1. Oncology

2. With regard to the spread of neoplasms, which of the following statements is false?
Metastatic cells enter the lymph nodes via the subcapsular space and later permeate the sinusoids of the node
Carcinoma in situ is a lesion with histopathologic characterisitics of malignancy but without detectable invasion beyond the basement membrane
Lymphatic involvement is common with epithelial neoplasms, whereas most sarcomas metastasize hematogenously
The Metastatic process is highly efficient, as evidenced by the fact that the number of circulating tunor cells correlates with the metastatic burden.
Answer: D

3. Regarding oncogenes and proto-oncogenes, which of the following statements are true?
Proto-oncogenes are proteins capable of inhibiting oncogenes.
Oncogenes are nucleic acid sequences unique to the viral genome.
Exposure to carcinogens causes insertion of oncogenes into the human genome.
Proto-oncogenes may be activated by mutation, amplification, or translocation.
Answer: D

4. Development of Cancer Most common tumor suppressor gene -
Oncogenes are genes that, when expressed, contribute to the devlopment of malignancy
Proto-oncogenes are genes found in normal tissues that, when activated by mutation, amplification or translocation become oncogenes and may lead to transformation of the cell to a malignant phenotype. e.g. - RET (?)
Tumor suppresor genes are different – the loss of their expression leads to devlopment of cancer.
Most common tumor suppressor gene -
Medullary Thyroid Cancer
p53

5. Regarding metastatic cancer, which of the following statements is true?
Axillary lymph node dissection is essential for staging a sarcoma of the breast
Melanoma tends to metastasize first to the lung, brain, and gastrointestinal tract.
Bone is frequently the site of metastasis for cancer of the breast and prostate.
Primary brain cancers have a predilection for metastasis to the lung.
Answer: C

6. Which of the following options is/are appropriate for treatment of metastatic cancer?
A Whipple procedure to relieve obstructive jaundice in a patient with adenocarcinoma of the head of the pancreas and multiple small metastatic lesions in the liver.
Resection of three liver lesions, metastatic from a colorectal primary tumor, in the absence of another site of disease.
Resection of two lung metastases from a sarcoma of the lower extremities in the absence of other metastatic disease.
Radiation therapy for a painful hip lesion in a patient with diffuse metastases from prostate cancer.
Answer: B,C,D

7. Which of the following historical characteristics of a mass suggest(s) malignancy?
Sudden devlopment of a painful, tender mass.
Slow, progressive, painless growth of mass.
Sudden dramatic enlargement of a previously stable-sized mass
A mass that waxes and wanes in size with or without associated tenderness.
Answer: B

8. Performing which of the following operations would be inappropriate without first obtaining a biopsy specimen confirming the presence of cancer?
Radical right hemicolectomy for an “apple core” narrowing of the ascending colon.
Modified radical mastectomy for a clinically and mammographically obvious breast cancer with overlying “skin puckering”.
A pancreaticoduodenectomy for a large, hard mass in the head of the pancreas that produces painless jaundice.
Parotidectomy for a 2 cm, slowly growing solid parotid mass without evidence of facial nerve dysfunction.
Answer: B

9. Which of the following tumors requires resection of the largest margin of normal tissue around the clinically obvious tumor to achieve an acceptable likelihood of control at the local primary site. Assume that no other treatment will be used.
Adenocarcinoma of the colon
Basal Cell carcinoma of the skin
Invasive breast cancer
Squamous carcinoma of the distal esophagus
Squamous carcinoma of the skin
Answer: D
Colon – 2cm
Esophageal and gastric malignancy can spread in submucosal plane as far as 10cm from primary site

10. Partial of complete resection of which of the following organs could be justified to prevent a future cancer?
Colon
Pancreas
Breast
Testicle
Thyroid
Answer: A, C, D, E in
FAP, BRCA1 or 2, Undescended testicle, MEN II

11. In which of the following circumstances would palliative surgery not be indicated?
Carcinoma of the body of the pancreas that produces severe back pain
A large gastric cancer obstructing the gastroesophageal junction, associated with two small liver metastses
A bleeding cecal cancer, 5cm in diamter, with multiple liver metastasis
Adenocarcinoma of the head of the pancreas with partial portal vein involvement
Answer: A

12. Which of the following statements concerning sentinel lymph node biopsy is not true?
The technique utilizes injection of a vital blue dye and/or radioactive tracer to identify the sentinel node
The sentinel node is the first draining node, from a particular location, in each basin.
There is only one sentinel node in each basin.
The technique is not useful in patients with suspicious palpable adenopathy.
Answer: C

13. Which of the following chemotherapeutic agents is/are known to cause nephrotoxicity?
Cisplatin
Carboplatin
Ifosfamide
Methotrexate
Cyclophosphamide
5-FU
Answer: A,D

14. Rapid Fire M Longitudinal incision
Most sensitive phase of cell cycle to radiation M
Extremity Sarcoma – method of excisional biopsy
Longitudinal incision
Ret proto-oncogene diagnostic for:
Medullary Thyroid Cancer -treatment?
Total Thyroidectomy
Adverse effect of Tamoxifen
DVT and endometrial CA

15. Alphabet Soup PSA -Prostate NSE Colon Ca -Small cell Lung CA Liver Ca
CEA
Colon Ca
AFP
Liver Ca
CA 19-9
Pancreatic Ca
CA 125
Ovarian Ca
Beta-HCG
Testicular CA, choriocarcinoma

16. Familial Cancer Syndromes
Breast/ovarian
BRCA1 – breast, ovary, colon, prostate
BRCA2 – “ “, GB/biliary tree, pancreas, stomach, melanoma
Cowden’s dis
breast, endometrium, thyroid
FAP
APC – colorectal, duodenal, gastric, medulloblastomas, osteomas
Familial melanoma
CDK4 – melanoma, pancreas, dysplastic nevi, atypical moles
HNPCC
colorectal, endometrial, tcc of ureter, stomach, sb, pancreas, ovary
Li-Fraumeni
p53 – breast/phyllodes, soft tissue and osteosarcoma, brain, adrenal, Wilms, pancreas, leukemia, neuroblastoma
MEN1
MEN1 – pancreas, parathyroid hyperplasia, pituitary
MEN2
RET – MTC, pheo, parathyroid hyperplasia

17. Familial Cancer Syndromes
NF1
NF1 – Neurofibromas/fibrosarcoma, AML, brain
NF2
NF2 – Acoustic neuromas, meningiomas, gliomas, ependymomas
Peutz-Jeghers
GI CAs, breast, testicular, pancreas, benign pigmentation of skin/mucosa
Retinoblastoma
RB – Rb, sarcomas, melanoma
Tuberous sclerosis
TSC1/2 – hamartomas, renal cell, astrocytoma
VHL
Renal cell, hemangioblastomas of retina and CNS, pheo
Wilms
WT – wilm’s, aniridia, genitourinary abnormalities, mental retardation

18. Familial Adenomatous Polyposis
APC gene, autosomal dominant
Scaffolding protein, cell adhesion, migration
Frameshift (68%), nonsense mutation (30%), deletion (2%)
1% of all colorectal cancers
>90% develop cancers
100s to 1000s of adenomatous polyps
Phenotype expressed in 20-30s with CA by 35-40
Polyps not inherently more cancerous
Extracolonic manifestations
UGI polyps, desmoid tumors, thyroid CA
Stomach/duodenum polyps(90%) by 70 years
Duodenal adenoCA 3rd cause of death

19. Familial Adenomatous Polyposis
Attenuated FAP
<100 adenomas
Proximal colonic polyp distribution
Cancer occurs 15 years later
Gardner’s syndrome
Colorectal CA, Osteomas of mandible/skull, epidermal cysts, skin/soft tissue tumors (desmoids and thyroid)
MYH-associated polyposis (MAP)
Autosomal recessive, 50% penetrance
Cancer occurs at 50 years
Extracolonic manifestations
Breast (18%)
UGI polyps (33%)

20. Hereditary Nonpolyposis Colorectal Cancer
Lynch’s Syndrome
Autosomal dominant, mismatch repair genes
5-10% of all colorectal CA’s
Type 1 (Colorectal), Type 2 (Extracolonic)
Right sided colon CAs (70% proximal to splenic flexure) at earlier age (~44)
Increased synchronous and metachronous lesions
Increased speed of tumor progression
Adenomas progress to CA in 2-3 years vs 8-10
Extracolonic
Endometrium/ovary

21. BRCA1 / BRCA2 Tumor suppressor gene
Frameshift or nonsense mutations with truncated protein products
DNA repair, gene expression regulation, cell cycle control
2 hit hypothesis
5-10% of all breast CAs are hereditary
25% of high-risk families have mutations
80% risk in 70 yo woman
Ovarian CA in 60%/27% (1 vs 2) ; Prostate CA in men

22. MEN 1 MEN 1 Autosomal dominant germline mutations
Tumor suppressor, Loss of fx mutations (80%)
Menin – transcription regulation, DNA repair
Parathyroid gland, pancreatic islet cell, pituitary gland
Lipomas, adrenal/thyroid adenomas, cutaneous angiofibromas, carcinoid tumors

23. MEN 2 ret proto-oncogene (re-arranged during transfection)
Tyrosine kinase receptor becomes constitutively activated
germline mutations
MEN 2A
MTC (100%), Pheocromocytoma (50%), Hyperparathyroidism (25%)
MEN 2B
MTC, Pheo, mucosal neuromas (tongue, lips)
Intestinal ganglioneuromatosis, marfanoid habitus
Sporadic ret mutations more common

24. Radiation Carcinogenesis
UV – skin
UVB most important (UVC filtered by ozone layer)
Formation of pyrimidine dimers repaired by nucleotide excision repair pathway
SCCA, basal cell, malignant melanoma
Xeroderma Pigmentosa
Autosomal recessive, NER gene mutations
Extreme photosensitivity, 2000x increased risk of skin CA
Ionizing – multiple cancers
Electromagnetic, particulate
Carcinogen at low doses, therapeutic agent at high doses
Causes inflammatory reaction with production of reactive oxygen and nitrogen species
Leukemias and solid organ (breast, colon, thyroid, lung) tumors
Head/neck irradiation in kids – thyroid CA as adults

25. Viral Carcinogenesis ~15% of all human tumors caused by viruses
Mostly cervical CA by HPV and HCC by HBV/HCV
Establish long-term persistent infections in target cells
EBV
Burkitt’s, Hodgkin’s, Immunosuppresion-related lymphoma, Nasopharyngeal CA
Hep B/C
HCC
HIV type I
Kaposi’s
HPV 16 & 18
Cervical, Anal
HTLV-1
Adult T-cell leukemia
H. pylori
Gastric adenoCA
Opisthorchis viverrini
CholangioCA, HCC
Schistosoma haematobium
Urinary bladder

26. Sensitivity/Specificity
Protein Tumor Markers
α-Fetoprotein – HCC
Oncofetal antigen – synthesized by hepatocytes, endodermal GI tissues
Normal <25 ng/ml (nonpregnant), half-life 5 days
10-20% of HCCs nondetectable levels
Also found in:
nonseminomatous testicular CA
> 5ng/ml in 20% of gastric, pancreatic 5% colorectal, lung
Hepatitis, inflammatory bowel dis, cirrhosis
Sensitivity/Specificity 25-75% / 76-94% ; PPV 9-50%
AFP and ultrasound = 100% in one study
Reflects tumor size ; correlates with stage and prognosis
>400 ng/ml associated with larger tumors
Drops after resection/ablation ; usually drops with chemo
<10 ng/ml if complete rsxn
AFP level (ng/ml)
Sensitivity/Specificity 20
30/80
100
72/56
400
70/94

27. Protein Tumor Markers Carbohydrate Antigen 19-9 – pancreatic CA
Upper limit normal 37 U/ml
Sensitivity/Specificity % / 68-92%
Not a good diagnostic marker, better for monitoring therapy response
Acute/chronic biliary dis elevates serum levels
Low sensitivity in early-stage disease
Benign biliary dis can have levels up to 400 U/ml, 87% with concentrations >70 U/ml
Pts with negative Lewisa blood group (10% pop) cannot synthesize CA 19-9
Present in CAs of biliary tree (95%), stomach (5%), colon (15%), HCC (7%), Lung (13%)
Levels correlate with tumor burden and tx response
95% of unresectable cancers have levels >1000 U/ml

28. Protein Tumor Markers Prostate specific antigen
Tissue specific, not cancer specific, not present post prostatectomy or in women
Elevated in BPH, prostatitis, massage, bx, and DRE
Widely used screening tool for prostate CA
1:8 cancers kills host if left untreated
Upper limit normal 4ng/ml, >10ng/ml suspicious for malignancy
Half-life 18 days
Upper limit increases with age
Measuring PSA as ratio to total volume or ratio of free to total PSA improves specificity when values in intermediate range
Levels should normalize within 2-3 weeks
If levels elevated for 6 months – relapse almost certain

29. Protein Tumor Markers Carbohydrate antigen 125
Present in the fetus and adult fallopian tubes, endometrium, endocervix, peritoneum, pleura, pericardium, amnion
NOT present in adult nor fetal ovarian epithelium
Upper limit normal 35 U/ml
Increased levels found in 80% ovarian cancers
Useful for monitoring disease course and recurrence
Sensitivity/Specificity 75% / 90% in pts with ovarian masses
Also present in cancer of: fallopian tube, endometrium, cervix, pancreas, colon, lung, liver
Elevated in endometriosis, adenomyosis, fibroids, PID, cirrhosis, ascites

30. Protein Tumor Markers α-Fetoprotein and Human Chorionic Gonadotropin
Nonseminomatous testicular cancers: embryonal CA, choriocarcinoma, yolk sac tumors, teratomas
HCG – 90% choriocarcinomas
AFP – 90-95% yolk sac tumors, 20% teratomas, 10% embryonal Cas
Pts with nonseminomatous testicular germ cell tumors: 50% HCG and 60% AFP, 90% either/or
AFP >500ng/ml or HCG >1000 ng/ml gives poor prognosis
Levels correlate with chemo response

31. THE END!