Neoplasia Flashcards
Female Patient comes in with abdominal
midline swelling. You preform differential diagnoses and
pregnancy test is negative. The patient complains that they
look pregnant but they are having normal periods. Biopsy of
a mass was taken from uterus and showed well
differentiated tumor that has the same smooth muscle as as
myometrium.
What is her diagnoses?
What would the condition be if the patient were male?
uterine leiomyoma
If patient were male
-BPH; benign prostatic hyperplasia; bladder is
obstructed and swollen bc of pressure of prostate
Patient comes in with painless swelling on the anterior thigh.
What’s the next step in clinical evaluation?
immediately scan for metastasis
Patient comes in with painless swelling on the anterior thigh. Scan shows metastasis, what’s the condition/prognosis?
Osteosarcoma the patient will likely die within 2 years
-Most common sarcoma is _______ or ________; Treatment for osteoma= _________
distal femur or proximal end of
tibia
Treat it by removing it
Women comes in saying she has regular periods but when she has sex she spots. What is the next step?
Papsmear
Papsmear shows disorganized hyperchromatic, enlarged, multipolar cells. But the basal membrane is not affected. What is her diagnoses?
-localized Carcinoma in situ of the cervix (no metastasis)
b/c tumor hasn’t breached the stroma
28yr old woman comes in with lump
in the breast. She tells you she has family history of breast cancer. You preform a mammogram and see a lesion that is heavily incorporated in breast tissue (pic) what is the diagnoses?
invasive ductal carcinoma of the breast
What’s the differential diagnosis of a fibroadenoma and an invasive ductal carcinoma of the breast?
The fibroadenoma is non-invasive (it’s encapsulated with well defined margins that are estrogen responsive) aka benign
Patient comes in with blurry vision and with strange behaviors. You do a CT and
patient has a brain tumor. The tumor cells are totally undifferentiated from brain tissue. Under further investigation the patient tells you he has been a smoker for many years. How would you treat the tumor?
radiation to lung because that is where brain tumor metastases from and when you kill lung cancer it will kill brain tumor
60 yr old Patient comes in with high BP, coughing and no medication will reduce it.
He is a smoker What is his diagnoses?
bronchogenic carcinoma metastases into a pheochromocytoma (adrenal tumor)
Describe the features of a phenochromocytoma
Pheochromocytoma is a type of neuroendocrine tumor that grows from cells called chromaffin cells. These cells produce hormones needed for the body and are found in the adrenal glands
Heavy smoker comes in and you diagnose bronchogenic carcinomas. What should you scan next?
adrenals and the brain
If you have tumors that hemorrhage how do you differentiate between tumors and herpes simplex (temporal hemorrhages)
Tumor won’t have neutrophils present
Common metastasis:
Prostate carcinoma = ______
Bone
Common metastasis:
Bronchogenic carcinoma = ______
Adrenals or brain
Common metastasis:
Neuroblastoma = ______
Liver & bones
Common metastasis:
Gliomas = ______
Rarely metastasize
Common metastasis:
Basal cell carcinoma = ______
Rarely metastasize
Common metastasis:
Gastric carcinomas = ______
Ovaries & liver
Common metastasis:
Nephroblastoma = ______
Liver
Common metastasis:
Pancrease & Colorectal Carcinomas= ______
Liver
Common metastasis:
Testicular carcinoma = ______
Lung
How do mesenchymal tumors spread
(mesenchymal organ=fat, fibrous
tissue, ligaments, skeletal muscle, smooth muscle, bone)
That will spread by blood.
How do carcinomas (from any 3 germ layers) spread?
By lymphatics
Patient comes with jaundice and weightless and metastasis to the liver. What’s the cancer?
3 possibilities
Gastric, Pancreatic, or Colon
Types of metastasis:
Describe direct seeding & what type of cancers spread like this?
Direct seeding is when the malignant neoplasm penetrates the body cavities:
Colon, ovary, appendix, stomach, pancreas, & sometimes breast
Patient comes in saying they lost 15 pounds 3 months without dieting or exercise but their abdomen is very distended. There is a mass in the abdomen full of fluid. When you cut you see fluid in the peritoneal cavity with tumors all over the peritoneal wall.
What is the diagnosis?
pseudomyxoma peritonea (tumors all over the peritoneal wall and lots of mucinous fluid)
Final diagnoses: mutinous cystadenocarcinoma from ovary or the
appendix (male)
She keeps losing weight but she’s not dieting. She is a smoker and says her periods are very irregular? On palpitations you feel two/bilateral masses in pelvis, what exam do you do next?
endoscopy because metastasis from stomach; (to know the ovarian cancer is from metastasized from stomach you will look for signet-ring morphology; if endoscopy is normal check breast)
Types of cancerous spread:
Describe Hematogenous spread
Mesenchymal tumors (mesenchymal organ=fat, fibrous tissue, ligaments, skeletal
muscle, smooth muscle, bone) will spread by blood.
Prostate spreads to the pelvis & lower spine via osteoblasts (look for dense lesions)
Thyroid spreads via osteolytic metastasis (look for black holes)
Breast spreads via osteoblastic and osteolytic
Male Patient above 60 comes in with recurrent back pain. He says he doesn’t have any urinary issues. Taking NSAIDS but the pain doesn’t go away. What is the 1st thing you should do?
-PROSTATE EXAM
Psa levels >10 =problem with prostate
(Then preform biopsy to confirm prostate cancer; Patient won’t have any urinary symptoms in prostate CANCER but will have back pain bc of the osteoblastic activity of metastases cancer cells)
Lady comes in saying her back has been killing her. She works as a lawyer’s secretary. You order an xray and don’t see anything. Order an MRI and see osteolytic (black hole) and osteoblastic (white spots) areas on lower spine. What is her diagnoses?
Order a mammography to diagnose breast cancer; The intervertebral vein that drains the blood from the breast connects to the batsons plexus in the spine. Therefor that is the
cause of metastasis to the spine.
Osteolytic lesions in proximal humerus, iliac, or vertebral column with normal thyroid panel but has Hypercalcemia
suspect thyroid carcinomas or multiple myoma
Hot nodule= inject dye and thyroid accepts it =graves
Cold nodule= dye is not taken up =cancer
Teenager comes in with shortness of breath, heavy breathing, on x-ray you see “cotton ball” appearance what is the next step?
check testicles
Teenager comes in with shortness of breath, heavy breathing, on x-ray you see “cotton ball” appearance. If one of the testis is missing (undescended) then what?
Do a pregnancy test; if it comes back positive
-choriocarcinoma of testis that has mestatsted to the lung
Teenager comes in with shortness of breath, heavy breathing, on x-ray you see “cotton ball” appearance. If one of the testis is missing (undescended) & pregnancy test is positive then what?
Check alpha feta proteins if they’re absent patient is not pregnant; if it were positive could be hydatiform mole
What are the most common tumors in the USA in men
1) Prostate 2) Lung 3) Colon
What are the most common tumors in the USA in women
1) Breast 2) Lung 3) Colon
Human papilloma virus (HPV)— an agent that is spread through sexual contact, is
responsible for what 2 types of cancers.
Cervical carcinoma and head and neck cancers
Cervical carcinoma and head and neck cancers are caused most commonly by what virus
Human papilloma virus (HPV)-
Epstein–Barr virus—-causes what 3 cancers
Burkitt lymphoma
Hodgkin lymphoma
Nasopharyngeal carcinoma (China)
HBV, HCV and Aflatoxins (green mold on peanut)(Aspergillus)(Asia and African)—
can cause what cancer?
Hepatocellular carcinoma
Alcohol consumption(USA)—-causes what type of cancer
Hepatocellular carcinoma
Helicobacter pylori(USA) and Nitrosamines(Japan) (smoked foods)—–cause what type of cancer
Gastric adenocarcinoma
Low fiber diet—–increases incidences of what type of cancer
Colorectal carcinoma
Bronchogenic carcinoma= most commonly caused by what
smoking
Mesothelioma= ________________________
asbestos exposure; never caused by smoking
Vinyl chloride- From smooth muscle= _______________________________
hepatic angiocarcoma bc exposure from PVC
pipes
Mesothelioma & lung cancers are caused by what
Asbestosis & silicosis
Colorectal carcinoma is caused by what?
Inflammatory bowel disease
Carcinoma in draining sinuses causes what conditions
Osteomyelitis & bacterial infection
Bladder carcinoma is caused by what
Chronic cystitis & schistosomiasis
Nonlethal genetic damage causing cancer when the patient
Develops cancer within the first 15 years of life or
genetics
Describe the molecular hallmarks of cancer
1.End of glycolysis for cancer cells give lactic acid even though there is oxygen
=Warburg effect**
2. Ability to evade the host
immune system
28 year old Patient comes in passing blood in stool. They tell you their father was diagnosed with a hereditary disease when he was young. Colonoscopy reveals normal colon; no polyps. CT scan shows growth in ileoceacal valve that looks like a cauliflower. what is the diagnoses?
-haaratomatous polyp
-Hereditary nonpolypos
*If women do ultrasound to rule out ovarian cancer and endometrial biopsy for cancer;
Do endometrial biopsy and pelvic ultrasound every year after 25
Describe the condition and its features
- Xeroderma Pigmentosum
-inherited loss of nucleotide excision repair
-skin cancers follow exposure to UV light
-will see basal cell in young children
What screening exams need to be done if family history of BRCA1 mutations for men & women respectively?
Man- prostate ultrasounds
Women- ovarian and breast cancer exams
. What screening to do with BRCA2 mutation in family history? Men & women
Man and women- breast exams as well as other cancers
Malignant lump found in breast. It is already metastasized to lymph node
What is the next step?
check for HER2 gene to determine treatment
Q. Did a pap smear on. 26 yr old and patient is HPV positive. And find malignant cells
on cervix. But she doesn’t understand that her best friend, who is also HPV positive,
doesn’t have the same malignancy on her cervix. What should you tell her?
-she has a genetic mutation ( p53 is polymorphic at amino acid 72, encoding for
arginine residue instead of lysine) making her more likely to developing cervical cancer
What is the cause of developing burrkitts lymphoma in African patients? & what are the effects of the tumor on the host
8, 14 translocation c-MYC oncogene
Effects on host:
1. Jaundice
2. Constipation
3. Weightless
4. Superior Vena cava syndrome
Patients gets up in the morning and
their face flushes like this. What’s wrong
with him & what if it’s seen in a child?
Adult: superior vena cava syndrome from
carcinoma of the bronchus
child= acute lymphoblastic leukemia; on
xray you see widened mediastinum with
shadow
Describe what paraneoplastic syndromes are & what condition is the most common
The cancers are don’t originate from the endocrine tissue but they secrete various hormones (aka ectopic hormone production)
Cushing syndrome
Describe the features of Cushing Syndrome
Excess ectopic ACTH & cortisol causing:
(1)overproduction of cortisol, hirsutism, hyperglycemia
(2)muscle wasting
(3)hypokalaemia with metabolic alkalosis
(4)Hypertension
(5) “Moon” face, abdominal striae and “Buffalo” hump
Describe the differential for cushings
cortisol test
Normally
cortisol is high in the morning & low by midnight
In Cushing’s
cortisol is high by midnight & low in the morning
cortisol is high by midnight & low in the morning
Cushings syndrome
How do you treat cushings syndrome?
Give dexamethasone (an external cortical steroid, will cause ACTH to be suppressed causing the cortisol levels to decrease)
Increased ACTH
Increased Cortisol
Rx with Dexamethasone causes cortisol to decrease (pituitary-dependent cushings)
A pituitary tumor, the ACTH is increased causing more cortisol production by the adrenal glands
if ACTH levels are suppressed & the cortisol levels do not decrease after administering dexamethasone, it suggests Cushing’s syndrome caused by a pituitary tumor.
Cushings vs pituitary tumor dependent cushings deff
Cushings: Normally, the administration of dexamethasone should suppress the production of ACTH & Cortisol
Pituitary dependent Cushings:
if cortisol levels do not decrease after administering dexamethasone & if ACTH levels are appropriately suppressed by the high cortisol levels
Describe the Syndrome of Inappropriate ADH secretion (SIADH)
-over production of ADH from tumor; tumor controls pituitary gland
-heavy association with small cell lung carcinoma
Patient comes in feeling weak and tired. His eyes appear sunken and he is dehydrated.
No history of head injury. In the ER you order a urine sample.
Results:
Electrolytes <130 (hyponatremia)
What is his diagnoses?
SIADH due to small cell lung carcinoma
-gradually give concentrated sodium
Why don’t you want to give more fluids in patients with SIADH syndrome?
*the retention of the urine causes the blood sodium to be diluted and decreases
osmolity- so if you give more fluids the patients blood will be MORE diluted and causes seizures -> can cause central pontine myelinosis
Urine Osmolality will be high in diabetes insipidus
if patients Electrolytes are below <120 then what will happen?
neurological symptoms; severe hyponatremia (caused by severe head trauma increasing ADH or from Small cell lung carcinoma)
heavily associated with SQUAMOUS cell carcinoma of the lung; it produces
parathyroid hormone-related protein that mimic PTH stimulates osteoclasts and
increases blood calcium;
Hypercalcemia
Describe the features of Hypercalcemia
heavily associated with SQUAMOUS cell carcinoma of the lung; it produces
parathyroid hormone-related protein that mimic PTH stimulates osteoclasts and
increases blood calcium;
If patient has hypercalcemia, show tetany, & are an aged smoker then suspect
squamous cell carcinoma causing hypercalcemia
Tumors most associated with paraneoplastic hypercalcemia are carcinomas of
the______, _______, & ______
breast, lung, kidney, and ovary.
Low calcium is considered _____ & under
High calcium is considered ____ & up
low 8 & under
high 11 & up
60 yr old Patient comes in saying their heart is skipping. They are a smoker. Blood
calcium is 11.2
squamous cell carcinoma
In the condition Acanthosis Nigerians a normal BMI is associated with ________ & a high BMI (32+) is associated with __________
Normal = GI adenocarcinomas
High BMI = Insulin resistance (Diabetes)
Describe neuromyopathic paraneoplastic syndrome
Antibodies that are induced against tumor cell antigens that cross-react with the host’s neuronal cell antigens (aka our own antibodies mistake our neuron antigens for the tumors antigens)
Antibodies that are induced against tumor cell antigens that cross-react with the host’s neuronal cell antigens (aka our own antibodies mistake our neuron antigens for the tumors antigens)
Describe neuromyopathic paraneoplastic syndrome
Antibodies against Purkinje cells (paraneoplastic cerebellar degeneration) can be due to which 3 types of cancers?
Small cell lung carcinoma
Gynecologic/breast cancers
Hodgkin lymphoma
Patient comes in with wide stumbling gait. No history of alcohol. No trauma history,
they keep falling down. The patient has down beating nystagmus (eyes slowly go
down) what is his diagnoses
neomyopathic paraneoplastic syndrome
Describe myasthenia gravis & how do you treat it?
- antibodies against ACH receptors
-associated with Thymoma
Rx. with cholinergic drugs
Describe the symptoms of myasthenia gravis
- Ptosis
- Diplopia
- Muscle weakens with increased movement
Describe the features of Lambert-Eaton Myasthenia syndrome
-antibodies against presynaptic calcium channels
-associated with small cell carcinoma
-symptoms improve with use (movement)
Describe the symptoms of Lambert-Eaton Myasthenia syndrome
- proximal muscle weakness and autonomic dysfunction.
- No clinical improvement is produced by anticholinesterase agents
- proximal muscle weakness and autonomic dysfunction.
- No clinical improvement is produced by anticholinesterase agents
symptoms of Lambert-Eaton Myasthenia syndrome
-antibodies against presynaptic calcium channels
-associated with small cell carcinoma
-symptoms improve with use (movement)
Lambert-Eaton Myasthenia syndrome
- Ptosis
- Diplopia
- Muscle weakens with increased movement
Myasthenia gravis symptoms
- antibodies against ACH receptors
-associated with Thymoma
Rx. with cholinergic drugs
Features of myasthenia gravis
Describe the features of Hypertrophic osteoarthropathy
associated with bronchogenic carcinomas
(1) periosteal new bone formation, primarily at the distal ends of long bones, (metatarsals, metacarpals, and proximal phalanges)
(2) arthritis of the adjacent joints
(3) clubbing of the digits
associated with bronchogenic carcinomas
(1) periosteal new bone formation, primarily at the distal ends of long bones, (metatarsals, metacarpals, and proximal phalanges)
(2) arthritis of the adjacent joints
(3) clubbing of the digits
Hypertrophic osteoarthropathy
. Patient comes in with coughing and shortness of breath. The patient has been a
smoker for 20 years. On exam his hands look like this with dorsal and plantar swelling
of fat pads and nail bed. They also have periostel bone formation in hand joints and
osteoarthitis in hand joints. What is the diagnoses?
-Lung cancer (do a CT) that causes hypertrophic osteoarthropathy
Migratory Thrombophlebitis (Trousseau syndrome)
-associated with pancreatic cancer which causes migratory thrombophlebitis
(Trousseau syndrome) ; Cancer is producing thrombolytic agents
Patient has superficial tender swelling of the legs. It looks like veracious veins. He tells you he has lost a lot of weight lately. You Treat the patient and he comes back in 3 months with the same problem. What is his diagnoses?
-pancreatic cancer-> causes migratory thrombophlebitis (Trousseau syndrome) ; Cancer is producing thrombolytic agents that cause this
Describe the features of nonbacterial thrombotic endocarditis
fibrinous vegetation’s form on the left sided cardiac valve leaflets particularly in
individuals with advanced mucin-secreting adenocarcinomas
Long history of diabetes (at least 10 years) and patient has stroke on left side. He
has recently lost a lot of weight. On CT you see a thrombus in the brain. And
echocardiogram shows vegetations in cardiac valve leaflets on ventricular side. what is
his diagnoses?
Gastric cancer creates mucin that gets into blood and bounces back on the valve
leaflets and will eventually clog aorta and or clot and go to brain Cause nonbacterial
thrombotic endocarditis. The valve will be normal with no murmurs
fibrinous vegetation’s form on the left sided cardiac valve leaflets particularly in
individuals with advanced mucin-secreting adenocarcinomas
Nonbacterial thrombotic endocarditis
Immunohistochemistry:
Keratin intermediate filaments in anything other than epithelial cells indicates _______
Carcinomas
Immunohistochemistry:
Vimentin intermediate filaments in anything other than mesenchymal cells indicates _______
Sarcomas
Immunohistochemistry:
Desmin intermediate filaments in anything other than muscle cells indicates _______
Uterine leiomyoma or Rhabdomyosarcoma
Immunohistochemistry:
Neurofilament intermediate filaments in anything other than CNS/PNS neurons & neural crest derivatives indicates _______
Pheochromocytoma or Neuroblastoma
Immunohistochemistry:
Glial fibrillary acidic protein intermediate filaments in anything other than glial cells indicates _______
Astrocytoma or Ependymomas
Serum tumor markers:
Alpha-fetoprotein is indicative of
Hepatoma or
Nonseminomatous testicular germ-cell tumors
Serum tumor markers:
Beta human chorionic gonadotropin (BhCG) is indicative of
Trophoblastic tumors or Choriocarcinoma
Serum tumor markers:
Calcitonin is indicative of
Medullary carcinoma of the thyroid
Serum tumor markers:
Carcinoembryonic antigen is indicative of
Carcinomas of the lung, pancreas, stomach, breast, & colon
Serum tumor markers:
CA-125 is indicative of
Malignant ovarian epithelial tumors
Serum tumor markers:
CA 19-9 is indicative of
Malignant pancreatic adenocarcinomas
Serum tumor markers:
Placental alkaline phosphatase is indicative of
Seminoma
Serum tumor markers:
PSA is indicative of
Prostate cancer
Serum tumor markers:
CA 15-3/CA 27-29 is indicative of
Breast cancer
Serum tumor markers:
LDH is indicative of
Testicular germ cell tumor, Ovarian dysgerminoma, etc
Serum tumor markers:
Neuron-specific enolase is indicative of
Neuroendocrine tumors, (small cell lung cancer, carcinoid tumors, & neuroblastoma)
Serum tumor markers:
Chromogranin is indicative of
Neuroendocrine tumors
BRCA1 and BRCA2 mutations occur in familial ________, these genes are
not inactivated in sporadic cases of ________
Breast cancers
Describe the features of Breast cancer
BRCA1 and BRCA2 mutations occur in familial breast cancers, these genes are
not inactivated in sporadic cases of breast cancer
What screening exams need to be done if family history of BRCA1 mutations
Man- prostate ultrasounds
Women- ovarian and breast cancer exams
What screening to do with BRCA2 mutation in family history?
Man and women- breast exams as well as other cancers
Malignant lump found in breast. It is already metastasized to lymph node
What is the next step?
-check for HER2 gene to determine treatment
Carcinogenesis:
cause permanent DNA damage; rapid irreversible
Initiators
Carcinogenesis:
Initiators
cause permanent DNA damage; rapid irreversible
Carcinogenesis:
Promoters
-induce tumor formation
Ex. Hep B virus is a INITIATOR causes damage
Interleukins1,6 and TNF alpha->Inflammation is a PROMOTOR for cancer
Carcinogenesis:
-induce tumor formation
promoters
Esophageal cancer from GERD:
ACID= _________
Chronic inflammatioin= __________ -> DNA damage
initiator & promoter
x. HPV and E6 and E7= ________
estrogen= __________
initiator & promoter
. Why don’t >65 year old women have papsmears?
-because without estrogen you won’t develop cervical cancer
Describe Direct- acting carcinogens
require no metabolic conversion; ex chemo therapy
-If you see bladder cancer. Always check if the patient has had any cancer
treatment before because direct-acting carcinogens
If African: check for parasites (schistoma)
Indirect- acting carcinogens
chemical that require metabolic conversion like Aflatoxin B1 from nuts; (some people eat nuts and are fine but if you have the conversion factor then you will develop cancer)
In indirect acting carcinogens most of the known carcinogens are metabolized by _________________________. The genes that encode these enzymes are ______________
cytochrome P-450-dependent
mono-oxygenases
polymorphic
How can an HPV infection cause cervical cancer?
HPV 16 and 18 cause cervical cancer b/c E6 protein degrades p53
Describe how EBV can cause the African form of Burkitt lymphoma, B-cell lymphoma in immunosuppressed persons, & Hodkins lymphoma
1) EBV infects B lymphocytes and epithelial cells of the oropharynx by CD21 receptors to
attach to and infect B cells
2) Latent membrane protein-1 (LMP-1), acts as an oncogene. LMP-1 activates the NF-κB
and JAK/STAT signaling pathways and prevents apoptosis by activating BCL2.
3) EBNA-2 trans activates host genes like cyclin-D lymphoma develops only in people with the acquisition of the t(8;14) translocation
which activate the c-MYC oncogene = Burkitt’s lymphoma
Describe the features of Hereditary Nonpolyposis Colon Cancer Syndrome
due to DNA mismatch repair genes being defective MSH2 and MLH1;
“proofreading” function is lost so errors gradually accumulate.
-also see micro satellite instability that are unstable and increase or decrease in
length( they are tandem repeats that remain constant without mutation)
-autosomal dominant
Describe the features of VHL (von Hippel-Lindau gene
-loss of function mutations associated with:
1.hereditary renal cell cancers,
2.pheochromocytomas,
3.hemangioblastomas of the central nervous system.
In the presence of oxygen, HIF1α is hydroxylated and binds to
VHL, leading to its ubiquitination and degradation but if mutated
HIF1α accumulates in the nuclei and turns genes encoding
vascular endothelial growth factor (VEGF) and PDGF.
Patient comes in with complaint of “seeing double”
-meningioma or ependymomas
Patient comes in with disorganized speech and decreased hearing (wernicke
aphasia- talking neatly but makes no damn sense). Chart States
familial history of similar symptoms, what is the diagnosis?
-bilateral schwannomas due to germline mutation in NF2 gene
Describe the features of Adenmatous polyposis coli (APC)
-downregulates growth promoting signaling pathways
- The -APC (5q21) locus is linked to familial adenomatous polyposis, an autosomal dominant disorder causing multiple colon polyps before the age of 20 with one mutant allele
Describe the role of the APC protein
- APC protein controls β-catenin activity. When β-catenin is active, it forms a complex with TCF, which enhances the growth of colonic cells by increasing the expression of MYC and cyclin D.
-downregulates growth promoting signaling pathways
- The -APC (5q21) locus is linked to familial adenomatous polyposis, an autosomal dominant disorder causing multiple colon polyps before the age of 20 with one mutant allele
features of Adenmatous polyposis coli (APC)
Patient comes in with blood in the stool. With a family history of colon cancer. Do
colonoscopy and see adenomatous polyposis coli. What is the next step?
-remove transverse and descending section of colon
Describe the features of familial gastric carcinoma
β-catenin binds to E-cadherin, which helps cells stick together during wound healing. Loss of-function mutations in the E-cadherin gene (CDH1) cause this.
If APC gene is mutated beta catenin cannot be degraded so there’s over proliferation
Describe the TGF-beta pathway
SMAD sends signals to R-SMAD to turn off genes that drive cell growth
-Mutational inactivation of SMAD4 is seen in 100% of pancreatic cancers
Describe the NF2 protein
NF2 gene mutations cause neurofibromatosis type 2, leading to acoustic nerve schwannomas. Somatic NF2 mutations are found in sporadic meningiomas and ependymomas.
1 Patient comes in with disorganized speech and decreased hearing (wernicke
aphasia- talking neatly but makes no damn sense). Chart States
familial history of similar symptoms
-bilateral schwannomas due to germline mutation in NF2 gene
Describe the role of P53
1) ATM and ATR are protein kinases that activate p53 in response to DNA damage. Mutations in these kinases increase the risk of cancer. Proof-readers detect mistakes and notify p53, which activates micro RNA that triggers apoptosis.
2) p53 also induces proteins like GADD45 for DNA repair. Once p53 completes its task, it calls MDM2 and MDMX. If there is a gain of function mutation, MDM2 unnecessarily kills p53, leading to tumor formation like sarcomas. Viral oncoproteins like HPV’s E6 protein inactivate p53, causing cervical carcinoma.
Describe the features of Li-Fraumeni syndrome
-Li Fraumeni will have ALOT of malignant tumors one after another usually
- 1 patient with 3 different cancers; due to loss of function of p53 via 1 mutant allele
ex. : ALL leukemia, osteosarcomas, rhabdomyosarcoma,
has ALOT of malignant tumors one after another usually
- 1 patient with 3 different cancers; due to loss of function of p53 via 1 mutant allele
-Li Fraumeni
Describe the features of familial retinoblastoma
retinoblastoma, when a white or red reflex seen in the eye when the retina is examined.
It’s caused by a mutation in a gene called RB, which increases the risk of developing retinoblastomas and osteosarcomas
How do you treat retinoblastomas & what does it put people at risk of?
removing the affected eye and surrounding muscles.
risk for developing osteosarcomas before the age of 25
For familial retinoblastomas, have _________ in the RB gene have been associated with other cancers such as_________ & _________.
somatic mutations
glioblastomas and small-cell carcinomas of the lung
Describe the features of neurofibromas (NF1)
- Cafe-au-lait spots
- Hamartomas
3.Lisch nodules
- Cafe-au-lait spots
- Hamartomas
3.Lisch nodules
Describe the features of neurofibromas (NF1)
Describe the features of Chronic myeloid leukemia
Caused by Robertsonian translocations causing non-receptor kinases
Which of the following genes control all these regulatory genes ______ & protein ______
gene = TP53
protein = P53
Patient comes in with sudden history of weightless and jaundice with increased direct
bilirubin suspect _________ what is the cause of this cancer?
suspect GI cancer or pancreatic cancer
What is the cause of this cancer?
-deletetion of p16
Pancreatic cancer are typically in the __________&_________
head of pancreas and block sphincter of odi
Oncogenes that mimic signal transducer proteins: z
Describe the role of the RAS oncogene
permanently activated because the inability to hydrolyze GTP leading to continuous stimulation of cells without any external trigger.
RAS oncogenes:
HRAS mutations cause
Bladder tumors
RAS oncogenes:
KRAS mutations cause
Colon and pancreatic cancer
RAS oncogenes:
NRAS mutations cause
Hematological tumors
RAS oncogenes:
BRAS mutations cause
Hairy cell leukemia, benign nevi (single mutation-moles)
Mutation of neurofibromin (NF-1), a protein that regulates cell growth, results in decreased ability to control cell division, causing __________
familial Neurofibromatosis type 1 (tumor growth in nerves).
42 year old patient comes in and has a tumor beside
the bronchus. He has been a smoker for 5 years. What is
the cause of his tumor formation?
ERBB1 gene mutation
2A =medullary carcinoma of thyroid; diagnose with blood calcitonin levels; patients
will have
bilateral pheno with high BP and tetany (bc hyper calcium)
Gastrin controls calcitonin levels. Higher gastrin levels lead to increased calcitonin levels. If a patient’s calcitonin levels remain high even after taking omeprazole for three days, it could indicate medullary thyroid cancer. The recommended treatment in this case is ____________-
prophylactic thyroidectomy.
Mutations in ERBB1cause
Squamous cell
carcinoma of the lung
Mutations in ERBB2 or HER2
Breast cancer
MEN 2A; RET protein
receptor extracellular
component
Medullary thyroid,
adrenal and parathyroid
(endocrine)
MEN 2B ; RET protein
receptor cytoplasmic
component dysfunctions tend to cause what cancers?
Medullary thyroid or
adrenal with mucosal
neuromas
Patient comes in with painless swelling on distal end of femur. What is his possible
diagnoses?
-osteostarcoma from overexpression of HST1
. Patient comes in with headache and difficulty with vision. On biopsy you see
astrocytes and diagnose astrocytoma. What is the probable cause?
-over-expression of PDGFB (more proteins are being produced)
Overexpression of proto-oncogene PDGFB can lead to
Astrocytoma’s
Overexpression/amplification of proto-oncogene HST1 & FGF3 (fibroblast growth factors) can lead to
Osteosarcoma & stomach cancer respectively
Cell cycle regulators:
CDK4 and CDK6 stimulate _______
cyclin D
Cell cycle regulators:
Cyclin D is stimulated by
CDK4 and CDK6
Cell cycle regulators:
CDK2 activates ________
cyclin E
Cell cycle regulators:
Cyclin E is activated by
CDK2
______ inhibits Cyclin D (CDK4, CDK6); so if there is a problem at the inhibitor there will be a problem with the __________
P16 inhibits Cyclin D (CDK4, CDK6)
G1 checkpoint/cyclin D
Phosphorylating the RB gene makes cells release ______, leading to cell proliferation. RB gene normally suppresses cell growth, but it can be affected by HPV, causing continuous cell division and errors. Loss or mutations of RB gene can lead to____________&__________. .
E2F
retinoblastomas and osteosarcomas
Somatic mutations of RB gene can result in ________&________
glioblastomas and small-cell lung carcinomas
Describe the role of the MYC gene
1) Stimulates cell division
2) activates telomerase
3) Activates cyclin D (1st step in cell synthesis)
Dysregulation of C-MYC expression from translocation of gene 8 to 14 leading to _________
Burkitt’s lymphoma (B-cell tumor)
N-MYC— __________
L-MYC— __________
N-MYC: neuroblastomas
L-MYC: small-cell cancers of the lung
If a patient has a negative EBV test and still has Burkitt’s lymphoma what is the condition
C-MYC dysregulation
If a patient has EBV positive test they will have what?
Jaw mass
Regulatory gene:
Growth promoting proto-oncogenes “gain of function” requires
One gene mutation
Tumor suppressor gene “loss of function mutations” requires
two genetic mutations to develop cancer
Describe the role of PTEN tumor suppressor gene
The “-PTEN” gene is responsible for stopping the production of proteins and lipids in our body. It does this by blocking a compound called P13k. If there is a mutation in this gene, it can result in the loss of its function, meaning it doesn’t work properly.
This mutation is mostly found in women.
Stomach cancer is most prevalent in
Japan
Breast cancer is most prevalent in
USA
Liver hepatoma is most prevalent in
Asia
Prostate cancer is most prevalent in
African American populations
Thyroglobulin is useful for identifying
Thyroid cancers
S100 is useful for identifying
Melanoma & neural tumors
CD markers is useful for identifying
Lymphomas/leukemias
101) A newborn male has a small, bright red, slightly elevated lesion over left eyelid. You inform the parents that the lesion is a benign vascular tumor that over time will most likely:
A) Progressively increase in size
B) First increase in size and then regress
C) First regress and then increase in size
D) Progressively regress
E) Stay stable with little growth
B) First increase in size and then regress
102) A 19-year-old primigravida gives birth to a premature male neonate who experiences
severe respiratory distress. After treatment is administered the distress resolves, and by two
weeks of age, the baby has adequate respiratory function. Abnormal retinal vascularization that extends into the vitreous is discovered on ophthalmic examination. The retinal findings in this patient are most likely related to which of the following?
A) Maternal terbutaline treatment
B) Maternal corticosteroid therapy
C) Neonatal antibiotic treatment
D) Neonatal oxygen supplementation
E) Neonatal surfactant supplementation
D) Neonatal oxygen supplementation
104) A 63-year-old male with advanced visceral cancer dies of extensive myocardial infarction.
Autopsy also reveals sterile non-destructive vegetations along the mitral leaflet edges. The
Neoplasia
pathogenesis of this patient’s vegetations is most similar to that of:
A) Hypercalcemia of malignancy
B) Distant metastases
C) Lambert-Eaton syndrome
D) Trousseau syndrome
E) Raynaud phenomenon
D) Trousseau syndrome
105) A 31-year-old female is brought to the ER with new-onset tonic-clonic seizures. MRI of the brain reveals a round 1.2 cm mass in the right temporal lobe. The biopsy of the mass show a neoplastic tissue containing a mutation in the gene that encodes BRAF, a protein kinase. Which of the following is the most likely diagnosis?
A) Glioblastoma
B) Melanoma
C) Prostate cancer
D) Renal cell carcinoma
E) Small cell lung cancer
B) Melanoma
106) A 44-year-old female presents to your office with skin changes on her right breast. Physical examination reveals focal dimpling of the skin and inversion of the nipple of the right breast. Biopsy of the breast tissue underlying these changes demonstrates invasive carcinoma. Which of the following is responsible for the physical exam findings in this patient?
A) Epithelial mucin-containing cells
B) Suspensory ligament infiltration
C) Regional lymph node metastasis
D) Dermal lymphatic hyperplasia
E) Pectoral fascia infiltration
B) Suspensory ligament infiltration
107) A 60-year-old male visits his physician with a history of difficulty climbing stairs and
difficulty breathing on exertion. He states that he has gained 15 kg (33lb) over the last few
months. Upon physical examination, he is found to have weakness in his proximal muscles and darkening of his skin. Chest x-ray was performed which demonstrated a mass in the lung. Laboratory investigations showed elevations in serum cortisol and adrenocorticotropic hormone levels. Which of the following studies would be the most appropriate for establishing the diagnosis?
A) Magnetic resonance imaging of the brain
B) Dexamethasone suppression test
C) Serum thyroid-stimulating hormone levels
D) Adrenocorticotropic hormone stimulation test
E) Serum cortisol levels at 8:00 AM
B) Dexamethasone suppression test
108) A 54-year-old female undergoes a thyroid scan for a palpable neck mass. It is determined
to be a ‘cold’ thyroid nodule. Fine-needle aspiration of the nodule shows spindle-shaped cells in an amorphous background. She has elevated serum calcitonin levels. Gene changes of which of the following is most likely responsible for this patient’s condition?
A) Activating mutation of RET proto-oncogene
B) Inactivation of Rb gene
C) Over-expression of RAS gene
D) Inactivation of p53 gene
E) Over-expression of bcl-2 gene
A) Activating mutation of RET proto-oncogene
109) After discovering a mass in her right breast, a 36-year-old Caucasian female is sent for a biopsy by her primary care physician. Histological evaluation of a biopsy specimen is shown below. What is the most likely diagnosis?
A) Ductal carcinoma in situ (DCIS)
B) Paget disease
C) Fibroadenoma
D) Sclerosing adenosis
E) Mammary duct ectasia
F) Medullary carcinoma
C) Fibroadenoma
110) A 36-year-old mildly obese woman with a diagnosis of high-grade cervical intraepithelial
neoplasia (CIN), is asking her physician how this could have happened. She is sexually active with multiple sexual partners and occasionally uses barriers as a contraceptive method because she has been taking oral contraceptives for six years. At age 12 she experienced menarche and her menstrual cycles have been regular ever since. She does not smoke, drink alcohol, or use any illicit drugs. Her family history is significant for her mother having breast cancer at the age of 40 and her aunt being diagnosed with ovarian cancer at age 58. Which of the following is the most significant factor that predisposes this patient to invasive cervical cancer?
A) Oral contraceptive use
B) Family history of cancer
C) Nulliparity
D) Multiple sexual partners
E) Early menarche
F) Obesity
D) Multiple sexual partners
111) A 4-month-old boy is brought to the clinic for a routine well child examination. He is up to date with his vaccination and his mother has no current complaints. On physical examination a right-sided white pupillary reflex is discovered. His family history is significant for his father being diagnosed with a retinal neoplasm and had his left eye enucleated as a child. Which of the following neoplasms is this child at the greatest risk of developing?
A) Acute lymphoblastic leukemia
B) Neuroblastoma
C) Ewing sarcoma
D) Osteosarcoma
E) Medulloblastoma
D) Osteosarcoma
112) A 58-year-old female undergoes surgery for the removal of bilateral ovarian masses.
Examination of the resected masses revealed poorly differentiated cells heavily loaded with
mucus. Which of the following is the most likely primary site of this patient’s disease if her ovaries were secondarily involved?
A) Lung
B) Breast
C) Stomach
D) Kidney
E) Bladder
F) Liver
C) Stomach
113) A 36-year-old male who has been recently diagnosed with colon cancer, reveals that his
father also was diagnosed with colon cancer and died at the age of 40 years old. Further history reveals that his younger sister suffers from endometrial cancer. You suspect that this patient’s cancer did not develop from a typical adenomatous polyp. If your suspicion is correct, which of the following cellular event impairment underlies this patient’s condition?
A) Apoptosis cascade
B) G-protein inactivation
C) Transcription factor inactivation
D) DNA mismatch repair
E) intercellular attachment
D) DNA mismatch repair
114) A 69-year-old patient with complaints of fatigue, weight loss and constipation, undergoes a colonoscopy which reveals a circumferential mass encircling the sigmoid colon. In this patient,measuring the level of carcinoembryonic antigen (CEA) would be helpful for which of the
following?
A) Grading of the tumor
B) Staging of the tumor
C) Determining the type of resection
D) Monitoring for tumor recurrence
E) Predicting 5-year survival
D) Monitoring for tumor recurrence
115) A 46-year-old male undergoes upper gastrointestinal endoscopy. He has a long history of nocturnal cough and sore throat. Microscopic findings on esophageal biopsy are shown on the slide below. Which of the following is this patient at greatest risk of developing?
A) Achalasia
B) Squamous cell carcinoma
C) Adenocarcinoma
D) Variceal bleeding
E) Leiomyoma
F) Crohn’s disease
C) Adenocarcinoma
116) During a routine screening colonoscopy, a 66-year-old Caucasian male is found to have a
small mucosal lesion (- 1cm) in his sigmoid colon. A histology of the biopsied lesion is shown below. Which of the following gene mutations is most likely demonstrated by the epithelial cells forming the lesion?
A) APC
B) DCC
C) K-RAS
D) p53
E) MSH2
A) APC
117) A 65-year-old man complains of difficulty in walking up the steps and difficulty in chewing. Past history suggestive of cigarette smoking 2 pack a day for 20 years and occasional alcohol drinker. He said most of the time he will be better in the evening than in the morning. Neurologic examination is significant for decreased deep tendon reflexes. Chest x-ray shows an irregular round mass in the upper lobe of his right lung. Which of the following is the most likely
diagnosis?
A) Myasthenia gravis
B) Lambert-Eaton myasthenic syndrome
C) Polymyositis
D) Polymyalgia rheumatica
E) Amyotrophic lateral sclerosis
F) Multiple sclerosis
G) Guillain-Barre syndrome
H) Fibromyalgia
B) Lambert-Eaton myasthenic syndrome
118) A 67-year-old male presents with anorexia and weight loss. Physical examination shows non-tender hepatomegaly. Laboratory tests revealed elevated serum alkaline phosphatase level and elevated alanine aminotransferase (ALT) level. CT scan of the abdomen is shown below.
The most likely cause of this patient’s liver changes is:
A) Hepatic adenoma
B) Hepatic angiosarcoma
C) Hepatocellular carcinoma
D) intrahepatic cholangiocarcinoma
E) Hepatoblastoma
F) Metastatic liver tumor
F) Metastatic liver tumor
119) A 66-year-old male with a history of alcoholic cirrhosis experiences progressive abdominal distention, malaise, and anorexia despite complete abstinence from alcohol. His serum alpha fetoprotein level (AFP) has increased substantially over the last six months. This patient most likely suffers from:
A) Viral hepatitis C
B) Hemochromatosis
C) Wilson’s disease
D) a1-antitrypsin deficiency
E) Hepatic abscess
F) Hepatocellular adenoma
G) Hepatocellular carcinoma
G) Hepatocellular carcinoma
120) A 68-year-old male visited a physician complaining of low back pain for the past two
months. He said pain is constant and not relieved by over-the-counter analgesics. He complains of difficulty, dribbling and increased frequency in passing in urine mainly at nights. Random blood sugar is 120mg/dl. Which of the following is most likely the cause for his back pain?
A) Inflammatory
B) Degenerative
C) Neoplastic
D) Infectious
E) Neuropathic
C) Neoplastic
121) A 26-year-old female visited a physician for a lump in the left breast which was identified while she was bathing two days ago. She told the physician; she is worried it may be a cancer because her aunt was diagnosed with breast cancer at the age of 36 years and cousin diagnosed with prostate cancer at 42 years of age. Core biopsy of the breast lump showed poorly differentiated malignant cells. Which of the following gene mutations most likely cause her condition?
A) Protein degradation
B) Signal transduction
C) DNA repair
D) intercellular adhesion
E) Angiogenesis
C) DNA repair
122) A 62-year-old male visited for an enlargement of the previous mole over the chest. On examination, irregular border and poorly demarcated mole is present over the left side of the chest. Culture of the tumor cells demonstrate a high mitotic and increased matrix metalloproteinases activity. The latter finding causes increased risk for which of the following?
A) Anaplasia
B) Proliferation
C) Apoptosis
D) Invasion
E) Encapsulation
D) Invasion
123) A 64-year-old male comes to the physician with a history of easy bruising and weight gain for past few months. He said he daily activities and eating habits was normal as before. On examination, His blood pressure is 160/100 mm Hg and pulse is 90/min and he has hyperpigmentation around the neck and axilla with central obesity. CT scan revealed an irregular mass in the right apical lung field. Which of the following is most likely responsible for
his symptoms?
A) Excessive cortisol production by the lung mass
B) Excessive ACTH production by the lung mass
C) Excessive ACTH production by the pituitary gland
D) Metastatic involvement of the adrenal glands
E) Metastatic involvement of the hypothalamus
B) Excessive ACTH production by the lung mass
124) A 26 -year-old Caucasian female visited for breast biopsy results and found to have
adenocarcinoma of breast. She had a left leg amputation due to osteosarcoma at the age of 14 years. Her mother died of colon cancer at the age of 32 and her aunt suffered from
rhabdomyosarcoma. Which of the following gene mutations might be responsible for this
patient’s condition?
A) Rb
B) BRCA-1
C) p53
D) NF2
E) APC
C) p53
125) A 44-year-old undergoes surgery for a recently discovered mass in her right breast. Biopsy from the mass reveal invasive ductal carcinoma. Which of the following gene mutations is indicative of this patient tumor prognosis?
A) N -myc
B) ERBB2
C) sis
D) ras
E) bcl-2
B) ERBB2
126) An 18-year-old boy with sore throat and high fever is found on physical examination to
have cervical lymphadenopathy. Lab studies revealed leukocytosis with numerous atypical
lymphocytes and a positive heterophile antibody test. This patient’s disease infective agent is strongly associated with which of the following malignancies?
A) Acute myeloid leukemia
B) Kaposi’s sarcoma
C) Gastric carcinoma
D) Nasopharyngeal carcinoma
E) Multiple myeloma
F) Cervical carcinoma
G) Hepatocellular carcinoma
D) Nasopharyngeal carcinoma
127) A 51-year-old male visits the physician due to easy tiredness and exertional dyspnea. He takes ibuprofen occasionally for the low back pain. Past medical history was insignificant.
Laboratory studies reveal:
Fecal occult blood testing is negative.
Hematocrit 36%
MCV 86/fL.
WBC 7,000/mm3
Platelets 170,000/mm3
Sodium 136 mEq/L
Potassium 4.5 mEq/L
AST 34 U/L
ALT 18 U/L
Bilirubin 0.8 mg/dL
Creatinine 2.0 mg/dL
Plasma protein electrophoresis reveals a high peak corresponding to
gamma-globulins. The most likely diagnosis is:
A) Iron deficiency
B) Cobalamin deficiency
C) Chronic lymphocytic leukemia
D) Aplastic anemia
E) Plasma cell neoplasm
F) Hodgkin lymphoma
G) Hypothyroidism
E) Plasma cell neoplasm
128) A 58-year-old chronic cigarette smoker presents with a swelling in the left side of the neck. Physical examination shows non-tender, non-mobile, hard mass in the left supraclavicular region. Biopsy reveals anaplastic cells that stain positive for keratin. Most likely the cells were metastasized from which of the following?
A) Lymphocytes
B) Epithelial surfaces
C) Muscle tissue
D) Endothelium
E) Glial cells
B) Epithelial surfaces
129) A 62-year-old male who presented with abdominal pain is diagnosed with a rare vascular tumor. This tumor is associated with past exposure to arsenic or polyvinyl chloride.
Immunohistochemically staining of the tumor cells is positive for the CD 31 cell marker. Which one is the most likely diagnosis?
A) Cavernous hemangioma
B) Liver angiosarcoma
C) Cystic hygroma
D) Port-wine stain
E) Kaposi’s sarcoma
F) Lymphangiosarcoma
B) Liver angiosarcoma
130) A 72-year-old man complains of fatigue, back pain, for the last several months. He has a low hemoglobin level, and his serum creatinine is 2.9 mg/dl. Renal biopsy shows atrophic tubules, many with large, obstructing eosinophilic casts. The patient most likely suffers from which of the following?
A) Ischemic tubular necrosis
B) Acute pyelonephritis
C) Hypersensitivity interstitial nephritis
D) NSAID-associated nephropathy
E) Aminoglycoside toxicity
F) Lead nephropathy
G) Papillary necrosis
H) Urate nephropathy
I) Multiple myeloma
I) Multiple myeloma
131) A 44-year-old female complains of abdominal pain for past 2 months. CT angiography demonstrates a highly vascularized tumor present in the liver. Which of the following will aid in angiogenesis for tumor cells?
A) lnterleukin-1 (IL-1)
B) lnterferon-y (INF-y)
C) Epidermal growth factor (EGF)
D) Fibroblast growth factor (FGF)
E) Somatomedin C
D) Fibroblast growth factor (FGF)
132) A 60-year-old male smoker with a history of recurrent hemoptysis visits the physician
complaining of recent headaches. On physical examination he has visible facial swelling and
conjunctival edema. There is also marked dilatation of the vessels of his neck and upper trunk. Heart sounds are clear on auscultation. Which of the following is the most likely cause of this patient’s condition?
A) Pericardial effusion
B) Pleural effusion
C) Superior sulcus tumor
D) Mediastinal mass
E) Hormone secretion
F) Autoimmune disease
G) Airway obstruction
D) Mediastinal mass
133) A 68-year-old female presents with lower abdominal discomfort. Physical examination
reveals an adnexal mass on the right side. This patient is most likely to have elevated levels of
which of the following?
A) CEA
B) CA 19-9
C) CA-125
D) Alpha-fetoprotein
E) HCG
C) CA-125
Describe the features of benign tumors
- No metastasis
- Mobile & soft
- Develop in a fibrous capsule
- Ends in -OMA
- Progressive & slow growth
- Clear origins & well differentiated
Describe the features of a malignant tumor
- Lack/poor differentiation (anaplasia)
- Metastasis (go to blood to make a thrombus or to tissues with the appropriate receptors
- ## Enlarged sinuses
What cancers is fine needle biopsy used for?
Breast, lymph, thyroid
Pros of fine needle biopsy
fast & easy
Diff benign vs metastatic
Evaluate axillary nodes
Cons of fine needle biopsy
Doesn’t show histological architecture
Can’t differentiate ductal carcinoma in situ vs invasive malignancy
PSA is for
Prostate & thyroid
ERBB2
Breast
Bland & small fibrinous vegetations on left cardiac valves that appear in people with mucin secreting adenocarcinomas can lead to emboli
Nonbacterial thrombotic endocarditis
Non-bacterial thrombotic endocarditis
Bland & small fibrinous vegetations on left cardiac valves that appear in people with mucin secreting adenocarcinomas can lead to emboli
Typically associated with bronchogenic carcinomas
1) Periosteal bone growth on long bones
2) Arthritis in adjacent joints
3) Clubbing digits
Hypertrophic osteoarthropathy
Hypertrophic osteoarthropathy
Typically associated with bronchogenic carcinomas
1) Periosteal bone growth on long bones
2) Arthritis in adjacent joints
3) Clubbing digits
Typically associated with pancreatic cancer
Acute disseminated intravascular coagulation caused by acute promyelocytic leukemia & prostatic adenocarcinoma
Trousseau (migratory thrombophitis)
Acanthosis nigricans
Usually happens to people 40yrs and up. It appears as patches of grey-black hyperkeratotic skin
Associated with GI adenocarcinomas
Usually happens to people 40yrs and up. It appears as patches of grey-black hyperkeratotic skin
Associated with GI adenocarcinomas
Acanthosis nigricans
Associated with thymomas
The body makes antibodies against Ach receptors
Ptosis
Diplopia
Skeletal muscle weakness that gets worse with exercise
Myasthenia gravis
Describe the features of Myasthenia gravis
Associated with thymomas
The body makes antibodies against Ach receptors
Ptosis
Diplopia
Skeletal muscle weakness that gets worse with exercise
The body makes antibodies against Ca2+ channels in the neuromuscular junction
Associated with Small cell lung cancer
Proximal muscle weakness
Autonomic dysfunction
Acetylcholinesterase DOESN’T HELP
Lambert Eaton Myasthenia Syndrome
Describe the symptoms of Lambert Eaton Myasthenia Syndrome
The body makes antibodies against Ca2+ channels in the neuromuscular junction
Associated with Small cell lung cancer
Proximal muscle weakness
Autonomic dysfunction
Acetylcholinesterase DOESN’T HELP
Associated with Squamous cell lung carcinoma
It can be induced by
1) osteolysis triggered by cancer (primary bone myeloma or lesions)
2) Calcemic humoral production from an osseous neoplasm
Paraneoplastic hypercalcemia
What are the cancers that typically present with hypercalcemia
Breast
Lung
Kidney
Ovarian
Paraneoplastic hypercalcemia
Associated with Squamous cell lung carcinoma
It can be induced by
1) osteolysis triggered by cancer (primary bone myeloma or lesions)
2) Calcemic humoral production from an osseous neoplasm
Excess serum corticotrophin & promelanocortin
Cushing’s with Small cell lung cancer
Only excess serum corticotrophin
Pituitary disease dependent Cushing’s
Excess ectopic ACTH leads to excess cortisol
1) Hirsutism (hair on face)
2) Hyperglycemia
3) Muscle wasting
4) Hypokalemia
5) Moon face
6) Purple abdominal striae
7) Buffalo hump
Signs of Cushing’s disease
Signs of Cushing’s disease
Excess ectopic ACTH leads to excess cortisol
1) Hirsutism (hair on face)
2) Hyperglycemia
3) Muscle wasting
4) Hypokalemia
5) Moon face
6) Purple abdominal striae
7) Buffalo hump
Associated with small cell lung cancer
1) Low urine output
2) High thirst
3) Hyponatremia
4) Altered mental state
5) Seizures
6) Coma & death
SIADH
SIADH
Associated with small cell lung cancer
1) Low urine output
2) High thirst
3) Hyponatremia
4) Altered mental state
5) Seizures
6) Coma & death
Most common in Squamous & small cell carcinoma
Except young adults it’s lymphoma
1) Neck & facial swelling
2) Shortness of breath
3) Cough
4) Hoarseness (worse when bending forward or supine)
5) Dilated neck veins
6) Increased colorectal veins on the anterior chest walls
Compressed phrenic & right recurrent laryngeal nerve
Superior vena cava syndrome
Superior vena cava syndrome
Most common in Squamous & small cell carcinoma
Except young adults it’s lymphoma
1) Neck & facial swelling
2) Shortness of breath
3) Cough
4) Hoarseness (worse when bending forward or supine)
5) Dilated neck veins
6) Increased colorectal veins on the anterior chest walls
Compressed phrenic & right recurrent laryngeal nerve
Chest x-ray shows a mass in the upper right-sided mediastinal
Shown in Superior vena cava syndrome
BRCA1 can lead to what cancers
Breast, ovarian, & prostate cancer
BRCA2 can lead to what cancers
Breast cancers in men/women, ovary, prostate, & pancreatic cancer
UV light exposure which causes cross-linking of pyrimidine residues which disrupt nucleotide excision repair
Usually seen with basal cell carcinoma
Xeroderma Pigmentosum
Describe the features of Xeroderma Pigmentosum
UV light exposure which causes cross-linking of pyrimidine residues which disrupt nucleotide excision repair
Usually seen with basal cell carcinoma
Periumbilical region (“Sister Mary Joseph node”)
Osteolytic metastases in Thyroid carcinoma
Osteoblastic vertebral metastases due to
Multiple liver metastases from pancreatic
Mucosal Neuroma’s in MEN2B
Hamartomatous polyp- usually ascending
Adenomatous polyposis coli –multiple and usually transverse
Fibroadenoma of the Breast
Adenocarcinoma of the Breast
Metastases from Colorectal Cancer Involvement of liver
Adenomatous polyposis coli –multiple and usually transverse
Breast carcinoma has a mixed picture
peritoneal cul-de-sac (Blumer’s shelf
PULMONARY METASTASIS DUE TO CHORIOCARCINOMA OF TESTIS
mutation on x3p
Higher risk of the following:
1) Hereditary renal cancers
2) Pheochromocytoma
3) Hemangioblastomas of the CNS
Von Hippel Lindau
Von Hippel Lindau is associated with a higher risk of what?
mutation on x3p
Higher risk of the following:
1) Hereditary renal cancers
2) Pheochromocytoma
3) Hemangioblastomas of the CNS
Familial colon carcinomas (in the cecum & proximal colon) due to a DNA mismatch repair of MSH2 & MLH1 (causing microsatellite instability)
Hereditary Nonpolysis Colon Cancer syndrome
Describe the features of Hereditary Nonpolyposis Colon Cancer syndrome
Familial colon carcinomas (in the cecum & proximal colon) due to a DNA mismatch repair of MSH2 & MLH1 (causing microsatellite instability)
Loss of function mutation CDH1 (E-Cadherin) causes what cancers?
Familial gastric carcinoma (WNT signaling pathway)
SMAD4 mutation (inactivation)
Pancreatic cancer (TGF-B pathway)
NF2 Germline mutation leads to which cancer
Bilateral Schwannomas of the acoustic nerve
Describe the features of Wilms tumor
A WT1 gene defect (pediatrics kidney cancer)
When a nephro/neuroblastoma spread to the liver
NF2 Somatic mutations can lead to what cancers
Meningiomas & Ependymomas
A WT1 gene defect (pediatrics kidney cancer)
When a nephro/neuroblastoma spread to the liver
Wilms tumor
Knudson’s (2-hit) hypothesis describes how
Sporadic & familial mutations lead to retinoblastomas
RB Germline mutations can lead to what cancer?
Retinoblastomas & Osteosarcoma
RB somatic mutations lead to what cancer?
Glioblastoma & small cell lung cancer
One mutated P53 gene
- onset at a younger age
- Multiple primary tumors (Sarcomas, breast cancer, leukemia etc)
Li Fraumeni syndrome
1) Soft & rubbery cutaneous tumors
2) Cafe-au-lait sports
3) Hamartomas (in the iris) aka lisch nodule
Neurofibromas
Neurofibromas
1) Soft & rubbery cutaneous tumors
2) Cafe-au-lait sports
3) Hamartomas (in the iris) aka lisch nodule
Mucosal Neuroma’s in MEN2B
BCR-ABL mutation leads to what cancer
CML & Acute lymphoblastic leukemia
BRAF mutation leads to what cancer?
Leukemia (100%)
Melanomas (60%)
Benign Nevi (moles) (80%)
Dysregulated c-MYC translocation (X8-X14) can lead to what cancers?
Burkitt’s lymphoma & B-cell tumors
N-MYC mutations lead to what cancer
Neuroblastoma
L-MYC mutations lead to what cancer
Small cell cancer of the lung
Germline mutation of P16 can lead to what cancer
Melanoma
Somatically mutated P16 can lead to what cancer?
Pancreatic carcinomas
Oncogenic tyrosine kinase pathway mutations lead to _____ % of cancers
80%
ERBB1 mutations can lead to
Squamous cell carcinomas of the lung
ERBB2 mutations can lead to
Over expression of HER2 & Breast cancer
MEN2B mutations lead to
Medullary thyroid & adrenal tumors
HRAS mutations can lead to
Bladder tumors (Increased GTP activity)
KRAS mutations can lead to
Colon and pancreatic cancer (Increased GTP activity)
NRAS mutations can lead to
Hematological tumors (Increased GTP activity)
NF1 mutations can lead to
Neurofibromas (peripheral myeline tumor) Decreased GTP activity
RET mutations can lead to
MEN2A & MEN2B tumors
Hep B & C, Aflatoxins (green peanut mold), & Alcohol all lead to what cancer?
Hepatocellular cancer
H.pylori (USA) &Nitrosamines (Japan) cause what cancer?
Gi adenocarcinoma
Low fiber diet leads to an increased risk in developing what cancer?
Colorectal cancer
Asbestos leads to what cancer?
Lung, esophageal, Gi, colon cancer & mesothelioma
Benzene leads to what cancer
Acute myeloid leukemia
Vinyl Chloride leads to what cancer
Hepatic angiosarcoma
Silicosis leads to what cancer
Lung cancer & mesothelioma
Irritable bowel disease leads to what cancer
Colorectal cancer
Osteomyelitis leads to what cancer
Draining sinuses cancer
Chronic cystitis leads to what cancer
Bladder cancer (schistomiasis)
Mutated proto-oncogene leads to what cancer
Gain of function mutation
HPV (16 & 18) Lead to what cancers
Head, neck, & cervical cancer
EBV leads to what cancers
Burkitt’s lymphoma
Hodgkin lymphoma
Nasopharyngeal carcinoma (china)
Hematogenous spread of cancer
Sarcomas & carcinomas usually spread via veins to capillary beds & go to the lungs & liver (via the batson plexus & caval blood flow)
Osteolytic spread to the bone causing dense lesions (spine or pelvis are common)
Thyroid & prostate cancer
Lung cancers are likely to spread to which nodes?
Perihilar tracheobronchial & mediastinal nodes
Breast cancers are likely to spread to which nodes?
First axillary nodes
Inner quadrant breast cancer spreads to which nodes?
Nodes along the mammary arteries
Prostatic cancer likely metastases to
Bone
Bronchogenic cancer likely metastases to
Adrenals & Brain
Neuroblastomas cancer likely metastases to
Liver & Bone
Gliomas & skin cancer
Rarely metastases
Appendiceal carcinomas & mucinous cystadenomas fill the peritoneal cavity with gelatinous mass the pressure leads to loss of function of the visceral organs
Pseudomyxoma peritoni
Describe the features of Pseudomyxoma peritoni
Appendiceal carcinomas & mucinous cystadenomas fill the peritoneal cavity with gelatinous mass the pressure leads to loss of function of the visceral organs
Pleomorphic tumor of skeletal muscles with
1) marked cellular atypia
2) nuclear pleomorphism
3) hyperchromatic nuclei
4) giant cell tumors
Rhabdosarcoma
Describe the features of Rhabdosarcomas
Pleomorphic tumor of skeletal muscles with
1) marked cellular atypia
2) nuclear pleomorphism
3) hyperchromatic nuclei
4) giant cell tumors
Tripolar & multipolar spindles
Loss of polarity
Large central areas of ischemic necrosis
Breached basement membrane
indicate
Malignancy
Invasive ductal carcinoma of the breast
PULMONARY METASTASIS DUE TO CHORIOCARCINOMA OF TESTIS
Fibroadenoma
Fibroadenoma of the Breast
