Underlying B-cell Lymphoma Research Articles

Secundaire hemofagocytaire lymfohistiocytose bij diffuus grootcellig B-lymfoom: een casus

Secondary hemophagocytic lymphohistiocytosis in diffuse large-cell B lymphoma: a case-report Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare, life-threatening and often misunderstood condition characterized by uncontrolled immune activation. Patients typically present with a pentad of symptoms including fever, hepatosplenomegaly, cytopenias affecting at least 2 of 3 cell lines, and elevated transaminase and ferritin levels. Familial hemophagocytic lymphohistiocytosis (FHL), the primary form, mainly occurs in pediatric age. The underlying pathogenesis is associated with genetic defects affecting cellular immunity (CD8+ T-lymphocytes and natural killer cells). The secondary forms (sHLH) mainly occur in adulthood and are linked to underlying processes such as autoimmune diseases, malignancies or infections. Recent revisions of the diagnostic criteria, including the H-score, offer valuable guidance for clinical decision-making. Early detection is crucial, followed by a prompt initiation of immunosuppressive therapies, such as corticosteroids, methotrexate, etoposide or eventually a hematopoietic stem cell transplantation (HSCT). This case-report illustrates a 79-year-old woman with sHLH secondary to an underlying B-cell lymphoma, underscoring the significance of recognition, diagnosis and treatment.

S2614 An Unconventional Presentation of Hemophagocytic Lymphohistiocytosis

Introduction: Hemophagocytic Lymphohistiocytosis (HLH) characterized as a cytokine storm secondary to a dysregulated immune state predominantly affects the pediatric population but, reports of adult cases are increasing. The cytokine storm mediated by natural killer cells, macrophages and cytotoxic lymphocytes can be triggered by a genetic variation, infection, malignancy, or rheumatologic disease. This case discusses an unconventional presentation of HLH. Case Description/Methods: A 61 year-old male with a past medical history of coronary artery disease, aortic stenosis, type 2 diabetes mellitus and chronic hepatitis with cirrhosis (of unknown etiology from prior workup) presented with lethargy and fevers. Physical exam was significant for jaundice and tender hepatosplenomegaly. Bloodwork showed: lymphopenia, neutropenia, direct hyperbilirubinemia, and transaminitis. Right upper quadrant ultrasound showed a diffusely echogenic nodular liver with gallbladder dilation in the absence of biliary ductal dilation. Patient was empirically treated for ascending cholangitis with broad spectrum antibiotics and was later found to have E.coli bacteremia. Given patients septic state he underwent percutaneous cholecystostomy tube placement without complication. A complete infectious, hematologic, and hepatologic workup found negative/normal: CMV, EBV, TB, HIV, COVID-19, parvovirus B19, viral hepatitis, DAT, ANA, RF, ANCA, AMA, ASMA, ceruloplasmin, alpha-1 antitrypsin, and C282Y/S/6/5/C. Fibrinogen, ferritin, D-dimer, triglycerides, CXCL-9, and CD-25 were found to be abnormal. Patient's former records were reviewed and showed: cirrhosis with lymphocytic infiltrate on liver biopsy, a normal endoscopy, and an inconclusive bone marrow biopsy only showing clusters of histiocytes. The patient met criteria for HLH and was started on dexamethasone and etoposide. The patients condition continued to worsen and he was transferred to a tertiary care center where he was diagnosed with T-cell histiocyterich diffuse large B-cell lymphoma on repeated biopsy with HLH. Discussion: In patients with high-grade fevers of unknown etiology and multi-organ failure, HLH should be on the differential despite the rarity of adult cases. This case represents an unconventional presentation of HLH in the setting of a confounding bacteremia from ascending cholangitis and underlying B-cell Lymphoma.

LETTER TO THE EDITOR Haemophagocytosis in a Patient with Diffuse Large B Cell Lymphoma

We report a case of a bone marrow biopsy specimen of a patient with history of weakness and bone pains since approximately three months. Past history was significant for blood and blood product transfusion. Examination findings revealed pallor with bilateral cervical and axillarylymphadenopathy. He had left sided facial swelling. Biopsy of facial mass was consistent with Diffuse Large B Cell Non-Hodgkin’s Lymphoma. He was advised for bone marrow examination as part of staging. Complete blood counts performed with bone marrow showed Hb: 9.6 gm/dl, Hct: 29.0 %, MCV: 87.9 Fl, MCH: 29.1 PG, WBC: 14.4 x10/L, ANC: 9.9 x 10/L and Platelets: 109 x 10/L. Peripheral blood film showed dimorphic blood picture with anisocytosis, poikilocytosis, dysplastic neutrophils, occasional metamyelocytes and few large platelets. Bone marrow aspirate was a cellular specimen showing numerous histiocytes and prominent areas of haemophagocytosis with a few showing panphagocytosis. Bone trephine showed normal cellularity for age with prominent increase in histiocytes. Although there was no evidence of involvement of bone marrow with underlying lymphoma in the sections examined, the panphagocytosis in the bone marrow was probably related to the underlying lymphoma. Malignant histiocytosis was first described by Rappaport as asystemic, progressive, invasive proliferation of morphologically atypical histiocytes and their precursors [1]. More appropriately, now it is viewed as a syndrome that can result from a variety of hematological malignancies [2]. Haemophagocytosis in bone marrow aspirate has been reported previously. Janka et al. in 1998 reported hemophagocytic syndrome associated with DLBCL exclusively in patients from Asian countries [3]. Takeshita M et al. [4] reported a series of 19 patients with malignant histiocytosis and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome. Two of the patients had an underlying B-cell lymphoma. Erythrophagocytosis was more profound in this series. Fig. (1AC) is showing prominent haemophagocytosis.

Folliculotropic T‐cell infiltrates associated with B‐cell chronic lymphocytic leukaemia or MALT lymphoma may reveal either true mycosis fungoides or pseudolymphomatous reaction: seven cases and review of the literature

Mycosis fungoides (MF) and pseudo-MF (or MF simulant) can be associated with B-cell malignancies, but distinction between a true neoplasm and a reactive process may be difficult. To report seven patients with B-cell malignancy and folliculotropic MF or pseudo-MF and emphasize on criteria allowing distinction between the two conditions. We retrospectively and prospectively included seven patients with B-cell malignancy who presented skin lesions histologically consisting in a folliculotropic T-cell infiltrate and reviewed the literature on the topic. Four men and three women had a chronic lymphocytic leukaemia (n=6) or a MALT-type lymphoma (n=1). Five patients had localized papules, and two had patches and plaques. Histological examination showed in all cases a diffuse dermal T-cell infiltrate with folliculotropic involvement and follicular mucinosis associated with clusters of the B-cell lymphoma, without significant expression of follicular helper T-cell markers. T-cell rearrangement studies showed a polyclonal pattern in the patients with papules and a monoclonal pattern in the cases of patches and plaques. Papular lesions had an indolent evolution, whereas patches and plaques persisted or worsened into transformed MF. Folliculotropic T-cell infiltrates associated with B-cell malignancies can be either a true folliculotropic MF or a pseudo-MF. The distinction between both conditions cannot rely only on the histopathological aspect, but needs both a clinical pathological correlation and the search for a dominant T-cell clone. Whether the neoplastic T and B cells derive from a common ancestor or the T-cell proliferation is promoted by the underlying B-cell lymphoma remains unsolved, but interaction between B and T cell in the skin does not appear to be dependent on a TFH differentiation of the T-cell infiltrate.

Perivascular Hemophagocytosis: Report of 2 Cases and Review of the Literature

Hemophagocytosis may be encountered in association with a variety of underlying conditions, including primary or familial disorders, and secondary forms induced by infections, malignancy, and metabolic disorders. It is usually observed in organs such as the spleen, lymph nodes, bone marrow, and central nervous system, but rarely in the skin. When hemophagocytosis coexists with a sepsis-like systemic disorder it is termed hemophagocytic syndrome or hemophagocytic lymphohistiocytosis. Recently, 2 cases with evidence of perivascular hemophagocytosis in skin biopsy specimens of patients without additional findings of hemophagocytic lymphohistiocytosis have been reported. We report 2 additional cases of patients with cutaneous lesions suggestive of leukocytoclastic vasculitis whose skin biopsies showed a perivascular and interstitial infiltrate of neutrophils with nuclear dust and extravasated erythrocytes, and the presence of histiocytes with phagocytized red blood cells and nuclear fragments. There was also evidence of fibrin in the walls of the venules. One patient presented with a sepsis-like clinical scenario, but an extensive work-up failed to demonstrate any underlying disease or infection. The second patient was asymptomatic at the time of presentation, but further work-up revealed an underlying B-cell lymphoma. Whether these histologic findings represent late lesions of leukocytoclastic vasculitis or an incomplete presentation as part of a hemophagocytic syndrome is debatable, because both are associated with activated immunity and cytokine release, which could account for the presence of hemophagocytosis. Although the histopathologic finding alone of hemophagocytosis is insufficient to label as a syndrome, it should incite the clinician for further systemic evaluation.

Translocation (8;22) in cold agglutinin disease associatedwith B-cell lymphoma

Cold agglutinin disease (CAD) is a hemolytic anemia due to anti-red cell autoantibodies that are reactive at cold temperatures. In the elderly, it may be associated with underlying B-cell lymphoma, usually a lympho-plasmacytic lymphoma variant. We report a case of CAD in an elderly Indonesian female, which was associated with a B-cell lymphoma that showed a histologic appearance consistent with large-cell lymphoma. Cytogenetic analysis revealed the presence of trisomies 3 and 12, which have been reported previously in B-cell lymphoma associated with CAD. In addition, a t(8;22) was found in 24 out of 28 metaphases. Translocation (8;22) is associated with Burkitt lymphoma or acute lymphoblastic lymphoma, French–American–British subtype L3. It has not been previously reported in B-cell lymphoma asssociated with CAD, and could represent a blastic transformation of the underlying B-cell lymphoma.

Cryofibrinogenemia in a Patient with B-Cell Lymphoma

Cryofibrinogenemia is an uncommon cause of intravascular coagulation necrosis of the skin and occurs as a result of vascular occlusion from cryoproteins, which reversibly precipitate in cold temperatures. The disease is associated with various conditions, most commonly neoplastic and thromboembolic diseases, and produces cutaneous manifestations such as purpura, ecchymoses, gangrene, and ulcerations. Diagnosis is based on clinical cutaneous manifestations, histopathology, and the laboratory detection of cryofibrinogen precipitation. Treatment is based upon resolution of the underlying disease process or condition, although some interventions have been reported to have therapeutic efficacy. We discuss the presentation, diagnosis, and treatment of a case of cryofibrinogenemia in a patient with underlying B-cell lymphoma.