Oncology Flashcards
Pt with neurologic symptoms (paraneoplastic syndrome) and anti-Hu and anti-Yo Abs
Small cell lung cancer (SCLC)
Assoc with smoking
Tx - platinum agent (ie carboplatin, cisplatin) with etopside
What is the best way to assess prognosis for melanoma?
The depth
Vertical growth
What cancers are associated with multiple endocrine neoplasia (MEN) type 1?
3 P’s
- Pancreas = Zollinger-Ellison
- Pituitary = elevated prolactin
- Parathyroid = Hx of renal stones and a neck nodule
A pt with Down syndrome is at an increased risk for which cancer?
ALL
Fatigue, easy bruising, weight loss, fever
Most common cause of firm fixed lumps in the axillary lymph nodes
Invasive ductal carcinoma
Overexpress HER2/neu
Bx = anastomising sheets of pleomorphic cells
Pt presents with high WBC count with basophilia. See PMNs at all stages of maturity. Immature myelocytes and segmented PMNs. Dx and Tx?
Chronic myelogenous Leukemia (CML)
Tx - Imatinib
t(9;22) Philadelphia chromosome; Bcr-Abl
Contituitively active tyrosine kinase
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?
von Hippel-Lindou Hematuria AD, VHL deletion on chr 3 Retinal, medullary, and cerebellar angiomas Bilateral renal cell carcinoma
Which two sites are common sites of metastasis?
Liver - GI tract drains to hepatic poratal
Lung
Due to high blood volume in both
A pt reports new onset tonic-clonic seizure and 4 month history of bloody stools
Turoct syndrome AD Colorectal and brain tumors APC gene = polyposis and medulloblastoma hMLH1 = DNA mismatch repair causring polyposis and glioblastoma multiforme
What are the 3 most common causes of cancer death in men?
- Lung
- Prostate
- Colorectal
A pt presents with crippling back pain. CT shows lesions in the spine Hgb - 10.2 Calcium - 13.1 Increased total protein Dx?
Multiple Myeloma
Increased total protein = IgG
Decreased levels of normal Ig’s make them prone to infections
Back pain = lytic bone lesions
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?
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
Bone tumor in the metaphysis of long bones in males 10-20 y/o
Osteosarcoma
Raises the periosteum causing either a triangular periosteal shadow (Codman triangle) or radial reactive bone formation (sunburst growth pattern)
A pt with Small cell Lung Carcinoma is at risk of which paraneoplastic syndrome?
Overproduction of ACTH and ADH
ACTH increases glucocorticoids causing Cushings syndrome (weight gain, redistribute body fat, striae, moon facies, poor wound healing)
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
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
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
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
What is primary biliary cirrhosis?
Autoimmune
Lymphocytic infiltrates and granulomas in the biliary tract
Increased mitochondrial Ab associated with CREST syndrome, RA, and celiac
What is the normal function of Rb?
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
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?
Meningioma
psammoma bodies, synctial, fibroblastic, transitional, secretory, and microcystic
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
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”
How do you distinguish Waldenstrom macroglobulinemia from Multiple myeloma?
Waldenstrom has syx of hyperviscosity (HA, vision changes)
Multiple myeloma = has bone and renal abnormalities
Which dz have a M spike on electrophoresis?
Waldenstrom macroglobulinemia
plasma cell dyscrasias
multiple myeloma
monoclonal gammopathy of undetermined significance (MGUS)
How do you identify Monoclonal gammopathy of undetermine significance from other dz’s with M spike?
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
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?
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
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
What are the 3 primary brain tumors of childhood that can result in hydrocehphalus by obstructing the fouth ventricle?
Medulloblastoma
Ependymomas
Hemangioblastomas
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
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
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)
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
What is the MOA of leuprolide
GnRH analog suppresses the release of LH in prostate cancer
What is the MOA of flutamid?
nonsteroidal antiandrogen competitvely inhibits androgens at the testosterone receptor
Pt with a cancer hx presents with ecchymoses, intracranial hemorrhage, focal neurologic signs
Metastatic melanoma
Frequent source of metastatic lesions in the brain
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
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
In which cancers do you see Psammoma bodies?
Papillary adenocarcinoma of the thyroid Serous papillary cystadenocarcinoma of the ovary Mesothelioma Meningioma PSaMMoma
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
Which cancers tend to metastasize to bone?
Permanently Relocated Tumors Like Bone Prostate Renal Cell Carcinoma Testes/Thyroid Lung Breast
Which cancers tend to metastasize to the brain?
Lots of Bad Stuff Kills Glia Lung Breast Skin (melanoma) Kidney (renal cell carcinoma) GI (colon)
Which cancers tend to metastasize to the liver?
Cancer sometimes penetrate Benign Liver Colon Stomach Pancreas Breast Lung
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
Paraneoplastic syndrome associated with Squamous lung carcinoma?
PTHrP causing hypercalcemia
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
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.
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
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)
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
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 +)
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
Tx used in ovarian cancer and an adjuvant in breast cancer that hyperstablizes microtubules?
Paclitaxel
Specific to M phase
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
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
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
Osteoblastic bone lesions are suggestive of which cancer in older men?
Prostatic adenocarcinoma
Osteolytic lesions are associated with which cancer?
Multiple myeloma
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)
Which drugs are known to cause Pulmonary fibrosis?
Busulfan Bleomyacin Amiodarone Methotrexate Nitrofurantoin Radiation therapy to the chest
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
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
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
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
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
Two types of cancer associated with Rb
Retinoblastoma (eye)
Osteosarcoma
LOF
RB binds and inactivates E2F and accelerates cell cycle progression
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
A pt presents with Barrett esophagus. What medication should they start?
Precursory to esophageal adenocarcinoma. Intestinal epithelium replaces normal squamous epithelium.
Tx - omeprazole
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
What is the MOA of Rituximab?
mAB against CD 20 (B lymphocytes)
Used in follicular lymphoma
t(11;14)
Mantle cell lymphoma
t(15;17)
Acute pro-myelocytic leukemia
Tx regimen for prostate cancer?
Eliminate Ball cancer
Etoposide
Bleomycin (or Ifosfamide)
Cisplatin
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)
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
Most common cause of vaginal bleeding in a post menopausal woman?
Endometrial cancer
Greatest risk factor - Tamoxifen use
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)
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)
What two things should make you think of pancreatic cancer
Smoking, obstructive jaundice
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
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
A pt with CML is at risk of developing if the condition progresses?
DIC occurs shortly before blast crisis in all types of leukemia
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
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
What is the function of the t(14;18) fusion protein?
chr 14 = Ig heavy chain
chr 18 = bcl-2, prevents apoptosis
MOA of doxorubicin?
DNA intercalation
Also daunorubicin
Bx of a lung lesion with scant cytoplasm, areas of necrosis, and “salt and pepper” nuclei
Small cell carcinoma
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
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
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
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
A pt presenting with n/v and diarrhea following methotrexate use should be supplemented with?
Folinic acid = leucovorin
Counters the myelosuppresive effect of methotrexate
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)
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
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
With a Dx of choriocarcinoma, what tx should the pt initiate?
Methotrexate
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
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)
EBC is associated with which conditions?
heterophile + mononucleosis
Oral hairy leukoplakia in HIV +
Lymphoproliferative disorders (Hodgkin and non-hodgkin lymphomas)
Nasopharyngeal carcinoma
Exposure to aniline dye increases risk of?
Aniline dye aka naphtalene increases risk of Transitional cell carcinoma of the bladder
Syx = hematuria, dysuria, incontinence
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
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
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
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
N-myc
Neuroblastoma
Malignancy of neural crest cells
2nd most common childhood malignancy in the adrenal medulla
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
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
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
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
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)
AE associated with methotrexate use?
Megaloblastic anemia, myelosuppresion
requires Leucovorin rescue to replace folic acid metabolites
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
Which factor that is overexpressed in many tumors is essential for angiogensis?
Vascular endothelial growht Factor (VEGF)
Required for metastasis
antagonists = sorafenib, sunitinib
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)
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
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
Which therapy used in prostate cancer can cause pulmonary fibrosis?
Bleomycin
Generates free radicals that bind DNA and causes breaks
A pt reports muscle weakness that improves with use. What malignancy is this associated with?
Small cell lung carcinoma
Lambert-Eaton syndrome = paraneoplastic dz
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
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
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)
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
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
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.
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
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
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
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 +)
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
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
Following a lumpectomy a pt is started on tamoxifen, what are the major side effects?
Increases endometrial hyperplasia and cancer Inhibits osteoclasts (prevents osteoporosis)
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 +
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
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
What lab finding could be expected in Hemolytic uremic syndrom following Ecoli infection?
Elevated serum indirect bilirubin
Peak of gamma-globulin on electrophoresis, anemia (fatigue/weakness), lytic bone lesions (back pain), renal insufficiency (amyloid deposition, hypercalcemia)
Multiple myeloma
Plasma cell neoplasm
Which 5 receptors are involved in the regulation of vomiting?
M1 D2 H1 5-HT3 Neurokinin 1 (NK1)
Blocking which two receptors is particularly useful in pts with persistent chemo induced vomiting?
5HT3
NK1
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
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
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
MOA of zidovudine and emtricitabine?
Nucleoside reverse transcriptase inhibitors. Must be converted to monophosphate form before they become active
MOA of enfuvirtide?
HIV fusion inhibitor
Blocks gp41 fusion
Site of action is outside of the cytoplasm
MOA of ritonavir?
HIV protease. Presents viral assembly and maturation
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
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.
In iron deficiency anemia, what is the level of: ferritin, transferrin, MCV?
Low Ferritn, MCV
High Transferrin
Transferrin = TIBC
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”,
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
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
How do tumor cells increase adhesion to the GBM?
increased expression of laminin
How do tumors detach from the surrounding cells?
decreased E-cadherin expression
Dapsone has the ability to cause hemolytic anemia in which demographic?
Pts with G6PD deficiency
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
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
Hepatic v. thrombosis AKA?
Budd-Chiari syndrome
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
A highly vascularized tumor in the normal liver parenchyma was reliant on what substance for its vascular development?
- Vascular endothelial growth factor
2. Fibroblast growth factor -
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
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
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
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.
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
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.
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.
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
Irreversible Cox1 and Cox2 inhibitor?
Aspirin
Inhibits via acetylation
NSAIDs = reversible
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)
Osteosclerotic lesions suggest?
Blastic bone growth - suspect Prostate adenocarcinoma
Lucent bone = lytic = MM
MOA of raltegravir?
Integrase inhibitor
Prevents the use of host cell machinery from being hijacked to synthesize HIV mRNA
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)
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
LN bx stains for cytokeratin. What cell lineage is the mass from?
Epithelial
Myeloperoxidase is a marker for?
Myeloid cells
Vimentin is a marker for?
Intermediate filament present in mesenchymal tissue
Chromogranin A is a marker for?
Neuron-specific enolase
Marker for neuroendocrine tumors
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
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
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
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
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
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
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”
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
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
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
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
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
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
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)
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
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.
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
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
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.
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
Anemia with parathesia?
B 12 deficiency
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
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
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
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
define anaplastic tumors
Bear no remeblance to their cell of origin
B cells originate from which region of the lymph node?
Germinal centers
X-linked (Bruton) agammaglobulinemia, defect in B cell maturation
Which enzyme inactivates 6-mercaptopurine?
Xanthine oxidase
*Allowpurinol increases the concentration of 6-MP
6-MP requires activation by HGPRT
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
