Pathology 4,5,6 : White Blood Cell Pathology Flashcards
Which is more prevalent in Acute WBC disease: Immature or Mature cells being produce ?
Immature, typically due to -blast expansion
In Chronic WBC disease you will see more mature cells being expanded,
What cells are typically seen in Lymphocytic Leukemia/Lymphomas ?
Lymphoid lineage cells: T and B cells.
What cells are typically seen in Myeloid Leukemia/Lymphomas ?
Myeloid lineage cells: Granulocytes/Monocyte (Neutrophil, Basophil, Eosinophil), Megakaryocytes (platelets).
What is leukopenia ?
Low levels of circulating WBCs
agranulocytosis (Neutrophils, Basophils and Eosinophils) often lead to fatal infections and sepsis !
What is often seen in conjunction with Leukopenia ?
anemia and thrombocytopenia ( especially if leukopenia is due to suppression of Common Myeloid Progenitor Cells)
Common causes of leukopenia are (4)…
Medications
Vitamin deficiencies
Malignancies ( Anything growing in the white bone marrow (malignancies) will cause leukopenia ).
Splenic sequestration (spleen can soak up WBC’s.)
Absolute Neutropenia (loss of neutrophils) is often caused by deficiencies in which vitamins ?
B12 /Folate –> Megaloblastic Anemia
Suppression of GRANULOCYTIC precursor cells ( –>Absolute Neutropenia and agranulocytosis) is often due to …
Exposure to certain medications:
Chemotherapy Chloramphenicol Sulfa drugs Chlorpormazine Clozapine (Anti-psychotic) **** ON BOARDS.
Suppression of MYELOID STEM CELLS (–>Absolute Neutropenia and Agranulocytosis) is often the result of…
Aplastic Anemia, Leukemias, Malignant Lymphomas
Besides being caused by ineffective or suppressed neutrophil production, Absolute Neutropenia can be cut to ACCELERATED REMOVAL of neutrophils in which organ ?
Spleen (Splenic Sequestration )
Also, increased removal can be caused by:
- Septicemia
- Immunologic damage to Neutrophils (As seen in Felty Syndrome: rheumatoid arthritis, splenomegaly and neutropenia.)
What is leukocytosis ?
Increased number of WBCs in blood (the type of cell lineage expanded really determines severity)
What is the most common cause of Leukocytosis of Neutrophils ?
Infection of some varying degree ( Pyogenic Bacterial Infections, Sepsis etc.)
Leukocytosis of Eosinophils in the absence of asthma, allergies or parasitic infections should direct you toward which pathology ?
Malignancies
Active Pulmonary Tuberculosis, Brucellosis/Rickettsiosis, Malaria and Inflammatory Bowel Disease can all lead to Leukocytosis of which WBC lineage ?
Monocytes.
Sustained activation of the immune system by acute viral infections, brucellosis , active TB and Malignancy will lead to an expansion of what WBC lineage ?
Lymphocytes (T and B cells)
Focus mainly on Sustained Activation due to Viral Infections.
What is the main differential between Reactive Leukocytosis and Acute Leukemia ?
Both will have increased levels of Leukocytes, however Acute Leukemia will be distinguished by the presence of BLASTS in peripheral blood.
A form of non-neoplastic leukocytosis which mimics acute/chronic leukemia…..
Leukemoid Rxn
What are the three main causes of a leukemoid Rxn ?
- Chronic inflammation
- Chronic infection
- Medications (Steroids) –> Demargination and release into blood stream
Enlargement of lymph node(s) of any etiology…
Lymphadenopathy
What is lymphadenitis ?
Painful enlargement of lymph nodes
What is Acute lymphadenitis ?
occurs in nodes draining organs infected with bacteria.
What is Acute Non-Specific Lymphadentis ?
lymph nodes with reactive changes secondary to infections, toxic products or foreign matter from wounds (Not just bacteria as in Acute lymphadenitis).
Do lymphadenitis and lymphadenopathy lead to organized or disorganized nodal architecture ?
Organized. Well marginalized germinal centers.
Follicular Hyperplasia seen in Chronic Non-Specific Lymphadenitis leads to the activation of which kind of cells ?
B Lymphocytes.
Sinus Histiocytosis (a subset of Chronic Non-Specific Lymphadenitis) is characterized by distension of sinusoids in lymph nodes draining…..
Primary carcinomas.
What is Paracortical Lymphoid Hyperplasia (a subset of Chronic Non-Specific Lymphadenitis) ?
reactive changes in T-lymphocyte regions which transform into immunoblasts
Sometimes seen with vaccines and exposure to certain drugs (phenytoin)
Malignant neoplasms of LYMPH NODES composed of MALIGNANT LYMPHOID cells ( More mature B and T-cells) are characterized as ….
Lymphomas
May also occur in lymphoid tissue outside of lymph nodes like the spleen
Neoplasms of HEMATOPOIETIC immature cells that involves the MYELOID BONE MARROW are characterized as …
Leukemia (also, Myeloproliferative diseases)
Localized or disseminated malignant proliferation of plasma cells or B-Cell lymphoid cells leading to the production of monoclonal Ab’s are known as
Plasma Cell Dyscrasias
What is a histiocytoses ?
Neoplasms of histiocytes (monocytes)
What is the Cell Surface Marker associated with pluripotent hematopoietic stem cells ?
CD 34+
NK cells have which cell surface marker ?
CD 56+
What cells are over-produced and lack differentiation in Acute Myeloblastic Leukemia ?
Myeloblasts (will not differentiate correctly but will expand their own lineage )
What cells are often depleted in Acute Myeloblastic Leukemia ?
RBC and Platelets
Acute Lymphoblastic Leukemia occurs due to over-expansion of which cells ?
Lymphoblasts
What are the two main categories of Malignant Lymphomas ?
Hodgkins
Non- Hodgkins
Pathologic diagnosis of Lymphomas requires both
Standard Tissue Light Microscopy and
Immunophenotyping by either immunocytochemistry or Flow Cytometry (Looks for markers on the cells). Which type of biopsy is preferred, fine needle aspirate or excisional ?
Excisional (need to see tissue architecture)
Of the 5 categories based on morphology, genotype, clinical features, immunophenotyping for characterizing lymphomas, what are the four associated with Non-Hodgkins ?
- Pre-Cursor B-Cell Neoplasm (Immature B-Cell)
- Peripheral B-cell Neoplasms (mature B-cells)
- Precursor T-cell Neoplasms (immature T-cells)
- Peripheral T-cell and natural killer cell neoplasms (mature T-cells and NK cells)
The fifth category based on morphology, genotype, clinical features, immunophenotyping for characterizing lymphomas is Hodgkins Lymphoma. What is major diagnostic difference between Hodgkins and Non-Hodgkins Lymphoma’s ?
Reed Sternburg Cells (CD30+)
On what cells will you see CD45 ?
ALL WBC’s !
List the CD marker that are Primarily T-cell associated ?
CD1, 3, 4, 5, 8.
LOW CD MARKERS ARE T-Cell
List the CD marker that are Primary B-cell associated ?
CD 10 ,19, 20, 21, 23 and 79
What drug is used for targeting CD20 on B-Cells ?
Rituximab.
List the CD marker that are Primarily NK-cell associated ?
CD 16, 56
Plasma cell associated CD marker…
CD 138
B-cell Acute Lymphoblastic Lymphoma ( in nodes) or Leukemia (bone marrow) is a Low or High grade disease ?
HIGH (Must be treated immediately)
What does it mean for a disease to be Acute ?
It means that it is composed of PRECURSOR cells and will often show expansion of lympho/myeloBLASTS.
Look for these in biopsy .
In an Acute lymphoma/leukemia, what is a good marker to look for to determine is the lineage is Lymphoid or Myeloid ? (this will also confirm the disease is due to acute precursors rather than more mature chronic cells)
TdT+ (terminal deoxynucleotidyl transferase)
This will tell you the cell lineage is LYMPHOID and that it is immature.
What does a lymphoblast look like in microscopy
Large nucleus
very little cytoplasm
no granules seen (would indicate it’s a granulocyte
lighter nucleus due to rapidly dividing chromatin.
What is the most common CATEGORY (5) of lymphoma ?
PERIPHERAL B-Cell Neoplasm (85% of all lymphomas)
Non-Hodgkins type.
There are many diseases that fall into this category (will be talked about later)…
- Small lymphocytic lymphoma/chronic lymphocytic leukemia
- Mantle Cell Lymphoma
- Follicular Lymphoma
- Hairy Cell Leukemia
- Diffuse Large B-Cell Lymphoma
- Burkitt’s Lymphoma
Small Lymphoctyic Lymphoma (a Peripheral B-Cell neoplasm ) is called what when leukocytes get greater than 4K lymphocytes ?
Chronic Lymphocytic Leukemia
What kind of cells are should you think of when you thing Small/Chronic Lymphocytic Leukemia ?
“Smudge Cells” ***
T- Cell Acute Lymphoblastic Lymphoma ( or Leukemia when bone marrow involved/circulating lymphoblast) is classified in which of the 5 major categories of lymphomas ?
Precursor T-Cell Lymphoma (you know it is precursor because it is an ACUTE lymphoma)
Is T-cell ACUTE lymphoblastic lymphoma a high or low grade disease ?
HIGH (Just like B-Cell ACUTE Lymphoblastic Lymphoma)
List some of the Peripheral T-Cell Lymphocytic Lymphomas (leukemias)
T
What are the 4 types (out of 5) of HODGKINS lymphoma that are associated with CD30* ?
Nodular sclerosis
Mixed cellularity
Lymphocyte-rich
Lympocyte depletion
What is the only type of HODGKINS lymphoma that is not associated with CD30 ?
Lymphocyte predominance
Non-Hodgkins Lymphomas (4 Classes) are distance from Hodgkins in that they do not express CD30+. On clinical exam you may find what kind of lymphadenopathy ?
rubbery, painless lymphadenopathy
Non-Hodgkins Lymphomas also present with “B-Type Symptoms”. What are these ?
fevers, chills, night sweats
These are due to proliferation of the lymphocytes
Non-Hodgkins Lymphoma will affect which body areas (depending on disease of course)
Various Lymph Node groups (Typical Spots) Oropharyngeal Region (Waldeyer’s Ring) GI Tract Bone Marrow Skin
Involvement of which organ may lead to malignant lymphoid cells to appearing in peripheral blood ?
Bone Marrow
If you start to see large amount of B/T-cells in the blood, they will likely have lymphoma (despite this being the presentation for leukemia ?), look out for blasts
What are the two variables that must be accounted for when trying gain a pathologic diagnosis from a lymph node (excisional biopsy )
Cell Type (B-cell, T-cell)
Pattern of Growth : Follicular (Nodular) or Diffuse
Which typically has a better prognosis : Follicular (Nodular) or Diffuse ?
Follicular (Nodular)
Diffuse is much more difficult to treat.
Which of the 5 categories of Lymphoma does Follicular Lymphoma fall into ?
Peripheral B-Cell Neoplasms
What is the major chromosomal translocation associated with Follicular Lymphoma ?
**Chromosome 14:18 translocation !
What does the Chromosome 14:18 translocation in B-Cell with follicular lymphoma cause ?
The promoter for Ig Heavy chain is fused with the Bcl-2 gene leading to Bcl-2 overproduction
Increased Bcl-2 seen in follicular lymphoma will have what effect ?
Bcl-2 is an anti-apoptotic molecule thus, it will lead to enhanced survival of B-cells and increased expansion.
What kind of lymphadenopathy will you see in Follicular Lymphoma ?
Painless generalized LAD (Lymphadenopathy) found typically in only at Nodal Sites (Not GI, CNS, testes), may see in Spleen, though.
Shows a waxing and waining course
What is the treatment model for Follicular Lymphoma ?
Low dose chemo, only when the patient is SYMPTOMATIC (B symptoms, lymphadenopathy)
Are the germinal centers in Follicular Lymphoma organized or disorganized ?
Disorganized (in comparison to Reactive lymphadenitis and lymphadenopathy)
What is the most common FORM of Non-Hodgkin Lymphoma ?
Diffuse large B-cell lymphoma (A Peripheral B-Cell Neoplasm)
Is Diffuse large B-cell lymphoma a low or high grade ?
High Grade !
What is different about Diffuse large B-cell lymphoma from Follicular Lymphoma in respect to its site of dissemination ?
Can arise ANYWHERE in the body,
CAN INVADE THE CNS**
Heterogeneous tumor markers for Diffuse Large B Cell Lymphoma include
Bcl-6, Bcl-2 and c-myc
What category of lymphoma is Burkitts Lymphoma ?
Peripheral B-cell Neoplasm. (A tumor of mature B-Cells)
What two disease are associated with Burkitt Lymphoma ?
EBV
Malaria
HIV
Typically a co-infection of EBV with one of the other two (more likely malaria)
What is the path-mnemonic term for biopsy of someone with Burkitt Lymphoma and what causes it ?
Starry sky pattern
Macrophages ingesting apoptotic cells
Is Burkitt Lymphoma treatable ?
VERY MUCH SO ! Needs to be down quickly however.
What is the MOST COMMON translocation associated with B-cells
8:14
What occurs in the translocation of 8:14 in Burkitt Lymphoma ?
The Ig heavy chain promoters is fused to c-myc !
What is the result of over-expression of c-myc ?
c-myc signals for proliferation while simultaneously stopping the apoptotic actions of bcd-2
(yes, i know. Bcl-2 is anti-apototic and over-expressed in Follicular Lymphoma (14:18). It actually has a dual role, c-myc just turns off its apoptotic tendencies)
What Category of Lymphoma does Mantle-zone Lymphoma fall into ?
Peripheral B-Cell Neoplasm (NHL)
What is the translocation associated with Mantle-zone Lymphoma ?
11:14
What occurs due to the 11:14 translocation ?
Ig Heavy Chain promoter is fused to the gene for Cyclin D leading to overproduction
What does overproduction of Cyclin D lead to in Mantle-zone Lymphoma ?
Cyclin D promotes the G–> S phase transition in the cell cycles causing mitosis to occur more readily –> large numbers of B-Cells.
Describe the germinal centers seen in Mantle-zone Lymphoma
Atrophic germinal center with homogeneous population of small lymphoid cells
Describe the cells seen in Mantle-zone Lymphoma
irregular nuclear outlines, condensed chromatin, scant cytoplasm
What do cells that over-express Cyclin D look like on immunostain ?
Brown
How do you treat Mantle-zone Lymphoma ?
You Don’t until it is symptomatic.
What Category of Lymphoma does Hairy Cell Leukemia fall into (yah, semantics are stupid on this one) ?
Peripheral B-Cell Neoplasm (NHL)
Chronic B-Cell Lymphoproliferative Disorder consisting of lymphoid cells in peripheral blood showing “hairy-like” cytoplasmic projections
What do Hairy Cell Leukemia cells stain positive for ?
TARTRATE RESISTANT ACID PHOSPHATASE (TRAP) !
Hairy Cell Leukemia is often seen in men with what co-morbidities ?
massive splenomegaly and pancytopenia
What are these ‘hairy cells’ seen in the blood despite being classified as a lymphoma ?
See them floating in the blood because the spleen is filled (splenomegaly)
What are the cell surface markers seen on Hairy Cells ?
The typical B-cell CD marker but also surface IgG, CD11c, CD25, CD103*
What is the treatment for Hairy Cell Leukemia
Cladribine (2-CDA; 2-chlorodeoxyadenosine
Mycosis Fungoides/Sezary Syndrome are in what category of Lymphoma ?
Peripheral T-Cell Neoplasm
Mycosis Fungoides/Sezary Syndrome T- cells Express CCR4, CCR10, CLA. What does this allow T-Cells to do ?
Home to the skin (don’t really need to know CD markers)
What are the 3 phases of Mycosis Fungoides
Premycotic phase
Plaque phase
Tumor phase
What is the major differential between Mycosis Fungoides and Sezary Syndrome
In Sezary Syndrome, skin involvement is manifested as a generalized exfoliative erytrhoderma.
What is characteristic of Sezary Cells ?
cerebriform nuclei
Rarely progress to tumors
What are Pautrier’s micro abscesses ?
Seen in microscopy of Sezary Syndrome . They are really just the macrophages eating he cells.
In Hodgkins Lymphoma the cells produce CD30 ( except in Lymphocte Predominance HL). What is characteristic of the dissemination pattern in HL ?
Arise is a single node or chain of nodes and spreads in an anatomically contiguous fashion
Of the 5 forms of Hodgkins Lymphoma (Nodular Sclerosis ,Mixed Cellularity,Lymphocyte-rich,Lymphocyte Depletion ,Lymphocyte Predominance ) Which is most common ?
Nodular Sclerosis (70% of HL)
What age groups are most likely to get HL ?
People at age 30 and at age 60 (bimodal)
Reed Sternburg Cells have which cell surface markers ?
CD15+, CD30+, Pax5+, CD45-
What kind of nucleus do Reed Sternburg Cells have ?
Bi-nucleate (these cells are though to arise from B-cells)
Mummification: shrinkage and pyknosis of malignant clone
Stage I HL :
- Involvement of single lymph node region (I) or
- Involvement of single extralymphatic lymph node site (Ie)
Stage II HL
Involvement of two or more LN on same side of diaphragm (i.e. Above or below the diaphragm.)
Stage III HL
Involvement of LN on both sides of diaphragm
May include spleen (IIIs), or limited contiguous extralymphatic organ/tissue (IIIe, IIIes
Stage IV HL
- Multiple or disseminated foci
- Involvement of one or more extralymphatic organs or tissues (with or without lymphatic involvement). If it grew from lymph into an organ its still stage III)
A or B staging ?
A = No symptoms B= Symptoms (fever, Chills and Night Sweats)
What will you see in the lymph nodes in Nodular Sclerosing HL ?
Diffuse infiltrate of T-lymphocytes, eosinophils, macrophages and plasma cells with fibrous connective tissue bands (Very good prognosis)
Frequent Lacunar cells and occasional RS cells
Very “Ratty” looking lymph-nodes
NO EBV association
What virus is associated with Mixed Cellularity HL ? (2nd most common , don’t worry too much about this.)
EBV
Which is the least common and yet most dangerous form of HL ?
Lymphocyte Depletion
Few lymphocytes but many RS cells
RS cells have classic phenotype (CD15+, CD30+, CD45-)
What patient are more prone to Lymphocyte Depletion HL ?
HIV+
Elderly
(there is also an association with EBV)
Lymphocte Predominance HL shows very few Reed Sturnberg cells but many Lymphocytes. What type of RS cells are often seen in this disease ?
Lymphohistiocytic RS cell variants (“popcorn cell”) within background of dendritic cells and B-lymphocytes (CD20+, BCL6+, CD15-, CD30-)
Is extra nodal presentation common in HL ?
NO it is very rare (much more common in NHL)
Plasma Cell Dyscrasias lead to the Neoplastic proliferation of plasma cell which produce Ig and Ig Fragments. What product can this lead to in the Urine ?
Bence-Jones Protein
What is the most common plasma cell dyscrasia ?
Monoclonal Gammopathy of Undetermined Significance
What are the respective urine M-Protein level and Bone Marrow Plasma Cell Concentrations seen in Monoclonal Gammopathy of Undetermined Significance ?
M protein level <10%
Differentiates MGUS from Multiple Myeloma (MGUS has a 1% chance of progressing to MM)
The neoplasm associated with Multiple Myeloma occurs where ?
In the bone marrow (Plasma Cell)
What are the respective urine M-Protein level and Bone Marrow Plasma Cell Concentrations seen in Multiple Myeloma ?
M protein levels >3 g/dL (Usually IgG, but sometimes IgA is produced)
Bone marrow plasma cells >10%
What are the two form of Multiple Myeloma ?
Smoldering and Symptomatic
What defines symptomatic MM ?
CRAB
Calcium- levels are elevated
Renal-Due to light chains in glomeruli
Anemia- (Due to overcrowding of bone marrow with plasma cells and bone destruction)
Bone Involvement- Lytic bone lesions from plasmactyomas –> Pathologic Fractures
When do you treat MM ?
In the symptomatic stage (CRAB)
Not really curable but many treatments
What causes the “Rouleux Formation” in RBC’s in MM ?
IgG sticking to the RBC –> staking
What Ig is typically produced in Waldenstrom’s Macroglobulinemia ?
plasmacytoid B-lymphocytes producing only IgM** (MM is IgG typically)
Due to multimeric configuration, IgM in Waldenstrom’s Macroglobulinemia can lead to what syndrome ?
HYPERVISCOSITY SYNDROME –>Sluggish blood.
Visual changes and stroke are common
What do plasma cells secrete in Amyloidosis ?
Light Chain (either lambda or Kappa)
What other disease is Amyloidosis associated with ?
Multiple Myeloma
What is the stain used to see amyloid ?
CONGO RED
Also, shows apple green birefringence.
Where do you often see skin changes in patients with amyloidosis ?
Periorbital regions, tongue and extremities.
In leukemias, what is necessary to differentiate myeloid vs lymphoid lineage ?
Flow cytometry
Acute Leukemias occur due to neoplasm of hematopoeitic mature or immature cells ?
Immature
In the marrow , what will replace normal maturing cells in ALL or AML ?
BLASTS !
What type of cells are typically low in ALL or AML ?
Overall pancytopenia Low neutrophils: infection, Low platelets: bleeding Low RBCs: anemia These cell types are all depleted when these blasts are created
What are the characteristics of Acute Leukemias ?
Abrupt onset
Clinical Symptoms related to depression of normal bone marrow function (bleeding or infection)
Bone pain/tenderness
Leukemic blast infiltration of organs
CNS involvement (ALL»»»>AML)
What demographic is mainly affected by Acute Lymphoblastic Leukemia ?
Predominantly a disease of children and young adults (boys, european descent)
Peak incidence: 4 years of age
80% of all childhood acute leukemias
Good Prognosis in kids (90% remission)
Very bad prognosis in adults
What are the characteristic signs of ALL ?
Bone Pain and Tenderness (filled w/ blasts)
Generalized Lymphadenopathy, Splenomegaly and Hepatomegaly: (more common in ALL than AML)
Central Nervous System Manifestations: Headache, vomiting and nerve palsies
Which translocation shows a better prognosis for children with ALL ?
12:21
What are the three factors associated with worse prognosis in ALL ?
Age < 2 (possible association with chromosome 11 translocations
ALL in adolescence or adulthood
Presence of t(9;22) Philadelphia chromosome
What demographic is mostly affected by Acute Mylelogenous Leukemia (AML)?
adults of middle/older age
What percentage of bone marrow must be Blasts to confirm a diagnosis of AML ?
20% blasts in bone marrow*… less than that is Myelodysplastic Syndrome.
WHAT IS THE CURE RATE OF AML (SORRY FOR CAPS)
Only 30% cure rate with treatment
What is the most treatable form of AML ?
M3: Promyelocytic (if you were to pick one, it would be this. Most treatable.)
M0
Minimally Differentiated AML (2-3%)
M1
AML without differentiation (20%)
M2
AML with maturation (30-40%) Most common form of AML.)
Auer Rods often Present
What translocation is often seen in M3 (promyelocytic) AML ?
(15;17) translocation to generate RARA/PML protein
What complication do patients with M3 AML often get ?
DIC
What is the treatment for M3 AML ?
All-trans retinoic acid (ATRA) and Arsenic Trioxide
M4
Acute Myelomonocytic Leukemia (15-20%)
shows both myelocytic and monocytic differentiation
+ non-specific esterase (Stain)
M5
Acute Monocytic Leukemia (10%)
associated with high incidence of organomegaly, lymphadenopathy and leukemic tissue infiltration
M6
Acute Erythroleukemia (5%)
megaloblastoid changes and some erythroid precursors with large or multiple nuclei
M7
Acute Megakaryocytic Leukemia (1%)
blasts of megakaryocytic lineage predominate
Reactive with platelet-related antibodies (GPIIb/IIIa or vWF)
What occurs to hematopoiesis in Myelodysplastic Syndromes.
Causes ineffective hematopoiesis (Maturation ARREST)
bone marrow partially or completely replaced by clonal progeny of abnormal stem cells
Leads to pancytopenia
What demographic usually gets Myelodysplastic Syndrome ?
Disease of older individuals (68 years median age)
What disease can Myelodysplastic Syndrome transform into ?
AML
What is the only real cure for MDS ?
Bone marrow Transplant
Can be treated with transfusion support and hypomethylating agents :
Decitabine
Azacitidine
What kind of patho-mnemonic cell types are seen in MDS ?
Pseudo Pelger-Huet Cell (Bi-lobed neutrophil)
Once again, what cells are path-mneomonic for Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma ?
SMUDGE CELLS
What is the Richter Transformation associated with CLL ?
CLL –> Diffust Large B-Cell Lymphoma (much more aggressive)
Hairy Cell Leukemia like Hairy Cell Lymphoma stain positive for….
Tartrate-Resistant Acid Phosphatase (TRAP)
Who do you sees HCL in ? What co-morbidities ?
Older Men
Pancytopenia, Splenomegaly.
What occurs in myeloproliferative diseases that leads to ineffective hematopoiesis ?
stem cell disorders showing MATURATION defects (Not arrest)
What disease (like MDS) can myeloproliferative (MPD) diseases transform to ?
AML (HIGH RATE OF TRANSFORMATION)
Polycytehmia Vera (MPD) occurs due to an overproduction of which cells ?
erythrocytes
What is the cause of Polycythemia Vera?
Jak2 mutation (95%) Constantly on
What is a classic sign of Polycythemia Vera, aquagenic pruritus ?
Aquagenic pruritus – get itchy after taking a hot shower
What risk is increased by having Polycythemia Vera ?
CVA or VTE’s
Essential Thrombocythemia is due to an over-expression of which cell type ?
megakaryocytes in bone marrow —> Platelets in blood
Usually exceed 600,000 per mm3 with abnormally large platelets
What are symptoms associated with Essential Thrombocythemia ?
Thrombosis
Bleeding (weird backwards effect)
Chronic myeloid leukemia occurs because too many of these cells are created …
Granulocytes (left-shifted neutrophilic precursors are produced)
What enzyme is abnormally low in Chronic myeloid leukemia ?
Alkaline Phosphatase
What translocation is commonly seen in Chronic myeloid leukemia ?
9:22 (this is the Philadelphia Chromosome)
What class of drugs are given to treat Chronic myeloid leukemia ?
BCR/ABL tyrosine kinase inhibitors
Imatinib (Gleevec)
Dasatinib (Tasigna)
Nilotinib (Sprycel)
Pomatinib (Iclusig
Myelofibrosis with Myeloid Metaplasia occurs due to a neoplastic transformation of which kind of cell ?
multipotent myeloid stem cell
What does the multipotent myeloid stem cell transformation cause to occur in the bone marrow space ?
deposition of collagen *
In Myelofibrosis with Myeloid Metaplasia you will see Maturing bone marrow cells outside bone marrow space in spleen, liver, lymph nodes. This is known as…
extramedullary hematopoiesis
usually see splenomegaly
What demographic typically gets Myelofibrosis with Myeloid Metaplasia ?
Usually occurs > 60 years of age or older
What stain can you use to visualize the collagen disposition in Myelofibrosis with Myeloid Metaplasia ?
Reticulin
What kind of appearance with RBC’s have in patients with Myelofibrosis with Myeloid Metaplasia ?
Dacrocyte (Myelophthisic appearance) Getting Squeezed out
Histiocytosis is …..
massive expansion of macrophage line.
What can occur in malignant Histiocytosis ?
macrophages in the bone marrow that has become malignant. Fills in the compartmemtn – get anemia, thrombocytopenia, neutropenia
Red pulp of spleen
Area heavy with macrophages, lots of RBC sequestration and destruction.
White pulp of spleen
splenic lymphoid tissues
Acute Traumatic Rupture of Splenic Capsule requires …
surgical repair/removal
What occurs in the thymus ?
T cell development, maturation, clonal selection
DiGeorge Syndrome is marked by Thymic Hypoplasia or Aplasia with absence of parathyroid gland. Deletion on this chromosome leads to this syndrome
22
Which branchial structures show impaired development in DiGeorge syndrome ?
of 3rd/4th branchial pouches
CATCH 22 (Di George)
Cardiac anomalies Abnormal facies Thymic aplasia Cleft palate Hypoparathyroidsim with hypocalcemia
Benign or encapsulated Thymoma is associated with…
aplastic anemia and PNH (paroxysmal nocturnal hematuria)
Type I Malignant Thymoma
Invasive Thymoma
cytologically benign but locally invasive
Type II Malignant Thymoma
Thymic Carcinoma
cytologically malignant
