-
Acute Leukemia
- Acute Leukemia:
- -neoplastic proliferation of blasts
- - >20% blasts in BM
- -crowd out normal hematopoiesis
- -usually seen in kids and teenagers
- Subtypes:
- 1. Acute Lymphoblastic Leukemia (ALL)
- -B-ALL
- -T-ALL
- 2. Acute Myelogenous Leukemia (AML)
- -Acute Promyelocytic Leukemia
- -etc
-
Chronic Leukemia
-background
-subtypes
- Chronic Leukemia:
- -neoplasm of mature circulating lymphocytes
- -characterized by high WBC
- -insidious onset
- -seen in older adults
- Subtypes:
- 1. Lymphoid
- -Chronic Lymphocytic Leukemia (CLL)
- -Small Lymphocytic Lymphoma (SLL)
- -Hairy Cell Leukemia
- -Adult T Cell Leukemia (ATLL) (NHL)
- -Mycosis Fungoides (NHL)
- 2. Myeloid
- -Chronic Myeloid Leukemia
- -Myeloproliferative Disorders
-
Myeloproliferative Disorders (MPD)
-background
-complications
subtypes
- Background:
- -neoplastic proliferation of mature myeloid cells
- -hypercellular bone marrow
- -increase in all cells of myeloid lineage
- Complications:
- -hyperuricemia and gout (turnover)
- -marrow fibrosis
- -transformation to acute leukemia
- Subtypes:
- -Chronic myeloid leukemia (CML) (Granylocytes)
- -Polycythemia Vera (RBCs)
- -Essential Thrombocythemia (Plts)
- -Myelofibrosis (megakaryocytes)
-
Lyphoma
-background
-subtypes
- -neoplastic proliferation of lymphoid cells that forms a mass
- -may arise in a LN or in extranodal tissue
Hodgkin Lymphoma (40%)
- Non-Hodgkin Lymphoma (60%)
- 1. Neoplasms of Mature B Cells:
- -Follicular lymphoma
- -Mantle Cell Lymphoma
- -Marginal Zone Lymphoma
- -Burkitt Lymphoma
- -Diffuse Large B cell Lymphoma
- 2. Neoplasms of Mature T Cells (also Chronic Leukemia)
- -Adult T Cell Lymphoma
- -Mycosis Fungoides/Sezary Syndrome
-
Leukemoid Reaction
-features
-vs. CML
- Features:
- -acute inflammatory response to infection
- -↑ WBC count
- -↑ neutrophils and neutrophil precursors (bands, Left shift)
- -↑ leukocyte alkaline phosphatase (killing to infection)
- vs CML:
- -↓ LAP (having a neoplastic party)
- -increased basophils
- -t(9;22)
-
Non-Hodgkin's vs Hodgkin's Lymphoma
-
Hodgkin's Lymphoma
-pathophysiology
-types and prognosis
- Pathophysiology:
- -proliferation of Reed-Sternberg cells
- -RS cells secrete cytokines that attract reactive lymphocytes and may lead to fibrosis
- Reed Sternberg Cells
- -binucleate or bilobed
- -"owl's eye"
- -CD30+, CD15+, CD20- (B cell origin)
![Image Upload 6](/flashcards/images/image_placeholder.png)
- Nodular Sclerosing Form:
- -most common
- -affects women and men equally
- -RS cells in lake-like spaces
- -nodules divided by bands of sclerosis
- -best prognosis
- Lymphocyte-Depleted Form:
- -most aggressive form
- -elderly and HIV positive
-
Follicular Lymphoma
-epidemiology
-pathophysiology
-presentation
-treatment
- Pathophysiology:
- -t(14;18)
- -translocation of heavy chain Ig (14) and Bcl2 (18)
- -Bcl2 promotes apoptosis
- -Bcl2 expressed in most cells in the body but not follicular B cells (want apoptosis during SHM)
- -expansion of follicle
- Presentation:
- -painless lymphadenopathy
- -indolent course
- -difficult to cure
- Treatment:
- -low dose chemo
- -rituximab
-
Mantle Cell Lymphoma
-epidemiology
-pathophysiology
- Epidemiology:
- -Older males
- Pathophysiology:
- -t(11;14)
- -translocation of cyclin D1 (11) and heavy chain Ig (14)
- -cyclin D1 promotes G1/S transition
- -expansion of mantle zone
-
Marginal Zone Lymphoma
- Pathophysiology:
- -associated with chronic inflammatory state
- -marginal zone is formed by activated cells
- -MALToma (H pylori)
- -expansion of marginal zone
-
Burkitt's Lymphoma
-epidemiology
-pathophysiology
-presentation
-pathology
- Epidemiology:
- -adolescents
- -young adults
- Pathophysiology:
- -t(8;14)
- -translocation of c-myc (8) and Ig heavy chain (14)
- -associated with EBV
- Presentation:
- -African form: jaw
![Image Upload 8](/flashcards/images/image_placeholder.png) - -Sporadic Form: abdomen or pelvis
- Pathology:
- -"starry sky" appearance (sheets of lymphocytes with interspersed MPs)
![Image Upload 10](/flashcards/images/image_placeholder.png)
-
Diffuse Large B-cell Lymphoma
-epidemiology
-pathophysiology
-prognosis
- Epidemiology:
- -usually older adults
- -20% in children
- -most common form of adult NHL
- Pathophysiology:
- -sporadic
- -transformation from low-grade lymphoma (follicular)
- -grow diffusely in sheets
- -may be mature T cell in origin (20%)
- Prognosis:
- -clinically aggressive
-
Multiple Myeloma
-epidemiology
-pathophysiology
-findings
-associated with
- Epidemiology:
- -most common primary bone tumor in elderly (>40-50)
- Pathophysiology:
- -malignant proliferation of plasma cells in the bone marrow
- -monoclonal: IgG (55%) or IgA (25%)
- Findings:
- -M spike on protein electrophoresis
![Image Upload 12](/flashcards/images/image_placeholder.png) - -high serum IL6 sometimes present
- -Bence Jones protein in urine
- -Rouleaux formation
- -numerous plasma cell with "clock face" chromatin and intracytoplasmic inclusions containing Ig
![Image Upload 14](/flashcards/images/image_placeholder.png)
- CRAB
- -hyperCalcemia
- -Renal insufficiency
- -Anemia (normochromic, normocytic)
- -Bone lytic lesions/Back pain
- Associated with:
- -increased susceptibility to infections
- -primary amyloidosis (AL)
- Distinguish from:
- -Waldenstrom's Macroglobulinemia
-
Waldenstrom Macroglobulinemia
-pathophysiology
-findings
- Pathophysiology:
- -B cell lymphoma with monoclonal IgM production
- -IgM is a pentamer → hyperviscosity
- Findings:
- -M spike (IgM)
- -lymphadenopathy
- -bone lesions are absent
- -visual and neurologic deficits (serum hyperviscosity)
-
MGUS
Monoclonal Gammopathy of Undetermined Significance
- Epidemiology:
- -common in elderly (5% of 70 yo)
- Pathophysiology:
- -monoclonal expansion of plasma cells with M spike
- -other features of multiple myeloma are absent
- Prognosis:
- -1% develop multiple myeloma every year
-
Acute Lymphoblastic Leukemia/Lymphoma (ALL)
-epidemiology
-pathophysiology
-B-ALL
-T-ALL
- Epidemiology:
- -<15 years
- -associated in children with Down syndrome (>5 years)
- Pathophysiology:
- -accumulation of lymphoblasts in bone marrow
- -lymphoblasts are TdT+, CALLA+
- -called lymphoma when forms a mass in the mediastinum (T-ALL)
- -may spread to CNS and testes
- B-ALL
- -most common type of ALL
- -CD10+, CD19+, CD20+
- -t(12;21): good prognosis
- -t(9;22) Ph+ (poor prognosis)
- T-ALL
- -CD2-CD8+
- -mediastinal thymic mass (lymphoma)
-
Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL)
-epidemiology
-pathophysiology
-findings
-complications
-SLL
- Epidemiology:
- -> 60 years old
- -most common leukemia over all
- Pathophysiology:
- -malignant proliferation of naive B cells
- -CD5+ (usually a T cell marker) and CD20+
- Findings:
- -smudge cells
![Image Upload 18](/flashcards/images/image_placeholder.png)
- Complications:
- -hypogammaglobulinemia: Infection (most common cause of death)
- -autoimmune hemolytic anemia
- -transformation to diffuse larger B-cell lymphoma (Richter transformation)
- SLL:
- -same as CLL but has increased peripheral blood lymphocytosis and generalized lymphadenopathy (Lymphoma)
-
Hairy Cell Leukemia
- Epidemiology:
- -adults (elderly)
- Pathophysiology:
- -proliferation of mature B cells
- Findings:
- -"hairy" cells
![Image Upload 20](/flashcards/images/image_placeholder.png) - -stains TRAP positive (tartrate-resistant acid phosphatase)
- -splenomegaly (accumulation in red pulp)
- -dry tap on BM bx
- Treatment:
- -cladribine (2-CDA, adenosine analog)
-
Adult T-Cell Leukemia/Lymphoma
-epidemiology
-presentation
- Epidemiology:
- -adults
- -associated with HTLV-1 (Japan, West Africa and Caribbean)
- Presentation:
- -rash
- -lymphadenopathy
- -HSM
- -lytic bone lesions with hypercalcemia
- -aggressive
- *can be confused with multiple myeloma
-
Mycosis Fungoides
-epidemiology
-pathophysiology
-presentation
-sezary syndrome
- Pathophysiology:
- -neoplastic proliferation of mature CD4 T cells
- Presentation:
- -localized skin rash, plaques and nodules (Pautier microabscesses)
- -indolent course
- Sezary syndrome:
- -spread to involve the blood
- -Sezary cells (cerebriform nuclei)
![Image Upload 22](/flashcards/images/image_placeholder.png)
-
Acute Myelogenous Leukemia (AML)
-epidemiology
-pathophysiology
-presentation
-acute promyelocytic leukemia
- Epidemiology:
- -median onset 65 years
- Pathophysiology:
- -neoplastic accumulation of myeloblasts (>20%) in BM
- -may also rise from myelodysplastic syndrome
- Presentation:
- -Auer rods (MPO aggregates)
![Image Upload 24](/flashcards/images/image_placeholder.png)
- Acute promyelocytic leukemia
- -t(15;17): M3 AML subtype
- -involves retinoic acid receptor
- -treat with all-trans retinoic acid (ATRA) (vitamin A): causes blasts to mature
- -treatment can release Auer rods → DIC
-
Chronic Myelogenous Leukemia (CML)
-epidemiology
-pathophysiology
-presentation
-labs
-complications
-treatment
- Epidemiology:
- -highest incidence at 30-60 years
- Pathophysiology:
- -neoplastic proliferation of mature myeloid cells (especially granulocytes)
- -t(9;12) Philadelphia chromosome
- -myeloid stem cell proliferation
- Presentation:
- -increased neutrophils, metameylocytes, basophils
- -splenomegaly
- -very low leukocyte alkaline phosphatase (vs. leukemoid reaction)
![Image Upload 26](/flashcards/images/image_placeholder.png)
- Labs:
- -↑ WBCs
- -↑ Platelets
- -↓ RBCs
- Complications:
- -may accelerate and transform to AML or ALL ("blast crisis")
- -enlarging spleen is often followed by transformation
- *mutation is in stem cell (can be myeloid or lymphoid)
- Treatment:
- -imatinib (inhibits bcr-abl tyrosine kinase)
-
Myeloproliferative Disorders
-basic principles
-presentation
-complications
-types
- -neoplastic proliferation of mature cells of myeloid lineage
- -older adults
- Common Presentation:
- -high WBC count
- -hypercellular bone marrow
- -cells of ALL myeloid lineages increased but classified based on dominant cells
- Complications:
- -increased risk of hyperuricemia and gout (high turnover)
- -progression to marrow fibrosis
- -transformation to acute leukemia
- Types:
- -Polycythemia Vera
- -Essential Thrombocytosis
- -Myelofibrosis
- -CML
-
Polycythemia Vera
-pathophysiology
-presentation
-labs
-treatment
- Pathophysiology:
- -abnormal clone of HSC with constituitively active JAK2 receptors
- -proliferation of RBCs without EPO stimulation
- Presentation:
- -due to hyperviscosity of blood
- -blurry vision and HA
- -increased risk of venous thrombosis (Budd Chiari syndrome)
- -flushed face
- -itching (especially after bathing)
- Labs:
- -↑ RBCs
- -↑ WBCs
- -↑ platelets
- Treatment:
- -phlebotomy
- -hydroxyurea
-
Essential Thrombocytosis
-pathophysiology
-presentations
-labs
- Pathophysiology:
- -similar to PV but specific for megakaryocytes
- -associated with JAK2 kinase mutation
- Presentation:
- -bleeding or thrombosis
- -rarely progresses to marrow fibrosis or acute leukemia
- Labs:
- -↑ platelets
- -normal RBCs (↑ in pathoma)
- -normal WBCs (↑ in pathoma)
-
Myelofibrosis
- Pathophysiology:
- -fibrotic obliteration of bone marrow
- -excessive proliferation of megakaryocytes → ↑ PDGF
- -PDGF causes fibrosis
- -30-50% have JAK2 mutation
- Presentation:
- -splenomegaly (extramedullary hematopoiesis)
- -tear drop cell
"Bone marrow is crying because it's fibrosed!"
-
t(9;22)
- Philadelphia Chromosome
- CML
Philadelphia CreaML cheese
-
t(8;14)
- Burkitt's lymphoma
- -C-myc activation
-
t(11;14)
- Mantle cell lymphoma
- -cyclin D1 activation
-
t(14;18)
- Follicular lymphoma
- -bcl2 activation
-
t(15;17)
M3 type of AML (responsive to ATRA)
-
Langerhans Cell Histiocytosis
- Pathophysiology:
- -proliferative disorders of dendritic cells from monocyte lineage
- -cells are functionally immature and don't stimulate T cells as APCs
- Presentation:
- -child with lytic bone lesions and skin rash
- Findings:
- -express S-100 (neural crest origin)
- -express CD1a
- -Birbeck granules ("tennis rackets")
![Image Upload 28](/flashcards/images/image_placeholder.png)
-
Polycythemias (associated diseases)
- Relative
- -decreased plasma volume
- -no associated disease
- Appropriate Absolute:
- -increased RBC mass
- -decreased O2 sat
- -associated diseases: lug disease, congenital heart disease, high altitude
- Inappropriate Absolute:
- -increased RBC mass
- -no change in O2 sat
- -associated disease: RCC, Wilms tumor, cyst, HCC, hydronephrosis
- -due to ectopic EPO
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