Oncology

1
Oncology
2
With regard to the spread of neoplasms, which of
the following statements is false?

1. Metastatic cells enter the lymph nodes via the
   subcapsular space and later permeate the
   sinusoids of the node
2. Carcinoma in situ is a lesion with
   histopathologic characterisitics of malignancy
   but without detectable invasion beyond the
   basement membrane
3. Lymphatic involvement is common with epithelial
   neoplasms, whereas most sarcomas metastasize
   hematogenously
4. 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?

1. Proto-oncogenes are proteins capable of
   inhibiting oncogenes.
2. Oncogenes are nucleic acid sequences unique to
   the viral genome.
3. Exposure to carcinogens causes insertion of
   oncogenes into the human genome.
4. Proto-oncogenes may be activated by mutation,
   amplification, or translocation.

Answer D
4
Development of Cancer

• 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?

1. Axillary lymph node dissection is essential for
   staging a sarcoma of the breast
2. Melanoma tends to metastasize first to the lung,
   brain, and gastrointestinal tract.
3. Bone is frequently the site of metastasis for
   cancer of the breast and prostate.
4. 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?

1. 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.
2. Resection of three liver lesions, metastatic from
   a colorectal primary tumor, in the absence of
   another site of disease.
3. Resection of two lung metastases from a sarcoma
   of the lower extremities in the absence of other
   metastatic disease.
4. 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?

1. Sudden devlopment of a painful, tender mass.
2. Slow, progressive, painless growth of mass.
3. Sudden dramatic enlargement of a previously
   stable-sized mass
4. 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?

1. Radical right hemicolectomy for an apple core
   narrowing of the ascending colon.
2. Modified radical mastectomy for a clinically and
   mammographically obvious breast cancer with
   overlying skin puckering.
3. A pancreaticoduodenectomy for a large, hard mass
   in the head of the pancreas that produces
   painless jaundice.
4. 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.

1. Adenocarcinoma of the colon
2. Basal Cell carcinoma of the skin
3. Invasive breast cancer
4. Squamous carcinoma of the distal esophagus
5. 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?

1. Colon
2. Pancreas
3. Breast
4. Testicle
5. 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?

1. Carcinoma of the body of the pancreas that
   produces severe back pain
2. A large gastric cancer obstructing the
   gastroesophageal junction, associated with two
   small liver metastses
3. A bleeding cecal cancer, 5cm in diamter, with
   multiple liver metastasis
4. 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?

1. The technique utilizes injection of a vital blue
   dye and/or radioactive tracer to identify the
   sentinel node
2. The sentinel node is the first draining node,
   from a particular location, in each basin.
3. There is only one sentinel node in each basin.
4. 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?

1. Cisplatin
2. Carboplatin
3. Ifosfamide
4. Methotrexate
5. Cyclophosphamide
6. 5-FU

Answer A,D
14
Rapid Fire

• 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
• -Small cell Lung 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
• Cowdens 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 wilms, 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
• gt90 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
• lt100 adenomas
• Proximal colonic polyp distribution
• Cancer occurs 15 years later
• Gardners 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

• Lynchs Syndrome
• Autosomal dominant, mismatch repair genes
• 5-10 of all colorectal CAs
• 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 Burkitts, Hodgkins, Immunosuppresion-related lymphoma, Nasopharyngeal CA
Hep B/C HCC
HIV type I Kaposis
HPV 16 18 Cervical, Anal
HTLV-1 Adult T-cell leukemia
H. pylori Gastric adenoCA
Opisthorchis viverrini CholangioCA, HCC
Schistosoma haematobium Urinary bladder
26
Protein Tumor Markers

• a-Fetoprotein HCC
• Oncofetal antigen synthesized by hepatocytes,
  endodermal GI tissues
• Normal lt25 ng/ml (nonpregnant), half-life 5 days
• 10-20 of HCCs nondetectable levels
• Also found in
• nonseminomatous testicular CA
• gt 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
• gt400 ng/ml associated with larger tumors
• Drops after resection/ablation usually drops
  with chemo
• lt10 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 67-92 / 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 gt70 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 gt1000
  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
• 18 cancers kills host if left untreated
• Upper limit normal 4ng/ml, gt10ng/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

• a-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 gt500ng/ml or HCG gt1000 ng/ml gives poor
  prognosis
• Levels correlate with chemo response

31
THE END!