A 44-year-old woman notes a lump in her left breast while taking a shower.

Her physician palpates a 3 cm firm, irregular, non-movable mass in the upper outer quadrant of her left breast on physical examination. A fine needle aspiration of this mass is performed, and the cells obtained are examined cytologically and are consistent with infiltrating ductal carcinoma. The mass is removed with lumpectomy along with an axillary lymph node dissection. Which of the following findings will best predict a better prognosis for this patient? No metastases in the sampled lymph nodes A change in bowel habits prompts a 53-year-old woman to see her physician. On physical examination there are no lesions noted on digital rectal examination, but her stool is positive for occult blood. A colonoscopy is performed and reveals a 6 cm friable mass in the cecum. A biopsy of this mass is performed and microscopic examination shows a moderately differentiated adenocarcinoma. Which of the following findings is most likely to be present in this patient? K-RAS mutation in the neoplastic cells A 45-year-old healthy woman has a routine check of her health status. She has no chest pain, cough, or fever. A chest x-ray is taken and shows a peripheral 2.5 cm diameter "coin lesion" in the right mid-lung field. Which of the following biologic characteristics best distinguishes this lesion as a neoplasm, rather than a granuloma? Uncontrolled (autonomous) growth A clinical study is performed to determine the incidence of cancers in different countries. The data show that persons born in Japan and continuing to reside there have an increased risk for cancer. Which of the following cancers is most likely seen with increased frequency in this population? Stomach A 48-year-old woman goes to her physician for a routine physical examination. A 4 cm diameter non-tender mass is palpated in her right breast. The mass appears fixed to the chest wall. Another 2 cm non-tender mass is palpable in the left axilla. A chest radiograph reveals multiple 0.5 to 2 cm nodules in both lungs. Which of the following classifications best indicates the stage of her disease? T4 N1 M1 A study is performed to analyze characteristics of malignant neoplasms in biopsy specimens. The biopsies were performed on patients who had palpable mass lesions on digital rectal examination. Of the following microscopic findings, which is most likely to indicate that the neoplasm is malignant? Invasion Review of a series of surgical pathology reports indicates that a certain type of neoplasm is diagnosed as grade I on a scale of I to IV. Clinically, some of the patients with this neoplasm are found to have stage I disease. Which of the following is the best

interpretation of a neoplasm with these designations? Well-differentiated and localized A 51-year-old man has worked for 10 years in a factory producing plastic pipe. He has noted weight loss, nausea, and vomiting worsening over the past 5 months. On examination he is afebrile. There is generalized muscle wasting. Laboratory studies show the serum alkaline phosphatase is 405 U/L with AST 67 U/L, ALT 55 U/L, and total bilirubin 1.2 mg/dL. An abdominal CT scan reveals a 12 cm right liver lobe mass. Liver biopsy reveals a neoplasm composed of spindle cells forming irregular vascular channels. The cells demonstrate vimentin positivity and cytokeratin negativity with immunohistochemical staining. Exposure to which of the following substances most likely led to development of this neoplasm? Vinyl chloride A child is born with a single functional allele of a tumor suppressor gene. At the age of five the remaining normal allele is lost through a point mutation. As a result, the ability to inhibit cell cycle progression until the cell is ready to divide is lost. Which of the following neoplasms is most likely to arise via this mechanism? Retinoblastoma of eye A 22-year-old woman goes to her physician for a routine examination. A palpable nodule is found in the right lobe of her thyroid gland. No lymphadenopathy is noted. A chest xray shows no masses. A fine needle aspirate of the nodule is performed and cytologic examination reveals cells present consistent with a papillary carcinoma of the thyroid. There are no other family members affected by this disorder. She works as a secretary for an accounting firm part time and is earning a college degree. Which of the following findings would you consider most relevant in her past history to indicate a risk factor for this neoplasm? Radiation therapy in childhood A 50-year-old man has felt vague abdominal discomfort for the past 4 months. On physical examination he has no lymphadenopathy, and no abdominal masses or organomegaly can be palpated. Bowel sounds are present. An abdominal CT scan shows a 20 cm retroperitoneal soft tissue mass obscuring the left psoas muscle. A stool specimen tested for occult blood is negative. Which of the following neoplasms is this man most likely to have? Liposarcoma A 52-year-old man has had increasing fatigue for the past 6 months. On physical examination he has a palpable spleen tip. Laboratory studies show a WBC count of 189,000/microliter. The peripheral blood smear shows many mature and immature myeloid cells present. Cytogenetic analysis of cells obtained via bone marrow aspiration reveals a t(9:22) translocation. This translocation leads to formation of a hybrid gene that greatly increases tyrosine kinase activity. Which of the following genes is most likely

translocated to cause these findings? ABL A clinical study is performed of oncogenesis in human neoplasms. It is observed that some neoplasms appear to develop from viral oncogenesis, with serologic confirmation of past viral infection. Which of the following neoplasms is most likely to arise in this manner? T-cell leukemia An experiment is designed to study the genetics of cancer. The study will link the appearance of cancer to specific gene abnormalities. Which of the following forms of cell molecular analysis is most useful to identify gene alterations involved in carcinogenesis? Single nucleotide polymorphisms A 29-year-old woman with a history of multiple sexual partners over the last 15 years has a routine physical examination with no abnormal findings. On pelvic examination, the cervix shows no abnormalities, but a Pap smear is taken and dysplastic cells are reported to be present. A cervical biopsy is performed and shows a low grade squamous intraepithelial lesion (LSIL), also known as cervical intraepithelial neoplasia dysplasia (CIN). Which of the following is the most therapy for this lesion? Surgical excision A 64-year-old man has noted a 5 kg weight loss along with increasing fatigue over the past year. He has experienced dull abdominal pain for the past week. He has developed abdominal distention with lack of stools in the past two days. On physical examination, bowel sounds are reduced. An abdominal CT scan reveals a mass involving the descending colon. At laparotomy, a partial resection of the left colon is performed, with removal of an encircling mass. Microscopically, the mass is found to be a moderately differentiated adenocarcinoma. Which of the following laboratory test findings is most likely to be present in this man? Microcytic hypochromic anemia A 14-year-old healthy girl has a 0.3 cm reddish, slightly raised nodule on the skin of the upper part of her chest found on a routine physical examination. She states that this lesion has been present for years and has not appreciably changed in size or color. Which of the following neoplasms is this nodule most likely to be? Hemangioma A 56-year-old man has had a chronic cough for the past year. He is a non-smoker. He had an episode of hemoptysis 3 days ago. No abnormal findings are noted on physical examination. A chest x-ray demonstrates a 6 cm perihilar mass. A sputum sample is collected, and the sputum cytology report reads "Atypical cells present suggestive of

squamous cell carcinoma." Which of the following environmental exposures is most likely to be associated with these findings? Radon A 60-year-old man who has a 90 pack year history of cigarette smoking has had a chronic cough for the past 10 years. He has begun to lose weight (3 kg) during the past year. No abnormal findings are noted on physical examination. He has a chest radiograph that reveals a right hilar mass. A sputum cytology shows atypical, hyperchromatic squamous cells. What is the most common initial pathway for metastases from this lesion? Lymphatics A 55-year-old man dies after a year-long illness. At autopsy her liver contains multiple tumor masses from 2 to 5 cm in size that are firm and tan and that grossly exhibit umbilication with central necrosis. The surrounding hepatic parenchyma appears normal. Which of the following characteristics of neoplasia is best illustrated by these findings? Advanced stage A 59-year-old man has had a worsening cough with chest pain for the past 6 months. On physical examination he has no remarkable findings. A chest x-ray shows a 3 cm left lung mass. A sputum cytology specimen yields cells diagnosed as a squamous cell carcinoma. A mediastinoscopy is performed and reveals metastases in a lymph node. He is given radiation therapy, and the mass diminishes in size. Which of the following cellular mechanisms is most likely to account for this tumor response? Generation of free radicals A 60-year-old woman has a firm mass with irregular borders felt in her left breast on a routine physical examination. A fine needle aspiration is performed and microscopic examination shows malignant cells. A left mastectomy with axillary lymph node dissection is performed. A tissue sample of this neoplasm is submitted for analysis by flow cytometry. Which of the following does flow cytometric analysis most likely provide? Determination of aneuploidy A 35-year-old woman had a firm nodule palpable on the dome of the uterus six years ago recorded on routine physical examination. The nodule has slowly increased in size and now appears to be about twice the size it was when first discovered. By ultrasound scan it is solid and circumscribed. She remains asymptomatic. Which of the following neoplasms is she most likely to have? Leiomyoma A 15-year-old boy has had lumps in his right neck for the past 5 months. On physical examination there is painless lymphadenopathy in the right cervical region. One of the

lymph nodes is biopsied and on microscopic examination shows many lymphocytes that are large, with clumped chromatin and occasional mitoses. The characterization of this population of lymphocytes as a neoplasm is best accomplished by which of the following methods? Gene rearrangement studies that demonstrate clonality A previously healthy 42-year-old man has a skin nodule on his right hand that has become larger and darker with more irregular outlines over the past 3 months. On physical examination this lesion is a 1.2 cm diameter, darkly pigmented, and slightly raised nodule on the dorsum of his right hand. No other skin lesions are noted. Three nontender enlarged lymph nodes are palpable in the right axilla. The lesion is excised and microscopic examination shows a neoplasm composed of darkly pigmented polygonal and spindle cells. Which of the following risk factors is most important for development of this neoplasm? Chronic exposure to ultraviolet radiation A a 27-year-old woman in excellent health has a routine health maintenance examination. A 2 cm firm, rounded mass is palpable beneath the skin of the left forearm. She has no difficulty using the arm and there is no associated pain with the mass, either in movement or on palpation. The overlying skin appears normal. The mass does not change in size over the next year. Which of the following neoplasms is she most likely to have? Lipoma A 41-year-old woman has noted a foul-smelling vaginal discharge for 3 weeks. On physical examination there is an exophytic 3 cm mass involving the ectocervix. Pap smear testing is performed; she has never had a previous Pap smear. Cytologic changes are present on this Pap smear that are consistent with squamous cell carcinoma. She is found to have a positive serologic test for syphilis. Her serum glucose is 157 mg/dL. She has been a commercial sex worker in the past. Which of the following is the most likely risk factor for her cervical carcinoma? Human papillomavirus infection A 60-year-old man with an 80 pack year history of smoking experiences an episode of hemoptysis. On physical examination he has puffiness of the face, some pedal edema, bruises of the skin, and a blood pressure of 165/100 mm Hg. A chest radiograph reveals a 5 cm right upper lobe lung mass. A fine needle aspirate of this mass yields cells consistent with small cell anaplastic ("oat cell") carcinoma. A bone scan shows no metastases. Immunohistochemical staining of the tumor cells is likely to be positive for which of the following hormones? ACTH A 45-year-old woman has noted a lump on her left shoulder that has enlarged over the

past 4 months. On physical examination there is an enlarged, non-tender supraclavicular lymph node. A biopsy of the node is performed and on microscopic examination there is a metastatic neoplasm. Which of the following is the most likely primary neoplasm? Adenocarcinoma of the stomach A 59-year-old man has had fatigue for the past year. The only abnormal physical examination finding is a positive stool guaiac test. Laboratory studies show a CBC with Hgb 10.0 g/dL, Hct 29.8&, MCV 73 fL, platelet count 300,000/microliter, and WBC count 8700/microliter. He is found on colonoscopy to have a 4 cm mass lesion arising on the mucosal surface of the transverse colon. An abdominal CT scan shows hepatic masses. He receives therapy with cetuximab directed at vascular endothelial growth factor (VEGF). Which of the following cell signaling pathways is most affected by this therapy? Notch Columnar epithelial cells from the colonic mucosa are studied to identify abnormalities in cell signaling pathways. Abnormal epithelial cells from colonic adenocarcinoma are shown to have a mutation that blocks hydrolysis of GTP-bound active RAS. Normal columnar cells have active RAS protein that undergoes hydrolysis to the inactive GDPbound form. Which of the following signaling pathways is most likely abnormally stimulated in the carcinoma cells? MAP kinase A 52-year-old woman feels a lump in her right breast and goes to her physician. On physical examination there is a 3 cm right breast mass fixed to the chest wall. This mass is biopsied and on microscopic examination shows nests of cells with marked hyperchromatism and pleomorphism. These cells are estrogen receptor positive. Flow cytometry is performed. Compared with surrounding non-neoplastic stromal cells, the neoplastic cells are more likely to be in which of the following phases of the cell cycle? S A 70-year-old man has an episode of hematemesis. Upper GI endoscopy reveals an irregular 4 cm gastric antral ulceration. Biopsies are performed and microscopically reveal adenocarcinoma. Molecular analysis shows DNA hypermethylation of the CDKN2 complex. Through which of the following mechanisms has this abnormal gene expression most likely occurred? Epigenetic alteration n an experiment, it is observed that chronic, increased exposure to ionizing radiation results in damage to cellular DNA. As a consequence, a protein is now absent that would arrest the cell in the G1 phase of the cell cycle. Subsequent to this, the cell is transformed to acquire the property of unregulated growth. The absent protein is most likely the product of which of the following genes?

p53 A 50-year-old woman notes a lump in her left breast. She goes to her physician's assistant, who palpates a 2 cm firm mass in her left breast. A fine needle aspiration biopsy is performed, and on microscopic examination a ductal carcinoma is seen. A poorer prognosis for the patient is most closely associated with which of the following findings? Aneuploidy by flow cytometry An epidemiologic study is performed to determine risk factors for development of malignant neoplasms. A statistical analysis of pre-existing medical conditions is done. Some pre-existing conditions are observed to precede development of malignant neoplasms, while others do not. Which of the following conditions is most likely to be statistically unrelated to subsequent malignancy? Uterine leiomyomas A 35-year-old man has noted several 1 to 2 cm reddish purple, nodular lesions present on the skin of his right arm which have increased in size and number over the past 3 months. The lesions do not itch and are not painful. He has had a watery diarrhea for the past month. On physical examination he has generalized lymphadenopathy and oral thrush. Which of the following infections is most likely to be related to the appearance of these skin lesions? Human herpesvirus 8 A 66-year-old woman has noted increasing abdominal girth for 3 months. On examination there is a fluid wave. Paracentesis yields cloudy fluid that cytologically contains clusters of malignant cells. An abdominal CT scan shows bilateral cystic and solid pelvic masses and multiple peritoneal nodules. She is treated with chemotherapy with an initial response, but a year later there is still residual tumor. Which of the following parameters of the neoplastic cells best predicts her diminished chemotherapy response? Growth fraction A 49-year-old man complains of pain in his left thigh for 3 months. On physical examination his thigh is increased in size, compared to the right. A plain film radiograph reveals the presence of a 15 cm solid mass that does not appear to arise from bone, but it does have infiltrative margins. A biopsy of this mass is taken, and on microscopic examination the mass is composed of highly pleomorphic spindle cells. Which of the following immunohistochemical markers is most likely to be demonstrated in the cells of this mass? Vimentin A clinical study is performed with patients who had a diagnosis of breast cancer. Characteristics of the grade, stage, molecular biology, and histologic type are analyzed. Of the following characteristics, which is most likely to be associated with the best prognosis for these patients?

Decreased nuclear/cytoplasmic ratio A 66-year-old man has noted darker urine for the past 2 weeks. A urinalysis shows hematuria. He is referred to a urologist who performs cystoscopy. A 3 cm mass is found in the dome of the bladder. Biopsies of the mass are taken and on microscopic examination show a urothelial carcinoma. Cells of this neoplasm demonstrate a single mutation causing cellular inability to hydrolyze GTP, thus resulting in cellular transformation. Which of the following oncogenes is most likely implicated in this case? RAS A 44-year-old woman who has had multiple sexual partners for the past 30 years has an abnormal Pap smear with cytologic changes suggesting human papillomavirus (HPV) infection. Without treatment, she is most likely to develop which of the following lesions? Squamous cell carcinoma in an epidemiologic study, "fallout" from nuclear bomb testing and from nuclear power plant disasters is observed to have released radioactive isotopes into the environment. One of these isotopes is found to be strontium-90. It is observed that the strontium-90 in soils goes into the food chain and eventually contaminates milk products. This contamination is most likely to increase the risk for which of the following neoplasms? Osteosarcoma A clinical trial of a new chemotherapy protocol is performed involving patients with lung carcinoma. It is observed that a response occurs that leads to DNA strand breakage and carcinoma cell death. The primary carcinomas are initially observed to decrease in size following therapy. However, after 3 months, the carcinoma is no longer regressing with this therapy. Altered expression of which of the following by the neoplastic cells has most likely resulted in this reduced response? DNA topoisomerase II In an experiment, biologic characteristics of neoplastic and non-neoplastic cells are analyzed in culture. It is observed that cell division in cells derived from malignant neoplasms, but not in normal cells, is aided by the presence of an enzyme which repairs progressive chromosomal shortening. The lack of chromosomal shortening allows the malignant cells to undergo many more divisions than the normal cells. Which of the following enzymes is most likely to have this effect? Telomerase A 62-year-old man has complained of pain on urination for the past week. He is afebrile. On cystoscopy, a slightly erythematous 1 cm diameter area is seen on the bladder mucosa. This area is biopsied and on microscopic examination shows cells with marked hyperchromatism and increased nuclear/cytoplasmic ratio involving the full thickness of the epithelium. However, these changes are confined to the epithelium above the basement membrane. Which of the following terms best describes these biopsy findings?

Carcinoma in situ A 32-year-old woman has noted dull pelvic pain for the last two months. On physical examination there is a mass palpated in the right lower quadrant. An abdominal ultrasound reveals an 8 cm mass involving the right ovary. The mass is surgically excised. On gross inspection, the surface of the mass is smooth, is not adherent to surrounding pelvic structure, and is cystic and filled with hair on sectioning. On microscopic examination there is squamous epithelium, tall columnar glandular epithelium, cartilage, and fibrous connective tissue. Which of the following neoplasms is she most likely to have? Teratoma A 54-year-old woman has an episode of coughing with blood-streaked sputum. On physical examination she appears cachectic. A chest x-ray shows an irregular mass lesion in the right lung. A transbronchial biopsy is done and on microscopic examination shows small cell anaplastic carcinoma. She is treated with a multidrug chemotherapy regimen and has a partial response. However, metastatic disease develops eight months later. A second chemotherapy protocol is tried, but no response is noted. Which of the following is the most likely reason for failure of the second protocol to elicit a response? P-glycoprotein expression A previously healthy 66-year-old man has been feeling tired for 5 months. He goes to his physician, who performs a complete physical examination, including stool guaiac, which is positive. A colonoscopy is performed, and a large, sessile 4.5 cm mass with surface ulceration is found in the cecum. A biopsy of this mass microscopically shows irregular glands with crowded, tall columnar cells having marked nuclear hyperchromatism. Which of the following gene alterations is he most likely to have? Acquired p53 gene mutation An 8-year-old boy has complained of difficulty swallowing for the past month. On physical examination he has a palpable, firm mass in the right neck. A head CT scan reveals a 7 cm solid soft tissue mass lateral to the esophagus on the right. A biopsy of this mass demonstrates pleomorphic spindle cells that are cytokeratin negative, CD45 negative, and vimentin positive. Which of the following neoplasms is he most likely to have? Rhabdomyosarcoma A 53-year-old woman feels a lump in her right breast. Her physician palpates an irregular 3 cm mass that is not movable because it appears fixed to the overlying skin, which is retracted. A mastectomy is performed and the pathologist on sectioning the breast finds a 3 x 3.5 cm ovoid mass that does not have discrete borders, but appears to infiltrate into the surrounding fibrofatty breast stroma. The mass is firm, white, and has a fibrous consistency. Which of the following features is most likely demonstrated by the gross appearance of this mass?

Desmoplasia A 66-year-old man has a routine physical examination and a stool sample is positive for occult blood. He undergoes colonoscopy and a 5 cm sessile mass is present in the sigmoid colon. Biopsy of the mass yields a diagnosis of adenocarcinoma. A chest x-ray shows multiple 1 to 3 cm nodules in both lungs. Presence of which of the following in the neoplastic cells is most likely to explain the formation of Beta-catenin A healthy 22-year-old woman undergoes a routine physical examination. A discrete, firm, rubbery, movable mass is found in the left breast. She has no axillary lymphadenopathy. The skin overlying the breast and the nipple appear normal. Which of the following neoplasms is most likely to be present? Fibroadenoma An epidemiologic study is performed involving patients of Asian ancestry with longstanding Epstein-Barr virus (EBV) infection. It is observed that these patients have an increased risk for development of malignant neoplasms in adulthood. Which of the following neoplasms is most likely to be found in these patients? Nasopharyngeal carcinoma A clinical study is performed involving children who have developed skin cancers, including squamous cell carcinomas and basal cell carcinomas. Molecular analysis of their cancer cells shows defective DNA repair from loss of nucleotide excision repair gene expression. Which of the following genes is most likely mutated in these chilren? XPA A 29-year-old woman feels a nodule in her neck. On examination there is a firm 2 cm mass in the right lobe of her thyroid. A fine needle aspiration shows cells consistent with papillary carcinoma. 2 years ago she had a lobular carcinoma excised from her left breast. Her 31-year-old sister was recently diagnosed with endometrial carcinoma. A 34year-old cousin has had colon cancer. Over 3 generations, 6 of 24 close relatives have had a malignancy, most diagnosed before age 35. Which of the following most likely explains the increased risk for cancer in these people? Multifactorial inheritance A study of malignant neoplasms reveals that some of them have a greater potential for invasion and metastases. Analysis of the cells of cancers that have metastasized reveals a mutation which results in decreased cell surface expression of E-cadherin. Which of the following genes is most likely mutated to produce these findings? beta-catenin An experiment is conducted in which proliferating cells are subjected to ionizing radiation. The ionizing radiation leads to arrest in a checkpoint that monitors completion of DNA replication. It is observed that there are increased numbers of chromosomal

abnormalities in these cells. Which of the following is the checkpoint affected by the ionizing radiation? G2/M