Hematology Exam 5 Flashcards
Briefly describe SCID
Congenital nonmalignant leukocyte disorder
Marked decrease in circulating T cells, poorly functioning B cells, hypogammaglobulinemia
What is the gamma chain deficiency (X-linked SCID)
Caused by mutation in the IL2RG gene on the X chromosome resulting in a severe decrease in T and NK cells, adequate number of B cells, but they are dysfunctional
What is the adenosine deaminase (ADA) deficiency SCID?
Mutation on the ADA gene on chromosome 20 resulting in decreased T, B and NK cells
What is Wiskott-Alrich (WAS) Syndrome?
Congenital nonmalignant WBC disorder
rare X-linked disease due to mutation in WAS gene characterized by decreased T cells and dysfunctional Tcells, Bcells, NK cells, neutrophils, and monocytes
What is 22Q11 Syndrome?
Absence/decreased size of thymus due to a missing part of chromosome 22 characterized by decreased T cells
What is Bruton Tyrosine Kinase Deficiency?
Congenital nonmalignant WBC disorder
X-linked agammaglobulinemia due to mutation of BTK gene - no serum antibodies and profoundly decreased or absent B cells
What is Chediak-Higashi Syndrome?
Congenital nonmalignant WBC disorder
Rare autosomal recessive disease of immune dysregulation due to a mutation in the CSI LYST gene
- associated with albinism and giant lysosomal granules in WBCs
What are LADs?
Leukocyte adhesion disorders - inability of neutrophils and monocytes to move from circulation to the site of inflammation
What is Schwachman-Diamond Syndrome (SDS)?
A defect in leukocyte motility caused by mutation in SBDS gene on chromosome 7
What is Chronic Granulomatous Disease?
Decreased ability of neutrophils to undergo a respiratory burst resulting in life-threatening catalase-positive bacterial and fungal infections
What is WHIM syndrome?
Warts, hypogammaglobulinemia, infections, myelokathexis (low numbers of circulating neutrophils because they are all in the BM) due to mutation on the CXCR4 gene
What are the two types of SCID (Severe Combined Immunodeficiency)
Gamma chain deficiency (X-linked)
ADA deficiency
What cells are seen in Pelger-Huet anomaly?
Pelger-Huet cells which have decreased segmented neutrophils (most of them are only bi-lobed and have dense chromatin) the nucleus looks like dumbbells
What type of cells are seen in Chediak-Higashi Syndrome?
Granulocytes/monocytes/lymphocytes with giant lysosomal granules
What type of cells are seen in neutrophil hypersegmentation?
Hypersegmented neutrophils –> >5 lobes on neutrophils
What type of cells are seen in Alder-Reilly anomaly?
large, darkly staining metachromatic cytoplasmic granules called Reilly bodies containing partially digested mucopolysaccharides
What is May-Hegglin Anomaly and what type of cells do you see with this disease?
Characterized by:
- thrombocytopenia
- Giant PLTs
- Large Dohle body-like inclusions
See dohle bodies on WBCs
What are lysosomal storage diseases?
Enzyme deficiencies that result in a buildup of undigested substrates within lysosomes called mucopolysaccharides
What are sphingolipidoses? What are the examples of them?
Disorder in which lipid catabolism is defective; such as Gaucher disease and Neimann-Pick disease
What are Gaucher cells?
distinctive macrophages that look like onion skin seen in Gaucher disease
What nonmalignant WBC disorder has a highest rate of incidence in Ashkenazi Jews?
Gaucher disease
What is Niemann-Pick Disease and what cells are seen with this disease?
Accumulation of fat in lysosomes that causes impaired organ function - Foam cells AKA Niemann-Pick cells and sea blue histiocytes
How are the different ways you can differentiate between a leukemoid reaction and a chronic myeloid leukemia?
- LAP score (High in LR and decreased in CML)
- Genetics (Normal in LR and positive for philadelphia chromosome/BCR-ABL in CML)
- Hemoglobin (Normal in LR and anemia in CML)
- Eos and Basos (Normal in LR and elevated in CML)
- Neutrophils (toxic gran/dohle seen in LR and pseudo-pelger-huet in CML)
- Platelets (normal in LR and abnormal in CML)
Leukoerythroblastosis
Increase in immature WBCs/RBCs - Presence of immature neutrophils, nRBCs, and dacrocytes
Agranulocytosis
Extremely low number of granulocytes
What is the most common cause of acquired neutropenia?
Medications (drug-induced)
Neutropenia
decreased neutrophils could be due to medications such as anticancer drugs
Neutrophilia
Increased neutrophils
Eosinophilia
Increased eosinophils seen with helminth infections or allergic reactions
Eosinopenia
Decreased eosinophils
Basophilia
Increased basophils associated with CML, allergic rhinitis, hypersensitive rxns
Monocytosis
Increased monocytes due to infections or postsplenectomy
Monocytopenia
Decreased monocytes due to anemia or steroid therapy
Describe toxic granulation and associated diagnosis
Dark, blue-black cytoplasmic granules in neutrophils associated with inflammation, infection, G-CSF
Describe Dohle bodies and associated diagnosis
Intracytoplasmic pale blue/round body adjacent to cellular membrane associated with infection, G-CSF, pregnancy, burns
Describe cytoplasmic vacuoles and associated diagnosis
Clear circular areas in cytoplasm that may contain an organism (rare) associated with bacterial infections
Intracellular organisms
bacteria that grow in white blood cells
Ehrlichia and Anaplasma - what are they and where do each of them grow
small intracellular bacteria transmitted by ticks to humans
Ehrlichia grows as a cluster in monocytes
Anaplasma grows as a cluster in neutrophils
What is pyknotic nuclei?
Very dark chromatin indicating cell is going to die
What is necrotic nuclei?
Rounded nuclear fragments with no chromatin pattern found in dead neutrophils
What do increased numbers of pyknotic and necrotic cells suggest?
An extended amount of time has elapsed between blood collection and blood film preparation
What is cytoplasmic swelling?
Variation in neutrophil size due to swelling of the cytoplasm or increased adhesion to the glass slide
morphological features of reactive monocyte
Thin/band-like segmented nuclei and irregular cytoplasmic borders that take on the shape of the RBCs surrounding it
Reactive lymphocyte morphology
Nucleoli may be visible
Increase in basophilic cytoplasm
Cytoplasm is indented by surrounding RBCs
Reactive vs Abnormal lymph
Reactive is used to refer to benign etiology
Abnormal is used to refer to malignant/clonal etiology
Morphology of a plasmacytoid lymph and what does its presence indicate in high numbers?
Has some features of plasma cells - very blue cytoplasm and if seen in high numbers suspect lymphoma or Waldenstrom’s Macroglobulinemia
What is the causative agent of infectious mononucleosis?
Epstein Barr Virus
What cells does Epstein Barr Virus infect?
Primarily infects B lymphs, so most circulating reactive lymphs are T cells
What population of people does epstein barr virus typically infect?
Mostly seen in young adults age 15-24 years
Lab findings of those with EBV
Absolute lymphocytosis with up to 50% or more reactive lymphs; Positive for heterophile antibodies
Clinical manifestations of EBV
Sore throat, dysphagia, fever, chills, cervical lymphadenopathy, fatigue, headache
Define and describe an MPN
clonal hematopoietic disorder that result in expansion, excessive production, and accumulation of mature RBCs/WBCs and PLTs that are predominantly chronic - may progress into acute leukemias
What are the four major MPNs?
Chronic myeloid leukemia (CML)
Polycythemia Vera (PV)
Essential Thrombocytopenia (ET)
Primary myelofibrosis (PMF)
What do EV, PV, and PMF have in common that is NOT associated with CML?
EV/PV/PMF are genetically related based on the presence of the JAK2 mutation and the ABSENCE of the philadelphia chromosome or BCR-AB1 fusion gene
What is ET associated with?
Thrombocytosis
What is PV associated with?
Erythrocytosis
What is MPF associated with?
Neutrophilia, left shift, fibrosis
What is CML associated with?
PRESENCE of the Philadelphia chromosome and/or the BCR-ABL1 fusion gene
What is REQUIRED for a CML diagnosis?
Presence of the philadelphia chromosome or the BCR-ABL1 fusion gene
MPNs may transform into ______ or _______.
AML or ALL (leukemic transformation)
What is the Philadelphia chromosome?
t(9;22) that produces a fusion gene called BCR-ABL1 that must be present to confirm a CML diagnosis
Where is the ABL1 gene found? BCR gene?
ABL1: chromosome 9
BCR: chromosome 22
How does the presence of Philly chromosome and BCR-ABL1 fusion gene lead to the findings seen in CML?
Increased clonal proliferation of myeloid cells secondary to a reduction in protein regulators
Describe CML (cell line most affected, clinical features, pathogenic mechanism, notable lab findings, treatment)
Affects myeloid cell line (increased immature neutrophils)
Clinical features: anemia, bleeding, splenomegaly, frequent infection
Lab findings: Increased basophils, eosinophils, neutrophils, platelets, decreased LAP score
Treatment: Imatinib mesylate (Gleevec)
What is Imatinib mesylate?
Gleevec; a tyrosine kinase inhibitor
PV cells affected
Increased RBCs, granulocytes, and PLTs
PV pathogenic mechanism
Neoplastic clonal stem cells function independently of erythropoietin for cell growth (erythropoietin independent erythropoiesis –> make RBCs without erythropoietin caused by mutated JAK2 gene
4 major criteria to diagnosis PV
Elevated HGB, HCT, or red cell mass
BM showing panmyelosis
Identificiation of the JAK2 V617F mutation
Low serum EPO levels
What cell line is increased with ET?
Increased megakaryopoiesis and thrombocytosis
What is the most common cause of death in ET patients?
Thrombosis and bleeding
What is the least common, but most aggressive MPN?
primary myelofibrosis (PMF)
What separates PMF from other MPNs?
Increase in circulating CD34+ cells (HSCs)
What is the pathogenic mechanism of PMF?
Mutation in 1 of 3 genes that affect the JAK-STAT pathway: JAK2 (V617F), CALR, or MPL
What is PMF characterized by?
Overproduction of collagen that leads to replacement of hematopoietic tissue leading to pancytopenia
What is seen in the peripheral blood and bone marrow of PMF?
Peripheral blood: dacrocytes and leukoerythroblastosis
Bone barrow: DRY TAP –> hypocellular
Describe MDSs as a group
A group of acquired clonal hematologic disorders characterized by progressive cytopenias and defects in erythroid, myeloid, and/or megakaryocytic maturation (DECREASED CELLS!)
What 2 morphological findings are common to all types of MDS?
Presence of progressive cytopenias despite cellular BM, and dyspoiesis in one or more cell lines
What is the most common morphological finding in the peripheral blood in dyserythropoiesis?
Oval macrocytes
What abnormal cell morphology is seen in dysmyelopoiesis?
abnormal granulation and cell features; ring shaped nuclei
What does dysmyelopoiesis indicate?
Nuclear-cytoplasmic asynchrony
What abnormal cells are seen in the bone marrow of dyserythropoiesis?
Nuclear bridging, ringed sideroblasts, RBC precursors with more than 1 nuclei
What abnormal cells are seen in dysmegakaryopoeisis?
Giant platelets, abnormal PLT granulation
What is MDS with single lineage dysplasia?
Dysplasia present in at least one myeloid lineage with one type of cytopenia
What is MDS with multilineage dysplasisa?
Dysplasia in two or more myeloid cell lines with one of more cytopenias
What is MDS with ringed sideroblasts?
Mutation of the gene SF3B1; ring sideroblasts present (iron containing mitochondria)
What is MDS with excess blasts?
Trilineage cytopenia with presence of Auer rods
What is MDS with DEL 5Q
The only WHO recognized MDS with defining cytogenetic abnormality that predominantly affects women - anemia without other cytopenias and hypolobulated megakaryocytes, NO auer rods
What Is MDS unclassifiable?
Only one cell line is dysplastic, but all cell lines are decreased
What are the MDS/MPNs?
Chronic myelomonocytic leukemia
Atypical chronic myeloid leukemia
Juvenile myelomonocytic leukemia
Refractory anemia with ring sideroblasts and thrombocytosis
What treatment is used for MDS/MPNs?
Lenalidomide
What are MDS/MPNs?
Myeloid neoplasms that share characteristics of BOTH MDS and MPNs
