WBC 3 Flashcards
1
Q
Plasma cell neoplasms are B cell proliferations that virtually always secrete what?
A
monoclonal Ig or Ig fragment
2
Q
what are the plasma cell neoplasms/dyscrasias and related disorders discussed?
ALL CAPS the common ones
A
- MULTIPLE MYELOMA
- Waldenstrom Macroglobulinemia
- heave chain disease
- Primary or Immunocyte-associated amyloidosis
- MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)
3
Q
Explain clusters and infiltrates of plasma cells?
A
If you see clusters of plasma cells then you sorry about discrasias but if you see infiltrates of them on biopsy it doesn’t always mean dyscrasia because they are a feature of chronic inflammation
4
Q
what is the most common and deadly of the plasma cell dyscrasias
A
Mutliple myeloma
5
Q
describe myeloma kidney
A
Bence jones proteins are light chains that deposit in kidney and are toxic to proximal tubular epithelial cells
6
Q
describe the lytic bone lesions of Multiple myeloma
A
- usually skull, vertebral bodies, ribs
- can be almsot anywhere
- tend to be in upper portion of body
- Not generally in long bones
7
Q
Describe the rouleaux formations of multiple myeloma
A
- RBCs seem to stack on one another
- caused by increased viscosity of blood
- due to elaboration of acute phase reactants like fibrinogen or fibrin
- decreases surface tension
- NOT pathopneumonic . . also seen in autoimmune disease like RA
8
Q
Differential Dx for hypercalcemia
A
- MM
- Sarcoid
- Vitamin D intoxication
- milk alkali syndrome
- hyperparathyroidism
9
Q
What are the bizarre multinucleated plasma cells in MM
A
- Flame cells
- Mott cells with multiple grapelike cytoplasmic droplets with inclusions
10
Q
What are the inclusions in a Mott cell of MM
A
- Russell bodies if cytoplasmic
- Dutcher bodies if nuclear
11
Q
2 nuclei in plasma cell . . cytoplasmic inclusions which are cluster if immunoglobulin
A
think multiple myeloma
12
Q
What is the most common manifestation of MM
A
IgG with kappa light chains . . monoclonal
13
Q
diagnosis of MM
A
-More than 3 gm/dL of serum Ig and/or more than 6 mg/dL of (urinary) Bence-Jones protein
14
Q
What is the most common monoclonal Ig (“M protein) in MM?
A
- IgG (55%)
- then IgA (25%)
15
Q
Excessive production and aggregation of M protein in MM of what types leads to symptoms related to hyperviscosity
A
IgA and/or IgG3 subtype
16
Q
What % of myelomas are nonsecretory?
What do they still have?
A
- 1%
- lytic bone lesions
17
Q
an infrequent variant of MM that presents as a single mass in bone or soft tissue
-what are the 2 types
A
solitary myeloma (plasmacytoma)
- osseous/intraosseous
- another that is soft tissue and not bone
18
Q
an uncommon variant of MM defined by a lack of symptoms and a High plasma M component (> 3 gm/dL)
-No bony lesions and no hypercalcemia
A
-Smoldering myeloma
19
Q
Epidemiology of MM
A
- higher in men and Africans
- older adults . . peak of 65-70
20
Q
important clinical features of MM
A
- Bone resorption –> pathological fractures and chronic pain
- Hypercalcemia –> confusion, weakness, lethargy, constipation, and polyuria and contributes to renal dysfunction
- Decreased normal Igs –> recurrent bacterial infections
- Cellular immunity is NORMAL
21
Q
explain Solitary myelomas (Plasmacytomas) and the progression to MM
A
- Osseous inevitably progress to MM but can take 10-20 years
- Extraosseous (extramedullary), particularly of upper respiratory tract are frequently cured by local resection and don’t tend to progress to MM
22
Q
entity that is a middle ground between multiple myeloma and monoclonal gammopathy of uncertain significance
A
Smoldering myeloma
23
Q
What is the most common plasma cell dyscrasia. NOT neoplasm`
A
MGUS
24
Q
Serum M protein level for MGUS
A
LESS than 3 gm/dL
25
What % of MGUS pts develop a symptomatic plasma cell neoplasm?
1%
26
How do you predict if smoldering myeloma or MGUS will progress to MM
you can't . .it's unpredictable. you need periodic assessment of serum M component levels and Bence Jones proteinuria
27
what translocation is good outcome for MM?
| more aggressive?
- Cyclin D1
| - Deletions of 13q, 17p, and t(4;14)
28
age for lymphoplasmacytic lymphoma
a B cell neoplasm of older adults .. usually 6th or 7th decade
29
Clinical features of Lymphoplasmacytic Lymphoma
- plasma cell component secretes monoclonal IgM, often in ammounts sufficient to cause a hyperviscosity syndrome known as Waldenstrom macroglobulinemia
- Complications from free light chains relatively rare
- Bony lytic lesions DO NOT occur
- COLD AGGLUTININS
30
hyperviscosity syndrome of lymphoplasmacytic lymphoma
- visual impairments
- Neurological problems
- Bleeding
- Cryoglobulinemia . . Taynaud phenomenon and bold uticaria
31
Treatment of lymphoplasmacytic lymphoma
incurable
32
increased number of what cells in lymphoplasmacytic lymphoma . . besides the B cells
Mast cells . . tissue macrophage
33
Epidemiology of Mantle Cell Lymphoma
- 5th or 6th decades
| - male predominance
34
The mutation in mantle cell lymphoma leads to overexpression of what?
cyclin D1 . . promotes G1 to S phase progression
35
Most common presentation for Mantle cell lymphoma
Painless lymphadenopathy
| -SPleen and gut symptoms also common
36
Prognosis and survival in Mantle cell lymphoma
Poor . . median survival 3 to 4 years
37
What variant of mantle cell lymphoma is associated with even shorter survival
Blastoid variant and a "proliferative" expression
38
Transformation of mantle cell lymphoma
can overtime to DLBCL
39
Morphology of mantle cell lymphoma
Expanding population of neoplastic cells resemble mantle cells , but NO PROLIFERATION CENTERS as in CLL/SLL
40
Mantle cell lymphoma has lymphomatoid polyposis. . . Tell me what this is
mucosal involvement of the small bowel or colon produces polyp-like lesions and makes you think it is IBD
41
Encompasses a heterogeneous group of B cell tumors that arise within lymph nodes, spleen or extranodal tissues . .the latter were originally notes at mucosal sites so thus often called "maltomas" . . especially in GI tract
Marginal Zone lymphoma
42
These arise in extranodal tissues exhibiting chronic inflammation of autoimmune or infectious etiology. may regress if inciting agents are eliminated
Give examples
Marginal Zone Lymphoma
- Salivary - Sjogren Syndrome
- Salivary - Hashimoto's thyroiditis
- Stomach - Helicobacter
43
Explain pathogenesis of Marginal Zone lymphoma
- Arise in chronically inflamed tissues that are in a continuum b/t reactive hyperplasia and full-blown lymphoma.
- They begin as polyclonal and acquire initiating mutations
44
Dry tap
Hairy cell leukemia
45
Rare but distinctive B cell neoplasm is predominantly a disease of middle aged white males. Median age 55. Male to female ratio 5:1. characteristic image seen on phase contrast microscopy
Hairy cell leukemia
46
What causes the dry tap in hairy cell leukemia
cells produce an ECM of reticular fibers and this meshwork acts like chronic inflammatory fibrosis so when you try to aspirate the bone marrow you can't get anything
47
Clinical manifestations of Hairy Cell leukemia
- Splenomegaly (often massive) is most common and sometimes only abnormal physical finding
- Hepatomegaly is less frequent and lymphadenopathy is rare
- Pancytopenia and splenic sequestration is seen in over half
- about 1/3 present with infections
48
Hairy cell leukemia has increased incidence of what and due to what?
atypical mycobacteria due to unexplained monocytopenia
49
What is on the surface of hairy cell leukemia cells that is helpful
IgG
50
What are the peripheral T cell and NK cell neoplasms
- Peripheral T cell lymphoma, unspecified (NOS)
- Anaplastic Large cell lymphoma (ALK pos)
- Adult T cell leukemia/lymphoma
- Mycosis Fungoides/Sezary Syndrome
- Large Granular Lymphocytic leukemia
- Extranodal NK/T cell lymphoma
51
Clinical symptoms of Peripheral T cell lymphoma, unspecified
- Lymphadenopathy
- sometimes eosinophilia
- pruritis,
- Fever
- Weight loss
52
What is the prognosis of peripheral T cell lymphoma unspecified?
significantly worse than B cell analogues
53
An uncommon entity defined by the presence of rearrangements in the ALK gene?
What chromosome is this?
Anaplastic Large Cell lymphoma
- chromosome 2p23
- ALK is not expressed in normal lymphocytes or other lymphomas so its detection is a reliable indicator
54
These tumor cells tend to cluster about venules and infiltrate lymphoid sinuses, mimicking the appearance of metastatic carcinoma
Anaplastic Large Cell lymphoma
55
Age for Anaplastic Large cell lymphoma
tend to occur in children or young adults
56
How do Anaplastic large cell lymphomas present?
Prognosis?
Age dependent prognosis?
soft tissue "masses"
- very good prognosis unlike other aggressive peripheral T cell neoplasms
- Morphologically similar lymphomas but WITHOUT ALK rearrangements occur in adults and have a poor prognosis
57
"Hallmark" horseshoe like or embryoid nuclei and abundant cytoplasm
Anaplastic large cell lymphoma
58
How do you diagnose Peripheral T cell lymphoma, unspecified
basically by saying its none of the other peripheral T cell neoplasms but has T cell markers
59
A neoplasm of CD4+ T cells only observed in adults infected with HTLV-1. occurs mainly where the virus is endemic i.e. Japan, W. Africa, and the Caribbean basin
Adult T-cell leukemia/lymphoma
60
What may adult T cell leukemia/lymphoma cause?
a progressive demyelinating disease of the CNS and spinal cord associated with tropical spastic paraparesis
61
tumor of CD4+ helper cells that home to the skin . . plaquelike manifestations
Mycosis Fungoides/Sezary Syndrome
62
Describe the Sezary Syndrome that comes with Mycosis Fungoides?
-A variant of generalized exfoliative erythroderma with an associated leukemia of "Sezary" cells with characteristic CEREBRIFORM NUCLEI
63
tumor cells are large lymphocytes with abundant blue cytoplasm and scant coarse azurophilic granules
Large Granular lymphocytic leukemia
64
What are the 2 variants of Large Granular lymphocytic leukemia
T cell and NK
65
What cell indices dominate the clinical picture of Large Granular lymphocytic leukemia
Neutropenia and anemia
66
What syndrome is associated with Large Granular lymphocytic leukemia and describe the syndrome
Felty syndrome: RA, splenomegaly and neutropenia
67
This peripheral T and NK cell neoplasm is highly associated with EBV and typically presents as a highly destructive nasopharyngeal mass . . less commonly involved the testes and/or skin
Extranodal NK/T cell lymphoma
68
Tends to surround and invade small vessels leading to extensive ischemic necrosis.
-Rare in US but 3% of NHL is Asia
Extranodal NK/T cell lymphoma
69
What is odd about the association of EBV and extranodal NK/T cell lymphoma concerning it's cell markers
it does NOT express CD21 which is the receptor for EBV
70
Average age at diagnosis of Hodgkin lymphoma
32
71
Describe the difference b/t HL and NHL
- NHLs frequently occur at extranodal sites and spread in an unpredictable fashion; multiple peripheral nodes; Noncontiguous spread; Waldeyer ring and mesenteric Nodes COMMONLY involved
- HL arises at a single node or chain of nodes (Cervical, mediastinal, para-aortic) and spreads first to contiguous lymphoid tissues; Mesenteric nodes and Waldeyer ring RARELY involved; extranodal presentation RARE
72
Reed Sternberg cell
Hodgkin lymphoma
73
explain what Reed Sternberg cells do
release a wide variety of cytokines, chemokines, and other factors that induce the accumulation of REACTIVE lymphocytes, macrophages, and granulocytes. they are aneuploidy and possess a diverse clonal chromosomal aberrations
74
A large cell with 2 nuclei and extremely large nucleoli with clearing around it and relatively abundant cytoplasm . . in a background of mononuclear cells that are NOT neoplastic but reactive . . the cell itself is neoplastic
RS cell
75
What are the 4 "classic" types of Hodgkin lymphoma . . what makes them classic?
- Nodular sclerosis
- Mixed cellularity
- lymphocyte rich
- lymphocyte depletion
-the RS cells have similar immunophenotypes (CD30+)
76
Describe the Nodular sclerosis type of Hodgkin
- most common
- uncommonly assoc. with EBV
- equal gender involvement
- Propensity for lower cervical, supraclavicular sites
- especially noted for frequent mediastinal involvement
- prognosis excellent
77
Describe the mixed cellularity type of Hodgkin
- RS cells and variants usually abundant
- RS cells infected by EBV in 7-%
- more common in males
- more commonly Biphasic in age
- Systemic symptoms (night sweats and weight loss)
- advanced tumor stage but prognosis is very good
78
Describe the lymphocyte-rich type of Hodgkin
- uncommon
- EBV in 40%
- very good to excellent prognosis
79
Describe the lymphocyte depletion type of Hodgkin
- Least common
- immunophenotyping essential as it must be distinguished from NHL .. . doesn't have background of reactive cells
- >90% EBV involvement
- predominantly elderly, in HIV+ of any age, and in non-industrialized countries
- overall outcome less favorable than other classic types
80
what is the NON classic type of Hodgkin
Lymphocyte predominance
81
Describe the lymphocyte predominance type of Hodgkin
- uncommon
- different immunophenotype
- L & H cells (Popcorn cells)
- 3-5% transform into a tumor resembling a diffuse, Large B cell lymphoma
- EBV Is NOT associated with this type
- CD20+, CD15 and 30 neg,
- young males with cervical or axillary lymphadenopathy; mediastinal
82
What are the most common subtypes of NHL in people with HIV/AIDS
primary central nervous system lymphoma
83
What are the "AIDS defining illnesses"
- Kaposi's sarcoma
- NHL
- cervical cancer
84
what expands in a virally infected lymph node with EBV
paracortex
85
In an HIV patient with normal T4 cell count that has a virally infected lymph node, what is seen? describe what this is
Brisk follicular hyperplasia
| -its a B cell response
86
```
What cytokines do TH1 cells produce?
What induces this subset?
What do the cytokines released do?
What do these defend against?
What is it's role in disease?
```
- IFN-gamma
- IFN-gamma, and IL-12
- Macrophage activation, Stimulation of IgG, antibody production
- Intracellular microbes
- Immune mediated chronic inflammatory diseases (often autoimmune)
87
```
What cytokines do TH2 cells produce?
What induces this subset?
What do the cytokines released do?
What do these defend against?
What is it's role in disease?
```
- IL-4, 5, 13
- IL-4
- stimulation of IgE, activations of mast cells and eosinophils
- Helminthic parasites
- Allergies
88
```
What cytokines do TH17 cells produce?
What induces this subset?
What do the cytokines released do?
What do these defend against?
What is it's role in disease?
```
- IL-17 and 22
- TGF-beta, Il-6, IL-1, IL, 23
- recruitment of neutrophils and monocytes
- extracellular bacteria and fungi
- Immune mediated chronic inflammatory diseases (often autoimmune)
89
for these you do not need blasts in the peripheral blood but instead in bone marrow
AML; acute myeloid leukemia
90
What are the 3 broad categories of myeloid neoplasm and generally describe them
- AML; an accumulation of immature myeloid forms (blasts) in the bone marrow suppresses normal hematopoiesis
- Myelodysplastic syndromes (MDS): ineffective hematopoiesis leads to cytopenias
- Myeloproliferative disorders (MPD) there is usually increased production of one or more types of committed/mature white/red cells of the myeloid series
91
The diagnosis of AML is based on the presence of what
at least 20% myeloid blasts in the bone marrow
| -Bone marrow exam is required if AML is suspected
92
What has worse prognosis MDS or MPD
generally MDS
93
MDS and MPD ----> AML
they often "transform" to AML
94
What are the WHO classifications of AML?
I: AML with genetic abberrations
II: AML with MDS-like features
III: AML, therapy related
IV: AML, NOS
95
What are the subtypes of MDS
- RA: refractory anemia
- RARS: above with ring sideroblasts
- RAEB: . . . excess blasts
- RAEB-t . . same as above but therapy related
- CMML: Chronic myelomonocytic leukemia (not actually a leukemia but can transform to AML)
- MDS, NOS
96
What are the subtypes of MPD?
- CML: Chronic myelocytic leukemia (not a leukemia but can transform to AML
- PV: polycythemia vera
- ET: essential thrombocytosis
- PM: progressive myelofibrosis
97
Give me the type I WHO AML genetic aberrations with their prognosis and FAB class
- t(8;21) . . M2 . . Favorable
- Inv(16) . . M4eo . . Favorable
- t(15;17) . . M3 (APL . . DIC) . . Intermediate
- t(11q23;v) . . M4,M5 . .. Poor
98
Give me the type II WHO AMLs with prognosis
- with prior MDS syndrome . . very poor
| - W/O prior myelodysplastic syndrome . . poor
99
What is the prognosis of AML, therapy related
Very poor
100
M0
- AML, minimally differentiated
- Blast lack definitive cytology and cytochemic markers of myeloblasts (MPO neg)
- express myeloid lineage antigens and resemble myeloblasts ultrastructurally
101
M1
- AML, without maturation
- >3% of blasts are MPO+
- few granules or Auer rods and little maturation beyond myeloblast stage
102
M2
- AML with myelocytic maturation (Most common)
- Full range of myeloid maturation through granulocytes
- Auer rods present in most
- often t(8;21)
103
M3
- APL
- most cells are hypergranular promyelocytes
- often with many Auer rods per cell
- younger pts (35-40)
- DIC
- t(15;17)
104
M4
- AML with myelomonocytic maturation
- myelocytic and monocytic diff.
- MPO+
- monoblasts are + for nonspecific esterases
- inv(16)
105
M5a/b
- AML with monocytic maturation
| - MPO- but nonspecific esterase+
106
M6a/b
- AML with erythroid maturation
| - dysplastic erythroid precursors
107
M7
-AML with megakaryocytic maturation
108
Cell markers of maturity for AML
- CD34: precursor/immature
- CD64: mature myeloid
- CD33: immature
- CD15: more mature
109
Clinical features of AML
- similar to ALL
- Fatigue (anemia), fever/infection (neutropenia), bleeding (thrombocytopenia)
- petechiae/echymoses/mucosal hemorrhages/hematuria
110
infections and AML
opportunistics: fungi, pseudomonas, commensals, pneumocystis
111
Tissue and AML
-skin/gingiva may be prominent especially with monocytic differentiation
112
localized tissue mass and AML
Granulocytic sarcoma
113
CNS and AML
spread occues but less commonly than ALL
114
Leukemia Cutis
AML . . monocytic type
115
prognosis of therapy related MDS
Worse
116
Blast % in MDS
<20%
117
Clinical features of MDS
- older adults (mean 70)
- progression to AML in 10-40%
- cytopenias more severe in pts with t-MDS with more rapid progression to AML and survival f only 4-8 months
118
Ring sideroblasts
MDS
119
Pseudo-Pelger-Huet cells
-neutrophils with only 2 nuclear lobes . . MDS
120
Pawn Ball megakaryocytes
Megakaryocytes with single nuclear lobes or multiple separate nuclei . . MDS
121
What is the pathogenic feature of MPD
presence of mutated, constitutively activated tyrosine kinases
122
Extramedullary hematopoiesis and MPD
common
123
Explain the spent phase of MPD
progression but not to AML. similar to hairy cell leukemia that generates extracellular reticulin and fibrils. All the cytokines and chemokines get elaborated and cause fibrinogenic effects . . . looks like MDS
124
CML is distinguished from of MPDs by the presence o what?
BCR-ABL . . chrom. 22 and 9 . . Philadelphia chromosome
| -GOOD PROGNOSIS
125
Clinical features of CML
- Adults . . 50 . .m>F
- insidious onset
- fatigue, weakness, weight loss, anorexia
- Abdominal fullness/pain (splenomegaly due to extramedullary hematopoiesis.
- If LUQ pain . .may be splenic infarct
126
Diagnosis of CML
- Leukocytosis; may be > 100,000
- <10% blasts
- bone marrow markedly hypercellular
127
Sea blue histiocytes and increased reticulin
CML
128
LAP utilization of CML
- Low in CML
| - High in reactive leukamoid reactions
129
Prognosis of CML
- 3 years survival without treatment
- 50% enter an "accelerated" phase which after 6 to 12 months enter a "blast crisis"
- other 50% develop and abrupt "blast crisis" with no accelerated phase
130
characterized by increased marrow production of red cells, granulocytes, and platletes (panmyelosis). but, the increase in red cells (polycythemia) is responsible for most of the symptoms in the disorder
Polycythemia vera
131
erythropoietin levels in PV
significantly suppressed
132
Clinical features of PV
- adults
- insidious onset; plethora, cyanosis, intense pruritus
- HCT>55%
- symptoms of hyperviscosity, major bleeding and thrombotic episodes
- Leukocytosis and thrombocytosis (often >500,000)
- about 25% first come to medical attention due to DVT, MI, or stroke
- Hyperuricemia common . . gout
133
Treatment of PV
- phlebotomy
| - JAK2 inhibitors
134
Thrombocytosis WITHOUT polycythemia
Essential thrombocytosis (ET)
135
ET is often associated with activating point mutations in what?
JAK2 (50%) or MPL (5-10%), a receptor tyrosine kinase that is normally activated by thrombopoietin
136
Clinical features of ET
- adults>60 usually
| - Often platelet forms are enlarged/abnormal
137
What is necessary for diagnosis of ET
- Bone Marrow biopsy
- megakaryocytes are substantially increased
- Thrombotic and bleeding
138
survival in ET
12 to 15 years
139
treatment of ET
chemo
140
progression to AML in ET
uncommon
141
The hallmark of this MPD is the development of obliterative marrow fibrosis by non-neoplastic fibroblasts
Primary myelofibrosis
142
Clinical features of primary myelofibrosis
- Least common MPD and difficult to treat
- >60
- early prominent megakaryopoiesis and granulopoiesis. often extensive EMG
- Abnormal megakaryocytes produce PDGF and TGF-beta, powerful fibroblast mitogens
- Activating JAK2 in 50-60%; MPL in 1-5%
- Prominent Splenomegaly
143
Spent phase and primary myelofibrosis
- most commonly goes to spend phase
- obliterates marrow leading to cytopenias and EMH
- aka "agnogenic myeloid metaplasia
144
blood smear in primary myelofibrosis
Normochromic normocytic anemia
| -leukoerythroblastic
145
Prognosis for primary myelofibrosis
-3-5 years
146
Vesicular nuclei with linear grooves or folds and vacuolated cytoplasm . ..Birbeck granules in cytoplasm containing Langerin
Langerhans Cell Histiocytosis
147
What are the 3 diseases in the category of Langerhans Cell Histiocytosis
- Multifocal/multisystemic Langerhans Histiocytosis (Letterer-Siwe disease)
- Unifocal and multifocal unisystem Langerhans cell histocytosis (eosinophilic granuloma)
- Pulmonary Langerhans cell histrocytosis
148
Describe Letterer-Siwe disease
- before 2 years
- cutaneous lesions resembling a seborrheic eruption
- Fevers, infections
- Bone lesions
- With chemo, 50% 5 year survival
- rapidly fatal if untreated
149
Describe the unifocal and multifocal eosinophilic granulomas
- Unifocal: skeletal system of older children. most commonly calvarium, ribs, femur
- multi: multiple erosive bony masses in young children; 50% have diabetes insipidus; Hand-Schuller-Christian triad: Calvarial bone defects, diabetes insipidus, and exophthalmos
150
describe treatment of eosinophilic granulomas
- many spontaneously regress
- chemo if multifocal
- Local excision or irradiation of unifocal
151
What does Pulmonary Langerhans cell histiocytosis present as?
What lobes?
Neoplastic if what mutations?
associated with what environmental factor?
Age?
Progression?
- bilateral interstitial disease
- Middle and upper
- BRAF
- cigarette smoking
- typically adults
- May regress spontaneously on cessation of smoking
