OBJECTIVE:
Work through the following cases of patients with cancer to determine risks, diagnostic methods, clinical assessment, and strategies for therapy that are applicable in the field of oncology.
CASE 1
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Clinical History:
A 53 year-old healthy woman has a routine screening mammogram. Her menarche was at age 12. Her last menstrual period was 3 years ago. She used oral contraceptives for 20 years, and she has no children. A maternal aunt and a cousin had breast cancer at age 64 and 67 respectively. There is no other family history of cancer. The mammogram shows a spiculated 2 cm lesion with calcifications in the outer upper quadrant of the left breast. There are no lesions in the right breast. On your physical examination, you observe that she is mildly obese. The breasts are normal on palpation. She has no axillary masses, bony tenderness or other abnormalities. The neurological exam is normal. A chest xray shows no abnormalities. A CBC shows a Hgb of 13.7 g/dL, Hct 41.2%, MCV 90 fL, platelet count 288,000/microliter, and WBC count 5,760/microliter.
Images for this patient:
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Image 1.4 - Gross appearance
Image 1.5 - Microscopic appearance
Image 1.6 - Immunohistochemistry - ER
Image 1.7 - Immunohistochemistry - HER2
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Questions:
What is this woman's risk for having breast cancer? Is she likely to be a carrier of mutations in the BRCA1 or BRCA2 gene? If a screening mammogram had been normal, what preventive treatment might you offer her? What would be the risks and benefits of such therapy? What do you do now to make a diagnosis? A mammographically-guided fine needle aspirate shows carcinoma. What staging tests would you order now? The staging tests are unremarkable. What is her clinical stage? What do you do now? A lumpectomy and axillary node dissection are performed. Pathological examination of the surgical specimen shows infiltrating ductal carcinoma, estrogen and progesterone receptor assays are positive. Staining for HER2/neu is negative. The specimen is 2.5 cm in its longest dimension, and the surgical margins are negative. Eighteen of eighteen axillary lymph nodes are negative for tumor. What is her final (pathological) stage? Flow cytometry of the tumor cells shows a high aneuploid fraction and a high S-phase. How would this affect the prognosis? What is her risk of developing recurrent disease? What should you do now? What is the patient's risk for developing a clinical depression? Should she be referred to a mental health professional as part of an overall treatment program?
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CASE 2
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Clinical History:
You have followed a 60 year-old man for many years. Routine health maintenance studies have been negative during that period. However, on the most recent health maintenance check, a guaiac test for fecal occult blood is positive. You put the patient on a low-meat diet and repeat the fecal occult blood test three times over the next three weeks. Two of the three follow-up tests are positive. There is no family history of colon cancer. Physical examination, including a digital rectal examination, is unremarkable.
Images for this patient:
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Image 2.3 - Gross appearance, colon
Image 2.4 - Microscopic appearance
Image 2.5 - Microscopic appearance, CK-20
Image 2.6 - Microscopic appearance, p53
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Image 2.8 - Gross appearance, liver
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Questions:
Why might one or more fecal occult blood tests be negative, even if the patient has colon cancer? How would you evaluate this patient? Colonoscopy shows a polyp at 30 cm. It is removed by a wire snare. At 50 cm a constricting mass is noted, which is biopsied. Pathology of the polyp shows a tubular adenoma (adenomatous polyp), without invasive cancer. The biopsy of the constricting mass shows adenocarcinoma. How commonly do adenomas and invasive carcinoma co-exist? How common are synchronous multiple primary invasive colon cancers? What tests would you order to stage this patient? A chest X-ray and CT scan of the liver are negative. The serum carcinoembryonic antigen (CEA) is 7.9 (normal 0-5.0). What do you do now? Discuss the indications for surgery with this patient. Explain the role of surgery in a patient with documented liver metastases. At surgery, a circumferential mass is noted near the splenic flexure. The liver is normal to palpation. A hemicolectomy and mesenteric lymph node dissection are performed. Pathology shows adenocarcinoma in the mass, extending through the muscularis. Three of 10 lymph nodes are positive for tumor. What is the patient's stage? The patient recovers from surgery. His post-op CEA falls to 3.6 (normal for non-smokers is 0 - 3 ng/mL). He receives six months of adjuvant chemotherapy consisting of fluorouracil and leucovorin. What is his prognosis at five years after surgery? How does the chemotherapy improve his prognosis? What follow-up studies are indicated? What will they look for? Three years after surgery, the patient's CEA rises to 6.1 ng/mL. His physical examination continues to be normal. A CT scan of the abdomen shows a single 3 cm mass in the caudate lobe of the liver, which as not present on previous scans. Otherwise the CT scan is unremarkable. A chest radiograph shows no identifiable metastases. A colonoscopy shows no lesions. What do you do now?
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CASE 3
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Clinical History:
You see a 63 year-old man in the outpatient clinic. He has no health insurance and has not had regular medical follow-up for some time. He has noted a "lump" in his neck for the past two months. It has grown from marble-sized to the size of a small golf ball during that time. He feels well, with no weight loss, chills, fever or night sweats. He has a mild "smoker's cough" that has been unchanged for the past few years. His exercise tolerance is unchanged at two flights of stairs. He is a heavy smoker (80 pack-years). Aside from minor surgical procedures, he has no significant past medical history. You examine the patient. He has nicotine-stained fingers. Lung exam shows his chest to be mildly hyperexpanded. There are occasional diffuse wheezes over the lung fields. There is no dullness to percussion. There is a 2.5 cm diameter fixed, gritty-feeling, non-tender mass at the base of the right sternocleidomastoid muscle, just above the clavicle. The remainder of the physical examination, including a screening neurological exam, is unremarkable.
Images for this patient:
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Image 3.4 - Microscopic appearance
Questions:
With the patient's heavy smoking history, you suspect that he has lung cancer with a metastasis to a lymph node in the neck. However, like any good medical student, you wish to broaden your differential diagnosis. What other cancers could produce metastases in this location? The chest radiograph shows a 5 cm mass involving the right hilum. There appears to be some nodular fullness at the right side of the mediastinum consistent with enlarged nodes in this area. There are no effusions or consolidation. Lung cancer seems likely. What do you do next? Fine needle-aspiration cytology of the neck mass shows malignant cells to be present. By immunohistochemical staining, the cells are positive for cytokeratins. Other special immunohistochemical stains, including neuron-specific enolase (NSE), leukocyte common antigen (LCA), thyroglobulin, prostate specific antigen (PSA), and vimentin are all negative. What type of cancer is this? Is it primary or metastatic? What do the special stains tell you? What other studies would you obtain to stage this patient? Based on the information provided above, what is his clinical stage? What types of treatments would you offer this patient?
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