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.
    Seminars in Cancer Biology 12/2013; 24. DOI:10.1016/j.semcancer.2013.12.001 · 9.33 Impact Factor
  • [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.
    06/2014; 7(2):57-70. DOI:10.1007/s12308-014-0202-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epstein-Barr virus (EBV) is known to play a key role in the development of several lymphoproliferative disorders (LPD), ranging from indolent lesions to highly aggressive lymphomas. Here, we describe an incidentally detected unique case of a localized EBV-positive large B cell LPD within a popliteal artery aneurysmal hematoma of a 91-year-old male. Histopathologic examination of an expanding right thigh mass demonstrated organizing hematoma with microscopic clusters of atypical large lymphoid cells with a non-germinal center B cell immunophenotype, a high proliferation rate by Ki-67 staining, and strong positivity for EBV-encoded RNA (EBER) by in situ hybridization. An 18-month follow-up revealed no evidence of disease progression. The presence of cytologically malignant EBV-positive large B cells supports a LPD, with a differential diagnosis that includes a spectrum of EBV-associated lesions, including diffuse large B cell lymphoma (DLBCL) of the elderly, DLBCL associated with chronic inflammation, as well as a variety of recently described indolent EBV-associated large B cell proliferations occurring in cardiac fibrin thrombi, atrial myxomas, and other unusual sites. This case is the first report of an indolent fibrin-associated EBV-positive LPD occurring in an aneurysmal hematoma of the extremity. This lesion may represent the indolent end of the spectrum of EBV-associated large B cell proliferations, and recognition of such lesions may prevent unnecessary aggressive treatment.
    09/2014; 7(3):139-143. DOI:10.1007/s12308-014-0213-4
Show more