Richter Transformation in CLL
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Questions and Answers

What characterizes accelerated/progressed CLL (a/pCLL)?

  • Presence of viral inclusions in lymph nodes
  • High Ki-67 index and preserved CD5/LEF-1 expression
  • Presence of diffuse sheets of large cells
  • Increased mitotic activity with expanded proliferation centers (correct)

    • Which of the following is true regarding the prognostic factors in DLBCL associated with CLL?

  • Clonal relationship between CLL and DLBCL clones is the most crucial factor (correct)
  • Histological features are the most important for prognosis
  • DLBCL clones are always clonally related to CLL
  • Patient age is the primary determinant of prognosis

    • What is a distinguishing feature of Pseudo-Richter syndrome?

  • Develops after cessation of ibrutinib therapy (correct)
  • Shows diffuse sheets of large lymphoid cells
  • Associated with low proliferation rates
  • Characterized by the presence of viral inclusions

    • In the context of HSV Lymphadenitis, which statement is accurate?

    <p>It mimics RT with necrosis and high proliferation rates but features viral inclusions. (C)</p> Signup and view all the answers

    How does the survival of clonally unrelated DLBCL compare to clonally related cases?

    <p>Clonally unrelated cases show significantly longer survival compared to related cases. (D)</p> Signup and view all the answers

    What is the most common type of aggressive lymphoma associated with Richter transformation?

    <p>Diffuse large B-cell lymphoma (D)</p> Signup and view all the answers

    Which genetic characteristic is associated with an increased risk of Richter transformation?

    <p>Shorter telomere length (B), IGHV-unmutated B cells (C)</p> Signup and view all the answers

    What is a common physical finding in patients experiencing Richter transformation?

    <p>Asymmetric and rapid growth of bulky lymph nodes &gt; 3 cm (C)</p> Signup and view all the answers

    Which clinical symptom is commonly associated with the onset of Richter transformation?

    <p>Night sweats (D)</p> Signup and view all the answers

    What laboratory finding is typically observed in patients with Richter transformation?

    <p>Anemia and thrombocytopenia (D)</p> Signup and view all the answers

    What percentage of CLL patients typically experience Richter transformation?

    <p>2-10% (C)</p> Signup and view all the answers

    Which cytogenetic abnormality is linked to an increased risk of Richter transformation?

    <p>del(11q22.3) (C)</p> Signup and view all the answers

    Which of the following is least likely to represent a clinical presentation of Richter transformation?

    <p>Decreased appetite without weight loss (C)</p> Signup and view all the answers

    What has been demonstrated about the relationship between HRS cells and CLL cells?

    <p>They may share a common precursor B-cell. (B)</p> Signup and view all the answers

    Which feature is NOT typically expressed by neoplastic cells of plasmablastic lymphoma?

    <p>CD20 (D)</p> Signup and view all the answers

    What is the prognosis for patients diagnosed with RS-PBL?

    <p>Grim with limited treatment options. (B)</p> Signup and view all the answers

    In B-lymphoblastic leukemia/lymphoma, what is a reported characteristic regarding the cells?

    <p>The blasts exhibit indented nuclei. (C)</p> Signup and view all the answers

    What is a prevalent demographic characteristic of patients developing RS-PBL?

    <p>Most patients are men aged 52–77. (A)</p> Signup and view all the answers

    Which of the following markers is typically NOT expressed by RS-PBL neoplastic cells?

    <p>CD5 (D)</p> Signup and view all the answers

    What characterizes the intervals between CLL diagnosis and RS-LBL development?

    <p>Ranges from 2 months to 7 years. (C)</p> Signup and view all the answers

    Which of the following statements about T-cell lymphomas in CLL patients is accurate?

    <p>They rarely develop in CLL patients. (D)</p> Signup and view all the answers

    What significantly affects the clinical outcome between clonally related and clonally unrelated DLBCL?

    <p>Genetic differences (D)</p> Signup and view all the answers

    In treating clonally unrelated CLL and DLBCL, how should the disease be managed?

    <p>As a secondary malignancy using de novo DLBCL protocols (B)</p> Signup and view all the answers

    What is the gold standard for the diagnosis of Richter Transformation (RT)?

    <p>Tissue biopsy of an affected lymph node (A)</p> Signup and view all the answers

    What is the median overall survival reported for patients diagnosed with HL-type Richter transformation?

    <p>2.6–3.9 years (A)</p> Signup and view all the answers

    Which imaging study is utilized to aid in the decision-making for biopsy site in suspected cases of RT?

    <p>Fluorodeoxyglucose PET/CT (A)</p> Signup and view all the answers

    What is the first-line treatment recommended for clonally related CLL and DLBCL?

    <p>R-CHOP chemotherapy (C)</p> Signup and view all the answers

    In cases of Richter transformation, what therapy is reserved for patients lacking response to R-CHOP?

    <p>Stem cell transplantation (A)</p> Signup and view all the answers

    What SUV value from PET/CT suggests the need for tissue evaluation?

    <p>SUV &gt; 5.0 (D)</p> Signup and view all the answers

    What histologic variant is most commonly associated with Richter Transformation (RT) in patients with Chronic Lymphocytic Leukemia (CLL)?

    <p>Diffuse large B-cell lymphoma (B)</p> Signup and view all the answers

    What is the primary method of consolidation following R-CHOP for clonally related cases if a donor is available?

    <p>Allogeneic stem cell transplantation (A)</p> Signup and view all the answers

    What differentiates clonally related CLL from clonally unrelated CLL in terms of immunoglobulin gene rearrangements?

    <p>They have similar rearrangements (C)</p> Signup and view all the answers

    What is a notable demographic characteristic of patients who most commonly develop DLBCL associated with CLL?

    <p>Men over 60 years of age (C)</p> Signup and view all the answers

    What is not a common pathologic feature of RS-DLBCL?

    <p>Presence of eosinophils (B)</p> Signup and view all the answers

    Which of the following treatments is specifically NOT advised for managing clonally unrelated CLL and DLBCL?

    <p>Treating as chronic lymphocytic leukemia (A)</p> Signup and view all the answers

    Which of the following is a key histopathological criterion for the diagnosis of DLBCL in Richter Transformation?

    <p>Diffuse growth pattern with large B-lymphoid cells (D)</p> Signup and view all the answers

    How long after the initial CLL diagnosis can DLBCL develop?

    <p>1.8 to 4.0 years (A)</p> Signup and view all the answers

    What distinguishes the branched model in the context of CLL and DLBCL clones?

    <p>Clones originate from a common precursor cell acquiring distinct genetic lesions. (A)</p> Signup and view all the answers

    During transformation to Hodgkin lymphoma (RS-HL), which characteristic is most commonly observed?

    <p>Hodgkin and Reed-Sternberg cells in a polymorphous inflammatory background. (B)</p> Signup and view all the answers

    Which option best describes the typical age range of patients when they undergo transformation to RS-HL?

    <p>30–88 years. (A)</p> Signup and view all the answers

    Which of the following features is NOT commonly associated with Hodgkin transformation of CLL?

    <p>A low-grade component of large lymphocytes. (A)</p> Signup and view all the answers

    Which protein markers are typically expressed by Hodgkin and Reed-Sternberg cells?

    <p>CD30, CD15, and PAX5 (dim). (D)</p> Signup and view all the answers

    What percentage of Hodgkin and Reed-Sternberg cells may exhibit positivity for CD20?

    <p>20–30%. (A)</p> Signup and view all the answers

    In CLL patients who undergo transformation, which type of component is mainly observed in the affected lymph nodes?

    <p>Low-grade component composed of small lymphocytes. (D)</p> Signup and view all the answers

    What is the prevalence of Hodgkin lymphoma development among patients with CLL?

    <p>Less than 1%. (D)</p> Signup and view all the answers

    Study Notes

    Richter Transformation (RT)

    • RT is a histological transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma.
    • Common transformation is to diffuse large B-cell lymphoma (DLBCL).
    • Classical Hodgkin lymphoma (HL) is a less common transformation.
    • Other lymphoma and leukemia types are very rare transformations (less than 1%).
    • RT typically develops during the disease course, not at presentation.
    • Incidence of RT in patients with CLL is 2-10%.
    • DLBCL-RT occurs in approximately 90% of cases.
    • Hodgkin lymphoma-RT occurs in approximately 10% of cases.
    • Other lymphoma and leukemia types make up less than 1% of transformations.

    Risk Factors

    • Advanced Rai stage (III-IV) at CLL diagnosis is associated with an increased risk of future RT.
    • Lymph nodes greater than 3 cm in size on physical examination are associated with an increased risk of RT.

    Biological Characteristics

    • Patients with CLL and leukemic B cells that are IGHV-unmutated have a 4-fold increased risk of RT compared to patients with IGHV-mutated cells.
    • Shorter telomere length, a marker of genetic instability, is associated with an increased risk of RT.
    • Phenotypic characteristics such as CD38 and CD49d status can be associated with RT risk.
    • Cytogenetic abnormalities, such as del(11q22.3), del(17p13), del(15q21.3), del(9p21), are also associated with RT risk.
    • Heritable germline polymorphisms in BCL2 and CD38 have been associated with a higher risk of transformation.

    Clinical Presentation

    • RT onset is often heralded by an accelerated and significant increase in lymphadenopathy (usually abdominal), splenomegaly, and B symptoms (fever, night sweats, weight loss).
    • Extra-nodal involvement is common, especially in the gastrointestinal tract, bone marrow, central nervous system, or skin.
    • Sometimes RT presents as an extra-nodal mass only.
    • Signs and symptoms of extranodal involvement may include early satiety, gastrointestinal bleeding, rash, pathologic fractures, headache, blurred vision, or dyspnea.
    • Physical examination may reveal asymmetric and rapid growth of bulky lymph nodes (greater than 3 cm), splenomegaly, or hepatomegaly.

    Laboratory Findings

    • Complete blood count (CBC) may show anemia, thrombocytopenia (platelet count less than 100 x 109/L), and new onset of absolute lymphocytosis (lymphocyte count greater than or equal to 5.0 x 109/L).
    • Biochemical investigations may show elevated serum beta-2 microglobulin (B2M) level (greater than 2 mg/L), elevated lactate dehydrogenase (LDH) (greater than 1.5 times the upper limit of normal), paraproteinemia, or hypercalcemia.

    Diagnosis

    • Tissue biopsy of an affected lymph node or extra-nodal site is the gold standard for diagnosing RT.
    • Imaging studies such as 18FDG PET/CT can aid in the decision of where to biopsy. An SUV (standardized uptake value) greater than 5.0 on PET/CT suggests areas warranting tissue evaluation. A lack of detectable lesions on 18FDG-PET scan is highly sensitive in excluding RT.
    • Biopsy should target the index lesion (most avid 18FDG uptake).
    • Excision biopsy is preferred over fine-needle aspiration.

    Histologic Variants

    • Diffuse large B-cell lymphoma (DLBCL): This is the most frequent histologic variant of RT. The development occurs approximately 1.8-4.0 years after initial CLL diagnosis and may occur before or after CLL therapy. The annual incidence rate of DLBCL in newly diagnosed CLL patients is 0.5% and ~1% in patients previously treated for CLL. DLBCL is most common in men over 60 years of age.

    • Pathologic features often include diffuse effacement of lymph nodes or extranodal sites by sheets of large cells with centroblastic morphology, although a minority of cases may show immunoblastic features. Mitotic figures, apoptotic bodies, a starry-sky pattern, and tumor necrosis are frequently seen.

    • The lymphoma cells typically exhibit a non-germinal center B-cell-like (non-GCB) immunophenotype (negative for CD10 and positive for MUM1), but approximately 20% have a GCB immunophenotype (positive for CD10 and/or BCL6, MUM1-).

    Other Associated Lymphomas

    • Hodgkin lymphoma: Less than 1% of CLL patients develop Hodgkin lymphoma transformation.
    • Plasmablastic lymphoma (PBL): This is an aggressive B-cell malignancy that exhibits features of plasma cells. Most PBLs arise de novo, although a few RS-PBL cases can arise in patients with CLL. Patients who develop RS-PBL are usually men between 52-77 years of age.
    • B-lymphoblastic leukemia/lymphoma (B-LBL): This is a rare but aggressive neoplasm derived from progenitor B-lymphoid cells usually involving bone marrow, peripheral blood, and sometimes lymph nodes.
    • T-cell lymphoma: CLL patients rarely develop T-cell lymphomas.

    Differential Diagnoses

    • Accelerated/progressed CLL (a/pCLL): This shows expanded proliferation centers but lacks the diffuse-sheets of large cells typical of RT.
    • Pseudo-Richter: Occurs after discontinuation of certain medications and may respond well to restarting them. Characterized by high Ki-67 index and preserved CD5/LEF-1 expression.

    Other Considerations

    • HSV Lymphadenitis can mimic RT (with necrosis and high proliferation rates ) appearing with viral inclusions. Should be treated with antivirals.
    • Other rare lymphomas, such as mantle cell and marginal zone lymphomas, may coexist with CLL.
    • Misclassification can affect treatment recommendations. Expert hematopathology and advanced diagnostics (FISH, IHC) are essential.

    Prognosis

    • Prognosis varies for different histological variants.
    • For DLBCL, the clonal relationship between CLL and DLBCL is the most important prognostic factor. Clonally unrelated DLBCL often have a longer survival (~5 years) compared to RT-associated DLBCL (8–16 months).
    • For HL-type RT, overall survival (OS) tends to be higher than DLBCL-type RT but inferior to de novo HL patients, with median OS reported of 2.6-3.9 years.

    Management

    • Different approach for clonal related vs clonal unrelated DLBCL type RT.
    • Clinally unrelated is treated as de novo DLBCL using R-CHOP as first line and possible subsequent stem cell transplant (SCT).
    • Clinally related is treated with chemoimmunotherapy followed by possible autologous or allogenic SCT.

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    Richter Transformation PDF

    Description

    This quiz covers the Richter transformation (RT) in chronic lymphocytic leukemia (CLL), including its histological transformations to aggressive lymphomas, such as diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma. It also discusses associated risk factors and biological characteristics. Test your understanding of RT and its implications.

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