Robbin's Review - Ch.7 (Neoplasia)

A 67-year-old man has noted a chronic cough for the past 3 months. On physical examination, there is mild stridor on inspiration over the right lung. A chest radiograph shows a 5-cm right hilar lung mass, and a fine-needle aspiration biopsy specimen of the mass shows cells consistent with squamous cell carcinoma. If staging of this neoplasm is denoted as T2N1M1, which of the following statements is most accurate? □ (A) A CT scan of the head shows a 2-cm right parietal mass □ (B) Serum chemistry shows an elevated corticotropin level □ (C) The mass had infiltrated the chest wall □ (D) The cancer is poorly differentiated □ (E) The tumor is obstructing the left mainstem bronchus

A. A CT scan of the head shows a 2-cm right parietal mass

In an experiment, cells from human malignant neoplasms explanted into tissue culture medium continue to replicate. This allows development of "immortal" tumor cell lines that are extremely useful for study of tumor biology and responses to therapeutic modalities. Which of the following molecular alterations that endows these tumor cells with limitless replicative ability in vivo and in vitro is most likely to be observed? □ (A) Activation of telomerase □ (B) Activation of cyclin genes □ (C) Inhibition of cyclin activators □ (D) Activation of vascular endothelial growth factor □ (E) Activation of BCL2 gene □ (F) Inability to repair errors in DNA replication

A. Activation of telomerase

During a routine health maintenance examination of a 40-year-old man, a stool guaiac test result was positive. A follow- up sigmoidoscopy showed a 1.5-cm, circumscribed, pedunculated mass on a short stalk, located in the upper rectum. Which of the following terms best describes this lesion? □ (A) Adenoma □ (B) Hamartoma □ (C) Sarcoma □ (D) Choristoma □ (E) Nevus

A. Adenoma

A 53-year-old man diagnosed with oral cancer and treated with radiation and chemotherapy 1 year ago now has a positron emission tomography (PET) scan of his neck that shows a single focus of increased uptake. This focus is resected and microscopic examination shows that it is a metastasis. Molecular analysis of this cancer shows p53, PTEN, and c-MYC gene mutations. Which of the following metabolic pathways is most likely upregulated to promote his cancer cell survival and proliferation? □ (A) Aerobic glycolysis □ (B) Gluconeogenesis □ (C) Hexose monophosphate shunt □ (D) Oxidative phosphorylation □ (E) Purine degradation

A. Aerobic glycolysis

A clinical study involves patients diagnosed with carcinoma whose tumor stage is T4N1M1. The patients' survival rate 5 years from the time of diagnosis is less than 50%, regardless of therapy. Which of the following clinical findings is most likely to be characteristic of this group of patients? □ (A) Cachexia □ (B) Cardiac murmur □ (C) Icterus □ (D) Loss of sensation □ (E) Splenomegaly □ (F) Tympany

A. Cachexia

In a clinical trial, patients diagnosed with malignant melanoma are treated by infusion of autologous CD8+ T cells grown in vitro. These CD8+ T cells are known to kill melanoma cells, but not normal cells. Which of the following target antigens is most likely recognized by these CD8+ T cells? □ (A) Class I MHC molecules with a melanoma cell peptide □ (B) Class I MHC molecules with a peptide from normal melanocytes and melanoma cells □ (C) Class I MHC molecules plus a peptide derived from carcinoembryonic antigen □ (D) Class II MHC molecules with a melanoma cell peptide □ (E) Class II MHC molecules with a peptide from normal melanocytes and melanoma cells □ (F) Class II MHC molecules with laminin receptors on melanoma cells

A. Clas I MHC molecules w/ a melanoma cel peptide

A 44-year-old woman sees her physician because she feels lumps in the right axilla. The physician notes right axillary lymphadenopathy on physical examination. The nodes are painless but firm. Which of the following is the most likely diagnosis? □ (A) Ductal carcinoma of the breast □ (B) Acute mastitis with breast abscess □ (C) Leiomyosarcoma of the uterus □ (D) Cerebral glioblastoma multiforme □ (E) Squamous dysplasia of the larynx

A. Ductal carcinoma of the breast

A 48-year-old woman notices a lump in her left breast. On physical examination, the physician palpates a firm, nonmovable, 2-cm mass in the upper outer quadrant of the left breast. There are enlarged, firm, nontender lymph nodes in the left axilla. A fine-needle aspiration biopsy is performed, and the cells present are consistent with carcinoma. A mastectomy with axillary lymph node dissection is performed, and carcinoma is present in two of eight axillary nodes. Which of the following factors is most likely responsible for the lymph node metastases? □ (A) Increased laminin receptors on tumor cells □ (B) Presence of keratin in tumor cells □ (C) Diminished apoptosis of tumor cells □ (D) Tumor cell monoclonality □ (E) Lymphadenitis

A. Increased laminin receptors on tumor cells

A 30-year-old man has a 15-year history of increasing numbers of multiple benign skin nodules. On physical examination, the firm nodules average 0.5 to 1 cm and appear to be subcutaneous. Further examination shows numerous oval 1- to 5-cm pigmented skin lesions. Ophthalmoscopic examination shows hamartomatous nodules on the iris. A biopsy specimen of one skin nodule shows a neoplasm that is attached to a peripheral nerve. Which of the following mechanisms of transformation is most likely related to the mutation that this patient has inherited? □ (A) Persistent activation of the RAS gene □ (B) Increased production of epidermal growth factor □ (C) Decreased susceptibility to apoptosis □ (D) Impaired functioning of mismatch repair genes □ (E) Inactivation of the RB gene

A. Persistent activation of the RAS gene

A 56-year-old woman has had vaginal bleeding for 1 week. Her last menstrual period was 10 years ago. On physical examination, a lower abdominal mass is palpated. An abdominal CT scan shows a 6-cm mass in the left ovary. A total abdominal hysterectomy is performed. Microscopically, the ovarian mass is a granulosa-theca cell tumor. The patient also is found to have an endometrial carcinoma, which resulted from increased estrogen production by the ovarian mass. Which of the following best describes the relationship between these two neoplasms? □ (A) Promotion of carcinogenesis □ (B) Tumor heterogeneity □ (C) Paraneoplastic syndrome □ (D) Genetic susceptibility to tumorigenesis □ (E) Mutation of a tumor suppressor gene

A. Promotion of carcinogenesis

A 33-year-old woman undergoes a routine physical examination as part of health maintenance screening. There are no abnormal findings. A Pap smear is obtained as part of the pelvic examination. Cytologically, the cells obtained on the smear from the cervix show severe epithelial dysplasia. Which of the following statements best explains the significance of these findings? □ (A) The lesion could progress to invasive cervical carcinoma □ (B) An ovarian teratoma is present □ (C) There has been regression of a cervical carcinoma □ (D) Antibiotic therapy would cure the lesion □ (E) Female relatives are at risk of acquiring the same condition

A. The lesion could progress to invasive cervical carcinoma

A 33-year-old man has experienced occasional headaches for the past 3 months. He suddenly has a generalized seizure. CT scan of the head shows a periventricular 3-cm mass in the region of the right thalamus. A stereotactic biopsy of the mass yields cells diagnostic of a large B cell malignant lymphoma. Which of the following underlying diseases is most likely to be found in this patient? □ (A) Diabetes mellitus □ (B) AIDS □ (C) Hypertension □ (D) Multiple sclerosis □ (E) Tuberculosis

B. AIDS

A 26-year-old woman has a lump in the left breast. On physical examination, the physician finds an irregular, firm, 2-cm mass in the upper inner quadrant of the breast. No axillary adenopathy is noted. A fine-needle aspirate of the mass shows carcinoma. The patient's 30-year-old sister was recently diagnosed with ovarian cancer, and 3 years ago her maternal aunt was diagnosed with ductal carcinoma of the breast and had a mastectomy. Which of the following genes is most likely to have undergone mutation to produce these findings? □ (A) BCL2 (anti-apoptosis gene) □ (B) BRCA1 (DNA repair gene) □ (C) EGF (epidermal growth factor gene) □ (D) ERBB2 (growth factor receptor gene) □ (E) HST1 (fibroblast growth factor gene) □ (F) IL2 (growth factor gene) □ (G) K-RAS (GTP-binding protein gene) □ (H) Lyn (tyrosine kinase gene)

B. BRCA1 (DNA repair gene)

An epidemiologic study of cancer deaths recorded in the last half of the 20th century is conducted. The number of deaths for one particular cancer increased markedly in developed nations. In 1998, more than 30% of cancer deaths in men and more than 24% of cancer deaths in women were caused by this neoplasm. Which of the following neoplasms was most likely identified by this study? □ (A) Breast carcinoma □ (B) Bronchogenic carcinoma □ (C) Cervical squamous cell carcinoma □ (D) Adenocarcinoma of the colon □ (E) Melanoma of the skin □ (F) Prostatic adenocarcinoma

B. Bronchogenic carcinoma

A 62-year-old man has had several episodes of hematuria in the past week. On physical examination, there are no abnormal findings. A urinalysis shows 4+ hematuria, and cytologic examination of the urine shows that atypical cells are present. The urologist performs a cystoscopy and observes a 4-cm sessile mass with a nodular, ulcerated surface in the dome of the bladder. Which of the following terms best describes this lesion? □ (A) Papilloma □ (B) Carcinoma □ (C) Adenoma □ (D) Sarcoma □ (E) Fibroma

B. Carcinoma

n a family of five children, a 12-year-old girl and a 14-year-old boy have been affected by skin nodules that have developed over the past 5 years. On physical examination, both children are of appropriate height and weight. The skin lesions are 1- to 3-cm maculopapular nodules that are erythematous to brown-colored and have areas of ulceration. Biopsy specimens of the skin lesions show squamous cell carcinoma. The children have no history of recurrent infections, and their parents and other relatives are unaffected. Which of the following mechanisms is most likely to produce neoplasia in these children? □ (A) Infection with human papillomavirus □ (B) Failure of nucleotide excision repair of DNA □ (C) Ingestion of food contaminated with Aspergillus flavus □ (D) Inactivation of p53 □ (E) Chromosomal translocation

B. Failure of nucleotide excision repair of DNA

An epidemiologic study of cancer deaths recorded in the last half of the 20th century is conducted. The number of deaths for one particular type of cancer has been decreasing in developed nations, despite the absence of widespread screening programs. Which of the following neoplasms was most likely to be identified by this study? □ (A) Angiosarcoma of the liver □ (B) Gastric adenocarcinoma □ (C) Glioma of the brain □ (D) Leukemia □ (E) Lymphoma of the lymph nodes □ (F) Pancreatic adenocarcinoma

B. Gastric adenocarcinoma

A 50-year-old woman has had easy fatigability and noted a dragging sensation in her abdomen for the past 5 months. Physical examination reveals that she is afebrile. She has marked splenomegaly, but no lymphadenopathy. Laboratory studies show her total WBC count is 250,000/mm3 with WBC differential count showing 68% segmented neutrophils, 11% band neutrophils, 6% metamyelocytes, 5% myelocytes, 5% myeloblasts, 3% lymphocytes, and 2% monocytes. A bone marrow biopsy is performed, and karyotypic analysis of the cells reveals a t(9;22) translocation. Medical treatment with a drug having which of the following modes of action is most likely to produce a complete remission in this patient? □ (A) Antibody binding to ERB-2 receptor □ (B) Inhibiting tyrosine kinase activity □ (C) Selective killing of cells in S phase □ (D) Activating caspases □ (E) Preventing translocation of β-catenin to the nucleus □ (F) Delivering normal p53 into cells with viral vectors

B. Inhibiting tyrosine kinase activity

A 61-year-old woman has felt a lump in her breast for the past 2 months. On physical examination, there is a firm, 2-cm mass in the right breast. An excisional biopsy specimen of the mass shows carcinoma. Immunoperoxidase stains for protease cathepsin D and matrix metalloproteinase-9 are performed on the microscopic tissue section and show pronounced cytoplasmic staining in the tumor cells. Which of the following characteristics is most likely to be predicted by this marker? □ (A) Angiogenesis □ (B) Invasiveness □ (C) Differentiation □ (D) Heterogeneity □ (E) Aneuploidy

B. Invasiveness

A 40-year-old man notices an increasing number of lumps in the groin and armpit. On physical examination, he has generalized nontender lymph node enlargement and hepatosplenomegaly. An inguinal lymph node biopsy specimen shows a malignant tumor of lymphoid cells. Immunoperoxidase staining of the tumor cells with antibody to BCL2 is positive in the lymphocytic cell nuclei. Which of the following mechanisms has most likely produced the lymphoma? □ (A) Increased tyrosine kinase activity □ (B) Lack of apoptosis □ (C) Gene amplifications □ (D) Reduced DNA repair □ (E) Loss of cell cycle inhibition

B. Lack of apoptosis

An epidemiologic study investigates the potential cellular molecular alterations that may contribute to the development of cancers in a population. Data analyzed from resected colonic lesions show that changes are occurring that show the evolution of a sporadic colonic adenoma into an invasive carcinoma. Which of the following best describes the mechanism producing these changes? □ (A) Activation of proto-oncogenes by chromosomal translocation □ (B) Stepwise accumulation of multiple proto-oncogene and tumor suppressor gene mutations □ (C) Extensive regeneration of tissues increasing the mutation rate in regenerating cells □ (D) Inheritance of defects in DNA repair genes that increase the susceptibility to develop cancer □ (E) Overexpression of growth factor receptor genes

B. Stepwise accumulation of multiple proto-oncogen and tumor suppressor gene mutations

A 42-year-old man is concerned about a darkly pigmented "mole" on the back of his hand. The lesion has enlarged and bled during the past month. On physical examination, there is a slightly raised, darkly pigmented, 1.2-cm lesion on the dorsum of the right hand. The lesion is completely excised. Microscopically, a malignant melanoma is present. Which of the following factors presents the greatest risk for the development of this neoplasm? □ (A) Smoking tobacco □ (B) Ultraviolet radiation □ (C) Chemotherapy □ (D) Asbestos exposure □ (E) Allergy to latex

B. Ultraviolet radiation

A 59-year-old man has recently noticed blood in his urine. Cystoscopy shows a 4-cm exophytic mass involving the right bladder mucosa near the trigone. Biopsy specimens are obtained, and the patient undergoes a radical cystectomy. Examination of the excised specimen shows that a grade IV urothelial cell carcinoma has infiltrated the bladder wall. Which of the following statements regarding these findings is most appropriate? □ (A) The neoplasm is a metastasis □ (B) The patient has a poorly differentiated neoplasm □ (C) A paraneoplastic syndrome is likely □ (D) The stage of the neoplasm is low □ (E) The patient is probably cured of the cancer

B. The pt has a poorly differentiated neoplasm

A 35-year-old man with a family history of colon carcinoma undergoes a surveillance colonoscopy. It reveals hundreds of polyps in the colon, and two focal 0.5-cm ulcerated areas. A biopsy specimen from an ulcer reveals irregularly shaped glands that have penetrated into the muscular layer. Which of the following molecular events is believed to occur very early in the evolution of his colonic disease process? □ (A) Mutations in mismatch repair genes. □ (B) Inability to hydrolyze GTP-bound RAS □ (C) Activation of the WNT signaling pathway □ (D) Loss of heterozygosity affecting the p53 gene □ (E) Translocation of BCL2 from mitochondria to cytoplasm

C. Activation of the WNT signaling pathway

A 50-year-old woman saw her physician after noticing a mass in the right breast. Physical examination showed a 2-cm mass fixed to the underlying tissues beneath the areola and three firm, nontender, lymph nodes palpable in the right axilla. There was no family history of cancer. An excisional breast biopsy was performed, and microscopic examination showed a well-differentiated ductal carcinoma. Over the next 6 months, additional lymph nodes became enlarged, and CT scans showed nodules in the lung, liver, and brain. The patient died 9 months after diagnosis. Which of the following molecular abnormalities is most likely to be found in this setting? □ (A) Inactivation of one BRCA1 gene copy □ (B) Deletion of one p53 gene copy □ (C) Amplification of the ERBB2 (HER2) gene □ (D) Deletion of an RB gene locus □ (E) Fusion of BCR and C-ABL genes

C. Amplification of the ERBB2

A 49-year-old man has a lump near his right shoulder that has been increasing in size for the past 8 months. On physical examination, the physician palpates a 4-cm, firm, nontender mass in the right supraclavicular region. The mass is excised, and microscopically it is diagnosed as follicular lymphoma. Karyotypic analysis of the cells shows a chromosomal translocation, t(14;18), involving the immunoglobulin heavy-chain gene. Which of the following genes is most likely to have undergone mutation to produce these findings? □ (A) APC (tumor suppressor gene) □ (B) BCL1 (cyclin gene) □ (C) BCL2 (anti-apoptosis gene) □ (D) BRCA1 (DNA repair gene) □ (E) C-MYC (transcription factor gene) □ (F) ERBB2 (growth factor receptor gene) □ (G) IL2 (growth factor gene) □ (H) K-RAS (GTP-binding protein gene) □ (I) p53 (DNA damage response gene)

C. BCL2 (anti-apoptosis gene)

A 49-year-old man experiences an episode of hemoptysis. On physical examination, he has puffiness of the face, pedal edema, and systolic hypertension. A chest radiograph shows a 5-cm mass of the right upper lobe of the lung. A fine-needle aspiration biopsy of this mass yields cells consistent with small-cell anaplastic carcinoma. A bone scan shows no metastases. Immunohistochemical staining of the tumor cells is most likely to be positive for which of the following? □ (A) Parathyroid hormone-related peptide □ (B) Erythropoietin □ (C) Corticotropin □ (D) Insulin □ (E) Gastrin

C. Corticotropin

A 50-year-old woman undergoes screening colonoscopy as part of a routine health maintenance workup. An isolated 1- cm pedunculated polyp is found in the sigmoid colon. The excised polyp histologically shows well-differentiated glands with no invasion of the stalk. Which of the following investigational research procedures can distinguish most clearly whether the polyp represents hyperplasia of the colonic mucosa or a tubular adenoma? □ (A) Histochemical staining for mucin □ (B) Flow cytometry to determine the frequency of cells in the S phase □ (C) Determination of clonality by pattern of X chromosome inactivation □ (D) Immunoperoxidase staining for keratin □ (E) Immunoperoxidase staining for factor VIII

C. Determination of clonality by pattern of X chromosome inactivation

A 75-year-old woman has reported a change in the caliber of her stools during the past month. On physical examination, there are no abnormal findings, but a stool sample is positive for occult blood. A colonoscopy shows a constricting mass involving the lower sigmoid colon, and the patient undergoes a partial colectomy. Which of the following techniques used during surgery can best aid the surgeon in determining whether the resection is adequate to reduce the probability of a recurrence? □ (A) Fine-needle aspiration □ (B) Serum carcinoembryonic antigen assay □ (C) Frozen section □ (D) Electron microscopy □ (E) Flow cytometry

C. Frozen section

A 66-year-old man with chronic cough has an episode of hemoptysis. On physical examination, there are no abnormal findings. A chest radiograph shows a 6-cm mass in the right lung. A sputum cytologic analysis shows cells consistent with squamous cell carcinoma. Metastases from this neoplasm are most likely to be found at which of the following sites? □ (A) Chest wall muscle □ (B) Splenic red pulp □ (C) Hilar lymph nodes □ (D) Vertebral bone marrow □ (E) Cerebrum

C. Hilar LNs

An epidemiologic study analyzes health care benefits of cancer screening techniques applied to a population. Which of the following diagnostic screening techniques used in health care is most likely to have had the greatest impact on reduction in cancer deaths in developed nations? □ (A) Chest radiograph □ (B) Stool guaiac □ (C) Pap smear □ (D) Serum carcinoembryonic antigen assay □ (E) Urinalysis

C. Pap smear

A 70-year-old woman reported a 4-month history of a 4-kg weight loss and increasing generalized icterus. On physical examination, she is afebrile, and her blood pressure is 130/80 mm Hg. An abdominal CT scan shows a 5-cm mass in the head of the pancreas. Fine-needle aspiration of the mass is performed. On molecular analysis, the neoplastic cells from the mass show continued activation of cytoplasmic kinases. Which of the following oncogenes is most likely to be involved in this process? □ (A) MYC □ (B) APC □ (C) RAS □ (D) ERBB2 □ (E) sis

C. RAS

A 22-year-old woman, who works as a secretary for an accounting firm, has noted a palpable nodule on the side of her neck for the past 3 months. On physical examination, there is a 2-cm, firm, nontender nodule involving the right lobe of the thyroid gland. A fine-needle aspiration biopsy specimen of the nodule shows cells consistent with carcinoma of the thyroid. No other family members are affected by this disorder. Which of the following would be considered most relevant in the woman's past medical history? □ (A) Chronic alcoholism □ (B) Ataxia telangiectasia □ (C) Radiation therapy in childhood □ (D) Blunt trauma from a fall □ (E) Exposure to arsenic compounds

C. Radiation therapy in childhood

A 53-year-old woman sees her physician because she has noticed a change in her bowel habits. On physical examination, there are no abnormal findings, but the test result for stool guaiac is positive. A colonoscopy is performed, and a 3-cm sessile mass is found in the cecum. A biopsy specimen of the mass shows a moderately differentiated adenocarcinoma confined to the mucosa. An abdominal CT scan shows no lymphadenopathy. Given this information, which of the following is the best course of action? □ (A) Perform a limited excision to "shell out" the lesion from its surrounding capsule □ (B) Assume that this represents a metastasis and search for a primary tumor elsewhere □ (C) Resect the tumor and some of the normal surrounding tissue □ (D) Remove the entire colon to prevent a recurrence □ (E) Observe the lesion for further increase in size

C. Resect the tumor and some of the normal surrounding tissue

A 40-year-old man has a history of intravenous drug use. Physical examination shows needle tracks in his left antecubital fossa. He has mild scleral icterus. Serologic studies for HBsAg and anti-HCV are positive. He develops hepatocellular carcinoma 15 years later. Which of the following viral characteristics best explains why this patient developed hepatocellular carcinoma? □ (A) Viral integration in the vicinity of protooncogenes □ (B) Viral capture of protooncogenes from host DNA □ (C) Viral-induced injury followed by extensive hepatocyte regeneration □ (D) Viral inactivation of RB and p53 gene expression □ (E) Viral infection of inflammatory cells with host immunosuppression

C. Viral-induced injury followed by extensive hepatocyte regeneration

A 69-year-old woman has experienced increasing malaise and a 10-kg weight loss over the past year. She dies of massive pulmonary thromboembolism. The gross appearance of the liver at autopsy is shown. Which of the following statements best characterizes the process that led to the patient's death? □ (A) A liver biopsy would have shown a dysplasia □ (B) This is a multifocal hepatic adenoma □ (C) A hepatocellular carcinoma has invaded locally □ (D) Colonic adenocarcinoma with metastases was present □ (E) The lesions should have been resected

D. Colonic adenocarcinoma w/ metastases was present

A study of patients treated with chemotherapy protocols for cancer shows that 10% of them subsequently develop a second cancer, a much higher incidence compared with a control group not receiving chemotherapy. These chemotherapy protocols included the alkylating agent cyclophosphamide. What is the most likely mechanism of action by this alkylating agent for development of the subsequent carcinomas in these treated cancer patients? □ (A) Activation of protein kinase C □ (B) Activation of endogenous viruses □ (C) Blockage of TGF-β pathways □ (D) Direct DNA damage □ (E) Inhibition of DNA repair □ (F) Inhibition of telomerase

D. Direct DNA damage

A 30-year-old woman who has had multiple sexual partners sees her physician because she has had vaginal bleeding and discharge for the past 5 days. On physical examination, she is afebrile. Pelvic examination shows an ulcerated lesion arising from the squamocolumnar junction of the uterine cervix. A cervical biopsy is performed. Microscopic examination reveals an invasive tumor containing areas of squamous epithelium, with pearls of keratin. In situ hybridization shows the presence of human papillomavirus type 16 (HPV-16) DNA within the tumor cells. Which of the following molecular abnormalities in this tumor is most likely related to infection with HPV-16? □ (A) Trapping of the RAS protein in a GTP-bound state □ (B) Increased expression of laminin receptor genes □ (C) Inability to repair DNA damage □ (D) Functional inactivation of the RB1 protein □ (E) Increased expression of epidermal growth factor receptor

D. Functional inactivation of the RB1 protein

A 23-year-old woman has noted a nodule on the skin of her upper chest. She reports that the nodule has been present for many years and has not changed in size. On physical examination, there is a 0.5-cm, dark red, nontender, raised nodule with a smooth surface. Which of the following is the most likely diagnosis? □ (A) Adenoma □ (B) Fibroadenoma □ (C) Hamartoma □ (D) Hemangioma □ (E) Leiomyoma □ (F) Lipoma □ (G) Melanoma □ (H) Nevus

D. Hemangioma

A 60-year-old man comes to his physician because he has noted a mass in his neck that has increased rapidly in size over the past 2 months. On physical examination, a firm, nontender, 10-cm mass in the left lateral posterior neck that appears to be fused to cervical lymph nodes is palpated. Hepatosplenomegaly is noted. A head CT scan reveals a mass in the Waldeyer ring near the pharynx. A biopsy of the neck mass is performed, and on microscopic examination the biopsy specimen shows abnormal lymphoid cells with many mitotic figures and many apoptotic nuclei. The patient is treated with a cocktail of cell cycle-acting chemotherapeutic agents. The cervical and oral masses shrink dramatically over the next month. Based on his history and response to treatment, the tumor cells are most likely to have which of the following features? □ (A) Limited capacity to metastasize □ (B) Polyclonality □ (C) Poor vascularity □ (D) High growth fraction □ (E) Strong expression of tumor antigens

D. High growth fraction

A 66-year-old woman has worked all of her life on a small family farm on the Kanto plain near Tokyo. She has had no previous major illnesses, but has been feeling increasingly tired and weak for the past year. On physical examination, she is afebrile, but appears pale. Laboratory studies show hemoglobin, 11.3 g/dL; hematocrit, 33.8%; platelet count, 205,200/mm3; and WBC count, 64,000/mm3. Immunophenotyping yields the findings shown in the figure. Assuming that the dominant cell population is clonal, which of the following viral agents is most likely involved in this patient's disease process? □ (A) Human papillomavirus □ (B) HIV-1 □ (C) Epstein-Barr virus □ (D) Human T cell lymphotropic virus type 1 □ (E) Hepatitis B virus

D. Human T cell lymphotropic virus type 1

An investigational study reviews cells from patients who had hereditary nonpolyposis colon cancer. The patients typically developed multiple lesions of the colon during middle age. Molecular analysis of the cells from the lesions shows changes in hPMS1, hPMS2, and hMLH1 genes. Which of the following principles of carcinogenesis is best illustrated by this study? □ (A) Tumor initiators are mutagenic □ (B) Tumor promoters induce proliferation □ (C) Many oncogenes are activated by translocations □ (D) Inability to repair DNA is carcinogenic □ (E) Carcinogenesis is a multistep process

D. Inability to repair DNA is carcinogenic

A 55-year-old man visits the physician because of hemoptysis and worsening cough. On physical examination, wheezes are auscultated over the right lung posteriorly. A chest radiograph shows a 6-cm perihilar mass on the right. A fine-needle aspiration biopsy yields cells consistent with non-small cell bronchogenic carcinoma. Molecular analysis of the neoplastic cells shows a p53 gene mutation. Which of the following mechanisms has most likely produced the neoplastic transformation? □ (A) Inability to hydrolyze GTP □ (B) Microsatellite instability □ (C) Lack of necrosis □ (D) Loss of cell cycle arrest □ (E) Transcriptional activation

D. Loss of cell cycle arrest

A 38-year-old woman has abdominal distention that has been worsening for the past 6 weeks. An abdominal CT scan shows bowel obstruction caused by a 6-cm mass in the jejunum. At laparotomy, a portion of the small bowel is resected. Microscopic examination shows that the mass is a Burkitt lymphoma. Flow cytometry analysis of a portion of the tumor shows a high S phase. Mutational activation of which of the following nuclear oncogenes is most likely to be present in this tumor? □ (A) ERBB2 □ (B) p53 □ (C) RAS □ (D) MYC □ (E) APC

D. MYC

A 55-year-old woman has felt an enlarging lump in her left breast for the past year. A hard, irregular 5-cm mass fixed to the underlying chest wall is palpable in her left breast. Left axillary nontender lymphadenopathy is noted. There is no hepatosplenomegaly. A chest CT scan reveals multiple bilateral pulmonary "cannonball" nodules. A left breast biopsy is performed, and on microscopic examination shows high-grade infiltrating ductal carcinoma. The appearance of the nodules in her lungs is most likely related to which of the following? □ (A) Proximity of the breast carcinoma to the lungs □ (B) Lymphatic connections between the breast and the pleura □ (C) Internal mammary artery invasion by carcinoma cells □ (D) Pulmonary chemokines that bind carcinoma cell chemokine receptors □ (E) Overexpression of laminin receptors on carcinoma cell surfaces □ (F) Overexpression of estrogen receptors within the carcinoma cell nuclei

D. Pulmonary chemokines that bind carcinoma cell chemokine receptors

During a routine health maintenance examination, a 46-year-old man is found to have an enlarged, nontender supraclavicular lymph node that is palpable on physical examination. The 2-cm node is excised. Histologically, the nodal architecture is effaced by a monomorphous population of small lymphocytes. Which of the following procedures would best confirm that the patient has a malignancy? □ (A) Peripheral WBC count and differential cell count □ (B) Flow cytometry of nodal tissue for DNA content □ (C) Electron microscopy to determine cellular ultrastructure □ (D) Southern blot analysis to show monoclonality □ (E) Determination of the serum lactate dehydrogenase level

D. Southern blot analysis to show monoclonality

A 58-year-old woman has experienced an increasing feeling of fullness in the neck for the past 3 months, and she has noted a 3-kg weight loss during that time. On physical examination, there is a firm, fixed mass in a 3 × 5 cm area in the right side of the neck. CT scan shows a solid mass in the region of the right lobe of the thyroid gland. A biopsy of the mass is performed; the microscopic appearance of the specimen is shown in the figure. All areas of the tumor have similar morphology. Which of the following terms best describes this neoplasm? □ (A) Adenoma □ (B) Well-differentiated adenocarcinoma □ (C) Squamous cell carcinoma □ (D) Leiomyoma □ (E) Anaplastic carcinoma

E. Anaplastic carcinoma

A 62-year-old man with a history of chronic alcoholism has noted a 6-kg weight loss over the past 5 months. Physical examination shows no masses or palpable lymphadenopathy. Laboratory studies include an elevated serum α-fetoprotein level. A stool guaiac test result is negative. Which of the following is the most likely diagnosis? □ (A) Prostatic adenocarcinoma □ (B) Pulmonary squamous cell carcinoma □ (C) Multiple myeloma □ (D) Pancreatic adenocarcinoma □ (E) Hepatocellular carcinoma

E. Hepatocellular carcinoma

A 39-year-old woman underwent a routine health maintenance examination for the first time in many years. A Pap smear was obtained, and the result reported was abnormal. On pelvic examination, a red, slightly raised, 1-cm lesion on the anterior ectocervix at the 2-o'clock position was excised and biopsied. The microscopic appearance on medium-power magnification is shown in the figure. Which of the following statements best characterizes the patient's condition? □ (A) A primary site should be sought □ (B) This is a high-grade lesion □ (C) The cell of origin is a fibroblast □ (D) A chest radiograph would show nodules □ (E) Local excision would be curative

E. Local excision would be curative

A 60-year-old woman has noted a feeling of pelvic heaviness for the past 6 months. On physical examination, there is a nontender lower abdominal mass. An abdominal ultrasound scan shows a 12-cm solid mass in the uterine wall. A total abdominal hysterectomy is performed, and on removal, the mass has the microscopic appearance of a well-differentiated leiomyosarcoma. One year later, a chest radiograph shows a 4-cm nodule on the right lower lung. A biopsy specimen of the nodule shows a poorly differentiated sarcoma. The patient's past medical history indicates that she has smoked cigarettes most of her adult life. Which of the following best explains these findings? □ (A) Development of a second primary neoplasm □ (B) Inheritance of a defective RB gene □ (C) Continued cigarette smoking by the patient □ (D) Loss of an oncogene □ (E) Metastasis from an aggressive subclone of the primary tumor

E. Metastasis from an aggressive sub clone of the primary tumor

An experiment involving carcinoma cells grown in culture studies the antitumor surveillance effects of the innate immune system. These carcinoma cells fail to express MHC class I antigens. It is observed, however, that carcinoma cells are lysed in the presence of one type of immune cell that has been activated by IL-2. Which of the following immune cells is most likely to function in this manner? □ (A) CD4+ lymphocyte □ (B) CD8+ lymphocyte □ (C) Macrophage □ (D) Neutrophil □ (E) NK cell □ (F) Plasma cell

E. NK cell

A 76-year-old man has experienced abdominal pain for the past year. On physical examination, the physician palpates an epigastric mass. An abdominal CT scan shows a 10-cm mass in the body of the pancreas. A needle biopsy specimen of this mass shows a moderately differentiated adenocarcinoma. Mutational analysis of the carcinoma cells shows inactivation of SMAD4 so that transcriptional activation of cyclin-dependent kinases with growth-suppressing effects is diminished. Which of the following regulatory pathways is most likely altered in this man's carcinoma? □ (A) BCL2 □ (B) β-catenin □ (C) MYC □ (D) p53 □ (E) TGF-β

E. TGF-beta

A 20-year-old man has a raised, irregular, pigmented lesion on his forearm that has increased in size and become more irregular in color over the past 4 months. Physical examination shows a 0.5 × 1.2 cm black-to-brown lesion with irregular borders. An excisional biopsy specimen shows a malignant melanoma that extends into the reticular dermis. Family history indicates that the patient's paternal uncle died of metastatic melanoma that spread to the liver after excision of a primary lesion on the foot. His grandfather required enucleation of the left eye because of a "dark brown" mass in the eyeball. Which of the following genes is most likely to have undergone mutation to produce these findings? □ (A) BCL2 (anti-apoptosis gene) □ (B) C-MYC (transcription factor gene) □ (C) IL2 (growth factor gene) □ (D) Lyn (tyrosine kinase gene) □ (E) p16 (cell cycle inhibition) □ (F) p53 (DNA damage response gene) □ (G) PDGF (growth factor overexpression)

E. p16

An epidemiologic study is performed to assess risks for cervical carcinoma. The cells from cervical lesions in a population of women are analyzed. Binding of certain viral proteins to pRB is found in patients in whom dysplastic cells are present. Viral proteins from which of the following are most likely to bind pRB, increasing the risk for dysplasia? □ (A) Cytomegalovirus □ (B) Epstein-Barr virus □ (C) Herpes simplex virus □ (D) Hepatitis B virus □ (E) HIV □ (F) Human papillomavirus □ (G) JC papovavirus

F. HPV

The mother of a 5-year-old boy notices that his abdomen is enlarged. On physical examination, the physician palpates an ill-defined abdominal mass. An abdominal CT scan shows a 9-cm mass in the region of the right adrenal gland. The mass is removed and microscopically appears to be a neuroblastoma. Cytogenetic analysis of tumor cells shows many double minutes and homogeneously staining regions. Which of the following genes is most likely to have undergone alterations to produce these findings? □ (A) BCL1 (cyclin gene) □ (B) BCL2 (anti-apoptosis gene) □ (C) IL2 (growth factor gene) □ (D) Lyn (tyrosine kinase gene) □ (E) K-RAS (GTP-binding protein gene) □ (F) N-MYC (transcription factor gene) □ (G) p53 (DNA damage response gene)

F. N-MYC (transcription factor gene)

A 51-year-old man who works in a factory that produces plastic pipe has experienced weight loss, nausea, and vomiting over the past 4 months. On physical examination, he has tenderness to palpation in the right upper quadrant of the abdomen, and the liver span is increased. Laboratory findings include serum alkaline phosphatase, 405 U/L; AST, 45 U/L; ALT, 30 U/L; and total bilirubin, 0.9 mg/dL. An abdominal CT scan shows a 12-cm mass in the right lobe of the liver. A liver biopsy is performed, and microscopic examination shows an angiosarcoma. The patient has most likely been exposed to which of the following agents? □ (A) Arsenic □ (B) Asbestos □ (C) Benzene □ (D) Beryllium □ (E) Nickel □ (F) Vinyl chloride □ (G) Naphthalene

F. Vinyl chloride

A 63-year-old man sees the physician because of cough and hemoptysis. He has a 65-pack-year history of smoking. A chest CT scan shows a 5-cm right hilar mass. Bronchoscopy is performed, and lung biopsy specimens show small-cell anaplastic lung carcinoma. His family history shows three first-degree maternal relatives who developed leukemia, sarcoma, and carcinoma before age 40 years. Which of the following genes is most likely to have undergone mutation to produce these findings? □ (A) APC (tumor suppressor gene) □ (B) BCL2 (anti-apoptosis gene) □ (C) ERBB2 (growth factor receptor gene) □ (D) K-RAS (GTP-binding protein gene) □ (E) NF1 (GTPase-activating protein) □ (F) p53 (DNA damage response gene)

F. p53 (DNA damage response gene)

A 5-year-old child has difficulty with vision in the right eye. On physical examination, there is leukokoria of the right eye, consistent with a mass in the posterior chamber. MR imaging shows a mass that nearly fills the globe. The child undergoes enucleation of the right eye. Molecular analysis of the neoplastic cells indicates absence of both copies of a tumor suppressor gene that controls the transition from the G1 to the S phase of the cell cycle. Which of the following genes is most likely to have the mechanism of action that produced this neoplasm? □ (A) BCR-ABL □ (B) BCL2 □ (C) hMSH2 □ (D) K-RAS □ (E) NF1 □ (F) p53 □ (G) RB

G. RB

A 32-year-old woman has experienced dull pelvic pain for the past 2 months. Physical examination shows a right adnexal mass. An abdominal ultrasound scan shows a 7.5-cm cystic ovarian mass. The mass is surgically excised. The surface of the mass is smooth, and it is nonadherent to surrounding pelvic structures. On gross examination, the mass is cystic and filled with hair. Microscopically, squamous epithelium, tall columnar glandular epithelium, cartilage, and fibrous connective tissue are present. Which of the following is the most likely diagnosis? □ (A) Adenocarcinoma □ (B) Fibroadenoma □ (C) Glioma □ (D) Hamartoma □ (E) Mesothelioma □ (F) Rhabdomyosarcoma □ (G) Teratoma

G. Teratoma

A 30-year-old man has a pheochromocytoma of the left adrenal gland; a sibling had a cerebellar hemangioblastoma. He undergoes adrenalectomy, and on microscopic examination there is extensive vascularity of the neoplasm. Mutational analysis of the neoplastic cells shows that both allelic copies of a gene have been lost, so that a protein that binds to hypoxia-induced factor 1 alpha is no longer ubiquinated, but instead translocates to the nucleus and activates transcription of VEGF. Which of the following genes is most likely mutated in this man? □ (A) APC □ (B) BCL2 □ (C) EGF □ (D) HER2 □ (E) HST1 □ (F) □ (G) VHL

G. VHL

A Pap smear obtained from a 29-year-old woman during a routine health maintenance examination is abnormal. She is currently asymptomatic, but has a history of multiple sexual partners. Cervical biopsy specimens are obtained. The representative microscopic appearance of a specimen is shown in the figure. Which of the following is the most likely diagnosis? □ (A) Adenocarcinoma □ (B) Carcinoma in situ □ (C) Dysplasia □ (D) Hamartoma □ (E) Melanoma □ (F) Mesothelioma □ (G) Small-cell anaplastic carcinoma □ (H) Squamous cell carcinoma

H. Squamous cell carcinoma