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Oncology I

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Oncology I

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    1. Oncology I Basic Science Conference April 21, 2005 Jason Frischer

    2. Question 1 A 45-year-old man has early satiety and epigastric pain. The abdominal CT shown is obtained. Biopsy shows the accompanying histology and immunohistochemical staining shows the tumor to be c-kit positive. Which of the following statements about this tumor is true? These tumors metastasize early to the lung They are often responsive to doxorubicin Surgical resection offers at least a 75% chance of a cure RT improves disease-free interval after resection Recurrent tumor after resection would likely respond to STI-571 (Gleevec)

    5. GIST Previously classified as a leiomyosarcoma Arise from the interstitial cells of Cajal, an intestinal pace maker These cells stain for CD-34 and possess the c-Kit protooncogene Imatinib or Gleevec is a tyrosine kinase receptor inhibitor in tumors that contain c-KIT mutations

    6. GIST

    7. GIST Surgical resection offers a 50% cure rate Chemo and RT do not work Recurrence is local Follow patients with PET scans

    9. Question 2 Which of the following patients is LEAST likely to benefit from a LN dissection? 45-year-old man with an 80 pack-year smoking history with non small cell carcinoma of the lung and mediastinal nodes 55-year-old male fishing capt. With a 2mm melanoma on the shoulder with palpable nodes in the axilla 32-year-old woman with papillary thyroid cancer and palpable nodes in the neck 48-year-old woman with 1.5 cm invasive ductal carcinoma of the breast with palpable nodes in the axilla 31-year-old man with biopsy confirmed prepyloric 1cm gastric adenocarcinoma

    11. Lymph Node Dissection Depends on the type of tumor and extent of local disease (presence of nodes) NSCLC offers no advantage from lymphadenectomy after staging is completed A pt. with melanoma and LNs should have a dissection (Sentinel LN) Thyroid cancer pts should have a lymph node dissection only if palpable nodes are detected. Prophylactic dissectin is not indicated Palpable nodes in Breast Ca warrant LN dissection

    12. Lymph Node Dissection Prognostic Factors in Breast Ca Tumor size -lymph/vessel invasion High grade -ER/PR status HER-2-neu -DNA ploidy Cell synthesis phase Lymph node status best predictor Resectable gastric cancer should have a LN dissection (D1 vs D2)

    13. Question 3 A 29-year-old man has a 3-cm non-keratinizing squamous cell carcinoma of the anal canal without inguinal adenopathy. The pt. is HIV + and has a CD4 count of 508 cells/mcl. Which of the following statements is TRUE? The pt. has clinical AIDS Non-karatinizing squamous cell carcinoma of the anal canal has a better prognosis than keratinizing squamous cell carcinoma This lesion is likely to have originated at or above the dentate line With appropriate treatment the likelihood for cure is greater than 90% This lesion is best treated with local excision and wound closure with local advancement or rotational flaps

    15. Anal Cancer Association between HIV and anal cancer (HPV) Unlike KS, anal cancer is not an indicator of HIV progression Keratinizing and non-keratinizing squamous cell carcinoma of the anal canal are similar in both biology and prognosis Non-keratinizing SCC often originates from above the dentate line

    16. Anal Cancer Size is the most important prognostic factor Tumors < 2cm have an 80% long term survival Increased mets with tumors > 2 cm Treatment is chemo/RT (Nigro protocol) APR for persistent or recurrent disease Local excision is not indicated

    17. Question 4 63 year-old man has a LAR for rectal cancer. Staging is T3 N0 M0 adenocarcinoma. Them most appropriate postoperative treatment would be Close follow up Adjuvant chemo with 5-FU and leukovorin Adjuvant chemo with 5-FU and irinotecan Adjuvant radiotherapy Adjuvant chemoradiotherapy

    20. Rectal Cancer This pt. has stage II carcinoma of the rectum. Stage II and III are at high risk for local and distant recurrence Treatment includes chemo with 5-FU and leukovorin plus RT Reduces recurrence rate by 34%

    21. Question 5 Genetic testing in patients with familial adenomatous polyposis (FAP) Can identify those with invasiva carcinoma Confirms the K-ras oncogene as the key genetic marker Has identified the adenomatous polyposis coli (APC) tumor suppressor gene as the causative entity Has identified FAP as part of the Lynch syndrome Is associated with a rate of 30% to 70% penetrance

    23. Genetics 2 categories of genes associated with colon cancer Oncogenes Protooncogenes are activated into oncogenes Initiate alterations in cell structure or function K-ras, S-ARC, and TRK Suppressor genes Found in the genotype of a normal cell Alterations occur when these genes are inactivated P53 (most common mutation in colon cancer) and APC

    24. Genetics 20% of new cases of colon cancer involve hereditary changes FAP is involved in < 1% of colon cancers Result of mutation in the tumor suppressor gene APC (90% penetrance) HNPCC (Hereditary NonPolyposis Colon Cancer) 1-3% of colon cancers 30 70% penetrance Part of Lynch Syndrome

    25. Genetics Familial Colon Cancer (FCC) Accounts for 20% of colon cancers No genetic markers

    26. Question 6 2 years after an AAA repair, a 76 year-old man has an obstructing colon stricture. At left colectomy, abdominal exploration reveals the lesion pictured here in the mid jejunum. Biopsy confirms carcinoid. Which of the following statements is NOT true? 50% of carcinoid tumors are found in the appendix Carcinoid has variable malignant potential The cell of origin is the Kulchitsky cell Treatment includes wide segmental resection Tumors are rarely multicentric

    28. Carcinoid Most frequent small bowel neoplasm Arise from Kulchitsky cell As enterochromaffin or argentaffin Located in the crypts of Lieberkuhn Half are located in the appendix Characteristic yellow, tan, or gray appearance

    29. Carcinoid Generally follow an indolent course May cause ulceration, bleeding, or obstruction 30% are multicentric Tumor size is predictive of metastasis < 1 cm rarely metastasize Treated with wide segmental resection

    30. Question 7 56 year-old woman has a left temple lesion as shown. Excisional biopsy shows a melanoma, Clarks level III and Breslow depth 1.1 mm. Initial management should consist of wide local excision and Interferon alpha-2b Sentinel node biopsy Adjuvant chemotherapy Radical neck dissection parotidectomy

    32. Melanoma Presence of nodes is the most important prognostic indicators and dictates therapy Node dissection for a lesion between 0.75 to 2.5 mm is controversial in the absence of clinically palpable LNs.

    33. Question 8 A 45 year-old man who has been HIV + for 15 years has a painful 3-cm neck mass. A 2-week course of antibiotics does not change the mass. Biopsy will most likely reveal Hodgkins lymphoma B cell lymphoma T cell lymphoma Metastatic lung carcinoma Kaposis sarcoma

    35. HIV and Cancer Increase in Kaposis sarcoma, skin cancers, cervical cancer, and most commonly non-Hodgkins lymphoma Increased 150 250 fold Lymphadenopathy in this pt. population should be regarded as lymphoma until proven otherwise

    36. Question 9 A 60 year-old asymptomatic man with a family history of colon cancer seeks advice on personal screening for colon cancer. The recommended screening test for colon cancer in this patient is Serial fecal occult blood tests Flexible sigmoidoscopy Virtual colography Colonoscopy Barium enema

    38. Colon Cancer Screening Full colonoscopy is now the current recommendation for all pt. > 50

    39. Question 10 55 year-old woman with a history of chronic indigestion has a heme positive stool test. Colonoscopy is negative. EGD shows a 10 cm submucosal mass in the midportion of the stomach on the greater curvature. Biopsies are negative. Wedge resection is performed. Which of the following statements is TRUE? Approximately 25% of these lesions are malignant The extent of resection affects long-term survival Fundic lesions are more likely to be benign Tumor behavior cannot be predicted from histological grade These lesions arise from smooth muscle in the gastric wall

    41. GIST GIST are most often found in the stomach Originate from stromal rather than epithelial or smooth muscle elements In the stomach, bleeding is characteristic Substantial malignant potential Tumor size and # of mitoses/hpf are the best predictors of malignant potential 75% of the tumors arising from the fundus are malignant

    42. Question 11 The tumor suppressor gene that predicts whether Barretts esophagus will progress to esophageal cancer is bcl-2 Ki-67 p53 APC H-ras

    44. p53 Tumor suppressor gene If mutated, removes its suppressor effects Over expression of p53 is seen in pts. With high grade dysplasia who subsequently develop cancer It is NOT clear if a pt. with HGD and shows no expression of p53 can safely be observed rather than undergo resection or ablation

    45. Question 12 Which of the following genetic factors directly affects apoptosis in breast cancer? P53 Bcl-2 HER2 BRCA PEG-3

    47. Genetics and Breast Cancer p53 gene produces a protein that prevents propagation of cells with abnormal DNA bcl-2 suppresses cell death bcl-2 is anti-apoptotic (bad) p53 down regulates bcl-2 in cells with abnormal DNA, thus triggering apoptosis HER2 is a tyrosine kinase (cell growth) HER2 overexpression occurs in DCIS and in more malignant tumors

    48. Genetics and Breast Cancer Epidermal growth factors (EGF) are known to be elevated in breast cancer Involved in vessel permeability and promotes invasiveness Progression elevated gen-3 (PEG-3) seems to be associated with tumor progression BRCA1 and 2 predispose to breast cancer

    49. Question 13 Patients who are at high-risk for developing distal esophageal adenocarcinoma may have all of the following characteristics EXCEPT Onset of reflux symptoms at an early age Severe nocturnal reflux symptoms Elderly white male smokers Presence of intestinal metaplasia in the gastric cardia Loss of p53 gene heterogeneity on chromosome 17

    51. Esophageal Cancer Distal esophageal cancer is strongly associated with chronic gastroesophageal reflux. Replacement of normal stratified squamous epithelium with columnar epithelium All pts. with Barrets esophagus are at increased risk for developing adenocarcinoma, a subset are at increased risk: Elderly white make smokers with esophagitis, ulceration, stricture, and bleeding Intestinal metaplasia often due to H. pylori are at a significantly lower risk of progressing to adenocarcinoma than pts. with Barretts. The metaplasia may regress with appropriate medical therapy

    52. Question 14 52 year-old woman has vague abdominal pain associated with eating. An ultrasound study of the right upper quadrant demonstrates a 12-mm sessile polyp in the gallbladder. There is no evidence of gallstones or wall thickening. The next step in management should be Observation Evaluation for familial polyposis Follow-up ultrasound every 6 months Laparoscopic cholecystectomy Open cholecystectomy

    54. Gallbladder Polyps Incidence is ~5% on ultrasound due to cholesterolosis < 1 cm Multiple - if multiple are seen then likely due to cholesterolosis Follow up ultrasounds 3 6 months Pedunculated polyps tend to be benign Sessile have the propensity to be malignant

    55. Gallbladder Polyps Open cholecystectomy is indicated when there are fewer than 3 polyps, for those larger then 1 cm, and for sessile polyps or those that show signs of eroded mucosa. Open cholecystectomy is preferred over laparoscopic to avoid inadvertent spillage Gallbladder cancer has tendency for peritoneal and port site seeding

    56. Question 15 Which of the following statements about sentinel lymph node (SLN) biopsy for melanoma is NOT true? Combining radiolymphoscintigraphy and intraoperative blue dye injection increases accuracy Radiolymphoscintigraphy is performed with Tc-99 The false-negative rate is higher for melanoma of the head and neck than for extremity melanoma SLN biopsy is associated with an overall survival benefit SLN biopsy is not useful after previous local excision of a melanoma

    58. Sentinel Lymph Node Incidence of melanoma is increasing in the US LN dissection is indicated in pts. with 1 to 2 mm thick melanomas and pts. over 60 Blue dye increases the success rate of SLN biopsies SLN biopsy does NOT affect survival Identifies the patients with occult mets and therefore allows you to give more aggressive treatments

    59. Question 16 A healthy 57 year old man has a 1.8 cm invasive adenocarcinoma of the anterior wall of the rectum, 2 cm from the dentate line. On rectal exam the lesion is hard, discrete, and ulcerated. CT scan is normal. Endorectal ultrasound shows extension into the muscularis propria. Recommended management would be Proctocolectomy and J pouch Transanal local excision with adjuvant chemo/RT APR RT Parasacral (Kraske) resection

    61. Colorectal Cancer

    62. Colorectal Cancer APR has survival rates of: 87% for T3 N0 68% for T3 N1-2 64% for Tany N1-2 Minimum of 2 cm distal to the tumor is required for adequate margins 6 cm suggested for poorly differentiated lesions LAR acceptable for lesions in the upper 1/3 of rectum Middle and distal 1/3s possible LAR

    63. Question 17 Which of the following statements about preoperative neoadjuvant chemo- and radiation therapy for rectal carcinoma is TRUE? This treatment decreases the # of pts. requiring APR Perineal healing is unaffected if APR is performed Anastomotic leak rates are increased if a LAR is performed Patients with T2 lesions benefit from this treatment Local recurrence rates are not improved overall

    65. Neoadjuvant therapy Inconclusive data Significant # of pts. can be clinically downstaged Allows for the avoidance of proctectomy Cure rates have not improved BUT local recurrence rates are reduced Does not affect leak rate in LAR Does cause problems with healing an APR

    66. Question 18 Which of the following statements about sentinel lymph node biopsy in malignant melanoma is TRUE? It should be done for all lesions regardless of depth It is positive in 5% to 10% of thin (< 0.76 mm) melanomas For lesions < 4 mm in depth, it should be performed to determine the need for completion lymphadenectomy Skip metastases can occur in 15% to 20% of cases Completion lymphadenectomy after a positive sentinel lymph node biopsy will show no further evidence of malignancy in > 90 % of cases

    68. Melanoma Melanomas < 0.76 mm in thickness are generally not considered for sentinel lymph node biopsy because the long-term survival after local excision alone is excellent SLN bx not warranted for lesions > 4mm Useful for intermediate depth For + SLN, completion lymphadenectomy will show further LN metastases in ~ 8%

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