A Patient with Chronic Lymphocytic Leukemia with Pancreatic Involvement

A 78-year-old female with a past medical history of hypertension, type 2 diabetes mellitus, and chronic lymphocytic leukemia was hospitalized for poor appetite, weight loss, and night sweats. On physical exam, there was no palpable lymphadenopathy, and her abdomen was soft and nondistended. Laboratory results showed a hemoglobin count of 13.3 g/dl, hematocrit 41.3%, white blood cell 68.4 × 103 μL with lymphocytes 92.0%, total bilirubin 0.4 mg/dL, aspartate transaminase 14 U/L, and alanine transaminase 15 U/L. CT of the chest, abdomen, and pelvis showed hypodense lesions within the pancreatic body (1.4 × 1.4 cm) and medial aspect of the pancreatic head (1.2 cm) as well as mild splenomegaly (13 cm craniocaudally). She subsequently underwent endoscopic ultrasound (EUS) with fine needle aspiration (FNA) of the pancreatic mass. Flow cytometry revealed expression of CD5 and CD23, consistent with chronic lymphocytic leukemia.

Download Full-text

Unusual Tissue – Unusual Issue: Pancreatic Heterotopia Presenting as Gastric Outlet Obstruction

Case Reports in Gastroenterology ◽

10.1159/000512427 ◽

2021 ◽

pp. 338-343

Author(s):

Thu L. Nguyen ◽

Shivani Kapur ◽

Stephen C. Schlack-Haerer ◽

Grzegorz T. Gurda ◽

Milan E. Folkers

Keyword(s):

Gastric Outlet Obstruction ◽

Epigastric Pain ◽

Outlet Obstruction ◽

Needle Aspiration ◽

Pancreatic Tissue ◽

Cystic Mass ◽

Pancreatic Heterotopia ◽

History Of

Pancreatic heterotopia (PH) is a common, but typically small (<1 cm), incidental and asymptomatic finding; however, PH should be considered even for large and symptomatic upper gastrointestinal masses. A 27-year-old white woman presented with a 3-week history of burning epigastric pain, nausea, early satiety, and constipation. Physical examination revealed epigastric and right upper quadrant tenderness with normal laboratory workup, but imaging revealed a 5-cm, partly cystic mass arising from the gastric antrum with resulting pyloric stenosis and partial gastric outlet obstruction. Endoscopic ultrasound-guided fine needle aspiration revealed PH – an anomalous pancreatic tissue lying in a nonphysiological site. The patient ultimately underwent a resection and recovered uneventfully, with a complete pathologic examination revealing normal exocrine pancreatic tissue (PH type 2) without malignant transformation. We report a case of heterotopic pancreas manifesting as severe gastric outlet obstruction, in addition to a thorough diagnostic workup and surgical follow-up, in a young adult. Differential diagnoses and features that speak to benignity of a large, symptomatic mass lesion (PH in particular) are discussed.

Download Full-text

The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions

10.20944/preprints202112.0282.v1 ◽

2021 ◽

Author(s):

Tadeusz Robak ◽

Magda Witkowska ◽

Piotr Smolewski

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Adverse Effects ◽

Kinase Inhibitors ◽

Clinical History ◽

Lymphocytic Leukemia ◽

Current Status ◽

Covalent Inhibitors ◽

History Of ◽

Reduced Toxicity ◽

Btk Inhibitors

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the ﬁrst irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efﬁcacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

Download Full-text

Advances in the biology and treatment of B-cell chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v85.2.307.bloodjournal852307 ◽

1995 ◽

Vol 85 (2) ◽

pp. 307-318 ◽

Cited By ~ 3

Author(s):

S O'Brien ◽

A del Giglio ◽

M Keating

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Residual Disease ◽

Autologous Bone Marrow ◽

Marrow Transplant ◽

Lymphocytic Leukemia ◽

Western Hemisphere ◽

Molecular Heterogeneity ◽

Prognostic Information ◽

New Agents ◽

History Of

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western hemisphere. Diagnosis and staging of CLL are usually straightforward, but predicting an individual patient's prognosis is still a challenge. Cytogenetic abnormalities provide important prognostic information in CLL and may show its molecular heterogeneity. A search for oncogene abnormalities continues, although no consistent defects have been identified. New agents such as fludarabine produce high complete remission rates and have generated interest in earlier treatment as a first step in a potential cure. Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy. Immunologic abnormalities and minimal residual disease persist in most patients in remission. Combining fludarabine with other active agents and devising effective postremission strategies may change the natural history of CLL.

Download Full-text

Chronic Lymphocytic Leukemia in Kuwait

Blood ◽

10.1182/blood-2019-127234 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5467-5467

Author(s):

Salem Alshemmari ◽

Ramesh Pandita ◽

Abdulaziz Hamadah ◽

Ahmad Alhuraiji

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Board Of Directors ◽

Mutational Analysis ◽

Staging System ◽

Lymphocytic Leukemia ◽

Advisory Committees ◽

Western Countries ◽

Mutational Status ◽

Study Results ◽

History Of

Background :Chronic lymphocytic leukemia (CLL) is common malignancy in Western countries. However, little known about this disease entity in our area. This study exploring the biology in out patients' population. Method:Patients with confirmed CLL under IGHV and TP53 mutational analysis at presentation or during follow up. We also integrated other clinical and biological parameter in this study. Results: A total of 137 cases were analyzed, median age 61 years (range:34-89); 30% of the cases age was<55 years at presentation. There was 108 males vs. 29 females M:F ratio 3.7. Two patients gave a family history of CLL, while 1 patient gave a history of other lymphoproliferative disorders. Binet staging system available in 134 cases, A: 109 (81.3%), B: 12 (9%), C:13 (9.7%). B2 macroglobulin elevated in 40/112 (36%) cases and 10/103 (10%) had M-spike. CD38 positivity reported in 37/112 (33%) of cases. Cytogenetics data evaluable in 85 cases: isolated del(13q): 35%, isolated trisomy 12 (16.5%), del(11q) (4.5%), del(17p)(2.4%). IGHV mutational status mutated vs unmutated: 40% vs 60%. Cases with available treatment information on 132 cases. Fifty cases required treatment due to disease progression. First line treatment Bendamustine-Rituximab (BR) 3 cases, Fludarabine Cyclophosphamide Rituximab (FCR) 30 cases and Chlorambucil with anti-CD 20 antibody 6 cases. At the time of review, 3 cases on ibrutinib (2 in 3rdline and 1 case in the 4thline). Conclusion: This is the first study to shed light on CLL in our area. There are biological differences between our patients' population and the western countries. Disclosures Pandita: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia

eLife ◽

10.7554/elife.02869 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 31

Author(s):

Jiguang Wang ◽

Hossein Khiabanian ◽

Davide Rossi ◽

Giulia Fabbri ◽

Valter Gattei ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Evolutionary History ◽

Directed Graphs ◽

Evolutionary Process ◽

Genetic Alterations ◽

Lymphocytic Leukemia ◽

Cross Sectional ◽

History Of ◽

Evolutionary Paths ◽

Clonal Replacement

Cancer is a clonal evolutionary process, caused by successive accumulation of genetic alterations providing milestones of tumor initiation, progression, dissemination, and/or resistance to certain therapeutic regimes. To unravel these milestones we propose a framework, tumor evolutionary directed graphs (TEDG), which is able to characterize the history of genetic alterations by integrating longitudinal and cross-sectional genomic data. We applied TEDG to a chronic lymphocytic leukemia (CLL) cohort of 70 patients spanning 12 years and show that: (a) the evolution of CLL follows a time-ordered process represented as a global flow in TEDG that proceeds from initiating events to late events; (b) there are two distinct and mutually exclusive evolutionary paths of CLL evolution; (c) higher fitness clones are present in later stages of the disease, indicating a progressive clonal replacement with more aggressive clones. Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

Download Full-text

Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models

Blood ◽

10.1182/blood-2011-01-329870 ◽

2011 ◽

Vol 118 (3) ◽

pp. 660-669 ◽

Cited By ~ 25

Author(s):

Maria Teresa Sabrina Bertilaccio ◽

Giorgia Simonetti ◽

Antonis Dagklis ◽

Martina Rocchi ◽

Tania Veliz Rodriguez ◽

...

Keyword(s):

Immune Response ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Adaptive Immune Response ◽

Lymphocytic Leukemia ◽

Fine Tuning ◽

Terminal Phase ◽

Lymphoid Malignancies ◽

History Of ◽

Molecular Patterns

Abstract Inflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R–like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eμ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.

Download Full-text

Concurrent Squamous Cell Carcinoma and Chronic Lymphocytic Leukemia Presenting as an Enlarging Neck Mass

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709619842904 ◽

2019 ◽

Vol 7 ◽

pp. 232470961984290

Author(s):

Prabhjot Bhinder ◽

Michael Chahin ◽

Lara Zuberi

Keyword(s):

Squamous Cell Carcinoma ◽

Chronic Lymphocytic Leukemia ◽

Cell Carcinoma ◽

Squamous Cell ◽

Neck Mass ◽

Lymphocytic Leukemia ◽

Secondary Malignancies ◽

Increased Risk ◽

History Of ◽

Tonsillar Squamous Cell Carcinoma

Chronic lymphocytic leukemia (CLL) patients are at an increased risk for developing more aggressive lymphomas via Richter’s transformation and of developing secondary malignancies. Despite the known association for secondary cancers, oropharyngeal cancers occur rarely. We present a case of a woman with a history of CLL who presented to our facility via transfer for impending airway compromise. Her initial workup was consistent with CLL; however, biopsies were taken of the neck mass because of its aggressive nature. She was treated with rituximab with good response. Final pathology showed evidence of CLL and tonsillar squamous cell carcinoma (SCC). Direct laryngoscopy and further biopsies yielded a diagnosis of unresectable oropharyngeal SCC. She was to be treated with chemotherapy and radiation for her SCC while holding treatment for CLL. This case demonstrates a rare and unexpected concurrent diagnosis.

Download Full-text

Peripheral T-Cell Lymphoma Arising in Patients With Chronic Lymphocytic Leukemia

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz109 ◽

2019 ◽

Vol 152 (6) ◽

pp. 818-827

Author(s):

Bianca M Van Der Nest ◽

Connull Leslie ◽

David Joske ◽

Dejan Radeski ◽

Rohen White ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Cell Lymphoma ◽

Large Cell ◽

Lymphocytic Leukemia ◽

Emission Tomography ◽

Peripheral T Cell Lymphoma ◽

Positron Emission ◽

History Of ◽

Large Cell Lymphoma ◽

Management Recommendations

Abstract Objectives To describe three further cases of anaplastic large cell lymphoma (ALCL) occurring in patients with preexisting chronic lymphocytic leukemia (CLL). We also reviewed the literature of previously published cases. Methods We discuss the clinical features, histopathology, and outcomes for three patients with ALCL and CLL from Perth, Australia. The cases were also included in a literature review of existing cases and comparisons were made with our cohort. Results The three patients included two men (aged 77 and 74 years) and one woman (aged 66 years). All had a history of untreated CLL with diagnosis established 4 to 16 years before. They had lymphadenopathy and/or cutaneous/soft tissue lesions that proved to be ALCL, ALK+ (one case) or ALCL, ALK– (two cases). Conclusions Further research is required in this area to establish prognostic and management recommendations. Increasing numbers of cases are being described. Positron emission tomography with computed tomography was not useful in our cohort for diagnosing progression.

Download Full-text

Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise

Case Reports in Oncological Medicine ◽

10.1155/2017/8247353 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

Adrian R. Bersabe ◽

Joshua T. Romain ◽

Erin E. Ezzell ◽

John S. Renshaw

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Airway Obstruction ◽

Head And Neck ◽

Cervical Lymphadenopathy ◽

Upper Airway ◽

Lymphocytic Leukemia ◽

Upper Airway Obstruction ◽

Airway Compromise ◽

History Of ◽

Prevalent Form

Chronic Lymphocytic Leukemia (CLL) is the most prevalent form of non-Hodgkin’s lymphoma (NHL) in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT) mass resulting in rapid airway compromise.

Download Full-text

Metastatic Renal Cell Carcinoma to the Parotid Gland in the Setting of Chronic Lymphocytic Leukemia

Case Reports in Medicine ◽

10.1155/2012/265708 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Robert Deeb ◽

Ziying Zhang ◽

Tamer Ghanem

Keyword(s):

Renal Cell Carcinoma ◽

Chronic Lymphocytic Leukemia ◽

Parotid Gland ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Metastatic Potential ◽

Lymphocytic Leukemia ◽

History Of ◽

Total Parotidectomy

Renal cell carcinoma (RCC) is infamous for its unpredictable behavior and metastatic potential. We report a case of a patient with a complex history of multifocal renal cell carcinoma and chronic lymphocytic leukemia (CLL), who subsequently developed a parotid mass. Total parotidectomy revealed this mass to be an additional site of metastasis which had developed 19 years after his initial diagnosis of RCC.

Download Full-text