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Block 2 > Cancer/Neoplasms > Flashcards

Cancer/Neoplasms Flashcards

1
Q

Heritable cancers

A
  • retinoblastoma: RB1
  • hereditary breast and ovarian cancer: BRCA1, BRCA2
  • Cowden syndrome: PTEN
  • familial adenomatous polyposis (FAP): APC
  • Lynch syndrome: MLH1, MSH2
  • Li-Fraumeni syndrome: TP53
  • multiple endocrine neoplasia type 1: MEN1
  • multiple endocrine neoplasia type 2: RET
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2
Q

Cancer cachexia

A

wasting of tissues due to excess catabolism and/or decreased nutrition

mediated by tumor necrosis factor (TNF)

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3
Q

Carcinoma vs. sarcoma

A

Carcinoma:
- epithelial cell origin
- cohesive lobules, glands, reactive stroma
- spreads through lymphatic ducts into lymph nodes

Sarcoma:
- mesenchymal cell origin
- spindle cells, no lobular patterns, connective tissue tumors, elongated nuclei/cytoplasm
- spreads through vasculature and blood stream into lungs/veins

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4
Q

Stains and tumor types

A
  • Carcinoma: keratin stain +
  • Lymphoma: CD45 stain +
  • Melanoma: S100 stain +
  • Smooth muscle tumor: smooth muscle actin stain +
  • Neuroendocrine tumor: keratin, synaptophpysin/chromogranin stain +
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5
Q

Keratin+

A

carcinoma, maybe neuroendocrine tumor

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6
Q

Smooth muscle actin+

A

smooth muscle tumor

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7
Q

CD45+

A

lymphoma

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8
Q

Synaphysin & Chromogranin

A

neuroendocrine tumor

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9
Q

S100+

A

melanoma

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10
Q

CDX2+

A

colorectal cancer

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11
Q

TTF1+

A

lung adenocarcinoma

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12
Q

Paraneoplastic syndrome

A

Signs and symptoms that occur in pts with cancer and cannot be explained by the tumor:
- unexplained anemia
- unintended weight loss
- hypercoagulable state => nonbacterial thrombotic endocarditis
- fatigue
- hypercalcemia: due to parathyroid hormone-related protein (PTHrP)
- Cushing syndrome: due to ACTH
- venous thrombosis (Trousseau syndrome)

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13
Q

Molecular changes associated with malignant tumors

A

CTLA4
- surface protein that binds to CD80/CD86 on APCs, turning them off
- early-acting in lymph nodes

PD1 & PD-L1/PD-L2
- PD expressed on activated T-cells, NK cells, B-cells, APCS
- PD-L1 expressed on tumor cells
- binding inhibits innate and adaptive immune responses
- late-acting in peripheral tissues

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14
Q

Tumor markers

A
  • Prostate specific antigen (PSA)
  • Carcinoembryonic antigen (CEA): colon, stomach, pancreas, breast
  • Alpha-fetoprotein (AFP): hepatocellular carcinoma, yolk sac/embryonal
  • Calcitonin: medullary carcinoma of the thyroid
  • CA-125: ovarian cancers
  • Syndrome of inappropriate antidiuretic hormone (SIADH), ADH: small cell lung carcinoma
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15
Q

Amyloidosis markers

A
  • Ab2m: b2 microglobulin = renal failure
  • AIAPP: islet amyloid = Type 2 diabetes
  • ATTR: transthyretin = senile cardiac amyloid
  • Acal: procalcitonin = medullary thyroid carcinoma
  • AL: immunoglobulin light chains = plasma cell dyscrasias
  • AA: serum amyloid associated = chronic inflammation
  • Ab: cerebral amyloid b = Alzheimer’s disease
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16
Q

Acute myeloid leukemia (AML)

A

Pathology:
- neoplasm conposed of >= 20% myeloid blasts
- t(15;17)(q22;q12), PML-RARA gene
- myeloid lineage: CD13+, CD33+, CD117+, MPO+

Symptoms:
- no mature neutrophils; lots of immature myeloblasts
- Auer rods in blasts = crystalized granules
- anemia, neutropenia, thrombocytopenia
- Disseminated intravascular coagulation (DIC)
- Leukostasis when WBC > 100,000/uL

Treatment:
- t(15;17) has favorable prognosis after tx with ATRA (all-trans retinoic acid) and arsenic

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17
Q

Myelodysplastic syndrome (MDS)

A
  • blast count < 20%
  • dysplastic hematopoietic precursors, but there can be mature cells
  • up to 40% of pts progress to AML
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18
Q

Myeloproliferative neoplasms (MPNs)

A
  • proliferation of one or more hematopoietic lineages, not necessarily immature blasts
  • mutation leading to constitutively active tyrosine kinase
  • splenomegaly and hepatomegaly common due to extramedullary hematopoiesis
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19
Q

Chronic myeloid leukemia (CML)

A

Pathology:
- t(9;22); BCR-ABL1 gene on Philadelphia chromosome
- tyrosine kinase always turned on ==> proliferation of mature and immature myeloid elements

Symptoms:
- seen in older patients
- peripheral blood leukocytosis: neutrophils and immature granulocyte precursors
- basophilia
- splenomegaly

Treatment:
- Imatinib, tyrosine kinase inhibitor
- chronic ML can become acute leukemia if blasts > 20%

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20
Q

Acute lymphoblastic leukemia (ALL)

A
  • proliferation and accumulation of neoplastic, immature lymphoid cells
  • B-cell ALL & T-cell ALL
  • CD34+, TdT+, CD10+
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21
Q

B-cell ALL (B-ALL)

A
  • most common childhood leukemia (80%)
  • t(12;21) ETV6-RUNX1 has good prognosis
  • arises in bone marrow; peripheral blood usually involved
  • CD10+, TdT+, CD19+, CD79+
  • serum lactate dehydrogenase (LDH) and uric acid commonly increased
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22
Q

T-cell ALL (T-ALL)

A
  • presents in adolescence
  • involves bone marrow and thymus (mediastinal mass)
  • CD10+, TdT+, CD1+, CD2+, CD3+, CD4+, CD5+, CD7+, CD8+
  • mutations in NOTCH1, FBXW7
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23
Q

Polycythemia vera (P. vera)

A
  • proliferation of erythrocytes (can also see panmyelosis)
  • increased Hgb and RBC mass; RBCs are normocytic and normochromic
  • mutations in JAK2 kinase
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24
Q

Primary myelofibrosis

A
  • megakaryocytic hyperplasia and bizarre dysplasia => eventual marrow failure due to fibrosis => hematopoiesis moves to spleen (extramedullary hematopoiesis) => splenomegaly
  • peripheral: teardrop RBCs, immature granulocytes, atypical platelets
  • bone marrow: tightly clustered megakaryocytes with cloud-like nuclei, increased marrow fibrosis, intrasinusoidal hematopoiesis
  • mutations in JAK2, CALR, MPL
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25
Q

Essential thrombocytothemia (ET)

A
  • proliferation of platelets (up to millions/uL)
  • bone marrow: clusters of “staghorn” megakaryocytes
  • mutations in JAK2, calreticulin, thrombopoietin receptor
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26
Q

Chronic lymphocytic leukemia (CLL)

A
  • most common leukemias of adults in the West
  • most of cancerous B-lymphocytes are in the blood
  • peripheral blood: small lymphocytes with scant cytoplasm, nucleus with clumped chromatin, smudge cells
  • lymph nodes: pseudofollicles with proliferation centers
  • CD19+, CD20+, CD22+, CD23+, CD5+
  • Richter transformation: when CLL transforms into more aggressive ALL
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27
Q

Small lymphocytic lymphoma (SLL)

A
  • just like CLL, but most of cancerous B-lymphocytes are in lymph nodes and lymphoid tissue
  • 4% of non-Hodgkin’s lymphoma
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28
Q

Hairy cell leukemia (HCL)

A
  • rare B-cell neoplasm: infiltration of lymphoma cells into bone marrow, blood, liver, spleen
  • hair-like projections on lymphoma cells
  • pancytopenia, splenomegaly (obliteration of white pulp), diffuse interstitial infiltrate of lymphoma cells in bone marrow
  • CD19+, CD20+, CD11c, CD25+, CD103+
  • BRAF oncogene mutation
  • Tx: alpha-interferon, purine analogues; good response to chemotherapy
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29
Q

Multiple myeloma (MM)

A
  • > 10% clonal plasma cells in bone marrow
  • serum M-protein > 30g/dL
  • atypical plasma cells: Mott cell (cytoplasmic inclusions), plasmablasts, Dutcher body (intranuclear inclusion), Rouleaux formation (linking of RBCs)
  • plasma cells stain CD138
  • IL-6, MLP1a => RANKL => bone lytic lesions
  • produces free immunoglobulin light chains (Bence Jones proteins) that enter the urine

Asymptomatic/smoldering MM:
- absence of organ dysfunction
- 75% of pts progress from plasma cell myeloma to multiple myeloma (multiple tumors) over 15 years

Symptomatic MM:
- CRAB symptoms: hyperCalcemia, Renal dysfunction, Anemia, lytic Bone lesions

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30
Q

Monoclonal gammopathy of unknown clinical significance (MGUS)

A
  • < 10% clonal plasma cells in bone marrow
  • serum M-protein < 30g/dL
  • no end organ damage
  • precursor to multiple myeloma; risk of progression is 1% per year
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31
Q

Waldenstrom macroglobulinemia (Lymphoplasmacytic lymphoma)

A
  • non-Hodgkin’s lymphoma associated with abnormal production of monoclonal IgM antibodies ==> increased serum protein level ==> hyperviscosity (decreased vision)
  • > 10% monoclonal B cells
  • seen in older adults
  • agglutination of RBCs ==> hemolytic anemia
  • Russell body inclusions in lymphocytes
  • MYD88 mutations
  • incurable
32
Q

Acute T-cell leukemia

A
  • caused by human T-cell leukemia virus (HTLV-1)
  • endemic in Japan, Caribbean, Central Africa
  • increased lymphocytes, skin rash, lymphadonepathy, hepatosplenomegaly, hypercalemia
  • CD2+, CD3+, CD5+, CD25+
  • clover-leaved lymphocytes
33
Q

Sezary syndrome

A
  • CD4+ T-cell lymphoma
  • triad: erythroderma, generalized lymphadenopathy, neoplastic T-cell population with cerebriform nuclei
  • CD2+, CD3+, CD5+, loss of CD7 and CD26
  • mycosis fungoides = more prolonged cutaneous disease
34
Q

Classical Hodgkin’s lymphoma (CHL)

A
  • monoclonal lymphoid neoplasm composed of mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells (owl-eyes)
  • associated with EBV infection
  • CD30+, CD15+, CD45-
  • 95% of all Hodgkin lymphomas
35
Q

Non-Hodgkin’s lymphoma

A
36
Q

Follicular lymphoma

A
  • most common indolent NH lymphoma
  • painless generalized adenopathy (lymph nodes swollen)
  • splenic expansion of white pulp
  • t(14;18), BCL2
  • CD19+, CD20+, CD10+, BCL2+, BCL6+, CD5-
  • centrocytes: small cells with irregular/cleaved nuclear contours
37
Q

Burkitt lymphoma

A
  • post-EBV infection
  • t(8;14)
  • African (endemic): mandible, viscera-kidney, ovary, adrenal
  • sporadic: ileocecum, peritoneum
  • starry sky appearance: high proliferation, high mitotic rate with numerous apoptotic cells
  • very aggressive, responds to aggressive chemotherapy
38
Q

Diffuse large B-cell lymphoma

A
  • most common form of NH lymphoma in USA (80% adults, 20% children)
  • large lymphoid cells with large nuclei, prominent nucleoli, frequent mitotic figures
  • rapidly enlarging mass
  • aggressive tumor, can be cured by chemotherapy
  • BCL-2/6 mutations
  • CD19+, CD20+, BCL6+
39
Q

MALT (marginal zone) lymphoma

A
  • t(11;18)
  • memory B cell hypermutation; marginal zones typically present in splenic white pulp and Peyer’s patches of colon
  • mucosa-associated lymphoid tumors
  • associated with inflammation
  • H. pylori gastritis ==> gastric MALT
  • CD19+, CD20+, CD3-
40
Q

Anaplastic large cell lymphoma (ALK)

A
  • ALK gene on chromosome 2p23
  • large anaplastic cells
  • horseshoe nucleus with voluminous cytoplasm
  • CD30+, ALK+
  • good prognosis
41
Q

Mantle cell lymphoma

A
  • B-cell lymphoma most common in adult men
  • lymphomatous polyposis = when mantle zone lymphoma involves the GI tract, typically presents as “polyps”
  • t(11;14)
  • CD5+, cyclin D1+
42
Q

Treatable cancers important to know

A

Acute promyelocytic leukemia (APL):
- t(15;17)(q24.1;q21.1)
- PML-RARA gene
- responds to ATRA (all-trans retinoic acid) and arsenic

Chronic myeloid leukemia (CML):
- t(9;22)(q34;q11)
- BCR:ABL1 gene fusion
- responds to Imatinib, a tyrosine kinase inhibitor

43
Q

Antineoplastic classes

A
  1. Alkylating agents: CCNS, work by adding alkyl to DNA ==> crosslinked DNA ; nitrogen mustards, nitrosoureas
  2. S-phase inhibitors: CCS, antimetabolites
  3. Anti-tumor antibiotics: CCNS and CCS
  4. Natural products
  5. Hormonal: gonadal antagonists, gonadotropin-releasing analogues, glucocorticoids, aromatase inhibitors
  6. Miscellaneous: L-Asparaginase, small molecule inhibitors, cytokines, monoclonal antibodies, bone marrow growth factors
44
Q

Alkylating agents

A

Nitrogen mustards:
- cyclophosphamide

Nitrosoureas:
- carmustine

Misc. alkylating agents:
- cisplatin
- procarbazine
- busulfan

45
Q

Cyclophosphamide

A
  • alkylates DNA at N7 of guanine
  • hemorrhagic cystitis (dysuria, hematuria)
  • tx with mesna

“go to the cyclopHOSPhamide (hospital) if you get hemorrhagic cystitis”

46
Q

Carmustine

A
  • lipid-soluble, can cross blood brain barrier
  • CNS toxicity

“carMUSTine cross BBB”

47
Q

Cisplatin

A
  • crosslink with DNA at N7 of guanine
  • nephrotoxic; treat with mannitol
  • neurotoxic: high-frequency hearing loss

“ciSPLATin goes your kidney and brain”
“CNN: cisplatin-nephrotoxity-neurotoxity”

48
Q

Procarbazine

A
  • generates free radicals
  • CNS dysfunction, peripheral neuropathy, leukemogenic (AML)
  • disulfiram-like reaction with ethanol
49
Q

Busulfan

A
  • crosslinks DNA
  • pulmonary fibrosis

“pulmonary fibusulfan”

50
Q

S-phase antimetabolites

A
  • methotrexate
  • 6-mercaptopurine (6-MG) & 6-thioguanine (6-TG)
  • 5-fluorouracil (5-FU)
  • cytarabine
  • gemcitabine
51
Q

Methotrexate

A
  • binds to site of DHFR, inhibiting formation of THF and IMP (d.n. purine synthesis)
  • hepatotoxicity
  • tx with Leucovorin
  • clearance depends on renal function
  • resistance via increased expression of P-glycoprotein transporter

“meDHROotrexate”

52
Q

6-Mercaptopurine & 6-Thioguanine

A
  • purine analogue; inhibits de novo synthesis (HGPRT)
  • 6-MP is inactivated by xanthine oxidase, which is inhibited by allopurinol
  • when used concurrently with allopurinol, dosage of 6-MP must be reduced to 25-33%

“-purine = purine analogue”

53
Q

5-Fluorouracil

A
  • 5-FU ==> 5F-dUMP, which inhibits thymidylate synthetase ==> starves cells of thymine
  • mucositis, hand-foot syndrome
  • when used with Leucovorin, a smaller dose of 5-FU is needed

“FU = middle finger up”
“uracil = pyrimidine”

54
Q

Cytarabine

A
  • pyrimidine analogue
  • inhibits DNA polymerase (most S-phase specific)
55
Q

Gemcitabine

A
  • inhibits ribonucleotide reductase
  • blocks formation of dNTPs
56
Q

Antitumor metabolites

A

CCNS:
- doxorubicin & daunorubicin
- dactinomycin
- mitomycin

CCS:
- bleomycin

57
Q

Doxorubicin & Daunorubicin

A
  • CCNS
  • intercalates DNA, inhibits topoisomerase II
  • cardiotoxic: dilated cardiomyopathy
  • tx with Dexrazoxane
  • multidrug resistance via P-glycoprotein

“ruby = heart = cardiotoxicity”
“Dexrazoxane for Doxorubicin”

58
Q

Dactinomycin

A
  • CCNS
  • intercalates between GC base pairs
59
Q

Mitomycin

A
  • CCNS
  • bioreductive alkylating agent generated via liver metabolism
  • best drug for hypoxic tumors
60
Q

Bleomycin

A
  • CCS, G2-phase specific
  • generates free radicals
  • enzyme bleomycin hydrolase causes resistance to bleomycin
  • pulmonary and skin toxicity because those areas are low in bleomycin hydrolase
  • minimal myelotoxicity

“pulmonary fibleomycin”
“bleomycins = blisters”

61
Q

Natural product antineoplastics

A
  • vincristine & vinblastine
  • paclitaxel (TAXOL) & docetaxel
  • etoposide & teniposide
62
Q

Vincristine & Vinblastine

A
  • M-phase specific
  • prevents mitotic spindle formation
  • Vinblastine = bone marrow suppression, low neurotoxicity
  • Vincristine = neurotoxicity, minimal myelotoxicity
  • resistance via P-glycoprotein transporter

“Chris Christie is a neurotoxic mayor, blocked bridge”

63
Q

Paclitaxel (TAXOL) & Docetaxel

A
  • M-phase specific
  • inhibits disassembly of microtubules
  • peripheral sensory neuropathy
  • multidrug resistance

“pacliTAXI drives you around blocked bridge”

64
Q

Etoposide & Teniposide

A
  • late S-G2 phase specific
  • inhibits DNA topoisomerase II
  • multidrug resistance

“teniPOSIde, etoPOSIde = posse, 2 or more people (topoisomerase 2)”

65
Q

Hormonal antineoplastics

A

Gonadal hormone antagonists:
- tamoxifen: competes for binding at estrogen receptor site
- flutamide: binds to androgen receptor

Gonadotropin-releasing hormone analogues:
- leuprolide: short-term increases testosterone, long-term inhibits testosterone release

Glucocorticoids:
- prednisone: dissolution of lymphocytes (ALL, lymphomas, myelomas)

Aromatase inhibitors:
- anastrozole & letrozole: advanced breast cancer

66
Q

Miscellaneous antineoplastics

A

L-asparaginase

Small molecule inhibitors:
- imatinib
- ibrutinib
- bortezomib & carfilzomib
- olaparib

Cytokines:
- alpha-interferons
- interleukin-2 (aldesleukin)

Monoclonal antibodies:
- rituximab: CD20
- trastuzumab: HER2
- cetuximab: EGFR
- bevacizumab: vascular EGF
- ipilimumab: CTLA-4
- pembrolizumab: PD-1 receptor
- atezolizumab: IgG Ab against PD-L1

67
Q

L-Asparaginase

A
  • CCNS
  • used for cancers that require exogenous asparagine for growth
68
Q

Imatinib

A
  • inhibits tyrosine kinase activity of BCR-ABL1 oncogene in CML
69
Q

Ibrutinib

A
  • blocks Bruton’s tyrosine kinase signaling in B-cells
  • mantle cell lymphoma, CLL, small lymphocytic lymphoma
70
Q

Bortezomib & Carfilzomib

A
  • 26S proteasome inhibitor
  • multiple myeloma
71
Q

Olaparib

A
  • inhibits poly ADP ribose polymerase (PARP) used in DNA repair
72
Q

Alpha-interferons

A

hairy cell leukemia, early CML, T-cell lymphomas

73
Q

Rituximab

A

interacts with CD20 in non-Hodgkin’s lymphoma cells

74
Q

Trastuzumab

A
  • binds to human epidermal growth factor receptor 2 (HER2)
  • female breast cancers that overexpress HER2
75
Q

Aplastic anemia

A

Pancytopenia caused by bone marrow failure
- may be due to virus infections, Fanconi anemia: DNA crosslink repair defect ⇒ bone marrow failure
- toxic drug exposure
- Normocytic or macrocytic anemia
- Hypocellular fat-filled marrow
- splenomegaly (extramedullary hematopoiesis)

76
Q

Pure red cell aplasia

A

Severe reduction in reticulocytes (immature RBCs) in circulation and bone marrow
- Abnormal T cell function
- IgG antibodies that target erythroblasts
- bone marrow: marked reduction or absence of erythroid precursors

77
Q

Agranulocytosis

A

Absence of granulocytes or severe neutropenia
- drug-induced
- oral ulcers, sore throat, fever
- absolute neutrophil count < 500/mm3

Block 2 (10 decks)

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