Microscopic Diffuse Large B-Cell Lymphoma (DLBCL) Occurring in Pseudocysts Do These Tumors Belong to the Category of DLBCL Associated With Chronic Inflammation?

Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0588, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 03/2012; 36(7):1074-80. DOI: 10.1097/PAS.0b013e3182515fb5
Source: PubMed


We report 2 cases of localized, microscopic diffuse large B-cell lymphoma (DLBCL) that were detected incidentally within pseudocysts. In case 1, the neoplasm was identified within a 26-cm, 860-g adrenal gland pseudocyst. In case 2, the neoplasm was detected within a 9-cm, 90-g paratesticular pseudocyst. In both cases, the neoplastic cells were large, had a nongerminal center B-cell immunophenotype, and were positive for Epstein-Barr virus (EBV)-encoded RNA detected by in situ hybridization. The most appropriate classification of these tumors using current World Health Organization classification is uncertain. The best fit seems to be DLBCL associated with chronic inflammation (DLBCL-CI), defined as DLBCL arising in the context of long-standing chronic inflammation and associated with EBV infection, with the prototype for this category being pyothorax-associated lymphoma. This term has been used by others in the literature for tumors similar to the cases reported here. However, in the 2 cases we report chronic inflammation was not a prominent feature, and the inflammatory cells that were present showed little relationship to the lymphoma cells. The findings in these cases have led us to question the role of chronic inflammation in pathogenesis. Perhaps the closed space of the pseudocyst, by preventing a cytolytic response to EBV-infected cells, results in local immunodeficiency that may be most important for pathogenesis. We also have concerns about using the term DLBCL-CI for these tumors. Perhaps the cases we report and the few other similar cases reported previously deserve their own category in a future version of the World Health Organization classification.

3 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: For decades, it has been known that patients with certain autoimmune and inflammatory disorders, such as rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS), have an increased risk of developing malignant lymphoma. Although the clinico-biological reasons for this association remain largely unknown, our knowledge has improved and new insights have been obtained. First, the direct link between autoimmunity and lymphomagenesis has been strengthened by large epidemiological studies showing a consistent risk increase of lymphoma associated with certain autoimmune/inflammatory conditions in independent cohorts from different countries. Second, a number of local and systemic disease-related risk factors in these diseases have been repeatedly linked to lymphoma development, with the prime examples being disease severity and the degree of inflammatory activity. Considering the key role of B- and T-cell activation in the pathogenesis of both autoimmunity and lymphoma, it is perhaps not surprising that longstanding chronic inflammation and/or antigen stimulation have emerged as major predisposing factors of lymphoma in patients with active autoimmune disease. Finally, increasing evidence suggests that lymphomas associated with autoimmunity constitute a different spectrum of entities compared to lymphomas arising in patients without any known autoimmune or inflammatory conditions, pointing to a different pathobiology. In this review, we summarize the recent literature that supports a direct or indirect link between immune-mediated disease and lymphoma and describe the characteristics of lymphomas developing in the different diseases. We also discuss molecular, genetic and microenvironmental factors that may come into play in the pathobiology of these disorders.
    No preview · Article · Dec 2013 · Seminars in Cancer Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extranodal lymphomas are a diverse group of low and high grade neoplasms of B-, T-, and NK-cell lineage, each with characteristic sites of origin, morphology, immunophenotype, genetic features, patterns of spread, and prognosis. The diversity is sometimes seen even within a single histologic type of lymphoma. This phenomenon is especially striking in the category of diffuse large B-cell lymphoma (DLBCL). DLBCLs as classified in the WHO Classification are clinically and pathologically heterogeneous (Swerdlow et al. 2008; Stein et al. 2008). Since the publication of the most recent edition of the WHO Classification of tumours of haematopoietic and lymphoid tissues (Swerdlow et al. 2008), a number of advances in the understanding of these lymphomas have been made. This review provides an overview of extranodal DLBCLs and describes recent updates regarding these lymphomas.
    No preview · Article · Jun 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: The human gammaherpesviruses, Epstein-Barr virus (EBV, or HHV4) and Kaposi sarcoma-associated herpesvirus (KSHV, or HHV8), are associated with lymphoma. EBV was first discovered in the 1960s in association with Burkitt lymphomas arising in sub-Saharan Africa, while the discovery of KSHV in 1994 was associated with Kaposi sarcoma tumors and driven by the AIDS epidemic. While EBV infection is ubiquitous, KSHV is restricted to certain populations. EBV-associated lymphoproliferative diseases are likewise more common than KSHV-associated lymphoproliferative disease. These two herpesviruses nonetheless share many characteristics. Particularly relevant to lymphoma and lymphoproliferative disease is the ability of these two viruses to infect and establish a reservoir of infection in lymphocytes. Whereas some herpesviruses establish latency in nondividing terminally differentiated cells such as neurons, the gammaherpesviruses establish latency in lymphocytes. The gammaherpesviruses have evolved mechanisms for persisting as extrachromosomal genomes in dividing cells. These cells may be driven to proliferate or be protected from cell death pathways by viral gene expression. The result may be a self-limited lymphoproliferation that establishes or maintains a reservoir of latently infected cells or, under certain circumstances, a malignant lymphoproliferation. © 2014 Springer Science+Business Media New York. All rights are reserved.
    No preview · Chapter · Jun 2014
Show more