Chronic lymphocytic leukemia: the pathologist's view of lymph node microenvironment
Section snippets
Histopathology and immunophenotype of CLL
The architecture of CLL lymph nodes is usually effaced and exhibits small, if any, residual germinal centers; more rarely, CLL infiltration has an interfollicular pattern, where germinal centers are more evident.2 The predominant diffuse population of small cells with clumped chromatin, regular nuclei, and scant cytoplasm is spaced out by vaguely nodular, clear-looking structures called proliferation centers (PC). The composition of PC encompasses a wider spectrum of neoplastic cells, including
Properties of CLL microenvironment
When considering the relationship between CLL cells and their microenvironment, we should take into account two main concepts. First, BM and secondary lymphoid organs have a different and yet imperfectly defined cellular and molecular milieu.1 Second, the dialog between microenvironment and neoplastic B cells is not necessarily unidirectional; rather, signals generated by each counterpart imply a feedback response generated by the target cell. Major players of microenvironmental stimuli are
Pathology of CLL–microenvironment interactions
The above-mentioned mechanisms are derived from in vitro models using flow cytometry and molecular methods, which brings up the question of how the physical interaction among CLL cells and microenvironmental players can be visualized. Available data are scant, especially considering the mysterious nature of PC.
Focusing on neoplastic B cells, immunohistochemistry has revealed that CLL cells are immunoreactive for BAFF-receptor, namely BAFF3 or BR-3. Although these studies have been performed in
Microenvironmental features of proliferation centers
PC are easily recognized in tissues involved by CLL, especially in lymph nodes; however, these structures remain largely unknown and apparently do not have a physiological counterpart in nonneoplastic lymphoid tissues.
PC are obviously characterized by increased proliferation rate (Figure 2) and express CD5, bcl-2, CD71, HLA-DC, and HLA-DR, whereas IgD, p27, and CD9 are down-regulated. Compared with the surrounding “classical” small CLL cells, PC preferentially or more strongly express MUM1/IRF4+
Conclusions
Despite significant advances in the understanding of CLL pathogenesis, studies have clarified the reciprocal relationships between neoplastic B cells and microenvironmental components. These issues are even more important when we analyze the tissues involved. The lymph node environment and especially the origin, nature, and properties of PC must be extensively studied because this anatomical structure represents the actual site of active replication and the ensuing acquisition of new genetic
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Chronic lymphocytic leukaemia
2016, Critical Reviews in Oncology/HematologyCitation Excerpt :Chronic lymphocytic leukaemia diagnosis does not require lymph node biopsy nor bone marrow aspirate/biopsy, since a typical immunophenotype performed on the peripheral blood is sufficient for a conclusive diagnosis. If lymph node biopsy is performed for clinical reasons (SLL cases, differential diagnosis), nodal involvement by CLL/SLL shows a pseudofollicular pattern where regularly-spaced pale areas (called “proliferation centres”), composed by larger cells, are divided by a background of smaller and darker cells (Ponzoni et al., 2011). Bone marrow infiltration may be interstitial, nodular and/or diffuse, and in most cases the lymphoid infiltrate represents >30% of the cellularity (Hallek et al., 2008).
The chronic lymphocytic leukemia microenvironment: Beyond the B-cell receptor
2016, Best Practice and Research: Clinical HaematologyCitation Excerpt :The common observation that CLL cells accumulate in vivo, but undergo spontaneous apoptosis in vitro, even in conditions that support the growth of other human B-cell lines [5]. The formation of “pseudofollicles” (also known as proliferation centers) in the secondary lymphoid organs, in which CLL are more likely express KI-67 or have paraimmunoblast or prolymphocyte morphology, compared to the quiescent circulating cell population [6]. These pseudofollicles may account for a turnover of 1%–2% of the entire clone [7].
Extracellular nicotinamide phosphoribosyltransferase (NAMPT) promotes M2 macrophage polarization in chronic lymphocytic leukemia
2015, BloodCitation Excerpt :Chronic lymphocytic leukemia (CLL) is a disease of mature B cells, which rely on the host environment for progression.5-7 Tumor-host interactions occur predominantly in protected niches in the lymph nodes (LNs) and in the bone marrow, known as proliferation centers.8,9 Within these areas, CLL cells are in contact with a population of CD68+ elements, resembling tumor-associated macrophages.10-13
Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells
2014, BloodCitation Excerpt :CLL cells cycle between the peripheral blood and lymphoid compartments. Activating signals from the lymphoid microenvironment promote the proliferation, survival, and chemoresistance of the malignant cells.34,35 In this study, we found an opposing contribution of functional RhoA and Tiam1/Rac1 to motility of resting CLL cells and microenvironment-induced survival/proliferation, respectively (Figure 5B).