leukemias ew

What is the defining feature of acute leukemia in the bone marrow?

Acute leukemia is defined by the accumulation of more than 20% blasts in the bone marrow.

What are the main clinical consequences of increased blasts in acute leukemia?

Increased blasts crowd out normal hematopoiesis, resulting in acute presentation with anemia (fatigue), thrombocytopenia (bleeding), or neutropenia (infection).

How do blasts typically appear in the blood of patients with acute leukemia?

Blasts are large, immature cells, often with punched out nucleoli, and they usually enter the bloodstream, resulting in a high WBC count.

How is acute leukemia classified?

Acute leukemia is subdivided into acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) based on the phenotype of the blasts.

What marker is characteristic of lymphoblasts in acute lymphoblastic leukemia (ALL)?

Lymphoblasts in ALL are characterized by positive nuclear staining for TdT, a DNA polymerase.

Which age group is most commonly affected by ALL, and what genetic condition is associated with increased risk?

ALL most commonly arises in children and is associated with Down syndrome (usually arises after the age of 5 years).

What are the key surface markers for B-ALL?

B-ALL lymphoblasts express TdT, CD10, CD19, and CD20.

What cytogenetic abnormality in B-ALL is associated with a good prognosis?

t(12

What cytogenetic abnormality in B-ALL is associated with a poor prognosis?

t(9

What are the key surface markers for T-ALL, and how does it typically present?

T-ALL lymphoblasts express markers ranging from CD2 to CD8 (e.g., CD3, CD4, CD7), do not express CD10, and usually present in teenagers as a mediastinal (thymic) mass. [page 3-4]

What is the defining feature of acute myeloid leukemia (AML) in the bone marrow?

AML is defined by the neoplastic accumulation of immature myeloid cells (myeloblasts) greater than 20% in the bone marrow.

What cytoplasmic marker is characteristic of myeloblasts in AML?

Myeloblasts in AML are usually characterized by positive cytoplasmic staining for myeloperoxidase (MPO).

What are Auer rods, and in which leukemia are they found?

Auer rods are crystal aggregates of myeloperoxidase (MPO) seen in myeloblasts of AML.

Which age group is most commonly affected by AML?

AML most commonly arises in older adults, with an average age of 50-60 years.

What is the genetic abnormality in acute promyelocytic leukemia (APL), and what is its clinical significance?

APL is characterized by t(15

What is the treatment for acute promyelocytic leukemia (APL)?

Treatment is with all-trans-retinoic acid (ATRA), a vitamin A derivative, which binds the altered receptor and causes the blasts to mature and eventually die.

What is a distinguishing clinical feature of acute monocytic leukemia?

Blasts in acute monocytic leukemia characteristically infiltrate the gums.

Which acute leukemia is associated with Down syndrome before the age of 5?

Acute megakaryoblastic leukemia is associated with Down syndrome and usually arises before the age of 5.

What are myelodysplastic syndromes, and how are they related to AML?

Myelodysplastic syndromes are pre-existing dysplasias that may progress to AML, especially after exposure to alkylating agents or radiotherapy. They present with cytopenias, hypercellular bone marrow, abnormal maturation, and increased blasts (

What is the most common cause of death in patients with myelodysplastic syndromes?

Most patients with myelodysplastic syndromes die from infection or bleeding.

What is chronic leukemia?

Chronic leukemia is a neoplastic proliferation of mature circulating lymphocytes, characterized by a high WBC count.

How does chronic leukemia typically present in terms of onset and age group?

Chronic leukemia usually has an insidious onset and is seen in older adults.

What is chronic lymphocytic leukemia (CLL)?

CLL is a neoplastic proliferation of naïve B cells that co-express CD5 and CD20

What is seen on a blood smear in CLL?

Increased lymphocytes and smudge cells are seen on blood smear in CLL.

What is small lymphocytic lymphoma?

Small lymphocytic lymphoma refers to the involvement of lymph nodes by CLL, leading to generalized lymphadenopathy.

What are the main complications of CLL?

Complications of CLL include hypogammaglobulinemia (infection is the most common cause of death), autoimmune hemolytic anemia, and transformation to diffuse large B-cell lymphoma (Richter transformation).

What is Richter transformation?

Richter transformation is the transformation of CLL to diffuse large B-cell lymphoma, marked clinically by an enlarging lymph node or spleen.

Which surface markers are co-expressed by CLL cells?

CLL cells co-express CD5 and CD20.

What is the most common cause of death in CLL patients?

Infection, due to hypogammaglobulinemia, is the most common cause of death in CLL patients.

What is a characteristic cell seen in CLL on blood smear?

Smudge cells are characteristic of CLL on blood smear.

What autoimmune complication can occur in CLL?

Autoimmune hemolytic anemia can occur as a complication of CLL.

How does CLL typically present clinically?

CLL typically presents with increased lymphocytes in the blood and may involve lymph nodes, leading to generalized lymphadenopathy.

What is hairy cell leukemia?

Hairy cell leukemia is a neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes.

Which enzyme is used as a marker for hairy cell leukemia?

Cells in hairy cell leukemia are positive for tartrate-resistant acid phosphatase (TRAP).

What are the main clinical features of hairy cell leukemia?

Clinical features include splenomegaly (due to accumulation of hairy cells in red pulp) and 'dry tap' on bone marrow aspiration (due to marrow fibrosis). Lymphadenopathy is usually absent.

What is a 'dry tap' in the context of hairy cell leukemia?

A 'dry tap' refers to the inability to aspirate bone marrow, which occurs due to marrow fibrosis in hairy cell leukemia.

What is the treatment for hairy cell leukemia?

Hairy cell leukemia has an excellent response to 2-CDA (cladribine), an adenosine deaminase inhibitor

Is lymphadenopathy common in hairy cell leukemia?

No, lymphadenopathy is usually absent in hairy cell leukemia.

What is adult T-cell leukemia/lymphoma (ATLL)?

ATLL is a neoplastic proliferation of mature CD4+ T cells.

Which virus is associated with ATLL, and where is it most commonly seen?

ATLL is associated with HTLV-1 and is most commonly seen in Japan and the Caribbean.

What are the clinical features of ATLL?

Clinical features of ATLL include rash (skin infiltration), generalized lymphadenopathy with hepatosplenomegaly, and lytic (punched-out) bone lesions with hypercalcemia.

What is mycosis fungoides?

Mycosis fungoides is a neoplastic proliferation of mature CD4+ T cells that infiltrate the skin, producing localized skin rash, plaques, and nodules.

What are Pautrier microabscesses?

Pautrier microabscesses are aggregates of neoplastic cells in the epidermis seen in mycosis fungoides.

What is Sezary syndrome, and what is a characteristic finding on blood smear?

Sezary syndrome occurs when mycosis fungoides cells spread to the blood, producing characteristic lymphocytes with cerebriform nuclei (Sezary cells) on blood smear.

What are myeloproliferative disorders (MPDs) and in which age group do they typically occur?

Myeloproliferative disorders (MPDs) are neoplastic proliferations of mature cells of myeloid lineage, typically occurring in late adulthood (average age 50-60 years).

What are the hematological features of MPDs and how are they classified?

MPDs result in a high WBC count with hypercellular bone marrow, and cells of all myeloid lineages are increased. They are classified based on the dominant myeloid cell produced.

What are the main complications of MPDs?

Complications of MPDs include increased risk for hyperuricemia and gout due to high cell turnover, progression to marrow fibrosis, or transformation to acute leukemia.

What is chronic myeloid leukemia (CML) and which cell type is characteristically increased?

CML is a neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors

What genetic abnormality drives CML and what protein does it produce?

CML is driven by t(9

What is the first line treatment for CML?

The first line treatment for CML is imatinib, which blocks tyrosine kinase activity.

What does splenomegaly indicate in CML?

Splenomegaly is common in CML. An enlarging spleen suggests progression to the accelerated phase of disease, and transformation to acute leukemia usually follows shortly thereafter.

To which acute leukemias can CML transform, and why?

CML can transform to AML (2/3 of cases) or ALL (1/3 of cases) since the mutation is in a pluripotent stem cell.

How is CML distinguished from a leukemoid reaction?

CML is distinguished from a leukemoid reaction by negative leukocyte alkaline phosphatase (LAP) stain, increased basophils, and presence of t(9

What is a leukemoid reaction and how does it differ from CML?

A leukemoid reaction is a reactive neutrophilic leukocytosis, not associated with t(9

What are the typical age group and hematological findings in CML?

CML is a type of myeloproliferative disorder that typically affects adults (average age 50-60 years) and presents with high WBC count and hypercellular bone marrow.

What is polycythemia vera (PV)?

PV is a neoplastic proliferation of mature myeloid cells, especially red blood cells (RBCs), but granulocytes and platelets are also increased.

Which genetic mutation is associated with polycythemia vera?

Polycythemia vera is associated with a JAK2 kinase mutation.

What are the main clinical symptoms of polycythemia vera?

Clinical symptoms are mostly due to hyperviscosity of blood: blurry vision and headache, increased risk of venous thrombosis, flushed face due to congestion (plethora), and itching, especially after bathing.

What is the first-line treatment for polycythemia vera?

The first-line treatment is phlebotomy

What is the risk of thrombosis in polycythemia vera?

There is an increased risk of venous thrombosis, such as hepatic vein, portal vein, and dural sinus thrombosis.

What causes the itching seen in polycythemia vera, especially after bathing?

Itching is due to histamine release from increased mast cells.

How is polycythemia vera distinguished from reactive polycythemia?

In PV, erythropoietin (EPO) levels are decreased and Sao₂ is normal. In reactive polycythemia due to high altitude or lung disease, Sao₂ is low and EPO is increased. In reactive polycythemia due to ectopic EPO production (e.g., renal cell carcinoma), EPO is high and Sao₂ is normal.

What is the prognosis of untreated polycythemia vera?

Without treatment, death usually occurs within one year.

What is myelofibrosis?

Myelofibrosis is a neoplastic proliferation of mature myeloid cells, especially megakaryocytes, associated with JAK2 kinase mutation.

What is the pathogenesis of myelofibrosis?

Megakaryocytes produce excess platelet-derived growth factor (PDGF), causing marrow fibrosis.

What are the clinical features of myelofibrosis?

Clinical features include splenomegaly (due to extramedullary hematopoiesis), leukoerythroblastic smear (tear-drop RBCs, nucleated RBCs, and immature granulocytes), increased risk of infection, thrombosis, and bleeding.

What causes the splenomegaly seen in myelofibrosis?

Splenomegaly is due to extramedullary hematopoiesis as the bone marrow becomes fibrotic and unable to produce blood cells.

What is a leukoerythroblastic smear and what does it indicate in myelofibrosis?

A leukoerythroblastic smear shows tear-drop RBCs, nucleated RBCs, and immature granulocytes, indicating extramedullary hematopoiesis.

What are the main complications of myelofibrosis?

Main complications include increased risk of infection, thrombosis, and bleeding due to ineffective hematopoiesis.

What is essential thrombocythemia (ET)?

ET is a neoplastic proliferation of mature myeloid cells, especially platelets. RBCs and granulocytes are also increased.

Which genetic mutation is associated with essential thrombocythemia?

ET is associated with a JAK2 kinase mutation.

What are the main symptoms of essential thrombocythemia?

Symptoms are related to an increased risk of bleeding and/or thrombosis.

Does essential thrombocythemia commonly progress to marrow fibrosis or acute leukemia?

ET rarely progresses to marrow fibrosis or acute leukemia.

Is there a significant risk for hyperuricemia or gout in essential thrombocythemia?

No, there is no significant risk for hyperuricemia or gout in ET.

What cell types are increased in essential thrombocythemia?

Platelets are especially increased, but RBCs and granulocytes are also increased.

What are non-Hodgkin lymphomas (NHL)?

Non-Hodgkin lymphomas (NHL) are neoplastic proliferations of lymphoid cells that form a mass, usually in lymph nodes, but can also arise in extranodal tissue.

How are non-Hodgkin lymphomas classified?

NHLs are classified based on cell type (B or T), cell size, pattern of growth, expression of surface markers, and cytogenetic translocations.

What is follicular lymphoma?

Follicular lymphoma is a neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules.

What genetic abnormality is associated with follicular lymphoma and what is its effect?

Follicular lymphoma is associated with t(14

How does follicular lymphoma typically present?

Follicular lymphoma presents in late adulthood with painless lymphadenopathy.

What is mantle cell lymphoma?

Mantle cell lymphoma is a neoplastic proliferation of small B cells (CD20+) that expands the mantle zone.

What genetic abnormality is associated with mantle cell lymphoma and what is its effect?

Mantle cell lymphoma is associated with t(11

What is marginal zone lymphoma and with which conditions is it associated?

Marginal zone lymphoma is a neoplastic proliferation of small B cells (CD20+) that expands the marginal zone, often associated with chronic inflammatory states such as Hashimoto thyroiditis, Sjögren syndrome, and H. pylori gastritis.

What is Burkitt lymphoma and what are its key features?

Burkitt lymphoma is a neoplastic proliferation of intermediate-sized B cells (CD20+) associated with EBV and characterized by a 'starry-sky' appearance on microscopy.

What genetic abnormality is associated with Burkitt lymphoma and what is its effect?

Burkitt lymphoma is associated with t(8

What is diffuse large B-cell lymphoma?

Diffuse large B-cell lymphoma is a neoplastic proliferation of large B cells (CD20+) that grows diffusely in sheets and is clinically aggressive.

How does diffuse large B-cell lymphoma present and what is its origin?

Diffuse large B-cell lymphoma can arise de novo or as transformation from a low-grade lymphoma (e.g., follicular lymphoma). It presents in late adulthood as an enlarging lymph node or extranodal mass.

What is a major complication of follicular lymphoma?

A major complication of follicular lymphoma is progression to diffuse large B-cell lymphoma, which presents as an enlarging lymph node.

How can follicular lymphoma be distinguished from reactive follicular hyperplasia?

Follicular lymphoma can be distinguished from reactive follicular hyperplasia by disruption of normal lymph node architecture, lack of tingible body macrophages in germinal centers, Bcl2 expression in follicles, and monoclonality.

What are the typical sites of involvement for the African and sporadic forms of Burkitt lymphoma?

The African form of Burkitt lymphoma usually involves the jaw, while the sporadic form usually involves the abdomen.

What characterizes Hodgkin lymphoma?

Hodgkin lymphoma is characterized by the presence of Reed-Sternberg (RS) cells, which are large B cells with multilobed nuclei and prominent nucleoli.

What is the classic microscopic appearance of Reed-Sternberg cells?

Reed-Sternberg cells have multilobed nuclei and prominent nucleoli, often described as 'owl-eyed' nuclei.

What are the main subtypes of Hodgkin lymphoma?

The main subtypes of Hodgkin lymphoma are nodular sclerosis, lymphocyte-rich, mixed cellularity, and lymphocyte-depleted.

Which is the most common subtype of Hodgkin lymphoma and what are its features?

Nodular sclerosis is the most common subtype, characterized by bands of sclerosis and lacunar cells in females.

What are the features of the mixed cellularity subtype of Hodgkin lymphoma?

The mixed cellularity subtype is associated with abundant eosinophils due to IL-5 secretion by Reed-Sternberg cells.

What are the features of the lymphocyte-depleted subtype of Hodgkin lymphoma?

The lymphocyte-depleted subtype is the most aggressive and is seen in elderly and HIV-positive individuals.

How does Hodgkin lymphoma typically present clinically?

Hodgkin lymphoma typically presents with painless lymphadenopathy, often localized to a single group of nodes, and B symptoms (fever, night sweats, weight loss).

How does Hodgkin lymphoma differ from non-Hodgkin lymphoma in terms of spread and cell composition?

Hodgkin lymphoma usually spreads in a contiguous fashion and is composed mainly of reactive inflammatory cells, with few neoplastic Reed-Sternberg cells. Non-Hodgkin lymphoma often has a noncontiguous spread and is composed mainly of neoplastic cells.

What is the significance of B symptoms in Hodgkin lymphoma?

B symptoms (fever, chills, night sweats) are due to cytokine release by Reed-Sternberg cells.