Misc Flashcards
1
Q
PNH
A
Xp22.1
PIG-A gene
Increased proportion of cells missing glycosylphosphatidylinositol (GPI)- linked protein
2
Q
1q21.1
RBM8A mutation
A
TAR
Auto recessive
3
Q
<5% marrow blasts with dysplasia changes
<2% peripheral blasts
A
Refractory Cytopenia of Childhood
RCC
-hgb<10, macrocytic RBC, plt<150, hypocellular BM (5-10%), micro-megakaryocytes
-rarely involves lymph nodes, spleen, or liver
4
Q
Mild neutropenia/thrombocytopenia
Exocrine pancreatic dysfunction
Marrow: vacuolated precursors and ringed sideroblasts
A
Pearson syndrome
Mitochondrial DNA deletion
5
Q
BRAF
*KIAA1549
*V600E
A
Low Grade Glioma
KIAA most common for pilocytic astrocytoma
6
Q
H3 K27M
A
Common histone mutation in DIPG
Or
High grade gliomas
7
Q
WT1 11p15.5
A
Wilms tumor
8
Q
WT1 + PAX6
A
WAGR
9
Q
WT1 exon 8 or 9
A
Denys-Drash
Kidney diffuse mesangial sclerosis
Wilms predisposition
10
Q
WT1 intron 9 donor splice site
A
Frasier syndrome
Wilms tumor predisposition
11
Q
DIS3L2 gene
Polydactyl
Fetal ascites
A
Perlman syndrome
Wilms tumor predisposition
12
Q
ASXL1 gene
Syndromic with intellectual disability
A
Bohring Opitz syndrome
Wilms tumor predisposition
13
Q
HR neuroblastoma adolescent
Mutation of tumor?
A
ATRX
Chromosome remodeling gene, 44% adolescent and adults
14
Q
ETV6-NTRK3 gene fusion characteristic in what?
A
Infantile fibrosarcoma
And
cellular congenital mesoblastic nephroma
15
Q
Germline 22q11.2
A
Mutation of INI -1 (or SMARCB1)
Assoc with rhabdoid tumor
16
Q
12:15 tumor translocation
A
Cellular congenital mesoblastic nephroma (CMN)
17
Q
11p13
A
Assoc with WAGR
18
Q
TP53
A
Anaplastic wilms
19
Q
Germline mutation chromosome 3
A
Von Hipple-Lindau
Risk for renal cell carcinoma (which is also assoc with FH-tumor predisposition syndrome)
20
Q
BCOR internal tandem duplicates
A
Clear cell carcinoma of the kidney
21
Q
Inversion of intron 22
Bleeding
A
Severe hemophilia A
Most common mutation
22
Q
Iron refractory iron deficiency anemia
Mutation?
A
TMPRSS6
(Homozygous deletions of both Matripase-2 genes)
23
Q
Hereditary hemochromatosis
Mutations?
A
C282Y - most common HFE mutation
H63D - another HFE mutation but less common
More rare:
TFR2
FPN1
HAMP
24
Q
Primary erythrocytosis
Mutation?
A
Erythropoietin receptor mutation = EPOR
25
Pathogenic variants in PTPN11
Noonan syndrome
26
Lynch syndrome
Non-polyposis colon cancer
MLH1
PMS2
27
Pathogenic variant SHDx
Pheochromocytoma
28
DICER1
Pleuropulmonary blastoma
Papillary thyroid cancer
Ovarian sex cord tumor +thyroid nodules
Sertoli-Leydig cell tumor and gynandroblastoma
Pineoblastoma
Pituitary blastoma
29
LiFraumeni Syndrome
TP53
Low hypodiploid ALL
Osteosarcoma
Anaplastic embyonal rhabdomyosarcoma
Anaplastic Wilms
Choroid plexus carcinoma
SHH Medulloblastoma
Adrenal corticocarcinoma
30
NBEAL2
Grey platelet syndrome
31
Somatic mutation assoc with CLOVES
PIK3CA
Also seen in Klippel-Trenaunay, and fibro-adipose vascular anomalies
CLOVES= congenital lipomatous overgrowth, vascular malformations, epidermal nevi, skeletal/spine abnormalities
32
AKT
Proteus syndrome
33
H3.3 G34R
High grade glioma less common histone mutation
Typically in cerebral hemispheres, teenagers and young adults
34
Medulloblastoma
WNT
Excellent prognosis
Genetic aberration: monosomy 6, nuclear beta-catenin
35
Medulloblastoma
Group3
Poor prognosis
Genetic aberration: i17q, MYC amplification
36
Medulloblastoma
SHH
Fair prognosis; poor of assoc with TP53
Genetic aberration: PTCH1/SMO/SUFU, GLI2
37
Germ cell tumors
Germinomas = non-secreting
Non-germinomatous germ cell tumors = secreting, worse outcome. +AFP and beta-HCG
Suprasellar/pituitary or pineal or both
38
Supracellar/pituitary tumor
Mixed solid&cystic mass
Squamous epithelium lining cystic cavity - often containing calcium and keratin
Craniopharyngioma
39
LCH molecular pathogenesis
BRAF-V600E
40
HLH cytotoxicity genes
PRF1
UNC13D
STX11
RAB27A
STXBP2
AP3B1
MUNC13-4
Auto recessive, familial HLH assoc with homozygous defects
41
HLH EBV assoc
Assoc with XLP: SH2D1A = XLP 1, XIAP, BIRC4 = XLP 2
More recently assoc with X-MEN syndrome (MAGT1)
42
Osteosarcoma predispositions
RB1
TP53
RECQL4 - DNA helicase/Rothmund-Thomson syndrome
Bone damage
NOTCH signaling accelerates
43
RB1 gene chromosome
Chromosome 13q14
A tumor suppressor gene
Assoc with MYCN amplification has worse outcomes
44
Genetic assoc with mediastinal germ cell tumor
Klinefelter syndrome (47XXY)
45
Genetic syndromes assoc gonadoblastoma/dysgerminoma
Swyer syndrome (46XY)
Turner syndrome (47XO)
Fraiser syndrome (WT1)
46
Germ cell tumors typically assoc with age <11yrs
Teratoma or yolk sac tumors
47
Category of Germinoma
Seminomas (testes)
Dysgerminomas (ovary) -may have elevated PLAP
Germinoma (extragonadal)
48
Category of Non-germinomas
Yolk sac - components of embryonic and extra embryonic endoderm
Embryonal carcinoma - undifferentiated cells
Choriocarcinoma - trophoblastic differentiation
49
GCT assoc with elevated serum AFP
Yolk sac ++++
Embryonal carcinoma +/-
Immature teratoma +/-
50
GCT assoc with elevated bHCG
Choriocarcinoma ++++
Embryonal carcinoma +/-
51
Ovarian GCT
Juvenile granulosa cell tumor - precocious puberty (ovarian-young children)
Sertoli-Leydig tumor - amenorrhea and or virilization (ovarian-adolescent)
52
Extragonadal tumor
Sacrococcygeal tumor’s presentation
Constipation, urinary retention, refusal to sit, unilateral swelling and buttock discoloration
53
Choriocarcinoma syndrome
Hemorrhaging into lung Mets or CNS
Very high bHCG >100,000
*always image brain
Tx: chemo (cisplat/etoposide, omit bleomycin)
54
For ovarian GCT concerns, obtain what to rule out stromal cell tumor?
Inhibin B
55
Normal levels of AFP and bHCG
AFP newborns >40,000 ng/mL
AFP adult < 10 (reached by 8-12mo.)
bHCG <5 IU/mL
56
Ovarian sex-cord tumor plus hyperpigmented macules
Peutz-Jegher syndrome
STK11 gene
“STicKs and stones (mcjagger)”
57
Juvenile granulosa cell tumor
Gene and syndrome
IGH1 & IGH2
Ollier disease (enchondromatosis) and
Mafucci syndrome (enchondromatosis + hemangiomas)
58
Hepatoblastoma mutations
WNT pathway: CTNNNB1 or APC
NFE2L2 (NRF2) mutation - worse prognosis
59
Hepatoblastoma clinical associations
Elevated AFP
Thrombocytosis due to HB cells secreting IL-1B to produce IL-6 -> growth factor secretion and thrombopoietin
60
Hepatoblastoma pathology
Epithelial (fetal+embryonal)
Pure fetal - excellent prognosis
Small cell undifferentiated- poor prognosis, low AFP <100, assoc with 22q11 (INI1/rhabdoid tumors), neg INI1 immunostaining
61
AFP in in fibrolamellar variant of HCC
Low or normal
62
Hepatocellular carcinoma risk factors
Congenital: tyrosenemia, biliary cirrhosis, glycogen storage disease, alpha1 antitrypsin def, hemochromatosis
Environmental: hep B&C, alcohol, anabolic steroids, aflatoxin, carcinogens
63
High risk of developing medullary thyroid carcinoma
MEN2A
Screen with calcitonin
MEN2B with RET mutation should have prophylactic thyroidectomy in first months of life
64
Germline abnormalities assoc with Neuroblastoma
Mutations in ALK *bilateral or multifocal disease
Or PHOX2B *neurologic abnormalities like hirshsprung and central hypoventilation
Both auto dominant
65
SMARCA4 assoc cancer
Small cell carcinoma of the ovary
(Rhabdoid tumor predisposition type2)
66
Examples of stromal sex cord tumors
Sertoli-Leydig
Juvenile granulosa cell tumors
Inhibin +
67
Metastatic bone lesions, BCOR, histology showing cords and nests of pale stained tumor cells with abundant extra cellular matrix separated
Clear cell carcinoma of the kidney
68
Nuclear expression of TFE3 and previous hx of cancer in patient with new renal mass
Translocation associated Renal cell carcinoma
The Xp11 translocation is found in the tumor, not Germline
69
Plasminogen activator inhibitor type 1 (PAI-1)
Inhibits plasminogen activator which promotes clotting so in it’s absence leads to excessive breakdown of clots - most commonly in the mucus secretions
-think of this when aminocaproic acid (an antifibrinolytic) really helps with epistaxis
70
VWD type where there is discrepancy between vWF antigen (normal) and vWF activity (very low)
Type 2M
(Ratio of 0.5 or less)
Test for mutation in exon 28 of the vWF gene
“Missing” the ability to bind to platelets -loss of function
Desmopressin is not helpful bc number is fine, it’s just dysfunctional. Treat with vWF concentrates, aminocaproic acid, hormone therapy
71
Thrombin time
Assesses the presence and function of fibrinogen
- add thrombin to plasma and measure time to clot. If prolonged, then fibrinogen is abnormal
72
End portion of the coagulation cascade
Prothrombin —(Xa)—> thrombin
Fibrinogen—(thrombin)—> fibrin
Fibrin + XIIIa = stable clot
*XIII—(thrombin)—> XIIIa
73
Hemophilia A
What to give if your ER doesn’t have factor VIII concentrate?
Desmopressin - to increase factor VIII as quickly as possible
FFP only has 1 IU/mL of factor VIII (10mL/kg infusion = 10% increase… ie not much). Cryo would be better
74
Clotting Factors not made in the liver
V - megakaryocytes
VIII - endothelial cells
vWF - endothelial cells
75
Thrombin prohemostatic mechanisms
Activates procoagulant factors (V, VIII, XI)
Activates antifibrinolytic factors (factor XIII, thrombin-activatable fibrinolysis inhibitor TAFI, activates platelets, converts fibrinogen to fibrin)
76
3 gene deletion alpha-thalassemia
Hb H disease
Visualized by supravital RBC staining such as brilliant cresyl blue (BCB)
77
Side effects of iron chelators
Neutropenia
Hearing loss
Growth failure
Cataract
Osteoporosis
78
Cryo contains…
Fibrinogen
Factor VIII
Factor XIII
vWF
79
Prothrombin complex concentrate contains…
Factors II
IX
X
+/- VII
80
Why saline wash RBCs before transfusion?
To remove potassium
Or give fresh RBCs and not stored
81
Epithelioid hemangioendothelioma (EHE)
WWTR1-CAMTA1 gene fusion (most common)
Epithelioid lesions arranged in nests, strands, trabecular patterns with I frequent vascular space
Malignant vascular tumor
Tx: obs, surgery, targeted therapy, sirolimus, MEK inhibitors
82
Pseudomyogenic hemangioendothelioma (PMH)
Loose fascicles of plump spindle and Epithelioid cells with abundant eos, cytoplasm, and coexpression of keratin and endothelial markers
?t(7;19)
serpine1-FOSB fusion gene
83
May-Hegglin anomaly
Mutation MYH9 (myosin heavy chainA)
Macrothrombocytopenia, neutrophils with dohle-like cytoplasmic inclusions
Bleeding out of proportion to the plt count
+high frequency hearing loss, nephritis, cataracts
84
Deficiency of the enzyme
B-Glucocerebrosidase
Gaucher
85
C-Mpl gene mutation
Congenital amegakaryocytic thrombocytopenia
Progress to pancytopenia within first few lives
1p34
86
Large plate thrombocytopenia
Bernard soulier
Grey platelets
MYH9
87
Platelet agg results
Bernard Soulier unable to interact with ristocetin/vWF bc glycoprotein 1b-IX causes plt adherence to vascular endothelium via vWF
Glanzmann thrombasthenia lack IIb-IIIa which binds Plts to fibrinogen -globally low except ristocetin
Absence of dense granules results in lack of 2nd wave to ADP and Epi (hermansky-pudlak)
88
Neonatal alloimmune thrombocytopenia
Maternal antibodies against paternally derived antigen expressed by the infant platelets (HPA-1a most common)
Keep plt >30K. Give maternal plts or random donor+IVIG
89
Neonatal autoimmune thrombocytopenia
Maternal history of ITP or thrombocytopenia
Less bleeding risk
Antibodies against common antigens on plt surface
90
Increased aggregation to low-dose ristocetin on plt agg
Platelet-type vWD and type 2B
91
Congenital TTP tx
FFP
92
Hermansky -Pudlak syndrome
Auto recessive
Lack of dense granules in the platelets (ATP, ADP, serotonin, calcium - no dense granules in “Hermona’s C.A.S.A”) -absent 2nd wave on plt agg for ADP
Assoc with oculocutaneous albinism, pulm fibrosis, strabismus, nystagmus
93
Contents of alpha granules
Fibrinogen, platelet factor 4, vWF, thrombospondin
94
Tx of bleeding secondary to uremia?
Desmopressin
95
Grey platelet syndrome
Auto recessive
Macrothrombocytopenia, splenomegaly, mild bleeding diathesis
Can be assoc with myelofibrosis
Absence of alpha granules
Plt agg defects with epi&ADP
96
Sickle cell mutation on beta globin
Beta globin 6: glutamic acid to valine
SC: bg6: glutamic acid to lysine
97
Other hemoglobinopathy beta globin mutations
Hgb E: bg26: glutamic acid to lysine
Hgb D (punjab): bg121: glutamic acid to glutamin
Hgb O (Arab): bg121: glutamic acid to lysine (hgb electrophoresis: migrates with hgbC)
98
SCD medication:
HU
Endari
Oxbryta (Voxelotor)
Crizanlizumab
HU: ribonucleotide reductive inhibitor. increases Hb F (dlt neutropenia)
Endari: L-glutamine. Antioxidant. No change in labs
Oxbryta (voxelotor): inhibits HbS polymerization, increases O2 affinity. Increases hgb
Adakveo (crizanlizumab): inhibits p-selectin preventing wbc/rbc/plt from sticking to each other. No changes in labs. IV wk0, wk2, q4wks after
99
Hemoglobin Lepore
Hemoglobin Constant Spring
Lepore: fusion btw delta (HbD) and beta (HbB)
Constant Spring: mutation in alpha globin termination codon leading to abnormal chain termination. Hgb electrophoresis has Very Slow migrating hgb
100
hgb electrophoresis values in thalassemia
Beta thal trait: hgb F nml-incr (1-10%)
Hgb a2 incr (3-10%)
Alpha thal trait: hgb F nml (0-2%)
Hgb a2 nml-decr (0-2.5%)
Iron def: hgb F nml (0-2%)
Hgb a2 nml-decr (0-2.5%)
101
Alpha thal
aa/aa normal
aa/a- Silent carrier
aa/- - Trait
a-/a- Trait
- -/a- Hgb H dz
- -/a^cs,a Hgb H-constant spring
- -/- - Hydrops fetalis
102
Alpha trait with excess gamma in neonate
Hgb Barts (gammax4) gamma 3-8%
103
Beta thal
Normal: b/b
B thal trait: b/b0; b/b+
B thal intermedia: b+/b+; b+/b0;
bE/b+; bE/b0
B thal major (Cooley’s anemia): b0/b0
Newborn screen: only F pattern
104
Mentzer index
MCV / RBC
< 13 = thal
> 13 = iron def
105
CML phases
Chronic phase: high wbc, “normal” maturation, small %myeloblasts, splenomegaly, minimal symptoms
Tx with a TKI
Accelerated phase: 10-30% blasts in PB/BM, Plt < 100k,
106
JMML poor prognostic features
> 1yr, > 9% monocytes, >2% peripheral blasts, PLt< 50K, elevated hgb, monosomy 7
AML-like
Worse prognosis
107
JMML
Elevated fetal hgb
Hypersensitivity of monocytes in response to GM-CSF
Many myeloid precursors on smear
Monocytosis with high WBC count (>100k)
Rarely > 20% BM blasts
Normal cytogenetics most common
108
Kaposiform-hemangioendothelioma
Assoc with Kasabach-Merritt phenomenon = coagulopathy caused by the lesion (hypogibrinogenemia and thrombocytopenia)
K-M is also associated with Tuffted angioma
Skin is tense, deep purple, shiny
Prox-1 positive stain
Tx: sirolimus, vincristine, steroids
109
Inheritance pattern of IL2RG SCID
X-linked
(Sister HCT donors are fine)
110
Types of SCID
ADA = T-,B-,NK-
RAG1 = T-,B-,NK+
IL2RG (common gamma chain) = T-,B+
111
Congenital hemangioma
Glut1 negative
GNAQ somatic mutation
Present at birth, fully formed - involution is variable (rapid, non, partial)
Can have a transient consumptive coagulopathy (thrombocytopenia and hypofibrinogenemia)
“Halo” present
112
Infantile hemangioma
Always GLUT-1 positive
113
Angiosarcoma
20% can be glut-1 positive
Reports of transformation of hemangiomas of the liver and lymphatic anomalies
Very aggressive
Firm, purpuric, mass-like
114
Capillary Malformations
Become darker with age
Ex: Sturge Webber syndrome
Tx: pulsed dye laser, ASA, mTor inhibitors
Somatic mutations: GNAQ, GNA11
115
Venous malformations
Bluish, soft compressible
Pain, Coagulopathy
Localized intravascular coagulopathy: increased Ddimer, low fibrinogen, low/normal plts
Syndrome: BRBN
TIE-2 mutation
Small percentage PIk3CA
Tx: DOAC, sirolimus, pik3 inhib (Alpelisib)
116
Gorham Stout Dz
Lymphatic anomalies
Hallmark: progressive bony disease with destruction through the cortext
Tx: mTor inhib, MEK inhib
KRAS
117
Kaposiform lymphangiomatosis
Areas of spindle cells
Coagulopathy
Multifocal
Poor prognosis
NRAS, CBL, PIk3CA
Tx: sirolimus, VCR, steroids
118
PIk3CA related overgrowth spectrum (PROS)
CLoVeS
klippel-Trenaunay
Megalocephaly-capillary malformation
Fibroadipose vascular anomaly
Fibroadipose hyperplasia
Hemihyperplasia-multiple lipomatosis syndrome
119
Fanconi inheritance
Auto recessive
Except Fanc B which is X-linked
120
SDS malabsorption testing by age
> 3yrs - pancreatic isoamylase
< 3 yrs - trypsinogen
121
Another name for sIL-2 receptor test
Soluble CD25
To test for HLH
122
WAS gene
Xp11.23
X-linked thrombocytopenia and WAS
123
CGD mutations
Most common mutated NADPH subunit is gp91phox (CYBB gene) - the only X-linked form
2nd MC = p47phox (NCF1 gene) - auto recessive
Less common, all auto recessive: p22phox, p67phox, p40phox
CGD testing: dihydrorhodamine 123 or nitroblue tetrazolium test
124
Dyskeratosis congenita patterns of inheritance
X-linked recessive- DKC1, Xq28 and encodes dyskerin
AutoDominant- TERC, TERT, TINF2
Auto recessive- CTC1, RTEL1, TERT, TERC, NOP10, NHP2, WRAP53
Or can be sporadic
125
Hypereosinophilic syndrome (HES)
Excess of IL-5
DVT is a common complication and rash
Abs Eos 1500+
Idiopathic or assoc with underlying trigger
Typically Tx underlying cause or Tx with steroids
