White blood Cell Disorders
What are the clinical findings of chronic myelogenous leukemia?
1. Generalized findings of fatigue and weight loss are common 2. Splenomegaly is the most consistent finding (50% to 60% of cases) due to metastasis 3. Hepatomegaly (8% of cases) and painless lymphadenopathy (6% of cases ) may aoccur
What are the types of leukemias?
precursor of the myeloid lineage would by AML. accumulation of cells in the immature Lymphoid lineage would be ALL Accumulation of mature lymphoid cells T cells or B cell is CL if there accumulation of mature myeloid cells would be myeloproliferative disorder for example if the RBCs are overproduced then we call it polycythemia vera, if the granulocytes are over produced then we cann it CML, if the platelets or the mekaryocytes are overproduced then we call ET and you get an increase in all of these cells but it is name according to the most dominant cell.
What is the unusual benign leukocyte reactions?
Leukemoid reaction Leukoerythroblastosis
What are the labortory findings of Myelodysplastic syndromes (MDSs)?
a. Severe pancytopenia is common. 1. Normocytic to macrocytic anemias Dimorphic RBC population (microcytic and macrocytic)is commonly present, which increases the RBC distribution width (RDW). 2. Leukoerythroblastosis b. Bone marrow findings 1. Ringed sideroblasts (nucleated RBCs with excess iron) are present 2. Myeloblasts account for <20% of the granulocytes. if the myeloblast are >20%, it has progressed to AML.
What is the treatment for follicular lymphoma?
. Treatment is reseved for patients who are symptomatic and involves low dose chemotherapy or rituximab (anti-CD20 antibody) E. Progression to diffusie large B cell lymphoma in time due to additional mutations, and is an important complication ; resents as an enlarging lymph node because the patient usually has multiple large lymph nodes but if all of a sudden starts to get large then its needs to be considered to the progression to diffuse large B cell lymphoma. F. Follicular lymphoma is distinguisehed from reactive follicar hyperplasia (which a patient just upon infection could get follicular hyperplasia which would just be in the cortex where the follicles normally live due to the B cells coming into the follicle and undergoing somatic hypermutation and dyingg by apoptosis and then tingle body macrophages comin and clean up the dead cells which are the white spaces and the darker area surrounding the germinal center is the mantle on the histo) by 1. Disruption of normal lymph node architecture (maintained in follicular hyperplasia) 2. Lack of tingible body macrophages in germinal centers (tingible body macropahges are present in follicular hyperplasia) 3. Bcl2 expression in follicles (not expressed in folliclar hyperplasia) 4. monoclonality which means its neoplasia (follicular hyperplasia is polyclonal)
What is the Clinical findings of myeloid metaplasia (MMM)?
1 Massive splenomegaly occurs with portal hypertension 2. Splenic infarcts commonly occrur arnd are associated with left sided pleural effusions
What is the clinical findings in acute leukemia?
1. Abrupt onset of signs and symptoms 2. Clinical findings a. Fever is common and usually indicated infection b. Bleeding common and is most often cuased by thrombocytopenia c Anemia causes fatigue
What is treatment of Chronic Myelogenous Leukemia?
1. Imatinib mesylate a. Oral tyrosine kinase inhibitor. b. More than 75% of patients have a major cytogenetic response (<35% of CLS are positive for Philadelphia chromosome after treatment) 2. Allogeneic stem cell transplantation is the only curative treatment. f. Prognosis is 90% 5-year survival rate
What are the clinical fndings in chronic leukemia?
1. Insidious onset of signs and symptoms 2. Hepatosplenomegaly 3. Generalized painless lymphadenopathy
What is lymphocytosis?
1. Lymphocytosis a. Definition-absolute lymphocyte count>5000 cells/mm3 in adults or >8000 cells/mm3 in children b. Causes 1. Viral (ex-mononucleosis and cytomegalovirus (CMV) 2. Bacterial (whooping cough (Bordetella pertussis) and tuberculosis. 3. Drugs is phenytoin and tetracycline 5. Neoplasia is chronic lymphocytic leukemia (CLL) c. Pathogenesis 1. increased production 2. Decreased entry into lymph nodes (ex-lymphocytosis-promoting factor produced by bordetella pertussis).
What is the stem cell lineage?
A hematopoietic CD34+ stem cell is the progenitor cell in the bone marrow and has the potential to create a myeloid stem cell ( can develop into a erythroblast that can develop into RBCs, a myeloblast that can develop into neutrophila basophils and eosinophils...a monoblast that can develop into monocytes, or a megakaryoblast that develops into megakaryocytes)and a lymphoid stem cell (which can form either a B lymphoblast to produce a Naive B cell that become trained to become plasma cellsor T lymphoblast that become Naive T cells that can become trained to become CD8 or CD4 T cells.)
What is Walden strom macroglobulinemia?
A. B-cell lymphoma with monoclonal IgM (is a pentamer a big globulin that increases the viscosity of the blood) production B. Clinical feature include. 1. generalized lymphadenopathy; lytic bone lesions are absent. 2. INcreased serum protein with M spike (comprised of IgM) 3. Visual and neurologic deficits (Increase viscosity can lead to retinal hemorrhage or stroke)-IgM (large pentamer) causes serum hyperviscosity 4. Bleeding-viscous serum results in defective platelet aggreagation. C. Acute complication are treated with plasmapheresis, which removes blood and then remove the IgM from the serum
What is infection mononucleosis? Where does the lymph node and spleen enlarge? WHat other organs enlarge? What test can you do?
A. EBV infection that results in a lymphocytic leukokcytosis comprised of reavtive CD8+ T cells; CMV is a less common cause 1. EBV is transmitted by saliva ("kissing disease'); classically affect teenagers. B. EBV primarily infects 1. Oropharynx (giving a sore throat), resulting in pharyngitis 2. Liver, resulting in hepatitis (EBV is an important cause for hepatitis) with hepatomegaly and elevated liver enzymes. 3. B cells C. CD8+ T-cell response (due to the recognition of the MHC class I proteins that are being expressed) leads to 1. Generalized lymphadenopathy (LAD, which are multiple lymph nodes becoming enlarged) due to T-cell hyperplasia in the lymph node paracortex ( this is where the T cells are found inside the cortex, the cortex is where the B cells are found and the outside of the ) 2. Splenomegaly due to T-cell hyperplasia in the periarterial lymphatic sheath.In the spleen, the red pulp (looks red) contains blood and the white pulp (looks blue) contains lymphoid tissue and this white pulp contain B cell and T cell areas and the T cell area will be expanded which is called the periarterial lymphatic sheath (PALS), which are the arteries that are in the white pulp of the spleen and that blue sheath around them and due to the hyperplasia of theese cells will cause splenomegaly. 3. High WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood. Nucleus is much bigger than the adjacent RBCs and they usually are the same size, and it has a lot of cytoplassm and it looks like a monocyte. D. The monospot test is used for screening 1. Detects IgM antibodies that cross with horse or sheep RBCs (heterophile antibodies these are antibodies that can bind RBC from another animal). 2. Usually turns positive within 1 week after infection 3. A negative monospot test could be that we tested too early or suggests CMV as a possible cause of IM!!!!! 4. Definitive diagnosis is made by serologic testing for EBV viral capsid antigen (every screening test must be followed by a confirmatory test). E. Complications 1. Increased risk for splenic rupture due to the splenomegaly and the capsule of the spleen could easily rupture: patients are generally advised to avoid contact sports for next year 2. ‹Rash if exposed to ampicillin 3. Dormancy of virus in B cells leads to increased risk for both recurrence and B-cell lymphoma, especially if immunodeficiency (HIV) develops
What are the basic principeles of leukopenia and leukocytosis?
A. Hematopoiesis occurs via a stepwise maturation of CD34+ hematopoietic stem cells B. Cells mature and are released from the bone marrow into the blood. C. A normal white blood cell (WBC) count is approximately 5-10 K/microL 1. A low WBC count (<5K) is called leukopenia 2. A high WBC count (>10K) is called leukocytosis 3. A low or high WBC count is usually due to a decrease or increase in one particular cell lineage or cell type.
What is Monoclonal Gammopathy of undetermined signigicance (MGUS)?
A. Increased serum protein with M spike on SPEP; other features of multiple myeloma are absent (no lytic lesion, hypercalcemia, AL amyloid, or Bence Jones proteinuria) B. Common in elderly (seen in 5% of 70-year-old individuals);1% of patient with MGUS develop multple myeloma each year.
What is the Benign qulaitative white blood cell disordrs?
Defects in structure/or functin of white blood cells (WBCs). B. Pathogenesis. is a defect in leukocyte structure. Example-membrane fusion defect in Chediak-Higashi syndrome 2. Defects in leukocyte function a. Leukocyte adhesion defect (LAD) Example-defiecient selectin or CD11a/CD18 adhesion molecules b. Phagocytosis defect Example decrease opsonins in bruton aggaglobulinemia c. Microbicidal defect an example is deficiency myeloperoxidase (MPO) or NADPH oxidase C. Clinical findings 1. Usual pathogens (seeatia marcescens) 2. Frequent infections and growth failure in children 3. Lack of an inflammatory response (production of cold absecesses) 4. Severe gingivitis
What is polycythemia?
a. Increased hemoglbin (HB), hematocrit (Hct) and RBC count b. Plasma volume (PV) varies with the type of polycythemia c. RBC count versus RBC mass 1. RBC count is the nuber of RBCs per microliter of blood 2. RBC mass is the total number of RBCs in the peripheral blood in Ml/kg.
What is the early pre B cell ALL?
a. Marker studeis for common acute lumphoblastic leukemia antigen(CALLA;CD10) are positive b. Marker studies for terminal deoxynucleotidyl transferase (TdT) are positive c. T.(12,21) translocation offers a faborable prognosis. d. Greater than 95% with this subtype achieve complete remission d. Greater than 95% with this subtype achieve complete remisision. At leadt 75% to 85% of patients are consider cured
What is a classic histo sign of multiple myeloma?
pile up like poker chips
What is Marginal Zone lymphoma
"Region outside of the mantle" Most lympho nodes do not have a marginal zone but it is formed when activation of cels through the germinal center because of example chronic inflammation. A. Neoplastic proliferation of small B cells (CD20+) that eexpands the marginal zone B. Associated with chronic inflammatory states such as Hashimoto thryoiditis, Sjogren syndrome (uniateral proliferation of the parotid gland years within the sjogren disease), and H pylori gastritis. 1. The marginal zone is formaed by post-germinal center B cells C. MALToma is marginal zone lymphoma in mucosal sites. 1. Gastric MALToma may regress with treatment of H Pylori.
What is the pathogenesis of chronic myelogenous leukemia?
1. Neoplastic clonal expansion of the pluripotential stem cell, this stem cell has the capacity to differentiate into a lymphoid or myeloid stem cell 2. T(9,22) translocation of the ABL proto-oncogene a. Proto-oncogene fuses with the break cluster region (BCR) on chromosome 22 (BCR-ABL fusion gene). b. Chromosome 22 with the translocation is called the Philadelphia chromosome.
What are neoplastic myeloid disorders?
A overview of neoplastic myeloid disorders 1. ALll myeloid disorders are neoplastic stem cell disordrs that may involve one or more stem cell lines. 2. Classification a. Chronic myeloproliferative disordrs b. Myelodysplastic syndrome c. Acutre myeoloblastic leukemia (AML)
What is Eosinophillic granuloma?
A. Benign proliferation of Langerhans cells in bne. B. classic presentation is pathlogic fracture in an adolescent; skin is not involved C. Biopsy shows Langerhans cells with mixed inflammatory cells, including numerous eosinophils. think of a adolescent patient with a pathologic fracture due to basketball you would start thinking of osteosarcoma, but you need to think about eosinpphillic granuloma too.
What is Hand-schuller-christian disease?
A. Malignant proliferation of Langerhans cells B. Classic presentation is scalp rash, lytic skull defects, diabetes insipidus and exophthalmos in a child greater than the age of 3
What is job syndrome?
An autosomal dominant (somtimes recessive) disorder of neutrophils. Most patients have unaffected parents. It iis due to mutation in STAT3, whose protein products act as transcipriton activator. There is also a reduction in T17 helpter T cells, which produce interleukin 17, a chemotactic agent for monocytes and neutrophils. There fore neutrophils and monocytes in these patients have abnormal chemotaxis, leading to "cold" soft tissue absecesses and recurrent pneumonias. THe most common pathogens are Staphlococcus aureus and Cadida species. Patiets have red hari, a leonine face (increased width of the nose, full lower lip), chronic eczema , eosinophilia, and increased serum IgE (hyperimmnoglobulin E syndrome ). Genetic testing is available to secure the diagnosis.
What is the Myeloproliferative disorders?
Chronic myeoid leukemia (CML) Polycythemia Vera (PV) Essential thrombocythemia (ET) Myelofibrosis
What is the Lettere-Siwe disease?
If the disease is named after someone then the disease is malignant and usually involved in the skin. A. Malignant proliferation of Langerhans cells B. Classic presentation is skin rash and cystic skeltal defects in an infant (<2 years old) C. multiple organs may be involved; rapidly fatal.
What are the disorders involving neutrophils?
Neutrophilic leukocytosis Neutropenia
What is the leukoerythrobastosis (leukoerythroblastic reaction)?
Presnece of immature bone marrow WBC's and nucleated RBCs (RBCS) in the peripheral blood (peripheralization" of the bone amrrow), irrespective of the total leukocyte count. b. Causes 1) Normal bone marrow example-sever acute hemolytic anemia (sickle cell disease) 2) abnormal bone marrow a. bone marrow infiltrative disease (amyloidosis) b. Metastatic melignancy (breast cancer) c. Granulomatous disease (tuberculosis (TB), systemic fungal disease, sarcoidosis) d. Hematologic malignacies (acute leukemia, multple myeloma) chronic myeloproliferative diseases (myelofibrosis with yeloid metaplasia). 3. Other causes include: massive trauma with multiple fractures. Paget disease of bone, and extramedullary hematopoiesis (EMG) c. Peripheral blood findings 1. Myeloblasts, progranulocytes, and other leukocytes precursors 2. Nucleated RBCs and tear drop RBCs (if fibrosis is present)
What is acute megakaryoblatic leukemia?
Proliferation of megakaryoblasts; lack MPO because they do not do the oxygen dependent killing that oxygen is useful for. Association with Down syndrome (before the age of 5) more ocmmonly ALL.
What cell type is found in nodular sclerosis subtype?
RS cells are sitting in big open spaces, and this spaces look like lkae
What are the subtypes of Hodgkin lymphoma?
Subtypes include 1. Nodular sclerosis 2. Lymphocyte-rich 3. Mixed cellularity (especially eosinophils) 4. Lymphocyte depleted D. Nodular sclerosis is the most common sybtype of HL (70% of all cases) 2. Classic presentation is an enlarging cervical or mediastinal lymph node in a young adult, usually female. 2. Lymph node is divided by broad bands of sclerosis that cut the lymph nodes into nodules; RS cells are present in lake-like spaces (lacunar cells) E. Imporatnt considerations regarding other subtypes of HL 1. Lymphocyte-rich has the best prognosis of all types 2. Mixed cellularity is oftern associated with abundant eosinophils (RS cells produce IL-5) and have eosinophilia. 3. Lymphocyte-depleted is the most aggressive of all types; usually seen in the elderly and HIV-positve individuals
What is neutrophillic leukocytosis?
a. Absolute neutrophil count >7500 cells/mm3 b. Cuases 1. Bacterial infection (acute appendicitis) 2. Sterile inflammation with nectosis (acute myocaridal infarction) 3. Drugs (corticosteroids) c. Pathogenesis 1. Increased bone marrow production or release of neutrophils 2. decreased activation of neutrophil adhesion molecules a. fewer neutrophils adhere to endothelial cells b. examples-corticosteroids catecholamines, and lithium
What is Atypical lymphocytosis?
a. Causes of atypical lymphocytosis 1. infection (mononucleosis, viral hepatitis, CMV infection and toxoplasmosis) 2. Drug (phenytoin) b. Pathogenesis of atypical lymphocytosis Definition -antigen-stimulated lymphocytes with prominent nucleoli and abundant blue cytoplasm.
What is Polvythemia era?
a. Defintion of malignnt inappropiate polycythemia b. pathogenesis 1. myeloid stem cell underrgoes clonal expansion 2. Most cases are due to mutation of the JAK2 gene on the short arm of chromosome 9. a. This gene plays a role in the signaling pathways tthat tell the body to generate heamtopoietic cells b. Same mutation may manifest as myelofibrosis with myeloid metaplasia or essential thrombocythemia 3. Polycythemia vera, there is increased production of RBCs, granulocytes (neutrophils, eosinophils, basophils mast cells and platelets c. Clinical findings 1. Hepatosplenogmegaly 2)ruddy (pthoric) face due to vessel congestion 3. THrombotic events a. Hyperviscosity related to the incrased RBC count/mass b. Sites of thrombosis-hepatic vein, dural sinus, and reitinal vein 4. Imparied CNS circulation leads to headach, burred vision, retinal vein engorgement, vertigo, transitent ischmic attacks and strokes. 5. Signs of increased histamine released from mast cells a. Pruritus after bathing very sommon inital complaint mast cells in the skin degranulate with changes in skin temp. b. Peptic ulcer disease, histamine stimulates prodcuinot of gastric acid 6 Gout, due to increased breakdown of nucleated cells with release of urines, which are converted to uric acid
What is the Chronic myelogenous leukemia?
a. EPidemiology 1. Median age for CML is 45 to 55 years old 2. Accoutns for 15% of adult leukemias 3. Risk factor-exposure to ionizing radiation
What is the infection mononucleosis (mono)?
a. Epidemiology 1. Caused by the Epstein-Barr virus (EBV) 2. Most common between the ages of 15 and 24 years old b. Pathogeneis 1. Primarily transmitte by kissing. virus initally replicates in epithelial cells in the oropharynx 2 Infection spreads to B cells in lymph nodes a. Virus attaches to CD21 rectptors on B cells. b. Bcells become antigenically stimulates, rolierate, and increases synthesis of IgM antibodies (heterophile antibodies). Cytoxic T cells are important in controlling the porliferation of infected B cells to prevent reltpses and ciruclate as atypical lymphocyte. c.Virus remains dormatnt in B cells; therefore mononucleosis may recur.
What is the Myelofibrosis with myeloid metaplasia (MMM)?
a. Epidemiology 1. Primarily occurs in persons >50 years old 2. Most common cause of massive splenomegaly in this group b. Pathogenesis 1. MMM is a clonal myeloproliferative disease 2. Most cases are due to mutation of the AK2 gene 3. Ineffective erythropoiesis, dysplastic megakaryocytes, increased number of immature granulocytes, and early onset of reactive myelofibrosis. Marrow fibrosis occurs earlier than in the other chronic myeloproliferative diseases. 4.Heamtopoiesis moves to the spleen, liver, and tother sites (EMH).
What is the pathogenesis of ALL?
a. clonal lymhoid staem cell disease b. Majority have numerical or sturctural chromosome chages (hyperploidy>50 chromsomes)
What is the essential thrombocythemia (ET)?
a. ptahogenesis 1. clonal myeloproliferative disease with eccess formation of dysplastic and defective platelets. 2. Most cases are due to mutation of the Jak2 gene, and recall that poly cythemia vera and MMM have the same mutation.
What are the general characteristics of chronic myeloproliferative disorders?
a. splenomegaly b. propensity for reactive bone marrow fibrosis ("spent phase") c Propensity for tansformationto acute leukemia.
What is the lymphopenia?
absolute lymphocyte count <1500 cells/mm3 in adults or <3000 cells/mm3 in children b causes 1. Huma immunodeficiency virus 2. Immunodeficiency disorders a. Digeroge syndrome (t-cell deficiency) b. Severe combines immunodeficiency (B and T cell deficiency) c. Bruton agammaglobinlinemia (B-cell deficiency) 3. Immune destruction (systemic lups ertythematosis) 4. Drug are corticosteroids, cyclophophamide, quinine, and cytotoxic chemotherpay. 5) Ionizing radiation ar lymphocytes are the most senstive celss to destruction by radiation c.Pathogenesis 1. Increased destruction (examples lysis of CD4 helper T cells by the human immunodeficciency) 2. Decreased production (example bruton agammaglobulinemia)
What is the lymphoid leukemias?
acute lymphoblastic leukemia (ALL) Adult T-cell leukemia Chronic lymphocytic leukemia (CLL)
What is the clinical findings of infectious mononucleosis?
c. Clinical findings. 1. Severe fatigue 2. Exudative tonsilities a. May be complicated by a group A streptococcus infection in 30% of cases, which emphasizes the importance of culture or other diagnostic tests to rule out group A steptococcal infection. b. Petechiae in posteroir palate 3. Tender hepatosplenomegaly a. Danger of liver/splenic rupture in contact sports . Hepatitis not chronic. 4. Generalized painful lymphadenopathy 5. Generalized, erythematous, prolonged pruritic rash may occcur if the patient is treated with ampicillin a. Rash does not mean that the patient is allergec to ampicillin or amoxicillin. b. Rash that commonly accompanies infection monocucleios is also generalized, however, it is faint, evanescent, and nonpruritic. 6.other findings include: Encephalitis, pancreatitis, Guiliain-barre/ syndrome, cranial nerve palsies, and myositis
What is relative polycythemia?
d. Relative polycythemia 1. overall, relative polycythemia is the most common type 2dfintion-increased RBC count is due to a decrease in plasma volume(PV) (example volume deption from sweating) 3. RBC mass is normal, and no increase in bone marrow production of RBCs 4. EPO and SAo2 are normal 5. Simple fluid replacement corrects polycythemia
What are the laboratory findings?
1. Atypical lymphocytosis atypical lymphoctyes usally account for>20% of the total WBC count. 2. Positive hetrophil antibody test a. Heterophile antibody test is the initial screening test for infection mononucleosis b. Test detects IgM antibodies against horsae (most common), sheep, and boving RBCs c. Test sensitvity is 87% and the specificity is 91%. 3. Anti-viral capsid antigen (VCA) antibodies a. High sensitivity and speicificty b. Devlops early in the infectionand persist for life 4. Anti-early capsid antigen (VCA) antibodies a. INCREASED WITH CHRIC INFECTIONS 5. ANTI-EPSTEIN-BARR NUCLEAR ANTIGEN (EBNA) antibodies a. High sensitivity and specificity b. Develops late in the infectin and persists for life 6 Serum transminases from hepatitis are markely increased, and juandice occurs in < 10% of cases
What is the pathogenesis of acute and chronic leukemia?
1. Block in stem cell differentiation leading to a monoclonal proliferation of of neoplastic leukocytes behin dthe block a. Acute leukemia-block occurs at a early stage of stem cell developent b. Chronic leukemia-block occurs at a later stage in stem cell development. Some evidence of maturatin in chronic leukemia 2. Leukemic cells a. Replace most of the bone marrow and crowd out normal hematopoiesis b. Enter the peripheral blood c. Metatastasice throughout the body.
What are the laboratory findings?
1. Bone marrow fibrosis 2. Peipheral WBC count range:10,000 to 50 ,000 cells/mm3. 3. Normocytic anemia a. Teardrop cells (dmaage RBCs.) are commonly present b. Leukoerythroblastosis is present 4. Plelet count is variable, and platelet s are morphologically abnormla 5. Leukocyte alkaline phophatase score is normal to increased. Recall that it is decreased in CML and increased in polycytthemia vera. Treatment 1.hydroxyyrea 2. Interferon-∂
What is chronic myeloproliferative disorders?
1. Classification a. Polycythemia b. Chronic myelogenous leukemia (CML) c. Myelofibrosis with myeloid metaplsia (MMM) d. Essential Thrombocythemia (ET)
What are the disorders involving monocytes:monocytosis?
1. Definition-absolute monocyte count >800 cells/mm3 2. causes a. Chronic inflmmation (examples-tuberculosis, subacutre infective endocarditis, and cirrhosis b. Autoimmune disease (ex-Rheumatoid arthritis) c. Malignancy (ex-carcinoma and malignant lymphomas) 3. Pathogenesis are immune response to chronic inflammation, autoimmune disease or malignancy.
What is absolute polycythemia?
1. Definition-increase in bone marrow production of RBCs and increase in RBC count and RBC mass. 2) Appropiate absolute polycythemia a. Hypoxic stimulus for EPO release b. Example-primaryu lung disease, cyanotic congenital heart disease, and high altitude. c. Decreased Sao2 d. Increased RBC count, RBC mass and EPO level e. NOrmal PC
What are the disorders of basophils; basophilia?
1. Defition is absolute basophil count >110 cells/mm3 causes chronic myeloproliferative disorder (polycytothemia vera)
What is disorders of eosinophils?
1. Eosinphila which is absolute eosinophil count >400 cells/mm3. b. causes 1. type 1 hypersensitivity reaction (bronchial asthma, reacting to penicillin, hay fever and atopic dermatitis. 2. Protozoal disease ( entamoeba fragilis (only protozoal infection with eosinophilia) 3. Invasive helminthic infection a. example is strongyloidiasis and hookworm infection. b. pinworms and adult ascariasis are not accompanied by eosinophilia (noninvasive) 4. Polyarteritis nodosa, Churg-Strauss syndrome 5. Addison disease (cortisol deficiency) 6. Job syndrome c. Pathogenesis 1. Release of eosinophil chemotactic factor form mast cells that type is type I hypersensitivity reaction (HSR) 2) No sequestering of eosinophils in lymph nodes and the example is hypocortisolism 2. Eosinopenia causes hypercortisolism (Cushing syndrome, corticosteroids) b. Pathogenesis is corticosteroids sequester eosinophils in lymph nodes and trigger apoptosis.
What is acute myeloblastic leukemia?
1. Epidemiology a. Median age of presentatio is 50 years old, with a range from 30 to 60 years old. b Fresnch american British (FAB) classification c. Risk factors 1 . Gentic factors-Down syndrome, TUrner syndrommee, and Klinfelter syndrome 2. Cheimcal/drugs-benzene and alkylating agents 3. Miscellaneous-inoizng radiation and MDS d. Cytogenetic abnormalities include 1. Mutations on chromosome 8 2. t(8,21)tranlocation
What is acute lymphoblastic leukemia (ALL)?
1. Epidemiology a. Most common leukemia and cancer in childres (newbornto 14 years of age) 1.. Adults can also develop ALL 2. Adults have a poorer prognosis than children with ALL b. peak incidence is 2to 10 years of age. c. Risk factors include: anitneoplastic agents, hodgkins lymphoma, ioning radiation, benzene exposure, and multile myeloma. d. immunologic classifcation for ALL is: 1. early pre-B-cell acuter lymphoblastic leukemia (80% of cases) 2. Pre- B, B ,and T cell acuter ummmphoblastic leukemia
What are the Myelodysplastic syndroms (MDSs)?
1. Epidemiology usually occur in men between 50 and 80 years old. 2. Pathogenesis a. Group of aacquired clona disorders that affect stem cells b . Characteristcally have cytopenias and hypercellular bone marrows. c. Classifcation 1. refractory anemia 2. refractory anemia with ringed sideroblasts. 3. Chroinc meylomonocytic leukemia 4. Refractory anemia with exces blast cells in transformation d. Frequently profresses to AML(30% of cases)
WHat are the lab findings of polycythemia vera?
1. INcreased RBC count, RBC mass, and PV 2. Decreased EPO a. EPO is decreased because O2 content is increased b Measuring serum levels of EPO is an excellent inital screen in diagnosisng polycythemia vera. 3. Normal Sao2 4. Hypercellular bone marrow with ibrosis that develops in late stages
What is acute and chronic leukemias?
1. Malignant diseases arising from bone marrotw stem cells, may inolve all cell lines. 2. More common in males than females 3. Risk factors a. Chromosomal abnormalities (exampled own syndrome and chromosome instability syndromes) b. Ionizing radiation (example, nuclear plant explosion) c. Chemicals is an example of bexene for myeloid and lymphoid leukemias d. Alkylating agents example busulfan. e. Chronic myeloproliferativ e diseases (polycythemia vera). f. Paroxysmal nocturnal hemoglobinuria (PNH) g. Cigarette smoking h. Immunodeficiency disease (example-wiskott-ALdrich sundrome which is classically characterized by ("TIE") Thrombocytopenia, immunodeficiency, and eczema with low IgM and increased IgE, and IgA due to mutations in WASP gene, which is a cytoskeletal glycoprotein) 4. Ages ranges for common leukemias and most common overall cancer in children. c. Person 40 to 60 years old 1. acute myeloblastic leukemia (AML) 2. Chronic myelogenous leukemia (CML) d. PErosns>60 years of age 1. Chronic lymphocytic leukemia (CLL 2. Chronic myelogenous leukemia.
What is the treatment?
1. Nonpharmacologic treatement is phlebtomoy to reduce hyperviscosity 2. Pharmacologic treatment a.Hydroxyyrea+plebotomy b. interferon-∂-2b g. Prognosis 1. WIthout treatment, the median survival is 6 to 18 months after diagnosis 2. With treament, the average survival time is 12 years.
What is the major and minor criteria of polycythemia vera?
1. Parameters that are measured for major citeria include: Hb, Hct, RBC count, RBC mass, and a test for the JAK2 V617F mutation in exon 14 2. Parameters that are evalutated forminor citeria include: A bone marrow exam, EPo level and in vitro demonstration of erythroid colony formation.
Whatis laboratory findings in acute leukemia?
1. Peripheral WBC count a. Ranges from <10,000 cells/mm3 (normal) to >100,000 cells/m3 are examples (myeloblasts, lymphoblasts, adn monoblasts. 2. Normocytic to macrocytic anemia (macrocytic if folic acid is depleted due to increased production of leukemic cells3. THrombocytopenia are usually <100,000 cells/mm3 4. Bone marrow findings a. Hyper ceullular with >20% blast cells b. Usually complelely replaced by blast cells
What are the laboratory findingss of essential thrombocythemia (ET)?
1. THobocytosis a. Platelet count is >600,000 cells/mm3 and is frequently >1 million cells/mm3. b Platelet morphology is abnormal 2. Mild neutrophilic leukocytosis 3. Basophilia is common 4. Bone marrow hypercellular and contains numerous megakaryocytes that appear abnormal (dysplastic) d. treatment is hydroxyurea.
What are the clinical findings of essential thrombocythemia (ET)?
1. bleeding is the most common finding, because the platelets are nonfunctional. b. Vessels thrombosis may also occur2. Splenomegaly
What is the laboratory findings in chronic leukemia
1.Peripheral WBC count a. count is similar to that of acute leukemia b. Blast cells are usually <10% of the toal WBC count c. Leukemic cells show evidence of mautration 2. Normocytic to macrocytic anemia and macrocyctic if folic acid is depleted because of increased production of leukemic cells 3. THrombocytopenia a. Usually <100,0000 cells/mm3 b. Exception is CML, in which thrombocytosis occurs in 35% of cases. 4. Bone marrow findings hypercellular with <10% blast cells
What are the laboratory findings of chronic myelogenous leukemia?
11. Initial peripheral EBC count ranges from 10,000 to 500,000 cells/mm3 a. Myeloid series is in all stages of development (sign of maturation) b. Basophilia is a consisntent finding 2 Normocytic to macrocytic anemia and macrocytic if folic acid is depleted in the production of leukemic cells 3. THrhombo cytosis occurs in 3% of cases (uncommon in leukemia_ a. Myeloblasts account for <10% of the myeloid cells. b. Marrow is hype cellular with marked myeloid hyperplasia. 5. Philadelphia chromosome is present in 95% of cases a. THis chromosome is not specific for CML and is present in other leukemias (ALL). b. Chromosome is not lost during therapy unless ∂-interferon is used 6. BCR-ABL fusion gene is present in 100% of cases fusion gene is present in 100% of cases Fusion gene is the most sensitive and specific test for chronic myelogenous leukemia 7. Decreased leukocyte alkaline phosphatase (LAP) score a. Stain for alkaline phosphatase in neoplastic granulocytes shows little to no uptake of the stain in the cytoplasm b. In benign granulocytes the stain is strongly positive 8. Blast crisis in CML a. Usually occurs in 5 years b. Increase in numbers of myeloblasts or lymphoblasts (25% of cases). c. NoAuer rods in myeloblasts.
What is acute monocytic leukemia?
2. Acute monocytic leukemia i. Proliferatin of monoblasts, usually lack MPO ii. Blasts characterisitcally infiltrate gums 3. Acute megakeryoblastic leukemia i. Proliferation of megakeryoblasts;lack MPO ii. Associated with Down syndrome (usually arises before the age of 5)
Whats acute monocytic leukemia?
2. Acute monocytic leukemia i. Proliferatin of monoblasts, usually lack MPO ii. Blasts characterisitcally infiltrate gums 3. Acute megakeryoblastic leukemia i. Proliferation of megakeryoblasts;lack MPO ii. Associated with Down syndrome (usually arises before the age of 5) E. AML may also arise from pre-existing dysplasia (myelodysplastic syndromes), espically with prior exposure to alkylating agents or radiotherapy.
What is the lymphadenopathy (LAD)?
A. LAD refers to enlarged lymph nodes 1. Painful LAD is usually seen in lymph nodes that are draining a region of acute infection (acute lymphadenitis) for example a strep throat which could cuase the lymph nodes in the neck to enlarge and become painful. 2. painless LAD can be seen with chronic inflammation (chronic lymphadenitis or autoimmune diseases), metastatic carcinoma (breast cancer that spreads to the axillary lymph nodes and they become enlarged and usually painless), or lymphoma. B. In inflammation, lymph node enlargement is due to hyperplasia of particular regions of the lymph node. 1. Follicular hyperplasia (B-cell region) is seen with rheumatoid arthrites and early stages of HIV infections due to the follicular dendritic cells which are CD4+ also, for example that results in generalized lymphadopathy. 2. Paracortex hyperplasia (T-cell regions) is seen with viral infections (infectious monocucleiosis and EBV) 3. Hyperplasia of sinus histiocytes live deep in the sinus of medulla andis seen in lymph nodes that are draining a tissue with cancer and it is becoming reactive.
What is multile myeloma?
A. Malignant proliferation of plasma cells in the bone marrow 1. Most common primary malignancy of bone; metastatic cancer, however, is the most common malignant lesion of bone overall 2. High IL-6 may be present; stimulates plasma cell growth and immunoglobulin production B. Clinical features include when you have a neoplastic proliferation of plasma cells, these cell have the ability to produce osteoclast activating factor and activates osteoclast through the RANK receptor. A. Bone pain with hypercalcemia-Neoplastic plasma cell activate the RANK receptor on osteoclasts, leading to bone destruction. Lytic, 'punched-out' skeletal receptor on osteoclasts leading to bone destruction. Lytic. 'punched-out' skeletal lesions are seen on x-ray., especially in the vertebrae and skulls; increased risk for fracture. 2. Elevated serum protein-Neoplastic plasma cells produce immunoglobulin; spike is present on serum protein electrophoresis (SPEP), most commonly due to monoclonal IgG or IgA. THe most abundant protein in the body is albumin, ∂1 band, ∂2 band, ß2 band and a gamma band (IgG, IgA, all of em) thats not higher than the ∂ band, but a sharp spike in the gamme region would be called an M spike and this would indicate due to a monoclonal imunoglobin. Multiple myeloma is usually IgG or IgA. 3. Increased risk of infection- Monoclonal antibody due to the production of one cell type of Ig lack antigenic diversity; infection is the most common cause of death in multiple myeloma 4. Rouleaux formation of RBCs on blood smear-increased serum protein decreases charge between RBCs 5. Primary AL amyloidosis-Over production of Free light chains circulate in serum and deposit in tissue that forms an aL amyloid also a primary amyloidosis 6. Proteinuria-free light chain is excreted in the urine as Bence Jones proteins; deposition in kidney tubules leads to risk for renal failure (Myeloma Kidney)
What is the follicular lymphoma?
A. Neoplasic proliferation of small B cells (CD20+) that form follicle-like nodules B. Presensts in late adulthood with painless lymphadenopathy. C. Driven by t(14;18) 1. BCL2 on chromosome 18 translocate to the Ig heavy chain locus on chromoosome 14 which is highly active.. 2. Results in oveerexpression of Bc12 (stabilizes the mitochondrial membrane), which inhbit apoptosis in the follicle of the lymph nodeis the one plas=ce where we want to have apoptosis because somatic hypermutation of the B cells and they are challenged by antigen and undergo somatic hypermutation to see if they can bind or produce antibodies that can bind against that antigen and if they pass they leave the germninal center of the lymph node and participate in inflammation but if they fail they undergo apoptosis and a translocation of BCL2 will cause follicular lymphoma. a lymph nodes contains dozens of follicles
What is the lymphoma?
A. Neoplasitic proliferation of lymphoid cells that form a mass; may arise in a lymph node or in extranodal tissue outside of the lymph node. B. Divided into NHL (60%) and HL (40%) 2. Lack of tingible body macrophages in germinal centers non-Hodgkin lymphoma (NHL,60%) and Hodgkin lymphoma (HL, 40%) C. NHL is further classified based on cell type (B versus T), cell size , pattern of cell growth(grow in a diffuse sheath or follicles), expression of surface markers to determine whether the cell are B or T cells, and cytogenetic translocations. 1. Small B cells(well differentiated neoplastic and look very similar to normal lymphocytes because they grow in a similar pattern. In the cortex you have the follicle mantle and on occasion we could generate the margin and these regions are the types of proliferations that can occur)- Follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma (CLL cells that involve tissue) 2. Intermediate-sized B cells - Burkttlymma) 3. Large B cells-diffuse large B cell lymphomae
What is acute myeloid leukemia?
A. Neoplastic accumulation of immature myeloid cells (>20%) in the bone marrow. B. Myeloblasts are usually characterized by positive cytoplasmic staining for myeloperoxidase (MPO) 1. Crystal aggregates of MPO may be seen as Auer rods C. Most commonly arises in older adults average age is 50-60 years) D. Subclassification based on cytogenetic abnormalities (predmominate mechanism to subclassify AML), lineage of immature myeloid cells, and surface markers. High yield subtypes include. 1. Acute promyelocytic leukemia (APL) i. Characterized by t (15;17), which involves translocation of the retinoic acid recptor (RAR) on chromosome 17 to chromosome 15; RAR disruption blocks maturation and promyelocytes (blasts) accumulate. ii.Abnormal promyelocytes contain numerous auer rods that increasae the risk for DIC iii. Treatment with all-trans retinoic acid (ATRA, a vitamin A derivative), wh'ich binds the altered receptor and causes the blast to mature to neutrophils (and eventually die). Clearly bigger than the RBCs, auer rodd and it has a punched out nucleolus WE can get a erythroblastic aml,, monoblastic aml or a megakaryoblast aml
What is acute lymphoblastic leukemia?
A. Neoplastic accumulation of lymphoblasts (>20%) in the bone marrow 1. Lymphoblasts are characterized by positive nuclear staining for TdT, a DNA polymerase 2. TdT is absent in myeloid blasts and mature lymphocytes B. Most commonly arises in childrens associated with Down syndrome (usually arises after the age of 5 years) C. Subclassified into B-ALL and T-ALL based on surface markers D. B-ALL is the most common type of ALL 1. Usually characterized by lymphoblasts (TdT+) that express CD10, CD19, and CD20. 2. Excellent response to chemotherapy; requires prophylaxis to the scrotum and CSF due to the blood barriers 3. Prognosis is based on cytogenetic abnormalities i. t(12,21) has a good prognosis; more commonly seen in children ii. t(9,22) has a poor prognosis; more commonly seen in adults (philadelphia+ALL) E. T-ALL is characterized by lymphoblasts (TdT+) that express markers randing from CD2 to CD8 (CD3, CD4, CD5, CD6 CD7). THe basts do not express CD10. 1. Usually presents in teenagers as mediatinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cell form a mass) picture is of the meninges tot the brain and all of the purple dots all represent ALL
What is the acute lymphocytic leukemia basic principles? What markers do they express? What is the relation to down syndrome? How can you distinguish from AML? Which translocations? good bad?
A. Neoplastic accumulation of lymphoblasts (>20%) in the bone marrow. We normally would see a certain amount of Blast that create mature cells that are pushed into the blood (1-2%). 1. Lymphoblasts are characterized by positive nuclear staining for TdT, a DNA polymerase 2. TdT is absent in myeloid blasts and mature lymphocytes B. Most commonly arises in children; associated with Down syndrome (usually arises after the age of 5 years) C. Subclassified into B-ALL and T-ALL baed on surface markers D. B-ALl is the most common type of ALL 1. Usually characterized by lymphoblasts (TdT+) that express CD10, CD19, and CD20. 2. Excellent response to chemotherapy requires prophylaxis to scrotum of CSF. 3. Prognosis is based on cytogenetic abnormalities. i. t(12:21) has a good prognosis; more commonly seen in children ii. t(9;22) has a poor prognosis; more commony seen in adults (philadelphia+ALL). E. T-ALL is characterized by lymphoblasts (TdT+) that express markers ranging from CD2 to CD* (CD#, CD4, CD7). The blasts do not express CD10. 1. Increased risk for splenic rupture;patients are generally advised to avoid contact sports for one month. 2. Rash if exposed to ampicillin 3. Dormancy of virus in B cells leads to increased risk for oth recurrence and B-cell lymphoma, espicially if immunodeficiency (HIV) develops.
What is Burkitt lymphoma?
A. Neoplastic proliferatio of intermediate sized B cells (CD20+) associated with EBV B. Classically presents as an extranodal mass in a child or young adult. 1. African form usually involves the jaw 2. Sporadic form usually involves the abdomen C. Driven by translocation of c-myc (chromosome 8) 1. t(8;14) is most common, resulting in translocation of c-myc to the Ig heavy chain locus on chromsome 14. 2. overexpression of c-myc, which is a nuclear regulator oncogene that activates multiple genes for the promotion of cell growth and it drives production of the tumor D. characterized by high mitotic index and starry sky appearance on microscopy
What is Hodgkin lymhoma (HL)?
A. Neoplastic proliferation of Reed-Sternberg (RS) cells, which are large B cells with mutilobed nuclei and prominent nucleoli (owl eye nuclei) clasiccaly positive for CD15 and CD30. B. RS cells secrete cytokines 1> Occasionally results in 'B' symptoms (fever, chills, weight loss, and night sweats) 2. Attract reactive lymhocytes, plasma, macrophages, and eosinophils 3. May lead to fibrosis C. Reactive inflammatory cells make up a bulk of the rumor and form the basis for classicication of HL. multi-lobed nucleus,large cell, clearly see the nucleolus, owl eyes surrounded around with the reactive cells.
What is acute leukemia?
A. Neoplastic proliferation of blasts; defined as the accumulation of >20% blasts in the bone marrow B. increased blasts "crowds out" normal hematopoiesis, and present with signs and symptoms of loss of the normal cells of the bone marrow resulting in an "acute" presentation with anemia (fatigue), thrombocytopenia (bleeding), or neutropenia (infection). C. Blasts usually enter the blood stream, resulting in a high WBC count. 1. Blasts are large, immature cells, often with punched out nucleoli, relatively immature and does not have much cytoplasam, but you may not be able to tell if these are lymphoblast (ALL, and tDt+ is the key marker) or myeloblast (AML, and MPO+ is the key marker, which can crystalize into an auer rod) D. Acute leukemia is subdivided into acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) based on the phenotype of the blasts
What is Hairy cell leukemia?
A. Neoplastic proliferation of mature B cells characterized by hairy cytopasmic processes B. cells are positive for tartrate-resistant acid phosphatase (TRAP) a trap stain would help identify these cells . C. Clinical features include splenomegaly which is common in most leukemia because the cells are going to go lymph nodes and lymphoid tissues (white pulp) but in this case due to accumlation of hair cells in and expansion of the red pulp) and "dry tap" on bone marrow aspiration (due to marrow fibrosis). Lymphadenopathy is usually absent. D. Excellent response 2-CDA (cladribine), an adenosine deaminase (part of purine degradation pathway) inhibitor; adenosine accumulates to toxic levels in neoplastic B cells. TRAPped in the red pulp, and bone marrow, they cant go the lymph node, and that why lyphoadenopathy is absent
What s iadult T-cell leukemia/ lymphoma (ATLL)?
A. Neoplastic proliferation of mature CD4+ T cells B. Associated with HTLV-1; most commonly seen in japan and the Carribbean C. clinical features include rash (one general principle of T cell leukemias is that they like to go to the skin and cause a rash) (skin infiltration), generalizedd lymphadenopathy with hepatosplenomegaly (mature lymphocytes like to got the lymph node and spleen, and lytic (punched out) bone lesions (not multiple myeloma!! THE RASH means its not multiple myeloma) with hypercalcemia.
What is the basic principles of myeloproliferative disorders?
A. Neoplastic proliferation of mature cells of myeloid linage;disease of late adulthood (average age is 50-60 years). B. Results in high RBC count with hypercellular bone marrow due to the increase production of granulocytes. 1. Cells of all myeloid lineages are increased; classified based on the dominant myheloid cell produced C. complications include 1. Increased risk for hyperuricemia, and gout due to high turnover of cells, and this could be like in PV when everytime a RBC is being created the nucleus has to be removed and degraded which activates the purine degradation pathway which cuases the production of uric acid. Same thihng wth CML when the overproduction of granulocytes die and are need to nuclear material need to be degraded. 2. Progression to marrow fibrosis this is called the step phase or burnt out phase or trasnformatin to acute leukemia.
What is chronic leukemia?
A. Neoplastic proliferation of mature circulating lymphocytes; characterized by a high WBC count (floating around in the blood) B. Usually insidious in onset and seen in older adults
What is polycythemia Vera(PV)? WHat mutation? symptoms
A. Neoplastic proliferation of mature myeloid cells, especially RBCs 1. Granulocytes and platelets are also increased B. Associated with JAK2 kinase mutation (SUPER HIGH YIELD) C. Clinical symptoms are mostly due to hyperviscosity of blood. 1. Blurry vision and headache 2. increased risk of venous thrombosis (classically Bus-Chiari syndrome can arise hepatic vein, portal vein and dural sinus) 3. Flushed face due to congestion (plethora) 4. itching, especially after bathing (due to histamine release from increased mast cells)CLASSIC D. Treatment is phlebotomy (decrease blood cell mass), second line therapy is hydroxyurea. 1. Without treatment, death usually occurs within one year E. PV must be distinguished from reactive polycythemia (increase RBC mass or count could be due to a reactive condtition) 1. In PV, erythropoietin (EPO) levels are decreased, and Sa02 is normal. 2. In reactive polycythemia due to high altitude or lung disease causing hypoxia, Sao2 is low, and EPO is increased .3 In reactive polycythemia due to ectopic EPO production from renal cell carcinoma, EPO is high and SAo2 is normal
What is chronic myeloid leukemia (CML)? What is highly associated with CML? How can you differentiate leukemoid reaction?
A. Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors are ,basophils are charaterically increased (basically B. Diven by t (9:22)(philadelphia chromosome)which generates a BCR-ABL fusion protein with increased tyrosin kinase activity and drives the overproduction of of neoplastic cells because it is a signal transducer that is an oncogene that has the ability to cause the signal of growth to the nucleus stimulating overgrowth. 1. FIrst line treatment is imatinib, which blocks tyrosine kinase activity. C. Splenomegaly is common (in the chronic phase). Enlarging spleen suggests progression to or a marker of the accelerated phase of disease;transformation to acute leukemia usually follow shortly thereafter. 1. Can transform to AML (2/3 of cases ) or ALL (1/3 of cases) since mutation can be in the a hematopoteric/pluripotent stem cell that can become a myeloblast or a lymphoblast or the myeloblast that forms the granulmocytes a blood smear of CML would show an increase amount of granulocytes and early precursors of the granulocytes, so the differential diagnosis is acute infection(leukemoid reaction or CML) D. CML is distinguished from a leukemoid reaction (reactive neutrophillic leukocytosis) by 1. Negative leukocyte alkaline phophatase (LAP) stain (are present in the secondary granules of granulocytes and this enzyme in useful in the purposes of inflammation...now cells that are arising due to in a leukemoid rection/inflammatory process are LAP positive because these cells are being generated to fight an infection). CML granulocytes have no intention on fighting the infection, and are LAP negative. 2. Increased basophils (absent with leukemoid reation...BASOPHILIA is HIGHLY ASSOCIATED WITH CML) 3. t(9;22) absent in leukemoid reaction
What is the myelofibrois?
A. Neoplastic proliferation of mature myeloid cells, especially megakaryocytes. 1. Associated with JAK2 kinase mutation (50% of cases) B. Megakaryocytes produce excess platelet-derived growth factors (PDGF) causing marrow fibrosis. C. CLincal features include 1. Splenomegaly due to extramedullary hematopoiesis because the fibrosis prevents the proper production hematopoesis in the bone marrow. 2. Leukoerythroblastic smear contain reticulin gates that inhibit cells from exiting into the blood until they are small enough to leave through the gate, but when extramedullary hematopoiesis happen we will not be able to prevent the cells from leaving the spleen and this is observed on a leukoerythroblastic smear (tear drop RBCs, nucleated RBCs, and immature granulocytes) 3. Increased risk of infection, thrombosis and bleeding due to bone marrrow i=unable to produce the produce elements and the extramedullary hematopoiesis from the spleen is unable to produce the proper amounts. way too may fibrosis or pink collagen dpeosited in the marrow space and only should be fat and bone marrow elements
What is Essential thrombocythemia (ET)?
A. Neoplastic proliferation of mature myeloid cells, especially platelets 1.RBCs and granulocytes are also increased but the key cells are platelets B. associated with HAK2 kinase mutation C. Symptoms are related to an increased risk of bleeding and/or thrombosis (if the platelets are over functioning) 1. Rarely proresses to marrow fibrosis or acute leukemia 2. No significatn risk for hyperuricemia or gout because the platelet doesnt have a nucleus ton of platelets but another disease that this can occur in is Iron deficiency anemia can also have a lot of platelets.
What is Chronic lymphocytic leukemia(CLL)?
A. Neoplastic proliferation of naive B cells that co-express CD5 (normally expressed on a T-cell), and CD20; most common leukemia overall. B.Increased lymphocytes and smudge cells are seen on blood smear C. Lymphocytes of CLL can do what lympocytes normally do and travel to the lymph node, and the involvement of lymph nodes leads to generalized lymphadenopathy this causes a mass and is called small lymphocytic lymphoma D. complications include 1. Hypogammaglobulinemia- (normally B cell become a plasma cell and secret immunoglobin but the neoplastic cell have no desire to become more mature) and as these cells take over the formation of hypogammaglobulinemia, and Infection is the most common cuase of death in CLL 2. Autoimmune hemolytic anemia, the cells normally don't make much immunoglobulin but if they do they do a bad job and create one against the patients own RBCs. 3.Transformation to diffuse large B-cell lymphoma (richter tranformation) marked clinically by an enlargin lymph node or spleen, and the patients already have small lymphocytic lymphoma and these cell can pick up more mutations and evtually transform into diffuse large B cell lymphoma. THe classic presentation would be a patient with an enlarging lymph node or enlarging spleen, and the reason why its enlarging is because it has a more aggressive tumor and its rapidly growing and enlarging the tissue.
What is the Mantle cell Lymphoma?
A. Neoplastic proliferation of small B cell (CD20+) that expands the mantle zone B. Preents in late adulthood with painles lymphadenopathy. C. driven by t(11(cyclin D:14 (immunogobilin heacy chain) 1. Cyclin D1 gene on chromsome 11 translocates to Ig heavy chain locus on chromosome 14. 2. Overexpression of cyclin D1 promotes G1/S transition in the cell by phosphorylating protein in the cell cycle facilitating neoplastic proliferations. "neoplastic proliferation immediately adjacent to the follicle" the mantel
What is the mycosis fungoides?
A. Neoplastic proliferations of mature CD4+ T cells that infiltrate the skin, producing localized skin rash, plaque and nodules usually multiple through the body. Aggregates of neoplastic cells in the epidermis are called Pautrier microabsecesses. B. Cells can spread into the blood ,proodcing Sezary syndrome. 1. Characteristic of lymphocytes with cerebriform nuclei Sexary cells) are seen on blood smear. nucleus appears to have a bunch of lobes almost like the brain because it has folding and are classic in sezary syndrome.
What is leukopenia? WHAT DO you treat cancer patients with?
A. Neutropenia refers to a decreased number of circulating neutrophils. Causes include 1. Drug toxicity (chemotherapy with alkylating agents)-prohibits the divison of cells like canacer cells and rapidly dividing cells (haematopoietic and progenitor cells). Damage to stem cells results in decreased production of WBCs, especially neutrophils. 2. Severe infection (gram-negative sepsis)-Increased movement of neutrophils into tissues results in decreased circulating neutrophils into tissues results in decreased circulating neutrophils 3. As a treatment, GM-CSF or G-GSF may be used to boost granulocyte production, thereby decreasing risk of infection in neutropenic patients and are used on paitent s inunder chemotherpay. B. Lymphopenia refers to a decreased number of circulating lymphocytes causes include 1. Immunodeficiency (DiGeorge syndrome due to a failure to develop the 3rd and 4th pharyngeal pouch that fail to develop the thymus so no T cell maturation or HIV) 2. High Cortisol state (exogenous corticosteroids or Cushing syndrome) induces apoptosis of lymphocytes 3. Autoimmune destruction (systemic lupus erythematosus of ten produce autoantibodies for cells int he blood) 4 Whole body radiation-the most sensitive cell in the body are lymphocytes are highly sensitive to radiation lymphopenia is the earliest change to emergy after whole body radiation.
What is leukocytosis?
A. Neutrophilic leukocytosis refers to increased circulating neutrophils. Causes include 1. Bacterial infection or tissue necrosis-induces release of marginated pool and bone marrow neutrophils, THese are the two driving factors for acute inflammation and this also will cause the bone marrow to release as many granulocytes and neutrophils as possible and releasing cells that are slightly immature and this i called the left shift; immature cells are characterized by decreased Fc receptors (CD16 which is the marker), which causes these immature neutrophils not to function as well. . How does acute inflammation tie in bro? (but did you kill it tho?) 2. High cortisol state-impaired adhesion, leading to release of marginated pool of neutrophils that sits in the blood vessels and stuck to the endothelium of the pulmonary vasculature (the other group is the neutrophils that are found in the serum), but this is what cuases the WBC count to go up. B. Monocytosis refers to increased circulating monocytes. Causes include chronic inflammatory states (autoimmune and infectious) and malignancy. C. Eosinophila refers increased circulating eosinophils. Causes include allergic reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma (there increase number of eosinophils with the tumor and with ciruclating around the blood due to increased IL-5 production). Eosinophilia is driven by increased eosinophil chemotactic factor. D. Basophilia refers to increased circulating basophils; classically seen in chronic myeloid leukemia E. Lymphocytic leukocytosis refers to increased circulating lymphocytes because these are going to be fought and handled by the CD8+ positive T-cells. Causes include: 1. Viral infections-T lymphocytes undergo hyperplasia in response to virally infected cells 2. Bordetella Pertussis infection bacteria produce lymphocytosis-promoting factor, which block circulating lymphocytes from leaving the blood to enter the lymph node, so after the lymphocytes are created in the bone marrow they enter the blood and then enter the lymph node to learn hot to make antibodies or to get stimulated to fight against infection
What is the Langerhans cell histiocytosis?
A.Langerhans cells are specialized dendritic cells found predominantly in the skin 1. Derived from bone marrow monocytes 2. Present antigen to naive T cells B. Langerhans cells histiocytosis is a neoplastic proliferation of langerhans cells 1. CharacteristicB irbeck (tennis racket) granules are seen on electron microscopy; cells are CD1a+ and S100+ by immunohistochemistry.
What is the neutropenia?
Absollute neutorphil count <1500 cells/mm3 b. Causes 1. Aplastic anemia 2. Immune destruction, examples systemic lypus erthmatosus (SLE), and parxysmal octurnal hemoglobinuria 3. Septic shock 4. Drugs, penicillin, cephalosporins, quindine, and sulfonamides 5. Rick borne diseases (Ehrlichoiosis, anaplasmosis, and babesiosis. 6. Viral infections, hepatitis, infeectious moncleosis 7. Bacterial infections (typhoid fever, bruecllosis, and tubercuosis) 8. Fungal infections (systemic fungal infections like histoplasmosis) 9 Ionizing radiation c. pathogenesis 1. Decreased production is aplstic anemia, ionizing radiation,and drugs 2. Increaed destructgion and destruction by complement, macropahges, and antibodeis 3. Activation of neutrophil adhesion molecules a. Increase the number of neutrophils adherinto endothelium a. Increase the number of neutrophils adhering to endothelium b example-endotoxins
What is Leukemoid reaction?
Absolute leukocyte count usually>25,000 to 30,000 cells/mm3 May involve neutrophils, lymphocytes, or eosinophils. b. Normal bone marrow response to cytokines released by cells (lymphocytes, stromal cells, macrophages ) to incfection (most common) or trauma c. Exmaples include: 1. Neutrophillic leukocytosis associated with perforated appendicitis 2. Lymphocytosis associated with whopping cough 3. Eosinophilia associated with cutanous larva migrans d. Pathogenesis is normal albeit exaggerated response to an infection
What is the starry sky appearance associated with?
Burkitt lymphoma The tumor cells are the sky and the tingible macrophages present in the tumor eating the tumor cells are the star.
How can AML arise from existing dysplasia?
E. AML may also arise from pre-existing dysplasia (myelodysplastic syndromes), espically with prior exposure to alkylating agents (chemotherapy) or radiotherapy. 1. these patients turn out to develop Myelodysplstic syndromes usally present with cytopenias, hypercellular bone marrow, abnormal maturation of cells, and increase blasts (<20%) 2. Most patients die due to cytopenia from infection of bleeding, through some progress to acute leukemia (>20% blasts).
What is inappropriate absolute polycythemia?
Ectopic production of EPO a. No hypoxic stimulus for EPO release; therefore it is an inappropriate absolute polycythemia. Ectopic release of EPO may occur in renal cell carcinoma (most common ) hepatocellular carcinoma. hb)Normal Sa02 c. Increased RBC count, RBC mass, and EPO level. d. Normal PV
What are the signs of metastatic disease?
a. Hepatosplenmegaly b. Generalized panless lymphadenopathy c. Headache from central nervous system (CNS) involvement especially common in ALL. d. Skin involvement, especially common in T-cell leukemias e. Testicles, especially common in ALL 4. Bone pain and tenderness and pain is due to bone marrow expansion by the leukemic cells.
What is the clinical findings of acute myeloblastic leukemia?
a. Weakness fatigue, bleeding, and fever (infection) b. Hepatosplenomegaly, painless generalized lymphadenopathy c. Gum infiltration (common in acute monocytic leukemia (M5)) 3. Laboratory findings a finding include normocytic anemia, thrombocytopenia, and leukocytosis b. Auer rods present in certain AML subtypes 1. splinter-shpaed to rod shaped structures in the cytosol of myeoblasts 2. onlypresent in AML (M2 and M3 subtypes). Not present in myeloblasts in CML, even when they go into a blast crisis c. Disseminated intravascular coagulation commonly occurs in AML 4. General treatment stragtegy , induction therapy, followed by consolidation therapy with otr withour radiation , followed by maintenance therapy. 5. Five year survival rate is 20%.
What is Diffuse large B cell lymphoma?
does not produce follicles, does not produce a mantle becasue it grows diffusely. A. Neoplastic proliferation of large B cells (CD20+) that grow diffusiely in sheets 1. Most common form of NHL 2. Clinically aggressive (high grade) because its not well differentia. B. arises sporadically or from tranformation of a low grade lymphoma (follicular lymphoma) 1. Presents in late adulthood as an enlargin lymph node or an extranodal mass.
WHat is commonly seen in myelofibrosis?
fibrosis of the bone marrow causes the RBC to be stressed leaving the reticulin gates and this causes the formation of the tear drop RBC and this cell is classicially seen in myelofibrosis.