ONCOLOGY
Occular Neoplasms
Retinoblastoma
Clinical Case:
Notes:
- retinoblastoma is a cancer of the retinal cells of the eye
- mutation in the RB1 = retinoblastoma gene on chromosome 13
--> good example of the two-hit hypothesis for gene mutations --> neoplasms - think RB1 --> baseball --> number #13 and the 2-hit hypothesis
- 2-hit hypothesis
- 1-hit - when you have germline defect in one pair of the RB1 gene on chromosome 13
--> this is called heterozygosity since you still have one good and intact gene - 2-hit - if you develop a mutation in the second gene, then you will develop retinoblastoma
--> this is called loss of heterozygosity
Oncology
*Treatments
Checkpoint
Inhibitors
*Chemotherapy
Head And Neck Cancers
HNSSC's
(Head and Neck Small Cell Carcinomas)
Notes:
- note that any cancers of the head and neck are mostly all squamous cell carcinomas
- most are caused by smoking and drinking and have primary sites in the oropharyngeal cavity
- they can then spread and invade to local lymph nodes of the neck
Benign Tumors
Neurofibromatosis (type 1)
Notes:
- note that Neurofibromatosis is a single gene autosomal dominant disorder
- there are 2 types of NF
- it has a mutation in the NF-1 gene = neurofibromatosis gene
- remember that Neurofibromatosis has Cafe Au Lait spots on their skin, which also gives prime = 17 - CAFE SPOT = all the possible symptoms of NF:
- C = cafe au lait spots
- A = axillary freckling (this is much more in NF 1 vs. NF2)
- F = fibromas (dermal often)
- E = eye Lisch Nodules (hamartomas around the iris of the eye)
S = scoliosis and skeletal bowing - P = pseudoarthrosis
- OT = Optic tumors (meningiomas, gliomas, astrocytomas, etc.)
- prime 17 = NF comes from mutation of NF-1 gene on chromosome 17
Clinical Presentation
Neurofibromatosis (type 2)
click to edit
Oncological *Mutations
- either in oncogenes or tumor-Supressing genes
Apoptosis
- both intrinsic and extrinsic Pathways
Extrinsic Apoptosis
- Fas / FADD death domain / Caspases 8 & 10
Lymphocytic Fas Apoptosis
- Auto-immune disease (RA and SLE)
- leukemia and other cancers
Notes
- the extrinsic pathway of apoptosis goes through the Fas receptor
- think of Fast suicide
- Fas is bound by FasL ligand
--> 3 Fas receptors form a trisomer - trisomer becomes the FADD = Fas associated death domain
- the FADD activates Caspases 8 and 10 that then initiate activer caspases 3 and 5
-- think of caspases 8 and 10 = "hateful 8 suicide squad" - note that the Fas / FADD / Caspases 8 and 10 are important for T lymphocytes to make sure they don't get out of control
- they can self activate their own Fas extrinsic apoptosis and also to nearby T cells
Case example:
Skin Cancer
Melanoma
Melanoma example
Clinical Case
Notes:
note the ABCDE of Melanoma lesions
A = assymetry
B = borders are irregular
C = colour is varient throughout --> red, brown, black
D = Diameter >=6 mm
E = Elvolving or changing
note that that melanocytes come from neural crest cells
Xeroderma Pigmentosum
- see dermatology
Neuro FM case 2
- the fibromas in neuro FM are benign fleshy macule papules
- they are from peripheral neuron myelin sheath
- Schwann cells --> derived from neural crest GAMES (+ ad med)
Notes:
- note that Neuro FM has both flesh coloured papules that grow larger and larger and accumulate and are benign
- note though that neuro FM can lead to malignancies in the brain
- they also present with multiple cafe au lai spots
- remember the mnemonic CAFE SPOTS for Neurofibromatosis
--> think of the fibromas as coffee cups on the trunk with spilled coffee
--> CAFE AU LAI with fibromas
Clinical Case
- remember that Neurofibromatosis has COFFEE CUPS on their back with SPILLED COFFEE
--> Cafe Au Lait spots = prime 17
CAFE SPOTs
- C = cafe au lait spots
- A = axillary freckling (this is much more in NF 1 vs. NF2)
- F = fibromas (dermal often)
- E = eye Lisch Nodules (hamartomas around the iris of the eye)
S = scoliosis and skeletal bowing - P = pseudoarthrosis
- OT = Optic tumors (meningiomas, gliomas, astrocytomas, etc.)
- prime 17 = NF comes from mutation of NF-1 gene on chromosome 17
Intrinsic = mitochondrial Apoptosis
- Cytochrome C release + ?
Apoptosis Overview: Intrinsic and Extrinsic Pathways
Apoptosis and Caspases
Notes:
- note that in both the pathways for apoptosis there are either initiator caspases or effector caspases
- extrinsic initiator caspases = 8 10
- the FADD activates Caspases 8 and 10 that then initiate activer caspases 3 and 5
Case example:
Caspases
Initiator Caspases7
--> 2 8 9 10
Effector Caspases7
--> 3 5
Pituitary Adenomas
- benign tumors that present with bitemporal hemianopsia = vision loss / bluriness
--> optic chiasm compression - present with headaches
Prolactinoma
- most common type of actively hormonal pituitary adenomas
- prolactin causes galactorhea
- prolactin inhibits GnRH from hypothal
--> hypogonadism in men and amenorrhea in women
Prolactinoma example
- most common type of actively hormonal pituitary adenomas
- prolactin causes galactorhea
- prolactin inhibits GnRH from hypothal
--> hypogonadism in men and amenorrhea in women
Notes:
- note that hyperprolactinema causes galactorhea in women
- prolactin also inhibits GnRH from hypothal
--> hypogonadism in men = decreased libido
--> amenorrhea in women
Case presentation:
Side Effects and Toxicities of Chemotherapy Agents
Alkylating Agents
Cisplatin
- 3 in ABCs of chemo toxicites
- ottotoxicity, nephrotoxicity, peripheral neuropathy
Notes:
- Cisplatin has a very high rate of high frequency hearing loss
- it has the symptoms ONE --> nephrotoxicity
--> ottotoxicity, nausea, emesis, nephrotoxicity
ABCs 123 of Chemo Toxicity:
1 A = Anthrocyclines - I toxic ruby heart
--> dilated cardiomyopathy
2 B = bleomycin - 2 hardenned lungs
--> pulmonary fibrosis
--> note also PF from AB = amiodarone + bleomycin, methotrexate, nitrofurantoin Abx
3 C = cisplatin- 3 pairs of organs affected
--> 2 ears = ottotoxicity
--> 2 kidneys = nephrotoxicity
--> 2 lower limbs = peripheral neuropathy
Anthracyclines - "toxic Ruby Hearts"
- end in "-rubicin" = toxic ruby heart
- doxorubicin
Clinical Case
Clinical Case
Notes:
- note that
*Radiation Therapy
*Bladder Cancer
- gross PAINLESS hematuria in OLDER MEN
--> TBC = trasnitional Bladder CA
--> UNTIL PROVEN OTHERWISE - smoking and workplace exposure to plastics or rubber are the biggest risk factors
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
*Heart Cancer
- primary tumors of the heart are rare
- most common 80% = left atrial myxoma
Myxoma Histology
- high vascular to myxomas since in the heart
- hemorrhage
- hemosiderin macrophages
--> like in Left HF
Clinical Cases
Clinical Case
Notes:
- note that
Clinical Case
*Specific Tumor Mutated Genes
*2 hit Hypothesis with oncogenes
Notes:
- Knudson's 2 hit hypothesis says that of the 2 major types of inherited genetic cancer mutations, the proto-oncogenes only require 1 hit for the oncogenes to have a gain of function mutation
- the tumor supressor genes, may have a one-hit inactivation of the gene
- the 2nd hit leads to malignancy
- note these are all autosomal dominant
ALK
- ALK cancer = LARGE ALK with LARGE LUNGS and LYMPHOMAS
--> large cell lymphomas
--> non-small cell lung cancer
APC - APC = ALWAYS PASS (away) CANCER = PC - Pancreatic and Colorectal
--> tumor supressor gene APC in pancreatic and colorectal cancer
ALK - VHL gene = Von Hippel Lindau / Von trap dominant kid can't stand due to kidney problems...
plays the HARP
--> RP kidney prolems
--> RCC and pheochromocytomas
*oncogene Mutations
*KRAS - MAPK gene mutation
- "KRAS" = Konstant Ras activation
--> GTP active form - "KRAS - MAPK = MA PK" = Messenger ADENOCARCINOMA of Pancreas / KOLON
*RET gene mutation
- "RET = RETTY your DOMINANT MEN 2 screen for BOTH"
- "MEN2" = MEdulla / EN2 = Endocrine organs x 2
--> adrenal medulla = pheochromocytoma
--> medulla of thyroid = either parathyroid or mucosal secreting - "2 screen for BOTH" - if you find RET mutation you have to screen for both mutations
Clinical Cases
Clinical Case
Notes:
- note that
Clinical Case
Ras Mutations
- Bras = GTP-bound oncoprotein
- cell surface --> nucleus transporter
Notes:
- note that TP53 in the tumor-supressor gene family is mutated in almost all cancers
- not as common as TP 53, but Ras GTP-bound transporter oncogene is the most common oncogene mutation
--> 20% of cancers have Ras mutation
Clinical Case
*Tumor Suppressor Mutations
*Home
*Cervical Cancer
- most are caused by HPV infection
*HPV and Cervical Cancer
- 1s, 6s , 8s Strains
- malignant HPV = strains 16, 18 and 31
--> sexual transmission
--> condoms - genital warts HPV = strains 6 and 11
--> skin to skin transmission
--> no protection
*Pancreatic Cancer
- APC gene mutation
--> "ALWAYS PASS (away) CANCER" - Any older person who presents
--> SMOKER
--> painless jaundice and palpable GB
= pancreatic cancer until proven wrong by a scan - smoking is the biggest risk factor for pancreatic cancer
*MEN1 gene
*RET gene = RETy MEN2 battle (first and second waves MEN 2 a/b)
*ALK gene mutation
- adenocarcinoma of LUNGS
- tyrosine Kinase receptor
*tp53 - LiFraumeni Syndrome = SBLA
- Mortal Kombat on a Truck
--> dropping TP53
*WILMS tumor = WT1 gene mutation
- nephroblastoma
Clinical Cases
Clinical Case
Notes:
- note that
Clinical Case
p53 ts gene and Li-Fraumeni Syndrome
Notes:
- remember "Li Frowns from tp53 BBS"
--> breast, brain, sarcomas
Clinical Case
*Carcinogens
- smoking is by far the biggest factor
*Kidney Cancer
- over 90% are RCC
"cannonball metastases" from RCC in lung
*Multiple Myeloma
- BAB the CRAB
M and M playing poker with BAB the CRAB and 2 GOBLINS = GOLD GOBLIN and APPLE GOBLIN
- BAB the CRAB
- antibodies of M and Ms POKER GAME = GOLD GOBLIN and APPLE GOBLIN
the river ELECTROPHORESIS of the first hand comes up as a SINGLE M PROTEIN SPIKE and the GOBLINS eat FRIED EGGS to pretend like they aren't nervous
- M protein SPIKE in M&Ms
M&M goes ALL in with his STACKS of RBCs along with his ROULEAX ROLLEX and the GOBLINS return by throwing in the KEYS to their own BENZ JONES GOBLIN CAR
- ROULEUX = stacked RBC CHIPS
- BENZ JONES GOBLIN CAR = Bence jone Ig light chains
*Lipomas
- sarcolipoma = the most common soft tissue tumour of adults
*sarcolipoma
- sarcolipoma = the most common soft tissue tumour of adults
- usually present in the pelvis area or the thighs are most common
--> note this is what Eamon had
*Li-Fraumeni Syndrome = LFS
- "LOU FERIGNO syndrome"
- caused by a p53 germline mutation
- autosomal dominant
- very high risk and penetrance for mutlple kinds of cancers
*Common hereditary cancer mutations
*Lynch Syndrome and HNPCC
*Common tumor markers
*Cardiac tumors
- myxoma most common
- comes from the left atrium
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
