Lymphocytic lymphoma/B-chronic lymphocytic leukaemia – An immunohistopathological study of peripheral B lymphocyte neoplasia

Swerdlow, Steven H.; Murray, Lesley J.; Habeshaw, J. A.; Stansfeld, A. G.

doi:10.1038/bjc.1984.225

Cited by 36 publications

(32 citation statements)

References 49 publications

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“…Since then, studies have been conducted in an attempt to correlate histological characteristics of lymph nodes with prognosis but most were flawed for a number of reasons, including lack of immunophenotypic studies, 8,9,20 limited numbers of subjects and short follow-up. 12,18,19 In our series, proliferative centers were found in 88% of the biopsies and their size and proliferation activity were important predictors of duration of survival from the time of biopsy. Thus, patients with either proliferation centers broader than 20x hpf or an increased proliferation rate within the proliferation centers as assessed by a mitotic count greater than 2.4 per proliferation centers and/or Ki-67 index greater than 40% per proliferation centers, had a particularly poor outcome.…”

Section: Discussionmentioning

confidence: 93%

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Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

Giné

Martı́nez²,

Villamor³

et al. 2010

Haematologica

163

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BackgroundThe concept of "accelerated" chronic lymphocytic leukemia is frequently used by both pathologists and clinicians. However, neither histological criteria to define this form of chronic lymphocytic leukemia nor its clinical correlates and prognostic impact have been formally defined in large series of patients. Design and MethodsTissue biopsies from 100 patients with chronic lymphocytic leukemia were analyzed for the size of proliferation centers and their proliferation rate as assessed by mitosis count and Ki-67 immunostaining. Histological patterns were correlated with main clinico-biological features and outcome. ResultsA suspicion of disease transformation was the main reason for carrying out tissue biopsy, which was performed at a median time of 14 months (range, 0 to 204 months) after the diagnosis of chronic lymphocytic leukemia. The biopsy showed histological transformation to diffuse large B-cell lymphoma in 22 cases. In the remaining 78 patients, the presence of expanded proliferation centers (broader than a 20x field) and high proliferation rate (either >2.4 mitoses/proliferation center or Ki-67 >40%/proliferation center) predicted a poor outcome and were selected to define a highly proliferative group. Thus, 23 patients with either expanded proliferation centers or high proliferation rate were considered as having "accelerated" chronic lymphocytic leukemia. These patients displayed particular features, including higher serum lactate dehydrogenase levels and more frequently elevated ZAP-70 than "non-accelerated" cases. The median survival from biopsy of patients with "non-accelerated" chronic lymphocytic leukemia, "accelerated" chronic lymphocytic leukemia and transformation to diffuse large Bcell leukemia was 76, 34, and 4.3 months, respectively (P<0.001). ConclusionsThe presence of expanded and/or highly active proliferation centers identifies a group of patients with "accelerated" chronic lymphocytic leukemia characterized by an aggressive clinical behavior.Key words: accelerated chronic lymphocytic leukemia, lymph node biopsy, ZAP-70. Haematologica 2010;95(9):1526-1533. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Giné E, MartinezExpanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

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Section: Discussionmentioning

confidence: 93%

“…[8][9][10]12,[18][19][20] The main reason for this is that tissue biopsy is not a standard procedure in the diagnostic work-up of patients with CLL. The commonest reason for performing a biopsy is to rule out histological transformation.…”

Section: -18mentioning

confidence: 99%

Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

Giné

Martı́nez²,

Villamor³

et al. 2010

Haematologica

163

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“…Paired LN and PB-CLL cells plus normal B cells were mixed with purified CD3 1 T cells from a healthy donor in an MLR, and the proliferation and activation status of the T cells was assessed by measuring 3 H thymidine incorporation and the expression of Ki67, CD69, and HLA-DR by flow cytometry. LN-CLL cells induced greater activation of both CD4 1 and CD8 1 T cells as measured by their higher expression of Ki67, CD69, and HLA-DR when compared with PB-CLL cells, and this was equivalent to that induced by normal B cells (Figure 2A and supplemental Figure 2A).…”

Section: Enhanced Capacity Of Ln-derived Cll Cells To Activate T Cellsmentioning

confidence: 99%

“…However, in vivo studies of tumor kinetics, using deuterated water, revealed higher than expected tumor cell turnover, with a birth rate of up to 2% per day. 2 The proliferative component of CLL appears to be confined to pseudofollicles or proliferation centers in secondary lymphoid tissues, 3,4 where interactions with non-neoplastic T cells 5,6 and follicular dendritic cells 7 take place, and promote tumor cell growth. 4 In contrast, very few CLL cells in the peripheral circulation show features of proliferation and those that do are believed to represent recent emigrants from the LN.…”

Section: Introductionmentioning

confidence: 99%

Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration

Pasikowska

Walsby

Apollonio

et al. 2016

Blood

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Key Points• LN-derived CLL cells have increased capacity for T-cell activation and superior immune synapse formation compared with those from PB.• Enhanced CLL cell immunologic function is also linked to PB circulating cells with the propensity to migrate.Several lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here, we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype, and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4 dim CD5 bright phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR). In addition, LN-CLL cells have higher expression of a4b1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergo transendothelial migration (TEM) and enter the proliferation centers of the LNs. Using an in vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4 dim CD5 bright with higher CD49d, CD80, CD86, and HLA-DR compared with those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49d hi CLL cells showed an enhanced capacity to activate T cells compared with CD49d lo subpopulations from the same patient. Thus, although PB-CLL cells have a reduced capacity to form immune synapses and activate CD4 1 T cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunologic function is not only modulated by microenvironmental interactions but is also a feature of a subpopulation of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T cells. (Blood. 2016;128(4):563-573)

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“…14 Although the size of PCs and the amount of paraimmunoblasts in lymph node sections did not show a correlation with clinical course, 15,16 the presence of more extensive PCs in follow-up biopsies compared with diagnostic biopsies has been reported. 17 Interestingly, a recent study suggested that an association may exist between the expanded and highly active PCs and an aggressive variant of CLL. 18 Recently, techniques were developed that allow for the application of fluorescence in situ hybridization (FISH) on paraffin-embedded fixed tissues.…”

Section: Introductionmentioning

confidence: 99%

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

et al. 2011

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Lymphocytic lymphoma/B-chronic lymphocytic leukaemia – An immunohistopathological study of peripheral B lymphocyte neoplasia

Cited by 36 publications

References 49 publications

Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

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