Case Report: Phenotypic Switch in High-Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements: A Potential Mechanism of Therapeutic Resistance in Lymphoma?

Lineage switch between myeloid and lymphoid in acute leukemia is well established as a mechanism for leukemic cells to escape chemotherapy. Cross-lineage transformation is also recognized in some solid tumors on targeted therapy, such as adenocarcinomas of the lung and prostate that transforms to neuroendocrine carcinoma on targeted therapy. Now lineage plasticity is increasingly recognized in mature lymphomas, such as small B-cell lymphomas transforming to histiocytic/dendritic cell sarcoma. However, there is no report of aggressive mature B-cell lymphoma switching from one histologic category to another upon targeted therapy. We report here a case of high-grade B-cell lymphoma with MYC and BCL6 rearrangements relapsing as a high-grade plasmablastic neoplasm with MYC and BCL6 rearrangements after R-CHOP and R-EPOCH therapy. Being aware of this rare scenario will help improve our understanding of the underlying mechanisms of therapeutic resistance and progression of lymphoma.

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Vitamin D-Dependent Induction of Cathelicidin in Human Macrophages Results in Cytotoxicity Against High Grade B-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.4108.4108 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4108-4108

Author(s):

Heiko Bruns ◽

Maike Büttner ◽

Mario Fabri ◽

Dimitrios Mougiakakos ◽

Joerg Thomas Bittenbring ◽

...

Keyword(s):

Vitamin D ◽

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Grade ◽

M2 Macrophages ◽

Vitamin D Metabolism ◽

Tumoricidal Activity ◽

Underlying Mechanisms

Abstract Infiltration by macrophages represents a characteristic morphological hallmark in high grade lymphatic malignancies such as Burkitt’s lymphoma (BL). Although macrophages can in principle target neoplastic cells and mediate antibody-dependent cytotoxicity (ADCC), tumor associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. The underlying mechanisms responsible for this observation remain unclear. Here we demonstrate that inflammatory M1 macrophages kill proliferating high grade B-cell lymphoma cells by releasing the antimicrobial peptide cathelicidin in a vitamin D-dependent fashion. Moreover, we show that cathelicidin directly induces cell death by targeting mitochondria of BL-cells. In contrast, anti-inflammatory M2 macrophages and M2-like TAMs in BL exhibit an altered vitamin D metabolism resulting in a reduced production of cathelicidin and consequently in inability to lyse BL cells. However, treatment of M2 macrophages with the bioactive form of vitamin D, 1,25D, or a vitamin D receptor agonist effectively induces cathelicidin production and triggers tumoricidal activity against BL cells. Furthermore, rituximab-mediated cytotoxicity of M2 macrophages is cathelicidin dependent and vitamin D treatment of 25D deficient volunteers improves rituximab-mediated ADCC against BL cells. These data indicate that activation of the vitamin D signaling pathway may activate antitumor activity of TAMs and improve the efficacy of ADCC. Disclosures No relevant conflicts of interest to declare.

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Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL

Acta Haematologica Polonica ◽

10.2478/ahp-2019-0018 ◽

2019 ◽

Vol 50 (3) ◽

pp. 109-115

Author(s):

Beata Grygalewicz

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

World Health ◽

High Grade ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Health Organization ◽

Large B Cell

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.

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Prognostication of High-Grade Diffuse Large B-Cell Lymphoma and the Role of MYC, BCL2, and Phosphohistone H3

American Journal of Clinical Pathology ◽

10.1093/ajcp/144.suppl2.145 ◽

2015 ◽

Vol 144 (suppl 2) ◽

pp. A145-A145

Author(s):

Qian Dai ◽

Shuko Harada ◽

Deniz Peker

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Grade ◽

Large B Cell Lymphoma ◽

Phosphohistone H3 ◽

Large B Cell

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A Challenging Case of A Myeloid Sarcoma Misdiagnosed as High Grade B-Cell Lymphoma

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.212 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S97-S97

Author(s):

A Herrmann ◽

B Mai ◽

S Elzamly ◽

A Wahed ◽

A Nguyen ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Myeloid Sarcoma ◽

Proliferation Index ◽

High Grade ◽

Cell Markers ◽

Thoracolumbar Region ◽

The Right

Abstract Introduction/Objective A 46-year-old female presented with severe back pain associated with progressive bilateral lower extremity weakness and paresthesia, urinary retention, and constipation. Computed tomography revealed a retroperitoneal mass encasing the right psoas muscle, obstructing the right kidney, and extending to the thoracolumbar region resulting in severe spinal compression. An epidural tumor resection was subsequently performed at an outside hospital. Methods Histological sections showed sheets of blastoid neoplastic cells with intermediate to large nuclei, irregular membranes, fine chromatin, and prominent nucleoli. Immunohistochemical stains showed that these cells were positive for CD43, CD79a (weak, focal), BCL2, C-MYC, and PAX5 (weak, focal) and negative for CD10, CD20, CD30, ALK1, BCL6, MUM1, and Tdt. The Ki-67 proliferation index was 75-80%. With this immunophenotype, this patient was diagnosed with a high grade B-cell lymphoma and transferred to our institution for further work-up. On review of the slides, further immunohistochemical testing was requested which revealed positivity for CD117 and myeloperoxidase (MPO). Results The overall morphological and immunophenotypical features are most compatible with myeloid sarcoma (MS) with aberrant expression of B-cell markers and this patient’s diagnosis was amended. Interestingly, the patient’s bone marrow examination only showed 2% myeloblasts with left shifted granulocytosis and concurrent fluorescence in situ hybridization (FISH) studies were negative. Conclusion A literature review showed that 40-50% of MS are misdiagnosed as lymphoma. MS can frequently stain with B-cell or T-cell markers, as seen in this case, which makes it challenging for an accurate diagnosis and sub- classification. In addition, our case is interesting in that there was only extramedullary presentation without bone marrow involvement. Typically, MS develops after the diagnosis of acute myeloid leukemia (AML) with an incidence of 3–5% after AML. It can also manifest de novo in healthy patients, who then go on to develop AML months to years later. Therefore, this patient will require close follow-up.

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