L13 – Haematological Malignancies Flashcards
What is the primary focus when assessing haematological malignancies?
To understand the clinicopathological features, diagnostic techniques, and classifications of common blood and lymphoid neoplasms.
What clinical presentation is suggestive of diffuse large B cell lymphoma (DLBCL)?
Patients often present with rapidly enlarging lymphadenopathy, B symptoms (fever, night sweats, weight loss), and laboratory abnormalities like elevated LDH.
How does immunohistochemistry aid in diagnosing DLBCL?
Markers such as CD20 and a high Ki67 proliferation index confirm the diagnosis and indicate the tumour’s aggressive nature.
What is the significance of detecting chromosomal translocations in lymphoma?
Translocations involving genes like c-myc, bcl2, or bcl6 provide diagnostic and prognostic information and can influence therapy decisions.
How is PCR used in the diagnosis of lymphoid malignancies?
PCR detects clonal rearrangements of immunoglobulin heavy chain or T cell receptor genes, confirming a neoplastic process.
What are the typical systemic features of high-grade lymphomas?
They often present with B symptoms, pancytopenia, hypercalcaemia, and sometimes organomegaly.
What laboratory finding is commonly elevated in patients with aggressive lymphomas?
Lactate dehydrogenase (LDH) is often elevated, reflecting high tumour turnover.
What distinguishes multiple myeloma from other haematological malignancies?
It is characterised by a clonal proliferation of plasma cells in the bone marrow with the production of monoclonal immunoglobulins.
What clinical symptoms are associated with multiple myeloma?
Patients typically experience bone pain, pathological fractures, recurrent infections, and renal failure.
Which laboratory test is key in the diagnosis of multiple myeloma?
Detection of Bence Jones protein in the urine and the presence of a monoclonal spike on serum protein electrophoresis.
What is the significance of hypercalcaemia in multiple myeloma?
It is a consequence of bone destruction and is a common metabolic abnormality in myeloma patients.
What clinical feature, such as pruritus after alcohol consumption, can be a clue for Hodgkin’s lymphoma?
Alcohol-induced pruritus is a recognised paraneoplastic phenomenon in Hodgkin’s lymphoma.
What staging system is used for Hodgkin’s lymphoma?
The Ann-Arbor staging system, which evaluates the extent of nodal and extranodal involvement.
How does Epstein–Barr Virus (EBV) relate to Hodgkin’s lymphoma?
EBV infection is associated with the pathogenesis of some Hodgkin’s lymphoma cases, particularly in younger patients.
What is acute myeloid leukaemia (AML)?
AML is a clonal malignancy of myeloid precursor cells, characterised by an accumulation of immature blasts in the bone marrow.
What are the typical clinical manifestations of AML?
Patients often present with fatigue, infections, bleeding, and symptoms related to anaemia and bone marrow failure.
How does flow cytometry assist in the diagnosis of AML?
It helps identify specific surface markers such as CD34 and other myeloid markers, confirming the lineage of the blasts.
What treatment modalities are typically used in AML?
Treatment generally involves combination chemotherapy (e.g. cytarabine and daunorubicin) along with supportive care.
What is the importance of the WHO classification in haematological malignancies?
It integrates morphology, immunophenotype, genetic and clinical features to provide a precise categorisation of these diseases.
How do myeloproliferative neoplasms differ from acute leukaemias?
Myeloproliferative neoplasms involve proliferation of mature cells and typically have a slower progression compared to acute leukaemias.
What role does immunophenotyping play in the diagnosis of lymphoid neoplasms?
It helps determine the cell lineage (B-cell vs T-cell) and maturation status, guiding both diagnosis and treatment.
How is clonality assessed in lymphoid malignancies?
Clonality is determined by detecting rearrangements in IgH or TCR genes via PCR.
What prognostic significance does a high Ki67 index have in lymphoma?
A high Ki67 indicates rapid cell proliferation and generally correlates with a more aggressive clinical course.
What is the clinical relevance of elevated LDH in lymphoma patients?
Elevated LDH is associated with high tumour burden and poorer prognosis.
How does the addition of rituximab to chemotherapy regimens affect outcomes in B cell lymphomas?
Rituximab improves survival rates by targeting CD20-positive cells, enhancing treatment response.
What distinguishes acute from chronic leukaemias in clinical presentation?
Acute leukaemias present rapidly with blast proliferation and severe marrow failure, while chronic leukaemias have a more indolent course with mature cells.
Which paraneoplastic syndromes are associated with haematological malignancies?
They can include hypercalcaemia, neuropathies, and autoimmune phenomena.
How does cytogenetic analysis guide prognosis in AML?
Specific chromosomal abnormalities stratify patients into risk categories, influencing therapy decisions.
What is the role of supportive care in managing AML?
Supportive care—including transfusions and infection prophylaxis—is critical due to bone marrow failure and treatment-related complications.
How are high-grade lymphomas managed differently from low-grade lymphomas?
High-grade lymphomas require aggressive chemotherapy regimens, while low-grade lymphomas may be managed with watchful waiting or less intensive therapy.
What is the significance of FISH in evaluating haematological malignancies?
FISH detects specific genetic abnormalities that aid in diagnosis, prognosis, and treatment planning.
Why is an integrated diagnostic approach important in haematological malignancies?
Combining clinical, histological, immunophenotypic, and molecular data ensures a comprehensive and accurate diagnosis for tailored treatment.
What are hematological malignancies?
Hematological malignancies are cancers affecting the blood, bone marrow, and lymphatic system.
What is the primary aim of studying hematological malignancies?
The aim is to understand their clinical pathology, diagnostics, and classification for effective management.
What are common diagnostic tools used in hematological malignancies?
Common tools include blood tests, biopsies, imaging, and molecular studies.
Why are ancillary molecular techniques important in diagnosing hematological malignancies?
They help identify genetic mutations and molecular markers essential for prognosis and treatment.
What classification system is used for hematological malignancies?
The WHO classification system is used.
What symptoms are commonly associated with hematological malignancies?
Symptoms include fever, night sweats, weight loss, and organ involvement.
What laboratory findings are indicative of hematological malignancies?
Cytopenia, hypercalcemia, and elevated LDH are indicative of malignancies.
Why is imaging important in hematological malignancies?
It helps assess disease extent and organ involvement.
What is the role of biopsy in diagnosing hematological malignancies?
A biopsy confirms malignancy and determines subtype.
What histological features suggest malignancy in hematological disorders?
Large abnormal cells, high mitotic activity, and architectural disruption suggest malignancy.
What is CD20, and what does it indicate?
CD20 is a B-cell marker used in lymphoma diagnosis.
How does Ki-67 help in diagnosing malignancies?
Ki-67 measures cell proliferation.
What does a high Ki-67 index suggest?
A high index indicates rapid tumor growth.
What is the significance of a diffuse growth pattern in lymphomas?
Diffuse patterns suggest aggressive lymphomas.
What are the characteristics of high-grade lymphomas?
They grow rapidly, are aggressive, and require intensive treatment.
What factors can predispose individuals to developing lymphomas?
Autoimmune diseases, immunosuppression, and viral infections.
How can autoimmune diseases contribute to lymphoma development?
Chronic immune stimulation can lead to mutations.
What role do immunosuppressive drugs play in lymphoma development?
They increase the risk by suppressing immune surveillance.
How can low-grade lymphomas transform into high-grade lymphomas?
Indolent lymphomas can transform into aggressive forms.
What organs can be involved in high-grade lymphomas?
Lymph nodes, bone marrow, GI tract, and brain.
What are systemic symptoms of high-grade lymphomas?
Fever, night sweats, weight loss, and fatigue.
How does hypercalcemia occur in hematological malignancies?
Bone resorption releases calcium into the blood.
What does elevated lactate dehydrogenase (LDH) indicate?
It indicates high cell turnover.
Why is radiological imaging crucial in lymphomas?
It detects lymph node and organ involvement.
What ancillary techniques are used to detect chromosomal translocations in lymphomas?
FISH detects chromosomal translocations.
How does fluorescence in situ hybridization (FISH) help in diagnosing hematological malignancies?
PCR identifies gene rearrangements.
What is the role of polymerase chain reaction (PCR) in diagnosing hematological malignancies?
MYC translocation is associated with aggressive disease.
What is MYC translocation, and why is it significant?
R-CHOP is a standard regimen.
What is the standard chemotherapy regimen for aggressive B-cell lymphomas?
It targets CD20+ cells.
How does rituximab work in treating lymphomas?
Bone pain, fractures, anemia, and kidney failure.
What are common presenting symptoms of plasma cell neoplasms?
“Punched-out” lytic lesions.
What imaging findings are characteristic of plasma cell neoplasms?
Eccentric nuclei, clock-face chromatin.
What are the histological features of plasma cells in neoplastic disorders?
CD138.
What immunohistochemical marker confirms plasma cell lineage?
A plasma cell cancer producing monoclonal proteins.
What is multiple myeloma?
They accumulate in bone marrow, causing organ dysfunction.
How do monoclonal plasma cells contribute to disease pathology?
Bone destruction, renal failure, anemia, and infections.
What are the common complications of multiple myeloma?
Bone marrow replacement reduces red blood cell production.
Why does multiple myeloma cause anemia?
Osteoclast activation leads to bone resorption.
How does multiple myeloma lead to bone destruction?
Immunosuppression increases infection risk.
Why are infections common in multiple myeloma?
Excess calcium release from bones.
How does hypercalcemia develop in multiple myeloma?
Tubular damage from light chains.
What causes renal failure in multiple myeloma?
Abnormal light chains found in urine.
What are Bence Jones proteins?
Light chains accumulate, damaging kidneys.
How does cast nephropathy develop in multiple myeloma?
Deposition of misfolded proteins in organs.
What is amyloidosis, and how is it related to multiple myeloma?
Detects bone lesions.
What is the significance of skeletal surveys in multiple myeloma?
Reduces tumor burden and relieves symptoms.
How does chemotherapy help in treating multiple myeloma?
Variable but often progressive.
What is the typical prognosis of multiple myeloma?
It involves clonal plasma cell proliferation.
What distinguishes multiple myeloma from other plasma cell disorders?
A group of disorders affecting plasma cells.
What are plasma cell disorders?
Identifies abnormal proliferation and infiltration.
What is the role of bone marrow examination in hematological malignancies?
Normal plasma cells are polyclonal, while malignant ones are monoclonal.
What are normal plasma cells, and how do they differ from malignant plasma cells?
Uncontrolled clonal expansion of cells.
What is the significance of clonal proliferation in hematological malignancies?
They can cause hyperviscosity and organ dysfunction.
How do paraproteins contribute to disease pathology in plasma cell neoplasms?
Increased blood viscosity due to excess proteins.
What is hyperviscosity syndrome?
It can cause headaches, bleeding, and visual disturbances.
How does hyperviscosity syndrome affect the body?
Plasmapheresis removes excess proteins.
How can hyperviscosity syndrome be managed?
It suggests a plasma cell disorder.
Why is the presence of monoclonal proteins in urine significant?
IgG, IgA, IgM, IgE, and IgD.
What are the different types of immunoglobulins produced in plasma cell neoplasms?
IgG and IgA.
What is the most common immunoglobulin involved in plasma cell neoplasms?
Reed-Sternberg cells and CD30 positivity.
What are the characteristics of Hodgkin lymphoma?
A large binucleated cell characteristic of Hodgkin lymphoma.
What is a Reed-Sternberg cell?
It confirms the presence of Reed-Sternberg cells.
Why is CD30 staining important in diagnosing Hodgkin lymphoma?
Bimodal distribution, common in young adults and elderly.
What are common epidemiological patterns of Hodgkin lymphoma?
Genetic mutations and EBV infection.
What environmental and genetic factors contribute to Hodgkin lymphoma?
EBV can transform B cells, contributing to malignancy.
How is Epstein-Barr virus (EBV) linked to Hodgkin lymphoma?
A system used to stage lymphomas.
What is the Ann Arbor staging system?
It classifies lymphomas based on spread.
How does the Ann Arbor staging system classify lymphoma?
Fever, night sweats, weight loss, and lymphadenopathy.
What symptoms are associated with Hodgkin lymphoma?
Alcohol-induced pain in affected lymph nodes.
How does alcohol consumption relate to Hodgkin lymphoma symptoms?
Generally favorable with treatment.
What is the prognosis of Hodgkin lymphoma?
Hodgkin lymphoma has high cure rates.
How does chemotherapy for Hodgkin lymphoma differ from treatment for other lymphomas?
Adriamycin, bleomycin, vinblastine, and dacarbazine.
What is the ABVD regimen?
It targets CD30+ cells.
How does brentuximab work in Hodgkin lymphoma treatment?
Acute and chronic leukemia.
What are the two main types of leukemia?
Acute forms progress rapidly, chronic forms are slower.
What differentiates acute from chronic leukemia?
Myeloid affects granulocytes, lymphoid affects lymphocytes.
What are myeloid and lymphoid leukemias?
Fatigue, infections, bleeding, and weight loss.
What symptoms are common in leukemia?
It leads to cytopenias.
How does leukemia affect blood cell production?
High blast count suggests leukemia.
What is the significance of blast cells in leukemia diagnosis?
It identifies abnormal cell populations.
How does flow cytometry aid in leukemia diagnosis?
CD markers help classify leukemia type.
What are the key markers in leukemia diagnosis?
They drive uncontrolled proliferation.
How do chromosomal abnormalities contribute to leukemia?
Trisomy 21 is linked to leukemia risk.
Why are individuals with Down syndrome more susceptible to leukemia?
Radiation and benzene exposure.
What environmental factors increase leukemia risk?
Prior chemotherapy can induce secondary leukemia.
How does previous chemotherapy increase the risk of leukemia?
Chemotherapy and targeted therapy.
What is the standard treatment for leukemia?
Transfusions, antimicrobials, and supportive care.
What supportive treatments are essential in leukemia management?
Some leukemias infiltrate the CNS.
How does leukemia affect the central nervous system?
To prevent fungal infections in immunocompromised patients.
Why are prophylactic antifungals used in leukemia patients?
Low platelets increase bleeding risk.
What is the significance of platelet counts in leukemia?
It results from massive cell lysis, causing metabolic disturbances.
What is tumor lysis syndrome, and why is it a concern in leukemia?
WHO classification integrates clinical, genetic, and molecular data.
What are the key principles of the WHO classification of hematological malignancies?
Cell morphology aids in diagnosis.
How does morphology aid in classifying hematological malignancies?
They refine classification and prognosis.
What role do genetic and molecular features play in classification?
Clinical presentation helps guide classification.
What is the importance of clinical presentation in classification?
It categorizes myeloid neoplasms like AML and CML.
How does the WHO classification categorize myeloid neoplasms?
It categorizes lymphoid neoplasms like lymphomas and leukemias.
How does the WHO classification categorize lymphoid neoplasms?
Accurate classification guides treatment and prognosis.
Why is it important to classify hematological malignancies accurately?
DLBCL is the most common aggressive B-cell lymphoma.
What is the relationship between diffuse large B-cell lymphoma and other lymphomas?
A rare lymphoma involving blood vessels.
What is intravascular large B-cell lymphoma?
A high-grade lymphoma with plasma cell features.
What is plasmablastic lymphoma?
It exhibits plasmacytoid differentiation.
How does plasmablastic lymphoma differ from other B-cell lymphomas?
Different subtypes have distinct prognoses and treatments.
What is the clinical significance of different lymphoma subtypes?
The clinical significance of different lymphoma subtypes lies in their distinct prognoses, treatment strategies, and survival rates. Accurate classification guides therapy and influences long-term management.
