Healthcare Quiz on CLL Features

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Questions and Answers

Which feature is characteristic of accelerated/progressed CLL (a/pCLL)?

Increased mitotic activity (correct)

Presence of diffuse sheets of large cells

Viral inclusions

High Ki-67 index

What is a significant characteristic of pseudo-Richter syndrome?

High Ki-67 index and preserved CD5/LEF-1 expression (correct)

Response to antiviral treatment

Involvement of mantle cell lymphoma

Presence of viral inclusions

Which statement best describes the prognosis of clonally unrelated DLBCL compared to clonally related DLBCL?

Clonally related DLBCL has longer survival of approximately 5 years.

Both have similar survival rates of approximately 5 years.

Clonally unrelated DLBCL has longer survival ranging from 8-16 months.

Clonally unrelated DLBCL has a significantly longer survival of around 5 years. (correct)

What role do expert hematopathology and advanced diagnostics play in the context of CLL?

They are crucial to avoid misclassification and determine appropriate treatment. Signup and view all the answers

What distinguishes HSV lymphadenitis from Richter's Transformation?

Features viral inclusions and is treated with antivirals. Signup and view all the answers

What is a distinguishing characteristic of the Hodgkin transformation in patients with CLL?

Presence of Reed-Sternberg cells in a lymphoid tissue Signup and view all the answers

What is the typical age range of patients when they undergo transformation to Reed-Sternberg Hodgkin lymphoma?

30–88 years Signup and view all the answers

Which immunohistochemical markers are commonly expressed by Reed-Sternberg cells?

CD30, CD15, PAX5 (dim) Signup and view all the answers

Which marker is commonly positive in neoplastic cells of RS-DLBCL?

CD19 Signup and view all the answers

Which histological subtype of Hodgkin lymphoma (HL) is most commonly associated with transformation from CLL?

Mixed cellularity Signup and view all the answers

What is the approximate percentage of RS-DLBCL cases that have a non-germinal center B-cell-like (non-GCB) immunophenotype?

80% Signup and view all the answers

What percentage of patients with CLL may develop Hodgkin lymphoma?

Less than 1% Signup and view all the answers

Which feature is often seen in RS-DLBCL linked to cell proliferation?

High Ki-67 proliferation index Signup and view all the answers

What is indicated by a standardized uptake value (SUV) greater than 5.0 in PET/CT imaging for tissue biopsy?

Indication for tissue evaluation Signup and view all the answers

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

Diffuse large B-cell lymphoma (DLBCL) Signup and view all the answers

In RS-DLBCL, what type of T-cell marker expression is generally observed?

Negative for CD5 Signup and view all the answers

Which of the following components is part of the inflammatory background seen in Hodgkin transformation?

Eosinophils Signup and view all the answers

What is the typical time frame for the development of DLBCL after the initial diagnosis of CLL?

1.8–4.0 years Signup and view all the answers

What is the relationship between the underlying CLL and RS-DLBCL in terms of clonal evolution?

70–80% of RS-DLBCL cases are clonally related to CLL Signup and view all the answers

Which statement about the branched model of clone development in DLBCL and CLL is true?

Clones acquire distinct genetic lesions from the same common precursor Signup and view all the answers

What is a common finding in the pathology of Hodgkin lymphoma?

Abundant necrotic tissue Signup and view all the answers

Which specific marker is indicative of a GCB immunophenotype in RS-DLBCL?

Positive for CD10 Signup and view all the answers

In the context of RS-DLBCL, what histopathological feature is essential according to WHO criteria?

Sheets of large B-lymphoid cells with increased nuclear size Signup and view all the answers

Which of the following statements is true regarding EBV in RS-DLBCL cases?

EBV-encoded RNA transcripts may be detected in some cases Signup and view all the answers

What role do imaging studies, particularly PET/CT, play in the decision-making for biopsy in suspected RT cases?

They determine optimal biopsy site and site selection Signup and view all the answers

How does RS-DLBCL typically arise in relation to CLL?

From a dominant CLL clone after acquiring additional mutations Signup and view all the answers

What finding in histologic evaluations is common in most cases of RS-DLBCL?

Starry-sky pattern and tumor necrosis Signup and view all the answers

What is the recommended procedure for biopsy when a lesion exhibits high avidity on PET/CT?

Excision biopsy of the index lesion Signup and view all the answers

What demographic group is most commonly affected by DLBCL associated with CLL?

Men over 60 years Signup and view all the answers

Which characteristics are typical of circulating HRS cells?

CD30+ in a polymorphous inflammatory background Signup and view all the answers

What is the typical age range for most patients who develop RS-PBL?

52-77 years Signup and view all the answers

Which molecular features are found in neoplastic cells of RS-PBL?

Monoclonal IGH and MYC rearrangement Signup and view all the answers

What describes the lymphoblasts found in B-lymphoblastic leukemia/lymphoma (B-LBL)?

Intermediate size with indented nuclei Signup and view all the answers

Which immunophenotypic marker is typically negative in RS-PBL neoplastic cells?

CD20 Signup and view all the answers

Which statement about RS-LBL is true?

It rarely occurs following a diagnosis of CLL. Signup and view all the answers

Which immunological features are associated with RS-PBL?

Expression of CD138 and ZAP-70 Signup and view all the answers

What is noted regarding the prognosis of patients with RS-PBL?

The prognosis is grim. Signup and view all the answers

What is the preferred treatment approach for clonally unrelated CLL and DLBCL?

R-CHOP regimen as a de novo DLBCL Signup and view all the answers

Which factor suggests that HL-type RT offers better overall survival than DLBCL-type RT?

Higher median OS of 2.6–3.9 years for HL-type RT Signup and view all the answers

What treatment strategy is recommended for clonally related CLL and DLBCL?

R-CHOP followed by reduced-intensity conditioned SCT Signup and view all the answers

In patients with de novo HL, how does their survival compare to those with HL-type RT?

They present a significantly better overall survival Signup and view all the answers

What is the role of SCT in the management of DLBCL-type Richter syndrome?

SCT is reserved for cases of lack of response after R-CHOP Signup and view all the answers

Which of the following statements about immunoglobulin gene rearrangements is accurate?

Different rearrangements are indicative of clonal unrelatedness Signup and view all the answers

How does Richter transformation affect the management of chronic lymphocytic leukemia?

It requires a specific treatment regimen different from CLL Signup and view all the answers

What is the standard therapy used as first line for DLBCL-type Richter syndrome?

R-CHOP regimen Signup and view all the answers

Study Notes

Richter Transformation (RT)

RT is a histologic transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma
Common transformation is to diffuse large B-cell lymphoma (DLBCL), less often to classical Hodgkin lymphoma.
Very rare transformation to plasmablastic lymphoma or other lymphoma/leukemia types
Occurs in 2-10% of CLL patients, usually during the disease course rather than at presentation
DLBCL-RT occurs in approximately 90% of cases, Hodgkin lymphoma-RT in ~10%
Less than 1% of CLL cases transform into Hodgkin lymphoma

Risk Factors for RT

Advanced Rai stage (III-IV) at CLL diagnosis
Lymph nodes greater than 3 cm on physical exam

Biological Characteristics of CLL-B Cells

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

Clinical Presentation of RT

Onset is often characterized by accelerated, increased lymphadenopathy (often abdominal), splenomegaly, and B symptoms (fever, night sweats, weight loss)
Extra-nodal involvement may occur, especially in the gastrointestinal tract, bone marrow, central nervous system (CNS), or skin
In some cases, RT presents solely as an extra-nodal mass
Early signs and symptoms of extranodal involvement may include satiety, gastrointestinal bleeding, rash, pathologic fractures, headache, blurred vision, or dyspnea.
Physical examination may reveal asymmetric and rapid growth of bulky lymph nodes (>3 cm) detected by physcial exam or imaging studies, accompanied by splenomegaly and/or hepatomegaly.

Diagnosis of RT

Laboratory Findings/CBC:
- Anemia
- Thrombocytopenia (<100 x 10⁹/L) is often observed
- New onset of absolute lymphocytosis (≥5.0 × 10⁹/L)
Biochemical Investigations:
- Elevated serum beta-2 microglobulin (B2M) (>2 mg/L)
- Elevated LDH (lactate dehydrogenase) levels (greater than 1.5 times the upper limit of normal)
- Paraproteinemia
- Hypercalcemia

Tissue Biopsy

Gold standard for RT diagnosis is biopsy of affected lymph node or extra-nodal site.
RT onset is uncommonly disseminated or simultaneous in all lymphatic regions.
18FDG-PET/CT imaging is useful to guide biopsy site selection.
Positive findings (SUV >5.0) in PET/CT scans would indicate that a tissue evaluation is necessary.
Biopsy should be directed at the index lesion, the lesion showing the most avid 18FDG uptake at PET/CT

Histologic Variants of Richter Transformation

Diffuse large B-cell lymphoma (DLBCL): The most frequent histologic variant of transformation.
- Development of DLBCL occurs within 1.8-4.0 years following the initial CLL diagnosis, occurring sometimes before or after CLL therapy.
- DLBCL incidence rate among newly diagnosed CLL patients is about 0.5% while in patients previously treated for CLL is around 1%.
- DLBCL most commonly arises in men over 60 years of age
Pathologic features of RS-DLBCL: Most cases show diffuse effacement of lymph nodes/extra nodal sites by large cells with centroblastic morphology.
- Immunoblastic features are seen in a minority of cases. Often exhibit mitotic figures and apoptotic bodies with a starry sky pattern. Tumor necrosis is common
Adherence to WHO criteria is important: Cells must exhibit diffuse growth throughout the neoplasm and have a nuclear size equal to or exceeding that of normal macrophage nuclei or twice the size of a normal lymphocyte;
Phenotypic characteristics: positive for B-cell markers (CD19, CD20, CD22), PAX5, monotypic surface immunoglobulin light chain; CD38, ZAP70, and CD49d are often positive, but CD5 and CD23 expression may be retained to a varying extent

Other Features

Non-germinal center B-cell-like (non-GCB) immunophenotype is seen in about 80% of RS-DLBCL cases (negative for CD10 and positive for MUM1)
20% of cases have a GCB immunophenotype, positive for CD10 and/or BCL6+, MUM1-
TP53 overexpression and a high Ki-67 proliferation index are frequent findings
Epstein-Barr virus (EBV) has been detected in some cases

Hodgkin Lymphoma

Less than 1% of CLL patients will transform to RS-HL
Transformation typically occurs during the seventh decade of life (range 30-88), primarily in men.
Hodgkin transformation is distinguished by the presence of Hodgkin and Reed-Sternberg cells in a polymorphic inflammatory background, different from that characteristic of CLL
Inflammatory background contains T-cells, histiocytes, potentially with abundant eosinophils
Immunohistochemistry commonly shows CD30, CD15, and PAX5 positivity.

Plasmablastic Lymphoma (PBL)

RS-PBL is aggressive B-cell malignancy related to DLBCL
Most common origin is de novo in the setting of immune deficiency
Fewer cases noted in CLL/SLL patients
Patient demographics and clinical characteristics:
- Majority of patients are men, age 52-77
- Serum/urine protein commonly detectible in some cases
- Typical plasmablast features exist along with residual CLL cells in some samples
Immunohistochemistry would show positivity for CD38, ZAP-70, CD138, BLIMP1, IRF4/MUM1, and XBP1
CD5, CD20, PAX5, and IRF8 are typically negative

B-lymphoblastic Leukemia/Lymphoma (LBL)

RS-LBL arises from progenitor B-lymphoid cells.
Primarily involves bone marrow, peripheral blood, and less commonly lymph nodes
Acute lymphoblastic transformation of CLL is rare
Age range most commonly reported is 42-76, with a majority of patients being men.
Typical interval between CLL diagnosis and RS-LBL is 2 months to 7 years

T-cell lymphomas

Rare in CLL patients, relationship poorly understood

Differential Diagnosis

Accelerated/progressed CLL (a/pCLL): Characterized by expanded proliferation centers and increased mitotic activity, but lacks diffuse sheets of large cells
Pseudo-Richter: Presents after discontinuation of ibrutinib. Responds well to therapy restarting characterized by high Ki-67 (proliferation) index and preserved CD5/LEF-1 expression.

Other Types of Lymphomas

Other rare T-cell and B-cell lymphomas (mantle cell and marginal zone lymphomas) may occasionally coexist with CLL.
HSV Lymphadenitis: mimics RT with necrosis high proliferation rates but features of viral inclusions. Diagnosed by immunohistochemistry and treated with antivirals.

Prognosis

Prognosis differs based on the histologic variant.
DLBCL: The most significant factor for prognosis is the presence or absence of a clonal relationship between CLL and the DLBCL clone
- Clonally unrelated cases present with longer survival (~5 years).
- Clonally related cases have a shorter survival (8-16 months)
HL-type RT: Patients tend to have better overall survival compared to DLBCL-type RT, though inferior to those who have de novo Hodgkin lymphomas
- Median OS in HL-type RT cases is reported to be between 2.6-3.9 years.

Management

DLBCL-type RT: For clonally unrelated CLL and DLBCL, treat as de novo DLBCL, usually with R-CHOP as first-line therapy, followed by SCT if needed
HL-type RT: The treatment approach is similar to DLBCL-type RT
Clonally related CLL and DLBCL: Initiate chemoimmunotherapy (R-CHOP), followed by a consolidation with reduced-intensity conditioned allogeneic or autologous SCT if an appropriate donor/fitness is available.

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Description

Test your knowledge on the characteristics of accelerated/progressed Chronic Lymphocytic Leukemia (a/pCLL) and pseudo-Richter syndrome. This quiz will challenge your understanding of these conditions and their unique features. Perfect for healthcare professionals or students in hematology.