Term
| what are the 3 categories of myeloid neoplasms |
|
Definition
acute myeloid leukemias
myeloproliferative disorders
myelodysplastic syndromes |
|
|
Term
| what are the 4 types of AML |
|
Definition
acute prolyelocytic leukemia
acute monocytic leukemia
acute megakaryoblastic leukemia
myelodysplastic syndrome |
|
|
Term
| what are the 4 myeloproliferative disorders |
|
Definition
chronic myeloid leukemia
polycythemia vera
primary myelofibrosis
essential thrombocythemia |
|
|
Term
| what is the general cellular process that leads to the symptoms in AML |
|
Definition
blast cells are unable to differentiate causing accumulation in the marrow
blasts crowd out normal hematopoiesis causing anemia, thrombocytopenia, and neutropenia. evuntally lead to marrow failure
blasts enter blood and and increase WBC count with large, immature (little cytoplasm) cells with punched out nucleolus |
|
|
Term
| what are the general clinical signs of AML 5 |
|
Definition
>55yo
abrupt onset: present within 3mo
depression of marrow function: fatigue, bleeding, fever, pallor, infection
bone pain and tenderness: marrow expansion, sub-periostral infiltration
if mass, will be discrete and granulocytic |
|
|
Term
| lab signs that distinguish AML 8 |
|
Definition
GRANULOCYTIC DIFFERENTIATION: MYELOPEROXIDASE AZUROPHILIC GRANULES IN AUER ROD CRYSTALIZATIONS
lysosomal non-specific esterase positive
blasts in peripherial blood and marro WBC<10000 or >100000
anemia, neutropenia, thrombocytopenia <100000 platelets0
acute leukemia: rare occurance where there is no blasts in blood
CD33: myeloid progenetor marker (also CD64, CD117, CD13-15) |
|
|
Term
| 4 characteristics of a AML on a wright gemisa stain |
|
Definition
fine chromatin
more cytoplasm
more granules
peroxidase positive |
|
|
Term
| cause of acute prolyeocytic leukemia |
|
Definition
| t(15l17) fuses RARA-PML blocking myeloid differentiation due to TF mutation |
|
|
Term
| TX prolyelocytic leukemia 3 |
|
Definition
take care of DIC first: EMERGENCY auer rods cause DIC
retinoic acid (vitA): overcomes block making neutrophiles and clearing tumor cells
chemo: use this too or pt will relapse |
|
|
Term
| prognosis of acute prolyelocytic leukemia |
|
Definition
|
|
Term
| how is acute monocytic leukemia diagnosed in the lab |
|
Definition
| positive for myeloperoxidase |
|
|
Term
| clinical signs of acute monocytic leukemia and why |
|
Definition
| proliferation of monoblasts that infiltrate gums causing ulceration and swelling |
|
|
Term
| 2 diagnostic criteria/associations for acute megakaryoblastic anemia |
|
Definition
lack myeloperoxidase
associated with down syndrom <5yo |
|
|
Term
| cause of myelodysplastic syndrome (AML) |
|
Definition
| exposure to alkylating agents or radiotherapy causes dysplasia of marrow cells, they are not permitted to enter the blood causing cytopenia and hypercellular marrow |
|
|
Term
| prognosis of myelodysplastic syndrome (AML) 2 |
|
Definition
death due to infection of bleeding
20% progress to acute leukemia |
|
|
Term
| general prognosis for AML 2 |
|
Definition
50% have long term disease
30% have long term disease with chemo
could benifit from marrow transplant |
|
|
Term
| risk factors for myelodysplastic syndrome 4 |
|
Definition
chemotherapy
alkylating agents
ionizing radiation
idiopathic |
|
|
Term
| explain the cellular changes in myelodysplastic syndrome |
|
Definition
| damage from risk factors causes loss of 5q or 7q which causes dysplasia in marrow cells and the marrow is replaced by transformed multipotential stems cells that can differentiate into RBC, granulocytes, platelets that are ineffective |
|
|
Term
| clinical signs of myelodysplastic syndrome 3 |
|
Definition
|
|
Term
| 3 signs in the marrow of myelodysplastic syndrome |
|
Definition
hyper or normocellular
megaloblastic erythroid precursors with Fe deposits in mitochondria (ringed sideroblasts)
granuulocyte precursors with abnormal granules |
|
|
Term
| prognosis of myelodysplastic syndrome 3 |
|
Definition
stem cells in marrow are unstable and could get mutations transforming it to AML
poor response to chemotherapy
mean survival 9-20mo |
|
|
Term
| general cause and cellular changes in chronic myeloproliferative disorders |
|
Definition
proliferation of myeloid progenitors that can terminally differentiate
involve activation of TK which generate signs mimicing hematopoietic GF |
|
|
Term
| clinical signs of chronic myeloproliferative disorders 4 |
|
Definition
later adult
high WBC
hypercellular marrow
may SEED nodes, liver, spleen (they make cancer too!) causing HSM and lymphadenopathy
hyperuricemia/gout: WBC break down products compete with uric acid
marrow fibrosis: marrow burns out, this causes transfer to acute leukemia |
|
|
Term
| cause of chronic myeloid leukemia |
|
Definition
95% t(9;22/phildalphia) fusion of BCR-ABL increases TK which mimics growth factors and causes a proliferation of GRANULOCYTES
5% subcytogenic BCR-ABL fusion along with other CH translocations |
|
|
Term
| clinical signs and stages 3 of CML |
|
Definition
pt 25-60yo
slow onset, non-specific symptoms
1. chronic: MASSIVE splenomeagly from extramedullary hematopoesis
2. accelerated: currently enlarging spleen, anemia, thrombocytopenia (only 50% have this phase)
3. transofrmation/blast crisis: transformation to acute leukemia (70%AML, 30%ALL) |
|
|
Term
|
Definition
leukocytosis >100000 (BASOPHILIA, neutrophils, myelocytes, metamyelocytes)
thrombocytosis
marrow hypercellularity
red pulp enlargement in spleen
leukocyte alkaline phosphatase LOW
t(9;22) ABL-BCR |
|
|
Term
|
Definition
marrow transplant: 70% curative, high risk
TK inhibitors |
|
|
Term
|
Definition
|
|
Term
| cause of polycythemia vera |
|
Definition
| JAK2 TK mutation activates EPO precursors increasing RBC |
|
|
Term
| clinical signs of polycythemia vera 17 |
|
Definition
middle age
slow onset
organ congestion and cyanosis: flushed face, HSM
extramedullary hematopoesis: HSM
thrombosis/infarct: heart, spleen, kidney
hemorrhage: GI, oropharynx, brain
headache
dizziness
hematemesis
melena
blurry vision
gout/hyperuricemia |
|
|
Term
| how do you distinguish polycythemia very from reactive and absolute polycythemia |
|
Definition
reactive: SaO2 increase
absolute: EPO increase
vera: no SaO2 increase, decreased EPO |
|
|
Term
| lab signs of polycythemia vera 4 |
|
Definition
decreased EPO
basophilia
HVT 60%
hypercellular marrow (progresses to spend with fibrosis leadiing to AML) |
|
|
Term
| tx of polycythemia vera 2 |
|
Definition
phelbotomy: decreased RBC mass
hydroxyurea |
|
|
Term
| prognosis of polycythemia vera 3 |
|
Definition
death w/o tx in 1y - vascular complications
10y survival - with phlebotomy
marrow failure --> AML |
|
|
Term
| cause of primary myelofibrosis |
|
Definition
JAK2 TK mutation increases megakaryocyte production
this crowds out and spends the marrow and shifts hematopoesis to spleen, liver, nodes causing HSM, anemia, thrombocytopenia, mild neutropenia |
|
|
Term
| clinical signs of primary myelofibrosis 5 |
|
Definition
HSM: once marrow fibrosed hematopoesis occurs in spleen, liver and nodes
increased infection, thrombosis, bleeding
hyperuricemia/gour |
|
|
Term
| why is there such fast fibrosis of marrow in primary myelofibrosis |
|
Definition
| megakaryocyte (platelet precursor) overproduction --> increased PDGF and TGFb which turn on fibroblasts in marrow |
|
|
Term
| lab signs in primary myelofibrosis marrow biopsy 6 |
|
Definition
fibroblasts
neoplastic megakaryocytes
abnormal RBC in odd shapes
leukoerythroblastosis
initially hypercellular with megakaryocytes
later hypocellular with fibrosis |
|
|
Term
| lab signs in blood biopsy in primary myelofibrosis |
|
Definition
abnormal RBC in odd shapes: PLIKILOCYTES, TEAR DROP RBC
immature WBC: leukoerythroblastosis, basophilia
large platelets: due to extramedullary hematopoesis
leukoerythroblastic smear |
|
|
Term
| what is leukoerythroblastosis |
|
Definition
| myelocytes and metamyelocytes |
|
|
Term
| what is a leukoerythroblastic smear |
|
Definition
| marrow contains reticulin gates to stop immature cells but in the spleen there are none so when it takes over hematopoesis (primary myelofibrosis) you seen myelocytes and metamyelocytes in the blood(nucleated RBC) |
|
|
Term
| primary myelofibrosis prognosis |
|
Definition
CML transformation
survive 4-5y
5-15% AML transformation |
|
|
Term
| what are langerhans cells, what do they do |
|
Definition
| immature dendritic skin cells derived from marrow monocytes that present antigen to nieve T cells |
|
|
Term
| cause of langerhans cells histocytosis |
|
Definition
| HLA-DR and CD1a cause neoplastic proliferation of langerhans cells that look histocytic rather than dendritic |
|
|
Term
| morphological characteristics of langerhans cells histocytosis 7 |
|
Definition
birbeck/tennis racket/HX bodies in cytoplasm (granules)
HLA-DR, MHC-II, CD1a, langerhin and S100 positive
vaculated cytoplasm |
|
|
Term
| what are the three langerhan cell histocytosis deasases |
|
Definition
letterer-swie disease (multisystem langerhands cell histocytosis/acute disseminated langerhans cell histocytosis)
eosinophilic granuloma (unifocal and multifocal langerhan cell histocytosis)
hans-schuller-christian disease |
|
|
Term
| clinical signs of letterer swie disease 10 |
|
Definition
<2yo
srborrhetic like erruptions
multifocal
if severe..
lymphadenopathy
pulmonary lesions
osteolytic bone lesions
HSM
marrow infiltration: pancythemia (recurrent otitis media and mastoiditis) |
|
|
Term
| tx and prognosis of letterer swie disease |
|
Definition
MALIGNANT
intense chemotherapy
rapidly fatal without tx
50% 5y survival with treatment |
|
|
Term
| cause of eosinophilic granuloma |
|
Definition
| expanding erosive accumulation of langerhans in medullary cavity of bones |
|
|
Term
| sings of unifocal eosinophilic granuloma 4 |
|
Definition
adolescent
skeletal lesions
asymptomatic (pain, tenderness)
pathological fracture: calvaria, ribs, femur |
|
|
Term
| prognosis of unifocal eosinophilic granuloma 2 |
|
Definition
heal spontaneously
cured with local excision or radiation |
|
|
Term
| signs of multifocal eosinophilic granuloma 10 |
|
Definition
in kids
multiple erosive bony lesions
infiltrate soft tissue: skin, lungs, stomach
diffuse skin erruptions: ears, scalp
ototis media, mastoiditis, URI
lymphadenopathy
HSM
50% involve posterior stalk and cause DI |
|
|
Term
| hans-schuller-christian disease clinical signs 4 |
|
Definition
lytic scalp defects
DI
exophalmos
>3yo |
|
|
Term
| hans-schuller-christian prognosis 2 |
|
Definition
spontaneous regression
often cured with chemo |
|
|
Term
| 8 things that cause massive (>1000g) splenomeagly |
|
Definition
myeloproliferative disorders: CML, primary myelofibrosis
chronic lymphocytic leukemia
hairy cell leukemia
lymphoma
malaria
gauchers
primary spleen tumor |
|
|
Term
| 13 things that cause moderate (500-1000g) splenomeagly |
|
Definition
portal HTN
splenic vein obstruction
acute leukemia
hereditary spherocytosis
thalassemia major
autoimmune hemolytic anemia
amyloidosis
neimann pick
metastic carcinoma/sarcoma
splenitis
TB
sarcoidosis
typhoid |
|
|
Term
| 6 things that cause mild (<500g) splenomeagly |
|
Definition
acute splenitis
mono
septicemia
intra abdominal infection
acute spleen congestion
SLE |
|
|
Term
|
Definition
enlarged spleen due to removal of excess circulation formed blood elements
most common and serious is platelets
second is RBC and PMN |
|
|
Term
| cause of thymic hyperplasia |
|
Definition
lymphoid follicles (germinal centers) in medulla with reactive B cells
present with myasthenia gravis, SLE, other autoimmune diseases |
|
|
Term
|
Definition
| neoplastic proliferation of thymic epithelial cells |
|
|
Term
| what does a thymoma look like: size, texture, color, location, cells around it |
|
Definition
firm and lobulated
white gray
15-20cm
encapsulated
in perithymic tissue
non-neoplastic thymocytes (immature T cells) by it |
|
|
Term
| what are the three types of thymoma, describe their cytological and biological agressiveness |
|
Definition
60% benigh: cytologically and biologicallt benign
20% malignant type I: cytologically benign, biologically malignant
5% malignant type II - cytologically and biologically malignant |
|
|
Term
| describe the cells in a benign thymoma |
|
Definition
medullary thymoma: spindled, elongated, medulla like
mixed thymoma: plump, round, cortical like |
|
|
Term
| where is the malignant 1 thymoma located |
|
Definition
locally invasive, occasionally metastasize
penetrates capsule and invades surroundiing vessels |
|
|
Term
| describe the epithelial cells of a malignant 1 thymoma |
|
Definition
abundant cytoplasm
round vasicular nuclei
some spindled epithelial cells |
|
|
Term
| what does a malignant 2 thymoma look like |
|
Definition
|
|
Term
| what tumors does malignant 2 thymoma behave like |
|
Definition
| squamous cell carcinoma or lymphoepithelioma like carcinoma |
|
|
Term
| what two cellular characteristics does malignant 2 thymoma have |
|
Definition
EBV genome included
many tymocytes around it |
|
|
