Pathoma 6 Flashcards
1
Q
Causes of neutropenia
A
drug toxicity or severe infection (gram-negative sepsis)
2
Q
Treatment of neutropenia
A
GM-CSF or C-CSF
3
Q
Causes of lymphopenia (name 4)
A
- Immunodeficiency (DiGeorge or HIV)
- High cortisol state
- Autoimmune destruction
- Whole body radiation
4
Q
Why does severe infection (gram-negative sepsis) cause neutropenia?
A
Increased movement of neutrophils into tissues results in decreased circulating neutrophils.
5
Q
Why does high cortisol state cause lymphopenia?
A
Induces apoptosis of lymphocytes
6
Q
Causes of neutrophilic leukocytosis (name 2)
A
- Bacterial infection or tissue necrosis
2. High cortisol state
7
Q
How would bacterial infection cause neutrophilic leukocytosis?
A
Induces release of marginated pool and BM neutrophils, including immature forms (left shift).
8
Q
What characterizes immature neutrophils?
A
decreased Fc receptors (CD16)
9
Q
Why does high cortisol state cause neutrophilic leukocytosis?
A
Impairs leukocyte adhesion, leading to release of marginated pool of neutrophils
10
Q
Causes of monocytosis
A
Chronic inflammatory state and malignancy
11
Q
Causes of eosinophilia
A
allergic reaction (type I HS), parasitic infxn, and Hodgkin lymphoma
12
Q
What drives eosinophilia?
A
IL5! (–> eosinophilic chemotactic factor)
13
Q
Cause of basophilia
A
CML
14
Q
Causes of lymphocytic leukocytosis
A
- Viral infection
2. Bordetella pertussis
15
Q
How does Bordetella pertussis cause lymphocytic leukocytosis?
A
Produces lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node
16
Q
EBV primarily infects:
A
- oropharynx
- liver
- b cells
17
Q
clinical symptoms of infectious mononucleosis
A
- Generalized LAD (T cell hyp. in LN paracortex)
- Splenomegaly (T cell hyperplasia in PALS)
- Leukocytosis with atypical lymphocytes (reactive CD8+ T cells)
18
Q
How does the monospot test work?
A
Screen by detecting IgM antibodies that cross react with horse or sheep RBCs (heterophile antibodies); usually turns positive within 1 week of infection; remember that neg could mean CMV
19
Q
Definitive diagnosis of infectious mononucleosis after a positive monospot
A
serologic testing for the EBV viral capsid antigen
20
Q
Complications of infectious mononucleosis
A
- Splenic rupture
- Rash with ampicillin
- Increased risk for B-cell lymphoma
21
Q
Definition of acute leukemia
A
> 20% blasts in BM –> crowd out normal hematopoiesis
22
Q
Describe blasts on blood smear
A
large, immature cells with punched out nucleoli
23
Q
+TdT and CD10+, CD19+, CD20+
A
B-ALL
24
Q
+TdT and positive for Cd2-8 (no CD10)
A
T-ALL
25
Neoplastic accumulation of lymph blasts (>20%) in the marrow is called:
ALL (acute lymphoblastic leukemia)
26
In ALL, the nucleus stains positive for:
TdT (in lymphoblasts, not myeloplasts)
27
In what populations does ALL most commonly present?
Under 5 and in pts with Down syndrome (>5)
28
How do you treat B-ALL?
chemotherapy with prophylaxis to scrotum and CSF
29
With what cytogenic abnormalities do you associated B-ALL?
t(12;21) - kids, excellent prognosis (12 flipped is 21);
| t(9;22) - adults, poor prognosis, Ph+
30
Thymic mass in a teenager (may present with difficulty swallowing), TdT+, CD2-8+
T-ALL
31
Auer rod
AML (acute myeloid leukemia), specifically APL (others may be MPO negative)
32
t(15;17)
APL (acute promyelocytic leukemia; subtype of ALL) - AT disruption blocks maturation and promyelocytes (blasts ) accumulate
33
Affinity for vitamin A derivative
APL
34
Abnormal promeylocytes in APL contain primary granules that increase the risk for?
DIC
35
Treatment of APL
All-trans-retinoic acid
36
How does ATRA work?
binds the altered receptor and causes the blasts to mature (and eventually die)
37
For what do myeloblasts stain positive?
MPO+ (sounds like only APL of all the ALL subtypes)
38
What do you call a proliferation of monoblasts (usually lack MPO) that characteristically infiltrate the gums?
Acute monocytic leukemia (subtype of ALL)
39
With what condition do you associated a proliferation of megakaryocytes?
Down syndrome; onset before 5
40
AML may arise from pre-existing dysplasia, called what? What patients are most at risk?
Myelodysplastic syndromes; prior exposure to alkylating agents or radiotherapy
41
Cytopenias + hypercellular bond marrow + abnormal maturation of cells + increased blasts (<20%)
Myelodysplastic syndromes
42
Neoplastic proliferation of mature circulating lymphocytes (high WBC count)
Chronic leukemia
43
What is the most common leukemia overall?
CLL
44
Neoplastic proliferation of naive B cells that co-express CD5 & CD20; smudge cells on smear
CLL
45
complications of CLL
1. hypogammaglobulinemia
2. autoimmune hemolytic anemia
3. transformation to diffuse large B cell lymphoma (Richter transformation);
46
How might you tell clinically whether CLL was progressing to large B-cell lymphoma?
Enlarging lymph node or spleen
47
tartrate-resistant acid phophatase (TRAP) positive
hairy cell leukemia
48
Hairy cell leukemia is a proliferation of?
mature B cells characterized by hairy cytoplasmic processes; TRAP+
49
Clinical features of hairy cell leukemia
Splenomegaly (hairy cells in red pulp) + dry tap (marrow fibrosis); no LAD
50
How do you treat hairy cell leukemia?
2-CDA (cladribine), an adenosine deaminase inhibitor
51
How does 2-CDA (cladribine) work?
Adenosine accumulates to toxic levels in neoplastic B cells
52
Neoplastic proliferation of mature CD4+ T cells associated with HTLV-1; most commonly seen in Japan and Caribbean
Acute T-cell leukemia/lymphoma (ATLL)
53
rash (skin infiltration);
generalized LAD with HSM;
lytic bone lesions w/ hypercalcemia
ATLL
54
neoplastic proliferation of mature CD4+ T cells that infiltrate the skin --> Pautrier microabscesses
mycosis fungoides
55
Cells with cerebriform nuclei on blood smear
Sezary cells (mycosis fungoides)
56
Types of acute leukemia
1. ALL
| 2. AML
57
Types of chronic leukemia
1. CLL
2. Hairy cell
3. ATLL
4. Mycosis fungoides
5. CML (also myeloproliferative disorder)
58
Types of myeloproliferative disorders
1. CML
2. PV
3. ET
4. myelofibrosis
59
Complications of all MPD
1. hyperuricemia and gout (high turnover)
| 2. progression to marrow fibrosis or transformation to acute leukemia
60
Neoplastic proliferation of mature myeloid cells, esp granulocytes and their precursors; basophilia
CML
61
Translocation in CML
t(9;22) --> BCR-ABL (non-receptor tyrosine kinase)
62
Treatment for CML
imatinib
63
neoplastic proliferation of mature myeloid cells, esp RBCs
Polycythemia vera
64
What diseases are associated with a JAK2 kinase mutation?
1. Polycythemia vera
2. Essential thrombocythemia
3. myelofibrosis
65
4 clinical symptoms/risks of PV
1. blurry vision + headache
2. venous thrombosis
3. flushed/ruddy face (plethora)
4. Itching, esp after bathing (inc. mast cells)
66
treatment for PV
Phlebotomy (second line: hydroxyurea)
67
Prognosis of PV
death within a year without treatment
68
EPO and SaO2 in PV
low epo; normal SaO2
69
EPO and SaO2 in reactive polycythemia due to high altitude or lung disease
high epo; low SaO2
70
EPO and SaO2 in reactive polycythemia due to ectopic EPO from RCC
high epo; normal SaO2
71
neoplastic proliferation of mature myeloid cells, esp platelets (also RBCs + granulocytes)
Essential thrombocythemia (increased risk of bleeding and/or thrombosis, but rarely other things)
72
neoplastic proliferation of mature myeloid cells, esp megakaryocytes
myelofibrosis
73
pathophys of myelofibrosis
megakaryocytes produce excess PDGF --> marrow fibrosis
74
tear-drop RBCs + nucleated RBCs + immature granulocytes on blood smear
"leukoerythroblastic smear" - myelofibrosis
75
clinical features of myelofibrosis
1. splenomegaly
2. leukoerythroblastic smear
3. inc. risk of infxn, thrombosis, bleeding
76
Region of lymph node associated with B cells
follicle
77
follicular hyperplasia is seen in:
RA + early HIV
78
region of lymph node associated w/ T cells
paracortex
79
paracortex hyperplasia is seen in:
viral infections (like mono)
80
hyperplasia of sinus histiocytes is seen in:
cancer (in LBN draining that area)
81
types of non-Hodgkin lymphomas
1. follicular
2. mantle cell
3. marginal celll
4. burkitt
5. diffuse large B cell
82
t(14;18)
Follicular lymphoma
83
What is the etiology of follicular lymphoma?
BCL2 on 18 translocates to the Ig heavy chain locus on 14 --> Bcl2 over expression --> no apoptosis --> cancer
84
Treatment of follicular lymphoma
Reserved for symptomatic pts; low-dose chemotherapy or rituximab (anti-CD20 antibody)
85
Presentation & progression of follicular lymphoma
presents in late adulthood with painless lymphadenopathy; can progress to diffuse large B-cell lymphoma
86
neoplastic proliferation of small B cells (CD20+) that expands the mantle zone
Mantle cell lymphoma
87
Translocation in mantle cell lymphoma
t(11,14)
88
Etiology of mantle cell lymphoma
Cyclin D1 gene on chromosome 11 translocates to Ig heavy chain on 14 --> over expression of D1 -- promotion of G1/S transition in cell cycle --> cancer
89
What cancer is associated with chronic inflammatory states, such as Hashimoto's thyroiditis, Sjogren syndrome, and H pylori gastritis?
Marginal zone
90
What forms the marginal zone?
post-germinal center B cells
91
What do you call marginal zone lymphoma in mucosal sites?
MALToma (NB: may regress with treatment of H pylori!)
92
High mitotic index plus starry sky on microscopy
Burkitt lymphoma
93
neoplastic proliferation of intermediate-sexed B cells associated with EBV
Burkitt lymphoma
94
extranodal mass involving jaw in child or young adult
African form of Burkitt lymphoma
95
extranodal mass involving the abdomen in child or young adult
Sporadic form of Burkitt lymphoma
96
most common translocation in Burkitt lymphoma
t(8;14)
97
oncogene in Burkitt lymphoma
c-myc
98
etiology of Burkitt lymphoma
Translocation of c-myc to the Ig heavy chain locus on 14 --> overexpression of c-myc --> promotes cell growth
99
Most common non-Hodgkin lymphoma
diffuse large B-cell lymphoma (neoplastic prolif. of large B cells that grow profusely in sheets)
100
presentation of diffuse large B cell lymphoma
in alate adulthood as an enlarging lymph node or an extra nodal mass; clinically aggressive (high grade); sporadic or transformation of a low-grade lymphoma (follicular lymphoma)
101
Enlarging cervical or mediastinal lymph node in a young female
Nodular sclerosis subtype (most common) of Hodgkin lymphoma
102
Reed-Sternberg cells
Hodgkin lymphoma
103
What are Reed-Sternberg cells?
Large B cells with multi lobed nuclei and prominent nucleoli; CD15+ & CD30+
104
fever, chills, weight loss, night sweats
B symptoms of Hodgkin lymphoma (sounds like TB)
105
RS cells secrete cytokines --> attraction of
reactive lymphocytes, plasma cells, macrophages, eos
106
1. Nodular sclerosis
2. Lymphocyte rich
3. Mixed cellularity
4. Lymphocyte-depleted
Subtypes of HL
107
Lymph node histology in nodular sclerosis subtype of HL
lymph node divided by bands of sclerosis; RS cells present in lake-like spaces (lacunar cells <-- does he mean spaces?)
108
Which subtype of Hodgkin Lymphoma has the best prognosis?
Lymphocyte-rich (and lymphocyte-depleted (elderly & HIV+) is the worst)
109
Why is the mixed cellularity subtype of Hodgkin lymphoma often associated with abundant eos?
Because RS cells produce IL-5
110
malignant production of plasma cells in the bone marrow; may have high IL6
multiple myeloma
111
Why do people with multiple myeloma (MM) have bone pain with hypercalcemia?
Neoplastic plasma cells activate the RANK receptor on osteoclasts --> lytic lesions on x ray, esp vertebrae and skull --> increased risk for fracture
112
Why do ppl w/ MM have elevated serum protein?
Neoplastic plasma cells produce Ig --> M spike on SPEP (usually IgG or IgA)
113
Why do ppl w/ MM have an increased risk of infection?
lack of antigenic diversity
114
What is a Rouleaux formation of RBCs on x-ray?
In multiple myeloma, increased serum protein decreases the charge btwn RBCs --> clump on top of each other like poker chips
115
In MM, free light chains circulate in serum and deposit on tissues. What is this phenomenon called?
Primary AL amyloidosis
116
Why are people with MM at increased risk for renal failure?
Proteinuria. Free light chain is excreted in urine as Bence Jones protein (deposition in tubules --> myeloma kidney / renal failure).
117
Six clinical features of multiple myleoma
1. Bone pain with hypercalcemia
2. Elevated serum protein (M spike on SPEP)
3. Inc risk of infxn
4 .Rouleaux formation of RBCs
5. Primary AL amyloidosis
6. Proteinuria --> Bence Jones protein --> renal failure
118
What proteins cause the M spike on SPEP in multiple myeloma
Monoclonal IgG or IgA
119
M spike on SPEP without other features of multiple myeloma
think MGUS (common in elderly; 1%/yr --> multiple myeloma)
120
B cell lymphoma with monoclonal IgM production
Waldenstrom macroglobulinemia
121
1. Generalized LAD with no lytic bone lesions
2. M spike on SPEP
3. Visual & neurologic deficits
4. Bleeding
Waldenstrom macroglobulinemia
122
What causes the M spike on SPEP in Waldenstrom macroglobulinemia?
IgM
123
How do you treat acute complications of Waldenstrom macroglobulinemia?
Plasmapheresis
124
What are Langerhans cells?
Specialized dendritic cells found predominantly in the skin that present antigen to naive T cells. They are derived from bone marrow monocytes
125
Birbeck (tennis racket) granules on EM; CD1a+ and S100+
Langerhans cell histiocytosis
126
Skin rash and cystic skeletal defects in an infant; multiple organs may be involved; rapidly fatal
Letterer-Siwe disease
127
Pathologic fracture in an adolescent with no skin findings; biopsy shows Langerhans cells with mixed inflammatory cells, including numerous eos)
Eosinophilic granuloma
128
Scalp rash, lytic skull defects, diabetes insipidus, and exophthalmos in a child
Hand-Schuller-Christian disease
