Chronic Lymphocytic Leukemia Presenting Research Articles

Rare cutaneous manifestation of B‐cell chronic lymphocytic leukaemia involving the toes

AbstractB cell chronic lymphocytic leukaemia (B‐CLL) presenting with cutaneous infiltration is rare, and when it occurs, it presents most commonly on the head and neck. We present the case of an 80‐year‐old woman with a 2‐month history of erythema, swelling and pain affecting all her toes. She had a history of B‐CLL diagnosed 20 years previously that had remained stable under observation without treatment. A toe skin biopsy showed a diffuse infiltrate of lymphoid cells occupying the dermis composed of small mature lymphoid cells with a monotonous appearance. On immunohistochemistry, the neoplastic lymphoid cells stained positive for the B‐cell marker CD20. Overall, the morphology and immunophenotype were consistent with cutaneous involvement by chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). We concluded that her symptoms were directly caused by skin infiltration of B‐CLL.

Paraneoplastic Cutaneous Leukocytoclastic Vasculitis as an Initial Presentation of Chronic Lymphocytic Leukemia.

Paraneoplastic Cutaneous Leukocytoclastic Vasculitis as an Initial Presentation of Chronic Lymphocytic Leukemia.

Acute kidney injury due to cryoglobulinemic glomerulonephritis as the initial presentation of Chronic Lymphocytic Leukemia

Cryoglobulinemic vasculitis presents with systemic vasculitis including vasculitic rash, fever, peripheral neuropathy and rarely renal involvement. This could be secondary to infections like hepatitis C, malignancies like myeloma, Non Hodgkin’s lymphoma and chronic lymphocytic leukemia. We encountered a patient who presented with fever, anemia, purpuric skin rash and acute kidney injury due to acute glomerulonephritis with nephritic picture and fluid overload that required hemodialysis.Investigations revealed hemolytic anemia, cryoglobulinemia, proliferative glomerulonephritis with Ig M intra-capillary deposits and hyaline thrombi. Bone marrow biopsy clinched the diagnosis of Chronic lymphocytic B cell lymphoma with CD 20 positivity. Treatment was instituted with Rituximab and Bendamustine. Plasmapheresis was done for hyperviscosity syndrome. With treatment, hemodialysis could be discontinued after 10 weeks and renal functions recovered partially with serum creatinine settling at 1.5 mg/dl. We present this case to highlight the presentation of chronic lymphocytic leukemia with cryoglobulinemic vasculitis that presented with purpura and rapidly progressive renal failure that required dialysis.

Relapsed Chronic Lymphocytic Leukemia Presenting with a Cardiac Mass: A Case Report

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the USA. (American Cancer Society, 2022) It is more prevalent in elderly males and commonly presents with a relatively benign course. Extra-medullary disease is very rare and is not well characterized. Skin and CNS involvement were reported to be the most common but other organs can also be involved. (Ratterman et al., 2014) We report a 51-year-old male patient with a past medical history of mutation negative CLL in remission, who presented with fatigue, dyspnea on exertion, night sweats and a neck mass. The physical examination revealed an enlarged non-tender left supraclavicular lymph node measuring 5-6 cm in diameter but was otherwise unremarkable. Laboratory investigations were notable for leukopenia and thrombocytopenia. Due to high suspicion for an underlying malignant process, a full body computerized tomography (CT) scan was obtained and showed an 8.8 cm soft tissue mass-like lesion occupying the majority of the right atrium and extending into the right ventricle, with probable pericardial involvement. Enlarged left supraclavicular and mediastinal lymph nodes were also present and had a mild mass effect on the traversing left internal thoracic artery and left pulmonary artery. A transesophageal echocardiogram and cardiac magnetic resonance imaging (MRI) (Figure 1) were done to better characterize the cardiac mass. They confirmed a large infiltrating mass (measuring 10 x 7.4 cm) in the right atrium and ventricle, extending into the inferior vena cava inferiorly and coronary sinus posteriorly. A bone marrow biopsy showed normocellular marrow with no infiltration. Left supraclavicular excisional lymph node biopsy was performed and histopathology was consistent with Small Lymphocytic Lymphoma (SLL)/CLL with increased proliferation index (up to 40% by KI-67 immunohistochemical stain) and normal karyotype. This confirmed extramedullary SLL/CLL relapse with lymphadenopathy and cardiac mass. The patient was started on chemo-immunotherapy with Obinutuzumab-Venetoclax with marked improvement in B symptoms and dyspnea. Cardiac infiltration by CLL B-cells has been shown on autopsies of CLL patients. (Schwartz et al., 1981) In practice, clinically significant cardiac or pericardial involvement by SLL/CLL is extremely rare with only a few case reports in literature. (Posch et al., 2021) (Nnaoma et al., 2019) (Goncalves et al., 2002) Extramedullary CLL disease suggests a more aggressive disease and warrants a high level of suspicion for diagnosis. (Ratterman et al., 2014) Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S2007 Chronic Lymphocytic Leukemia Presenting as Colonic Ulcers

Introduction: Chronic Lymphocytic Leukemia (CLL) accounts for 25% of leukemias. One can present with hepatomegaly, splenomegaly, and lymphadenopathy. CLL infiltration in the gastrointestinal (GI) mucosa is rare. Colonic CLL can develop late in the disease course with mild to no GI symptoms. Awareness of CLL and its various extra-nodal presentations allow for prompt diagnosis and treatment. Case Description/Methods: An 80-year-old female with untreated CLL presented with 2 months of rectal bleeding. She denied weight loss, anorexia, night sweats, blood thinners, and NSAID use. She had WBC 34.3, platelets 139, and a normal Hgb of 13.2. Colonoscopy showed ulcerations at the ileocecal valve and transverse colon, a 30 mm ascending colon polyp, and multiple 10-20 mm transverse and descending colon polyps. Pathology showed only chronic inflammation of the ulcerated regions, and a sessile serrated adenoma at the ascending colon. The remaining polyps were not removed due to concern for cancer and potential colectomy. A CT chest, abdomen, and pelvis was unremarkable. Tumor markers showed CEA 8 and normal Ca19-9 and Ca-125. Due to an unclear diagnosis, a second colonoscopy was performed with repeat biopsies and removal of all polyps in the descending and sigmoid colon. Pathology results were negative for inflammatory bowel disease and infection. The polyps were tubular adenomas and hyperplastic. However, immunohistochemical analysis was positive for CD5/CD43 and CD23, indicative of CLL in the ulcerated mucosa. Treatment options were discussed with surgery and oncology. The patient was offered right colon resection or endoscopic removal of the remaining polyps prior to chemotherapy (Figure). Discussion: Colorectal lymphomas are rare and account for 1% of all GI malignancies with CLL usually found proximal to the hepatic flexure. In this case, the presence of ulcerations and large polyps were concerning for colorectal cancer. However, the initial work-up was negative. After a repeat colonoscopy, testing for specific CLL markers was requested. In a review of literature, chemotherapy alone for colonic CLL had a perforation risk of 15%. While it is unclear if surgical treatment is beneficial, it is a potential option. Due to the high risk of perforation on chemotherapy, recommendations included right hemicolectomy or endoscopic removal of the remaining polyps prior to starting treatment. This demonstrates the importance of knowing the varying presentations of colonic CLL as its treatment may require multidisciplinary discussion.Figure 1.: Colonic ulcers located at the transverse colon (top left) and IC valve (top right). H&E stain of the colonic mucosa (bottom) that showed positive markers for CLL on IHC analysis.

Chronic Lymphocytic Leukemia Involving the Liver Without High-Grade Transformation

Chronic lymphocytic leukemia is most frequently encountered among the elderly population. Hepatic infiltration may be present at the time of diagnosis, but significant extranodal involvement rarely occurs without high-grade transformation. Abnormal liver enzymes have important prognostic implications in terms of staging the disease and initiating treatment. We describe an atypical presentation of chronic lymphocytic leukemia in a patient who presented with rising liver enzyme levels, extensive hepatic infiltration, and portal hypertension but with no evidence of high-grade transformation on liver biopsy.

Pleural effusion as an unusual presentation of chronic lymphocytic leukemia

Pleural effusion as an unusual presentation of chronic lymphocytic leukemia

Characterisation of a New Clinical Presentation of Chronic Lymphocytic Leukemia with Symptomatic Nasopharyngeal Mucosa Involvement

Patients with chronic lymphocytic leukemia (CLL) are prone to infectious complications, including Ears, Nose and Throat (ENT) infections due to the humoral immunodepression and/or to the immunosuppression related to the therapy. However, specific CLL infiltration in non-lymphoid regions of the head and neck causing ENT symptoms but unrelated to an infection is not well described. Extra-nodal localizations of CLL cells, including involvement of the mucosa of the rhinopharynx is uncommon and poorly reported. Here, we retrospectively analyzed the clinical, histopathologic and molecular features of 25 CLL patients with specific head and neck involvement. To date, this is the largest cohort reporting this new entity of CLL also named Nasal Associated Lymphoid Tissue (NALT) CLL.All patients had proven CLL prior to symptoms. Median time between ENT manifestation and CLL was 3 years [1-11 years]. Symptoms included chronic coughing (44%), antero-posterior nasal discharge (44%), nasal congestion (33%) and pharyngitidis (33%). ENT examination evidenced cervical lymphadenopathies in 68 % of cases, a granular aspect of the mucosa of the pharynx in 56%, enlarged tonsil (37%) or adenoids (37%). All patients underwent a biopsy of the mucosa of the nose or the throat. Histology and immunochemistry analysis demonstrated an infiltration of small lymphocytes CD20+, CD5+ and CD23+, consistent with a phenotype of CLL. The infiltration was diffuse in 50% of biopsies and perivascular in 38%.Patients with NALT-CLL had a poor prognosis: the majority was IGHV unmutated (n=18/25, 72%). Furthermore, they all required a treatment according to IWCLL criteria few time after the first ENT symptoms (median time 2 years), indicating that NALT-CLL is associated with a more progressive disease.To characterize the genetic background of NALT-CLL, we analyzed the cytogenetic data and NGS sequencing of 13 CLL-associated mutations from peripheral CLL cells. The karyotype was normal in only 2/24 cases (8%) and complex (>3 abnormalities) in 5/24 cases (20%). Half of the patients had a trisomy 12(12/24; 50%), while 13q, 17p and 11q deletions were found in 29%, 8% and 4% respectively. Eleven patients harbored one mutation (44%) while 9 patients had 2 to 5. Mutation of the NOTCH1 pathway was found in half of the cases (11/25 NOTCH1 and 2/25 FBXW7 mutated cases). TP53 and SF3B1 mutations occurred respectively in 20% (5/25 cases) and in 12% (3/25 cases).To gain insight into the molecular mechanism associated with involvement of the rhinopahrynx, we studied the expression of 70 genes related to cell migration and cell adhesion pathways using a qPCR array in the peripheral CLL cells of patients with NALT (n=4) compare to no NALT-CLL (n=4). Genes significantly up regulated with a fold change >2 included the chemokine receptors CCR7 (p=0.05) and CCR5 (p=0.04), the receptor involved in leukocyte trafficking CXCR3 (p=0.01) or the chemoattractant chemokine-like factor CKLF. By targeted qPCR, we confirmed the up regulation of CCR7 (p=0.002), CXCR3 (p=0.04) and CCR5 (p=0.03) in the cohort NALT-CLL patient (n=25) as compared to 20 age-matched CLL patients without head and neck symptoms (77% with unmutated IGHV, 30% with NOTCH1 mutation and 30% with trisomy 12). Up regulation of those targets was independent of the presence of NOTCH1/trisomy12 aberration or of the IGHV mutation status. These results suggest an increased migratory capacity of the leukemic CLL cells into the rhynopharynx mucosa related to a higher expression of these receptors involved in cell trafficking and migration. In line with these results, immunohistochemistry analysis of 5 patients with nasal involvement showed a strong staining of the CCR7 marker on the membrane of CLL cells infiltrating the mucosa. Interestingly, the staining of CCL21, the cognate ligand of CCR7, was positive in the vessels of the mucosa, suggesting that the recruitment and the transendothelial migration of CLL cells into the mucosa occur through a local secretion of CCL21 by the vessels.In summary, we report here a new presentation of CLL associated with symptomatic and specific ENT localization. CLL cells are predominantly IGHV unmutated, harbor NOTCH1 mutation and/or trisomy12 and show a higher expression of the chemokine receptors CCR7, CCR5 and CXCR3. We are currently studying the expression of those receptors by flow cytometry and the enhanced migratory capacity toward CCL21 through an in vitro chemotaxis assay. DisclosuresLetestu: AbbVie: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Janssen: Research Funding, Speakers Bureau. Cymbalista: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTRA ZENECA: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly-LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Poster: CLL-140: Chronic Lymphocytic Leukemia Presenting as a Solitary Breast Mass

Poster: CLL-140: Chronic Lymphocytic Leukemia Presenting as a Solitary Breast Mass

CLL-140: Chronic Lymphocytic Leukemia Presenting as a Solitary Breast Mass

An 80-year-old woman with a past medical history of hypertension and no prior history of malignancy underwent a screening mammogram followed by a breast ultrasound that showed a right breast mass. She remained asymptomatic. The physical exam did not reveal any palpable lymphadenopathy nor hepatosplenomegaly. Peripheral blood smear showed absolute lymphocytosis of 69% with a normal total white blood cell count of 8.1 without dysplastic cells, blasts, anemia, or thrombocytopenia. Breast ultrasound showed an irregular hypoechoic mass measuring 0.7 x 0.5 x 0.5 cm. Subsequent US-guided core biopsy showed non-Hodgkin B-cell lymphoma positive for cluster designation (CD)20 and CD5. Bone marrow aspirate and core biopsy revealed clusters of small-to-medium atypical lymphocytes positive for CD20, CD79a (weak), with a co-expression of CD5 (strong) and CD23CD138, findings that are compatible with Small Lymphocytic Lymphoma (SLL)/Chronic Lymphocytic Leukemia (CLL). Positron Emission Tomography scan showed an uptake within the right breast only. She is being managed with observation and close follow-up. Breast lymphoma (BL) represents around 0.5% of malignant breast neoplasms. Diffuse Large B-Cell Lymphoma (DLBCL) and follicular lymphoma are the predominant subtypes. SLL and CLL are subtypes of non-Hodgkin lymphoma originating from a B-cell lineage. While there have been reported cases of CLL and SLL manifesting as BL, the incidence still is very low and limited to case reports. Moreover, they have been reported to be found concomitantly with breast carcinoma. Most BL are asymptomatic when found incidentally on screening imaging, as in our patient. A hypoechoic round mass is the most common reported appearance. There are no current established guidelines for the treatment of BL. In our patient, we followed the recommendations for managing CLL. Not all breast masses are adenocarcinoma. It is critical to keep in mind the differential diagnosis lymphoproliferative disorders, melanoma, lung cancer, and gynecological malignancies.

Richter transformation of chronic lymphocytic leukaemia presenting as otitis externa

Richter transformation of chronic lymphocytic leukaemia presenting as otitis externa

Chronic Lymphocytic Leukemia Presenting as Scleral Nodule

Chronic Lymphocytic Leukemia Presenting as Scleral Nodule

Chronic Lymphocytic Leukaemia Presenting with Pancytopenia: ARare Haematological Coincidence

Chronic Lymphocytic Leukaemia (CLL) is commonly associated with autoimmune cytopenias but CLL presenting with pancytopenia is a rare occurrence. Here, we present a case of 56-year-old male patient, who presented with pallor, mild hepatosplenomegaly, right-sided pleural effusion in chest x-ray, pancytopenia and his bone marrow showed infiltration by mature appearing lymphoid cells making a diagnosis of CLL. Despite the frequency of these immune mediated cytopenia, only few cases of pancytopenia have been described so far to the best of our knowledge. Hence, to emphasise the rarity of such haematological coincidence we are presenting this case report. CLL generally presents with persistent absolute lymphocytosis on peripheral smear with an absolute monoclonal lymphocyte count of more than 5000/cumm. There is a common association with Autoimmune Haemolytic Anaemia (AIHA) and Immune Thrombocytopenia (ITP) and the association is called as Evan’s syndrome. Its pathogenesis is associated with autoimmune process. AIHA, ITP, and Pure Red Cell Aplasia (PRCA) are commonly associated complications seen in CLL. The pathogenesis of AIHA and ITP are antibody this inplace of the reactions and abnormal T cell activity is noted in the pathogenesis of PRCA. Despite of the frequency of these immune mediated cytopenias noted in CLL, bone marrow was seen to be hypercellular in most of the cases and marrow hypoplasia have been reported in only 2 cases reported in literature so far. In the present case, although pancytopenia was present on peripheral blood smear examination but bone marrow was hypercellular for age with diffuse infiltration by monoclonal mature appearing lymphoid cells which makes this case all the more interesting. Despite repeated blood transfusions,antiviral drug Tenofovir and aggressive supportive measures for 6 months, he developed right-sided pleural effusion and succumbed to his illness.

Chronic lymphocytic leukemia presenting as pulmonary involvement in an elderly patient: a case report

Chronic lymphocytic leukemia presenting as pulmonary involvement in an elderly patient: a case report

CLL-155: Differential Diagnosis of Aplastic Anaemia in Chronic Lymphocytic Leukaemia

A 73-year-old lady presented in September of 2019 with pancytopenia on a background of 17p and 13q deleted chronic lymphocytic leukaemia (CLL) on ibrutinib. The diagnosis of CLL was made in 2008 and no treatment was required until she developed progressive cytopenias in January of 2019, with a lymphocyte count of 193.8 ×109/L. Fluorescence in-situ hybridisation (FISH) demonstrated 17p and 13q deletions and she was commenced on ibrutinib. She developed atrial fibrillation but otherwise tolerated the therapy well. She represented with significant fatigue and bleeding in September of 2019 and her blood count revealed a haemoglobin (Hb) of 8.2 g/dL, a platelet count of 6 ×109/L, a lymphocyte count of 32 ×109/L, a neutrophil count of 0.24 ×109/L and a reticulocyte count of References [1] Zonder JA, Keating M, Schiffer CA. Chronic Lymphocytic Leukemia presenting in association with Aplastic Anemia. Am. J. Hematol. 2002 71:323–327. [2] Castiglioni MG, Scatena P, Pandolfo C et al. Rituximab Therapy of Severe Aplastic Anemia Induced by Fludarabine and Cyclophosphamide in a Patient Affected by B-cell Chronic Lymphocytic Leukemia. 2006 Sep;47(9):1985-6. [3] Singal R, Winfield DA, Greaves M. Bone marrow aplasia in B cell chronic lymphocytic leukaemia: Successful treatment with antithymocyte globulin. J Clin Pathol 1991; 44:954-956. [4] Vitale C, Ahn IE, Sivina M et al. Autoimmune cytopenias in patients with chronic lymphocytic leukemia treated with ibrutinib. Haematologica 2016; 101:e257.

Chronic lymphocytic leukemia, a rare cause of pituitary stalk thickening.

This case highlights a rare presentation of chronic lymphocytic leukemia (CLL). CNS involvement by CLL is rare, and only 5 cases with pituitary or hypothalamic involvement have previously been reported. Unfamiliarity with this disease complication may lead to a delay in diagnosis and treatment.This case highlights a rare presentation of chronic lymphocytic leukemia (CLL). CNS involvement by CLL is rare, and only 5 cases with pituitary or hypothalamic involvement have previously been reported. Unfamiliarity with this disease complication may lead to a delay in diagnosis and treatment.

Pure Red Cell Aplasia and Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia; Case Report and Literature Review

This paper outlines the case report of Chronic Lymphocytic Leukemia (CLL) presenting with two immune dysregulation phenomena, Autoimmune Hemolytic Anemia (AIHA) and Pure Red Cell Aplasia (PRCA) in the same patient. CLL, despite an immune deficient state, harbors autoimmunity presenting in the form of cytopenias. Autoimmune cytopenias are associated with poor prognosis and warrant different therapeutic approach.

Chronic Lymphocytic Leukemia Presenting as Irritative Lower Urinary Tract Symptoms and Non-Visible Hematuria: An Atypical Urology Presentation

Chronic lymphocytic leukemia (CLL) is an uncommon hematological disease affecting people with recurring infection and is associated with increased risk of progression to high-risk cancer. Bladder CLL is a rare disease hence prognosis and best treatment option is not clearly understood. CLL commonly affects middle-aged women. It presents as abdominal pain, urinary difficulty, fatigue and general symptoms like fever, weight loss and loss of appetite. Chemotherapy, surgery, and radiation is the mainstay of treatment. Prognosis depends on multiple factors including subtype, stage of lymphoma, the progression of the condition, response to treatment, and overall health of the patient. The risk of recurrence and progression to other cancer is very high in bladder CLL which necessitates a strict follow-up protocol. We present a case of an 87-years-old patient presenting with persistent non-visible hematuria and storage lower urinary tract symptoms. Hematuria workup leads to the diagnosis of CLL. Hematology multi-disciplinary team recommended follow up.

A rare case of atypical chronic lymphocytic leukaemia presenting as nephrotic syndrome

Chronic lymphocytic leukaemia (CLL) is characterised by a lymphocytosis of mature-appearing clonal CD5+, CD23+ B lymphocytes. CLL cells arise from the bone marrow and infiltrate lymphoid tissues such as lymph...

An unusual presentation of Chronic Lymphocytic Leukaemia as delirium

An unusual presentation of Chronic Lymphocytic Leukaemia as delirium