5. • 4 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
6. • 5 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
7.
8. • 7 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
9. • 8 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
10. • 9 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
11. • 10 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
12. • 11 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
13. • 12 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
14. • 13 In 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
15. • 14 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
16. • 15. 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
17. • 16 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