Chapter 13: Hodgkin Lymphoma and Myeloid Neoplasms Flashcards
1
Q
What are the role of Reed-Sternberg cells in Hodgkin Lymphoma?
A
Release factors that induce the accumulation of reactive lymphocytes, macrophages, and granulocytes
2
Q
Activation of which TF is a common event in class Hodgkin Lymphoma?
A
NF-kB
3
Q
The lacunar variant of Reed-Sternberg cells are associated with what subtype of HL?
A
Nodular sclerosis subtype
4
Q
What markers are expressed by Reed-Sternberg cells in the “classical” subtypes of HL vs. the lymphocyte predominant subtype?
A
- Classical = CD15+ and CD30+ and PAX5+
- Lymphocyte predominant = CD20+ and BCL6
5
Q
The nodular sclerosis type of HL has a propensity to involve which strucutres; most commonly in whom?
A
Lower cervical, supraclavicular, and mediastinal nodes of adolescents and young adults
6
Q
Which 3 subtypes of HL are most often associated with EBV?
A
- Mixed cellularity type
- Lymphocyte depletion type
- Lymphocyte-rich
7
Q
Which subtype of HL has the worst overall prognosis?
A
Lymphocyte depletion type
8
Q
The mixed cellularity type of HL arises most often in what age groups and has a predominance for what sex?
A
- Biphasic age distribution (peaks in young adults and then older adults)
- Male predominance
9
Q
Common presenting features of mixed cellularity type of HL?
A
Commonly has systemic sx’s, such as night sweats and weight loss
10
Q
How is the lymphocyte-rich type of HL distinguished from the lymphocyte predominant subtype?
A
By presence of mononuclear variants and diagnostic Reed-Sternberg cells w/ a “classical” immunophenotypic profile
11
Q
The lymphocyte depleted type of HL occurs most frequently in whom?
A
More common in older males, HIV-infected, and developing countries
12
Q
Describe the morphology of the Reed-Sternberg cell variants found in the lymphocyte predominant type of HL.
A
- Multilobed nucleus resembling popcorn kernel (“popcorn cell”)
- Known as lymphohistiocytic variant
13
Q
Majority of patients with lymphocyte predominant type of HL are what sex/age; how do they present?
A
Typically males, usually <35 y/o presenting w/ cervical or axillary LAD
14
Q
Which 2 subtypes of HL are more likely to be (stage III-IV) and present with sx’s such as fever, night sweats and weight loss?
A
- Mixed-cellularity type
- Lymphocyte depletion type
15
Q
What is the most important prognostic variable for HL with current treatment protocols?
A
STAGE
16
Q
How is stage II vs. stage III HL and NHL classified?
A
- Stage II: involvement of 2+ LN regions on same side of diaphragm
- Stage III: involvement of LN regions on both sides of diaphragm
17
Q
Diagnosis of Acute Myeloid Leukemias (AML) is based on what?
A
Presence of >20% myeloid blasts in the bone marrow
18
Q
What are the 2 most common chromosomal rearrangements seen in AML?
A
t(8;21) and inv(16)
19
Q
Acute promyelocytic leukemia (APL - M3) is associated with what translocation?
A
t(15;17)
20
Q
What is seen morphologically in Acute promyelocytic leukemia (APL); high incidence of what complication?
A
- Numerous Auer rods, often in budles within individual progranulocytes
- Primary granules very prominent
- High incidence of DIC
21
Q
AML with what genetic aberration is associated with a poor prognosis?
A
Translocations involving MLL on chromosome 11q23
22
Q
AML with t(11q23;v); diverse MLL fusion genes usually shows some degree of what differentiation?
A
Monocytic
23
Q
How does AML with t(8;21) differ from those with inv(16) rearrangements in terms of morphology?
A
- t(8;21): shows full range of myelocytic differentiation; Auer rods easily found = AML w/ myelocytic maturation (M2 subtype)
- inv(16): myelocytic and monocytic differentiation; abnormal eosinophilic precursors w/ abnormal basophilic granules = AML w/ myelomonocytic maturation (M4 subtype)
24
Q
Prognosis of AML w/ MDS-like features?
A
Poor
25
AML with monocytic maturation is characterized by what clinically?
High incidence of **organomegaly**, **LAD**, and **tissue\* infiltration**
26
Which type of AML is represented by the FAB class M1, M2, M3, and M4?
- **M1** = AML **_without_** maturation; ≥3% blasts MPO (+)
- **M2** = AML with **myelocytic** maturation - **t(8;21)**
- **M3** = Acute **Promyelocytic** leukemia - **t(15;17)** - **P** and **3**
- **M4** = Acute **myelo-monocytic** leukemia - **inv(16)** - has **4 letters**
27
How do myeloblasts differ from monoblasts in terms of staining?
- **Myeloblasts** = **MPO (+)** = have **Auer rods**
- **Monoblasts** = **nonspecific esterase (+)** = **lack Auer rods**
28
Which CD markers are positive on myeloid blasts?
**CD34(+)** and **CD33 (+)**
29
What are the most common presenting signs/sx's of AML?
- **Fatigue (anemia)** + **bleeding** **(thrombocytopenia****)**+**fever/infection****(neutropenia****)**
- **Spontaneous mucosal** and **cutaneous** bleeding very common
30
Fungal skin infections, leukemia cutis, orbital granulocytic sarcoma, and infiltration of the gingiva are common features of which type of AML?
Acute **monocytic** leukemia (**M5a/b**); any with **monocytic differentiation**
31
Which type of AML is associated with an increased bleeding tendency due to the release of procoagulants and fibrinolytic factors from leukemic cells?
**Acute promyelocytic leukemia** - **t(15;17)**
32
AML occasionally presents as a localized soft-tissue mass known variously as what?
**Myeloblastoma**, **granulocytic sarcoma**, or **chloroma**
33
Which gene/chromosome is one of the most common forms of aneuploidy in a wide range of myelodysplastic tumors?
***MYC*** on chromosome **8**
34
In myelodysplastic syndromes what are the **three common morphological** findings within the erythroid lineages?
- **Ring sideroblasts** = erythroblasts w/ iron-laden mitochondria visible
- **Megaloblastoid maturation**, resembling that seen in B12/folate deficiency
- **Nuclear budding abnormalities**, misshapen, often polypoid, outlines
35
Which special form of neutrophils is commonly observed with myelodysplastic syndromes?
**Pseudo-Pelger-Huet cells** = neutrophils w/ **only 2 nuclear lobes**
36
Primary MDS is most commonly seen in whom and presents how when symptomatic?
- Primarily **older adults** (mean age = **70**)
- Presents w/ **weakness** (**anemia**), **infections** (**neutropenia**), and **hemorrhages** (**thrombocytopenia**)
37
Which type of MDS has the highest frequency and most rapid transformation to AML + the most grim prognosis with a median survival of only 4-8 months?
**t-MDS** = secondary to previous **genotoxic drug** or **radiation therapy**
38
What are the 2 common molecular causes of myeloproliferative disorders?
- **Mutated**, constitutively activated **tyrosine kinases**
**or**
- **Acquired** aberrations in **signaling** pathways that lead to **GF-independence**
39
Chronic myelogenous leukemia is distinguished from the other myeloproliferative disorders by the presence of which mutation?
**t(9;22) --\>** ***BCR-ABL***
40
In CML, what is seen in the marrow, which cells predominate; which finding is characteristic?
- **Marrow** is markedly **hypercellular** due to **massively** ↑ maturing **granulocytic precursors** --\> ↑ **eosinophils** and **basophils**; will also have ↑ **megakaryocytes**
- **Characteristic** = scattered macrophages w/ abundant **wrinkled**, **green-blue cytoplasm** so-called **sea-blue histiocytes**
41
What is characteristic finding in the blood of pt with CML?
- **Leukocytosis**, often **\>100,000 cells/mm3**
- Predominantly **neutrophils, band forms, meta-myelocytes, eosinophils**, and **basophils**
- **Platelets** are often ↑↑↑
42
Characteristic finding in the spleen of pt with CML?
**Spleen** is typically **MASSIVE**
43
CML primarily occurs in which age group?
**Adults** (**5th-6th decade**) can also occur in **children** and **adolescents**
44
Typical presentation of CML?
- **Insidious** onset w/ **mild-moderate anemia**, **fatigue**, **weight loss, anorexia**
- Sometimes **dragging sensation** in **abdomen** from **massive spleen** is 1st sx
45
What is typical behavior of untreated CML; describe the phases that may be seen?
- Typical **slow progression** w/ **moderate anemia** for a **few years**
- 50% enter **accelerated phase**, which enters **blast crisis** after **6-12 months**; resembling **acute leukemia**
- Some may be **AML-like** and others **ALL-like**
46
How can leukocyte alkaline phosphatase (LAP) help distinguish CML from a leukemoid rxn?
**LAP** = **low** in **CML** and **high** in **reactive states**
47
Polycythemia Vera is strongly associated with activating point mutations of what; which AA substitution is most common?
**JAK2 kinase** (**Valine** --\> **Phenylalanine** at residue **617**)
48
Which cells will be increased in PCV and how can it be distinguished from other causes of hemoconcentration?
- ↑ **red cells**, granulocytes, and **abnormally large** **platelets**
- Transformed progenitor cells have ↓ requirements for **EPO** so the **EPO levels will be** ↓
49
What is characteristic of the **spent phase** seen late in course of PCV both in the marrow and organs?
- **Hypercellular marrow ---\> Extensive marrow fibrosis**
- Accompanied by ↑ extramedullary hematopoiesis in **spleen** and **liver**, leading to **prominent organomegaly**
50
When does PCV most often arise and how does it present?
- **Insidious** onset, usually **adults** of **late middle age**
- Sx's due to ↑ **red cell mass** and **hematocrit** = **plethoric** and **cyanotic**; HA, dizziness, HTN, GI sx's, and **minor hemorrhages** (epistaxis, gums)
- **Intense pruritus** and **peptic ulceration** may occur
- **Hyperuricemia** --\> symptomatic **gout**
51
Due to the abnormal blood flow in PCV many patients first come to medical attention due to what complications?
- **DVT, MI****,**or**stroke**
- Thromboses of **hepatic vein** can produce **Budd-Chiari** and in **portal**/**mesenteric vs.** can cause **bowel infarction**
52
What is typical hematocrit, WBC, and platelet count in PCV?
- **Hematocrit** = ≥60%
- **WBC** = 12,000 - 50,000 cell/mm3 (**basophilia**)
- **Platelets** = \>500,000+
53
What is prognosis of PCV without treatment; what is standard tx?
- **Without** tx, death from **bleeding** or **thrombosis** occurs within **months**
- **Phlebotomy** extends **median survival** to about **10 years**
54
How likely is progression from PCV to AML?
**1-2%** transform to AML
55
Essential thrombosis (ET) is associated with activating point mutations in what?
**JAK2 kinase**
56
What is the primary manifestation of Essential Thrombocytosis (ET) and how is it distinguished from PCV and primary myelofibrosis?
- Manifests clinically with ↑↑↑ **platelets**
- Distinguished based off **absence** of **polycythemia** and **marrow fibrosis**
57
What is the bone marrow cellularity like in Essential Thrombocytopenia (ET), which cell is markedly increased?
- Bone marrow only **mildly** hypercellular
- **Megaryocytes** are **markedly** ↑↑↑ in both **numbers** and **size** ---\> since they produce **platelets**
58
Typical finding on peripheral smear of Essential Thrombocytosis?
- **Abnormally large platelets** and counts can be **\>1,000,000/mL**
- Often **mild leukocytosis**
59
Who is most often affected by essential thrombocytosis; what are common presenting signs/sx's; which is a characteristic finding?
- **Primarily adults \>60 y/o**, but may occur in **young adults**
- **Thrombosis** and **hemorrhage** are **major manifestations**
- May be **mild organomegaly**
- **Erythromelagia**, a **throbbing** and **burning** of **hands** and **feet**
60
Complications of Essential Thrombocytosis?
Same as PCV = **DVT,** **MI, stroke**, and **portal/hepatic V. thrombosis**
61
What is necessary for diagnosis of Essential Thrombocytosis and what is prognosis?
- **Bone marrow biopsy** needed for diagnosis: substantially ↑ **megakaryocytes**
- **Indolent clinical course** w/ median survival **12-15 years**
62
What is the hallmark of Primary Myelofibrosis?
Development of **obliterative marrow fibrosis** --\> **cytopenia** + **extensive extramedullary hematopoiesis**
63
Which activating mutation is commonly seen with Primary Myelofibrosis?
**JAK2 kinase**
64
How to megakaryocytes play a major role in pathogenesis of primary myelofibrosis?
Synthesize **PDGF** and **TGF-β = fibroblast mitogens**
65
The chief pathologic feature of Primary Myelofibrosis is what?
**Extensive** deposition of **collagen** in the **marrow** by **NON**-neoplastic **fibroblasts**
66
Which complication of the spleen is shared between CML and primary myelofibrosis?
**Spleen** is **markedly enlarged** and **subscapular infarcts** = **common**
67
Which characteristic blood findings in primary myelofibrosis are due to the extensive marrow distortion?
- Premature release of nucleated **erythroid** and **early granulocyte** progenitors = **leukoerythroblastosis**
- **Teardrop-shaped red cells** (Da**CRY**ocytes)
68
Which feature of primary myelofibrosis may sometimes be the only finding?
**Marked splenomeagly** (just like CML)
69
Primary myelofibrosis is most often seen in whom and comes to attention how?
- Typically **\>60 y/o**
- Often comes to attention due to **progressive anemia** (fatigue) and **splenomegaly** (sensation of fullness in LUQ)
70
What is prognosis of Primary Myelofibrosis; death from what; risk of transformation to AML?
- Typically **3-5 year survival**
- Threats to life = **intercurrent infections**, **thrombotic episodes** and or **bleeding related** episodes
- **5-20%** transform to **AML;** with **extensive** myelofibrosis, AML sometimes arises at **extra-medullary sites**, including LNs and soft tissue
71
Typical blood smear finding in Primary Myelofibrosis?
**Normochromic, normocytic anemia** + **leukoerythroblastic** smear
