Pathology Flashcards
What kind of cells are seen with liver disease and states of cholesterol dysregulation?
Acanthocytes or spur cells
What is seen in RBCs with lead poisoning, in sideroblastic anemias and myelodysplastic syndromes?
Basophilic stippling
What causes basophilic stippling seen on peripheral blood smears?
Aggregation of residual ribosomes
What type of RBCs are seen in bone marrow infiltration like myelofibrosis?
Tear drop cells or dacrocyte
What type of RBCs are seen in G6PD deficiency?
Bite cells or degmacyte
What type of RBCs are seen in end-stage renal disease, liver disease, or pyruvate kinase deficiency?
Burr cells or echinocytes
What type of RBCs are seen in hereditary ellptocytosis?
Elliptocytes
What causes elliptocytes to form?
Spectrin mutation (membrane protein)
What type of RBCs are seen in megaloblastic anemia?
Macro-ovalocyte
What type of neutrophils are seen in megaloblastic anemia?
Hypersegmented PMNs
What is seen on RBCs in sideroblastic anemia?
Ringed sideroblasts
What causes ringed sideroblasts seen in bone marrow?
Excess iron in mitochondria
What type of RBCs are seen in microangiopathic hemolytic anemias, including DIC, TTP/HUS, HELLP syndrome, and mechanical hemolysis?
Schistocytes
Fragmented RBCs and helmet cells are referred to what?
Schistocytes
What type of RBCs are seen in sickle cell anemia?
Sickle cells
What type of RBCs are seen in hereditary spherocytosis, drug- and infection-induced hemolytic anemia?
Spherocytes
What type of RBCs are seen in HbC disease, asplenia, liver disease, ant thalassemias?
Target cells
In what are Heinz bodies seen in RBCs?
G6PD deficiency
What causes Heinz bodies in G6PD deficiency?
Precipitation of Hb from oxidation of Hb-SH to S-S
In what disease are Howell-Jolly bodies seen?
Functional hyposplenia or asplenia
What type of anemia will have decreased iron, increased TIBC, decreased ferritin and increased free erythrocyte protoporphyrin?
Iron deficiency anemia
Iron deficiency anemia lab findings
Increased TIBC, protoporphyrin
Decreased iron, ferritin
What phenomenon is seen on RBCs in iron deficiency anemia?
Central pallor
Fatigue, conjunctival pallor, pica, and koilonychia is seen in which type of anemia?
Iron deficiency anemia
Triad of iron deficiency anemia, esophageal webs, and dysphagia seen in iron deficiency anemia?
Plumber-Vinson syndrome
Glossitis, cheilosis and Plumber-Vinson syndrome are common manifestations in what type of anemia?
Iron deficiency anemia
A cis deletion in a-thalassemia occurs more commonly in which race?
Asian populations
A trans deletion in a-thalassemia occurs more commonly in which race?
African populations
How many allele deletions are seen in a-thalassemia with no a-chains?
4 allele deletion
How many allele deletions are seen in a-thalassemia with HbH disease and very little a-chain?
3 allele deletion
How many allele deletions are seen in a-thalassemia with less clinically severe anemia?
2 allele deletion
How many allele deletions are seen in a-thalassemia with no anemia and is clinically silent?
1 allele deletion
What is a complication of a 4 allele deletion in a-thalassemia in a developing fetus?
Hydrops fetalis
What globulin type is produced in excess in a-thalassemia with a 4 allele deletion?
y-globulin (forms y4: Hb Barts)
What is a complication of Hb Barts in developing fetus?
Hydrops fetalis
What globulin type is produced in excess in a-thalassemia with a 3 allele deletion?
B-globin (forms HbH)
Which type of thalassemia is prevalent in Mediterranean populations?
B-thalassemia
What causes B-thalassemia?
Point mutations in splice sites and promoter sequences
An HbA2 > 3.5% on electrophoresis is diagnostic of which type of B-thalassemia?
B-thalassemia minor
Individual with chipmunk facies with extramedullary hematopoiesis with hepatosplenomegaly has which type of B-thalassemia?
B-thalassemia major
What risk is increased in B-thalassemia major?
Parvovirus B19 induced aplastic crisis
When does B-thalassemia major become symptomatic in a newborn
After 6 months (HbF is protective)
Which B-thalassemia has underproduction of B chain and usually asymptomatic?
B-thalassemia minor
Which B-thalassemia has absent B chains with severe microcytic, hypochromic anemia with target cells and increased anisopoikilocytosis?
B-thalassemia major
Which type of B-thalassemia presents with mild to moderate sickle cell disease?
HbS/B-thalassemia heterozygote
Which B-thalassemia is a heterozygote, major or minor?
Minor
Which B-thalassemia is a homozygote, major or minor?
Major
What enzymes does lead inhibit that cause decreased heme synthesis and increased RBC protoporphyrin
Ferrochelatase and ALA dehydrogenase
Which RNA molecule is inhibited by lead?
rRNA (cause of basophilic stippling)
Where are lead lines seen in lead poisoning?
Gingivae and metaphyses of long bones
What is used for chelation in kids?
Succimmer
What are first line treatments for lead poisoning?
Dimercaprol and EDTA
What are genetic causes for sideroblastic anemia?
X-linked defect in ALA synthase gene
What are acquired causes for sideroblastic anemia?
Myelodysplastic syndromes
What is the most common cause of reversible causes for sideroblastic anemia?
Alcohol
What are reversible causes for sideroblastic anemia?
Alcohol, lead, vitamin B6 deficiency, copper deficiency and isoniazid
Lab findings in sideroblastic anemia
Increased iron, ferritin
Normal to low TIBC
What is the treatment for sideroblastic anemia?
Pyridoxine
Which B vitamin is a cofactor for ALA synthase?
Pyridoxine (B6)
Cancer drug that causes megaloblastic anemia and folate deficiency
Methotrexate
What enzyme is inhibited by methotrexate that causes megaloblastic anemia?
Dihydrofolate reductase
What are findings seen in folate deficiency?
Increased homocysteine
Normal methylmalonic acid
No neurological symptoms
Glossitis
Where is folate absorbed in the body?
Jejunum
What is the source for folate?
Green veggies and fruits
What fish parasite can cause vitamin B12 deficiency?
Diphyllobothrium latum
What are findings seen in vitamin B12 deficiency?
Increased homocysteine and methylmalonic acid
Neurological symptoms
What neurological tracts are affected in vitamin B12 deficiency?
Spinocerebellar tract, lateral corticospinal tract, and dorsal column dysfunction
Where is vitamin B12 stored in the body?
Liver
Which depletes first, folate or B12?
Folate
How is vitamin B12 deficiency diagnosed?
Schilling test (malabsorption vs diet)
What is a source for B12?
Meats and eggs
Where in the body is vitamin B12 absorbed?
Ileum
What is needed for proper absorption of vitamin B12?
Intrinsic factor
What are the most common causes of extravascular hemolysis?
Hereditary spherocytosis and autoimmune hemolytic anemia
What are common findings in extravascular hemolysis?
Urobilinogen in urine
No hemoglobinuria or hemosiderinuria
Spherocytes in blood smear
Decreased haptoglobin
What are common lab findings in intravascular hemolysis?
Hemosiderinuria, hemoglobinuria, urobilinogen in urine
Increased unconjugated bilirubin (maybe)
Schistocytes in blood smear
What are common causes of intravascular hemolysis?
Mechanical hemolysis
Paroxysmal nocturnal hemoglobinuria
Microangiotpathic hemolytic anemias
Produced by liver and binds ferroportin on intestinal mucosal cells and macrophages inhibiting iron transport
Hepcidin
Findings in anemia of chronic disease
Decreased iron
Increased TIBC, ferritin
Viral agents that can cause aplastic anemia?
Parvovirus B19, EBV, HIV, hepatitis virus
Common causes of aplastic anemia
Radiation and drugs, viruses, Fanconi anemia, and idiopathic
Common lab findings in aplastic anemia
Decreased reticulocyte count
Increased EPO
What immunosuppressive agents can be used for aplastic anemia?
Antithymocyte globulin and cyclosporine
Autosomal dominant disorder causing extravascular hemolysis due to a defect in proteins interacting with RBC membrane skeleton and plasma membrane
Hereditary spherocytosis
What are the membrane proteins that interact with RBC membrane skeleton?
Ankyrin, band 3, protein 4.2 and Spectrin
What do RBCs look like in hereditary spherocytosis?
Small, round RBCs with no central pallor
What is the MCHC in hereditary spherocytosis?
Increased
What is the treatment for hereditary spherocytosis?
Splenectomy
What lab findings are seen in hereditary spherocytosis?
Positive osmotic fragility test
Normal to decreased MCV
Common infection that is seen in hereditary spherocytosis
Parvovirus B19 causing aplastic crisis
What organ in enlarged in hereditary spherocytosis?
Spleen
Most common enzymatic disorder of RBCs
G6PD deficiency
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant
Presents with back pain, hemoglobinuria a few days after oxidant stress with Heinz bodies on blood smear
G6PD deficiency
Autosomal recessive disease that causes hemolytic anemia in newborn and presents with increased levels o f 2,3 BPG
Pyruvate kinase deficiency
What ATP levels are seen in pyruvate kinase deficiency?
Decreased
Defect in GPI anchor for decay-accelerating factor causes hemolysis of RBC at night due to complement-mediated lysis and red-pink urine in the morning due to hemoglobinuria
Paroxysmal nocturnal hemoglobinuria
What are lab findings in Paroxysmal nocturnal hemoglobinuria?
CD55/59 negative RBCs on flow cytometry
What is a common triad in Paroxysmal nocturnal hemoglobinuria?
Coombs negative hemolytic anemia
Pancytopenia from aplastic crisis
Venous thrombosis = main cause of death
What is the treatment for Paroxysmal nocturnal hemoglobinuria?
Eculizumab
What is the target of eculizumab?
Terminal complement inhibitor
What population with HbS is usually asymptomatic?
Newborns
Autosplenectomized patients are at increased risk of what type of organisms?
Encapsulated organisms
Which bacteria is common in patients with autosplenectomy due to sickle cell anemia?
S pneumoniae
What is a common bacterial cause of osteomyelitis in sickle cell anemia?
Salmonella osteomyelitis
Common cause of death of adults with sickle cell anemia
Acute chest syndrome
How is sickle cell anemia diagnosed?
With gel electrophoresis
What is the treatment for sickle cell anemia?
Hydroxyurea, hydration, and folic acid supplementation
What is aplastic crisis in sickle cell anemia caused by?
Parvovirus B19
What is the mutation in HbC disease?
Glutamic acid to lysine in B-globin
What is seen on blood smear of HbC patient?
Crystals inside RBCs, target cells
Dactylitis, acute chest syndrome, priapism, avascular necrosis, and stroke are considered what in sickle cell disease?
Painful crisis (vaso-occlusive)
Autoimmune hemolytic anemia seen in SLE and CLL or drugs like a-methyldopa are associated with what type of immunoglobulins?
IgG
Is IgG autoimmune hemolytic anemia considered warm or cold?
Warm
Autoimmune hemolytic anemia seen in CLL, Mycoplasma pneumoniae infections and infectious Mononucleosis are associated with what type of immunoglobulins?
IgM
Is IgM autoimmune hemolytic anemia considered warm or cold?
Cold
RBCs that are damaged when passing through obstructed or narrowed vessel lumen as seen in DIC, TTP/HUS, SLE, HELLP syndrome and malignant HTN causes what type of hemolytic anemia?
Microangiopathic hemolytic anemia
RBCs damaged by prosthetic heart valves and aortic stenosis cause what type of hemolytic anemia?
Macroangiopathic hemolytic anemia
What type of RBC findings are seen in micro and macroangiopathic hemolytic anemia?
Schistocytes (helmet cells)
What type of infections also cause hemolytic anemia?
Malaria and Babesia infections
What are lab values in iron deficiency anemia?
Serum iron: decreased
Transferrin/TIBC: increased
Ferritin: decreased
% transferrin saturation: markedly decreased
What are lab values in anemia of chronic disease?
Serum iron: decreased
Transferrin/TIBC: decreased
Ferritin: increased
% transferrin saturation: no change
What are lab values in hemochromatosis?
Serum iron: increased
Transferrin/TIBC: decreased
Ferritin: increased
% transferrin saturation: markedly increased
What are lab values in pregnancy/OCP use?
Serum iron: no change
Transferrin/TIBC: increased
Ferritin: no change
% transferrin saturation: decreased
Which protein transports iron in blood?
Transferrin
Which protein is primary storage for iron?
Ferritin
What is used to indirectly measure transferrin value?
TIBC
Which receptors are decreased in immature neutrophils?
CD16 and Fc receptors
Increased neutrophil precursors like band cells and metamyelocytes is what kind of shift?
Left shift
What are the group of hereditary or acquired conditions of defective heme synthesis that lead to the accumulation of heme precursors called?
Porphyrias
What substance accumulates with ferrochelatase and ALA dehydratase inhibition or defect?
Protoporphyrin and ALA
What conditions can inhibit ferrochelatase and ALA synthase?
Lead poisoning
Common cause of lead poisoning in adults
Environmental exposure
Common symptoms of lead poisoning in adults
Headache, memory loss, demyelination
Common cause of lead poisoning in children
Exposure to lead paint
Common symptoms of lead poisoning in children
Mental deterioration
Autosomal dominant mutation that causes a deficiency in porphobilinogen deaminase leads to an accumulation of which heme precursors?
Porphobilinogen and ALA
Autosomal dominant mutation in which there is increased porphobilinogen and ALA heme precursors causing painful abdomen, port-wine colored urine, polyneuropathy and psychological disturbances
Acute intermittent porphyria
Blistering cutaneous photosensitivity and hyperpigmentation exacerbated by alcohol and has tea-colored urine - what is the heme precursor that accumulates?
Uroporphyrin
What is the deficient enzyme in porphyria cutanea tarda?
Uroporphyrinogen decarboxylase
What is the inheritance pattern of porphyria cutanea tarda?
Autosomal dominant
What is the rate-limiting enzyme in the heme synthesis pathway?
ALA synthase
How does increased heme affect ALA synthase?
Decreases activity
How does decreased heme affect ALA synthase?
Increases activity
X-lined sideroblastic anemia has a defect in which heme synthesis enzyme?
ALA-synthase
What enzymes are inhibited in lead poisoning?
Ferrochelatase and ALA dehydratase
Inhibition of ferrochelatase leads to an increase in which heme precursor?
Protoporphyrin
Inhibition of ALA dehydratase leads to an increase in which heme precursor?
ALA
How does glucose affect heme synthesis?
Decreases ALA synthase activity
What is the mechanism cell death in iron poisoning?
Peroxidation of membrane lipids
What is the treatment for iron poisoning?
Chelation and dialysis
Which chelators are used in iron poisoning?
IV deferoxamine or oral deferasirox
What is the most common test used to follow patients on warfarin?
INR
What lab test looks at function of the common and extrinsic pathway?
PT
What factors are analyzed in PT test?
I, II, V, X, VII
What lab test looks at function of the common and intrinsic pathway?
PTT
What factors are analyzed in PTT test?
All factors except VII and XIII
How are coagulation disorders diagnosed?
With mixing study
A mixing study will have what results with clotting factor deficiencies?
Correction of PT and PTT
A mixing study will have what results with acquired inhibitors?
No correction
Hemophilia A will increase which coagulation test, PT or PTT or both?
Increased PTT
Hemophilia B will increase which coagulation test, PT or PTT or both?
Increased PTT
Hemophilia B will increase which coagulation test, PT or PTT or both?
Increased PTT
Christmas disease is a defect in which coagulation factor?
Factor IX
Hemophilia B is also called what?
Christmas disease
What is the treatment for hemophilia?
Missing factor plus desmopressin
Liver disease will lead to a deficiency of all coagulation factors except which?
Factor VIII
What does a defect in platelet plug formation cause?
Increased bleeding time (BT)
Coagulation disorders, like hemophilia, lead to what type of hemorrhage?
Macrohemorrhage
Platelet disorders, like Bernard-Soulier, lead to what type of hemorrhage?
Microhemorrhage
Bleeding into joints, easy bruising, or bleeding after trauma or surgery are examples of macrohemorrhage seen in what disorders?
Coagulation disorders like hemophilia
Bleeding into mucus membranes, epistaxis, petechiae and purpura are examples of microhemorrhage seen in what disorders?
Platelet disorders like Bernard-Soulier syndrome
What fails to adhere in Bernard-Soulier syndrome?
Platelet-to-vWF adhesion
What is defective in Bernard-Soulier syndrome?
GpIb
Defect in platelet plug formation caused by decreased GpIb
Bernard-Soulier syndrome
What type of platelets are seen in Bernard-Soulier syndrome?
Large platelets
What fails to adhere in Glanzmann thrombasthenia?
Platelet-to-platelet adhesion
What is seen on blood smear in Glanzmann thrombasthenia?
No platelet clumping
What is defective in Glanzmann thrombasthenia?
GpIIb/IIIa integrin
What is increased in vitamin K deficiency, PT, PTT or both?
PT and PTT are both increased
What is the bleeding time (BT) in vitamin K deficiency?
BT is normal
What disease is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure?
Hemolytic uremic syndrome (HUS)
Common cause of HUS in children
EHEC E coli O157:H7
What is an additional finding in children affected with HUS that is not seen in adults?
Bloody diarrhea
What is the PT/PTT in HUS?
Normal PT/PTT
What type of RBCs are seen in HUS?
Schistocytes
What is the most common cause of thrombocytopenia in kids and adults?
Immune thrombocytopenia
What is the cause of immune thrombocytopenia
Anti-GpIIb/IIIa antibodies
What is common cause of immune thrombocytopenia in kids?
Post-viral infection
What is common cause of immune thrombocytopenia in adults?
Women mainly 2ndry to lupus
What is the mechanism of immune thrombocytopenia?
Anti-GpIIb/IIIa antibodies cause splenic macrophage consumption of platelet-antibody complex
What are common lab findings in immune thrombocytopenia?
Increased megakaryocytes on bone marrow bx
What is the treatment for immune thrombocytopenia?
Steroids, IVIG
When is splenectomy required for immune thrombocytopenia?
In refractory cases
Presents with neurologic and renal symptoms, fever, thrombocytopenia, and microscopic hemolytic anemia with schistocytes on blood smear in a female.
Thrombotic thrombocytopenic purpura (TTP)
What is the cause of TTP?
ADAMTS-13 deficiency
What are common lab findings in TTP?
Schistocytes, increased LDH, and normal coagulation parameters
What is the treatment for TTP?
Plasmapheresis and steroids
What coagulation defect is seen in von Willebrand disease?
Increased PTT and BT
What coagulation factor is deficient in von Willebrand disease?
Factor VIII
What fails to adhere in von Willebrand disease?
Platelet-to-vWF adhesion
What is the inheritance pattern in von Willebrand disease?
Autosomal dominant
Most common inherited bleeding disorder?
von Willebrand disease
What is the treatment for von Willebrand disease?
Desmopressin
How does desmopressin treat von Willebrand disease?
Releases vWF stored in endothelium
Most common cause of inherited hypercoagulability inherited by Caucasians
Factor V Leiden
G to A DNA point mutation causing an Arg506Gln mutation near the cleavage site
Factor V Leiden
Inherited mutation that causes recurrent pregnancy losses
Factor V Leiden
Increases risk of thrombotic skin necrosis with hemorrhage after administration of warfarin due to decreased ability to inactivate factors Va and VIIIa
Protein C and S deficiency
Mutation in 3’ untranslated region leading to increased production of prothrombin causing increased plasma levels and venous clots
Prothrombin gene mutation
What type of blood products are indicated for acute blood loss or severe anemia?
Packed RBCs
What type of blood products are indicated for stopping significant bleeding?
Platelets
What type of blood products are indicated for DIC, cirrhosis, or immediate anticoagulation reversal?
Fresh frozen plasma/prothrombin complex concentrate
What type of blood products are indicated for coagulation factor deficiencies involving fibrinogen and factor VIII?
Cryoprecipitate
What is the risk of infection transmission in blood transfusions?
Low
What is the cause of hyperkalemia in blood transfusions?
Lyse of RBCs in old blood units
What causes hypocalcemia in blood transfusions?
Citrate in blood chelates calcium
What is the strongest predictor of prognosis in Hodgkin lymphoma?
Stage
Which has a better prognosis, Hodgkin lymphoma or non-Hodgkin lymphoma?
Hodgkin lymphoma
What type of cells that are specific for Hodgkin lymphoma are seen on histology?
Reed-Sternberg cells
What virus is associated with Hodgkin lymphoma?
EBV
Which gender is more commonly affected by Hodgkin lymphoma?
Men (except nodular sclerosing type)
What age group is commonly affected by Hodgkin lymphoma?
Bimodal: Men > 55 years and young adults
How are lymph nodes affected in Hodgkin lymphoma?
Localized, single group of nodes with contiguous spread
How are lymph nodes affected in non-Hodgkin lymphoma?
Multiple lymph nodes involved, extranodal involvement common, noncontiguous spread
What cell types are affected in non-Hodgkin lymphoma?
Mostly B-cells; a few are T-cell types
What age group is affected by non-Hodgkin lymphoma?
Both children and adults
What diseases are associated with non-Hodgkin lymphoma?
Autoimmune diseases and HIV
Which type of Hodgkin lymphoma commonly affects young women?
Nodular sclerosis type
Which type of Hodgkin lymphoma has the best prognosis?
Lymphocyte rich
Which type of Hodgkin lymphoma has eosinophilia in immunocompromised patients?
Mixed cellularity
What causes eosinophilia in Hodgkin lymphoma mixed cellularity type?
Increased IL-5
Which type of Hodgkin lymphoma is more commonly seen in immunocompromised patients?
Lymphocyte depleted
Which type of Hodgkin lymphoma has the worst prognosis?
Lymphocyte depleted
What age group is commonly affected by Burkitt lymphoma?
Adolescents or young adults
What chromosomal translocation is seen in Burkitt lymphoma?
t(8;14) of c-myc and heavy-chain Ig
Which chromosome has the c-myc gene located on it?
Chromosome 8
Which chromosome has the heavy-chain Ig gene located on it?
Chromosome 14
Non-Hodgkin lymphoma with “starry sky” appearing sheets of lymphocytes with interspersed “tingible body” macrophages
Burkitt lymphoma
What virus is associated with Burkitt lymphoma?
EBV
In which group of people is the endemic form of Burkitt lymphoma with typical jaw lesions common?
Africans
What area of the body is affected by the sporadic form of Burkitt lymphoma?
Pelvis or abdomen
On what chromosome is the BCL-2 gene located?
Chromosome 18
What age group is affected by diffuse large B-cell lymphoma?
Typically adults, some children
What chromosomal translocation is seen in diffuse large B-cell lymphoma?
Alterations to BCL-2 and BCL-6
What does BCL-2 inhibit?
Apoptosis
Non-Hodgkin lymphoma that presents with painless “waxing and waning” lymphadenopathy with follicle-like nodules throughout lymph node
Follicular lymphoma
What is the chromosomal translocation seen in follicular lymphoma?
t(14;18) heavy-chain Ig and BCL-2
What is the most common type of non-Hodgkin lymphoma in adults?
Diffuse large B-cell lymphoma
What is the histology of grade 1 follicular lymphoma?
Small cleaved cells
What is the histology of grade 2 follicular lymphoma?
Mixture of large and small cells
What is the histology of grade 3 follicular lymphoma?
Large cells
What is the treatment for follicular lymphoma?
Low-dose Rituximab
What is the target of Rituximab
CD20
What CD marker is seen on small B-cells of follicular lymphoma?
CD20+ B-cells
Very aggressive type of non-Hodgkin lymphoma where patients present with late-stage disease
Mantle cell lymphoma
What age group is affected by mantle cell lymphoma?
Adult males
What is the chromosomal translocation in mantle cell lymphoma?
t(11;14) cyclin D1 and heavy-chain Ig
What cell surface marker is seen in mantle cell lymphoma?
CD5+
What age group is affected by marginal zone lymphoma?
Adults
What is the chromosomal translocation in marginal zone lymphoma?
t(11;18)
What diseases are associated with marginal zone lymphoma?
Sjogren syndrome, chronic gastritis
What is the typical presentation of marginal zone lymphoma?
Unilateral parotid gland enlargement
What age group is affected by primary central nervous system lymphoma?
Adults
Which non-Hodgkin lymphoma is considered an AIDS-defining illness?
Primary central nervous system lymphoma
What is commonly seen on MRI in primary central nervous system lymphoma?
Mass lesions on MRI
Primary central nervous system lymphoma needs to be distinguished from what other disease that also presents with mass lesions on MRI?
Toxoplasmosis
The pathogenesis of primary central nervous system lymphoma involves what type of infection?
EBV infection
Which lymphoma is associated with IV drug use, caused by HTLV and presents with cutaneous lesions?
Adult T-cell lymphoma
Lytic bone lesions and hypercalcemia in a person of Japanese descent with a history of IV drug use has what diagnosis?
Adult T-cell lymphoma
What countries have a higher incidence of adult T-cell lymphoma?
Japan, Caribbean, and West Africa
Adult with skin patches characterized by atypical CD4+ cells with “cerebriform” nuclei and intraepidermal neoplastic cell aggregates has what condition?
Mycosis fungoides
What can mycosis fungoides progress to?
Sezary syndrome
What can follicular lymphoma progress to?
Diffuse large B-cell lymphoma
What is the cause of hypercalcemia in multiple myeloma?
Increased osteoclast activity
What is the cause of renal failure in multiple myeloma?
Light chains deposited in kidney
What is the cause of Rouleaux formation seen in RBCs
Loss of charge between RBCs
What are common findings in multiple myeloma?
CRAB: HyperCalcemia Renal involvement Anemia Bone lytic lesions/Back pain
What are the Ig light chains in urine ?
Bence Jones protein
What are the X-ray findings in multiple myeloma?
Punched out lytic bone lesions
What is the most common primary tumor arising within bone?
Multiple myeloma
What percentage of monoclonal plasma cells in bone marrow must be present in multiple myeloma?
> 10%
What malignancy presents with M-spike on serum protein electrophoresis, “fried-egg” appearing plasma cells with “clock-face” chromatin and intracytoplasmic inclusions?
Multiple myeloma
What Ig globulin make up the M-spike in multiple myeloma?
IgG > IgA
B-cell lymphoma with hyperviscosity syndrome and no CRAB findings or lytic lesions on X-ray and IgM M-spike
Waldestrom macroglobulinemia
What is the treatment for Waldestrom macroglobulinemia?
Plasmapheresis
Presents with bone marrow < 10% monoclonal plasma cells, is asymptomatic and no CRAB findings
MGUS
What is the rate of MGUS developing into multiple myeloma?
1-2% per year
What is the most common cause of death in multiple myeloma?
Infections
Neutrophils with bilobed nuclei typically seen after chemotherapy
Pseudo-Pelger-Huet anomaly
What percentage of blasts are seen in acute leukemia?
> 20%
Cause of anemia in leukemia?
Decreased RBCs
Cause of infections in leukemia?
Decreased WBCs
Cause of hemorrhage in leukemia?
Decreased platelets
Leukemia in the skin?
Leukemia cutis
What trisomy is associated with T-ALL?
Down syndrome
What type of markers are seen in T-ALL T-cells?
CD2+ and CD8+ (TdT+ cells)
T-ALL commonly affects what age group?
Teenagers
What common finding is seen in T-ALL?
Thymic mass (presents as SVC-like syndrome)
Which chromosomal translocation is associated with a better prognosis in Acute Lymphoblastic Leukemia/Lymphoma?
t(12;21) seen in kids
Which type of Acute Lymphoblastic Leukemia/Lymphoma is more common and has a better prognosis, B-ALL or T-ALL?
B-ALL
Acute Lymphoblastic Leukemia/Lymphoma may spread to what parts of the body?
CNS and testes
What translocation is considered the Philadelphia chromosome?
t(9;22)
What cell surface marker is seen on B-ALL B-cells?
CD10+ marker
Which age group affected by Acute Lymphoblastic Leukemia/Lymphoma has the worst prognosis?
Adults ( usually have Philadelphia chromosome)
What is the most common adult leukemia?
Chronic lymphocytic leukemia (CLL)
What is the age range for Chronic lymphocytic leukemia?
> 60 years
What cell surface markers are associated with Chronic lymphocytic leukemia?
CD20, CD23, CD5
What type of cells are seen on a peripheral blood smear?
Smudge cells
What type of anemia is associated with CLL?
Autoimmune hemolytic anemia
What is the danger of CLL?
Richter transformation
What is Richter transformation?
CLL transforming into an aggressive lymphoma like diffuse large B-cell lymphoma
Lymphoid neoplasm with cells that have filamentous, hair-like projections on LM that stains with tartrate-resistant acid phosphatase
Hairy cell leukemia
What age group is affected by hairy cell leukemia?
Adult males
A mature B-cell tumor that has a dry tap on aspiration and patients present with splenomegaly and pancytopenia
Hairy cell leukemia
What is the treatment for hairy cell leukemia?
Cladribine or Pentostatin
What is the median age of onset for acute myelogenous leukemia (AML)?
65 years
What are typical myeloperoxidase positive inclusions seen in AML?
Auer rods
What risk factors are associated with AML?
Exposure to alkylating chemotherapy, radiation, and myeloproliferative disorders
What trisomy is associated with AML?
Down syndrome
APL responds well to what treatment?
All-trans-retinoic acid (vitamin A)
What is the effect of all-trans-retinoic acid (vitamin A) in APL?
Induces differentiation of promyelocytes
What is the chromosomal translocation seen in APL?
t(15;17)
Which myeloid neoplasm is defined by the Philadelphia chromosome, t(9;22) and myeloid stem cell proliferation?
Chronic myelogenous leukemia
What age group gets CML?
All age groups; peaks at 45-85 years; median age 65 years
Myeloid neoplasm that presents with dysregulated production of mature and maturing granulocytes like neutrophils, metamyelocytes and basophils
Chronic myelogenous leukemia
What is a complication of CML?
May accelerate and transform to AML, ALL - considered a “blast crisis”
What is a complication if cell with Auer rod ruptures?
DIC
What is the treatment for CML?
Imatinib
What is the mechanism of Imatinib?
Bcr-Abl tyrosine kinase inhibitor
What is the value of leukocyte alkaline phosphatase in CML?
Low due to low activity of malignant neutrophils
Which myeloproliferative disorder is associated with the Philadelphia chromosome?
CML
What is the treatment for Polycythemia vera?
Phlebotomy, Hydroxyurea, Ruxolitinib
What is the target of Ruxolitinib?
JAK1/2 inhibitor
Presents with intense itching after hot shower, severe burning pain and red-blue discoloration due to episodic blood clots in vessels of the extremities
Polycythemia vera
Lab findings in polycythemia vera
Increased: RBCs, WBCs, Platelets
Positive: JAK2 mutations
Lab findings in essential thrombocythemia
Increased: Platelets
Positive: JAK2 mutations (30-50%)
Characterized by massive proliferation of megakaryocytes and platelets with blood smear showing markedly increased number of platelets that are large or abnormally formed
Essential thrombocythemia
Is erythromelalgia more common in Polycythemia Vera or Essential Thrombocythemia?
PV > ET
Lab findings in myelofibrosis
Decreased: RBCs
Variable: WBCs, Platelets
Positive: JAK2 mutations (30-50%)
What causes obliteration of bone marrow in myelofibrosis?
Increased fibroblast activity
Teardrop RBCs and massive splenomegaly with fibrosis of bone marrow is seen in what myeloproliferative disorder?
Myelofibrosis
Lab findings in CML
Increased: WBCs, Platelets
Decreased: RBCs
Positive: Philadelphia chromosome: t(9;22)
Translocation associated with Burkitt lymphoma (c-myc activation)
t(8;14)
Translocation associated with CML (Bcr-Abl hybrid), ALL (less common and poor prognosis)
t(9;22) - Philadelphia chromosome
Translocation associated with mantle cell lymphoma (cyclin D1 activation)
t(11;14)
Translocation associated with follicular lymphoma (Bcl2-activation)
t(14;18)
Translocation associated with APL (M3 type of AML)
t(15;17)
Translocation associated with marginal zone lymphoma
t(11;18)
Which chromosome causes the overexpression of the other genes seen in Burkitt lymphoma, mantle cell lymphoma, and follicular lymphoma?
Chromosome 14
EM shows Birbeck granules that look like tennis rackets or rod-shaped and cells express S-100 and CD1a; also seen are lytic bone lesions in a child - what is the disease?
Langerhans cells histiocytosis
