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The American Journal of Case Reports Mar 2020BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+... (Review)
Review
Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma; Small Cell Variant: A Real Diagnostic Challenge. Case Presentation and Review of Literature.
BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+ B-lymphocytes. Their distinction is crucial since MCL is a considerably more aggressive disease. Composite lymphoma consisting of CLL/SLL and MCL has been rarely reported. This type of composite lymphoma may be under-diagnosed as the 2 neoplasms have many features in common, both morphologically and immunophenotypically. CASE REPORT We report the case of a 57-year-old male patient who presented with a 4-month history of recurrent abdominal pain and distention with hepatosplenomegaly. Peripheral blood showed a high leukocytes count (46.7×10³/uL) with marked lymphocytosis of 35.0×10³/uL, mostly small mature-looking, with some showing nuclear irregularities, with approximately 3% prolymphocytes. Immunophenotyping by flow cytometry and immunohistochemistry revealed 2 immunophenotypically distinct abnormal CD5+monotypic B-cell populations. Fluorescence in situ hybridization (FISH) on peripheral blood demonstrated IGH/CCND1 rearrangement consistent with t(11;14) in 65% of cells analyzed. Accordingly, based on compilation of findings from morphology, flow cytometry, immunohistochemistry, and FISH, A diagnosis of composite lymphoma consisting of MCL; small cell variant and CLL/SLL was concluded. CONCLUSIONS We describe a case of composite lymphoma of MCL (small cell variant) and CLL/SLL that emphasizes the crucial role of the multiparametric approach, including vigilant cyto-histopathologic examination, immunophenotyping by flow cytometry and immunohistochemistry, as well as genetic testing, to achieve the correct diagnosis.
Topics: Biomarkers, Tumor; Composite Lymphoma; Diagnosis, Differential; Flow Cytometry; Gene Rearrangement; Humans; Immunohistochemistry; Immunophenotyping; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Male; Middle Aged; Oncogene Proteins, Fusion
PubMed: 32150530
DOI: 10.12659/AJCR.921131 -
Translational Cancer Research Jul 2023B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell tumor with an aggressive clinical course and poor prognosis. It is characterized by prominent splenomegaly...
BACKGROUND
B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell tumor with an aggressive clinical course and poor prognosis. It is characterized by prominent splenomegaly and prolymphocytes exceeding 55% of the lymphoid cells in the blood. Purine analog-based chemo-immunotherapy is the first-line therapy for B-PLL. Owing to its rarity, there are few reports on the efficacy of bendamustine and rituximab (BR) regimen. Our study presents three cases of BR being effective in the treatment of B-PLL and provides experience for clinical treatment.
CASE DESCRIPTION
This report describes the cases of three male patients (median age: 66 years old) who initially presented with abdominal discomfort. Physical examinations and imaging revealed splenomegaly, while a peripheral blood (PB) smear revealed a prolymphocyte count exceeding 70% of the lymphoid cells. Therefore, the three patients were diagnosed with B-PLL. Further molecular detection showed that they harbored P53 abnormalities (17p deletion/ mutation) associated with resistance to conventional chemotherapies. In addition, one of the patients had a highly complex karyotype and multiple gene mutations. All patients underwent four cycles of BR, and two of them received two further cycles of rituximab monotherapy. Ultimately, the patients achieved a complete response (CR) that lasted for 25, 33, and 34 months, respectively, with a median follow-up time of 34 months. The adverse events of the BR mainly included a grade 3 haematological toxicities. Also, the treatment was well-tolerated.
CONCLUSIONS
This case series suggests that BR regimen is promising for bringing deep remission to patients with B-PLL. Prospective trials are still required for further elucidation.
PubMed: 37588745
DOI: 10.21037/tcr-23-828 -
Journal of Hematopathology Jun 2022Aggressive subtypes of non-Hodgkin lymphoma may uncommonly be referred to clinical oncologists for treatment of acute leukemia, due to an elevated or rapidly rising...
Aggressive subtypes of non-Hodgkin lymphoma may uncommonly be referred to clinical oncologists for treatment of acute leukemia, due to an elevated or rapidly rising white blood cell count (WBC), with circulating neoplastic cells that morphologically resemble leukemic blasts seen in acute myeloid or lymphoblastic leukemia. We describe six cases of non-Hodgkin lymphoma that mimicked acute leukemia and were identified in the pathology records of the Brigham and Women's Hospital. The patients were older adults (mean age 70 years), who presented with leukocytosis (mean 79.7 × 10/L) with circulating neoplastic cells (mean 57%), which mimicked leukemic blasts, thrombocytopenia, and anemia (4/6 patients). In each case, immunophenotypic analysis identified a population of mature B cells or mature T cells. We identified 15 additional cases of non-Hodgkin lymphoma in the literature that mimicked acute leukemia; considering all 21 cases, 11 had an appearance of acute lymphoblastic leukemia, 4 had an appearance of acute monocytic leukemia, and 6 had an appearance of acute leukemia unable to be further categorized. In general, patients exhibited poor overall survival. These cases illustrate the importance of comprehensive immunophenotypic analysis in the initial evaluation of hematolymphoid neoplasms, and that occasional cases of non-Hodgkin lymphomas can resemble acute leukemia at initial presentation.
PubMed: 35496359
DOI: 10.1007/s12308-022-00493-9 -
Journal of Investigative Medicine High... 2021B-cell prolymphocytic leukemia (B-PLL) is a rare leukemia characterized by rapidly increasing leukocytosis with splenomegaly and lymphadenopathy. Treatment strategies...
B-cell prolymphocytic leukemia (B-PLL) is a rare leukemia characterized by rapidly increasing leukocytosis with splenomegaly and lymphadenopathy. Treatment strategies are largely based on studies of chronic lymphocytic leukemia (CLL). Antibodies against the cell surface protein CD20 are considered to be first-line therapy. A 76-year-old male with known CLL presented 2 weeks after starting chemoimmunotherapy for newly refractory CLL after failing ibrutinib therapy. White blood cell count was elevated at 226.7 × 10/µL. Fluorescent in situ hybridization analysis of a bone marrow specimen showed new development of complex cytogenetics. Flow cytometry revealed B cells appearing slightly dimmer on CD45 and brighter on CD20 compared with typical B-CLL suggestive of less mature lymphocyte forms. The patient was diagnosed with B-PLL and started on obinutuzumab and venetoclax with rapid normalization of white blood cells. This case recapitulates the challenges in diagnosing and treating B-PLL. Ibrutinib resistance is a growing area of study with several proposed mechanisms of acquired resistance. The pathogenesis of B-PLL is not completely understood, although mutations in are presumed to play a role.
Topics: Aged; Humans; Immunotherapy; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Male
PubMed: 33533282
DOI: 10.1177/2324709621990767 -
Journal of Basic and Clinical Pharmacy Mar 2016Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature-appearing lymphocytes in blood, bone marrow, lymph nodes, and spleen with a median...
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature-appearing lymphocytes in blood, bone marrow, lymph nodes, and spleen with a median lymphocyte count of 20-30 × 10(9)/L at the time of diagnosis. In half of the patients, the lymphocyte count doubles over a period of 1-year and cyclic rise up to 50 × 10(9)/L can occur in untreated patients while in others the count may remain stable for years. Based on the cytogenetic and molecular studies, it has been demonstrated that multiple clones may occur in CLL and clonal evolution is a frequent occurrence. The transformation of CLL to a high-grade non-Hodgkin's lymphoma such as diffuse large B cell lymphoma, Hodgkin lymphoma, and prolymphocytic leukemia is well documented. Whereas the transformation of CLL to acute leukemia occurs in <1% cases and this contrasts the almost invariable progression in patients with chronic myeloid leukemia. Here, we report a rare case of a 55-year-old lady, a diagnosed case of CLL transforming into B-cell acute lymphocytic leukemia over a very short interval of 1 week period.
PubMed: 27057127
DOI: 10.4103/0976-0105.177702 -
Journal of Investigative Medicine High... 2018We report the case of a patient with B-cell prolymphocytic leukemia who was successfully treated with the novel humanized monoclonal antibody obinutuzumab. This patient...
We report the case of a patient with B-cell prolymphocytic leukemia who was successfully treated with the novel humanized monoclonal antibody obinutuzumab. This patient was previously treated with the combination of rituximab and bendamustine and had recurrent infusion reactions. Her treatment with rituximab and bendamustine was discontinued when she developed disease progression after 3 cycles of therapy. She was then treated with obinutuzumab 1000 mg on day 1 of every cycle and chlorambucil 0.5 mg/kg on days 1 and 15 every 28 days to which she had greater tolerability. After 4 cycles of treatment, she had resolution of her clinical symptoms, massive splenomegaly, and normalization of her white blood cell count.
PubMed: 30038912
DOI: 10.1177/2324709618788674 -
Leukemia & Lymphoma 2016Previous experiments demonstrated that survival and proliferation of chronic lymphocytic leukemia (CLL) cells depends upon complex cross-talk between CLL cells and...
Previous experiments demonstrated that survival and proliferation of chronic lymphocytic leukemia (CLL) cells depends upon complex cross-talk between CLL cells and accessory cells in the tissue microenvironment. To further dissect these interactions in situ, we analyzed lymph nodes from 43 different patients infiltrated by CLL cells for expression of the chemokine CCL3, Ki-67, macrophages, and T cell subsets by immunohistochemistry. CCL3 expression was detected in 24 of 43 cases (56%), particularly in prolymphocytes and paraimmunoblasts within the proliferation centers. Significantly higher numbers of CD3+ T cells and CD57+ cells were noticed in CCL3 positive cases. Furthermore, denser infiltration of CLL lymph node tissues by CD57+ cells correlated with higher proliferation rates of the CLL cells. In conclusion, we demonstrate an association of CCL3 expression by CLL cells with increased numbers of CD3+ T cells and CD57+ cells in the lymph node microenvironment, which may promote CLL cell survival and proliferation.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chemokine CCL3; Disease Progression; Female; Gene Expression; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphocyte Count; Macrophages; Male; Middle Aged; T-Lymphocyte Subsets; Tumor Microenvironment
PubMed: 26458057
DOI: 10.3109/10428194.2015.1068308 -
International Journal of... Apr 2018T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread...
T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread disease at presentation. Despite high response rate seen with alemtuzumab, the disease relapse is inevitable. This was a retrospective observational study done at a tertiary cancer center in South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were studied for the clinical characteristics, pathological findings and treatment outcomes. Seven patients were diagnosed as T-PLL over a period of 5 years. The median age at diagnosis was 51 years. In the present series, 6 patients (86%) had splenomegaly and 3 had hepatomegaly (43%). Generalized lymphadenopathy was seen in 4 (57%) patients at presentation. Skin lesions were seen in 5 (71%) patients, whereas pleural effusion was seen in only one patient (14%). All had elevated total leukocyte count, with more than 1, 00,000/dL in 4 patients. The median survival was 5 months with different chemotherapy (CT) regimens (5 patients treated with CT and 2 received best supportive care). T-PLL is a rare disease with no definite treatment guidelines. At present, the best outcomes are achieved if treatment with alemtuzumab is followed by stem cell transplant, but the disease invariably relapses. Countries where affordability remains a big challenge, the best approach needs to be defined beyond the monoclonal antibodies and transplant.
PubMed: 30233775
DOI: No ID Found -
Cureus Sep 2019B-cell prolymphocytic leukemia (B-PLL) is a rare malignancy of mature B-cells with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features...
B-cell prolymphocytic leukemia (B-PLL) is a rare malignancy of mature B-cells with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features characterized by late onset (median age 69 years), an aggressive clinical course, refractoriness to chemotherapy, and median survival of around three years. Treatment is influenced by the presence or absence of specific high-risk genetic mutations like 17P/TP53 deletion, the presence of which translates into poor prognosis. Patients without 17P deletion, who are <70 years, without significant co-morbidities, are initially treated with a combination chemotherapy regimen used for chronic lymphocytic leukemia (CLL) such as fludarabine, cyclophosphamide, and rituximab. On the other hand, patients with a 17P deletion, age >70 years, with multiple co-morbidities, receive ibrutinib or alemtuzumab as the initial therapy. Relapsed or refractory cases are managed with BCL-2 signaling inhibitors like venetoclax. We discuss the case of an 84-year-old male with B-PLL (positive TP53 mutation), resistant to ibrutinib therapy, with extremely high white blood cell (WBC) counts, thus creating a dilemma regarding the best treatment in the second-line setting.
PubMed: 31700732
DOI: 10.7759/cureus.5629 -
El Bisturi 2016Prolymphocytic leukemias (PLLs) are rare mature lymphoid disorders of B- and T-cell subtypes with distinct features and an aggressive clinical course. PLL represents...
Prolymphocytic leukemias (PLLs) are rare mature lymphoid disorders of B- and T-cell subtypes with distinct features and an aggressive clinical course. PLL represents only 2% of all mature lymphocytic leukemias in adults. T-PLL represents 20% of all PLLs cases. T-cell prolymphocytic leukemia (T-PLL) is more rare and more rapidly progressive and aggressive than B-PLL; it is generally resistant to conventional chemotherapy, and historically the median survival has been about 7 months. Clinicians will often only see a case of T-PLL once every 5 to 10 years, which makes recognition of the disorder difficult. The prognosis is poor and there is no curative therapy. We report a 77-year-old male patient with T-PLL presenting with WBC count of 1,115,000. We will discuss the clinical, morphologic, immunophenotypic and cytogenetic features of this rare entity. A distinctive hematologic aspect of T-PLL is a rapidly rising white blood cell count with a doubling time of weeks to months. The key morphologic feature in the diagnosis of T-PLL is a population of more than 55% prolymphocytes in the peripheral blood. The diagnosis can be made on peripheral blood by flow cytometry where a monoclonal lymphocyte population will show positivity for T-cell markers. T-PLL is characterized by complex chromosomal abnormalities, which suggests that chromosomal aberrations might occur progressively during the course of the disease, thus explaining the aggressive nature of this condition. The main challenge as a clinician treating T-PLL is to deliver long-term disease-free survival. The most important predictor of outcome is response to alemtuzumab therapy (Campath). Knowledge of the disrupted pathways and mechanisms underlying activation and proliferation in T-PLL has raised the possibility of developing future and promising treatment approach that targets these pathways and signals by the use of future molecule inhibitors. T-PLL is a rare disease and careful attention should be given to correctly diagnose this T-cell leukemia. Physicians should be aware of this unusual entity. With the advent of alemtuzumab, although much progress has been made in the treatment of this disease, autologous or allogeneic hematologic stem cell transplant (HSCT) still remains the only hope for cure.
PubMed: 29238632
DOI: No ID Found