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Non-Melanoma Skin Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Irene De Francesco, Sean Whittaker, Stephen L. Morris
PCFCL is derived from follicle center cells, with a follicular, follicular and diffuse, or diffuse growth pattern. The infiltrate consists of cleaved centrocyte-like cells with only a few large centroblasts. It must be differentiated from lymphomas with a diffuse growth pattern and monotonous proliferation, which are classified as PCLBCL-leg or other. Immunophenotype studies can help in the diagnosis. PCFCL consistently expresses Bcl6, but unlike nodal and secondary cutaneous follicular lymphomas, PCFCL rarely expresses Bcl2 and does not show the t(14:18) characteristically found in systemic follicular lymphomas.177
The lymphoreticular system and bone marrow
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Follicular lymphomas (FLs) are tumours derived from germinal centre (follicle centre) cells, and they at least partially retain a follicular architecture. FLs usually arise within lymph nodes, and are often found to be disseminated at presentation, with involvement of multiple nodes, spleen, and bone marrow. The cells are a mixture of small cleaved centrocytes and larger centroblasts, with the number of the latter determining the grade. Lower-grade tumours are indolent but seldom curable and will transform into a more aggressive form, diffuse large-cell lymphoma, in 25% of cases (see Case History 9.2). A proportion of grade 3 tumours is potentially curable by chemotherapy. The follicle centre cells in FL express the anti-apoptotic protein BCL2 as a result of the t(14;18) translocation, and this promotes cell proliferation (Figure 9.14).
The Lymphoid System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
When examining a lymphoid follicle, it is possible to clearly identify the light zone comprised of large, light-staining centrocytes and FDCs, the dark zone comprised of darkly stained centroblasts, and the surrounding mantle zone comprised of small, dark B-cells. The Ig variable genes of centroblasts diversify by somatic hypermutation, exit the cell cycle, and reexpress B-cell receptors as they become centrocytes located in the light zone. Centrocytes are then subject to selection based on the ability to bind antigens presented by FDC. Centrocytes with low-level affinity pass back into the dark zone and undergo apoptosis, whereas higher affinity cells survive in the germinal center and differentiate and proliferate into antibody-forming cells and memory B-cells. The apoptosis of lymphocytes that results in a starry sky appearance occurs most frequently in the dark zone of the follicle, but as demand increases for antibody production, greater cell turnover accompanied by tingible-bodied macrophages in the pale germinal center becomes apparent. B-cell maturation and differentiation result in the formation of early stage plasma cells, which translocate to the medullary cords where after further maturation produce and release antibodies.
Advances in therapeutic strategies for primary CNS B-cell lymphomas
Published in Expert Review of Hematology, 2022
Safaa Ramadan, Tommaso Radice, Ahmed Ismail, Stefano Fiori, Corrado Tarella
Diffuse large B-cell lymphomas (DLBCLs) represents 95% of PCNSL histologic subtypes, and the remaining 5% include other histological subtypes, such as Burkitt’s, low grade B-, or T-cell lymphomas [20]. Morphologically, PCNSL cells are in the form of centroblasts and have a uniform immunophenotype that overlaps the germinal center and activated B-cell subtypes. PCNSL cells typically express CD19, CD20, and CD79a, and significant expression of BCL6 has been reported in up to 80% of cases and BCL2 in up to 93% of cases [21,22]. PCNSL cells also strongly express IRF4/MUM1 in approximately 95% of cases. CD10 is documented in up to 20% of cases, whereas plasma cell markers CD38 and CD138 are usually negative. This CD10− BCL6+ IRF4/MUM1+ phenotype indicates the non-germinal center B-cell subtype and is associated with bad prognosis [23].
KMT2A-rearranged diffuse large B-cell lymphoma in a child: a case report and molecular characterization
Published in Pediatric Hematology and Oncology, 2021
Shota Kato, Yasuo Kubota, Masahiro Sekiguchi, Kentaro Watanabe, Aya Shinozaki-Ushiku, Junko Takita, Mitsuteru Hiwatari
A 19-month-old female with right facial nerve palsy was referred to The University of Tokyo Hospital. She had no personal or family history of cancer. Magnetic resonance imaging (MRI) revealed a tumor lesion that filled the right temporal bone (Figure 1A). Enhanced computed tomography showed bilateral renal involvement (Figure 1B). The tumor tissue in the right temporal bone obtained by biopsy was composed of middle- to large-sized centroblasts with a MIB-1 proliferation index of 80–90%. The immunohistochemical study revealed a mature B-cell phenotype in that the centroblasts were positive for CD10, CD 20, CD79a, and BCL2, and negative for CD3, CD5, terminal deoxynucleotidyl transferase, and Epstein-Barr virus-encoded small RNA in situ hybridization. BM samples aspirated from the bilateral ilia showed a normal karyotype and no morphological evidence of tumor invasion. Thus, the patient was diagnosed with DLBCL, which was compatible with the germinal center B-cell-like subtype (Figures 1C–F). Since tumor cells were detected in the cerebrospinal fluid, Murphy’s stage of the disease was stage IV.
Pushing the boundaries of in situ hybridisation for mRNA demonstration: demonstration of kappa and lambda light chain restriction in follicular lymphoma
Published in British Journal of Biomedical Science, 2019
A Warford, M Rahman, JA Hughes, G Gerrard, DA Ribeiro
As the precursor to protein, mRNA is present in all B-cells expressing kappa and lambda immunoglobulin. mRNA levels reflect the B-cell maturation. Accordingly, in naïve and memory cells of this lineage levels are very low compared with B-cells that are synthesising immunoglobulin in response to antigen challenge. Cells in the latter category include centrocytes and centroblasts that contain moderate amounts of mRNA and plasma cells that contain an abundance of mRNA. Unlike immunoglobulin protein, mRNA is never secreted and, accordingly, its demonstration should be free of non-specific background. This indeed has been shown to be so in tissue sections in which kappa and lambda light chain mRNA has been demonstrated using in situ hybridisation (ISH) [4,5]. A drawback of the use of ISH has been its lack of sensitivity in comparison with ICC due to the lower copy number and lability of mRNA in B-cell NHLs that are not synthesising immunoglobulin. Follicular lymphomas are representative of such a situation and while successful demonstration of mRNA light chain restriction has been reported [6], the method has not been routinely adopted. Potentially the branched DNA ISH (BDISH) method, that combines specificity via couplet oligonucleotide hybridisation and employs an ultra-sensitive detection procedure, could address this issue [7]. Accordingly, the purpose of this study was to establish if the BDISH method could demonstrate light chain restriction in follicular lymphoma and to compare the results with ICC.