Leukemia, Myeloproliferative Disorders, Lymphadenopathy, and Lymphoma Flashcards

Flashcards for Acute and Chronic Leukemia, Myeloproliferative Disorders, Lymphadenopathy, and Lymphoma

What is the precursor for B and T cells?

Lymphoid blast

What type of cells does Myeloid blast can produce?

RBCs, Monocytes, Granulocytes and megakaryocytes

How is acute leukemia defined?

Accumulation of >20% blasts in the bone marrow

What are the three acute presentations of leukemia and why?

Anemia (loss of RBCs), thrombocytopenia (platelets can’t be formed), or neutropenia (neutrophils can’t be formed)

3 key features of Blasts

Very large (look at the size compared to an RBC) , Immature cell (doesn’t have much cytoplasm) , Punched out nucleolus (if you look at the nucleus it appears that a part of it has been hole punched out. This is the nucleolus

If there is an accumulation of Myeloid blasts this is called?

AML

If there is an accumulation of Lymphoid blasts this is called?

ALL

Key marker used to determine that the blast is a lymphoid blast

Tdt. Tdt is a DNA polymerase and it is present ONLY in the nucleus of lymphoid blasts.

Key marker to determine that the blast is a myeloid blast

Myeloperoxidase (MPO)

ALL (acute lymphoid leukemia)

Positive TdT (DNA polymerase that is present in the nucleus) ◦TdT is absent in myeloid blasts and also mature lymphocytes. This makes it a great marker that is specific to lymphoid blasts.

ALL (acute lymphoid leukemia)

Most commonly arises in children , Associated with Down syndrome after the age of 5

How is ALL subcalssfied ?

B-ALL and T-ALL. ◦Differentiated through surface markers , ◦Both B-ALL and T-ALL have Tdt positivity

B-ALL

most common type of ALL, Classical surface markers are CD10, CD19, CD20 , Has an excellent response to chemotherapy

B-ALL requires prophylaxis to the ?

scrotum and CSF

t(12;22)

has a good prognosis of B-ALL , more commonly seen in kids

t(9;22)

has a poor prognosis of B-ALL, classic Philadelphia chromosome seen in CML, subtype is seen in adults

T-ALL characteristic

Presents as a Thymic mass and in Teenagers

Acute lymphoblastic lymphoma vs acute lymphoblastic leukemia

mass in the thymus instead of in free flowing blood

Auer rod

aggregate of crystallized myeloperoxidase (MPO) , Because we see an Auer rod we know that this blast must be a myeloid blast

AML is subclassified into 3 ways:

By their cytogenetic abnormalities (Predominant mechanism of subclassification), Lineage of myeloid blast , Surface markers

A classic type of AML is

t(15;17) which is also called Acute Promyelocytic Leukemia

t(15;17) Acute Promyelocytic Leukemia

this translocation disrupts in the retinoic acid receptor (RAR). When this RAR is disrupted it prevents the ability of the cells to mature. So instead of maturing , promyelocytes accumulate, The promyelocytes contain numerous Auer Rods which have the potential of activating the coagulation cascade so there is a risk of DIC

How to treat t(15;17) Acute Promyelocytic Leukemia

ATRA is a derivative of vitamin A can bind to disrupted RAR and cause the promyelocyte to mature and to become neutrophils

Acute megakaryoblastic Leukemia is associated with

Down syndrome before the age of 5

Acute monocytic Leukemia is characterized by

monoblasts characteristically infiltrate the gums

Reasons AML may also arise from pre-existing dysplasia

prior exposure to alkylating agents (chemotherapy) or radiotherapy, Tend to develop Myelodysplastic Syndromes

Define Chronic leukemia

neoplastic proliferation of mature lymphocytes flowing around in the blood , results in a high WBC,Insidious onset, symptoms present very slowly and patients are often asymptomatic and they can live a long time with this disease, Seen in in older people

Define Chronic lymphocytic leukemia (CLL)

neoplastic proliferation of naive B cells (naive B cells are still considered mature) , These cells co-express CD5 and CD20 , Blood smear shows increased lymphocytes and smudge cells

Define small lymphocytic lymphoma

When CLL goes to the lymph nodes and cause a mass

Complications of Chronic lymphocytic leukemia (CLL)

Hypogammaglobulinemia , Autoimmune hemolytic anemia , Transformation to diffuse large B-cell Lymphoma

Hairy cell Leukemia

neoplastic proliferation of Mature Memory B cells, Characterized by hairy cytoplasmic processes (seen on peripheral blood), Cells are positive for TRAP (this is an enzyme, tartrate resistant acid phosphatase)

Clinical Feature of Hairy cell Leukemia

Splenomegaly (red pulp), Usually absent lymphoadenopathy , Dry tap with bone marrow aspiration

Hairy cell Leukemia treatment

Excellent response to a drug called 2-CDA , adenosine deaminase inhibitor. This causes adenosine to accumulate to toxic levels in the neoplastic B cells

Define ATLL (Adult T cell leukemia lymphoma)

Neoplastic proliferation of mature CD4+ T cells , Associated with HTLV-1 (human T cell leukemia virus 1). This virus is particularly seen in Japan and Caribbean

Classic Clinical Features of ATLL

Rash (a general principal of T cell leukemias is that they like to go to skin and cause rash), Generalized lympadoenapthy and Hepatosplenomegaly , Lytic bone lesions with hypercalcemia

Define Myeloproliferative Disorders

all of the cells, 1.RBCs, 2.Neutrophils/Basophils/ eosinophils, 3.monocytes, 4.megakaryocytes are increased, but they are classified based on the dominant myeloid cell produced, Neoplastic proliferation of mature cells of myeloid lineage , Disease of late adulthood, Results in a high WBC count with hypercellular bone marrow

Common complications of Myeloproliferative Disorders

increased risk of hyperuricemia and gout , Progression to marrow fibrosis , Transformation to acute leukemia

Define Chronic Myeloid Leukemia (CML)

Neoplastic proliferation of mature myeloid cells, especially granulocytes, Basophils are characteristically increased, Driven by a t(9;22)

t(9;22)

translocation causes a fusion of BCR-ABL. ABL is a tyrosine kinase that phosphorylates JAK-STAT signalling pathways and eventually leads to proliferation and cell cycle progression. When ABL is fused with BCR, it can dimerize and become constituvely active. drives the overproduction of neoplastic cells

First line treatment for CML

Imatinib , Blocks excessive tyrosine kinase activity

Three phases of CML

Chronic phase (Splenomegaly is common), Accelerated phase (If the spleen is enlarging and becoming bigger it is a marker of this phase), Tranformation phase —> progresses to acute leukemia (Transformation to acute leukemia when it occurs result in either AML (2/3) or ALL (1/3)

How to differentiate CML from leukemoid reaction

CML granulocytes are LAP negative, CML is associated with increased basophils, CML granulocytes exhibit t(9;22)

Define Primary Myelofibrosis

Neoplastic proliferation of mature myeloid cells, especially megakaryocytes , Associated with JAK2 Kinase mutation , Megakaryocytes produce excess PDGF (Platlet Derived Growth Factor)

Clinical features of Primary Myelofibrosis

Splenomegaly due to extramedullary hematopoiesis, Leukoerythroblastic smear, Increased risk of infection, thrombosis and bleeding (due to pancytopenia)

What are tear drop cells and what are they associated with?

Associated with myelofibrosis, RBCs are generated with stiff fibrosis surrounding , they will be stretched and warped into these tear drop shapes as they try to leave and enter into the blood

Define Lymphadenopathy (LAD)

LAD is enlargement of lymph nodes, Painful LAD is seen with acute infection , Painless LAD is seen with 1. chronic inflammation, 2. metastatic carcinoma, or 3. lymphoma

Hyperplasia regions of Lymphadenopathy (LAD)

Follicles: Rheumatoid arthritis and early HIV, Paracortex: Viral infection, Sinus Histiocytes: Lymph node draining tissue with cancer

Define Lymphoma

neoplastic proliferation of lymphoid cells that forms a mass , May arise in lymph node or in extranodal tissue , Divided into Non-Hodgkins Lymphoma (NHL) and Hodgkin lymphoma (HL)

NHL Classified by:

Cell type , Cell size, Pattern of cell growth - ex. Do the cells grow in a diffuse sheet or do they form follicles, Expression of surface markers, Cytogenetic translocations

Key lymphomas that arise from small neoplastic B cells.

Follicular lymphoma, Mantle Cell lymphoma, Marginal zone lymphoma, small lymphocytic lymphoma (when CLL involves the lymph nodes)

Define Follicular Lymphoma

Neoplastic small B cells (CD20+) that make follicle-like nodules, Clinically presents in late adulthood with painless LAD, Driven by t(14;18)

t(14;18)

BCL2 on chromosome 18 translocates to Ig heavy chain locus on chromosome 14, Results in overexpression of BCL2, which inhibits apoptosis

Follicular Lymphoma treatment

Low dose Chemotherapy or rituximab is the treatment reserved for symptomatic pt

Complication of Follicular Lymphoma

Progression to diffuse Large B cell lymphoma - can pick up additional mutations over time, Presents as an enlarging lymph node

Differentiating between follicular Lymphoma from follicular hyperplasia

Disruption of normal lymph node architecture, Lack of tingible body macrophages in the Germinal Centers, Expression of BLC2 in follicles , Monoclonality

Mantle Cell Lymphoma

Neoplastic small B cells (CD20+) that expand the mantle zone, Clinically present in late adulthood with painless LAD, Driven by t(11;14)

t(11;14)

Cyclin D1 on chromosome 11 tranlocates to Ig heavy chain on chromosome 14, Overexpression of cyclin D1 promotes G1/S transition in cell cycle -> rapid proliferation

Marginal Zone Lymphoma

Neoplastic small B cells (CD20+) that expand marginal zone, Associated with chronic inflammatory states, t(11;18)

H.pylori gastritis

overtime you can get a marginal zone lymphoma in mucosal site (ex. Stomach). This is called a MALToma. A Gastric MALToma, in the mucosa of the stomach can possibly regress if the H.pylori is treated

Burkitt Lymphoma

Neoplastic intermediate-sized B cells (CD20+), Associated with EBV, Classically this tumor presents as an extranodal mass in child or young adult

Forms of Burkitt Lymphoma

African form - usually produces a mass in the jaw or facial bones, Sporadic form - usually produces a mass in the abdomen

Burkitt Lymphoma driven by

Driven by translocations of c-myc (chromosome 8), lots of growth, High mitosis rate and starry-sky appearance

Define Diffuse Large B Cell Lymphoma (DLBCL)

Neoplastic large B cells (CD20+) that grow diffusely in sheets , Most common form of NHL, Clinically aggressive

Hodgkin Lymphoma

you have rare neoplastic cells, called Reed-Sternberg cells that create cytokines that draw in other inflammatory cells which then results in the production of a mass , Neoplastic proliferation of Reed-Sternberg cells

Define Reed-Sternberg cells

A Large B cell with multilobed nuclei and prominent nucleoli , They are CD15+ and CD30+ (there is no CD20 expression here, despite being a B cell)

What do Reed-sternberg (RS) cells secrete?

cytokines , As a result a subset of these patients can present with “B” symptoms (fevers, chills and night sweats)

Hodgkin Lympoma subtypes:

Nodular sclerosis (most common, 70% of cases), Lymphocyte-rich, Mixed cellularity , Lymphocyte-depleted

Nodular Sclerosis subtype

Classic presentation is the patient having an enlarging cervical neck lymph node or mediastinal lymph node in a young adult, usually female, Biopsy reveals a lymph node that is divided by bands of fibrosis

hallmark of Nodular sclerosis subtype of Hodgkin’s lymphoma

Reed-sternberg cells often sit in the big open spaces/ Lacunar Cells

Important considerations regarding other subtypes of Hodgkin Lympoma

Lymphocyte-rich subtype has the best prognosis, Lymphocyte-depleted subtype has the worst prognosis (seen in elderly and HIV positive individuals), Mixed cellularity subtype is associated with abundant eosinophils (IL-5)

CD10, CD19, CD20 will be found on

follicular lymphoma, diffuse large B cell lymphoma, burkitt’s lymphoma

CD5, CD19, CD20 will be found on

chronic lymphocytic leukemia