Neoplasia (MoD) Flashcards
1
Q
“Seminoma” type of cancer
A
Germ cell tumor
2
Q
“Teratoma” type of cancer
A
Cancers from more than one cell type
3
Q
Malignant histologic features
A
o Incr. nucleus size, decr. cytoplasm (incr. N:C ratio)
o Abnormal mitotic figures (e.g. tripolar mitoses)
o Architectural disarray
o Anaplasia (sheets of large tumors growing in disorganized fashion)
o Pleimorphism (different cells in the same tumor)
4
Q
How do most sarcomas spread?
A
Hematogenous
5
Q
How do most carcinomas spread?
A
Lymphatics (remember the exceptions though)
6
Q
Where does breast cancer usually metastasize?
A
Axillary lymph nodes
7
Q
Examples of microbial carcinogens
A
HPV, EBV, HHV-8, hep B & C, heliobacter pylori, Clonorchis sinensis
8
Q
What does “growth fraction” refer to? Why is it important?
A
Proliferating pool of cells in neoplasia growth; susceptibility to chemotherapy depends on growth fraction
9
Q
Ways to measure cell proliferation rate
A
o Mitotic figure count (5 mitoses/10 hpf)
o Proliferation Index (proliferating cells/G0)
o Flow cytometry (S-phase)
o Immunohistochemistry (proliferation markers, e.g. PCNA)
10
Q
Symptoms and most common cause of carcinoid syndrome
A
Serotonin excess causes diarrhea, bronchospasm, flushing, sweating, can lead to heart failure; GI carcinoid metastatic to liver (less commonly lung carcinoid)
11
Q
How is hypercalcemia a paraneoplastic syndrome?
A
Associated with squamous cell carcinoma of the lung
12
Q
What is “Trousseau’s sign” of malignancy? What cancers is it associated with?
A
Abnormal clotting (e.g. venous thrombosis or DIC); GI, pancreatic, lung
13
Q
What determines the grade of a cancer? What determines stage? Which is more important?
A
Mitoses, differentiation, necrosis; size + spread; Stage is the most important prognostic factor
14
Q
Cancer(s) associated with CEA?
A
Colon, pancreas, lung (carcinoembryonic antigen)
15
Q
Cancer(s) associated with CA-19-9?
A
Pancreatic cancer
16
Q
Cancer(s) associated with CA-125?
A
Ovarian cancer
17
Q
Cancer(s) associated with AFP?
A
Hepatocellular + yolk sac tumors, also ataxia-telangiectasia
18
Q
10 hallmarks of cancer
A
o Ras activation o Inactivate E cadherin o Produce CSF3/G-CSF o Bcl-2 overexpression o Express PD-L1 o Activate telomerase o Rb loss o Produce VEGF o Inactivate hMSH2 o GLUT1 overexpression
19
Q
Classes of proto-oncogenes
A
o Growth factors o Growth factor receptors o Signal transducers o Transcription factors o Anti-apoptotic proteins o Cell cycle regulators
20
Q
What type of molecule is myc/c-myc?
A
Transciption factor (oncogene)
21
Q
What type of molecule is erb-1/erb-2?
A
Growth factor receptor (oncogene)
22
Q
What type of molecule is abl?
A
Signal transducer (oncogene)
23
Q
What type of molecule is ras? How can it be activated?
A
Signal transducer (oncogene); by inhibiting GAPs (otherwise incr. internal rate of GTP hydrolysis) or activating guanine nucleotide exchange factors
24
Q
Tumor suppressor classes + examples
A
o Cell cycle inhibitors: p16INK4A(CDKN2A) o Cell adhesion: E cadherin o DNA repair: hMSH2, ATM o Transcription regulators: Rb, p53 o Signal transduction: NF-1, APC
25
What type of molecule is APC? What is its function?
Tumor suppressor preventing signal transduction; prevents signal transduction by promoting degradation of beta-catenin
26
What type of molecule is NF-1? How does it function?
GAP (tumor suppressor); NF-1 incr. internal GTPase activity of Ras, thusly inactivating it
27
What type of molecule is ATM? How does it function?
Tumor suppressor involved in DNA repair; binds to double stranded breaks in DNA, then phosphorylates p53
28
Possible (medical) treatment for BRCA-linked ovarian cancer?
PARP (poly ADP ribose polymerase) inhibitors blocking transcription
29
Cancer associated with CHRPE (hypertrophy of retinal pigment spot)?
Familial adenomatous polyposis
30
Genes associated with Lynch syndrome (HNPCC)? What do these encode for?
MLH1, MSH2; DNA mismatch repair proteins
31
Melanoma evaluation
ABCDE: Asymmetry, Border irregularity, Color variation, Diameter, Evolution
32
"Naked nuclei" on skin biopsy
Merkel cell carcinoma
33
What type of skin lesion expresses factor XIIIa and contains collagen I?
Dermatofibroma
34
What are Pautrier's microabscesses?
Atypical lymphocyte aggregates seen in adult (CD4) T cell lymphoma/leukemia, Sezary syndrome, Mycosis fungoides
35
What is Sezary syndrome? What disease is it associated with?
Cutaneous T cell lymphoma with tumor cells in the blood, generalized erythema and systemic manifestations (high mortality)
36
"Islands of cuboidal cell surrounded by basement membrane-like material"
Cylindroma: benign eccrine neoplasm (adnexal neoplasm)
37
Schwannoma IHC and histologic presentation
S-100; "palisading spindle cells"
38
Fibromatosis IHC presentation
Mutation in beta catenin
39
List the benign vascular tumors, what is their IHC presentation?
[Cavernous] hemangioma, pyogenic granuloma (misnomer); CD31 & CD34
40
Granular cell tumor IHC and histologic presentation
S-100 (spindle cell origin); "Round cells with pink cytoplasmic granules"
41
Dermatofibrosarcoma Protuberans (DFSP) IFC profile
CD34
42
Synovial sarcoma IHC profile
Express epithelial markers (cytokeratin and epithelial membrane antigen)
43
Leiomyosarcoma IHC profile
Smooth muscle actin and desmin
44
Angiosarcoma IHC profile
CD31 & CD34
45
Rhabdomyosarcoma IHC profile
Desmin & myogenin
46
"Grape-like growth in genitourinary tract of a child"
Botryoid variant of embryonic rhabdomyosarcoma
47
Wilm's tumor chromosome and associated clinical presentation
11p (WT-1); WAGR - Wilm's tumor, Aniridia, Genitourinary defects, Retardation
48
Cowden syndrome gene and cancers
PTEN; Papillary papules, Thyroid cancer, Endometrial (and breast) cancer, iNtestinal hamartomatous polyposis, RCC, macrocephaly, hyper pigmented macules of the glans
49
Von Hippel Lindau locus and cancers
3p (VHL gene); brain (hemangioblastomas also of spinal cord) cancer, "kidney" (cysts, clear cell, pheos) cancers, also endolymphatic sac tumors
50
Peutz-Jeghers syndrome gene and presentation
STK11; hamartomatous intestinal polyps, mucocutaneous hyperpigmentation (dark blue to brown spots around eyes and mouth)
51
Basal cell nevus syndrome gene(s) and symptoms
PTCH & SUFU; basal cell carcinoma, jaw cysts, macrocephaly, coarse facial features, medulloblastoma (cerebellum) + calcification of fall cerebri
52
Gene(s) associated with hereditary melanoma
INK4A, CDK4, CDKN2A
53
Multiple Endocrine Neoplasia type 2 gene and symptoms
RET; medullary thyroid cancer, tall stature, mucosal neuromas of lips and tongue, pheochromocytoma, parathyroid adenomas
54
Ataxia-telangiectasia genetic etiologies and clinical presentation
ATM gene (DNA repair, loss or homozygous mutation) and 7:14 translocation; Progressively clumsy gait, slurred speech, oculomotor apraxia, choreoathetosis, telangiectasia of conjunctivae (abs eye finding on PE), frequent infections and elevated AFP
55
Disease(s) associated with ATM mutation
Ataxia-telangiectasia, breast cancer, recently pancreatic cancer
56
Cancer associated with Auer rods
AML (no Auer rods for ALL) and APML
57
What does MBL stand for? Why is it important?
Monoclonal B cell lymphocytosis; precursor to CLL
58
MBL/CLL presentation
Usually asymptomatic, but monoclonal B lymphocytes expressing kappa light chain and CD19, CD20 (but weak), CD23, CD5 positive on flow cytometry
59
Reed-Sternberg cells
Classic Hodgkin's lymphoma (remember they're CD30+, CD20-)
60
Classic Hodgkin's lymphoma subtypes and features
o Reed-Sternberg cells
o CD15+, CD20-, CD30+, CD45-
o Subtypes: nodular sclerosis (lacunar cells, mediastinum), mixed cellularity (abdominal, splenic), lymphocyte-rich (early), lymphocyte poor (older, advanced, BM, HIV)
61
Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) features
o Lymphocytic and/or histolytic cells also called "popcorn bodies"
o CD15-, CD20+, CD30-, CD45+
62
What differentiates aggressive from indolent non-hodgkin's lymphoma?
Elevated LDH (but also night sweats, weight loss, rapid growth + sometimes pain/tender LN)
63
Mantle Cell Lymphoma (MCL)
o CD5+, CD20+ (bright), CD23-
o t(11;14) - Ig heavy chain from chromosome 14 with Cyclin D1 from chromosome 11
o Cyclin D1+ (upregulated)
o Sox-11+ (completely unique)
o Aggressive
o Associated with GI lymphomatous polyposis
64
Follicular lymphoma
```
o t(14:18) - Ig heavy chain from 14 with Bcl-2 from 18
o CD10+ indolent/small B cell lymphoma (completely unique)
o "Centrocytes" - cleaved lambda restricted B lymphocytes (CD10+, CD5-)
o Indolent, but can transform
o Derived from germinal center
```
65
Cyclin D1 function
Phosphorylates Rb, causing E2F to be released and leading to G1 to S transition
66
What are the only two B cell malignancies that express CD5?
CLL and MCL
67
Hairy cell leukemia
o Immunophenotype: CD11c, CD25, CD103, TRAP
o Molecular: BRAF V600E
o "Dry tap" on LP (reticulin fibrosis)
o Indolent disease of middle-aged white men
68
Cause and symptoms of Lymphoplasmocytic Lymphoma
MYD88 L265P mutation (recently); vision loss from Waldenstrom's Macroglobulinemia (malignant B cells transform into plasma cells, secrete IgM which causes hypersensitivity), autoimmune hemolysis (cold agglutinin probably from IgM), association with hep C, anemia, HSM
69
Immunophenotype of Primary Mediastinal (thymic) B cell Lymphoma
CD30+
70
Immunophenotype of primary effusion lymphomas
CD30+, CD138+
71
"neoplastic cells with defective homing receptors/adhesion molecules..."
Intravascular LBCL
72
Burkitt's Lymphoma
o Immunophenotype: CD10+, Bcl6+, Bcl2-, Smlg+
o "Starry sky appearance," basophilic cytoplasm with vacuoles
o t(8;14) MYC translocation
o All subtypes associated with EBV
o Extremely aggressive "mature form of ALL"
73
T cell Large Granular Lymphocytic leukemia
o Associated with Felty syndrome (RA, splenomegaly, neutropenia)
o Large T lymphocytes with 'azurophilic granules' (contain perforin + granzyme)
o IHC profile: CD2, CD3, CD8, CD57
74
Mycosis fungicides/Sezary syndrome Immunophenotype
CD4+, CD7-
75
Peripheral T cell lymphoma NOS symptoms and immunophenotype
Eosinophilia, pruritus; CD2, CD3, CD4, CD30
76
Anaplastic large cell lymphoma gene, translocation and pathologic hallmark
ALK; t(2;5); large anaplastic cells with horseshoe nuclei and voluminous cytoplasm
77
Multiple myeloma clinical indications
Bence-Jones proteins, M component and CRAB (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions e.g. fracture susceptibility)
78
Cancers associated with EBV
Burkitt's lymphoma, Hodgkin's lymphoma, B cell lymphoma in immunocompromised (e.g. AIDS), extranodal NK/T cell lymphoma, nasopharyngeal carcinoma
79
EBV genes and effects
o LMP-1: mimics CD40, causing B cell proliferation (stimulates Nf-kB and JAK/STAT)
o EBNA-2: unregulated cyclin D1, phosphorylating Rb causing it to release E2F (G0 to G1 transition)
80
HBx protein function, associated virus and cancer(s)
Activates growth promoting genes, binds p53; hepatitis B; hepatocellular carcinoma
81
Virus associated with "tax" gene? What does this gene do?
HTLV-1; dysregulates cell cycle and causes genome instability
82
What does MALT stand for? Associated pathogen and translocation?
Mucosal Associated Lymphoid Tissue lymphoma; H pylori; t(11;18) in antibiotic-refractory cases
83
What are Downey cells?
Atypical T lymphocytes seen in EBV infection
84
Disease associated with Paul-Bunnell heterophile antibody? What antibody can be "confused" with them?
EBV; Forssman antibodies (remember they need to be removed before doing the heterophiles antibody test)
85
How do you determine normal % cellularity of bone marrow?
100-age
86
AML generalized and subtype presentations
Anemia, fatigue, SOB, low Hgb, low platelets, elevated WBC, elevated blasts (> 20%) on BM biopsy
o Tumor lysis: elevated uric acid, phosphorous and LDH, hyperkalemia, hypocalcemia, AKI
o DIC: bleeds (ICH, GI, muscle)
o Leukostasis: big blast cells stuck in capillaries of lungs and brain, causing SOB, hypoxia, confusion and seizures
87
Translocation(s) associated with AML
t(8;21), also remember trisomy 4
88
APML presentation and associated mutation(s)
Emergency: DIC, hemorrhage (ICH + abd), pancytopenia
o NPM1: "good" mutation (function = centrosome stabilization and protein synthesis) associated with improved outcomes
o FLT3-ITD: "bad" gain-of-function mutation, higher rate of relapse
o IDH1/IDH2: conversion of isocitrate to alpha-ketoglutarate, mutation leads to 2-hydroxyglutarate, which inhibits TET2
o p53: poor response to chemo, poor survival
o C-Kit
Also t(8;21) and t(15;17)
89
"erythroid ringed sideroblast..."
Myelodysplastic Syndrome
90
MDS disease hallmark(s)
Dysplastic morphology on BM biopsy:
o Erythroid: ringed sideroblasts, myeloblast maturation and nuclear budding
o Neutrophils: Pelger-Heut abnormality
o Megakaryocytes: pawn ball nuclei
91
What disease is often mistaken for MDS? Why? How to differentiate?
Copper deficiency; anemia and neutropenia; thrombocytopenia rare in copper deficiency but peripheral neuropathy present
92
Most common gene associated with MPN
JAK2V617
93
Disease associated with CSF3R mutation
Chronic neutrophilic leukemia
94
Philadelphia translocation is pathognomonic for what disease?
t(9;22) pathognomonic for CML
95
Gene associated with TKI resistance? What cancer are these used to treat? What side effect/toxicity is shared by all TKIs?
BCR-ABL1 T315I; CML; bone marrow suppression
96
Polycythemia Vera symptoms and labs
Sx: pruritus (esp after hot shower), thrombosis (e.g. Budd-Chiari syndrome - hepatic portal vein), erythrocytosis, fatigue, visual disturbances, facial plethora
Labs: Incr. Hgb, JAK2V617F or JAK-2 exon 12 mutations, low to normal EPO, incr. LDH
97
"teardrop-shaped RBCs..." pathognomonic of what?
Primary Myelofibrosis (PMF)
98
Mutations common to ET and PMF
JAK2, CALR, MPL
99
Histologic findings associated with lymphoid hyperplasia (in HIV)
Follicular + inter follicular hyperplasia ("naked follicles"), dissolution of cortical germinal centers (follicular lysis), hyalinization of germinal centers (profound lymphoid depletion)
100
Virus and cancer associated with koliocytes
HPV; squamous cell carcinoma cervix
101
Where is P17 found?
HIV-1 vision membrane
102
Lymphomas and translocations associated with HIV
Non-Hodgkin's lymphomas - DLBCL, Burkitt's, CNS lymphoma, primary effusion lymphoma; t(8;14), t(8;2), t(8,22)
103
Important histologic features of Kaposi's sarcoma
Spindle-to-epithelioid atypical epithelial cells, hemosiderin granules
104
Cryptosporidiosis symptoms (at least in AIDS)
Chronic wasting, electrolyte imbalances, diarrhea, cysts in stool (dx via acid fast on stool)
105
Everything from this block that increases LDH ;)
Pneumocystis jiroveci, aggressive non-Hodgkin lymphoma, APML (spontaneous tumor lysis), Polycythemia Vera
