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B-lymphoproliferative disorders: a proposed unified pathogenetic pathway.

The clinical features of lymphoproliferative diseases associated with paraproteinemia are briefly reviewed and correlated with current immunologic concepts in an effort to clarify the pathophysiology of B-lymphocyte disorders. B-lymphocyte maturation proceeds in a predictable manner from the Pre-B cell to the formation of idiotype specific plasma cells and memory B-lymphocytes. The immunoglobulin isotype produced by the mature plasma cell is determined by a site specific process of gene switching which proceeds from mu to alpha production. Lymphoproliferative diseases are the result of disorde

Mouse red-cell rosettes in B-lymphoproliferative disorders.

A high proportion of peripheral-blood lymphocytes formed spontaneous rosettes with mouse red cells in 22 out of 23 cases of chronic lymphocytic leukaemia (CLL); the proportion was significantly higher than in 19 cases of other B-lymphoproliferative disorders (non-CLL group) and in 19 normal controls. Intermediate findings were obtained in 10 cases of "hairy" cell leukaemia. Blast cells from various types of acute leukaemia did not bind mouse red cells. Pre-treatment of the lymphocytes with neuraminidase led to a significant increase in the proportion of rosettes in CLL only. This test may prov…

Chromosomes and transformation of lymphocytes in lymphoproliferative disorders.

In chronic lymphocytic leukaemia the majority of circulating lymphocytes which responded to phytohaemagglutinin in vitro were found to have normal karyotypes. A minor population of cells in patients treated with chemotherapy had an increased number of chromosomal rearrangements as compared with cells from normal controls and untreated patients with chronic lymphocytic leukaemia. Probably bonemarrow and lymph-node cells also had a normal karyotype.In the other lymphoproliferative disorders the peripheral blood lymphocytes had either normal karyotypes or chromosomal abnormalities attributable to…

[T-cell lymphoproliferative disorders: Epidemiology, pathophysiology, and diagnosis].

Mature T-cell lymphoproliferative disorders are rare and aggressive hematologic malignancies characterized by marked clinical and biological heterogeneity. Their incidence is rising worldwide, with significant geographic disparities, particularly between Western countries and Asia. Several environmental, occupational, and infectious risk factors have been suggested, although no causal link has been firmly established. Diagnosis is often delayed due to nonspecific initial presentations and requires close collaboration among hematologists, internists, pathologists, and other specialists. The 202…

Clinicopathologic characteristics of lymphoproliferative disorders involving the kidney.

OBJECTIVE: Lymphoproliferative disorders can involve the kidney, which is associated with a worse prognosis. The objective of this study was to review the clinical and histologic characteristics of patients with lymphoproliferative disorders involving the kidneys. METHODS: Cases with lymphoproliferative disorders showing renal involvement were retrieved from the institutional pathology database for the past 20 years. Data regarding patient demographics, clinical presentations, lymphoma subtypes, history of lymphoma, treatments received, chemotherapy regimens, and patient outcomes were extract…

[Diagnosis and management of EBV-positive lymphoproliferative disorders].

Epstein-Barr virus (EBV) has the ability to immortalize not only B cells but also T and natural killer (NK) cells. The virus may also contribute to the onset of EBV-positive lymphoproliferative disorders (EBV-LPDs) by inducing the introduction of gene mutations. It is known that B cell EBV-LPDs (B-EBV-LPDs) develop with preexisting immunodeficiency, but the onset mechanism of T cell and NK cell EBV-LPDs (T-EBV-LPDs and NK-EBV-LPDs), also known as chronic active EBV disease and associated diseases, is unclear. The diagnosis of both EBV-LPDs requires the quantitative examination of EBV-DNA in th…

Primary cutaneous CD30+ lymphoproliferative disorders with DUSP22 translocation.

Primary cutaneous CD30+ lymphoproliferative disorders (LPD) encompass a broad category of clonal T cell proliferations with varied clinical presentations. Classically, lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (ALCL) have been recognized as distinct clinicopathological entities according to their differing clinical features. Recently, a subset of LyP and both cutaneous and systemic ALCL have been shown to carry a DUSP22 translocation [1-3], a defining molecular feature for the novel entity "LyP with DUSP22t" [1]. In cutaneous biopsies, both primary cutan…

Liquid Biopsy in Cancer: Focus on Lymphoproliferative Disorders.

Within the context of precision medicine, the scientific community is giving particular attention to early diagnosis and intervention, guided by non-invasive methodologies. Liquid biopsy (LBx) is a recent laboratory approach consisting of a non-invasive blood draw, which allows the detection of information about potential prognostic factors, or markers to be used for diagnostic purposes; it might also allow the clinician to establish a treatment regimen and predict a patient's response. Since the discovery of circulating tumor cells (CTCs) in the nineteenth century, the possibility of integrat

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… Liquid Biopsy in Lymphoproliferative Diseases Acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), lymphomas, and plasma cells dyscrasias, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM) [ 118 ] belong to the group of lymphoproliferative disorders. …

Genomic Analysis of Cutaneous CD30-Positive Lymphoproliferative Disorders.

Primary cutaneous CD30+ T-cell lymphoproliferative disorders are the second most common cutaneous lymphomas. According to the World Health Organization, CD30+ T-cell lymphoproliferative disorders include primary cutaneous anaplastic large cell lymphoma (C-ALCL) and lymphomatoid papulosis (LyP) as well as borderline lesions. C-ALCL and LyP are thought to represent two ends of a spectrum of diseases that have different clinical presentations, clinical courses, and prognoses in their classic forms but share the same histology of medium to large CD30+ atypical lymphoid cell infiltrates. Because th…

CD30 expression and survival in posttransplant lymphoproliferative disorders.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of transplantation. For refractory and relapsed PTLD new therapies are needed, such as the antibody-drug conjugate brentuximab vedotin that targets CD30. There is limited knowledge of CD30 expression in various subtypes of PTLD and its correlation to clinicopathological features. Therefore, we studied the expression of CD30 in PTLD following solid organ transplantation and correlated CD30 expression to PTLD subtype, Epstein-Barr virus (EBV)-status, intratumoral regulatory T-cells (Tregs)

Primary Cutaneous CD30+ Lymphoproliferative Disorders: a Comprehensive Review.

PURPOSE OF REVIEW: Primary cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPDs) are the second most common cutaneous lymphomas after mycosis fungoides and Sezary syndrome. They include primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP), and borderline lesions. The purpose of this literature review is to consolidate the available evidence on the primary cutaneous CD30+ LPD in order to define the tools for correct diagnosis and appropriate treatment. RECENT FINDINGS: The current body of knowledge regarding the clinical features, histopathologic …

Improving CD20 antibody therapy: obinutuzumab in lymphoproliferative disorders.

Soon after the anti-CD20 monoclonal antibody rituximab began to change the management of indolent and aggressive B cell lymphomas, development of alternative antibodies - including chemoimmunoconjugates - was undertaken. Among humanized and fully human CD20 antibodies, obinutuzumab has emerged as one antibody that seems to have lived up to the promise of improved efficacy based on in vitro and preclinical experiments. The data available, thus, far establish obinutuzumab's preferred role as the anti-CD20 antibody of choice in chronic lymphocytic leukemia and untreated follicular lymphoma, as we

Myeloproliferative and lymphoproliferative disorders: State of the art.

Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal disorders complicated mainly by vascular events and transformation to myelofibrosis (for PV and ET) or leukemia. Although secondary malignancies, in particular, lymphoproliferative disorders (LPNs), are rare, they occur at a higher frequency than found in the general population, and there has been recent scientific discussion regarding a hypothetical relationship between treatment with JAK inhibitors in MPN and the risk of development of LPN. This h…

Clinicopathological features of clinical methotrexate-related lymphoproliferative disorders.

Methotrexate (MTX) is one of the potent drugs for autoimmune diseases (ADs), especially for rheumatoid arthritis. Recent studies suggest that MTX should be immediately withdrawn when patients with AD develop lymphoproliferative disorder (LPD). However, biopsy cannot be performed for diagnosis because LPD regresses quickly after MTX withdrawal, thus making clinical MTX-LPD (c-MTX-LPD) challenging to diagnose. In this study, among the 28 patients with c-MTX-LPD, seven developed a proven LPD (p-LPD) after suspicious LPD (s-LPD) regression, six of which were Hodgkin lymphoma. Four of seven patient

Ocular Inflammatory Disorders in Autoimmune Lymphoproliferative Syndrome (ALPS).

PURPOSE: To describe inflammatory ocular findings in patients with autoimmune lymphoproliferative syndrome (ALPS). METHODS: A retrospective review of medical records for ALPS patients seen at the National Eye Institute between 2003 and 2013. RESULTS: A total of 29 ALPS patients previously referred for ocular or visual symptoms or with a history of prolonged corticosteroid use, were identified. Mean age was 20 years (range: 4-66 years). The majority were male (n = 21, 72.4%) and Caucasian (n = 24, 82.8%). Ten (34.5%) had abnormal ocular findings, the most common of which was an ocular inflamm

Hepatitis C virus-related lymphoproliferative disorders: an overview.

Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among human cancer viruses. HCV-associated manifestations also include porphyria cutanea tarda, lichen planus…

T-cell and NK-cell posttransplantation lymphoproliferative disorders.

Posttransplantation lymphoproliferative disorders (PTLDs) of T-cell or natural killer (NK)-cell origin are an uncommon heterogeneous group of lymphoid proliferations that fulfill the criteria for one of the T- or NK-cell lymphomas/leukemias. This report summarizes 130 T/NK-cell PTLDs reported in the literature or presented at the Society for Hematopathology/European Association for Haematopathology Workshop on T/NK-cell malignancies. The T/NK-cell PTLDs occur at a median of 66 months following transplantation and are usually extranodal. The most common types reported are peripheral T-cell lymp…

Primary cutaneous lymphoproliferative disorders with dual lineage rearrangement.

We present a series of 15 cases of cutaneous lymphoma and pseudolymphoma with dual lineage rearrangement identified among approximately 1200 cases of cutaneous lymphoproliferative disorders assessed in our 4 institutions during the last 8 years in which the results of both T-cell receptor and immunoglobulin heavy chain rearrangement investigations were available. On the basis of the clinicopathologic information, the cases were retrospectively subdivided into 2 categories: (1) cases with definite features of cutaneous lymphoma or pseudolymphoma (n = 11) and (2) cases with unclassifiable diseas…

Chemokine receptor expression in B-cell lymphoproliferative disorders.

Chemokine receptors are expressed by many cells, including lymphoid cells, and function to mediate cell trafficking and localization. Normal B-cells have been reported to express CXCR3, CXCR4, CXCR5, CCR6 and CCR7, however changes in chemokine receptor expression during B-cell development and in B-cell lymphoproliferative disorders (BCLPDs) are incompletely understood, and could provide important information about normal B-cell development and about behavior of neoplastic B-cells. The objective was to perform a systematic study of chemokine receptor expression on B cells from normal subjects a…