Solid Tumor Flashcards
(181 cards)
1
Q
What is the percentage of patients with lung cancer that will die of their disease?
A
70%
2
Q
What are the risk factors for lung cancer?
A
smoking + asbestos smoking passive smoke asbestos radon nickel radiation
3
Q
How does quitting smoking affect lung cancer risk?
A
It takes 10-15 years to reduce risk by 75%, but the risk never approaches 0
4
Q
What is the best way to screen for lung cancer in former heavy smokers?
A
CT
5
Q
When should lung cancer screening start?
A
55 for heavy smokers
typically until age 74-79
6
Q
What are the 2 nonsurgical sampling techniques used for lung cancer testing?
A
Fine needle aspiration (cytology) Core biopsy (surgical pathology)
7
Q
What is a hamartoma?
A
- Most common benign neoplasm in the lung
- Tissue elements normally found in lung but occurring as disorganized proliferation
- “Coin” lesions with popcorn calcifications
- Well-circumscribed
- Slow-growing
- Varying amounts of mesenchymal elements (cartilage, fat, connective tissue, muscle, bone)
- Entrapped respiratory epithelium
8
Q
What is a typical carcinoid of the lung?
A
Neuroendocrine tumor Central, involves the airway Well-circumscribed Fills bronchial lumen Monomorphic Fine "salt and pepper" chromatin
9
Q
What is small cell lung cancer?
A
Typically large central mass with bulky mediastinal adenopathy • Scant cytoplasm • Inconspicuous/absent nucleoli • Nuclear molding • Crush artifact • Numerous mitoses (>10/2mm2) • Necrosis typically poor prognosis
10
Q
What are the 2 driver mutations in lung epithelial tumors?
A
KRAS
EGFR
11
Q
What is large cell carcinoma?
A
•Non-small cell carcinoma that lacks cytological, architectural and immunohistochemical features of small cell carcinoma, adenocarcinoma and squamous cell carcinoma
12
Q
What is sarcomatoid carcinoma?
A
- Pleomorphic Carcinoma
* Non-small cell carcinoma with at least 10% spindle and/or giant cells
13
Q
Which primary cancers tend to met to the lungs?
A
breast prostate GI gynecological tract head and neck
14
Q
How does lung cancer present?
A
- Cough
- Dyspnea
- Hemoptysis
- Chest Pain
- Hoarseness- recurrent laryngeal nerve
- SVC Syndrome
- Wheezing
15
Q
What are systemic symptoms of lung cancer?
A
Weight loss, malaise Clubbing Hypertrophic Pulmonary Osteoarthropaty SIADH (SCLC) Hypercalcemia (squamous) Cushings Syndrome (SCLC) Horner's Eaton-Lambert Syndrome (SCLC) hypercoagulable state of malignancy
16
Q
How are the different stages of lung cancer treated?
A
IA: surgery IB: surgery and chemo IIA: surgery and chemo IIB: surgery and chemo IIIA: chemo, surgery, radiation IIIB: chemoradiation IV: chemo
17
Q
Which chemo agents are usually given in lung cancer?
A
Typically a platinum agent (preferably cisplatin, if not possible then carboplatin) + a second agent (premetrexed, docetaxel, gemcitabine, etc)
18
Q
How is metastatic lung cancer treated?
A
2 agents
Platinum + second agent
In this case, cisplatin and carboplatin are the same for survival
19
Q
How does cisplatin work?
A
inhibits DNA synthesis by the formation of DNA cross-links, disrupts DNA function
20
Q
What are the side effects of cisplatin?
A
- Neurotoxicity
- Nausea/vomiting
- Ototoxicity (can’t use in patients with hearing aids)
- Nephrotoxicity – need to hydrate!
- Electrolyte disturbances
21
Q
What is paclitaxel and how does it work?
A
–Taxane: disruption of microtubule function (stabilizer), including cell-cycle arrest & apoptosis
22
Q
What are the side effects of paclitaxel?
A
- Alopecia
- Decreased blood counts
- Neuropathy
- Hypersensitivity reaction
- Arthralgias/myalgias
- Fatigue
- Nail changes
23
Q
What is pemetrexed?
A
–Antimetabolite: inhibits folate-dependent enzymes involved in purine & pyrimidine synthesis - thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT)
–Multitargeted folate analogue
24
Q
What are the side effects of premetrexed?
A
well-tolerated! •Decreased blood counts •Nausea •Fatigue •Rash •Supplementation with B12 and folic acid to reduce side effects
25
What is erlotinib and how does it work?
Oral therapy!
–Tyrosine kinase inhibitor: inhibitor of epidermal growth factor receptor (EGFR)
•Intracellular phosphorylation inhibited which prevents further downstream signaling
26
What are the side effects of erlotinib?
* Rash
* Diarrhea
* Nausea
* Fatigue
27
Who sees the most improvement with erlotinib?
EGFR mutation
females
never smokers
Asians
28
What is etoposide?
–Topoisomerase inhibitor: forms complex with DNA and toposisomerase II, preventing re-ligation of DNA strands and causing breakage
29
What is the #1 cancer in women?
Breast
30
What is the #1 cancer cause of death in women?
Lung
31
Is BRCA 1 or 2 more common?
BRCA 1
32
What are risk factors for breast cancer?
```
BRCA mutations
Chest wall irradiation
Increased breast density
Family history
First child born after age 30 (or no children)
Menarche before 12
Menopause after 55
Hormone replacement therapy for more than 5 years
Postmenopausal obesity
More than 2 drinks per day
```
33
What cancers are associated with BRCA?
```
Breast
Male breast
Ovarian
Prostate
Melanoma (not huge risk)
Pancreatic (not huge risk)
```
34
Where do most lesions from the breast arise?
Terminal duct lobular unit
35
What is the differential for breast lumps?
* Fibrocystic changes – common 40-50% of lumps, usually diffusely tender, pain can be cyclical or constant. Frequently nodular breast tissue on physical exam
* Fibroadenoma – benign solid mass, often firm and mobile
* Cyst – commonly found in premenopausal and perimenopausal women
* Fat Necrosis – benign mass which develops after trauma, post-procedure, radiation therapy
* Galactocele – milk retention cyst common in breast feeding women
* Breast cancer
36
What is associated with gynecomastia?
```
relative estrogen excess
cirrhosis
Klinefelter’s (47XXY)
estrogen secreting tumor
estrogen therapy
digoxin therapy
•Physiologic gynecomastia most common in puberty and older age
•No clear cut association with development of carcinoma
```
37
What is a fibroadenoma?
* Most common benign tumor of the female breast
* Usually appears in young women
* Peak incidence in the 3rd decade of life
* A benign fibroepithelial tumor usually solitary but can be multiple
* Rarely associated with carcinoma
38
What is intraductal papilloma?
* Benign papillary neoplasm within a duct
* Papillary = tree-like growth
* Identified peripherally or centrally
* Centrally: nipple duct – presents with bloody nipple discharge
* 1.5-2x risk of developing invasive cancer in patients with multiple peripheral intraductal papillomas
39
Which benign breast diseases have no increased risk of cancer?
* Mild hyperplasia
* Apocrine metaplasia
* Cysts
* Duct ectasia
* Fibroadenoma
40
Which benign breast diseases have a mildly (1.5-2x) increased risk of cancer?
* Moderate or florid hyperplasia
* Papilloma with fibrovascular core
* Adenosis (sclerosing or florid)
41
Which benign breast diseases have a moderately (4-5x) increased risk of cancer?
* Atypical Ductal Hyperplasia
* Atypical Lobular Hyperplasia
* Borderline Lesions
42
What is Atypical Ductal Hyperplasia?
ADH/Borderline lesion: proliferative lesion where some criteria of carcinoma in situ are met but not all
•Non-obligatory precursor of cancer, may progress to ductal carcinoma in situ
•Prevalent in ~5% of biopsies
•4-5x risk of developing invasive breast cancer
•Cancer risk is bilateral
•Risk persists for 20+ years
•Prognosis of ADH-associated cancer is the same as cancer lacking ADH
•~30% of patients with ADH on biopsy have invasive cancer on excision
43
What is Lobular Carcinoma in Situ?
Lobular Carcinoma In Situ (LCIS)
Neoplastic transformation of epithelial cells with distinct phenotype: small cell size and E-cadherin negative. Primarily present in recognizable lobules and surrounded by myoepithelium
•Typically multifocal and bilateral
•6-11 fold increase of development of invasive cancer
•Bilateral risk for development of invasive cancer
•75% of invasive cancers are ductal type
•Considered primarily a marker for invasion but is also a non-obligatory precursor for invasive lobular carcinoma at a low rate
44
Who should receive breast MRI?
•BRCA mutation carriers
•Other hereditary breast cancer syndromes (i.e., Li-Fraumeni, Cowden’s syndrome)
•Lifetime breast cancer risk 20-25%+, largely based on family history
•Prior chest irradiation
Should begin yearly at age 25
45
How does tamoxifen work?
Selective Estrogen Receptor Modulator (SERM)
| Reduces risk of invasive ER+/PR+ breast cancer, improves bone health in post-menopausal women
46
What are the side effects of tamoxifen?
Hot flashes
Thromboembolism (stroke, PE, DVT)
Endometrial cancer (postmenopausal women)
Cataracts
47
How does anastrazole work?
Aromatase inhibitor
Prevents peripheral conversion of androstenedione to estrone and testosterone to estradiol
Reduces risk of invasive ER+/PR+ breast cancer
48
What are the side effects of anastrazole?
Arthralgias
Decreased bone density, increased risk of fracture
Hot flashes (1/3rd)
49
Who should get anastrazole? Who should get tamoxifen?
Tamoxifen can be used in pre- and post-menopausal women for
Anastrazole should only be used in postmenopausal women
Neither should be used in patients with history of blood clots
50
What is Ductal Carcinoma in Situ?
* Neoplastic transformation of epithelium within ducts or lobules surrounded by myoepithelial cells
* Non-obligatory precursor to invasive breast cancer
* Characterized by nuclear grade and histologic patterns: comedo, solid, cribiform, clinging, and papillary type
* Usually detected by microcalcifications on mammography
* Up to 25% of breast cancer
* High grade and large size predicts likelihood of multifocality and invasion
* 8-10x risk of invasive carcinoma
* Risk is primarily ipsilateral
51
How is DCIS treated?
Surgery (mastectomy, breast-sparing)
| should also use radiation and chemoprevention (if ER+/PR+)
52
Is breast cancer typically lobular or ductal?
10% lobular, 90% ductal
53
What is Invasive Lobular Carcinoma?
* An infiltrating carcinoma resembling the cells of LCIS
* Histologically showing classical “Indian file” pattern and targetoid “bull’s eye” pattern
* Composed of relatively small cells with scanty cytoplasm, sometimes vacuolated (E-cadherin negative)
* Represents approximately 10% of breast cancer with a higher than usual incidence of bilaterality (approximately 20%)
54
What is Luminal A breast cancer?
ER+
low grade
excellent prognosis
55
What is Luminal B breast cancer?
ER+ (but less than luminal A)
higher grade and higher proliferation than luminal A
worse prognosis than luminal A
56
What is Her-2 Enriched breast cancer?
Her2+
Usually ER-
poor prognosis
57
What is Basal-like Breast Cancer?
Triple negative
High grade, high proliferation
A lot of variation
58
What are the stages of breast cancer?
* Stage 0: Cancer cells are present in the lining of a breast lobule or duct but have not spread to the surrounding tissue – DCIS
* Stage I: Tumor is <2 cm, lymph nodes are NOT involved
* Stage II: Tumor can range from 2-5 cm OR ≤3 lymph nodes are involved
* Stage III: Locally advanced cancer; tumor larger than 5 cm OR ≥4 lymph nodes
* Stage IV: Metastatic; cancer spread to other parts of the body such as: bone, liver, lung, or brain
59
Which women with breast cancer gain most from chemo?
triple negative
poly is better than single agent chemo
anthracycline is most effective
60
How does doxorubicin work?
intercalates DNA, inhibitor of topoisomerase II, generation of free radicals
Metabolism: Liver
61
What are the side effects of doxorubicin?
GI – nausea/vomiting, stomatitis, diarrhea
Bone marrow suppression
Alopecia
Cardiotoxicity – usually late and irreversible
Secondary malignancy – AML/MDS
62
How does cyclophosphamide work?
Mechanism of Action: Cross links DNA preventing to cell division and DNA synthesis
Metabolism: Liver
63
What are the side effects of cyclophosphamide?
GI – nausea/vomiting
Bone marrow suppression
Hemorrhagic cystitis – at high does (MESNA reduces this)
Secondary malignancy – AML/MDS and bladder cancer (hemorrhagic cystitis)
Impaired fertility
64
How do paclitaxel and docetaxel work?
Taxanes
Class: Antimicrotubule agent
Mechanism of Action: Stabilizes microtubules and inhibits disassembly interfering with late G2 phase and inhibiting replication
Metabolism: Liver
65
What are the side effects of taxanes?
GI – nausea/vomiting, mucositis, diarrhea
Alopecia
Bone marrow suppression
Peripheral neuropathy
66
Where is the Her2 gene?
17q
67
How does trastuzamab work?
Mechanism of Action: monoclonal antibody binds to the extracellular domain of HER-2 mediating antibody-dependent cellular toxicity by inhibiting proliferation of cells which overexpress HER-2
("herceptin")
68
What are the side effects of trastuzamab?
Cardiomyopathy – need to follow with echocardiogram, usually reversible
Infusion reaction
69
How does palbociclib work?
Mechanism of Action: Small molecule cyclin-dependent kinase inhibitor of CDK 4 and 6, prevents progression from G1-S phase.
Metabolism: liver
Extends progression-free survival in HR+/Her2- breast cancer
70
What are the risk factors for esophageal squamous cell cancer?
```
–Smoking
–Alcohol
–History of caustic ingestion
–Betel nut chewing
–HPV?
Associated medical conditions:
–Achalasia
–Tylosis
–Plummer-Vinson syndrome
```
71
What are the risk factors for esophageal adenocarcinoma?
```
Male
white
GERD
smoking
obesity
h pylori
Barrett's
```
72
How is Barrett's treated?
PPIs
| endoscopic observation
73
How is esophageal cancer treated?
•Early lesions (T1a) = Endoscopic mucosal resection
•Advanced lesions (≥T1b, nodal involvement) =
–SCC: Surgery or definitive chemoradiation (preferred for cervical esophagus, T4b)
–EAC: Neoadjuvant chemoradiation (Carboplatin + Paclitaxel), then surgery
•Metastatic disease
–Palliative chemotherapy (HER2 testing in EAC)
–Obstruction: stenting, radiation
–Bleeding: radiation
74
What are the 2 types of gastric cancer?
intestinal (glandular)
| diffuse (poorly differentiated, infiltrates layers of the stomach)
75
What are the risk factors for gastric cancer?
```
•Environmental
–H pylori infection
–Smoking
–High salt intake
–Dietary nitrites (?)
•Associated medical conditions
–Prior gastric surgery (esp. Bilroth for PUD)
–Pernicious anemia
–Obesity (cardia tumors)
–Gastric ulcers (+), Duodenal ulcers (-)
```
76
What are the signs of gastric cancer?
```
•Weight loss, early satiety
•Pain
•Vague GI symptoms—nausea, indigestion
•GI bleeding—melena or hematemesis
•Clinical signs (late):
–Sister Mary Joseph node
–Virchow’s node
–Ascites
–Krukenberg tumor
•Cutaneous paraneoplastic manifestations (rare, nonspecific) :
–Acanthosis nigricans
–Seborrheic keratoses
–Tripe palms
•Trousseau’s syndrome
```
77
What is TNM criteria?
T: depth of tumor invasion
N: number of nodes involved
M: distant metastasis
78
Why is pancreatic cancer so deadly?
Due to mutations, tumor stromal interactions and immunosuppressive microenvironment. (likely no T cells)
Difficulty of early detection or risk stratification.
Due to position of pancreas, age and lack of modifiable risk factors.
Resistance to chemotherapy
79
What is mutated in pancreatic cancer?
Almost all tumors have activating KRAS mutations.
Most have additional mutations in tumor suppressor pathways.
The number of mutations is prognostic- more is bad.
80
What is distinct about the morphology of pancreatic ductal adenocarcinoma?
Dense tumor stromal response
| Note: impairing the stroma does not cause remission (causes bigger tumors)
81
What are risk factors for pancreatic cancer?
```
Strong:
Cigarette Smoking
Genetic Syndromes
Age
Weaker:
Diabetes 5+ years
Obesity/physical activity
Diet
Chronic Pancreatitis for more than 7 years
```
82
What are signs of pancreatic cancer?
```
Most common presenting symptoms:
–Weight loss
–Abdominal pain
–Depression
Other important flags:
–New onset diabetes
–Blood clot (unprovoked)
- Jaundice
```
83
Why is pancreatic cancer often unresectable?
Grows into the nearby important arteries
84
Which treatments are used in pancreatic cancer?
Surgery if possible
Gemcitabine
Can try chemo and radiation to allow for surgery
FOLFIRINOX
85
What is the most common cancer in men?
Prostate`
86
In which race is prostate cancer most common?
African Americans
87
What is PSA?
•Glycoprotein enzyme produced by prostate epithelial cells
–Functions to liquefy semen
–Tissue barrier between prostate lumen and blood are disrupted in cancer
•Adopted as a screening tool for prostate cancer
Cut off is currently 4.0
88
When can PSA be elevated (not including prostate cancer)?
BPH
prostatitis
just after ejaculation
urinary retention
89
What are common symptoms of prostate cancer?
–Urinary frequency, urgency, nocturia, hesitancy
–Hematuria, hematospermia(uncommon)
–Bony pain in metastatic setting
90
Where does prostate cancer typically arise?
peripheral zone (zone 1)
91
What is the weight of a normal prostate?
7-20 gm
92
Where is BPH typically found?
Hyperplasia almost exclusively in the transition zone (around the urethra)
93
What are the 3 layers of skin?
Epidermis
Dermis
Subcutis (inner)
94
What are the 3 kinds of cells found in the epidermis?
Keratinocytes (squamous)
Melanocytes
Langerhans cells
95
What is responsible for the differences in skin tones?
```
# of melanocytes is stable between people of different races
Dependent on the size of melanosomes or pigment granules and how they're distributed
```
96
What is found in the dermis?
collagen
97
What is found in the subcutis?
lobules of fat and fibrous septae
98
What is seborrheic keratosis?
Most common benign neoplasm of squamous cell origin
Typically occur in people 40 and older
Have raised, rough surface with well-circumscribed margin
Flesh-colored, brown, or black
99
What is verruca vulgaris?
Common wart
Caused by papilloma virus, which is found in nuclei of keratinocytes in the upper portion of the epidermis (but not the lower)
100
What is solar keratosis?
Common premalignant neoplasm of keratinocytes
Found in sun-damaged skin
Present as rough, slightly elevated papules or plaques which are usually pink or brown
Can be locally aggressive but rarely metastasize
101
What is basal cell carcinoma?
Common skin cancer
Grow relatively slowly
Almost never metastasize
Can be papules or nodules or look like eczema
102
Who gets basal cell carcinoma?
People exposed to the sun, particularly UVB
Bad genetics
Common in fair-skinned people, super uncommon in African Americans
103
How is basal cell carcinoma treated?
Local control (excision, curettage, etc)
104
What is squamous cell carcinoma?
Variable tumor
| Uncommonly metastastizes
105
Who gets squamous cell carcinoma?
Immune deficient patients
People with light skin
Patients with psoriasis
Transplant patients
106
What is the Gleason Score? What is high risk? Low risk?
```
•Prostate cancers can have areas with different Gleason grades
•Gleason score: sum of the two most commonly seen Gleason grades
–eg: Gleason 3+3 = 6
Gleason 3+4 = 7
Gleason 4+3 = 7
•Gleason score 6: Low risk
•Gleason score 7: Intermediate risk
•Gleason 8-10: High risk
```
107
What are the risks of prostatectomy?
sexual dysfunction/impotence
| incontinence
108
What are the risks of external beam radiation in prostate cancer?
```
radiation proctitis
enteritis
cystitis
sexual dysfunction
low risk for urinary incontinence
```
109
What are the risks of brachytherapy in prostate cancer?
urinary retention
proctitis
sexual dysfunction
110
Is brachytherapy done with external beam radiation?
Sometimes in higher risk prostate cancer
111
When is observation appropriate for prostate cancer?
PSA 10 or below
Gleason score 6
T1c or confined to one lobe of the prostate
112
How is metastatic prostate cancer treated?
Androgen deprivation therapy with surgical orchiectomy or medical orchiectomy (GnRH agonist to overload the system and then bicalutamide to counter "flare")
113
What is castrate resistant prostate cancer?
* Hormone sensitive prostate cancer often becomes resistant to hormonal therapy after an average of 2 years.
* This is termed castrate resistant prostate cancer (CRPC).
* Metastatic CRPC is the lethal form of prostate cancer.
114
How can castrate resistant prostate cancer be treated?
```
•Chemotherapy
–Docetaxel, cabazitaxel
•Secondary hormonal manipulation
–Abiraterone
–Enzalutamide
•Immune therapy
•Radium 223
```
115
What is abiraterone?
CYP17 hydroxylase inhibitor
Shuts down androgen system preventing production of steroids
Needs to be taken with steroids
116
What kind of cancer are most hand and neck cancers?
squamous cell
117
What are common symptoms of head and neck cancer?
* Hoarseness
* Fullness in nose / ear
* Difficulty swallowing
* Mass in neck, mouth
* Non healing oral sores/plaques
* Jaw pain
* Unexplained weight loss
118
What are the demographics of head and neck cancer?
•2.5 men : 1 woman
–4:1 oropharynx
–7:1 larynx
•Median age 60
119
What are risk factors for head and neck cancer?
•Tobacco and Alcohol
–75% attributed
–RR increased by 40 fold for those with 40 pack-year hx and over 30 drinks/week
•Viruses – HPV, EBV
•Diet (Vitamin A deficiency, Iron deficiency)
•Occupational Exposure
–Nickel, radium, mustard gas, chromium and leather tanning / woodworking byproducts increase sinonasal tract tumors.
120
What strand of HPV is seen in head and neck cancer?
HPV 16
121
How is head and neck cancer treated?
Stages I and II: surgery or radiation
| III and IV: surgery, radiation, and chemo
122
How does fluororacil work?
inhibits thymidylate synthesis
123
How do platinums work?
crosslink DNA
124
How do taxanes work?
microtubule stabilization
125
Do patients with HPV and head and neck cancer do better or worse?
HPV = better prognosis
126
How can you treated advanced head and neck cancer?
cetuximab
| anti-EGFR monoclonal antibody
127
What is vemurafenib?
Oral pill that inhibits BRAF kinase (which is a proto-oncogene)
128
What is ipilimumab?
Immunotherapy
Approved for treatment in metastatic melanoma
Lots of side effects but very potent
Can only take 4 doses
129
What is nivolumab?
Immunotherapy
Approved for treatment in metastatic melanoma
Fewer side effects than ipilimumab - more tumor-specific
Sometimes used with ipilimumab
Used alone in PD-1 high tumors
130
What are the stages of cervical dysplasia?
```
Normal
LSIL/CIN I (mild dysplasia)
HSIL CIN II (moderate dysplasia)
HSIL CIN III (severe dysplasia)
carcinoma in situ
```
131
Which strains of HPV are covered by vaccine?
6, 11, 16, 18 in quad
16 and 18 in bivalent
Vaccines contain no viral DNA - just capsid protein and envelope
132
What kinds of cancer are seen in cervix?
Squamous cell most common
| Adenocarcinomas are sometimes seen
133
How is cervical cancer treated?
radiation for all stages
radical surgery for IA, IB, IIA
Adjuvant chemo can be given in high risk patients or intermediate if needed (dependent on tumor size and depth of invasion)
134
What forms of radiation are used in cervical cancer?
External beam
| brachytherapy
135
What are the demographics of uterine cancer?
* Median Age 61
* 25% diagnosed before the menopause
* 5% diagnosed before age 40
136
What are risk factors for uterine cancer?
```
Atypical Hyperplasia
Obesity (the heavier the worse it is)
Unopposed Estrogen
Estrogen use
Late Menopause
Diabetes
Nulliparity
Early Menarche (less than 12 y/o)
OCPs are protective
```
137
How does uterine cancer typically present?
Abnormal bleeding
138
What kinds of cancer is uterine typically?
Adenocarcinoma (90-95%)
| Sarcoma (5-10%)
139
What is Lynch Syndrome?
•Hereditary nonpolyposis colon cancer (HNPCC) syndrome
•Autosomal dominant
–Mismatch repair (MMR) genes
–MLH1, MSH2, MSH6, PMS2
•Tumors display microsatellite instability (MSI)
•High risk of colon and endometrial cancers
•Other tumors: ovary, stomach, biliary tract, ureter, renal, CNS
140
How is uterine cancer treated?
•Surgery
–Hysterectomy
–Lymphadenectomy (value and role controversial)
•Adjuvant therapy in IA grade 3 and above
–Radiation
–Chemotherapy
–Chemoradiation
141
What are signs and symptoms of ovarian cancer?
* Abdominal mass
* Pelvic mass
* Pleural effusion
* Ascites
* Abdominal pain
* Early satiety
* Nausea and vomiting
* Abdominal distension
* Constipation
142
What hereditary syndromes are seen in ovarian cancer?
BRCA 1
BRCA 2
Lynch II (Hereditary Non-polyposis Colorectal Cancer Syndrome)
143
How is ovarian cancer treated?
Surgery
| Chemo (not always performed in early stage cancer)
144
What kind of chemo is used in ovarian cancer?
Paclitaxel
Carboplatin
Intraperitoneal chemo is used in advanced cancer
145
What do granulosa cell tumors do?
Secrete estrogen and inhibin
146
What are Sertoli-Leydig cell tumors? When are they seen?
* Young women (average 25 yo)
* Secrete androgen
* Often acute symptoms
* Microscopic features:
* Top: well differentiated, composed of well-defined tubules, separated by interspersed Leydig cells
* Bottom: poorly differentiated, minimal tubule formation
147
What is a sarcoma?
A cancer of the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. (NCI)
148
What is a leiomyosarcoma?
Cancer of the smooth muscle
149
What is a chondrosarcoma?
Cancer of the cartilage
150
What is a rhabdomyosarcoma?
Cancer of the skeletal muscle
151
Which sarcomas are seen in pediatrics?
Rhabdomyosarcoma
Osteosarcoma
Ewing's sarcoma
152
What is the cellular change in rhabdomyosarcoma?
PAX-FKHR gene fusion
153
How do osteosarcomas present?
Pleomorphic high grade tumor composed of fibroblast, myofibroblasts and histiocytes.
Found in extremities 70-75% of the time.
Patients present with a painless mass of several months’ duration.
Lesions are destructive in nature.
Sclerosis is present from either tumor new bone formation or reactive sclerosis.
Plain films reveal permeative lesion with cortical destruction.
“Codman’s triangle” of bone appears as tumor elevates periosteum from underlying bone.
Cortical soft tissue extension may produce radiating spicules of bone called “sunray”.
“Sunburst” pattern of distal femur
Lace-like osteoid deposition is very characteristic of this neoplasm.
154
What is Ewing's Sarcoma?
Primitive small and round blue cell tumor possibly related to primitive neuroectodermal cells.
Presentation of pain and a mass at the site of tumor with constitutional symptoms including fever, anemia, leukocytosis, and an increased erythrocyte sedimentation rate.
Most often permeative in appearance (multiple small holes).
Often have an “onion skin” type of periostitis.
Characterized by EWS-FLI1 gene fusion product.
sheets of tightly packed, round cells with very scant cytoplasm ("round blue cell tumor").
155
How are pediatric sarcomas treated? Adult sarcomas?
Pediatric: chemotherapy, sometimes +surgery
Adult: surgery, sometimes +chemotherapy
156
What is the most common bone cancer in adults over 40?
Met from somewhere else
157
What does GIST express?
c-kit
158
What is GIST treated with?
Imatinib
159
How common is colon cancer?
3rd most common cancer, 3rd most deadly
160
What are risk factors for colon cancer?
```
Strong:
Advanced age
FAP / HNPCC
Long-standing UC/Crohn’s colitis
Moderate:
High red meat diet
Previous adenoma or cancer
Family history of adenoma or cancer
Modest:
High fat diet
Smoking and alcohol consumption
Obesity
Cholecystectomy
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161
What are protective factors for colon cancer?
```
Moderate:
High physical activity
Aspirin / NSAID use
Modest:
High vegetable/fruit diet
High fiber diet
High folate/methionine intake
High calcium intake
Postmenopausal hormone therapy
```
162
How does FAP change colon cancer tumor progression?
Tumor initiation is accelerated (age 5-20)
Tumor progression is normal (10-20 years)
100% risk of tumor
163
How does Lynch Syndrome change colon cancer tumor progression?
Normal tumor initiation (30-50 y/o)
Accelerated tumor progression (1-3 years)
Up to 80% risk of tumor development
164
What is FAP? What is the mutation?
```
1% of all colorectal cancer
100-1000s of adenomas
APC gene mutations
Autosomal dominant
Risk of extracolonic tumors (desmoids, duodenal cancer thyroid, brain)
Risk of CRC=100% if untreated
May see hyperpigmentation of retina
```
165
How is FAP managed?
Sigmoidoscopy at 10–12 years and every 2 years to assess polyp burden
Colectomy
Upper GI surveillance for adenomas
Genetic counseling
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How is Lynch Syndrome managed?
Start yearly colonoscopies at 20-25
| Transvaginal ultrasounds yearly starting at 25-35 for endometrial cancer
167
When should CRC screening start for average risk people?
age 50
168
What does right colon CRC present as?
```
occult bleeding
obstruction (mild)
anemia
abdominal mass
"apple core" lesion
```
169
What does left colon CRC present as?
```
gross bleeding
major obstruction
anemia (not as significant as right colon)
change in bowel habits
pain
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170
When is polypectomy effective?
1) Stalk margin is negative
2) No lymphatic/vascular invasion
3) Tumor is not poorly differentiated.
171
What is a Spitz nevus?
Benign melanocyte tumor
Used to be believed to be malignant and would result in mutilating surgical intervention
Has a "frightening" histological appearance (lots of mitotic figures)
172
What are the risk factors for melanoma?
Genetics (particularly first degree family member with hx melanoma)
Sun exposure
173
What is dysplastic nevus syndrome?
Autosomal dominant disorder
Affected individuals have 10s-100s of nevi on legs, body, and butt
Risk of developing melanoma
174
Which mutations are associated with melanoma?
Hereditary: CDK4, CDKN2A
Sporadic: BRAF, PTEN, N-RAS, C-Kit
175
What is lentigo maligna melanoma?
Begins as a flat, irregularly shaped, brown to black area of pigmentation on scalp, face, and neck
Emerges typically in 40s-50s
Will eventually "break through" the basement membrane, invade the dermis, and become metastatic
176
What is superficial spreading melanoma?
Most common type of melanoma
Can be found anywhere other than palms, soles, and mucous membranes
Borders are irregular and often notched
Multicolored ("American Flag"): brown, black, blue, red, white
Invades horizontally and then eventually vertically (years) and becomes metastatic
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What is Acral-lentiginous melanoma?
Occurs on palms, soles, and mucous membranes
| Only melanoma typically seen in African Americans
178
What is nodular melanoma?
Accounts for 10% of melanoma
Pretty much only grows down, so becomes metastatic very quickly (pretty much never in situ)
Can be pink or black
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How is melanoma treated?
Everyone has surgical excision
Some benefit from adjuvant interferon-alpha (but lots of side effects)
Now vemurafenib has shown to be very effective in patients with V600 mutation (BRAF)
CTLA4 inhibitor ipilimumab also shows some success along with PD-1 inhibitor (nivolumab) - in combo or solo agents
180
What neoplastic syndromes are associated with HCC?
hypoglycemia (due to liver damage)
erythrocytosis (elevated Hct)
hypercalcemia
181
How is HCC treated?
Surgical resection
| Sorafenib (TKI - blocks VEGFR and Raf kinase) improved survival despite no tumor shrinkage
