Diseases Exam 4 Flashcards
Chronic Myeloid Leukemia
Things you must know:
- Neutrophilic leukocytosis
- Basophilia
- Philadelphia chromosome t(9:22)
- Three phases
Pathophysiology: t(9:22) creates BCR-ABL fusion protein which is an uncontrolled tyrosine kinase causing defects in normal neutrophil differentiation.
Lab findings: +++ WBC, Neutrophilia w/ left shift, basophilia, low hemoglobin, +platelet count (at first), decreased LAP (leukocyte alkaline phosphatase)
Clinical findings:
Sx: Slow onset, fever, fatigue, night sweats, abdominal fullness
Signs: Splenomegaly, hepatomegaly
Phases: Chronic phasee (stable counts, easily controlled, 3-4 years if untreated) then 50/50 go to Accelerated phase (unstable counts, blast crisis within 6-12 months) or to Blast crisis (acute leukemia, high mortalitiy).
Remission:
Hematologic remission - no splenomegaly, WBC
Cytogenetic - no t(9:22)
Molecular - no BCR/ABL
Chronic Myeloproliferative Disorders
Things you must know:
- Malignant proliferation of myeloid cells (not blasts, but maturing cells) in blood, bone marrow
- Four disorders: CML (neutrophiils), PV (RBCs), ET(platelets), MF (everything)
- Occur only in adults
- Long course
Features common to all disorders: Increase WBC w/ left shift, hypercellular marrow, splenomegaly, may evolve into acute leukemia, mutatated tyrosine kinases
Polycythemia vera
Things you must know:
- High RBC (makes blood sludgy)
- Different from seconary polycythemia (smoker, high-altitude, tumor, etc.) –> look to EPO
- Thrombosis and hemorrhage
- Jak-2 mutation
Signs: headache, pruritis, dizziness, thrombosis, infarction
Symptoms: spleno/hepatomegaly, plethora (flushing)
Mutated JAK-2: activity increased in PV. Cells grow on their own. Important for Dx and drug therapy.
Treatments and Prognosis:
Rx: phlebotomy, maybe myelosuppressive drugs
Prognosis: median survival: 9-14 years, death from thrombosis or hemorrhage, leukemic transformation in some patients (not as common as in CML)
Essential Thrombocythemia
Things you must know:
- Very high platelet count in blood (>600,000 –> often over 1,000,000)
- Can occur in young women
- Diagnosis of exclusion
- Thrombosis and hemorrhage
Dx: platelets > 600,000, Hgb
Hg
Chronic Myelofibrosis
Things you must know:
- Panmyelosis –> then marrow fibrosis
- Extramedullar hematopoeisis
- Teardrop RBCs
Sx: LUQ fullness, weakness, fatigue, palpitations
Signs: Marked splenomegaly, pallor, tachycardia
Treatment: supportive, maybe myelosuppressive drugs early on
Prognosis: Median survival: 3-5 years, death from marrow failure, leukemic transformation
Multiple Myeloma
Things you must know:
- Monoclonal plasma cell proliferation
- Monoclonal gammopathy (M-spike)
- Decreased normal immunoglobulins
- Osteolytic lesions. (hypercalcemia)
Lab findings: M- spike (generally IgG never IgM), Bence-jones protein (light chains) in urine, decreased normal Ig
Important tests: Serum protein electrophoresis, Serum immunoelectrophoresis, and urine immunoelectrophoresis
Clinical features: bone pain (80%), bruising/bleeding, infx, hypercalcemia (osteolytic lesions), renal failure, hyperviscosity (decreased vision, purpura, confusion.
Classic triad: anemia, bone pain, renal failure.
Average age of Dx: 69 years old.
Major COD: infection or renal failure
Treatment: Dexamethasome, Melphalan, Cyclophosphamide, or autologous peripheral blood stem cell transplant (PBSC), thalidomide, lenalidomide, bortezomib
Support w/ Bisphosphonates, and EPO
Morphology:
Blood: anemia, rouleaux, flame cells, russell bodies, dutcher body, and mott cell.
Marrow: plasma cells, amyloid (congo red stain + polarized lens)
Can develop from MGUS (monoclonal gammopathy of undertermined significance) –> cmall M spike w/o myeloma symptoms.
Prognosis: Conventional chemo 3-4 years. Intensive = variable depending on age
Other plasma cell tumors: Solitary plasmacytoma, plasma cell leukemia, waldenstrom macroglobulinemia, MGUS.
Waldenstrom macroglobulinemia
- Lymphoplasmacytoid lymphoma -lymphoid cells that act plasma cell like
- Make IgM (give away)
- Hyperviscosity syndrome–> may present w/ retinal problems.
Chronic lymphocytic leukemia
Pathophysiology: CLL is an uncontrolled clonal accumulation of mature lymphocytes. Mutated IgV-H genes. Often BCL-2 gene rearrangement (prevents apoptosis)
Things you must know:
- Small, mature lymphocytes (=small lymphocytic lymphoma)
- B cell, but CD5+ (weird!)
- Long but inexorable course
Dx: Lymphocytosis >5000/ml, flow cytometry (CD5+, CD19+, CD20+, CD23+), cytogenetics (FISH)
KNOW CD5+ and TdT-!
Always get FISH studies w/ CLL.
Sx: progressive adenopathy, fatigue, malaise, weight loss, fevers
CBC = + or +++WBC and hypogammaglobinulinemia
Tough DDX vs. Mantle Cell Lymphoma (Nasty aggressive NHL Key indicator is CD23-)
Autoimmune sequelae and Richter’s transformation are long-term complications (AIHA, Pure red cell aplasia, Idiopathic thrombocytopenic purpura (ITP), neutropenia)
Staging: Rai system. 0-4. Median survival Rai 0 is > 10 years; Rai 1 = 7 years; Rai 3 = 2-5 years
Prognosis: Better if IgV-H mutation, Worse if CD38+, ZAP70+; counts (how are normal cells), adenopathy, BM pattern
Death from infection!
Most common leukemia in adults (older than 40). Median age of dx is 65 years.
Median survival = 9 years.
Rx = Conservative (not always treating) Ibrutinib (very effective, but extreme cost toxicity.)
Rebound Angiogenesis
Rapid growth of cancer when an angiogenesis inhibitor is stopped.
Chronic lymphoproliferative disorders
Things you must know:
- Malignant proliferation of lymphocytes in blood, marrow
- Occur only in adults
- Many disorders; CLL most important
- Long course; indolent but incurable
Hairy Cell Leukemia
Things you must know:
- Hairy cells
- Splenomegaly w/o lymphadenopathy
- Pancytopenia (and monocytopenia)
- TRAP stain +
Clinical findings: Older (40-60)
M:F = 5:1
Hypercellular bone marrow w/ moth eaten appearance.
Reticulin fibrosis (chicken-wire appearance)
Prolymphocytic Leukemia
Things you must know:
- Prolymphocytes
- Splenomegaly w/o lymphadenopathy
- Rare
- Aggressive
Labs: ++ WBC, -Hgb, -platelets
Large Granulated Lymphocyte Leukemia
Things you must know:
- Large granulated lymphocytes
- T-cell
- Neutropenia
- Long survival
Clinical findings:
- Infections (neutropenia)
- Long survival
Immunophenotype: T cells
Labs: +WBC, Neutropenia
Follicular Hyperplasia
Things you must know:
- Large, irregular follicles
- Mixture of cells in germinal centers
- Tingible body macrophages
- B-cell response to some immune stimulus.
Interfollicular Hyperplasia
Things you must know:
- Expanded area between follicles
- Mixture of cells
- Partial effacement
- T-cell response to some immune stimulus
Non-Hodgkin Lymphoma
Things you must know:
- Malignant proliferation of lymphoid cells (blasts or mature cells) in lymph nodes
- Skips around the body
- Many subtypes
- Most are B cells
Sx: Painless, firm lymphadenopathy; extranodal manifestations,
“B” Sx: weight loss, night sweats, fever
Low grade = older patients, indolent (incurable), small mature cells, non-destructive
High grade = Children sometimes, Aggressive (curable), Big ugly cells, destructive
Classification: Working = Low, Intermediate, High grade; REAL/WHO = B-cell vs. T-cell.
Types:
Low Grade = SLL, Malt lymphoma, Follicular lymphoma, mycosis fungoides
High Grade = Large cell lymphoma, Lymphoblastic lymphoma, Burkitt lymphoma
Small lymphocytic lymphoma
Things you must know:
- Small mature lymphocytes
- Same disease as CLL
- B-cell lesions, but CD5+
- Long course, death from infx
Richter’s transformation = bad
Marginal Zone Lymphoma
Things you must know:
- Actually a bunch of lymphomas
- Marginal zone pattern
- Malt lymphoma
- H. pylori
Mantle Cell Lymphoma
Things you must know:
- Mantle zone pattern
- Small angulated lymphocytes
- t(11:14) - bcl-1 and IgH; Cyclin D1 positive
- Aggressive and Nasty
Ddx vs CLL = Mantle cell = Cd23-
Follicular lymphoma
Things you must know:
- Follicular pattern
- Small cleaved cell, mixed or large cell
- Grade 1, 2, or 3
- t(14:18) and - IgH and bcl-2
Butt cells!
Stage I = Single node (90% 5 yrs.)
Stage II = Two or more nodes on same side of diaphragm (90% 5 yrs.)
Stage III = Lymph nodes on both sides of (40% 5 yrs.)
Stage IV = Diffuse extranodal involvement (40% 5 yrs.)
A= no additional symptoms B = weight loss, night sweats, fever
Mycosis Fungoides/Sezary Syndrome
Things you must know:
- Skin lesions
- Blood involvement
- Cerebriform lymphocytes
- T-cell immunophenotype.
Histo: Pautrier microabscess in skin; Sezary cells (cerebriform appearance)
Diffuse Large Cell Lymphoma
Things you must know:
- Large B cells
- Extranodal involvemnet
- Grows rapidly –> poor prognosis
Lymphoblastic Lymphoma
Things you must know:
- Two types: B and T
- Lymphoblasts in diffuse pattern
- Same as ALL
- T-lymphoblastic lymphoma often in teenage male w/ mediastinal mass.
Burkitt Lymphoma
Things you must know:
- Child w/ fast-growing, extranodal mass
- Starry-sky pattern (has tingible body macrophages)
- t(8:14) (c-myc)
- Same as Burkitt leukemia
African type (jaw) and non african type (abdominal mass)
Adult T-cell Leukemia/Lymphoma
Things you must know:
- Japan/Caribbean basin (moving into US. Florida now?)
- HTLV-1
- Skin lesions, hypercalcemia
- very aggressive
Hodgkin Lymphoma
Things you must know:
- Younger patients, good prognosis
- Contiguous spread (not jumping)
- Five subtypes
- Reed Sternberg cell (One huge giant cell. Giant nuclei with distinct large nucleoli (Owl’s eye))
Subtypes: Nodular lymphocyte predominance Hodgkin lymphoma (best outcome ---> young healthy male) Classical Hodgkin lymphoma: -Nodular sclerosis -Lymphocyte rich -Mixed cellularity -Lymphocyte depletion
Prognosis is based on stage, not subtype. Subtypes have different prognosis based on when they are normally caught not on the virulence of the disease.
Rx and Prognosis:
- Surgery, chemo, radiation
- Prognosis depends on stage
- Concern about creating secondary leukemia
Nodular L-P Hodgkin Lymphoma
Things you must know:
- Asymptomatic young male with cervical lymphadenopathy
- Good prognosis
- B cell origin
- Popcorn cells
Nodular Sclerosis Hodgkin Lymphoma
Things you must know:
Most common subtype
Good prognosis (early stage)
Lacunar cells
Mixed cellularity Hodgkin Lymphoma
Things you must know:
- Worse prognosis
- Usually disseminated at presentation
- Classic Reed-Sternberg cells
- Mixture of background cells.
Lymphocyte-Rich Hodgkin Lymphoma
Things you must know:
- Uncommon
- Usually localized at presentation
- Popcorn cells
Lymphocyte Depletion Hodgkin Lymphoma
Things you must know:
- Rare
- Often disseminated at presentation
- Classic Reed-Sternberg cells
- Collagen or reticulin background.
Bruton’s Agammaglbulinemia or XLA immunodeficiency
Mutated BTK gene encoding the enzyme Bruton’s Tyrosine Kinase.
Key enzyme involved in signal transduction downstream of the pre-BCD and BCr.
Mutated in immunodeficiency XLA. –> very few circulating B cells and negligible serum Ig.
85% of agammaglobulinemia (AKA Bruton’s Agammaglobulinemia)
MHC I deficiency
Causes decreased amount of CD8+ T cells.
Increased susceptibility to viral infections.
Can be due to a deficiency in TAP proteins. (autosomal recessive)
MHC II deficiency
A mild form of SCID that is due to a failure of gene regulation.
Onset after 6 months.
Hypoglobulinemia.
Low CD4+ counts.
Autosomal recessive trait.
Treat w/ Hematopoetic stem cell trasnplant (HSCT).
Common variable immunodeficiency CVID
Impacts later stages of B-cell development.
Results in reduced serum Ig, memory B cells, class switch recombination, and B-cell activation
Mutations in CD40 ligands on T-cells, CD-19, and others have been implicated in CVID patients.
