Subjective Gynaecology Quiz

40 The answer is C: Hyperplasia. The cellular and molecular
mechanisms of hyperplasia are related to the control of cell
proliferation and provide a basis for further genetic changes
that can lead to neoplasia. Endometrial hyperplasia refers to
a spectrum that ranges from simple glandular crowding to
conspicuous proliferation of atypical glands. These changes
are often diffi cult to distinguish from carcinoma. The risk of
developing endometrial cancer increases with higher degrees
of endometrial hyperplasia. Estrogen exposure is thought to
be a risk factor for both endometrial hyperplasia and endometrial
carcinoma. Neoplastic transformation may occur in the
setting of a metaplastic epithelium (e.g., cancers of the lung,
cervix, stomach, and bladder); however, metaplasia (choice
E) does not precede the development of uterine adenocarcinoma.
The other choices do not represent risk factors for
cancer.
Diagnosis: Endometrial adenocarcinoma

2 The answer is D: Inactivation of tumor suppressor proteins.
Unlike RNA tumor viruses, whose oncogenes have
normal cellular counterparts, the transforming genes of DNA
viruses are not homologous with any cellular genes. This
conundrum was resolved with the discovery that the gene
products of oncogenic DNA viruses inactivate tumor suppressor
proteins. For example, proteins encoded by the E6 and
E7 genes of HPV16 bind p53 and pRb. The other choices are
involved in the pathogenesis of neoplasia, but they are not
specifi c for HPV.
Diagnosis: Cervical intraepithelial neoplasia, HPV infection

3 The answer is B: Carcinoma in situ. Most carcinomas begin
as localized growths confi ned to the epithelium in which they
arise. As long as these early cancers do not penetrate the basement
membrane on which the epithelium rests, such tumors
are labeled carcinoma in situ. When the in situ tumor acquires
invasive potential and extends directly through the underlying
basement membrane, it is in a position to compromise
neighboring tissues and metastasize. Carcinomatosis (choice
C) is a clinical term used to describe widespread dissemination
of cancer. Koilocytosis (choice E) implies the presence of
squamous cells with perinuclear halos and nuclear changes. It
is indicative of human papillomavirus infection and carries an
increased risk of carcinoma. Atypical and complex hyperplasia
(choices A and D) refer to proliferative lesions of the glands
within the uterine endometrium.
Diagnosis: Cervical carcinoma, carcinoma in situ

19 The answer is E: Neuroendocrine granules. Neuroendocrine
tumors may synthesize a number of hormones. The presence
of small, membrane-bound granules with a dense core is a feature
of these neoplasms. Dense granules are visible by electron
microscopy. In this way, electron microscopy may aid in the
diagnosis of poorly differentiated cancers, whose classifi cation
is problematic by light microscopy. Carcinomas often exhibit
desmosomes and specialized junctional complexes, which
are structures that are not typical of sarcomas or lymphomas.
Myelin fi gures (choice D) are seen in patients with inherited
lysosomal storage disease. Councilman bodies (choice A) are
apoptotic hepatocytes (acidophilic bodies).
Diagnosis: Small cell carcinoma of lung, paraneoplastic
syndrome

32 The answer is B: Flushing and wheezing. Carcinoid syndrome
is a systemic paraneoplastic disease caused by the release of
hormones from carcinoid tumors (via neuroendocrine granules)
into venous blood. Symptoms of fl ushing, bronchial
wheezing, watery diarrhea, and abdominal colic are caused by
the release of serotonin, bradykinin, and histamine. Carcinoids
are neuroendocrine tumors of low malignancy that are most
commonly located in the submucosa of the intestines (e.g.,
appendix, terminal ileum, and rectum). The other choices are
not associated with this paraneoplastic syndrome.
Diagnosis: Carcinoid tumor, paraneoplastic syndrome

14 The answer is B: Metastases to regional lymph nodes. The
choice of surgical approach or treatment modalities is infl uenced
more by the stage of a cancer than by its cytologic
grade. The signifi cant criteria used for staging vary with
different organs. Commonly used criteria include (1) tumor
size, (2) extent of local growth, (3) presence of lymph node
metastases, and (4) presence of distant metastases. The other
choices refl ect grade of the tumor.
Diagnosis: Renal cell carcinoma

31 The answer is C: Lymphocytes. Four DNA viruses (human
papillomavirus, Epstein-Barr virus [EBV], hepatitis B virus,
and herpesvirus-8) are incriminated in the development of
human cancers. EBV was the fi rst virus to be unequivocally
linked to the development of a human tumor. In 1958, Burkitt
described a form of childhood lymphoma in a geographical
belt across equatorial Africa, which he suggested might have
a viral etiology. A few years later, Epstein and Barr discovered
viral particles in cell lines cultured from patients with Burkitt
lymphoma. African Burkitt lymphoma is a B-cell tumor, in
which the neoplastic lymphocytes invariably contain EBV in
their DNA and manifest EBV-related antigens. EBV does not
infect the other choices.
Diagnosis: Burkitt lymphoma, EBV

38 The answer is D: Seeding of body cavity. The photograph
shows a loop of small bowel and mesentery studded with small
nodules of metastatic cancer. Malignant tumors that arise in
organs adjacent to body cavities (e.g., ovaries, gastrointestinal
tract, or lung) may shed malignant cells into these spaces. Such
body cavities include principally the peritoneal and pleural
cavities, although occasional seeding of the pericardial cavity,
joint space, and subarachnoid space are observed. Tumor cells
in these sites grow in masses and often produce fl uid (e.g.,
ascites or pleural fl uid), sometimes in massive quantities.
Although the other choices provide routes for tumor metastasis,
they do not lead to peritoneal carcinomatosis in patients
with ovarian cancer.
Diagnosis: Ovarian cancer, carcinomatosis

4 The answer is B: E-cadherin. Cadherins are Ca2+-dependent
transmembrane glycoproteins that mediated cell–cell adhesion.
E-cadherin is expressed on the surface of all epithelia
and mediates cell adhesion by “zipper-like” interactions.
Overall, cadherins suppress invasion and metastasis. Thus, it
is perhaps not surprising that the expression of E-cadherin is
reduced in most carcinomas. Desmin (choice A) is an intermediate
fi lament protein found in cells of mesenchymal origin.
Lysyl hydroxylase (choice C) is involved in the posttranslational
modifi cation of collagen. P selectin is a cell adhesion
molecule that mediates the margination of neutrophils during
acute infl ammation. Telomerase (choice E) is increased in certain
malignancies.
Diagnosis: Breast cancer

34 The answer is B: Leiomyoma. Leiomyoma is the most common
benign tumor of the uterus, usually arising in women of
reproductive age. It originates from smooth muscle cells of the
myometrium. None of the other choices are benign tumors of
smooth muscle.
Diagnosis: Leiomyoma of uterus

8 The answer is D: Cytokeratins. Tumor markers are products
of malignant neoplasms that can be detected in cells or body
fl uids. Useful tumor markers include immunoglobulins, fetal
proteins, enzymes, hormones, and cytoskeletal proteins. Carcinomas
uniformly express cytokeratins, which are intermediate
fi laments. Alpha-fetoprotein (choice A) is a marker for
yolk sac carcinoma and hepatocellular carcinoma. Calretinin
(choice B) provides a marker for mesothelioma. Carcinoembryonic
antigen (choice C) is a marker for colon carcinoma
and many other malignancies. Synaptophysin (choice E) is a
marker for neuroendocrine tumors, including small cell carcinoma
of the lung.
Diagnosis: Squamous cell carcinoma of lung

26 The answer is E: Teratoma. Teratomas are benign tumors
composed of tissues derived from all three primary germ layers:
ectoderm, mesoderm, and endoderm. They are most common
in the ovary but also occur in the testis and extragonadal
sites. Teratocarcinomas (choice D) are malignant tumors that
harbor embryonal carcinoma stem cells. Adenoma (choice A)
is a benign tumor of epithelial origin. Chondroma (choice B)
is a benign cartilaginous tumor. Hamartoma (choice C) is disorganized
normal tissue.
Diagnosis: Mature teratoma

27 The answer is C: Japan. The highest incidence of stomach
cancer occurs in Japan, where the disease is almost ten times
as frequent as it is among American whites. A study of Japanese
residents of Hawaii found that emigrants from Japanese
regions with the highest risk of stomach cancer continued to
exhibit an excess risk in Hawaii. By contrast, their offspring
who were born in Hawaii had the same incidence of this cancer
as American whites. The highest incidence of colorectal
cancer is found in the United States (choice E).
Diagnosis: Gastric cancer

28 The answer is E: Xeroderma pigmentosum. Xeroderma
pigmentosum is an autosomal recessive disease in which
increased sensitivity to sunlight is accompanied by a high
incidence of skin cancers, including basal cell carcinoma,
squamous cell carcinoma, and malignant melanoma. Several
xeroderma pigmentosum genes are involved in nucleotide
excision of ultraviolet-damaged DNA. Li-Fraumeni syndrome
(choice C) refers to an inherited predisposition to develop
cancers in many organs due to germline mutations of p53.
Ataxia telangiectasia (choice A) features cerebellar degeneration,
immunologic abnormalities, and a predisposition to
cancer. The mutated gene codes for a nuclear phosphoprotein
involved in regulation of the cell cycle and DNA repair.
Patients with hereditary albinism (choice B) are also at high
risk for development of squamous cell carcinoma of the skin,
but they do not have a defect in DNA excision repair. Patients
with neurofi bromatosis (choice D) develop benign cutaneous
neurofi bromas.
Diagnosis: Xeroderma pigmentosum

1 The answer is E: Telomerase. Somatic cells do not normally
express telomerase, which is an enzyme that adds repetitive
sequences to maintain the length of the telomere. Thus, with
each round of somatic cell replication, the telomere shortens.
The length of telomeres may act as a “molecular clock” and
govern the lifespan of replicating cells. Because cancer cells
and embryonic cells express high levels of telomerase, the
reactivation of this enzyme may be important for maintaining
stem cell proliferation. Most human cancers show activation
of the gene for the catalytic subunit of telomerase: human
telomerase reverse transcriptase. P selectin (choice D) is a cell
adhesion molecule that mediates the margination of neutrophils
during acute infl ammation. The

15 The answer is B: Asbestos. The characteristic tumor associated
with asbestos exposure is mesothelioma of the pleural
and peritoneal cavities. This cancer has been reported to
occur in 2% to 3% of heavily exposed workers. The pipe fi tters
in shipyards were the most exposed workers. Many of
these workers developed mesotheliomas 20 to 40 years after
exposure. It is reasonable to surmise that mesotheliomas of
both the pleura and the peritoneum refl ect the close contact
of these membranes with asbestos fi bers transported to them
by lymphatic channels. Like the polycyclic aromatic hydrocarbons,
afl atoxin B1 (choice A) can bind covalently to DNA
and is among the most potent liver carcinogens recognized.
Beryllium (choice C) and silica (choice E) cause lung disease,
but they are not carcinogenic.
Diagnosis: Mesothelioma

18 The answer is A: Adenoma. Benign tumors arising from a
glandular epithelium are termed adenomas. Patients with a
prolactin-secreting pituitary adenoma present with amenorrhea
and galactorrhea. Ectopic islands of normal tissue are
called choristomas (choice B). Localized, disordered differentiation
during development results in a hamartoma (choice C).
Papillomas (choice D) do not occur in the pituitary. Benign
tumors that arise from germ cells and contain all three germ
layers are termed teratomas (choice E).
Diagnosis: Pituitary adenoma, prolactinoma

33 The answer is B: Melanoma. The photograph shows pigmented
cells in the vertebral bodies of a person who died
of malignant melanoma. This autopsy fi nding illustrates the
point that accurate tumor identifi cation depends on morphologic
resemblance to normal tissue. Tumor emboli in this case
probably reached bone after surviving passage through the
pulmonary microcirculation. None of the other tumors show
pigmentation.
Diagnosis: Melanoma

35 The answer is E: Protooncogene activation. The best-known
example of an acquired chromosomal translocation in a human
cancer is the Philadelphia chromosome, which is found in 95%
of patients with CML. The c-abl protooncogene on chromosome
9 is translocated to chromosome 22, it is placed in juxtaposition
to the breakpoint cluster region (bcr). The c-abl gene
and bcr region unite to produce a hybrid oncogene that codes
for an aberrant protein with very high levels of tyrosine kinase
activity, which generates mitogenic and antiapoptotic signals.
Diagnosis: Chronic myelogenous leukemia, Philadelphia
chromosome

16 The answer is C: Invasion of the underlying basement
membrane. The fi rst event in tumor cell invasion is breach
of the basement membrane that separates an epithelium from
the underlying mesenchyme. After invading the interstitial tissue,
malignant cells penetrate lymphatic or vascular channels
(choice D). In the lymph nodes, communications between the
lymphatics and venous tributaries allow malignant cells access
to the systemic circulation. The other choices are important
for tumor metastases, but they occur later than basement
membrane invasion.
Diagnosis: Adenocarcinoma of colon

17 The answer is E: Loss of cell cycle restriction point control.
Cancer cells often display loss of cell cycle restriction
point control through mechanisms such as overexpression
of cyclin D1, loss of Cdk inhibitors, or inactivation of the
pRb or p53 proteins. The p53 gene is deleted or mutated in
75% of cases of colorectal cancer and frequently mutated in
numerous other tumors. The p53 protein is a negative regulator
of cell division. Inactivating mutations of p53 cause loss of
cell cycle restriction point control and allow cells with damaged
DNA to progress through the cell cycle. Malignant cells
have increased cellular motility (see choice A), reduced stem
cell differentiation (see choice B), decreased cell adhesion
(see choice C), and decreased susceptibility to apoptosis (see
choice D).
Diagnosis: Adenocarcinoma of colon

22 The answer is E: Stomach. Acanthosis nigricans is a cutaneous
disorder marked by hyperkeratosis and pigmentation
of the axilla, neck, fl exures, and anogenital region. It is of
particular interest because more than half of patients with
acanthosis nigricans have cancer. Over 90% of cases occur in
association with gastrointestinal carcinomas (primarily stomach
cancer). The other tumors are uncommon causes of acanthosis
nigricans.
Diagnosis: Paraneoplastic syndrome, acanthosis nigricans

30 The answer is E: Gene amplifi cation. Chromosomal alterations
that result in an increased number of copies of a gene
have been found primarily in solid tumors. Such aberrations
are recognized as (1) homogeneous staining regions (HSRs);
(2) abnormal banding regions on chromosomes; or (3) double
minutes, which are visualized as small, paired cytoplasmic
bodies. In some cases, gene amplifi cation has been shown to
involve protooncogenes. For example, HSRs may be seen in
neuroblastomas and are all derived from the N-myc protooncogene.
The presence of N-myc HSRs is associated with up to
700-fold amplifi cation of this gene and is a marker of advanced
disease with a poor prognosis. Although the other choices are
mechanisms for protooncogene activation, they do not cause
upregulation of N-myc in patients with neuroblastoma.
Diagnosis: Neuroblastoma

43 The answer is E: Sunlight. Basal cell carcinoma (BCC) is the
most common malignant tumor in persons with pale skin.
BCC usually develops on the sun-damaged skin of people with
fair skin and freckles. There is a direct correlation between
total exposure to sunlight and the incidence of BCC, as well
as squamous cell carcinoma and melanoma. The deleterious
effects of sunlight (UV radiation) include enzyme inactivation,
mutagenesis, and cell death. Divalent metal cations such
as nickel, lead, cadmium, cobalt, and beryllium (choice B)
can react with biomolecules and induce cancer. Most metalinduced
cancers occur in an occupational setting; however the
carcinogenic mechanisms are unknown.
Diagnosis: Basal cell carcinoma

44 The answer is C: Cell cycle. The surgical specimen reveals
thousands of small adenomatous polyps on the mucosal surface
of the colon. Patients with adenomatous polyposis coli
have mutations in the APC tumor suppressor gene. Most cases
are familial, but 30% to 50% represent new mutations. The
mean age for occurrence of symptoms is 36 years. Without
the APC protooncogene, cells are unable to downregulate
signals from E-cadherin to b-catenin to nuclear transcription
factors (myc and cyclin D) that regulate cell cycle progression.
Autophagy (choice B) is a normal catabolic process in
which cellular components and organelles are degraded in
lysosomes. Autophagy is often a response to cell injury. It is
also believed to protect cells from intracellular pathogens and
slow the progression of various chronic diseases, including
cancer.
Diagnosis: Adenomatous polyposis coli

7 The answer is B: Paraneoplastic syndrome. Cancers may produce
remote effects, collectively termed paraneoplastic syndromes.
For example, the secretion of corticotropin (ACTH)
by a tumor leads to clinical features of Cushing syndrome,
including hyperglycemia and hypertension. Corticotropin
production is most commonly seen with cancers of the lung,
particularly small cell carcinoma. Adrenal and pituitary metastases
(choices A and D) would lead to loss of adrenal function
(Addison disease). Although pituitary adenoma (choice C) is
a possible cause of Cushing syndrome, this choice would be
unlikely in a patient with lung cancer.
Diagnosis: Small cell carcinoma of lung, paraneoplastic
syndrome

11 The answer is A: Aniline dyes. Transitional cell carcinoma is
the most common malignant tumor of the urinary bladder,
and the incidence of bladder cancer is increased in aniline dye
workers. These azo dyes are converted to water-soluble carcinogens
in the liver. They are excreted in the urine, where
they primarily affect the transitional epithelium of the bladder.
Benzene exposure (choice C) is associated with leukemia.
Vinyl chloride exposure (choice E) has been associated with
hepatic angiosarcomas.
Diagnosis: Transitional cell carcinoma of bladder

36 The answer is B: CD4. CD4 is a cluster-differentiation antigen
of helper T lymphocytes. HMB-45 and S-100 (choices D and
E) are markers for malignant melanoma, among other tumors.
Calcitonin (choice A) is a peptide hormone. Desmin (choice
C) is an intermediate fi lament protein found in cells of mesenchymal
origin.
Diagnosis: Mycosis fungoides

39 The answer is D: Loss of heterozygosity. Retinoblastomas are
malignant ocular tumors of young children. In cases of hereditary
retinoblastoma, an affected child inherits one defective Rb
allele together with one normal gene. This heterozygous state
is not associated with any observable changes in the retina
because 50% of the Rb gene product is suffi cient to prevent
the development of retinoblastoma. However, if the remaining
normal Rb allele is inactivated by deletion or mutation,
the loss of its suppressor function leads to the appearance
of a neoplasm. This genetic process is referred to as loss of
heterozygosity. The other choices have not been associated
with the loss of tumor suppressor genes in somatic cells.
Diagnosis: Retinoblastoma

42 The answer is A: Adenoma. The patient shows signs and
symptoms of Cushing syndrome (upper truncal obesity and
hypercortisolism). The surgical specimen reveals a circumscribed
tumor of the adrenal cortex that produces cortisol.
Histologic examination of this tumor reveals nests of clear,
lipid-laden epithelial cells. None of the other choices describe
a benign tumor of glandular epithelial origin.
Diagnosis: Adrenal adenoma, Cushing syndrome

20 The answer is A: Apoptosis. Many human cancers show
abnormalities in the control of apoptosis. For example, follicular
B-cell lymphomas display a characteristic chromosomal
translocation in which the bcl-2 gene is brought under
the transcriptional control of the immunoglobulin light-chain
gene promoter, thereby causing overexpression of bcl-2. As a
result of the antiapoptotic properties of bcl-2, the neoplastic
clone accumulates in lymph nodes. Since its demonstration
in follicular lymphomas, bcl-2 expression has been observed
in a variety of other human cancers. None of the other choices
describes the function of bcl-2.
Diagnosis: Follicular lymphoma

The answer is D: Pancreas. Radiologic evidence of “canon
ball” lesions in the liver or lung suggests metastatic cancer.
The liver is involved in a third of all metastatic cancers, including
half of those of the gastrointestinal tract, breast, and lung.
Other tumors that characteristically metastasize to the liver
are pancreatic carcinoma and malignant melanoma. Liver
metastases are the most common cause of massive hepatomegaly.
Visible secretions of tumor cells, such as mucin or
serous fl uid, provide important clues for tumor diagnosis.
Mucin-secreting glandular epithelium and mucin-secreting
adenocarcinoma are expected in the pancreas. None of the
other organs are composed of glandular epithelial cells or produce
mucin.
Diagnosis: Metastatic cancer

The answer is B: Carcinoembryonic antigen (CEA). Colorectal
cancer is asymptomatic in its initial stages. As the tumor
grows, the most common sign is occult blood in feces,
especially when the tumor is in the proximal portion of the
colon. Chronic, asymptomatic bleeding typically causes
iron- defi ciency anemia. Adenocarcinomas of the colon usually
express CEA, a glycoprotein that is released into the circulation
and serves as a serologic marker for these tumors
CEA is also found in association with malignant tumors of
the pancreas, lung, and ovary. AFP (choice A) is expressed by
hepatocellular carcinoma and yolk sac tumors. Chromogranin
(choice D) is expressed by neuroendocrine tumors. Chorionic
gonadotropin (choice C) is secreted by choriocarcinoma.
Diagnosis: Colon cancer

The answer is D: Ischemia and infarction. Angiogenesis is a

requirement for the continued growth of cancers, whether primary

or metastatic. In the absence of new vessels to supply the

nutrients and remove waste products, malignant tumors do

not grow larger than 1 to 2 mm in diameter. In general, causes

of tumor cell death in situ include (1) programmed cell death

(apoptosis); (2) inadequate blood supply, with consequent

ischemia; (3) a paucity of nutrients; and (4) vulnerability to

specifi c and nonspecifi c host defenses. The CT scan provided

for Question 21 shows central necrosis (umbilication) in most

of the metastatic tumor nodules. None of the other choices are

likely causes of tumor necrosis.

Diagnosis: Metastatic cancer

29 The answer is D: Lung. Lung carcinoma is the cause of most
cancer-related deaths in the United States and Western Europe
in men and women. The second most common cause of death
from cancer in women is breast cancer (choice B). One of the
most common fi ndings in patients with cancer is anemia,
but the mechanism for this paraneoplastic syndrome is not
clear. The anemia is usually normocytic and normochromic,
although iron defi ciency anemia is common in cancers that
bleed into the gastrointestinal tract.
Diagnosis: Lung cancer

5 The answer is D: Resemblance to normal tissue of origin. To
establish criteria for therapy, many cancers are classifi ed
according to histologic grading schemes or by staging protocols
that describe the extent of spread. Cancer grading refl ects
cellular characteristics. Low-grade tumors are well differentiated,
whereas high-grade tumors lack differentiated features
(anaplasia). The general correlation between cytologic grade
and the behavior of a neoplasm is not invariable. Indeed, there
are many examples of tumors of low cytologic grades that
exhibit substantial malignant properties. The other choices
pertain to cancer staging.
Diagnosis: Prostate cancer

6 The answer is C: Desmoplastic change. Secondary descriptors
are used to refer to a tumor’s morphologic and functional
characteristics. Papillomatosis (choice E) describes frond-like
​​​​​​​structures. Medullary (choice D) signifi es a soft cellular tumor,
whereas scirrhous or desmoplastic implies dense fi brous
stroma. Colloid carcinomas (choice A) secrete abundant
mucus. Comedocarcinoma (choice B) is an intraductal neoplasm
in which necrotic material can be expressed from the
ducts.
Diagnosis: Breast cancer

12 The answer is E: Plasminogen activator. Malignant cells and
stromal cells associated with cancers elaborate a variety of proteases
that degrade basement membrane components. Such
enzymes include the urokinase-type plasminogen activator
(u-PA) and matrix metalloproteinases. u-PA converts serum
plasminogen to plasmin, a serine protease that degrades
laminin and activates type IV procollagenase. Changes in the
expression of u-PA, the u-PA receptor, and PA inhibitors have
been reported in different cancers. Metastatic cells would be
expected to show reduced expression of collagens (choice A)
and cadherins (choice C). Desmin (choice B) is found in cells
of mesenchymal origin.
Diagnosis: Squamous cell carcinoma of skin

13 The answer is A: Acquired immunodefi ciency. Kaposi sarcoma
is the most common neoplasm associated with
acquired immunodefi ciency syndrome (AIDS). The neoplastic
cells contain sequences of a novel virus, HHV-8, which
is also known as Kaposi sarcoma–associated herpesvirus. In
addition to infecting the spindle cells of Kaposi sarcoma,
HHV-8 is lymphotropic and has been implicated in two
uncommon B-cell lymphoid malignancies, namely, primary
effusion lymphoma and multicentric Castleman disease.
Like other DNA viruses, the HHV-8 genome encodes proteins
that interfere with the p53 and pRb tumor suppressor
pathways. The other choices are hereditary conditions
associated with cancer; however, these patients do not typically
acquire Kaposi sarcoma. The predominant malignancy
seen in patients with ataxia telangiectasia (choice B) is lymphoma/
leukemia.
Diagnosis: Kaposi sarcoma, AIDS

37 The answer is B: Disorganized normal tissue. Localized, disordered
differentiation during embryonic development results
in a hamartoma, a disorganized caricature of normal tissue
components. Such tumors, which are not strictly neoplasms,
contain varying combinations of cartilage, ducts or bronchi,
connective tissue, blood vessels, and lymphoid tissue. Ectopic
islands of normal tissue (choice C), called choristoma, may
also be mistaken for true neoplasms. These small lesions are
represented by pancreatic tissue in the wall of the stomach or
intestine, adrenal rests under the renal capsule, and nodules of
splenic tissue in the peritoneal cavity.
Diagnosis: Hamartoma

10 The answer is C: DNA repair. Breast (BR) cancer (CA) susceptibility
genes (BRCA1 and BRCA2) encode tumor suppressor
proteins involved in checkpoint functions related to progression
of the cell cycle into S phase. BRCA1 and BRCA2 proteins
also promote DNA repair by binding to RAD51, a molecule
that mediates DNA double-strand repair breaks. The other
choices may be abnormal in neoplasia, but they are not primarily
affected by BRCA1.

41 The answer is C: Metastatic carcinoma of the lung. This
patient’s lung shows numerous nodules of metastatic carcinoma
corresponding to “cannon ball” metastases seen
radiologically. Pulmonary metastases are more common than
primary lung tumors, and the histologic appearance of most
metastases resembles that of the primary tumor. Persons with
ulcerative colitis (such as this patient) have a higher risk of
colorectal cancer than the general population. The risk is
related to the extent of colorectal involvement and the duration
of the infl ammatory disease. Carcinoid tumor of the lung
(choice A) and primary lung cancer (choice B) would not typically
show multiple, circumscribed nodules. Miliary tuberculosis (choice D) and sarcoidosis (choice E) feature mm-sized
infl ammatory nodules (minute granulomas).
Diagnosis: Metastatic cancer, metastatic carcinoma of the lung

9 The answer is D: Polycyclic aromatic hydrocarbons. Polycyclic
aromatic hydrocarbons, originally derived from coal tar, are
among the most extensively studied carcinogens. These compounds
produce cancers at the site of application. Since polycyclic
hydrocarbons have been identifi ed in cigarette smoke,
it has been suggested (but not proved) that they are involved
in the pathogenesis of lung cancer. Afl atoxin B1 (choice A), a
natural product of the fungus Aspergillus fl avus, is among the
most potent liver carcinogens. Asbestos (choice B), a mineral,
is associated with mesothelioma and adenocarcinoma of lung.
Industrial workers exposed to high levels of vinyl chloride
(choice E) in the ambient atmosphere developed angiosarcomas
of the liver.
Diagnosis: Squamous cell carcinoma of lung

25 The answer is A: Epigenetic modifi cation. Hypermethylation
of many tumor suppressor and DNA repair genes has been
demonstrated in human tumors. The pathways controlled by
these genes are, therefore, suppressed. For example, the normal
p53 gene can be inactivated by hypermethylation. Thus,
aberrant methylation of tumor suppressor genes may be an
epigenetic mechanism for a “second hit,” leading to loss of
heterozygosity. Unlike genetic changes in cancer, epigenetic
changes are reversible, and a search for drugs that infl uence
DNA methylation is under way. The other choices are unrelated
to DNA methylation.
Diagnosis: Colon cancer