Oncology Flashcards
History and PE of acute leukemias
Rapid onset w/ si/sx of anemia (pallor, fatigue), thrombocytopenia (petechiae, purpura, bleeding), and bone pain (medullary expansion and periosteal involvement)
Hsm and swollen/bleeding gums
Blasts
immature blood cells
BM findings in acute leukemia
BM with 20-30% blasts
AML = myeloblasts
ALL = lymphoblasts
AML vs ALL blasts appearance
AML: large, uniform myeloblasts with round or kidney-shaped nuclei and prominent nucleoli
ALL: large, uniform lymphoblasts- large cells w/ high N:C ratio
Leukostasis
Occurs when WBC is very high
Blasts occlude the microcirculation -> pulmonary edema, CNS symptoms, ischemic injury, and DIC
Leukemoid reaction vs. CML
Both have increased WBC count, but leukemoid reaction has increased LAP
Leukemoid reaction: leukocytosis 2/2 infection/sepsis
Auer rods
Rods present in APL
APL treatment
all-trans retinoic acid
-ATRA therapy
APL associations
Increased incidence of DIC
Chromosomal translocation: q15,17
Treatment of acute leukemia
Patients should be well hydrated prior to therapy
High WBC = start allopurinol to prevent TLS
Chemotherapeutic agents; antibiotics, transfusions, and colony-stimulating factors are also used
BM transplantation may be required for those who do not achieve remission
Treatment of leukostasis
Hydroxyurea +/- leukopharesis to rapidly decrease the WBC
Ages of leukemia
0-20: ALL
20-40: AML
40-60: CML
60-80: CLL
CLL
Clonal proliferation of functionally incompetent lymphocytes
-accumulates in BM, blood, LN, spleen, liver
Involves well-differentiated B cells
Diagnosis of CLL
-cell markers
Biopsy is rarely required for diagnosis Clinical picture (fatigue, malaise, infection, LAD, splenomegaly) Flow cytometry: CD5, CD20, CD2 positive together (normally CD5 is T cell specific while CD20 and CD2 are B cell specific)
Peripheral smear: abundance of small, normal appearing lymphocytes and ruptured smudge cells on smear
-smudge cells 2/2 cover slip crushing fragile leukemic cells
Labs: granulocytopenia, anemia, thrombocytopenia 2/2 marrow infiltration
Abnormal leukemic function = hypogammaglobulinemia
Tx of CLL
Palliative treatment, often withheld until pts are symptomatic
-ie recurrent infection, anemia, thrombocytopenia, splenomegaly, LAD
Tx: chemo
Not curable, but long dz-free intervals can be achieved
CML
Clonal proliferation of myeloid progenitor cells -> leukocytosis with excess granulocytes and basophils
-sometimes increased erythrocytes and platelets also
CML = BCR-ABL translocation must be present (Philadelphia chromosome of q(9,22)
Sx of CML
Anemia, splenomegaly (LUQ pain and early satiety), hepatomegaly, constitutional symptoms
Disease phases of CML
Chronic: without treatment, usually anemia, splenomegaly, constitutional symptoms
Accelerated: transition to blast crisis -> increased peripheral and BM blood counts
-suspected when diff shows abrupt increase in basophils and thrombocytopenia
Blast crisis: resembles acute leukemia
Blast crisis
Occurs in CML
Increased basophils and thrombocytopenia
Resembles acute leukemia
Granulocytes in all stages of maturation
CML
Lab values in CML
Low LAP
High LDH, uric acid, and B12levels
Diagnosis of different leukemias
Acute: Circulating blasts in the peripheral blood, leukocytosis
CLL: Flow cytometry, lymphocytosis, granulocytopenia, anemia, thrombocytopenia, smudge cells
CML: luekocytosis (very high), granulocytes in all stages of maturation
Treatment of CML
Chronic: Imatinib, a non-receptor tyrosine kinase inhibitor
Blast crisis: same as for acute leukemia; can also involve dasatinib + stem cell transplantation
Hairy Cell Leukemia
Malignancy of well-differentiates B lymphocytes, usually affects older males
Presents: pancytopenia, BM infiltration, splenomegaly
Hx: weakness, fatigue, bruising and petechiae, infection (esp w/ MAC), abdominal pain, early satiety, weight loss
Dx of Hairy Cell Leukemia
Hairy cells in the blood, marrow, or spleen
TRAP staining: tartrate-resistant acid phosphatase staining of hairy cells, electron microscopy, and flow cytometry are helpful in distinguishing hairy cells
CBC: leukopenia
Peripheral smear: hairy cells OR monocytes with abundant pale cytoplasm and cytoplasmic projections
Treatment of Hairy Cell Leukemia
10% don’t need therapy
Those who develop progressive pancytopenia and splenomegaly need therapy
-mainstay = nucleoside analogs ie cladribine
Can also use splenectomy and IFN-a
Non-Hodgkins Lymphoma definition
Diverse group of diseases characterized by progressive clonal expansion of B cells, T cells, and/or NK cells
-2/2 chromosomal translocation especially t(14,18), the inactivations of tumor suppressor genes, or the introduction of exogenous genes by oncogenic viruses
MALT gastric lymphoma
a/w H pylori infection
Origin of most NHLs
B cell origin
NHL disease staging
Ann Arbor classification
Based on number of nodes and whether the disease involves sites on both ides of the diaphragm
Hodgkins Disease definition
Predominantly B cell malignancy with an unclear etiology
Types:
-nodular sclerosing: peak in the 3rd decade
-lymphocyte-depleting type: peak around age 60
Pel-ebstein fevers
1-2 weeks of high fever alternating with 1-2 afebrile weeks
-rare sign specific for Hodgkin’s disease
Alcohol induced pain
Rare sign specific for Hodgkin’s disease
Anemia + bone pain + renal failure
Multiple myeloma
Multiple myeloma: which cells
Clonal proliferation of malignant plasma cells, which then produce excessive Ig (IgA or IgG0 or Ig fragments
Diagnosis of Multiple Myeloma
> 10% plasma cells in the bone marrow
lytic bone lesions
M protein
M proteins
Present in MM, MGUS, CLL, lymphoma, Waldenstrom’s macroglobulinemia, and amyloidosis
Diagnostic tests for multiple myeloma
Skeletal survey, bone marrow biopsy, UPEP, SPEP,CBC
Treatment of Multiple Myeloma
Chemotherapy: melphalan + prednisone + other agents
Melphalan = oral alkylating agent
Waldenstrom’s macroglobulinemia
Clonal B cell disorder -> malignant monoclonal gammopathy
Elevated IgM -> hyperviscosity syndrome, coagulation abnormalities, cryoglobulinemia, cold agglutinin disease (autoimmune hemolytic anemia), and amyloidosis
Cryoglobulinemia
IgM disorder usually seen in HCV
Palpable purpura + proteinuria + hematuria + arthralgias + hsm + hypocomplementemia
Cold agglutinins
IgM disorder which causes numbness upon cold exposure
-seen with EBV, mycoplasma infection, and Waldenstroms
Waldenstrom’s symptoms
Lethargy, weight loss
Raynaud’s phenomenon
Neuro problems: AMS, sensorimotor peripheral neuropathy, blurry vision
Organ dysfxn affecting skin, GI, kidneys, lungs
MGUS is a precursor
Waldenstrom’s diagnosis
Labs: elevated ESR, uric acid, LDH, and alk phos
BM biopsy: abnormal plasma cells with Dutcher bodies
-Dutcher bodies = PAS + IgM deposits around the nucleus
SPEP and UPEP and immunofixation are helpful
Treatment of Waldenstrom’s
Plasmapharesis to remove excess IgG
Chemo to treat underlying pathology
Amyloidosis
-definition and classification
Extracellular deposition of protein fibrils
Types:
- AL: plasma cell dyscrasia. deposition of monoclonal light chains. a/w MM and Waldenstroms
- AA: deposition of acute phase reactant serum amyloid A. a/w chronic inflammatory dz ie rheumatoid arthritis, infections, and neoplasms
- Dialysis related: deposition of B2 microglobulin which accumulates in patients with long term dialysis requirements
- Heritable: deposition of abnormal gene products ie transthyretin which is prealbumin; heterogenous group of disorders
- Senile-systemic deposition of otherwise normal transthyretin
Major sites of amyloid deposition
Kidneys, heart, liver
Amyloidosis diagnosis
Tissue biopsy showing apple green birefringence on Congo red stain under polarized light
Definition of neutropenia
ANC < 1500
Acute neutropenia infections
S aureus, Pseudomonas, E. coli, Proteus, Klebsiella sepsis
Chronic/autoimmune neutropenia infections
Recurrent sinusitis, stomatitis, gingivitis, perirectal infection
Treatments for neutropenic fever
Broad spectrum antibiotics ie cefipime
Anti-fungals
G-CSF to shorten duration of neutropenia
IVIG and allogenic BM transplant can help
Causes of secondary eosinophilia
NAACP Neoplasm Allergies Asthma Collagen vascular disease Parasites
CSF eosinophilia
Suggestive of drug reaction or infection with cocci or a helminth
Hematuria + eosinophilia
Schistosomiasis
Hyperacute transplant rejection
-timing, pathophys, tissue findings, prevention, tx
Timing: Within minutes Pathophys: 2/2 preformed antibodies Tissue findings: vascular thrombi; tissue ischemia Prevention: check ABO before Tx: cytotoxic agents
Acute transplant rejection
-timing, pathophys, tissue findings, prevention, tx
Timing: 5 days - 3 months
Pathophys: T-cell mediated
Tissue findings: tissue destruction ie increased GGT, alk phos, LDH, BUN, or Cr
Prevention: n/a
Tx: confirm w/ sampling of tissue; tx with corticosteroids, antilymphocyte antibodies ie OKT3, tacrolimus, or MMF
Chronic transplant rejection
-timing, pathophys, tissue findings, prevention, tx
Timing: months to years
Pathophys: Chronic immune reaction causing fibrosis
Tissue findings: gradual loss of organ function
Prevention: n/a
Treatment: No treatment
Graft vs Host Disease
T cells from the donor organ starts to attach the person needing the transplant
-affected tissues include skin, liver, GI
Timing: acute = 100 days
Pathophys: 2/2 MHC incompatibilitiy
Sx: skin changes, cholestatic liver dysfunction, obstructive lung disease, GI problems
Tx: high-dose corticosteroids
