Elaine S Jaffe

National Institutes of Health | NIH · Laboratory of Pathology

Peripheral T-cell lymphomas (PTCL) have marked biologic and clinical heterogeneity, which confounds treatment decisions. Advances in circulating tumor DNA (ctDNA) assays employing next generation sequencing (NGS) has improved the detection of molecular relapse and driver mutations in diffuse large B-cell lymphoma, and highlight the potential utilit...

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma with an immunoblastic/large cell morphology and plasmacytic differentiation. The differential diagnosis with Burkitt lymphoma (BL), plasma cell myeloma (PCM) and some variants of diffuse large B-cell lymphoma (DLBCL) may be challenging due to the overlapping morphological, genetic and im...

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell malignancies with approximately one-third of cases designated as PTCL-not otherwise specified (PTCL-NOS). Using gene expression profiling (GEP), we have previously defined two major molecular subtypes of PTCL-NOS; PTCL-GATA3 and PTCL-TBX21 that have distinct biological diff...

Histiocytic sarcoma is a rare malignant neoplasm that may occur de novo or in the context of a previous hematologic malignancy or mediastinal germ cell tumor. Here, we performed whole exome sequencing and RNA-sequencing (RNA-Seq) on 21 archival cases of primary histiocytic sarcoma. We identified a high number of genetic alterations within the RAS/R...

Background: Patient-derived tumor xenografts (PDX) are powerful tools to study cancer biology, cancer genomics and developmental therapeutics. A common problem in the development of PDX models is proliferation of atypical lymphocytes at the implantation site, which often overtake or limit the growth of the original tumor. This atypical lymphocyte p...

Background: Patient-derived tumor xenografts (PDX) are powerful tools to study cancer biology, cancer genomics and developmental therapeutics. A common problem in the development of PDX models is proliferation of atypical lymphocytes at the implantation site, which often overtake or limit the growth of the original tumor. This atypical lymphocyte p...

Follicular lymphoma is the most common indolent B cell lymphoma, accounting for 20% of all non‐Hodgkin lymphomas. Transformation of follicular lymphoma to a more aggressive lymphoma is a well‐characterized phenomenon that occurs in 30% of cases at 10 years following diagnosis ². Follicular lymphoma most frequently transforms to diffuse large B cell...

Patients with classic hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more c...

Intravascular large B‐cell lymphoma (IVLBCL) is a rare, aggressive, extranodal large B‐cell lymphoma characterized by growth of tumor cells within the lumen of vessels, particularly capillaries. Programmed cell death‐ligand 1 (PD‐L1) is a cell surface glycoprotein that interacts with programmed death 1 (PD‐1) on the T‐cell surface, leading to modul...

Peripheral T-cell lymphoma (PTCL) is a group of complex clinicopathological entities, often associated with an aggressive clinical course. Angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) are the 2 most frequent categories, accounting for >50% of PTCLs. Gene expression profiling (GEP) defined molecular signature...

Primary effusion lymphoma (PEL) is an aggressive HIV-associated lymphoma with a relatively poor prognosis in the era of effective HIV therapy. Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent, and ∼80% of tumors are coinfected with Epstein-Barr virus (EBV). A better understanding of how KSHV-related immune dysregulation contributes to the n...

Burkitt-like lymphoma with 11q aberration is characterized by pathological features and gene expression profile resembling those of Burkitt lymphoma but lacks the MYC rearrangement and carries an 11q-arm aberration with proximal gains and telomeric losses. Whether this lymphoma is a distinct category or a particular variant of other recognized enti...

Primary cutaneous lymphomas are a heterogeneous group of T- and B-cell lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) consensus classification has served as a golden standard for the diag...

To evaluate the feasibility and clinical efficacy of the combination of alemtuzumab with dose-adjusted etoposide/cyclophosphamide/doxorubicin/vincristine/prednisone (DA-EPOCH) as upfront therapy for untreated aggressive T and NK cell lymphomas, a phase 1/2 trial was conducted. Thirty patients were treated with the study regimen, consisting of alemt...

The new provisional lymphoma category Burkitt-like lymphoma with 11q aberration recently described comprises cases similar to Burkitt lymphoma (BL) on morphological, immunophenotypic and gene expression level but lacking the IG-MYC translocation. They are characterized by a peculiar imbalance pattern on chromosome 11, but the landscape of mutations...

Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation resulting in overexpression of cyclin D1. However, a small subset of cyclin D1-negative MCL (cyclin D1– MCL) has been recognized, and approximately half of them harbor CCND2 translocations while the primary event in cyclin D1–/D2– MCL remains elusive. To identify oth...

Background: MYC gene rearrangement is present in approximately 10% of aggressive B-cell lymphomas, with half also harbouring a BCL2 gene rearrangement. Multiple retrospective studies of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone) have shown a worse outcome in patients with MYC rearrangement (a...

Classical Hodgkin lymphoma (CHL) is characterized by an inflammatory background and Hodgkin/Reed‐Sternberg (HRS) cells. The HRS cells exhibit abundant amphophilic cytoplasm, large nuclei, vesicular chromatin and prominent inclusion like nucleoli. Disorders other than CHL may contain HRS – like cells. The HRS cells express CD30 in 90‐96% and CD15 in...

The Hodgkin lymphomas are a family of unique lymphoma subtypes, in which the nature of the neoplastic cell was enigmatic for many years. Much of the mystery has been solved, with all forms now considered to be of B‐cell origin, in most cases of germinal centre derivation. Today we recognize Hodgkin lymphoma as an eponym that encompasses multiple en...

In this issue of Blood, Hellmuth et al provide new insights into the molecular genetic profile of duodenal-Type follicular lymphoma (FL), with comparisons to both typical advanced-stage nodal FL and a lesser number of cases of FL with limited stage disease.1. Copyright © 2011 by The American Society of Hematology; all rights reserved.

The "WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue" notes instances of Burkitt lymphoma/leukemia (BL) with IG-MYC-rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL we investigated 13 preBLL cases (including one cell line) of which 12 were...

Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the diagnosis relies on consensus of histopathology, clinical variables, and presentation, giving rise to diagnostic inaccuracy in routine practice. Previous studies have demonstrated that PMBCL can be dis...

Castleman Disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8) whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is...

Limited information is available regarding interstitial lung disease (ILD) in Erdheim–Chester disease (ECD), a rare multisystemic non-Langerhans cell histiocytosis. Sixty-two biopsy-confirmed ECD patients were divided into those with no ILD (19.5%), minimal ILD (32%), mild ILD (29%), and moderate/severe ILD (19.5%), based on computed tomography (CT...

Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) are pathologically and clinically heterogeneous. In many instances, similar features are shared by a spectrum of IA-LPDs in clinically diverse settings. The World Health Organization (WHO), however, classifies IA-LPDs by their immunodeficiency setting largely according to the parad...

B cell receptor (BCR) signaling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1. Gene expression profiling identified two major DLBCL subtypes, known as germinal center (GC) B cell-like (GCB) and activated B cell-like (ABC)2,3, wit...

Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively...

Intratumoral viral load at necropsy. VL, viral load, log10 copies per 104 cells. DLBCL, Diffuse large B cell lymphoma; BL, Burkitt lymphoma-like tumor; Sar, Fibrosarcoma; Ca, Carcinoma. (TIF)

Number of double and triple gammaherpesvirus infections in cases and controls. (TIF)

Primary antibodies and working conditions used in IHC. (DOCX)

Characterization of all tumours tested including sites, gross exam, histologic and in situ hybridization observations. (DOCX)

Characteristics of PCR assays developed to detect rhesus gammaherpesviruses. RRV, rhesus rhadinovirus; RLCV, rhesus lymphocryptovirus; RFHV, rhesus retroperitoneal fibromatosis virus; gB, glycoprotein B; pol, polymerase. All probes were labeled with FAM (reporter) and TAMRA (quencher). Highlighted bases (bold) indicate areas of sequence variability...

Immunohistochemistry and ISH staining on positive and negative control cell lines LCL 8664 and Ramos, respectively, demonstrating cross reactivity of EBV antibodies and specificity of probes for RLCV. (TIF)

Inter-Assay estimated copy variation for serial dilution of plasmid fragment, copy number from 101 to 106. The average copy number was calculated from ten PCR assays in triplicate. (DOCX)

Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract is a new provisional entity in the 2016 revision of the World Health Organization classification. The disease has an indolent course and progression to aggressive T-cell lymphoma has rarely been reported. We describe a case of a 37-year-old male with indolent T-...

Human herpes virus 6 (HHV-6) is a member of the β-herpesvirinae subfamily. Most people acquire HHV-6 primary infection early in life and reactivation may occur, most often in immunocompromised individuals, leading to various clinical manifestations. HHV-6 infected cells may be identified in lymph nodes in both reactive and neoplastic conditions. Ca...

Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immu...

Key Points A new molecular assay identifies conventional and leukemic nonnodal MCL with differing clinicobiological features. The integration of the novel assay with genetic alterations identifies subsets of MCL patients with different management and outcome.

Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-...

Background Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted...

BACKGROUND Diffuse large B cell lymphomas (DLBCL) are phenotypically and genetically heterogeneous. Gene expression profiling identified subgroups of DLBCL (activated B-cell [ABC], germinal center B-cell [GCB], and Unclassified) based on cell-of-origin that are associated with differential response to chemotherapy and targeted agents. We sought to...

The term Castleman disease encompasses several distinct lymphoproliferative disorders with different underlying disease pathogenesis, and clinical outcomes. It includes unicentric and multicentric diseases with limited versus significant systemic symptoms, respectively. Importantly, the histopathologic features encountered in the various forms of C...

Chimeric antigen receptor (CAR) T cell therapy using an anti-CD19 binding domain has been shown to be effective in adults with lymphoma and may represent an alternative treatment strategy in pediatric lymphoma, although experience in this younger age group is limited. Loss of the target antigen, as a mechanism of tumor escape following immunotherap...

Key Points Accurate GZL diagnosis remains challenging, with >60% of patients with presumed GZL having the diagnosis reclassified on consensus review. Treatment with DLBCL-based therapy appears most effective for GZL (including R-CHOP); however, new therapies are needed to improve outcomes.

Isolated MYC rearrangement without other recurrent genetic abnormalities is rare in B lymphoblastic leukemia/lymphoma (B-ALL/LBL), with most cases reported in pediatric patients. We report 3 adult cases with lymphoblasts showing a precursor B cell immunophenotype, and isolated MYC/IGH translocation. All 3 cases occurred in male patients with initia...

Brain biopsy in patients presenting with subacute encephalopathyis never straightforward and only undertaken when a ‘treatable condition’ is a realistic possibility. This 63 year old right handed, immunocompetent Caucasian woman presented with an 8 month history of rapidly progressive right-sided hearing impairment, a 4 month history of intermitten...

Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is associated with chronic inflammatory disorders. We present an indolent pancolonic MALT lymphoma occurring in a 39-year-old female with history of autoimmune hepatitis requiring liver transplant in 1997 and ulcerative colitis diagnosed in 2004. Random biopsies from a gros...

Benign and malignant proliferations of histiocytes and dendritic cells may be encountered in lymph nodes. Reactive histiocytic and dendritic cell infiltrates occur in response to diverse stimuli and in addition to causing lymphadenopathy, may be present unexpectedly in lymph nodes excised for other indications. This review summarizes the pathogenes...

Graphical Abstract Highlights d Exome sequencing in 1,001 DLBCL patients comprehensively identifies 150 driver genes d Unbiased CRISPR screen in DLBCL cell lines identifies essential oncogenes d Integrative analysis connects genomics, CRISPR hits, and clinical outcome d A genomic risk model of survival outperforms existing risk-assessment methods

The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-...

Mediastinal gray-zone lymphoma lies intermediate between nodular-sclerosis classic Hodgkin’s lymphoma and primary mediastinal B-cell lymphoma (a subtype of diffuse large B-cell lymphoma), with overlapping clinical, histologic, and molecular features. Genetic characteristics shared among these tumors include frequent 9p24.1 copy-number alterations,...

The immune system plays a major role in the elimination of tumors. CD8 T cell infiltration is known to be a good prognostic indicator. The development of therapies based on checkpoint inhibitor antibodies was an important breakthrough in increasing survival by limiting the exhaustion of cytotoxic cells and increasing tumor cell eradication. However...

Pediatric-type follicular lymphoma (PTFL) is a B-cell lymphoma with distinctive clinicopathological features. Recently, recurrent genetic alterations of potential importance for its pathogenesis that disrupt pathways associated with the germinal center reaction (TNFRSF14, IRF8), immune escape (TNFRSF14), and anti-apoptosis (MAP2K1) have been descri...

Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept phase Ib study of ibrutinib monotherapy followed...

Improved delineation of lymphoid malignancy biology has prompted refinement of the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors with a new framework introduced in 2016. This knowledge has provided valuable insights regarding management. Early clonal proliferations have been set apart given their limited p...

Significance Activating Janus kinase (JAK) mutations occur only in a minority of T-cell malignancies, which would appear to limit the clinical application of JAK inhibition for these diseases. Our study suggests that targeting JAK might be of value in treating diverse forms of anaplastic lymphoma kinase (ALK) ⁻ anaplastic large cell lymphoma (ALCL)...

Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker—the proliferation signature—using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that...

This review reflects the trajectory of my career in hematopathology, and my personal reflections on scientific advances in the field. During the course of more than 40 years, the approach to classification of hematological malignancies has evolved from descriptive approaches, based on either cytological or clinical features, to a modern approach, w...

Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molec...