Robbins - Unit 1 - Neoplasia

Question 1

1.40 y/o man with hx of IV drug abuse. Physical shows needle track in left antecubital fossa. He has mild scleral icterus. Serologic studies show HBsAg and anti-HCV positive. He develops hepatocellular carcinoma 15 yrs later. Which of the following viral characteristics best explains why this pt. developed hepatocellular carcinoma?

Answer 1

C) Viral-induced injury followed by extensive hepatocyte regeneration

(C) Although the hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes do not encode for any transforming
proteins, the regenerating hepatocytes are more likely to develop mutations, such as inactivation of p53. HBV does not
have a consistent site of integration in the liver cell nuclei, and it does not contain viral oncogenes. Many DNA viruses,
such as human papillomavirus, inactivate tumor suppressor genes, but there is no convincing evidence that HBV or HCV
can bind to p53 or RB proteins. Also, the HBV-encoded regulatory element, called HBx, disrupts normal growth of infected
hepatocytes. Neither HBV nor HCV infects immune cells.

Question 2

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?

Answer 2

A) increased laminin receptors on tumor receptor cells

(A) Several pathologic mechanisms play a role in the development of tumor metastases. The tumor cells first must
become discohesive and detach from the primary site and then attach elsewhere to become metastases. Tumor cells tend
to have many more laminin receptors than do normal cells, allowing them to attach more readily to basement membranes
at distant sites. Keratin is a marker of epithelial differentiation, not metastatic ability. A reduction in apoptosis allows
greater proliferation, but not metastases. Monoclonality is a feature of neoplasia, but further tumor heterogeneity helps to
increase the chance for metastases to occur. Inflammation probably does not play a major role in metastasis

Question 3

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?

Answer 3

D) Functional inactivation of the RB1 protein

(D) The oncogenic potential of human papillomavirus (HPV), a sexually transmissible agent, is related to products of two
early viral genes—E6 and E7. E7 binds to RB protein to cause displacement of normally sequestered transcription factors,
which nullifies tumor suppressor activity of the RB protein. E6 binds to and inactivates the p53 gene product. Trapping of
GTP-bound RAS protein can occur in many tumors but is not related to HPV infection. Laminin receptor expression
correlates with metastatic potential of a malignant neoplasm. Inability to repair DNA damage plays a role in some colon
and skin cancers. Increased epidermal growth factor receptor expression is a feature seen in many pulmonary squamous
cell carcinomas, and the related ERBB2 (HER2) receptor is seen in some breast carcinomas.

Question 4

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

Answer 4

NK cells

(E) Several types of immune cells can recognize and help destroy tumor cells. Tumor antigens that are displayed via
MHC class I molecules can be recognized by cytotoxic CD8+ cells. Many cancers do not display their antigens well,
however, and when MHC class I molecules are not displayed, NK cells are triggered to target these cells for lysis.
Macrophages may work in concert with CD8+ cells and NK cells to phagocytize and kill tumor cells when up-regulated by
interferon-γ. CD4+ “helper” cells do not play a direct anticancer role. Neutrophils are ineffective against cancer cells, but
may be attracted to areas of tumor necrosis. Plasma cells may produce antibodies directed against tumor antigens, but
such antibodies are ineffective in controlling tumors.

Question 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

Answer 5

A) Ductal carcinoma of the breast

A) Lymphatic spread, especially to regional lymph nodes draining from the primary site, is typical of a carcinoma.
Infection from a breast abscess can spread to the lymph nodes, but the resulting nodal enlargement is typically associated
with pain—a cardinal sign of acute inflammation. Sarcomas uncommonly metastasize to lymph nodes. Central nervous
system (CNS) malignancies rarely metastasize outside of the CNS. Dysplasias do not metastasize because they are not
malignancies

Question 6

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)

Answer 6

p16 - cell cycle inhibition

(E) This patient has a family history of malignant melanoma. Familial tumors often are associated with inheritance of a
defective copy of one of several tumor suppressor genes. In the case of melanomas, the implicated gene is called p16, or
INK4a. The product of the p16 gene is an inhibitor of cyclin-dependent kinases. With loss of control over cyclin-dependent
kinases, the cell cycle cannot be regulated, favoring neoplastic transformation. BCL2 is present in some lymphoid
neoplasms. The C-MYC gene is mutated in various carcinomas, but is not known to be specifically associated with
melanomas. The IL2 mutation is associated with some T cell neoplasms. The Lyn mutation is seen in some
immunodeficiency states. p53 mutations occur in many cancers, but not specifically in familial melanomas. PDGF can be
overexpressed in some central nervous system gliomas and some osteosarcomas

Question 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

Answer 7

Teratoma

(G) A teratoma is a neoplasm derived from totipotential germ cells that differentiate into tissues that represent all three germ layers: ectoderm, endoderm, and mesoderm. When the elements all are well differentiated, the neoplasm is “mature”
(benign). Adenocarcinomas have malignant-appearing glandular elements. Fibroadenomas have a benign glandular and
stromal component; they are common in the breast. Gliomas are found in the central nervous system. Hamartomas contain
a mixture of cell types common to a tissue site; the lung is one site for this uncommon lesion. A mesothelioma arises from
the lining of thoracic and abdominal body cavities. A rhabdomyosarcoma comprises cells that poorly resemble striated
muscle; most arise in soft tissues.

Question 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

Answer 8

A) persistent activation of the RAS gene

(A) This patient has clinical features of neurofibromatosis type 1. The NF1 gene encodes a GTPase-activating protein
that facilitates the conversion of active (GTP-bound) RAS to inactive (GDP-bound) RAS. Loss of NF1 prevents such
conversion and traps RAS in the active signal-transmitting stage. All other listed mechanisms also are involved in
carcinogenesis, but in different tumors.

Question 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

Answer 9

d) direct DNA damage

(D) Chemical carcinogens have highly reactive electrophile groups that can directly damage DNA, leading to mutations.
Direct-acting agents, such as alkylating chemotherapy drugs, do not require conversion to a carcinogen. Some agents,
such as polycyclic hydrocarbons, require metabolic conversion to a carcinogen and are called indirect-acting agents.
Phorbol esters are examples of promoters of chemical carcinogenesis that cause tumor promotion by activating protein
kinase C. This enzyme phosphorylates several substrates in signal transduction pathways, including those activated by
growth factors, and the cells divide. Forced cell division predisposes the accumulation of mutations in cells previously
damaged by exposure to a mutagenic agent (initiator). The TGF-β pathways work via growth inhibition. Proteins such as
p53 that function in DNA repair pathways can become nonfunctional through mutation. Viral infections such as hepatitis B
and C tend to promote growth by binding to p53 and inactivating its protective function. Telomerase activity is not affected
by carcinogens.

Question 10

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

Answer 10

C) Determination of clonality by pattern of X chromosome inactivation

(C) A true neoplasm is a monoclonal proliferation of cells, whereas a reactive proliferation of cells is not monoclonal.
Reactive and neoplastic cellular proliferations may have similar histochemical and immunohistochemical staining patterns
based on the type of cells that are present. Flow cytometry is effective at indicating the DNA content, aneuploidy, and
growth fraction, but does not indicate clonality

Question 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
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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

Answer 11

d) Human T cell lymphotropic virus type 1

(D) The largest cell population, determined to be clonal, is marking for CD4. This patient has a T cell leukemia, which
develops in approximately 1% of individuals infected with human T cell lymphotropic virus type 1. Human papillomavirus is
best known for causing squamous epithelial dysplasias and carcinomas. HIV-1 infection causes AIDS. Infection with
Epstein-Barr virus is associated with various cancers, including Burkitt lymphoma and nasopharyngeal carcinoma.
Infection with hepatitis B virus may result in hepatic cirrhosis, in which hepatocellular carcinoma may arise.

Question 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

Answer 12

c) Amplification of the ERBB2 (HER2) gene

C) Increased expression of ERBB2 (HER2) can be detected immunohistochemically in the biopsy specimen. One third
of breast cancers may show this change. Such amplification is associated with a poorer prognosis. Detection of a specific
gene product in the tissue has value for determination of prognosis. BRCA1 and p53 mutations, if inherited in the germ
line, can predispose the patient to breast cancer and other tumors. With BRCA1, there is family history of breast cancer,
and p53 mutation predisposes to many types of cancers. An inherited deletion of RB gene predisposes to retinoblastoma.
The BCR-ABL fusion product, seen in chronic myeloid leukemia, results from t(9;22).

Question 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

Answer 13

B) Failure of nucleotide excision repair of DNA

(B) The children described in the question have an autosomal recessive condition known as xeroderma pigmentosum.
Affected individuals have extreme photosensitivity, with a 2000-fold increase in the risk of skin cancers. The DNA damage
is initiated by exposure to ultraviolet light; however, nucleotide excision repair cannot occur normally in xeroderma
pigmentosum. Human papillomavirus is a sexually transmitted disease that is associated with the development of genital
squamous cell carcinomas. Aspergillus flavus, found on moldy peanuts and other foods, produces the potent hepatic
carcinogen aflatoxin B1. Inactivation of the p53 tumor suppressor gene is found in many sporadic human cancers and in
some familial cancers, but these cancers are not limited to the skin. Chromosomal translocations are often involved in the
development of hematologic malignancies, although they are not often seen in skin cancers

Question 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

Answer 14

d) Loss of cell cycle arrest

(D) The p53 mutation involving both alleles is one of the most common genetic mutations in human cancers, including
the most common—lung, colon, and breast cancers. The loss of this tumor suppressor indicates that the cell cycle is not
properly arrested in the late G1 phase; when DNA damage occurs, DNA repair cannot be completed before the cell
proliferates. Inability to hydrolyze GTP is a result of RAS oncogene activation. Microsatellite instability occurs with
mutation in genes, such as hMSH2, that repair DNA damage. BCL2 mutation is one of the best-known mechanisms for
apoptotic arrest in neoplasms. Transcriptional activation is a feature of the MYC proto-oncogene.

Question 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

Answer 15

RB

(G) The RB gene is a classic example of the two-hit mechanism for loss of tumor suppression. About 60% of these
tumors are sporadic. Others are familial, and there is inheritance of a mutated copy of the RB gene. Loss of the second
copy in retinoblasts leads to the occurrence of retinoblastoma in childhood. Researchers do not know why patients who
inherit a mutant RB gene through the germline develop retinoblastoma rather than other types of tumors. The RB gene
controls the G1 to S transition of the cell cycle; with loss of both copies, this important checkpoint in the cell cycle is lost.
The BCR-ABL fusion gene in chronic myelogenous leukemia is an example of overexpression of a gene product producing
neoplasia. The BCL2 gene is an inhibitor of apoptosis. The hMSH2 gene is present in most cases of hereditary
nonpolyposis colon cancer and functions in DNA repair. Many cancers have the K-RAS gene, which acts as an oncogene.
The NF1 gene product acts as a tumor suppressor; this is a component of neurofibromatosis (which usually does not
involve the eye), and the neoplasms typically appear at a later age. Many cancers have the p53 tumor suppressor gene
mutation, but this is not typical of childhood ocular neoplasms.

Question 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

Answer 16

D) High growth fraction

(D) Some neoplasms, including certain lymphomas, have a high proportion of cells in the replicative pool (i.e., have
high growth fraction). They grow rapidly and respond rapidly to drugs that kill dividing cells. Monoclonality rather than
polyclonality is typical of malignant tumors. Similarly, poor vascularity would not favor rapid growth. Tumors that are highly
antigenic are likely to be controlled by the immune system and not to be rapidly growing.

Question 17

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
Robbins & Cotran Review of Pathology Pg. 103
□ (D) Leiomyoma
□ (E) Anaplastic carcinoma

Answer 17

E) Aplastic carcinoma

(E) The cells shown in the figure show marked pleomorphism and hyperchromatism (anaplasia). A bizarre tripolar
mitotic figure is present. This degree of anaplasia is consistent with a malignancy. An adenoma is a benign tumor of
glandular origin. Adenocarcinomas and squamous cell carcinomas show differentiation into glandular or squamous tissues.
Leiomyomas are benign mesenchymal tumors of smooth muscle origin.

Question 18

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

Answer 18

B) Pt. has a poorly differentiated neoplasm

(B) Cancer grading systems are typically denoted by I to III or I to IV, and increase with worse differentiation (more
anaplasia). A transitional cell carcinoma would be expected at this site. Bladder cancers are not commonly associated with
paraneoplastic syndromes. Infiltration through the wall indicates a high stage. The cure rate for this high-grade, high-stage
cancer is poor. Determination of the presence of metastases is part of staging, not grading.

Question 19

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

Answer 19

C) Pap smear

(C) Because Pap smear screening can detect dysplasias and in situ carcinomas that can be treated before
progression to invasive lesions, deaths from cervical carcinoma have steadily decreased since this screening method
became widely available in the last half of the 20th century. A chest radiograph is an insensitive technique for detecting
early lung cancers. Use of stool guaiac has had a minimal effect on rates of death from colorectal carcinomas, but
physicians are cautioned not to indicate “rectal deferred” on the physical examination report, and hence contribute to the
problem. Serum tumor markers have not proved useful as general screening techniques, although they are useful in
selected circumstances. Urine cytology is better than urinalysis for detection of urothelial malignancies, but it does not
have a high sensitivity

Question 20

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

Answer 20

d) Southern blot analysis to show monoclonality

(D) Monoclonality is the hallmark of a malignancy. In the diagnosis of a leukemia, the WBC count is helpful, but not
definitive. The DNA content analysis alone cannot define a malignancy; Southern blot analysis for T-cell or B-cell receptor
gene rearrangements can define monoclonality. Electron microscopy is an adjunct to diagnosis of the type of tumor.
Lactate dehydrogenase levels are often increased with lymphoid proliferations, but are not diagnostic of the type of
proliferation

Question 21

21. 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

Answer 21

b) Stepwise accumulation of multiple protooncogene and tumor suppressor gene mutations

(B) Development of colonic adenocarcinoma typically takes years, during which time numerous mutations occur within
the mucosa, including mutations involving such genes as APC (adenomatous polyposis coli), K-RAS, and p53. The
accumulation of mutations, rather than their occurrence in a specific order, is most important in the development of a
carcinoma. Activation of proto-oncogenes, extensive regeneration, faulty DNA repair genes, and amplification of growth
factor receptor genes all contribute to the development of malignancies, but they are not sufficient by themselves to
produce a carcinoma from an adenoma of the colon.

Question 22

22. A 49-year-old man has a lump near his right shoulder that has been increasing in size for the past 8 months. On
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    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)

Answer 22

c) BCL2 (anti-apoptosis gene)

C) This is an example of chromosomal translocation that brings BCL2, an anti-apoptosis gene, close to another gene
(immunoglobulin heavy-chain gene). The BCL2 gene becomes subject to continuous stimulation by the adjacent enhancer
element of the immunoglobulin gene, leading to overexpression. The APC gene is mutated in sporadic colon cancers and
cancers associated with familial polyposis coli. The BCL1 gene is mutated in mantle zone lymphoma, with t(11;14) that
brings the cyclin gene on chromosome 11 to the immunoglobulin enhancer gene on chromosome 14. The BRCA1 and
ERBB2 gene mutations are seen in some breast cancers. The IL2 mutation may be present in some T cell neoplasms. KRAS
and p53 mutations are present in many cancers, but not typically lymphoid malignancies.

Question 23

23. 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

Answer 23

h) squamous cell carcinoma

(H) Notice on the figure that the disorderly, atypical epithelial cells involve the entire thickness of the epithelium and
extend through the underlying basement membrane, a process known as invasion. The ectocervix and the squamous
metaplasia of endocervix give rise to squamous cell carcinoma. Carcinoma in situ is confined to the epithelium; if the
basement membrane is breached, the lesion is no longer in situ, but rather invasive. An adenocarcinoma is a malignant
neoplasm arising from glandular epithelium, such as the endocervix or endometrium, not the ectocervix. A dysplastic
process could precede development of carcinoma in situ and squamous carcinoma; dysplasia involves only part of the
thickness of the epithelium. A hamartoma contains a mixture of cell types common to a tissue site. Melanomas are
malignant and tend to enlarge quickly; many are darkly pigmented. The benign counterpart to the melanoma is the nevus,
which is quite common; nevi are usually light brown. A mesothelioma arises from the mesodermally derived lining of
thoracic and abdominal body cavities. Small-cell anaplastic carcinomas of the lung are aggressive neoplasms that are
unlikely to be diagnosed in situ.

Question 24

24.

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
Robbins & Cotran Review of Pathology Pg. 105
□ (D) Leukemia
□ (E) Lymphoma of the lymph nodes
□ (F) Pancreatic adenocarcinoma

Answer 24

b) gastric adenocarcinoma

(B) The decrease in the number of gastric cancers may be related to reduced numbers of dietary carcinogens or a
decrease in the prevalence of Helicobacter pylori infection; however, the exact reason is obscure. Angiosarcomas of the
liver are quite rare; they are epidemiologically linked to vinyl chloride exposure. Cerebral gliomas are not as common as
carcinomas; an urban legend links them to cell phone use, but legitimate epidemiologic studies have not made this link.
Leukemias and lymphomas are not as common as carcinomas. Pancreatic adenocarcinoma is the sixth most common
cause of cancer deaths in men and women, and the death rate is typically double the incidence because the prognosis for
pancreatic cancer is so poor.

Question 25

25. 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)

Answer 25

b) BRCA1 (DNA gene repair)

(B) Approximately 5% to 10% of breast cancers are familial, and 80% of these cases result from mutations in the
BRCA1 and BRCA2 genes. Onset of these familial cancers occurs earlier in life than the sporadic cancers. The protein
products of these genes are involved in DNA repair. BCL2 is overexpressed in some lymphoid neoplasms. ERBB2
overexpression is present in some sporadic breast cancers; other EGF alterations can be seen in lung, bladder,
gastrointestinal, ovarian, and brain neoplasms. The HST1 mutation is seen in some gastric cancers. IL2 overexpression is
associated with some T cell neoplasms. K-RAS overexpression is seen in many cancers, including some breast cancers,
but the early age of onset and family history in this case strongly suggest BRCA mutations. The Lyn mutation is seen in
some immunodeficiency states.

Question 26

26. 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

Answer 26

f) vinyl chloride

(F) Vinyl chloride is a rare cause of liver cancer. This causal relationship was easy to show, however, because hepatic
Robbins & Cotran Review of Pathology Pg. 119
angiosarcoma is a rare neoplasm. Arsenic is a risk factor for skin cancer. Asbestos exposure is linked to pleural malignant
mesothelioma and to bronchogenic carcinomas in smokers. Benzene exposure is linked to leukemias. Beryllium exposure
can produce interstitial lung disease and lung cancer. Nickel exposure increases the risk of respiratory tract cancers.
Exposure to naphthalene compounds is a risk factor for cancer of the urinary tract.

Question 27

27. 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?
Robbins & Cotran Review of Pathology Pg. 106
□ (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

Answer 27

e) local excision would be curative

(E) The figure shows an in situ carcinoma of the squamous cervical epithelium with neoplastic growth above the
basement membrane. Such cancers, limited to the epithelium, are noninvasive, and local excision has a 100% cure rate. In
situ lesions do not give rise to metastases. Lesions limited to the epithelium are low grade. Because it originated in the
epithelium, this neoplasm is not derived from fibroblasts.

Question 28

28. 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

Answer 28

b) invasiveness

(B) The elaboration of various enzymes by tumor cells aids in degradation of extracellular matrix and invasiveness.
Cathepsin D is a cysteine proteinase that cleaves various substrates, such as fibronectin and laminin. High levels of this
enzyme in tumor cells are associated with greater invasiveness. Angiogenesis can be mediated by basic fibroblast growth
factor and vascular endothelial cell growth factor. Differentiation, heterogeneity, and aneuploidy are regulated by protooncogenes
and tumor suppressor genes.

Question 29

29. 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

Answer 29

c) radiation therapy in childhood

(C) Radiation is oncogenic. Cancers of thyroid and bone often develop after radiation exposure; leukemias also can
occur. Hepatocellular carcinomas can arise in cirrhosis caused by chronic alcoholism. Ataxia telangiectasia is an inherited
syndrome that carries an increased risk of development of leukemias and lymphomas. Trauma is not a risk factor for
development of cancer, although traumatic episodes often are recalled and irrationally associated with subsequent health
problems. Arsenic exposure, which is uncommon, leads to lung and skin cancers.

Question 30

30. 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

Answer 30

f) HPV

(F) Human papillomavirus (HPV) types 16, 18, and 31 encode proteins that bind p53 with high affinity, resulting in loss
of tumor suppressor activity. Seventy-five percent to nearly 100% of squamous epithelial dysplasias and carcinomas of the
cervix are associated with HPV infection. Cytomegalovirus and herpes simplex virus do not participate directly in
carcinogenesis. Epstein-Barr virus is associated with some malignant lymphomas and nasopharyngeal carcinomas.
Hepatitis B virus is associated with hepatocellular carcinomas arising in the setting of regeneration in chronic liver injury.
HIV does not affect pRB, but the loss of immune regulation promotes development of lymphomas and Kaposi sarcoma.
The JC papovavirus is associated with development of progressive multifocal leukoencephalopathy.

Question 31

31. 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?
    Robbins & Cotran Review of Pathology Pg. 107
    □ (A) Prostatic adenocarcinoma
    □ (B) Pulmonary squamous cell carcinoma
    □ (C) Multiple myeloma
    □ (D) Pancreatic adenocarcinoma
    □ (E) Hepatocellular carcinoma

Answer 31

E) HEPATOCELLULAR CARCINOMA

(E) α-Fetoprotein is a tumor marker for hepatocellular carcinomas and some testicular carcinomas. The serum
prostate-specific antigen is a helpful marker for prostatic adenocarcinoma. Squamous cell carcinomas of any site do not
have useful specific tumor markers. A serum immunoglobulin level with protein electrophoresis aids in the diagnosis of
myeloma. Gastrointestinal tract adenocarcinomas, including those arising in the pancreas, may be accompanied by
elevations in the serum carcinoembryonic antigen level

Question 32

32. 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

Answer 32

c) corticotropin

(C) This patient has Cushing syndrome resulting from ectopic corticotropin production by the tumor, a form of
paraneoplastic syndrome common to small-cell carcinomas of the lung. Hypercalcemia from a parathormone-related
peptide (PrP) is more typically associated with pulmonary squamous cell carcinomas. Erythropoietin production with
polycythemia is more likely to be associated with a renal cell carcinoma. Insulin and gastrin production are most often seen
in islet cell tumors of the pancreas.

Question 33

33. During a routine health maintenance examination of a 40-year-old man, a stool guaiac test result was positive. A followup
    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

Answer 33

A) adenoma

(A) A discrete small mass such as that described is probably benign. Adenomas arise from epithelial surfaces. A
hamartoma is a rare benign mass composed of tissues usually found at the site of origin. A sarcoma is a malignant
neoplasm arising in mesenchymal tissues. A choristoma is a benign mass composed of tissues not found at the site of
origin. A nevus arises in the skin.

Question 34

34. 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

Answer 34

b) lack of apoptosis

(B) Overexpression of the BCL2 gene prevents apoptosis, allowing accumulation of cells in lymphoid tissues.
Increased tyrosine kinase activity results from mutations affecting the ABL oncogene. Gene amplifications typically affect
the ERBB2 (HER2) and MYC oncogenes. Reduced DNA repair occurs in the inherited disorder xeroderma pigmentosa.
Loss of cell cycle inhibition results from loss of tumor suppressor genes such as p53.

Question 35

35, 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

Answer 35

c) RAS

(C) The RAS oncogene is the most common oncogene involved in the development of human cancers. Mutations of
the RAS oncogene reduce GTPase activity, and RAS is trapped in an activated GTP-bound state. RAS then signals the
nucleus through cytoplasmic kinases. The MYC oncogene is a transcriptional activator that is overexpressed in many
tumors. The APC gene can cause activation of the WNT signaling pathway. The ERBB2 oncogene encodes growth factor
receptors that are amplified in certain tumors. The sis oncogene encodes platelet-derived growth factor receptor-β, which
is overexpressed in certain astrocytomas.

Question 36

36. 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

Answer 36

D) hemangioma

(D) The small, discrete nature of this mass and its unchanged size suggest a benign neoplasm. The red color suggests
vascularity. A hemangioma is a common benign lesion of the skin. Adenomas arise in glandular epithelium, such as the
colon. Fibroadenomas arise in the breast. A hamartoma contains a mixture of cell types common to a tissue site.
Leiomyomas, which are white, arise from smooth muscle and are most common in the uterus. Lipomas are yellow fatty
tumors. Melanomas are malignant and tend to increase in size quickly; many are darkly pigmented. The benign
counterpart to the melanoma is the nevus, which is quite common; nevi are usually light brown.

Question 37

37. 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)

Answer 37

f) p53 (DNA damage gene)

(F) p53 is the most common target for genetic alterations in human neoplasms. Most are sporadic mutations, although
some are inherited. The inheritance of one faulty p53 suppressor gene predisposes to a “second hit” that eliminates the
remaining p53 gene. Homozygous loss of the p53 genes dysregulates the repair of damaged DNA, predisposing
individuals to multiple tumors, as in this case. The APC gene is mutated in sporadic colon cancers and in familial polyposis
coli. The BCL2 gene is mutated in some non-Hodgkin lymphomas. The ERBB2 gene is one of the EGF receptor family
members amplified in some breast cancers. The EGF mutation is most often seen in squamous cell carcinomas of the
lung. K-RAS mutations are present in many cancers, but not typically lymphoid malignancies. The NF1 gene mutation is
seen in neurofibromatosis type 1.

Question 38

38. 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) MYC
    □ (G) VHL

Answer 38

g) VHL

G) Angiogenesis is a key feature of neoplasms because the growing tumor needs a blood supply, and up-regulation of
factors such as VEGF and FGF help to keep the cancer growing. The von Hippel–Lindau (VHL) gene acts as a tumor
suppressor, and it normally produces a protein that binds to hypoxia-induced factor 1 alpha so that it is cleared. VHL
mutation leads to loss of this binding protein and activation of angiogenesis factors. Individuals with VHL syndrome have
various neoplasms, including pheochromocytomas, renal cell carcinomas, and hemangioblastomas. The other listed genes
have products that do not directly act on angiogenesis pathways.

Question 39

39. 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

Answer 39

A) Class I MHC molecules with a melanoma cell peptide

(A) All human nucleated cells express MHC class I antigens. CD8+ T cells recognize peptides presented by MHC
class I antigens. In many tumors, especially melanomas, the tumor cells produce peptides that can be presented by MHC
class I molecules. Such tumor-specific peptides are not produced by other cells, so the CD8+ T cells specific for such
peptides lyse melanoma cells, but not normal melanocytes or other normal cells

Question 40

40. 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

Answer 40

b) carcinoma

B) A large, irregular, ulcerated mass such as that described is most likely malignant, and the epithelium of the bladder
gives rise to carcinomas. A papilloma is a benign, localized mass that has an exophytic growth pattern. An adenoma is a
benign epithelial neoplasm of glandular tissues. A sarcoma is derived from cells of mesenchymal origin; sarcomas are
much less common than carcinomas. A fibroma is a benign mesenchymal neoplasm.

Question 41

41. 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

Answer 41

c) hilar lymph nodes

(C) Carcinomas metastasize through lymphatics most often, usually to regional nodes first. Hematogenous metastases
are possible, however. About half of all cerebral metastases arise from the lung. Soft-tissue metastases are rare, as are
splenic metastases.

Question 42

42. 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
Robbins & Cotran Review of Pathology Pg. 110
□ (C) A hepatocellular carcinoma has invaded locally
□ (D) Colonic adenocarcinoma with metastases was present
□ (E) The lesions should have been resected

Answer 42

d) colonic adenocarcinoma with metastases was present

The figure shows the appearance of metastatic lesions from a malignant neoplasm with multiple tumor masses
present. Dysplastic lesions do not produce large masses. Although some benign tumors, such as leiomyomas of the
uterus, can be multiple, this is not the rule in the liver, and hepatic adenomas are rare. Although hepatocellular carcinomas
can have “satellite” nodules, widespread nodules such as those seen in the figure are more characteristic of metastases.
Resection of multiple metastases is usually fruitless.

Question 43

43. 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

Answer 43

c) frozen section

(C) The rapid frozen section of resection margins helps to determine whether enough of the colon has been resected.
Fine-needle aspiration is used for preoperative diagnosis. Serum tumor markers may aid in preoperative diagnosis or
postoperative follow-up of neoplasms. Electron microscopy requires at least 1 day to perform and helps to determine the
cell type. Flow cytometry can be performed in several hours, but it is useful mainly for prognostic information and is not a
“stat” procedure.

Question 44

44. 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

Answer 44

e) metastasis from an aggressive subclone of the primary tumor

(E) Although neoplasms begin as monoclonal proliferations, additional mutations occur over time, leading to subclones
of neoplastic cells with various properties. This subcloning may allow metastases, greater invasiveness, resistance to
chemotherapy, and morphologic differences to occur. Because sarcomas of the lung are rare, the lung mass is statistically
a metastasis. Inheritance of a mutant RB gene is most likely to lead to childhood retinoblastomas. Pulmonary sarcomas
are not related to smoking tobacco. Loss of tumor suppressor genes, not oncogenes, is related to tumor development.

Question 45

45. 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

Answer 45

a) activation of telomerase

A. Chromosomal telomere shortening in normal human cells limits their replicative potential and gives rise to
replicative senescence. This occurs because most somatic cells lack the enzyme telomerase. By contrast, 90% or more
human tumor cells show activation of telomerase, explaining continued tumor growth in the body and “immortalized” cell
lines. All other pathways listed cannot affect telomerase shortening, which is the rate-limiting step in indefinite replication
of cells.

Question 46

46. 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
    Robbins & Cotran Review of Pathology Pg. 111
    □ (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

Answer 46

d) inability to repair DNA is carcinogenic

(D) Patients with hereditary nonpolyposis colon carcinoma (HNPCC) inherit one defective copy of mismatch repair
genes. Several human mismatch repair genes are involved in the development of HNPCC. Mismatch repair defects have
microsatellite instability. Microsatellites are tandem repeats found throughout the genome. Normally, the length of these
microsatellites remains constant. In HNPCC, these satellites are unstable and increase or decrease in length. Although
HNPCC accounts for only 2% to 4% of all colon carcinomas, microsatellite instability can be detected in about 15% of all
sporadic colon carcinomas. Mutations in mismatch repair genes can be detected by the presence of microsatellite
instability. The other listed options are not characteristic of HNPCC.

Question 47

47. 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

Answer 47

d) MYC

(D) The MYC oncogene is commonly activated in Burkitt lymphoma because of a t(8;14) translocation. The MYC gene
binds DNA to cause transcriptional activation of growth-related genes such as that for cyclin D1, resulting in activation of
the cell cycle. ERBB2 (also known as HER2) encodes growth factor receptor located on the cell surface. p53 and APC are
tumor suppressor genes that are inactivated in many cancers, including colon cancer (APC). RAS oncogene encodes a
GTP-binding protein that is located under the cell membrane.

Question 48

48. 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

Answer 48

D) Pulmomary chemokines that bind carcinoma cell chemokine receptors

(D) There is increasing evidence that localization of cancer metastases is influenced by the expression of chemokine
receptors by cancer cells and elaboration of their ligands (chemokines) by certain tissues. In the case of breast cancer, the
carcinoma cells express CXCR4 chemokines. Vascular, lymphatic, or basement membrane

Question 49

49. 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

Answer 49

a) The lesion could progress to invasice cervical carcinoma

(A) Epithelial dysplasias, especially severe dysplasias, can be precursors of carcinomas. This is a key reason for Pap
smear screening; the incidence of cervical carcinoma decreases when routine Pap smears are performed. Teratomas
show well-differentiated elements derived from all the germ cell layers, and they do not manifest as epithelial dysplasias.
Severe dysplasias are not amenable to antibiotic therapy. Cervical dysplasias are not hereditary. Regression of a
malignancy is rare.

Question 50

50. 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?
    Robbins & Cotran Review of Pathology Pg. 112
    □ (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

Answer 50

c) Resect the tumor and some of the normal surrounding tissue

(C) A malignant neoplasm has a tendency to invade locally. A benign neoplasm is often well circumscribed, although a
true capsule is uncommon, and compressed normal surrounding tissue appears to form a discrete border. Such a solitary
mucosal lesion is unlikely to represent a metastasis, and the localized lesion can be resected easily. If there is no family
history, a familial cancer with high risk of recurrence from multiple polyps is unlikely; local excision is adequate. The biopsy
specimen shows a malignant lesion; it must be removed before it increases in size and invades locally or metastasizes.

Question 51

51. 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

Answer 51

b) inhibiting tyrosine kinase activity

B) This patient has a classic history and t(9;22) translocation with chronic myelogenous leukemia. The translocation
causes uncontrolled tyrosine kinase activity of the BCR-ABL fusion gene. These patients undergo remission with drugs
that inhibit tyrosine kinases. Antibodies to ERB-2 receptors are beneficial in certain breast tumors with amplification of this
gene. Agents that activate caspases theoretically may help in many cases, especially when apoptosis is blocked as in
tumors with BCL2 overexpression. Translocation of β-catenin to the nucleus occurs in colon cancers when there is
mutational loss of APC genes. Delivery of p53 into cells by viral vectors has not yet been proven to be valuable in cancer
treatment, and it is not used in chronic myelogenous leukemia.

Question 52

52. 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

Answer 52

c) Activation of the WNT signaling pathway

(C) The patient has a classic history of familial adenomatous polyposis with numerous adenomatous polyps and
malignant transformation. The earliest event in the APC → adenocarcinoma sequence is loss of APC gene function. This
prevents the destruction of β-catenin in the cytoplasm, which translocates to the nucleus and coactivates transcription of
several genes. The APC → β-catenin are components of the WNT signaling pathway. Mutations in mismatch repair genes
give rise to hereditary nonpolyposis colon cancer syndrome from loss of ability to repair DNA damage. Loss of cell cycle
G1 arrest occurs with p53 loss late in the sequence. The BCL2 gene is not involved in the transition from adenoma to
carcinoma. RAS activation occurs after the sequence is initiated by the APC (gatekeeper) gene.

Question 53

53. 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

Answer 53

a) promotion of carcinogenesis

(A) Estrogen, similar to many other hormones and drugs, by itself is not carcinogenic, but it is responsible for
stimulation of endometrial growth (hyperplasia), which has a promoting effect when mutations occur to produce carcinoma.
Tumor heterogeneity does not refer to two separate kinds of neoplasms; it refers to heterogeneity with a given tumor or
metastasis. A paraneoplastic syndrome results from ectopic secretion of a hormone by tumor (e.g., lung cancer cells
producing corticotropin). Inherited susceptibility can never be completely excluded when an individual has two tumors; this
can occur in patients with inherited mutations in the p53 gene. In this case, however, there is a clear hormonal basis for
the second tumor. Faulty tumor suppressor genes are not involved in hormonal promotion of a neoplasm.

Question 54

54. 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

Answer 54

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

(A) The M1 designation indicates that distant metastases are present. Elevated corticotropin levels indicate secretion
of an ectopic hormone that may produce a paraneoplastic syndrome. A T2 designation indicates that the overall size of the
tumor is not large. The TNM system is used for staging, not grading.

Question 55

55. 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

Answer 55

B) AIDS

(B) Primary or secondary immunodeficiency diseases carry an increased risk of neoplasia, particularly lymphomas. B
cell lymphomas of the brain are 1000-fold more common in patients with AIDS than in the general population. Patients with
diabetes mellitus can experience various complications, although not neoplasia. Hypertension can lead to central nervous
system hemorrhages. Multiple sclerosis is a demyelinating disease and carries no significant risk of neoplasia.
Tuberculosis as a chronic infection may lead to amyloidosis, not neoplasia

Question 56

56. 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

Answer 56

E) TGF-beta

(E) TGF-β inhibits cell proliferation by activation of growth-inhibiting genes, such as the CDKIs. All pancreatic cancers
and 83% of colon cancers have at least one mutational event in a TGF-β pathway. The BCL2 family of genes acts as
regulators of apoptosis. The β-catenin pathway seen with the APC gene is involved with growth regulation; loss of the
APC gene loci leads to failure in destruction of β-catenin, which translocates to the cell nucleus, where it functions as a
transcription factor promoting growth. The MYC gene is a target of the activated RAS pathway. The p53 protein is
involved in tumor suppression.

Question 57

57. 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

Answer 57

b) bronchogenic carcinoma

(B) Incidence of lung cancers increased dramatically in the 20th century because of the popularity of cigarette
smoking. As the number of individuals in a population who smoke increases, so do the number of cases of lung cancers.
Some cancers of the urinary tract, oral cavity, esophagus, and pancreas also are causally related to smoking. Breast,
prostate, and colon cancers remain common in developed nations, but the number of cases has not increased sharply.
Pap smear screening markedly decreases numbers of cases of cervical cancers. There has been a marked increase in
melanomas, but there are still far fewer cases of melanomas than of lung cancers.

Question 58

58. 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

Answer 58

f) N-MYC (transcription factor gene)

(F) Double minutes and homogeneously staining regions seen on a karyotype represent gene amplifications.
Amplification of the N-MYC gene occurs in 30% to 40% of neuroblastomas, and this change is associated with a poor
prognosis. The BCL1 and BCL2 genes are mutated in some non-Hodgkin lymphomas. The IL2 mutation may be present in
some T cell neoplasms. The Lyn mutation is seen in some immunodeficiency states. K-RAS and p53 mutations are
present in many cancers, but not typically childhood neoplasms.

Question 59

59. 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

Answer 59

b) UV radiation

(B) Worldwide, increasing numbers of skin cancers occur because of sun exposure. The ultraviolet light damages the
skin and damages cellular DNA, leading to mutations that escape cellular repair mechanisms. Smoking tobacco is related
to many cancers, but skin cancers are not typically associated with this risk factor. Chemotherapeutic agents have
carcinogenic potential, particularly alkylating agents such as cyclophosphamide, but leukemias and lymphomas are the
usual result. Asbestos exposure increases lung carcinoma risk in smokers and can lead to rare mesotheliomas of pleura.
Allergic reactions do not promote cancer.

Question 60

60. 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

Answer 60

a) cachexia

(A) Cachexia is a common finding in advanced cancers, and weight loss without dieting in an adult is a “red flag” for
malignancy. The exact cause for this is unknown, but increases in circulating factors such as tumor necrosis factor may
play a role. Cardiac murmurs may occur in the development of nonbacterial thrombotic endocarditis, a feature of a
hypercoagulable state that may occur with advanced malignancies. Icterus is most likely to occur when there is obstruction
of the biliary tract by a mass (e.g., as in pancreatic cancer), but metastases are unlikely to cause such an obstruction.
Neurologic abnormalities may occur in local tumor growth impinging on nerves, but dull constant pain is the most likely
abnormality in malignant neoplasms that invade nerves. Metastases to the spleen are uncommon. Tympany is uncommon
in cancer because obstruction by a mass tends to be incomplete and develop over a long time. (Hint: an empty beer keg is
tympanitic when percussed.)

Question 61

61. 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

Answer 61

a) aerobic glycolysis

(A) The PET scan is based upon selective uptake of a glucose derivative into tumor cells. The Warburg effect occurs
when cancer cells shift their metabolism to aerobic glycolysis for selective growth advantage under harsh circumstances.
Glycolysis also yields pyruvate for anabolic demands of increased tumor doublings. The p53 and c-MYC genes favor this
metabolic change, while PTEN inhibits tumor cell autophagy, giving cancer cells an edge in growth. Cancer cells are less
differentiated than normal cells and thus have decreased ability to do many complex biochemical processes, so they favor
a simple one—glycolysis. Gluconeogenesis is a function of hepatocytes in response to decreased caloric intake. The HMP
shunt and Krebs cycle are more useful to normal cells maintaining themselves at the status quo. Neoplasms generate
large amounts of purines from cell divisions and cell turnover that must be eliminated as uric acid, but neoplastic cells do
not perform this task.