Neoplastic DO Flashcards
1
Q
what are four main types of WBC neoplasms?
A
1) . malignant lymphomas
2) . leukemias
3) . polycythemia vera
4) . plasma cell disorders
2
Q
what type of tumors are found with non-Hodgkin’s lymphoma? where do these tumors arise? distribution at diagnosis?
A
monoclonal solid tumors of B or T cells; arise in lymphoid tissues (usually nodes); usually widely distributed at diagnosis
3
Q
what is the usual way of acquiring mutations in non-Hodgkin’s?
A
chromosomal translocations
4
Q
the main types of non-Hodgkin’s lymphoma (5)
A
1) . diffuse large B cell lymphoma
2) . follicular lymphoma
3) . small lymphocytic lymphoma
4) . MALT lymphoma
5) . Burkitt’s lymphoma
5
Q
three treatment options for non-hodgkin’s
A
chemo, radiation and immunotherapy
6
Q
non Hodgkin’s: _________ type is more important than ______ in prognosis
A
histologic type > stage
7
Q
NHL more common in what gender? two specific risk factors for it?
A
men
H. pylori (MALT lymphoma of stomach) and immunocompromise (several NHL)
8
Q
what type of symptoms in non-hodgkins?
A
B symptoms: fatigue, malaise, night sweats, fever, weight loss
9
Q
where do the majority of non-Hodgkin’s originate? how do most present?
A
in the nodes and present as non tender lymphadenopathy
10
Q
where do NHL’s metastasize?
A
other lymphoid tissues and bone marrow (follow cell of origin, B or T)
11
Q
B cell NHL goes to where in lymph node?
A
goes to germinal centers and mantles, outer white pulp
12
Q
T cell NHL goes to where in lymph node?
A
superior mediastinum, paracortical zones, inner white pulp
13
Q
follicular lymphomas form follicles where? what’s their origin? what’s their prognosis?
A
in nodes; B cell; better prognosis
14
Q
what are the two translocations for follicular lymphomas?
A
11:14 or 14:18
15
Q
follicular lymphoma: ___ heavy chain becomes contiguous with oncogene product
A
Ig
16
Q
most NHL look ______ and lack __________ __________
A
bland and lack normal variability
17
Q
most NHL and HL produce __________- _____ dysfunction with propensity towards infection
A
generalized-cell
18
Q
most common NHL?
A
diffuse large B cell
19
Q
Diffuse Large B cell: patient type? some related to what two infections? often _______ at presentation
A
older adults
related to EBV or HIV infection
often multifocal (nodal and extranodal)
20
Q
progression and treatment of diffuse Large B cell
A
rapidly fatal if untreated
R-CHOP protocol (rituximab and chemo)
21
Q
what does diffuse large B cell histology look like?
A
no follicles being formed, very bland and uniform
22
Q
follicular NHL: / of adult NHL in US. patient type? where is it found? symptomatic?
A
1/3 of US adults
older adults
usually only nodal involvement and asymptomatic
23
Q
prognosis of follicular NHL? treatment?
A
slow growing, prolonged survival; if healthy then offered chemo, if going to die from something else first then just clinically follow
24
Q
50% of follicular NHL may transform into which type of NHL?
A
diffuse large B cell
25
small lymphocytic NHL: ___-_________ B cell form. lacks formation of what? patient type? where is it found at diagnosis?
well-differentiated; lacks follicle formation; older adults, often systemic involvement at diagnosis
26
follicular NHL histology looks like?
large purple circles (space between)
27
progression of small lymphocytic?
slow, seldom fatal
28
small lymphocytic: "______ ____ of chronic lymphocytic leukemia"
solid phase
29
histology of small lymphocytic
small bluish purple dots very close together
30
Burkitt's Lymphoma is a ___ cell lymphoma. endemic where? common arises from what body part?
B cell lymphoma (B cell proliferation); endemic in Africa; commonly arises in jaw (from cervical lymph nodes) and involves abdomen
31
which type of NHL is the fastest growing solid tumor in humans?
Burkitt's lymphoma
32
burkitts: patient type? endemic cases strongly linked to what infection?
children and young adults; EBV infection
33
burkitts treatment?
curable with chemo
34
what is the translocation for burkitts?
8: 14 (myc oncogene moved next to Ig heavy chain gene)
| * *cell multiplies explosively when told to make antibodies
35
histology for burkitts
"starry sky"
lipid droplets inside macrophages
(macrophages engulf lipid from dead tumor cells)
36
hodgkins: curable? patient type? usually presents as what two types of mass?
common, usually curable; affects young adults (15-140) and less commonly older adults (>55); neck or mediastinal mass
37
Hodgkin's: origin of malignant cell? name of malignant cell?
unknown, likely B cell
| Reed- Sternberg (R-S) cell
38
what is required for diagnosis of HL?
R-S cell
39
HL: tumor masses comprised largely of what?
inflammatory reaction to CA
40
R-S cells: account for what minority of tumor cells? what do nuclei look like? what do Nucleoli look like? surrounded by what color cytoplasm?
<1%
bi-lobed (mirror image) nuclei
owl's eye nucleoli
pink/lavender cytoplasm
41
R-S cells: CD15 is _________ (except one type called nodular lymphocyte predominant)
positive
42
R-S cells are typically surrounded by what?
reactive lymphocytes
43
HL: ________ is more important in diagnosis
staging
44
HL: __________ lymphadenopathy. mass usually limited to _____ _______
painless; above diaphragm
45
HL: "___-____" fevers...what type of symptoms?
Pel-Ebstein
| B symptoms: intermittent spiking fevers, night sweats, weight loss
46
how is the prognosis for people with HL B symptoms?
worse prognosis than asymptomatic people
47
5 different types of HL
1) . nodular/follicular lymphocyte predominant
2) . lymphocyte predominant (classical)
3) . mixed cellularity
4) . lymphocyte depleted
5) . nodular sclerosis
48
nodular lymphocyte predominant: negative for what? noted for late _________
CD15 negative
| late recurrence is common (these patients are followed more closely)
49
lymphocyte predominant: mostly ____, __________ lymphocytes. RS cells may be very ________
small, monotonous
| rare
50
Mixed cellularity: many ____ cells and variants
RS
51
lymphocyte depleted: mostly ________ cells, often _________ stage at presentation
cancer cells; advanced stage
52
which type of HL is the most common?
nodular sclerosis
53
nodular sclerosis: presence of _______ _______ bands
dense collagen
54
what is the main reason for typing HL?
to rule in/out nodular lymphocyte predominant type
55
Stage I of HL
one node group or organ
56
Stage II of HL
one side of the diaphragm involving 2 or more lymph node groups
57
Stage III of HL
two or more lymph node groups on both sides of the diaphragm
58
Stage IV of HL
extra nodal involvement- marrow or two extra lymphatic organs (skin, liver, lung)
59
Stage IV can be further classified into what two types?
A- no systemic symptoms
| B- means fever, weight loss (>10%), or night sweats
60
staging of HL involves what 3 tests?
node biopsy, CT chest/abd, PET
61
treatment of stage 1 and 2A
radiation
62
HL: get biopsy of _________ _____ _______ in suspected advanced disease
bilateral bone marrow
63
HL Stages IIB and higher treatment
combination chemo (50% cure rate at stage IV)
64
what is a leukemia?
replacement of bone marrow by cancerous blood cells (usually originates in packed marrow), which then spills over into bloodstream
65
leukemias can be what two types of cells?
lymphocytes OR myeloids (lymphoma is always lymphocytes)
66
leukemias can infiltrate which tissues?
liver, spleen, nodes, brain
67
what s the most common CA of children?
leukemia
68
is there a staging system for leukemia?
no due to infiltrative nature of WBC
69
acute leukemia: cells that fail to ______, differentiation is ______
mature (blast stage); poorly-differentiated
70
is acute or chronic leukemia more dangerous?
acute is more aggressive and deadly (death within weeks-months)
71
acute leukemia presents with what two things?
acute cytopenia (marrow replaced by cancer cells) and bone pain/aches from marrow expansion
72
acute leukemias: _________ bleeding present
spontaneous
73
chronic leukemia: cells that _______, differentiation is _____
mature; well-differentiation
74
chronic leukemia patients present with one of two things on lab tests?
present with cytopenia OR leukocytosis
75
chronic leukemia: what can happen to organs? (2)
organomegaly or lymphadenopathy
76
how is chronic leukemia usually found?
secondarily by testing of a mass or cytopenia on labs
77
lymphoid leukemias are precursors of? infiltrate what two things?
precursors of lymphocytes; spleen and nodes
78
myeloid leukemias are usually precursors of ___________. Interfere with maturation of?
granulocytes (can be erythrocyte or platelet precursors tho)
maturation of all blood cells
79
4 leukemias
1) . acute lymphoblastic leukemia (ALL)
2) . acute myeloid leukemia (AML)
3) . Chronic lymphocytic leukemia (CLL)
4) . chronic myeloid leukemia (CML)
* **ALL can be seen in adults but AML, CLL, CML more adult
80
what is the classic childhood leukemia?
ALL
81
leukemias can be caused by what three chromosomal probs?
translocations, inversions, and deletions (unknown how these chromosomes changes occur)
82
leukemia disrupts genes that do what?
regulate blood cell development
83
what is the Philadelphia chromosome?
characteristic of CML (some acute leukemias) where part of chromosome 9 is switched (translocated) with a part of chromosome 22 = new chromosome 22 has new BCR-ABL gene
84
what does the new BCR-ABL gene code for?
a tyrosine kinase = potent oncogene
85
ALL: peak incidence age? prognosis for adult ALL? risk factors for ALL?
4 y/o
worse prognosis for adult ALL
few risk factors known but radiation exposure and Down's
86
signs and symptoms of ALL (6)
fatigue/SOB, fever, night sweats, bruising/bleeding (bleeding gums), bone pain, increased infectious risk
87
ALL is what type of mutation?
spontaneous
88
ALL: ______ involvement more common; what two organs can be enlarged? two other things seen in ALL
CNS; spleen and liver; petechiae and lymphadenopathy
89
ALL: CBC results
>30% lymphoblasts (anemia, thrombocytopenia)
90
ALL: bone marrow biopsy results
packed marrow, >20% lymphoblasts
91
besides CBC and biopsy, what two other tests might you do for ALL?
LP (to assess CNS involvement) or CT chest/abd
92
what are the three phases of chemo for ALL?
1) . induction therapy- kills tumor cells (initial phase)
2) . consolidation therapy- knock off surviving cells (maintains remission)
3) . maintenance therapy- prolongs symptom free survival
93
ALL: cancerous and normal marrow cells die by the _______ and what pours into the blood?
pound; K, uric acid, get metabolic acidosis
94
ALL: if chemo fails what is next tx?
bone marrow transplant (kill off marrow again before transplant)
95
___% of children with ALL get apparent cure
90%
96
AML: leukemia of __________. potential risk factors? (6)
adulthood; downs, radiation exposure, benzene, previous CA chemo, CML, smoking
97
signs/symptoms of AML
SAME AS ALL: fatigue/SOB, night sweats, bruising/bleeding, bone pain, increased infectious risk (same lymph swelling, organ enlargement, etc as ALL)
98
one staging classification of AML M0-M7
```
M0- minimal differentiated
M1- AML with granulocyte maturation
M2/M3- slightly more mature, heading down granulocyte pathway (MOST COMMON ONES)
M4/M5- going down monocyte pathway
M6- trying to become erythrocytes
M7- trying to become platelets
```
99
which stage of AML are auer rods present?
a lot in M3, little in M2 (red stained rods)
100
what do auer rods mean?
tells you that cells are immature granulocytes (no lobed nucleus yet)
101
AML: biopsy results
packed marrow, myeloid line precursors with varying maturation
102
AML: CBC results
>30% myeloblasts, anemia, thrmbocytopenia
103
untreated AML is fatal within ______. treatment?
weeks
| tx: chemo (3 stages), M3 stage responds best; bone marrow transplant less common in adults
104
what spills into blood when a person has AML?
SAME AS ALL type
| hyperkalemia, hyperuricemia, and metabolic acidosis
105
CLL: usually cancer of ?
immature, nonfunctional B cells
106
what is CLL's "liquid phase of small lymphocytic lymphoma?"
when the cancer cells spill into the blood stream and invades other tissues to form small masses
107
what is the only known risk factor for CLL?
ataxia-telangiectasia
108
what is the most common cause of adult leukemia?
CLL (peak incidence >60yr)
109
what is the most common mutation for CLL?
deletion of chromosome 14 long arm (good prognosis)
110
CLL: CBC results
lymphocytes (>5000/ul, often much higher)
111
CLL: bone marrow biopsy results
infiltration with mature lymphocytes
112
CLL histology results
"smudge cells"
| CA cells deficient in cytoskeletal vimentin, fragile and crush on smear (higher smudges have better prognosis)
113
CLL: cancer cells can infiltrate ______ ______. (can get what three things from this?)
lymphoid tissues: lymphadenopathy, splenomegaly, and small lymphocytic lymphoma
114
CLL: if infiltrates the marrow, what two things can it cause?
anemia and thrombocytopenia
115
CLL: are cancer cells functional?
NO, defects in complement fixation and antibody production
116
what is the problem with bacteria/infection in people with CLL?
When there's a defect in antibody production, you get a decrease in optimization of the immune system. If the body can't optimize (place antigen and complement protein on bacteria) appropriately, it cant identify bacteria and macrophage wont destroy it. Encapsulated bacteria flourish
117
what three bacteria can flourish with CLL?
S pneumo, S aureus, H flu
118
small percentage of CLL turn into?
diffuse large-cell lymphoma (rapidly fatal Richter's syndrome)
119
CLL: symptomatic? survival risk?
often asymptomatic; untreated survival measured in years
120
high risk/troublesome CLL treated with?
ibrutinib (tyrosine kinase inhibitor)- stops abnormal B cells from dividing
121
typical presentation for CLL?
adult with unexplained lymphocytosis with leukocytosis
122
CML results in overgrowth of? which type of precursors dominate?
normally maturing and functional myeloid cells; granulocyte precursors dominate
123
CML: patient type? two known risk factors for it? cancer cells contain what special chromosome?
middle-age adults
radiation and benzene
Philadelphia chromosome
124
survival for CML?
people can live months to years with this
125
CML: CBC results
```
ridiculously high WBC (>100K)
high basophil count
marked left shift (immature leukocyte)
low leukocyte alkaline phosphatase
anemia and thrombocytopenia
```
126
why do you get anemia and thrombocytopenia in CML?
CA cells crowd out the bone cells
127
what test is not normally required for CML?
bone marrow biopsy
128
how do granulocytes show up on histology for CML?
they are black because they are negative for alkaline phosphatase
129
what is the chronic phase of CML?
non specific symptoms, where patient has anemia and thrombocytopenia (variable length)
130
what is thrombocytopenia?
low platelet count
131
what is the accelerated phase of CML?
```
*if the pt lives long enough*
lasts 6-12 months
massive splenomegaly
basophilia
typical leukemia symptoms (fever, night sweats, weight loss, bone pain)
```
132
what is a blast crisis? how long does it last? what forms in the blood? what do cancer cells infiltrate? tx?
- terminal event of someone with CML where cancer turns from mature chronic to acute immature leukemia
- lasts 3 months or less
- increased immature WBC forms in blood (>30% blasts)
- infiltrate CNS and lymphoid organs
- responds poorly to tx
133
what is leukostasis? what can it cause? what leukemia is it found in?
- plugging of small vessels due to massive numbers of WBC (BLOOD SLUDGING)
- can cause brain ischemia and infarcts of other organs
- found in CML blast crisis
134
CML treatment: what controls symptoms? what suppresses cancer cells? curative?
symptoms: busulphan and hydroxyurea
suppresses cancer cells: alpha-interferon +/- cytarabine
newer drug: Imatinib & dasatinib
allogenic bone marrow transplant may be curative
135
what is polycythemia? what two things is it due to?
abnormally high hemoglobin
- relative rise due to loss of plasma volume (dehydration)
- absolute rise due to increased red cell mass
136
absolute rise in hemoglobin can be what two types?
primary: problem with red blood cells (red cell mass)
| secondary- problem elsewhere
137
what are five secondary causes of absolute rise in hemoglobin?
1) . renal artery insufficiency/stenosis
2) . emphysema/sleep apnea
3) . anabolic steroid use
4) . post-kidney transplant
5) . altitude (>10,000 ft)- hypoxia induces it
138
what is polycythemia vera (PV)?
proliferation of myeloid stem cells
139
PV: sensitive to what cell type? what do most cells mature into? are these cells functional?
erythropoietin-sensitive; mostly mature into red cells (high WBC and platelets as well); all are fully functional
140
PV: affects what patient type? what is the problem with PV?
older middle age individuals
| problems mainly due to increased blood viscosity (blood sludges up)
141
what are five results of increased blood viscosity due to PV?
organ congestion (plethoric face), venous thrombosis (DVTs common), venous rupture (thinning of walls) and hemorrhage, decreased cardiac output, platelet dysfunction later
142
what type of mutation occurs in PV?
JAK2 (janus, tyrosine, kinase)
143
what does JAK2 mutation do?
its a cytokine receptor (that stays turned on) that stimulates RBC, platelet, and neutrophil development
144
besides cytokine activation, what two things also result from a JAK2 mutation?
essential thrombocytosis and primary myelofibrosis
145
PV: normal stem cells eventually replaced by what? survival rates? death occurs due to?
normal cells replaced by mutated cells; generally normal survival rates; death due to transformation into AML
146
how do you diagnose someone with PV?
A1 + A2 + A3
| OR A1 + A2 + any B
147
A1-B4 values for PV
```
A1-Hct > 52% male, 46% female
A2-normal pO2
A3-splenomegaly
B1-platelet > 400K
B2-WBC > 12K
B3-leukocyte alk phos > 100
B4-elevated vit B12
```
148
what is the minor mystery of PV?
itchiness after hot shower
149
two treatments for PV
therapeutic phlebotomy to control RBC mass or JAK2 inhibitors (ruxolitinib)
150
what does treatment with chemo do to PV?
increased transformation to AML
151
what are five types of plasma cell dyscrasias?
1) . multiple myeloma
2) . MGUS
3) . Waldenstrom's macroglobulinemia
4) . amyloidosis B
5) . lymphoplasmacytic lymphoma
152
what happens to bone marrow in multiple myeloma (aka plasma cell myeloma)? present in what % of people
there are multiple punched out lytic lesions in the marrow and cortex BUT only present in 50% of affected patients
153
plasma cell myeloma patient type? what type of CA?
older black men (over 70); differentiated B cell cancer
154
PCM: cells secrete what? what can detect them?
a complete immunoglobulin (M protein) and/or at least a light chain (kappa or lambda, never both)
**basically activated B cells are creating antibodies
detectable on serum or urine protein electrophoresis
155
PCM: always involves what?
bone (only 50% of cases will you see lytic lesions)
156
PCM: disruption of bone and marrow leads to ________
anemia (neutropenia and thrombocytopenia less common)
157
bone lysis in PCM causes?
hypercalcemia
158
PCM: light chain secretion plugs what and therefore leads to?
renal tubules, leading to renal insufficiency ("myeloma kidney")
159
most PCM tumors secrete what M protein type? what % only secrete light chains?
IgG- 55%
| light chain only- 18% (bence jones protein)
160
most myelomas produce what two things?
both complete and BJ proteins
161
what is a common finding on serum electrophoresis for PCM? urine electrophoresis?
serum: complete immunoglobulin seen "M spike"
urine: Bence-jones proteins, since they are filtered at glomerulus
162
what are two main differences seen on normal serum protein electrophoresis vs PCM electrophoresis?
smaller albumin level and way elevated antibody level ("Y") on PCM
163
what is the usual method of diagnosis for PCM?
serum M protein and/or urine bence-jones protein (serum level >3g/dl)
164
what is seen on bone marrow biopsy for PCM?
>10% plasma cells (normal is about 3%)
| **don't really need this test tho
165
what are signs of end organ damage in PCM?
1) . lytic bone lesions/osteoporosis
2) . anemia
3) . hypercalcemia: STONES, BONES, GROANS
4) . myeloma kidney- decreased GFR*
166
what are some paraneoplastic problems associated with PCM? (7)
1) . Osteoporosis
2) . Pathologic fractures
3) . Hypercalcemia
4) . Infections (suppression of normal plasma cells)
5) . Anemia & neutropenia (crowding out of normal cells)
6) . Kidney failure (BJ precipitates in renal tubules)
7) . Plasma cell leukemia (terminal stage)
167
treatment for PCM
high dose chemo to kill existing marrow
maybe allogenic bone marrow transplant
high mortality*
168
asymptomatic "smoldering" PCM patients man only require what to manage disease?
prophylactic bisphosphonates
169
what is MGUS?
benign monoclonal proliferation of plasma cells, which then produce a lot of antibodies
170
__% of MGUS go on to develop plasma cell myeloma
25%
171
MGUS: tumor cells produce what?
single complete immunoglobulin (usually IgG)
172
MGUS:
<10%, <3g
| NO end organ damage
173
tx for MGUS?
precursor to PCM so follow these patients for the rest of their lives
174
difference between PCM and MGUS?
don't get hypercalcemia or spitting out of light chains (no renal insufficiency) in MGUS
175
MGUS vs PCM electrophoresis
PCM: smaller albumin spike but higher antibody (Y) spike
