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Hematology/Oncology > Neoplasia (MoD) > Flashcards

Neoplasia (MoD) Flashcards

1
Q

“Seminoma” type of cancer

A

Germ cell tumor

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2
Q

“Teratoma” type of cancer

A

Cancers from more than one cell type

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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)

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4
Q

How do most sarcomas spread?

A

Hematogenous

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5
Q

How do most carcinomas spread?

A

Lymphatics (remember the exceptions though)

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6
Q

Where does breast cancer usually metastasize?

A

Axillary lymph nodes

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7
Q

Examples of microbial carcinogens

A

HPV, EBV, HHV-8, hep B & C, heliobacter pylori, Clonorchis sinensis

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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

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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)

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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)

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11
Q

How is hypercalcemia a paraneoplastic syndrome?

A

Associated with squamous cell carcinoma of the lung

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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

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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

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14
Q

Cancer(s) associated with CEA?

A

Colon, pancreas, lung (carcinoembryonic antigen)

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15
Q

Cancer(s) associated with CA-19-9?

A

Pancreatic cancer

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16
Q

Cancer(s) associated with CA-125?

A

Ovarian cancer

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17
Q

Cancer(s) associated with AFP?

A

Hepatocellular + yolk sac tumors, also ataxia-telangiectasia

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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
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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
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20
Q

What type of molecule is myc/c-myc?

A

Transciption factor (oncogene)

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21
Q

What type of molecule is erb-1/erb-2?

A

Growth factor receptor (oncogene)

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22
Q

What type of molecule is abl?

A

Signal transducer (oncogene)

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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

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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
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25
Q

What type of molecule is APC? What is its function?

A

Tumor suppressor preventing signal transduction; prevents signal transduction by promoting degradation of beta-catenin

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26
Q

What type of molecule is NF-1? How does it function?

A

GAP (tumor suppressor); NF-1 incr. internal GTPase activity of Ras, thusly inactivating it

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27
Q

What type of molecule is ATM? How does it function?

A

Tumor suppressor involved in DNA repair; binds to double stranded breaks in DNA, then phosphorylates p53

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28
Q

Possible (medical) treatment for BRCA-linked ovarian cancer?

A

PARP (poly ADP ribose polymerase) inhibitors blocking transcription

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29
Q

Cancer associated with CHRPE (hypertrophy of retinal pigment spot)?

A

Familial adenomatous polyposis

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30
Q

Genes associated with Lynch syndrome (HNPCC)? What do these encode for?

A

MLH1, MSH2; DNA mismatch repair proteins

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31
Q

Melanoma evaluation

A

ABCDE: Asymmetry, Border irregularity, Color variation, Diameter, Evolution

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32
Q

“Naked nuclei” on skin biopsy

A

Merkel cell carcinoma

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33
Q

What type of skin lesion expresses factor XIIIa and contains collagen I?

A

Dermatofibroma

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34
Q

What are Pautrier’s microabscesses?

A

Atypical lymphocyte aggregates seen in adult (CD4) T cell lymphoma/leukemia, Sezary syndrome, Mycosis fungoides

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35
Q

What is Sezary syndrome? What disease is it associated with?

A

Cutaneous T cell lymphoma with tumor cells in the blood, generalized erythema and systemic manifestations (high mortality)

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36
Q

“Islands of cuboidal cell surrounded by basement membrane-like material”

A

Cylindroma: benign eccrine neoplasm (adnexal neoplasm)

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37
Q

Schwannoma IHC and histologic presentation

A

S-100; “palisading spindle cells”

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38
Q

Fibromatosis IHC presentation

A

Mutation in beta catenin

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39
Q

List the benign vascular tumors, what is their IHC presentation?

A

[Cavernous] hemangioma, pyogenic granuloma (misnomer); CD31 & CD34

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40
Q

Granular cell tumor IHC and histologic presentation

A

S-100 (spindle cell origin); “Round cells with pink cytoplasmic granules”

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41
Q

Dermatofibrosarcoma Protuberans (DFSP) IFC profile

A

CD34

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42
Q

Synovial sarcoma IHC profile

A

Express epithelial markers (cytokeratin and epithelial membrane antigen)

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43
Q

Leiomyosarcoma IHC profile

A

Smooth muscle actin and desmin

44
Q

Angiosarcoma IHC profile

A

CD31 & CD34

45
Q

Rhabdomyosarcoma IHC profile

A

Desmin & myogenin

46
Q

“Grape-like growth in genitourinary tract of a child”

A

Botryoid variant of embryonic rhabdomyosarcoma

47
Q

Wilm’s tumor chromosome and associated clinical presentation

A

11p (WT-1); WAGR - Wilm’s tumor, Aniridia, Genitourinary defects, Retardation

48
Q

Cowden syndrome gene and cancers

A

PTEN; Papillary papules, Thyroid cancer, Endometrial (and breast) cancer, iNtestinal hamartomatous polyposis, RCC, macrocephaly, hyper pigmented macules of the glans

49
Q

Von Hippel Lindau locus and cancers

A

3p (VHL gene); brain (hemangioblastomas also of spinal cord) cancer, “kidney” (cysts, clear cell, pheos) cancers, also endolymphatic sac tumors

50
Q

Peutz-Jeghers syndrome gene and presentation

A

STK11; hamartomatous intestinal polyps, mucocutaneous hyperpigmentation (dark blue to brown spots around eyes and mouth)

51
Q

Basal cell nevus syndrome gene(s) and symptoms

A

PTCH & SUFU; basal cell carcinoma, jaw cysts, macrocephaly, coarse facial features, medulloblastoma (cerebellum) + calcification of fall cerebri

52
Q

Gene(s) associated with hereditary melanoma

A

INK4A, CDK4, CDKN2A

53
Q

Multiple Endocrine Neoplasia type 2 gene and symptoms

A

RET; medullary thyroid cancer, tall stature, mucosal neuromas of lips and tongue, pheochromocytoma, parathyroid adenomas

54
Q

Ataxia-telangiectasia genetic etiologies and clinical presentation

A

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
Q

Disease(s) associated with ATM mutation

A

Ataxia-telangiectasia, breast cancer, recently pancreatic cancer

56
Q

Cancer associated with Auer rods

A

AML (no Auer rods for ALL) and APML

57
Q

What does MBL stand for? Why is it important?

A

Monoclonal B cell lymphocytosis; precursor to CLL

58
Q

MBL/CLL presentation

A

Usually asymptomatic, but monoclonal B lymphocytes expressing kappa light chain and CD19, CD20 (but weak), CD23, CD5 positive on flow cytometry

59
Q

Reed-Sternberg cells

A

Classic Hodgkin’s lymphoma (remember they’re CD30+, CD20-)

60
Q

Classic Hodgkin’s lymphoma subtypes and features

A

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
Q

Nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) features

A

o Lymphocytic and/or histolytic cells also called “popcorn bodies”
o CD15-, CD20+, CD30-, CD45+

62
Q

What differentiates aggressive from indolent non-hodgkin’s lymphoma?

A

Elevated LDH (but also night sweats, weight loss, rapid growth + sometimes pain/tender LN)

63
Q

Mantle Cell Lymphoma (MCL)

A

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
Q

Follicular lymphoma

A 
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
Q

Cyclin D1 function

A

Phosphorylates Rb, causing E2F to be released and leading to G1 to S transition

66
Q

What are the only two B cell malignancies that express CD5?

A

CLL and MCL

67
Q

Hairy cell leukemia

A

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
Q

Cause and symptoms of Lymphoplasmocytic Lymphoma

A

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
Q

Immunophenotype of Primary Mediastinal (thymic) B cell Lymphoma

A

CD30+

70
Q

Immunophenotype of primary effusion lymphomas

A

CD30+, CD138+

71
Q

“neoplastic cells with defective homing receptors/adhesion molecules…”

A

Intravascular LBCL

72
Q

Burkitt’s Lymphoma

A

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
Q

T cell Large Granular Lymphocytic leukemia

A

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
Q

Mycosis fungicides/Sezary syndrome Immunophenotype

A

CD4+, CD7-

75
Q

Peripheral T cell lymphoma NOS symptoms and immunophenotype

A

Eosinophilia, pruritus; CD2, CD3, CD4, CD30

76
Q

Anaplastic large cell lymphoma gene, translocation and pathologic hallmark

A

ALK; t(2;5); large anaplastic cells with horseshoe nuclei and voluminous cytoplasm

77
Q

Multiple myeloma clinical indications

A

Bence-Jones proteins, M component and CRAB (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions e.g. fracture susceptibility)

78
Q

Cancers associated with EBV

A

Burkitt’s lymphoma, Hodgkin’s lymphoma, B cell lymphoma in immunocompromised (e.g. AIDS), extranodal NK/T cell lymphoma, nasopharyngeal carcinoma

79
Q

EBV genes and effects

A

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
Q

HBx protein function, associated virus and cancer(s)

A

Activates growth promoting genes, binds p53; hepatitis B; hepatocellular carcinoma

81
Q

Virus associated with “tax” gene? What does this gene do?

A

HTLV-1; dysregulates cell cycle and causes genome instability

82
Q

What does MALT stand for? Associated pathogen and translocation?

A

Mucosal Associated Lymphoid Tissue lymphoma; H pylori; t(11;18) in antibiotic-refractory cases

83
Q

What are Downey cells?

A

Atypical T lymphocytes seen in EBV infection

84
Q

Disease associated with Paul-Bunnell heterophile antibody? What antibody can be “confused” with them?

A

EBV; Forssman antibodies (remember they need to be removed before doing the heterophiles antibody test)

85
Q

How do you determine normal % cellularity of bone marrow?

A

100-age

86
Q

AML generalized and subtype presentations

A

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
Q

Translocation(s) associated with AML

A

t(8;21), also remember trisomy 4

88
Q

APML presentation and associated mutation(s)

A

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
Q

“erythroid ringed sideroblast…”

A

Myelodysplastic Syndrome

90
Q

MDS disease hallmark(s)

A

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
Q

What disease is often mistaken for MDS? Why? How to differentiate?

A

Copper deficiency; anemia and neutropenia; thrombocytopenia rare in copper deficiency but peripheral neuropathy present

92
Q

Most common gene associated with MPN

A

JAK2V617

93
Q

Disease associated with CSF3R mutation

A

Chronic neutrophilic leukemia

94
Q

Philadelphia translocation is pathognomonic for what disease?

A

t(9;22) pathognomonic for CML

95
Q

Gene associated with TKI resistance? What cancer are these used to treat? What side effect/toxicity is shared by all TKIs?

A

BCR-ABL1 T315I; CML; bone marrow suppression

96
Q

Polycythemia Vera symptoms and labs

A

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
Q

“teardrop-shaped RBCs…” pathognomonic of what?

A

Primary Myelofibrosis (PMF)

98
Q

Mutations common to ET and PMF

A

JAK2, CALR, MPL

99
Q

Histologic findings associated with lymphoid hyperplasia (in HIV)

A

Follicular + inter follicular hyperplasia (“naked follicles”), dissolution of cortical germinal centers (follicular lysis), hyalinization of germinal centers (profound lymphoid depletion)

100
Q

Virus and cancer associated with koliocytes

A

HPV; squamous cell carcinoma cervix

101
Q

Where is P17 found?

A

HIV-1 vision membrane

102
Q

Lymphomas and translocations associated with HIV

A

Non-Hodgkin’s lymphomas - DLBCL, Burkitt’s, CNS lymphoma, primary effusion lymphoma; t(8;14), t(8;2), t(8,22)

103
Q

Important histologic features of Kaposi’s sarcoma

A

Spindle-to-epithelioid atypical epithelial cells, hemosiderin granules

104
Q

Cryptosporidiosis symptoms (at least in AIDS)

A

Chronic wasting, electrolyte imbalances, diarrhea, cysts in stool (dx via acid fast on stool)

105
Q

Everything from this block that increases LDH ;)

A

Pneumocystis jiroveci, aggressive non-Hodgkin lymphoma, APML (spontaneous tumor lysis), Polycythemia Vera

Hematology/Oncology (3 decks)

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