (UHGPS); the former develops in a background of atypical lipomatous tumors/well differentiated liposarcoma, whereas the latter shows no specific line of diffe...

The evaluation and categorization of adrenocortical neoplasms remain among the most challenging areas in adrenal pathology. The Weiss system, first introduced 25 years ago, provides specific guidelines for differentiating adrenocortical adenoma from adrenocortical carcinoma and is considered the standard for determining malignancy in tumors of the...

Pathologists use various panels of immunohistochemical (IHC) stains to identify the site of tissue of origin for metastatic tumors, particularly poorly or undifferentiated cancers of unknown or uncertain origin. Although clinicians believe that immunostains contribute greatly to determining the probable primary site among 3 or more possibilities, o...