Flashcards in WBC Hematopathology Part 2 Deck (188):
Peripheral T-cell tumors are what % of NHL's in US and Asia?
Peripheral T cell and NK cell tumors are most common where?
In Far East
How do nodes appear in peripheral T cell neoplasms?
Diffuse effacement of nodal architecture
Markers for T-cell neoplasms? 2
1. Pan-T Markers (CD2/3/5)
2. CD4 or CD8 possibly
What defines a T-cell malignancy?
Clonal T-cell receptor gene rearrangements
How do T cell neoplasms generally present? (5)
How do T cell neoplasms respond to therapy?
Respond poorly due to being so aggressive
5 Peripheral T cell neoplasms?
1. Anaplastic large cell lymphoma
2. Adult T-cell leukemia/Lymphoma
3. Mycosis Fungoides and Sezary Syndrome
4. Large Granular Lymphocytic Leukemia
5. Extranodal NK/T-Cell lymphoma
Anaplastic Large Cell lymphoma has what rearrangement?
This produces what?
Rearrangement of ALK gene on chromosome 2p23
Active tyrosine kinases
What is the hallmark cell in Anaplastic Large Cell lymphoma
Large, anaplastic cells
What does Anaplastic Large Cell lymphoma's lymph node pattern mimic? (2)
1. Metastatic carcinoma
2. Hodgkin lymphoma variants
Anaplastic Large Cell lymphoma with ALK rearrangement are seen in what population?
What is prognosis?
Anaplastic Large Cell lymphoma without ALK rearrangement is seen in what population?
What is prognosis?
Adult T-cell leukemia/lymphoma is seen in adults infected with what?
Where is HTLV-1 seen in the world? 3
Clinical findings in Adult T-cell leukemia/lymphoma? 4
1. Skin lesions
4. Elevated WBC count with multilobulated CD4's
Prognosis of Adult T-cell leukemia/lymphoma?
Less than a year, extremely aggressive
Mycosis Fungoides and Sezary syndrome are two manifestations of what?
What are the hallmark cells involved?
Cutaneous T-cell lymphoma
Peripheral CD4 T cells wth a crebriform appearance
How does Mycosis FUnoides present as?
Where do the T cells go?
Inflammatory pre-mycotic phase and progresses through a plaque phase to a tumor phase.
Sezary syndrome has what main presentation?
What is prognosis?
Generalized exfoliative erythroderma
Incurable but long survival
Large granular lymphocytic leukemia is seen how?
What population mainly has it?
What organs does it avoid?
With granules which is strange for lymphocytes
Lymph nodes and liver
Hallmark of Large granular lymphocytic leukemia?
Lymphocytes in peripheral blood and BM with blue cytoplasm and scattered azurophilic granules
Two symptoms of Large granular lymphocytic leukemia?
Two variants of Large granular lymphocytic leukemia
Which is more severe?
Which has splenomegaly and lymphocytosis?
T cell: Mild/Lymphocytosis + Splenomegaly
NK Cell: Aggressive
What are the five subtypes of hodgkin lymphomas?
– Nodular sclerosis
– Mixed cellularity
– Lymphocyte depletion (rare)
– Lymphocyte predominance (LP)
Which of the hodgkin subtypes are classical hodgkin lymphoma?
First four (not LP) since the R-S cells have similar immunophenotype
What makes LP different from other hodgkin subtypes?
Malignant cells express a different B-cell phenotype (CD20, CD15 and CD30 -)
Hodgkin lymphoma neoplasm is located where in body?
What virus causes some of these?
Best prognosis indicator?
Germinal center or post-germinal center B lymphocytes
Clinical stage is great indicator
Side effects of chemo/radiotherapy against Hodgkin lymphoma?
2. Acute leukemia
3. Lung cancer
5. breast cancer
6. Gastric cancer
How does one avoid the cancers caused by chemo and radiotherapy?
Use new drug combinations and less of the drugs
What is Stage I Hodgkin?
Involvement of single lymph node region or single extra-nodal site
Stage II hodgkin?
Two or more lymph node regions (or extranodal sites) on same side of diagphragm
Stage III Hodgkin's
Involvement of lymph node regions on both sides of the diaphragm.
May include spleen or localized extranodal disease
Stage IV Hodgkin's
Diffuse extralymphatic disease in liver BM, lung, skin
Most common Hodgkin subtype?
Nodular sclersosis is what % of HL?
Difference in sexes?
Sexes are equal
What are the two histo signs of nodular sclerosis?
Bands of collagen fibrosis
R-S cells in nodular sclerosis have what markers?
1. Positive for CD15 and CD30
2. Negative for CD45 and other B and T markers
Age of nodular sclerosis patients?
1. young adults
Mixed cellularity hodgkin lymphoma is the most common form of HL in what group of patients?
Males older than 50
Immunophenotype of mixed cellularity hodgkin?
Same as Nodular
1. Positive for CD15 and CD30
2. Negative for CD45 and other B and T markers
Patients with mixed cellularity hodgkin are more likely to present how?
Advanced disseminated disease
Prognosis remains really good
RS cells in mixed cellularity hodgkin contain what at 70%?
Lymphocyte-Rich hodgkin lymphoma has what cell predominate?
How to distinguish between Lymphocyte Rich and Lymphocyte Predominance?
Lymphocyte Rich has frequent mononuclear R-S cells of characteristic HL immunophenotype
Lymphocyte-Rich hodgkin lymphoma is associated with what virus at 40%
Prognosis of Lymphocyte-Rich HL?
Very good to excellent prognosis
What is the least common form of hodgkin lymphoma?
What cells are low in Lymphocyte-Depletion?
Which are high?
What is immunotype for these cells?
Abudant R-S cell variants
Age and patient group of Lymphocyte depletion HL?
EBV positive in what % of Lymphocyte depletion HL?
What is prognosis in Lymphocyte depletion HL?
Lymphocyte predominance HL is what patient group?
Males younger than 35
Lymphocyte predominance HL is characterized by what cells?
Other cells (2)
Lymphohistiocytic variant cells/Popcorn cells
Reactive lymphocytes and histiocytes
Are RS cells present in Lymphocyte predominance HL?
Yes, but very rare
L and H cells have what markers? (4)
What does this mean?
1. Positive for CD20 and BCL6 (b cell lymphoma characteristic)
2. Negative for CD15 and CD30 (RS cells)
This is really a B-cell lymphoma
Is LP associated with EBV?
three major categories of myeloid neoplasms?
Acute myeloid leukemias
What is AML?
blockage in differentiation of early myeloid cells which causes blasts to accumulate in BM and then circulate in peripheral blood
What is Myelodysplastic syndrome?
Terminal differentiation of early myeloid cells occurs but is disordered and ineffective
How is MDS marked?
Presence of dysplastic marrow precursors and peripheral blood cytopenias
What is a myeloproliferative disorder?
Neoplastic clone retains capacity to undergo terminal differentiation with dysregulated goal.
Myeloproliferative disorders result in what peripheral blood?
Increased RBC's, WBC's and platelets
Acute myeloid leukemia is due to what?
Acquired oncogenic mutation blocking normal cell differentiation --> Accumulation of myeloblasts in marrow
AML leads to what?
Which appears how (3)
Anemia, thrombocytopenia, neutropenia
Acute Myeloid Leukemia occurs when?
What age most?
Peaks after 60
Acute myeloid leukemia signs and symptoms resemble what?
Related to what?
Acute lymphoblastic leukemia
Splenomegaly and lymphadenopathy
How might AML rarely prsent?
Infiltration of what suggests monocytic types?
Discrete tissue mass like a sarcoma or myeloid tumor
Infiltration of skin and gingiva
Diagnosis of AML
What is done first?
What is the key diagnostic finding?
Greater than 20% myeloblasts in BM
Cytogenetic abberations in AML? (2)
1. Disrupt genes encoding TF's for normal differentiation
2. Activate mutated tyrosine kinases --> Constant proliferation signals
The M3 AML affects what population most?
What does it progresss to?
What stains do you do for AML? 3
1. Myeloperoxidase (myelocytic)
2. Specific esterase (myelocytic)
3. Nonspecific esterase (monocytic)
Markers of AML? 4
What are the WHO classifications of AML? 4
1. AML with particular genetic abnormalities
2. AML with MDS-like features
3. AML, therapy related
4. AML not otherwise specified
AML has what particular genetic abnormalities?
Using FAB classification, which AML's are precursor of neutrophils?
M0 through M3
Using FAB classification, which AML has both myeloid and monocytic precursors?
M4 and M4 eos
Under FAB classification, which AML's are precursors of different things?
M7: Acute megakaryocytic
Chemo can get you into complete remission but 5 year survival is low.
High risk forms of AML and relapsing AML are treated with what?
Main histo findings of AML? 2
Acute promyelocytic leukemia (APL/AML-M3) exhibits what genetic mutation?
What protein forms in APL/M3?
Fusion of retinoic acid receptor alpha (RARA) and PML gene to make a product that blocks myeloid maturation at promyelocyte stage
How to overcome RARA-PML block in APL?
Vitamin A derivatives and chemo
APL is associated with what two things
What is the key cell finding in AML?
Auer rods in a Faggot cell
What is cause of most myelodysplastic syndromes?
What is identified in 70% of myelodysplastic syndromes?
Clonal chromosome abnormality in chromosomes 5, 7, 8, 20
What is the mean age of onset of myelodysplastic syndromes
Symptoms of myelodysplastic syndromes appear similar to what?
Pancytopenia: Infeciton, anemia, hemorrhage
What are the subtypes of myelodysplastic syndromes classified based on? 3
1. Number of blasts
2. cell lines
3. Presence of ring sideroblasts
What must be excluded before a diagnosis of myelodysplastic syndromes can be made?
All non-clonal causes for dysplasia must be disproved such as drugs, growth factor therapy, virus, immune disorder, vitamin deficient, too much zinc
How do myelodysplastic syndromes respond to therapy?
Poorly, but some may live more than 5 years.
What do younger patients with myelodysplastic syndromes get for treatment?
what is main cause of death in myelodysplastic syndromes?
Marrow failure: Thrombocytopenia and neutropenia
Myeloproliferative disorders have what mutation?
Mutated tyrosine kinases causing GF-independent proliferation
What are four features of myeloproliferative disorders?
1. Increased marrow proliferation (RBC, WBC, PLT)
2. Neopalstic stem cells seed secondary hematopoietic organs (hepatosplenomegaly)
3. Variable transofrmation to a spent phase with marrow fibrosis and peripheral cytopenis
4. Variable transformation to acute leukemias
Four main forms of myeloproliferative disorders?
1. Chronic Myeloid leukemia
2. Polycythemia Vera
3. Essential thrombocytosis
4. Primary myelofibrosis
Chronic myeloid leukemia affects what age mainly?
What is main physical symptom of CML?
WBC count in CML?
Other cells present (2)
Over a 100,000
Eosinophils and basophils
CML has what % blasts?
What does bone marrow show?
What is the Leukocyte Alkaline Phosphatase (LAP) score?
less than 10%
Decreased leukocyte alkaline phosphatase score
Untreated survival of 3 years
50% of CML patients enter what phase?
what does this entail (4)
1. increasing anemia
3. More mutations
4. Blast crisis eventually
50% of CML patients enter wha tother phase?
There is a 30:70 ratio of what?
30% are B cell ALL and 70% are AML
Treatment for CML?
Gleevec inhibits BCR-ABL fusion product of the mutated tyrosine kinase gene t(9;22)
What % get remission with Gleevec in CML?
What is treatment of choice in younger CML patients?
Increase in concentration of erythrocytes in the blood
2 forms of polycythemia
1. Relative polycythemia
2. Absolute polycythemia
What changes in relative polycythemia?
Increase in hematocrit due to a decrease in plasma volume.
NO CHANGE IN TOTAL RBC mass
Causes of relative polycythemia (2)
1. Diminished plasma volume due to shock
2. Stress polycythemia
Absolute polycythemia is due to what?
Increase in total red cell mass
Two types of absolute polycythemia
Primary polycythemia is characterized by what
Secondary polycythemia is characterized by what?
High or normal EPO
Appropriate EPO production occurs when?
Hypoxia and arterial O2 desaturation (high altitude, smoker, methemoglobinemia,)
Inappropriate EPO production occurs when (2)
2. Renal pathology
Polycythemia Vera has signs and symptoms due to what?
EPO-independent increase in RBC mass
Polycythemia has strong association with what mutation?
Increased blood volume and viscosity are due to what in polycythemia vera?
Increase in RBC cell mass
HCT = Over 60%
WBC: = High
PLT = High
Basophils = High
6 main signs of polycythemia vera?
1. Mild hepatosplenomegaly
2. Panhyperplasia and Decreased Iron
3. Plethora (ruddy red complexion)
5. Intense pruritis
6. Major bleeding and thrombotic episodes
Polycythemia vera has an age of what?
60 years old
Death of polycythemia?
Bleeding or thrombosis
RBC mass in polycythemia vera can be kept maintained by what?
After 10 years what happens to Polycythemia vera patients?
Transition into spent phase with extramedullary hematopoiesis and splenomegaly
Major criteria for polycythemia vera? (2)
Minor criteria (2)
1. Elevated Hb
2. Presence of JAK2 mutation
1. BM biopsy showing hypercellularity with trilineage growth
2. Serum EPO decreased
3. Endogenous erythroid colony formation in vitro
Essential thrombocytosis is an increase in proliferation confined to what elements?
Megakaryocytic elements (platelets)
Diagnosis of essential thrombocytosis is described how?
Diagnosis of exclusion since all myelo-proliferative disorders can be associated with thrombocytosis
PLT count in essential thrombocytosis?
Greater than 600,000
Bone marrow of essential thrombocytosis appears how?
Hypercellular with increased abnormal megakaryocytes
Platelets appear how in essential thrombocytosis?
Enlarged and functionally abnormal
50% of essential thrombocytosis is associated with what mutation?
Course of essential thrombocytosis?
Long asymptomatic periods with occaisional thrombotic or hemorrhagic crises
Two progressions of essential thrombocytosis?
1. Spent phase of myelofibrosis
2. Transform to AML
Survival of essential thrombocytosis?
Primary myelofibrosis has its fibrosis occur where early?
Marrow fibrosis has what effect on body?
Suppress hematopoiesis --> pancytopenias --> Spleen and liver respond --> Extreme hepatosplenomegaly
What cell type increases and appears strange in primary myelofibrosis?
What does this stimulate?
Stimualtes benign fibroblasts to lay down collagen and form marrow fibrosis
What mutation is in 50-60% of primary myelofibrosis?
Peripheral blood in primary myelofibrosis demonstrates what? 2
Leukoerythroblastosis and Teardrop cells
Primary myelofibrosis appears in what age?
4 symptoms to present with?
older than 60
Cell changes in Primary myelofibrosis? 4
1. Increase basophils
2. Abnormal platelet morphology
3. Increased abnormal megakaryocytes
4. Marked marrow fibrosis
Survival length in Primary myelofibrosis?
Langerhans Cell histiocytosis is what?
Clonal proliferation of dendritic antigen-presenting cells normally found in many organs
What do cells contain in Langerhans Cell histiocytosis?
S-100 and CD1a antigens
Old name for Langerhans Cell histiocytosis?
Three entities of Langerhans Cell histiocytosis?
Multifocal multisystem LCH
Unifcoal and multifocal unisystem LCH
Multifocal multisystem LCH occurs when in life?
Main cell and its appearance?
Before age 2
Monocytic cell with convoluted/folded nucleus
Agressive and fatal if untreated. Chemo can keep you alive
Unifocal and multifocal unisystem LCH involves what action?
Erosive accumulations of Langerhans cells in medullary cavities of bones
What bones are usually involved in Unifocal and multifocal unisystem LCH? 3
Unifocal and multifocal unisystem LCH age?
Spontaneous regression or chemo
Unifocal and multifocal unisystem LCH has unifocal lesions in what ages?
Older children or adults
Pulmonary LCH involves what patient group mainly?
Pulmonary LCH can be defined as what better?
Four splenic functions that impact disease states?
Phagocytosis of blood cells and particulate matter
Sequestration of formed blood elements
Splenic insufficiency/Asplenia is due to what? 2
Splenectomy is due to what? (2)
1. Traumatic injury that ruptures spleen
2. Hemolytic anemias
Autoinfarction can be due to what?
Sickle cell disease
Splenic insufficiency/Asplenia results in what?
What is this due to?
Increased susceptibility to sepsis by encapsulated bacteria
Loss of filtering and Ab production
Vaccinate these people appropriately
What is hypersplenism characterized by?
2. Anemia, leukopenia, thrombocytopenia
3. Hyperplasia of marrow precursors of deficient type
Correction of hypersplenism blood cytopenias is done by what?
Massive splenomegaly is a weight of what?
Weight > 1000 grams
Moderate splenomegaly is what weight?
Mild splenomegaly is what weight?
< 500 grams
Nonspecific acute splenitis is what?
Nonspecific reaction to any blood-borne infection
What happens within the spleen in Nonspecific acute splenitis? 2
Congestion of red pulp with neutrophils
Plasma cells throughout spleen
Congestive splenomegaly definition?
What type of disorders cause this?
Enlargement due to chronic venous congestion
Disorders leading to splenic or portal vein hypertension
1. Central venous congestion
2. Cirrhosis of liver
3. Portal vein thrombosis
What is Congestive splenomegaly usually associated with?
Primary splenic neoplasms are how common?
Most common type?
Tumors in lymphohematopoietic system
What is more common in congenital anomalies: hypoplasia or complete absence?
What is a common finding in congenital anomalies of spleen?
Accessory spleen (spleniculi)
When are accessory spleens really important? 2
Setting of splenectomy in treatment of
1. Hemolytic anemias
Splenic rupture is precipitated by what?
1. Crushing injury
2. Severe blow
When does spontaneous splenic rupture occur?
Minor physical insult to a spleen that is fragile by underlying condition like mono, malaria, lymph cancers
Are chronically enlarged spleens likely to rupture?
No. Fibrosis makes them tough
Thymus plays a big role in what? (2)
1. T-cell differentiation
3 frequent disorders of thymus?
1. Developmental disorder
2. Thymic hyperplasia
Di-Geroge syndrome definition:
Thymic hypoplasia or apalasia with parathyroid developmental failures
Symptoms of DiGeorge Syndrome (CATCH-22) 5
Why are thymic cysts important?
Thymic neoplasms are often associated with cysts
Does a normal thymus have lympoid follicles?
B-cell germinal centers/follicles in medulla of thymus suggest what?
Thymic Follicular Hyperplasia
What disease has Thymic Follicular Hyperplasia the most?
What is the treatment?
Thymoma is what?
Thymic tumor in which neoplastic element is epithelial
3 types of thymoma?
1. Noninvasive (most common and benign)
3. Thymic carcinoma (most malignant/severe)
Thymic carcinomas are usually what type of carcinoma?