Oncology Flashcards

1
Q

Pt with neurologic symptoms (paraneoplastic syndrome) and anti-Hu and anti-Yo Abs

A

Small cell lung cancer (SCLC)
Assoc with smoking
Tx - platinum agent (ie carboplatin, cisplatin) with etopside

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2
Q

What is the best way to assess prognosis for melanoma?

A

The depth

Vertical growth

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3
Q

What cancers are associated with multiple endocrine neoplasia (MEN) type 1?

A

3 P’s

  1. Pancreas = Zollinger-Ellison
  2. Pituitary = elevated prolactin
  3. Parathyroid = Hx of renal stones and a neck nodule
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4
Q

A pt with Down syndrome is at an increased risk for which cancer?

A

ALL

Fatigue, easy bruising, weight loss, fever

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5
Q

Most common cause of firm fixed lumps in the axillary lymph nodes

A

Invasive ductal carcinoma
Overexpress HER2/neu
Bx = anastomising sheets of pleomorphic cells

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6
Q

Pt presents with high WBC count with basophilia. See PMNs at all stages of maturity. Immature myelocytes and segmented PMNs. Dx and Tx?

A

Chronic myelogenous Leukemia (CML)
Tx - Imatinib
t(9;22) Philadelphia chromosome; Bcr-Abl
Contituitively active tyrosine kinase

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7
Q

A pt has worsening vision in his right eye. He has angiomas over the retina and a small hemangioblastoma in the cerebellum. Dx and what else might they develop?

A
von Hippel-Lindou
Hematuria
AD, VHL deletion on chr 3
Retinal, medullary, and cerebellar angiomas
Bilateral renal cell carcinoma
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8
Q

Which two sites are common sites of metastasis?

A

Liver - GI tract drains to hepatic poratal
Lung
Due to high blood volume in both

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9
Q

A pt reports new onset tonic-clonic seizure and 4 month history of bloody stools

A
Turoct syndrome
AD 
Colorectal and brain tumors
APC gene = polyposis and medulloblastoma
hMLH1 = DNA mismatch repair causring polyposis and glioblastoma multiforme
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10
Q

What are the 3 most common causes of cancer death in men?

A
  1. Lung
  2. Prostate
  3. Colorectal
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11
Q
A pt presents with crippling back pain.  CT shows lesions in the spine
Hgb - 10.2
Calcium - 13.1
Increased total protein
Dx?
A

Multiple Myeloma
Increased total protein = IgG
Decreased levels of normal Ig’s make them prone to infections
Back pain = lytic bone lesions

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12
Q

30 y/o female presents with severe knee pain x months but does not recall an injury. PE = effusiion. XR fx at the epiphyseal end of the femur. What cancer is associated?

A

Giant cell tumor
Benign primary bone tumor, but locally aggressive. Usually distal femur or proximal tibia
On XR = double bubble or soap bubble sign
Bx = oval or spindle-shaped cells along with scattered multinucleated cells
20-40 y/o women

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13
Q

Bone tumor in the metaphysis of long bones in males 10-20 y/o

A

Osteosarcoma
Raises the periosteum causing either a triangular periosteal shadow (Codman triangle) or radial reactive bone formation (sunburst growth pattern)

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14
Q

A pt with Small cell Lung Carcinoma is at risk of which paraneoplastic syndrome?

A

Overproduction of ACTH and ADH
ACTH increases glucocorticoids causing Cushings syndrome (weight gain, redistribute body fat, striae, moon facies, poor wound healing)

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15
Q

Pt is post-menopausal, 40pack year hx presents with progressive constipation and frequent urination. CXR shows circular lesion overlying the left hilum. Decreased serum phosphorus

A

Central bronchogenic carcinoma
progressive constipation and frequent urination = hypercalcemia, suggests a cancer producing parathyroid homone-related peptide (PTHrP)
Squamous cell carcinoma is a bronchogenic carcinoma that produces excess PTHrP

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16
Q

pt presents with RUQ pain and a bruit over the liver. On bx = lack of portal areas, trabeculae are composed of multiple layers of malignant hepatocytes with high nuclear-to-cytoplasm ratio and pleiomorphic

A

Hepatocellular Carcinoma
Bruit is heard if tumor partially obstructs a. flow to the liver.
HCC assoc with elevated alpha-fetoprotein levels
Chronic HCV and/or HBV -> cirrhosis -> predisposes individual to HCC

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17
Q

What is primary biliary cirrhosis?

A

Autoimmune
Lymphocytic infiltrates and granulomas in the biliary tract
Increased mitochondrial Ab associated with CREST syndrome, RA, and celiac

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18
Q

What is the normal function of Rb?

A

Prevents cell-cycle progression past the G1/S checkpoint
Normally binds the E2F transcription factor in quiescent cells
LOF is associated with osteosarcoma and retinoblastoma

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19
Q

50 y/o female presents with HA localizing to the right side of her head. MRI shows a tumor attached to the dura mater. Bx confirms tumor arises from arachnoid. Dx and additional histology?

A

Meningioma

psammoma bodies, synctial, fibroblastic, transitional, secretory, and microcystic

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20
Q

Pt presents with fatigue, weakness, weight loss x 4 mo. Vision is deteriorating, several severe nosebleeds. PE hepatosplenomegaly, increased total protein level. Electrophoresis reveals a large spike in the gamma region. No skeletal changes

A

Waldenstrom macroglobulinemia
Weakness, weight loss, hyperviscosity
B cell neoplasm with IgM overproduction leads to:
impaired cranial blood flow (HAs), impaired ocular blood flow (visual disturbances)
NO bone lesions or renal dysfunction
monoclonal “M spike”

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21
Q

How do you distinguish Waldenstrom macroglobulinemia from Multiple myeloma?

A

Waldenstrom has syx of hyperviscosity (HA, vision changes)

Multiple myeloma = has bone and renal abnormalities

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22
Q

Which dz have a M spike on electrophoresis?

A

Waldenstrom macroglobulinemia
plasma cell dyscrasias
multiple myeloma
monoclonal gammopathy of undetermined significance (MGUS)

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23
Q

How do you identify Monoclonal gammopathy of undetermine significance from other dz’s with M spike?

A

asymptomatic due to lower levels of protein in the serum (no viscosity syx)
Some pts may experience polyneuropathy
Premalignant lesion that may progress to multiple myeloma

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24
Q

7 y/o presents with ataxia and labs show HCT 55%. Gadolinium scan reveals a primary brain tumor. Bx = foamy stromal cells within a highly vascular neoplasm. Dx?

A

von Hippel-Lindau (VHL)
AD, chr 3
brain tumor = hemangioblastoma, primary brain tumor found in the cerebellum of children
VHL will have increased erythropoietin producing a secondary polycythemia

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25
5 y/o is brought to the ED with projectile vomiting and HA. Trouble walking x 2 mo. PE truncal ataxia and papilledema. CT shows a mass at the cerebellar vermis and enlarged ventricles. Dx and histology?
Medulloblastoma, most common childhood tumor of the cerebellar midline primitive neuroectodermal tumor with small blue cells (Homer-wright cells) arranged in rosettes surroundign a PMN. High nuclear:cytoplasmic ratios Gait disturbances and ataxia = cerebellar vermis HA, papilledema = obstructive hydrocephalus
26
What are the 3 primary brain tumors of childhood that can result in hydrocehphalus by obstructing the fouth ventricle?
Medulloblastoma Ependymomas Hemangioblastomas
27
67 y/o landscaper presents with a flesh-colored pearly papule with a central telangiectasia on his right forearm. Bx shows islands of tumor within mucinous dermis
Basal cell carcinoma | Locally invasive but usually non-metastatic
28
A 65 y/o smoker has a trasnbronchial bx showing several layers of well differentiated, organized squamous epithelia contained above the basement membrane. What term describes this change?
Metaplasia | Normal bronchi = pseudostratified columnar ciliated epithelium
29
What DNA-alkylating agent is very commonly used in breast cancer and what should it be coadministered with to prevent AE's?
Cyclophosphamide | Give with Mesna to avoid hemorrhagic cystitis (counteracts acrolein)
30
A pt presents with worsening low back pain, increased urinary frequency and blood in the urine. Imagine reveals osteoblastic metastasis to vertebral bodies. Dx and Tx?
Prostate cancer PSA > 4 Tx - Leuprolide and flutamide
31
What is the MOA of leuprolide
GnRH analog suppresses the release of LH in prostate cancer
32
What is the MOA of flutamid?
nonsteroidal antiandrogen competitvely inhibits androgens at the testosterone receptor
33
Pt with a cancer hx presents with ecchymoses, intracranial hemorrhage, focal neurologic signs
Metastatic melanoma | Frequent source of metastatic lesions in the brain
34
Of all of the cancers that metastasize to the brain, which two are likely to cause intracranial bleeds?
Renal cell carcinoma Melanoma Because they are very vascular and prone to hemorrhage
35
A brain mass is resected and pathology describes whorls of fibrous tissue and calcified concentric rings. Dx?
Meningothelial On CT - avidly enhancing mass with dural attachment Second most common primary brain tumor in adults Slow growing, from meningothelial cells Calcified concentric rings = psammoma body
36
In which cancers do you see Psammoma bodies?
``` Papillary adenocarcinoma of the thyroid Serous papillary cystadenocarcinoma of the ovary Mesothelioma Meningioma PSaMMoma ```
37
A pt with chronic renal insufficiency is dx'd with transitional cell carcinoma of the bladder. What chemo drug should be avoided?
Cisplatin AE's nephrotoxicity and acoustic nerve damage. Pts should be vigorously hydrated Other nephrotoxc agents = streptomycin, nitrosoureas, methotrexate, mithramycin, cyclophosphamide. Bleomycin should also be avoided because renal insufficiency worsens pulmonary syx
38
Which cancers tend to metastasize to bone?
``` Permanently Relocated Tumors Like Bone Prostate Renal Cell Carcinoma Testes/Thyroid Lung Breast ```
39
Which cancers tend to metastasize to the brain?
``` Lots of Bad Stuff Kills Glia Lung Breast Skin (melanoma) Kidney (renal cell carcinoma) GI (colon) ```
40
Which cancers tend to metastasize to the liver?
``` Cancer sometimes penetrate Benign Liver Colon Stomach Pancreas Breast Lung ```
41
Pt presents with tonic clonic seizure due to hyponatremia. Which cancer is at fault?
Small cell lung cancer Paraneoplasmic syndromes: 1. Secretes ADH causing SIADH 2. Secretes ACTH causing Cushing syndrome 3. Lambert-Eaton myasthenic syndrome b/c host Ab cross-reacts with presynaptic calcium channels
42
Paraneoplastic syndrome associated with Squamous lung carcinoma?
PTHrP causing hypercalcemia
43
A large adenocarcinoma of the stomach at the pyloric zone near the pyloric sphincter on the lesser curvature would cause what other syx due to mass effect?
Jaundice Adenocarcinoma impinges the omental foramen which is partially formed by the hepatoduodenal ligament. This ligament also contains the bild duct, hepatic a., and hepatic portal v. Obstruction of bile duct = cholestasis and conjugated hyperbilirubinemia
44
What two injection tx's are used in age-related neovascular macular degeneration by inhibiting vascular endothelial growth factor (VEGF)
``` Ranibizumab = mAB that binds VEGF Pegaptanib = pegylated anti VEGF aptamer. ```
45
What other cancer drugs in a mAB against VEGF?
Bevacizuman Use in colon, breast, non small cell lung cancer AE = HTN and risk of bleeds
46
What is the MOA of bleomycin?
binds DNA and causes single stranded and double stranded breaks Use bleo in melanoma, sarcoma, squamous cell carcinoma, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell tumors AE = pulmonary fibrosis (Ground glass appearance on CXR)
47
Bx of a LN shows numerous irregularly sized follicles and the neoplastic cells appear similar to normal germinal cener B lymphoctyes
Follicular lymphoma t(14;18) bcl-2 anti-apoptotic gene Syx of waxing and waning painless lymphadenopathy tx - rituximab and/or cytotoxics
48
Smudge cell on smear. Dx and defect in which cell line?
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) Defect in B cell (CD5/CD19/CD20/CD23 +)
49
GM-CSF is coadministered with myelosuppressive chemo to prevent complications. This therapy increases cell types differentiated from which precursor?
Myeloid Stem Cell Produces: PMNs, basophils, eosinophils, macrophages, and platelets Avoids neutropenia and thrombocytopenia in the pt NOTE will not correct anemia
50
Tx used in ovarian cancer and an adjuvant in breast cancer that hyperstablizes microtubules?
Paclitaxel | Specific to M phase
51
Acute promyelocytic leukemia (APL) is type 3 acute myelogenous leukemia (AML) is characterized by which translocation?
t (15;17) | fusion of PML with retinoic acid receptor
52
To which family of molecules does the oncogene ras belong to?
GTP binding proteins Ras is a g protein that cycles between the activated ras-GTP and inactive ras-GDP. Involved in signal transduction leading to cell growth, differentiation, and survival
53
What medication should be given to prevent the Cushings syndrome associated with small cell lung cancer?
Ketoconazole or metyrapone | Binds 11-b-hydroxylase in the adrenal and inhibits ACTH activity
54
Osteoblastic bone lesions are suggestive of which cancer in older men?
Prostatic adenocarcinoma
55
Osteolytic lesions are associated with which cancer?
Multiple myeloma
56
An oncologist recommends a drug that causes DNA strand breaks through formation of free radicals. What is the drug and what is the most severe toxicity?
Bleomycin - produces superoxide and hydroxide free radicals that lead to DNA cleavage Toxicity - Interstitial pulmonary fibrosis (~10% of pts)
57
Which drugs are known to cause Pulmonary fibrosis?
``` Busulfan Bleomyacin Amiodarone Methotrexate Nitrofurantoin Radiation therapy to the chest ```
58
Pt presents with a palpable mass in the flank and multiple tumors in the lung. Removal of the mass shrinks the lung foci. Which immunotherapeutic agent would benefit this pt?
Recombinant IL-2 (aldesleukin) Following removal of the renal cell carcinoma (RCC) pts often have immune-mediated antitumor activity IL-2 stimulates T cell proliferation and augments this response
59
Pt presents with dizziness, tinnitus, and poor balance x 3 mo presents with a mass at the cerebellopontine angle. Bx = compact areas of spindle cells with pink cytoplasm that form whorls and palisades
Acoustic Schwannoma
60
A toddler presents with a nontender mass in the abdomen. Also partial loss of the child's iris. Dx?
WAGR syndrome Wilms tumor Aniridia (partial or complete lack of the iris) Genital anomalies (Gonadal dysgenesis, hypospadias, cyrptorchidism) Mental retardation
61
52 y/o woman presents with eczematous and ulcerated lesion of the left nipple. What should she be evaluated for?
Pt is presenting with Paget dz of the breast and should be evaluated for Ductal breast carcinoma (always present in paget's) Bx of paget's halo-like cells
62
How do most tumors become resistant to chemotherapy?
Tumor cell alteration of the drug target | Chemo selects for cells that are insensitive the same way abx do with bacteria
63
Two types of cancer associated with Rb
Retinoblastoma (eye) Osteosarcoma LOF RB binds and inactivates E2F and accelerates cell cycle progression
64
A pt with BRCA1 mutation begins chemo and experiences myelosuppression that is reversed Leucovorin. What was the chemo drug?
Methotrexate S phase Folic acid analog and inhibits dihydrofolate reductase AE = myelosuppresion
65
A pt presents with Barrett esophagus. What medication should they start?
Precursory to esophageal adenocarcinoma. Intestinal epithelium replaces normal squamous epithelium. Tx - omeprazole
66
A pt presents with B syx, lymphadenopathy, and mediastinal lymphadenopathy. Dx?
``` Hodgkin lymphoma, nodular sclerosing subtype mediastinal lymphadenopathy = sclerosing subtype Lacunar cells (a variant of RS) cytoplasmic retraction occurs during tissue fixation and calloagen deposition ```
67
What is the MOA of Rituximab?
mAB against CD 20 (B lymphocytes) | Used in follicular lymphoma
68
t(11;14)
Mantle cell lymphoma
69
t(15;17)
Acute pro-myelocytic leukemia
70
Tx regimen for prostate cancer?
Eliminate Ball cancer Etoposide Bleomycin (or Ifosfamide) Cisplatin
71
When is tamoxafin contraindicated?
SERM, estrogen antagonist in breast but estrogen agonist in endometrium bone and hepatic tissue Do not use in women at risk for endometrial carcinoma (ie still has their uterus)
72
A pt presenting with gout shortly after initiating cytotoxic chemotherapy has what and has risk of developing?
Tumor lysis syndrome - increased uric acid, potassium, phosphate and decreased calcium Risk of dangerous cardiac arrhythmia due to excess K+ Tx with allopurinol, glucose, insulin
73
Most common cause of vaginal bleeding in a post menopausal woman?
Endometrial cancer | Greatest risk factor - Tamoxifen use
74
Pt presents with episodic bouts of sweating, tachycardia, and HTN. Father and brother had similar syx. Dx and what else is she likely to develop?
Pheochromocytoma Confirm dx with urine catecholamines and vanillylmandelic acid Likely to be either MEN2A or MEN2B and pt is at risk of developing - thyroid and parathyroid cancer (2A) or thyroid and multiple mucosal neuromas (2B)
75
Pt presents with back pain, jaundice, fever, night sweats, anorexia. Strange swelling in arms and legs lasting days and then arising in a new place. Dx the tumor and what is causing the vascular pathology?
Dx - pancreatic cancer Causing a neoplastic syndrome called Trousseau's syndrome: migratory thrombophlebitis due to liberation of clotting factors (ie tissue factor)
76
What two things should make you think of pancreatic cancer
Smoking, obstructive jaundice
77
What is Zollinger-Ellison syndrome?
Caused by a gastrinoma (gastrin secreting tumor of the pancreas or duodenum), often presents as duodenal ulcers (epigastric pain relieved by eating) Associated with MEN1
78
A smoking pt presents with a FHx significant for paternal grandfather with a MI, breast cancer in his sister. He presents with flank tenderness and a palpable mass. Dx?
Renal Cell Carcinoma (histology = unusually clear cells with cytoplasm rich in lipids and glycogen) Increased incidence of RCC in smokers and pts with VHL
79
A pt with CML is at risk of developing if the condition progresses?
DIC occurs shortly before blast crisis in all types of leukemia
80
Expression of which tumor cell protein determines if a pt will respond to tamoxifen
Estrogen receptors (and or progesterone) Correlates with better prognosis If a breast tumor has estrogen receptors it will require antiestrogen therapy regardless of its staging
81
Pt presents with jaundice and epigastric pain with a palpable nontender gallbladder. What should you be concerned about?
Pancreatic cancer Courvoisier sign = jaundice + palpable nontender gallbladder This sign is strongly associated with pancreatic cancer Tx = resection
82
What is the function of the t(14;18) fusion protein?
chr 14 = Ig heavy chain | chr 18 = bcl-2, prevents apoptosis
83
MOA of doxorubicin?
DNA intercalation | Also daunorubicin
84
Bx of a lung lesion with scant cytoplasm, areas of necrosis, and "salt and pepper" nuclei
Small cell carcinoma
85
Pt presents with dysarthria, worsening HA, n/v. MRI shows area of necrosis and localized edema. On bx - foci of necrosis amid highly anaplastic pseudopalisading cells
Glioblastoma multiforme Most common malignant brain tumor in adults Characterized by hemorrhagic and necrotic foci surrounded by pseudopalisading cells
86
MOA of exemestane?
aromatoase inhibitor prevents conversion of testosterone to estradiol and androstenedione to estrone. Used in post menopausal women with hormone-responsive breast cancer Use after a tomoxifen regimen
87
During treatment of multiple myeloma a pt states that he has been stumbling and feeling tingling in his feet. Which drug caused this?
Vincristine | Causes neurotoxicity including areflexia and peripheral neuritis
88
Bx of ovarian masses demonstrate malignant cells with an off-center nucleus and stains heavily for mucin. Where did this metastasize from?
The stomach | This is a krukenberg tumor and the ovary is a site for metastasis for gastric adenocarcinomas
89
A pt presenting with n/v and diarrhea following methotrexate use should be supplemented with?
Folinic acid = leucovorin | Counters the myelosuppresive effect of methotrexate
90
18 y/o presents with inability to balance and retinal hemangioblastomas. FHx significant for a mom with a brain tumor. What else is he likely to develop?
Renal Cell Carcinoma | VHL = hemangioblastoma + bilateral RCC (flank pain, palpable mass, hematuria)
91
36 y/o Asian male presents with a demyelinating dz with bilateral lower extremity weakness, back pain, and urinary incontinence. Gradual progression over years. Eczamatous exudative rash affecting his scalp, axillaie, and groin. Hypercalcemia. Which virus caused this?
Juman T cell Lymphotrophic virus 1 Causes adult T lymphocyte leukemia and myelopathy Adult TLL commonly presents with skin lesions and lytic bone lesions which can lead to hypercalcemia Myelopathy = progressive course including lower extremities, back, and urinary incontinence
92
Where do Wilm's tumors originate from?
Embryonic renal cells from the embryonic kidney (metanephros) Deletion of the tumor suppressor gene WT1 on chromosome 11
93
With a Dx of choriocarcinoma, what tx should the pt initiate?
Methotrexate
94
What AE's suggest that a pt needs leucovorin rescue following methotrexate tx?
Pt presents with mild icterus, enlarged red painful tongue, sores in the corners of the mouth
95
4 y/o presents with projectile vomiting and HA following a 2 month history of increasing clumsiness. Nystagmus in all direction and truncal ataxia. What is the dx and histology?
Medulloblastoma Arises in the cerebellum and is associated with increased intracranial pressure histology = deep staining nuclei with scant cytoplasm (sheets of anaplastic cells with deeply staining nuclei) arranged in pseudorosettes (Homer-wright rosettes)
96
EBC is associated with which conditions?
heterophile + mononucleosis Oral hairy leukoplakia in HIV + Lymphoproliferative disorders (Hodgkin and non-hodgkin lymphomas) Nasopharyngeal carcinoma
97
Exposure to aniline dye increases risk of?
Aniline dye aka naphtalene increases risk of Transitional cell carcinoma of the bladder Syx = hematuria, dysuria, incontinence
98
What is the histology of the cancer that is the leading cause of both men and women
Lung adenocarcinoma | Glandular differentiation or mucin production with possible bronchoalveolar spread
99
What is the histology of the most common form of breast cancer?
Ducatal carcinoma in situ | Malignant cells limited to ducts and lobules with calcification present
100
What is the MOA of leuprolide?
Use in prostate cancer GnRH agonist that binds the receptor constantly. Initially increases gonadotropin levels, but in the long term decreases FSH and LH
101
A pt with epidermal growth factor receptor 2 (ERBB2) positive breast cancer be treated?
ERBB2 = Her 2 tx with trastuzumab. mAb against ERBB2. Ab dependent cytotoxicity
102
N-myc
Neuroblastoma Malignancy of neural crest cells 2nd most common childhood malignancy in the adrenal medulla
103
What would be found on kidney bx of a pt with Multiple myeloma?
Fibrillary deposits in the mesgangium and subendothelium that stain positive with Congo red (apple green birefringence) Multiple myeloma can lead to systemic primary amyloidosis
104
Which two lung cancers have a strong association with smoking?
Squamous cell Small cell Lung cancer is the leading cause of Superior vena cava syndrome
105
A pt with a tumor in the apex of the right lung has a fixed and dilated tumor. Where is the compression?
Pancoast tumor | Compression of second-order (pregang) sympathetic neuron causes Horner syndrome
106
A young pt presents with many polyps on colonoscopy. Dx and at risk of developing?
``` Familial adenomatous polyposis (FAP) AD, chr 5 Rectal bleeding in a 20-40 y/o Assoc with: Turcot syndrome - risk of CNS tumors Gardner syndrome - thyroid, liver, and kidney cancer ```
107
A woman following resection of an ER+ breast tumor is put on chemo to prevent relapse. What is the drug and potential AE's?
Raloxifene, SERM | can produce syx of menopause in a premenopausal woman (ie hot flashes)
108
AE associated with methotrexate use?
Megaloblastic anemia, myelosuppresion | requires Leucovorin rescue to replace folic acid metabolites
109
A pt presents with a swollen abdomen and appears icteric. She is HCV, HBV negative and has never consumed alcohol. She is an immigrant from china. What carcinogen is likely responsible?
Aflatoxin Intercalates into host DNA Produced by Aspergillus flavus growing on peanuts Still a problem in Asia and Africa
110
Which factor that is overexpressed in many tumors is essential for angiogensis?
Vascular endothelial growht Factor (VEGF) Required for metastasis antagonists = sorafenib, sunitinib
111
What tumor marker is elevated in hepatocellular carcinoma?
Elevated alpha fetoprotein RF's for HCC = HBV, HCV, Wilson's, hemochromatosis, alcoholic cirrhosis, alpha1-antitrypsin deficiency, aflatoxin AFP is also a marker in germ cell tumors (yolk sac)
112
Bx of an ovarian tumor reveals mature and immature follicles. Dx?
Stuma ovarii Monodermal teratoma present with hyperthyroidism syx Increased risk of malignant thyroid carcinoma
113
What increases a woman's risk for breast cancer?
Late menopause (>55) Older female Early menarche (30) FHx of first degree relative with breast cancer at a young age
114
Which therapy used in prostate cancer can cause pulmonary fibrosis?
Bleomycin | Generates free radicals that bind DNA and causes breaks
115
A pt reports muscle weakness that improves with use. What malignancy is this associated with?
Small cell lung carcinoma | Lambert-Eaton syndrome = paraneoplastic dz
116
A pts mammography is positive for a micro-calcifcation that is suggestive of infiltrating ductal carcinoma. What secondary method of prevention will reduce her mortatlity?
Annual mammography | Promotes early detection
117
What is the function of the cell that carries the primary mutation in multiple myeloma
Produces Ab Multiple myeloma is a cancer of plasma cells Hypercalcemia, dehydration, ARF, anemia, bone pain. Punched out bony lesions
118
A pt presents with weight loss, painless jaundice, and migratory thrombophlebitis. Dx?
Pancreatic cancer Trousseau's syndrome painless enlargement of RUQ = enlarged gallbladder Pt at increased risk of clotting events (DVT, PE)
119
7 y/o presents with short stature, hypothyroid like syx, polyuria, bilateral pailledema TSH is low. MRI shows an enhancing multilobulated suprasellar mass with ring calcification in the sella turcica. Dx?
Craniopharyngioma Most common supratentorial tumor in children. Present with increased ICP (HA, n/v), endocrine dysfunction (DI, stunted growth), and visual disturbances Tx - surgery or radiation
120
A pt presents with a lesion suspicious of melanoma and some neurological syx: wobbly gait, peripheral neuropathy. Dx?
Xeroderma pigmentosum (XP) Defective nucleotide excision repair proteins Numerous melanomas, basal cell, and squamous cell carcinomas at a young age. Cross linking of pyrimidine residues due to UV radiation 20% of XP pts have neuro syx
121
Which cell cycle nonspecific alkylating agent can be used in the management of CML?
Busulfan Inhibits DNA synthesis by crosslinking Toxicity = pulmonary fibrosis, hyperpigmentation, seizures.
122
5 days following initiation of chemotherapy a pt presents with flank pain, dysuria, vomiting, and altered mental status. On labs: hyperkalemic, hyperphosphatemia, high uric acid. What drug should have been given for prophylaxis?
Allopurinol Tumor lysis syndrome = electrolyte abnormalities Allopurinol will block uric acid synthesis by inhibiting xanthine oxidase
123
If a pt has blastic bone lesions due to prostatic adenoma, what would be seen on labs for: PSA, Ca2+, Alk Phos
High PSA and Alk Phos Low Calcium Alk phos is high when bone is being made
124
A heavy smoker is at risk for which type of bladder cancer?
Transitional cell carcinoma Most common bladder cancer Painless hematuria is highly suggestive of cancer in adults Histology: increased epithelial cell layers with abn maturation from basal layer to superficial Other RFs: Radiation (prostate tx), cyclophosphamide, aniline
125
On endoscopy a bx is taken from a red, irregular lesion in the distal esophagus. What findings are likely?
Barret's esophagus, benign metaplasia of the distant esophagus squamous cells of the esophagus -> goblet and simple columnar cells of the GI tract (mucin +)
126
A boy is dx'd with large B lymphocyte lymphoma. What tx is he likely to receive?
Rituximab anti CD20 Ab advanced dz would be treated with R-chop: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
127
A woman being treated for ovarian cancer is presenting with hearing loss. What tx is she receiving?
Cisplatin Alkylating-like agent that Cross-links DNA and denatures the helix structure Cell cycle non specific Used in testicular, bladder, ovarian, and lung carcinoma Toxicity - nephrotoxicity and acoustic nerve damage
128
Following a lumpectomy a pt is started on tamoxifen, what are the major side effects?
``` Increases endometrial hyperplasia and cancer Inhibits osteoclasts (prevents osteoporosis) ```
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Tartrate-resistant acid phophatase (TRAP) is a marker for?
Hairy cell leukemia Low grade B cell neoplasm causing bone marrow suppresion -> anemia, thrombocytopenia which causes easy fatigue and bruising and splenomegaly On flow HCl cells are CD25/CD11c +
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Thyroid cancer with psammoma bodies and "orphan annie" nuclei
Papillary carcinoma of the thyroid RF - exposure to ionizing radiation "Cold" lesion on scintiscan Good prognosis
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Where does the classical complement cascade bind to IgG?
C1 molecule will initiate the complement cascade by binding to the Fc region of the HEAVY Ig chain, near the hinge region. Can bind IgG or IgM Phagocytic cells bind the Fc region of the light chains
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What lab finding could be expected in Hemolytic uremic syndrom following Ecoli infection?
Elevated serum indirect bilirubin
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Peak of gamma-globulin on electrophoresis, anemia (fatigue/weakness), lytic bone lesions (back pain), renal insufficiency (amyloid deposition, hypercalcemia)
Multiple myeloma | Plasma cell neoplasm
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Which 5 receptors are involved in the regulation of vomiting?
``` M1 D2 H1 5-HT3 Neurokinin 1 (NK1) ```
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Blocking which two receptors is particularly useful in pts with persistent chemo induced vomiting?
5HT3 | NK1
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A pt presents with fatigue and palpitations x 6 months. She is stressed, has a poor diet due to time, postmenopausal, no stool changes. Hgb 8.5 and hypochromic microcytes on smear. Dx?
Iron deficiency anemia due to occult blood loss occult loss does not always present with dark or bright red stools, so don't rule out GI bleed just because she doesn't have stool changes check - ferritin, TIBC, and order endoscopy
137
What is the function of neuropeptide Y?
Polypeptide neurotransmitter found in the central and autonomic nervous systems. Role in apetite and pain perception. Potential target for obesity drugs
138
A HIV pt is given a drug that is structurally unrelated to nucleosides and is not phosphorylated intracellularly. Inhibits synthesis of DNA from RNA. What is the drug?
Nevirapine, efavirenz Nonnucleoside reverse transcriptase inhibitors Do NOT require activation by phospharylation AEs - hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis
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MOA of zidovudine and emtricitabine?
Nucleoside reverse transcriptase inhibitors. Must be converted to monophosphate form before they become active
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MOA of enfuvirtide?
HIV fusion inhibitor Blocks gp41 fusion Site of action is outside of the cytoplasm
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MOA of ritonavir?
HIV protease. Presents viral assembly and maturation
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A pt dies due to infection. At autopsy he has bone deformities and hepatosplenomagaly. Clumps of erythroid precursor cells are in the liver and spleen. What caused this?
Chronic hemolysis erythroid precursors in liver and spleen = extramedullary hematopoiesis Associated with chronic hemolytic anemias
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A kid with beta thalassemia major has a live bx that shows Kupffer cells with coarse, yellowish-brown cytoplasmic granules. What is in these granules?
Hemosiderin Iron overload is a common complication of chronic hemolytic anemia and frequent blood transfusions. Chelation therapy is indicated to reduce parenchymal iron deposition.
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In iron deficiency anemia, what is the level of: ferritin, transferrin, MCV?
Low Ferritn, MCV High Transferrin Transferrin = TIBC
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54 y/o presents with progressive general weakness and easy fatigability x 2mo. PE - pallor, abdominal distension, massive splenomegaly with the splenic tip crossing the midline. Pancytopenia on labs. Unable to aspirate bone marrow. Dx and findings on smear?
Hairy cell leukemia Lymphocytes with cytoplasmic projections Indolent B cell neoplasm predominantly found in middle aged men. Bone marrow filure, infiltration into the reticuloendothelial system causes massive splenomegaly, "dry taps",
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In colon cancer, which feature would suggest the worst prognosis?
Tumor penetration into the muscularis propria Prognosis in all cancers is related to stage, not grade (differentiation) Stage A - confined to mucosa C - lymph node involvement D - distant metastasis C and D are bad news
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What enzyme helps tumors invade through the basement membranes and access the circulation?
Metalloproteinases Zinc-containing enzymes that degrade the ECM. Participate in normal tissue remodeling but tumors can exploit their activity to metastasize
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How do tumor cells increase adhesion to the GBM?
increased expression of laminin
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How do tumors detach from the surrounding cells?
decreased E-cadherin expression
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Dapsone has the ability to cause hemolytic anemia in which demographic?
Pts with G6PD deficiency
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What is the MOA of rasuricase?
Converts uric acid into a more soluble metabolite Rasuricase = recombinant version of urate oxidase that is not present in humans, but occurs naturally in many mammals. It converts uric acid to allantoin which is soluble and excreted in urine Tumor lysis syndrome = hyper P, K, uricemia and hypocalcemia Prevention = hydration and hypouricemic agents like allopurinol or rasburicase
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Pt presents with sudden abdominal pain and ascites. Labs: anemia, reticulocytosis, leukopenia, thrombocytopenia. Flow - CD 55, CD 59 deficiency. Hepatic v. thrombosis on CT. Dx?
Paroxysmal nocturnal hemoglobinuria Anemia is due to acitvation of complement Triad of hemolytic anemia + hypercoagulability + pancytopenia = PNH PIGA mutation = absence of glycosylphophatidylinositol anchor and associated deficiency of CD55/CD59 complement inhibitor proteins
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Hepatic v. thrombosis AKA?
Budd-Chiari syndrome
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A child with frequent infections has very low serum levels of all immunoglobulin types. But, child does develop a large indurated nodule withing 48 hours of a intradermal inj of Candida Ag. Dx and he has a lack of which structures?
X-linked agammaglobulinemia (Bruton) Lack of germinal centers in the lymph node Defect in B cell maturation causes a sever Ig deficiency but T cell function remains intact. Due to the absence of B cells, primary lymphoid follicles and germinal centers will not form in the lymph nodes
155
A highly vascularized tumor in the normal liver parenchyma was reliant on what substance for its vascular development?
1. Vascular endothelial growth factor | 2. Fibroblast growth factor -
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A SLE pt presents with a nonocclusive thrombus in the R. popliteal v. Labs show increased PTT. Dx?
Antiphospholipid antibody syndome (lupus anticoagulant) Ab against platelet phospholipids causing an increase in coagulation time. Causes prolonged bleeding time despite causing clotting in vivo Assoc with recurrent thrombosis and miscarriages
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8 year old boy presents with small stature, severe HA, decreased visual fields bilaterally. CT shows a calcified cyst in the suprasellar region compressing the pituitary stalk. What would be expected on labs?
Growth hormone deficiency Craniopharyngioma is the most common childhood supretentorial tumor. Presents with HA and bitemporal hemianopia. Derived from remnants of Rathke pouch and can appear as a calcified cyst
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An in vitro study identified a tumor cell line that become resistant after exposure to various anticancer agents. The cells expressed an cell surface glycoprotein that had what function?
ATP dependent transporter Human multidrug resistance (MDR1) gene codes for P-glycoprotein, a transmembrane ATP dependent efflux pump protein with a broad specificty for hydrophobic compounds. Reduces influx of of drugs into the cytosol and increases efflux from the cytosol Verapamil, diltiazem, and ketaconazole decrease the action of this transporter
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Pt presents with sudden onset of numbness over one arm and side of her face. She has had weakness, HA, SOB x several days. Strength and reflexes are intact. On labs she has low Hgb, Platelets with elevated BUN and Cr. PT and PTT WNL and urine + for RBCs and protein, schistocytes on smear. Dx and pathogenesis?
Thrombotic Thrombytopenic purpura Impaired regulation of vWF (ADAMTS13 mutation) ADAMTS13 usually cleaves vWF but the uncleaved multimers are more prothrombotic and cause microvascular thrombosis, microangiopathic hemolytic anemia, and thrombocytopenia.
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If you see a pt with anemia with schistocytes, thrombocytopenia, and acute kidney injury you should think....?
Thrombotic thrombocytopenic purpura (TTP) | ADAMTS13 deficiency leads to a defect in vWF cleavage/inactivation
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Main medication for post chemo nausea?
Ondansetron 5-HT3 antagonist These receptors are on the presynaptic terminals of the vagus nerve in the GI tract.
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A OSA pt has polycythemia due to decreased oxygen delivery to which organ?
Kidney | Hypoxia is sensed by renal cortical cells and they release erythropoietin.
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Following exposure to CCl4 liver tissue shows fatty change and necrosis. Why?
Free radical injury P450 system in the liver usually oxidizes substances like this to detoxify the blood, but oxidation of CCl4 causes free radicals that react with structural lipids causing their degradation and formation of H2O2 (lipid peroxidation). The peroxides form new radicals and continue the vicious cycle
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Irreversible Cox1 and Cox2 inhibitor?
Aspirin Inhibits via acetylation NSAIDs = reversible
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Pt presents with fatigue and pallor. Labs: low Hgb, erythrocyte count, MCV, and reticulocytes. fe and B12 WNL and BM bx shows absence of erythroid precursors but preserved myeloid and megakaryocytic elements. Dx?
Thymic tumor Pure red cell aplasia is a form of bone marrow failure due to hypoplasia of marrow erythroid elements with normal leukocythes and platelets. Associated with thymoma, lymphocytic leukemias, and parvo B19 Removal of tumor cures (PRCA)
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Osteosclerotic lesions suggest?
Blastic bone growth - suspect Prostate adenocarcinoma | Lucent bone = lytic = MM
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MOA of raltegravir?
Integrase inhibitor | Prevents the use of host cell machinery from being hijacked to synthesize HIV mRNA
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Pt presents with abdominal pain and MRI reveals mesenteric v. thrombosis. Labs low Hgb, platelets, haptoglobine and high Total bili, lactate dehydrogenase. Flow shows cD55 absence on RBCS. What is the most likely pathologic renal finding?
Hemosiderosis Paroxysmal nocturnal hemoglobinuria - due to gene defect causing uncontrolled complement mediated hemolysis. Triad = hemolytic anemia (hemoglobinuria), pancytopenia, and thrombosis in weird sites. Chronic hemolysis = iron deposition in kidney (Hemosiderosis)
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67 y/o presents with back pain and fatigue and pain is worse when lying flat. Hgb - 8.5 Serum Cr - 2.2 Serum Ca 2+ - 10.6 He is tx with boronic acid-containing dipeptide with high affinity for the catalytic site of proteasome. tx causes?
Cell apoptosis Pt has MM - plasma cells produce large amounts of mIg. These neoplastic plasma cells are particularly susceptible to proteasome inhibition due to the large amount of proteins they manufacture. This leads to accumulation of toxic intracellular and proapoptotic proteins increases cellular apoptosis Boronic acid containing bipeptide = bortezomib
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LN bx stains for cytokeratin. What cell lineage is the mass from?
Epithelial
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Myeloperoxidase is a marker for?
Myeloid cells
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Vimentin is a marker for?
Intermediate filament present in mesenchymal tissue
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Chromogranin A is a marker for?
Neuron-specific enolase | Marker for neuroendocrine tumors
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A female has a strong FHx of ovarian and uterine cancer and LN bx stained + for cytokeratin and also overexpress a 185kD glycoprotein. The protein spans the cell membrane and has inctracellular tyrosine kinase activity. Fxn?
Accelerates cell proliferation Her2/neu oncogene encodes for a 185 kD transmembrane glycoprotein that has intracellular tyrosine kinase acitivty. Member of the family of epidermal growth factor receptors. Overexpression -> increased rates of breast and ovarian Cancer
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A non-small cell lung cancer can have consecutive tumor kinase activity due to a fusion protein (EML4-ALK) that promotes carcinogenesis. This is most similar to?
CML t(9;22), BCR-ABL - fusion protein with constitutive tyrosine kinase activity Tx - Imatinib
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Tx of Non small cell lung cancer?
Crizotinib Targets the kinase activity of EML4-ALK fusion protein Dz affects young female non-smokers Not a translocation
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12 y/o boy presents with HA and gait instability x mo. MRI finds a large mass with cystic and solid areas in the cerebellum. Dx?
``` Pilocytic astrocytoma Most common brain tumor in kids Astrocytes Cystic and solid components on MRI Pilocytic astrocytes and rosenthal fibers Good prognosis ```
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If you see a cerebellar tumor in a child what is your differential?
Pilocytic astrocytoma - cystic and solid on MRI | Medulloblastoma - always solid on MRI
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Describe medulloblastomas
Second most common brain tumor of childhood, but most common malignant childhood brain tumor Only in the cerebellum (usually vermis) Solid on MRI Sheets of small blue cells with hyperchromatic nuclei and scant cytoplasm Highly malignant, poor prognosis HA and cerebellar dysfunction
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Describe ependymomas
3rd most common brain tumor in kids Ependymal lining of the ventricle and can obstruct flow of CSF. Present with hydrocephalus Gland like "rosettes"
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Pt presents with back pain and B syx with a lytic lesion over a vertebral body. Genetics show a single point mutation causing an activation mutation that promotes high replication rates in the cells. Which gene is involved?
KRAS | activation of proto-oncogenes leads to cell proliferation
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What happens when you have a PM in a tumor suppresor gene?
Get an inactivation mutation that eliminates regulation of the cell cycle (APC, BRCA1, RB, TP53
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24 y/o female presents with fever, dyspnea, and productive cough with yellow sputum x 3 days. Bronchial breath sounds and crackles in RLQ. High leukocytes with a predominance of banded PMNs and lymphocytes. Leukocyte alkaline phosphate is elevated. What would be on smear?
Basophilic oval inclusion in mature PMN's (Dohle bodies) Leukemoid rxn is a benign leukocytosis in response to infection, malignancy, or acute hemolysis. Leukocyte alk phos can be increased or wNL. Smear = increased bands, early mature PMN precursors,a nd granules (Dohle bodies) in the PMNs Blue = ribosomes bound to RER Associated with sepsis
184
A pt presents with left sided Horner syndrome. What type of cancer do they have and where is the mass?
Adenocarcinoma in the apex of the left lung | NOTE: ipsilateral adenocarcinoma
185
A boy presents with fatigue, easy bruising, and frequent epistaxis x 2 weeks. He is pancytopenic. Dx?
Idiopathic aplastic anemia Usually due to a toic effect or autoimmune response causing apoptosis of pluripotent stem cells (pancytopenia) Bx - hypocellularity with abundance of fat cells
186
What is the most common indolent non-Hodgkin lymphoma in adults?
``` Follicular lymphoma B cell origin Painless waxing and waning lymphadenopathy t(14;18) bcl-2 overexpression ```
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East African with a rapidly enlarging left jaw mass. Bx = numberous mitotic figures and apoptotic bodies are observed on histopathologic exam. Dx and genetics?
Burkitt Lymphoma c-Myc oncogene overexpression "starry sky" = macrophages and apoptotic bodies in a sea of medium sized lymophocytes t(8;14)
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8 y/o presents with dyspnea, tachypnea, inspiratory stridor, dysphagia. Hematopoietic cells (blasts) on smear. The neoplastic cells in this condition normally give rise to?
T lymphocytes Blast cells in periphery = leukemia ALL is the most common malignancy of childhood. Most are B-ALL but T-ALL is a mediastinal mass that can cause respiratory syx, dysphagia, and SVC syndrome
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A mAb is designed to block a specific cell surface receptor on T cells facilitating the destruction of cancer cells by T cells capable of recognizing tumor ag. What is the surface receptor?
Programmed death receptor (PD-1) binds to its ligand (PDL-1) to Downregulate the immune response against tumor cells by inhibiting cytotoxic T cells. Many cancers evade the immune response by over expressing PD-L1 mABs that block Pd-1 help prevent T cell inhibition and promote apoptosis of the tumor cells.
190
A woman presents with a breast tumor that is: Estrogen receptor + Progesterone receptor + Human Epidermal growth factor receptor 2 (3+/overexpressed) mAB therapy is started, what is the most likely target of the drug?
Tyrosine kinase receptor HER2 is a tyrosine kinase receptor that is overexpressed in 20% of breast cancer pts. Blockade with trastuzumab downregulates cellular proliferation and promotes apoptosis
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Pt presents with low RBCs, low platelets, low WBCS but normal PT, PTT following a URI. What would be seen on Bone marrow bx?
Hypocellular marrow filled with fat cells and marrow stroma Aplastic anemia -> pan cytopenia and bone marrow is replaced by fat cells Absence of splenomegaly Typically produces a dry tap
192
Female presents with multiple DVT events but normal PTT. PTT remains normal after administration of Protein C in vitro. Dx?
Factor V Leiden Inherited Va becomes resistant to inactivation by activated protein C.
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A pt in renal failure begins to bleed from his catheter site. What lab values are expected?
Prolonged Bleedign time PT, PTT, Platelet count all WNL Pt has uremia - suspect this in pts with significat renal dysfunction. Uremic toxin impair platelet aggregation and adhesion Qualitative platelet disorder Dialysis removes the toxins and partially reverses this
194
Anemia with parathesia?
B 12 deficiency
195
Pt has a loss of expression mutation affecting a protein found on the basolateral surface of hepatocytes and enterocytes. Dx?
``` Primary hemochromatosis (HFE protein mutation) Inactivation of HFE causes decreased hepcidin synthesis by hepatocytes because the cells think that there is an iron deficiency. This leads to increased DMT1 expression by enterocytes leading to iron overload. At increased risk for liver cirrhosis and HCC ```
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Pt has several enlarged hard lymph nodes in the right inguinal area inferior to the inguinal ligament. Bx shows malignant cells. Where is the original tumor?
Orifice of the anal canal Most of the cutaneous lymph from the umbilicus down drains into the superficial inguinal lymph nodes Testes drain into the para-aortic and those nodes are much deeper
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Which cells secrete a substance that controls iron storage and release by other cells in iron homeostasis?
Hepatic parenchymal cells Secrete hepcidin which is the central regulator of iron homeostasis. High iron levels = high hepcidin. Interacts with ferroportin to store and disperse iron
198
Which anti-inflammatory agent will not impair platelet aggregation
Celecoxib Selective Cox 2 inhibitor, no side effects of bleeding and gastrointestinal ulcers Cox 1 has a physiologic role in many tissues, but Cox 2 is preferentially expressed at sites of inflammation
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define anaplastic tumors
Bear no remeblance to their cell of origin
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B cells originate from which region of the lymph node?
Germinal centers | X-linked (Bruton) agammaglobulinemia, defect in B cell maturation
201
Which enzyme inactivates 6-mercaptopurine?
Xanthine oxidase *Allowpurinol increases the concentration of 6-MP 6-MP requires activation by HGPRT
202
Why do pts with von Willebrand dz have bleeding cessation following desmopressin administration?
Increase in endothelial protein release desmopressin alleviates bleeding through endothelial release of vWF vWD = AD