RUbins - Unit 1 - Neoplasia Flashcards
- A 25-year-old man presents 1 week after discovering that
his left testicle is twice the normal size. Physical examination
reveals a nontender, testicular mass that cannot be transilluminated.
Serum levels of alpha-fetoprotein and human
chorionic gonadotropin are normal. A hemiorchiectomy is
performed, and histologic examination of the surgical specimen
shows embryonal carcinoma. Compared to normal
adult somatic cells, this germ cell neoplasm would most
likely show high levels of expression of which of the following
proteins?
(A) Desmin
(B) Dystrophin
(C) Cytochrome c
(D) P selectin
(E) Telomerase
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 other choices are not
involved in malignant transformation.
Diagnosis: Embryonal carcinoma
A 25-year-old woman presents for a gynecologic examination.
The cervical Pap smear shows “koilocytic atypia” characterized
by perinuclear halos and wrinkled nuclei (shown in
the image). A cervical biopsy reveals invasive squamous cell
carcinoma. Molecular tests for human papillomavirus (HPV)
in the tumor cells are positive. Which of the following mechanisms
of disease best explains the role of HPV in the pathogenesis
of neoplasia in this patient?
A) Activation of cellular oncogenes
(B) Enhanced transcription of telomerase gene
(C) Episomal viral replication
(D) Inactivation of tumor suppressor proteins
(E) Insertional mutagenesis
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
- The patient described in Question 2 undergoes a hysterectomy.
In addition to a focus of invasive carcinoma, the pathologist
identifi es dysplastic squamous cells occupying the entire
thickness of the cervical epithelium, with no evidence of epithelial
maturation. The basal membrane in these areas appears
intact. Which of the following terms best describes this cervical
lesion?
(A) Atypical hyperplasia
(B) Carcinoma in situ
(C) Carcinomatosis
(D) Complex hyperplasia
(E) Koilocytic atypia
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
4 A 62-year-old woman presents with a breast lump that she discovered
6 days ago. A breast biopsy shows lobular carcinoma
in situ. Compared to normal epithelial cells of the breast lobule,
these malignant cells would most likely show decreased
expression of which of the following proteins?
(A) Desmin
(B) E-cadherin
(C) Lysyl hydroxylase
(D) P selectin
(E) Telomerase
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
5 An 80-year-old man complains of lower abdominal pain,
increasing weakness, and fatigue. He has lost 16 lb (7.3 kg)
in the past 6 months. The prostate-specifi c antigen test is
elevated (8.5 ng/mL). Rectal examination reveals an enlarged
and nodular prostate. A needle biopsy of the prostate discloses
invasive prostatic adenocarcinoma. Histologic grading of
this patient’s carcinoma is based primarily on which of the
following criteria?
(A) Capsular involvement
(B) Extent of regional lymph nodes involvement
(C) Pulmonary metastases
(D) Resemblance to normal tissue of origin
(E) Volume of prostate involved by tumor
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
A 50-year-old woman presents with a lump in her breast.
A 4-cm fi rm and fi xed mass is noted on breast examination.
Excisional biopsy reveals malignant cells that form glandlike
structures and solid nests, surrounded by a dense collagenous
stroma. A connective tissue stain (trichrome) of
the biopsy is shown in the image. Which of the following
descriptive terms best describes the blue areas observed in
this specimen?
(A) Colloid carcinoma
(B) Comedocarcinoma
(C) Desmoplastic change
(D) Medullary carcinoma
(E) Papillomatosis
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
7 A 65-year-old man complains of muscle weakness and a dry
cough for 4 months. He has smoked two packs of cigarettes
daily for 45 years. A chest X-ray shows a 4-cm central, left
lung mass. Laboratory studies reveal hyperglycemia and
hypertension. A transbronchial biopsy is diagnosed as small
cell carcinoma. Metastases to the liver are detected by CT scan.
Which of the following might account for the development of
hyperglycemia and hypertension in this patient?
(A) Adrenal metastases
(B) Paraneoplastic syndrome
(C) Pituitary adenoma
(D) Pituitary metastases
(E) Thrombosis of the renal artery
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
8 A 60-year-old man presents with a 4-month history of increasing
weight loss, wheezing, and shortness of breath. He has
smoked two packs of cigarettes a day for 40 years. His past
medical history is signifi cant for emphysema and chronic
bronchitis. A chest X-ray shows a 10-cm mass in the left lung.
Bronchoscopy discloses obstruction of the left main stem
bronchus. A biopsy is obtained (shown in the image). Immunohistochemical
studies of this biopsy specimen would most
likely show strong expression of which of the following tumor
markers?
(A) Alpha-fetoprotein
(B) Calretinin
(C) Carcinoembryonic antigen
(D) Cytokeratins
(E) Synaptophysin
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
9 Which of the following potent carcinogens was most likely
involved in the pathogenesis of lung cancer in the patient
described in Question 8?
(A) Afl atoxin B1
(B) Asbestos
(C) Azo dyes
(D) Polycyclic aromatic hydrocarbons
(E) Vinyl chloride
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
10 A 33-year-old woman discovers a lump in her left breast on
self-examination. Her mother and sister both had breast cancer.
A mammogram demonstrates an ill-defi ned density in
the outer quadrant of the left breast, with microcalcifi cations.
Needle aspiration reveals the presence of malignant, ductal
epithelial cells. Genetic screening identifi es a mutation in
BRCA1. In addition to cell cycle control, BRCA1 protein promotes
which of the following cellular functions?
(A) Apoptosis
(B) Cell adhesion
(C) DNA repair
(D) Gene transcription
(E) Transmembrane signaling
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.
Diagnosis: Breast cancer
11 A 60-year-old man who worked for 30 years in a chemical
factory complains of blood in his urine. Urine cytology
discloses dysplastic cells. A bladder biopsy demonstrates
transitional cell carcinoma. Which of the following carcinogens
was most likely involved in the pathogenesis of bladder
cancer in this patient?
(A) Aniline dyes
(B) Arsenic
(C) Benzene
(D) Cisplatinum
(E) Vinyl chloride
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
- A 60-year-old man presents with an ulcerated, encrusted,
and infi ltrating lesion on the sun-exposed dorsal aspect of a
fi nger (shown in the image). A biopsy reveals squamous cell
carcinoma. The metastatic potential of this neoplasm would
be enhanced by upregulation of the gene for which of the following
proteins?
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 A 45-year-old man presents with a 9-month history of a
reddish nodule on his foot. Biopsy of the nodule discloses
a poorly demarcated lesion composed of fi broblasts and
endothelial-like cells lining vascular spaces. Further work-up
identifi es similar lesions in the lymph nodes and liver. The
tumor cells contain sequences of human herpesvirus-8
(HHV-8). This patient most likely has which of the following
diseases?
(A) Acquired immunodefi ciency
(B) Ataxia telangiectasia
(C) Li-Fraumeni syndrome
(D) Neurofi bromatosis type I
(E) Xeroderma pigmentosum
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
14 During a routine checkup, a 50-year-old man is found to
have blood in his urine. He is otherwise in excellent health.
An abdominal CT scan reveals a 2-cm right renal mass. You
inform the patient that staging of this tumor is key to selecting
treatment and evaluating prognosis. Which of the following is
the most important staging factor for this patient?
(A) Histologic grade of the tumor
(B) Metastases to regional lymph nodes
(C) Proliferative capacity of the tumor cells
(D) Somatic mutations in the p53 tumor suppressor gene
(E) Tumor cell karyotype (aneuploidy)
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
15 A 68-year-old man who has worked in a shipyard and manufacturing
plant all his adult life complains of a 4-month history
of chest discomfort, malaise, fever, night sweats, and weight
loss. A chest X-ray reveals a large pleural effusion. The patient
dies 5 months later of cardiorespiratory failure. The lung at
autopsy is shown in the image. This malignant neoplasm is associated with environmental exposure to which of the following
carcinogens?
A) Afl atoxin B1
(B) Asbestos
(C) Beryllium
(D) Ionizing radiation
(E) Silica
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
16 A 58-year-old woman with colon cancer presents with
3 months of increasing shortness of breath. A chest X-ray
reveals numerous, bilateral, round masses in both lungs. Histologic
examination of an open-lung biopsy discloses malignant
gland-like structures, which are nearly identical to the
colon primary. Which of the following changes in cell behavior
was the fi rst step in the process leading to tumor metastasis
from the colon to the lung in this patient?
(A) Arrest within the circulating blood or lymph
(B) Exit from the circulation into a new tissue
(C) Invasion of the underlying basement membrane
(D) Penetration of vascular or lymphatic channels
(E) Stimulation of angiogenesis within the pulmonary
metastases
The answer is C: Invasion of the underlying basement
membrane. The first 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 A 68-year-old man complains of recent changes in bowel
habits and blood-tinged stools. Colonoscopy reveals a 3-cm
mass in the sigmoid colon. Biopsy of the mass shows infi ltrating
malignant glands. These neoplastic cells have most likely
acquired a set of mutations that cause which of the following
changes in cell behavior?
(A) Decreased cellular motility
(B) Enhanced stem cell differentiation
(C) Increased cell-cell adhesion
(D) Increased susceptibility to apoptosis
(E) Loss of cell cycle restriction point control
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
18 A 35-year-old woman complains of nipple discharge and irregular
menses of 5 months duration. Physical examination reveals a
milky discharge from both nipples. MRI shows an enlargement
of the anterior pituitary. Which of the following is the most likely
histologic diagnosis of this patient’s pituitary tumor?
(A) Adenoma
(B) Choristoma
(C) Hamartoma
(D) Papilloma
(E) Teratoma
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
- A 60-year-old man presents with a 6-month history of increasing
weight loss and fatigue. Physical examination reveals conspicuous
hepatomegaly. An abdominal CT scan reveals multiple
“canon ball” nodules in the liver (shown in the image). A CTguided
biopsy reveals a mucous-secreting adenocarcinoma.
This patient’s metastatic liver cancer most likely originated in
which of the following anatomic locations?
(A) Adrenal medulla
(B) Bone marrow
(C) Brain
(D) Pancreas
(E) Urinary bladder
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
31 An 8-year-old African boy presents with swelling in his jaw
and massive facial disfi guration. Biopsy reveals a tumor invading
the bone marrow of the jaw. The pathogenesis of this
malignant neoplasm is associated with a virus that exhibits a
tropism for which of the following cells?
(A) Chondrocytes
(B) Fibroblasts
(C) Lymphocytes
(D) Macrophages
(E) Osteocytes
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
- A 55-year-old woman presents with increasing weight loss
and fatigue and subsequently dies of metastatic cancer. The
vertebral column at autopsy is shown in the image. What is
the diagnosis?
(A) Chondrosarcoma
(B) Melanoma
(C) Multiple myeloma
(D) Osteosarcoma
(E) Rhabdomyosarcoma
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
38 A 67-year-old woman presents with a massively swollen
abdomen. The patient was diagnosed with papillary, serous
cystadenocarcinoma of the ovary 3 years ago. She dies in a
hospice 1 month later. At autopsy, the peritoneum is studded
with small tumors (shown in the image), and there are 4 L
of ascites. Which of the following routes of tumor metastasis
accounts for these autopsy findings?
(A) Direct tumor extension
(B) Hematogenous spread
(C) Lymphatic spread
(D) Seeding of body cavity
(E) Venous spread
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
41 A 53-year-old woman with a longstanding history of ulcerative
colitis presents with increasing chest pain and shortness of
breath of 2 months duration. She reports four recent episodes
of hemoptysis. The patient subsequently develops overwhelming
sepsis and expires. A section through the right lung
is examined at autopsy (shown in the image). What is the
appropriate diagnosis?
(A) Carcinoid tumor of the lung
(B) Primary adenocarcinoma of the lung
(C) Metastatic carcinoma of the lung
(D) Miliary tuberculosis
(E) Sarcoidosis
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 tubercu-losis (choice D) and sarcoidosis (choice E) feature mm-sized
infl ammatory nodules (minute granulomas).
Diagnosis: Metastatic cancer, metastatic carcinoma of the lung
42 A 50-year-old woman presents with a 2-year history of upper
truncal obesity and depression. Serum levels of glucose and
cortisol are elevated. A CT scan of the abdomen reveals a 2-cm
suprarenal mass. The surgical specimen is shown in the image.
If this neoplasm is benign, which of the following is the most
appropriate diagnosis?
(A) Adenoma
(B) Chondroma
(C) Lipoma
(D) Papilloma
(E) Teratoma
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
43 A 65-year-old man presents with a pearly papule on his
upper lip (patient shown in the image). A biopsy reveals
buds of atypical, deeply basophilic keratinocytes extending
from the overlying epidermis into the papillary dermis.
Which of the following carcinogenic stimuli was the most
important risk factor for development of this patient’s skin
cancer?
(A) Aflatoxin B1
(B) Divalent metal cations
(C) Aromatic amines and azo dyes
(D) Vinyl chloride
(E) Sunlight
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 A 28-year-old man with a familial disease affecting the gastrointestinal
tract undergoes a colectomy. The surgical specimen
is shown in the image. Molecular studies demonstrate a germline
mutation in the APC gene. The normal product of this gene (protooncogene) primarily regulates which of the following
cell behaviors?
(A) Apoptosis
(B) Autophagy
(C) Cell cycle
(D) Differentiation
(E) Motility
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
