Neoplasia Exam

1. A 44-year-old woman notes a lump in her left breast while taking a shower. The nurse practitioner palpates a 3 cm firm, irregular, non-movable
mass in the upper outer quadrant of her left breast on physical examination. A fine needle aspiration of this mass is performed, and cytologically
the cells are consistent with infiltrating ductal carcinoma. The mass is removed with lumpectomy along with an axillary lymph node dissection.
Which of the following findings will best predict a better prognosis for this patient?

a. Tumor cells strongly estrogen receptor positive

b. No metastases in the sampled lymph nodes
c. Flow cytometric analysis with aneuploidy and a high S-phase
d. One relative who had a similar type of breast cancer
e. High cytologic tumor grade

(B) CORRECT. The lack of metastases suggests a lower stage and a better prognosis. In general, stage is a better indicator of prognosis than
grade. In general, low stage cancers are more amenable to surgical resection and chance for cure.

2. A change in bowel habits prompts a 53-year-old woman to see her physician. On physical examination there are no lesions noted on digital
rectal examination, but her stool is positive for occult blood. A colonoscopy is performed and reveals a 6 cm friable exophytyic mass in the cecum.
A biopsy of this mass is performed and microscopic examination shows a moderately differentiated adenocarcinoma. Which of the following
laboratory findings is most likely to be present in this patient?

a. K-RAS mutation in the neoplastic cells

b. Neoplastic cells positive for vimentin
c. Stool culture with Shigella flexneri
d. Presence of HIV-1 RNA
e. DNA topoisomerase I autoantibody

A) CORRECT. Many human carcinomas are associated with RAS mutations that contribute to oncogenesis. Many types of mutations can be
present, and in general multiple mutations are present. Sporadic cancers in adults can have many of the same mutations, such as APC and
mismatch repair, that are found in familial cancers, but they are aquired and not inherited.

3. An experiment is conducted in which proliferating cells are subjected to ionizing radiation. The ionizing radiation leads to arrest in a checkpoint
that monitors completion of DNA replication. It is observed that there are increased numbers of chromosomal abnormalities in these cells. Which
of the following is the checkpoint affected by the ionizing radiation?

a. G0/G1 b. G1/S c. S/G2 d. G2/M e. M/G0

(D) CORRECT. This is the second checkpoint in the cell cycle; ionizing radiation activates this checkpoint, resulting in chromosomal abnormalities
in mitosis.

4. A clinical study is performed to determine the incidence of cancers in different countries. The data show that persons born in Japan and
continuing to reside there have an increased risk for cancer. Which of the following cancers is most likely seen with increased frequency in this
population?

a. Breast
b. Colon
c. Lung
d. Stomach
e. Uterus

(D) CORRECT. Gastric cancers are more prevalent in Japan. Is this genetics or environment? The risk goes down with emigration and subsequent
generations living outside of Japan. The prevlance of H. pylori infection may play a role. Incidence of gastric cancer has diminished in the U.S. The
health care system in Japan has effective screening programs that diagnose many cases at the curable early gastric cancer stage.

5. A 48-year-old woman has a routine physical examination. A 4 cm diameter non-tender mass is palpated in her right breast. The mass appears
fixed to the chest wall. Another 2 cm non-tender mass is palpable in the left axilla. A chest radiograph reveals multiple 0.5 to 2 cm nodules in both
lungs. Which of the following TNM classifications best indicates the stage of her disease?

a. T1 N1 M0 b. T1 N0 M1 c. T2 N1 M0 d. T3 N0 M0 e. T4 N1 M1

(E) CORRECT. She has a large invasive (high T) primary tumor mass with axillary node (N > 0) and lung (distant) metastases (M1).

6. A study is performed to analyze characteristics of malignant neoplasms in biopsy specimens. The biopsies were performed on patients who had
palpable mass lesions on digital rectal examination. Of the following microscopic findings, which is most likely to indicate that the neoplasm is
malignant?
a. Pleomorphism b. Atypia c. Invasion d. Increased nuclear/cytoplasmic ratio e. Necrosis

(C) CORRECT. Metastasis would be an even better indicator, but invasion of adjacent tissues suggests malignancy more than the other items
listed here. Size increasing beyond 1 cm is also a risk for malignancy in a colonic polypoid lesion.

7. Review of a series of surgical pathology reports indicates that a certain type of neoplasm is diagnosed as grade I on a scale of I to IV. Clinically,
some of the patients with this neoplasm are found to have stage I disease. Which of the following is the best interpretation of a neoplasm with
these designations?
a. Unlikely to be malignant b. Arising from epithelium c. May spread via lymphatics and bloodstream
d. Has an in situ component e. Well-differentiated and localized
(E) CORRECT. A well-differentiated (low grade) and localized (lower stage) malignant neoplasm often has both a low grade and low stage. In such
cases surgery to excise the lesion is more likely to be curative.

8. A 51-year-old man has worked for 10 years in a factory producing plastic pipe but not following safety standards. He has noted weight loss,
nausea, and vomiting worsening over the past 5 months. On examination he is afebrile. There is generalized muscle wasting. Laboratory studies
show the serum alkaline phosphatase is 405 U/L with AST 47 U/L, ALT 35 U/L, and total bilirubin 1.2 mg/dL. An abdominal CT scan reveals a 12
cm right liver lobe mass. Liver biopsy reveals a neoplasm composed of spindle cells forming irregular vascular channels. With immunohistochemical
staining the cells demonstrate vimentin positivity and cytokeratin negativity. Exposure to which of the following substances most likely led to
development of this neoplasm?
a. Benzene b. Radon c. Cyclophosphamide d. Asbestos e. Vinyl chloride

(E) CORRECT. This is a rare cause of cancer. However, this causal relationship is easy to demonstrate, because hepatic angiosarcoma is a rare
neoplasm. What else could happen in the future? At least a hundred new chemical compounds are dumped into the environment each year. The
elevated alkaline phosphatase is characteristic for hepatic metastases as well as bone metastases.

9. A child is born with a single functional allele of a tumor suppressor gene. At the age of five the remaining normal allele is lost through a point
mutation. As a result, the ability to inhibit cell cycle progression until the cell is ready to divide is lost. Which of the following neoplasms is most
likely to arise via this mechanism?
a. Breast ductal carcinoma b. Pulmonary small cell anaplastic carcinoma c. Ocular retinoblastoma
d. Cerebral astrocytoma e. Chronic myeloid leukemia

(C) CORRECT. The RB gene is the classic example of the 'two hit' mechanism for loss of tumor suppression. About 60% of these tumors are
sporadic, while 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.

10. A 22-year-old woman goes to her physician for a routine examination. A palpable nodule is found in the right lobe of her thyroid gland. No
lymphadenopathy is noted. A chest x-ray shows no masses. A fine needle aspirate of the nodule is performed and cytologic examination reveals
cells present consistent with a papillary carcinoma of the thyroid. There are no other family members affected by this disorder. She works as an
administrator for an accounting firm part time and is earning a college degree. Which of the following findings would you consider most relevant in
her past history to indicate a risk factor for this neoplasm?
a. Chronic alcoholism b. Radiation therapy in childhood c. Ataxia telangiectasia d. Blunt trauma from a fall
e. Occupational exposure

(B) CORRECT. Radiation is oncogenic. Cancers of thyroid and bone often develop in children with radiation exposure. Leukemias can occur as
well.

11. A 50-year-old man has felt vague abdominal discomfort for the past 4 months. On physical examination he has no lymphadenopathy, and no
abdominal masses or organomegaly can be palpated. Bowel sounds are present. An abdominal CT scan shows a 20 cm retroperitoneal soft tissue
mass obscuring the left psoas muscle. A stool specimen tested for occult blood is negative. Which of the following neoplasms is this man most
likely to have?
a. Melanoma b. Hamartoma c. Adenocarcinoma d. Lymphoma e. Liposarcoma

(E) CORRECT. Sarcomas are big and bad. They arise in soft tissues derived from mesenchymal (connective) tissues. Retroperitoneum is a typical
location for a sarcoma arising in an adult. Sarcomas are much less common than carcinomas in adults.

12. A 52-year-old man has had increasing fatigue for the past 6 months. On physical examination he has a palpable spleen tip. Laboratory studies
show a WBC count of 189,000/microliter. The peripheral blood smear shows many mature and immature myeloid cells present. Cytogenetic
analysis of cells obtained via bone marrow aspiration reveals a t(9:22) translocation. This translocation leads to formation of a hybrid gene that
greatly increases tyrosine kinase activity. Which of the following genes is most likely translocated to cause these findings?

a. p53 b. RB c. ABL d. NF-1 e. RAS

(C) CORRECT. This is the 'Philadelphia chromosome' of chronic myelogenous leukemia (CML) and an example of an abnormal fusion gene driving
cell proliferation. Therapy with a biologic agent such as a tyrosine kinase inhibitor (TKI), a monoclonal antibody that targets the abnormal protein
produced by the BCR-ABL fusion gene is often effective. First generation TKIs include imatinib, and more effective 2nd generation TKIs include
dasatinib, nilotinib, and bosutinib.

13. A clinical study is performed of oncogenesis in human neoplasms. It is observed that some neoplasms appear to develop from viral
oncogenesis, with serologic confirmation of past viral infection. Which of the following neoplasms is most likely to arise in this manner?

a. Retinoblastoma b. Small cell anaplastic carcinoma c. T-cell leukemia d. Prostatic adenocarcinoma

e. Hepatic angiosarcoma

(C) CORRECT. Human T-lymphocytotropic virus (HTLV) infection can lead to T-cell leukemia. However, few human cancers arise as a result of
viral oncogenesis. Some viruses, such as hepatitis viruses B and C, result in cellular proliferation that increases the risk for subsequent mutations
that drive carcinogenesis.

14. An experiment is designed to study the genetics of cancer. The study will link the appearance of cancer to specific gene abnormalities. Which
of the following forms of cell molecular analysis is most useful to identify gene alterations involved in carcinogenesis?
a. Florescence in situ hybridization b. Flow cytometry c. Immunohistochemistry d. Single nucleotide polymorphisms
e. Tumor marker expression

(D) CORRECT. SNPs can be analyzed to find alterations present in cancer cells. One could analyze multiple histologically similar cancers to
determine what gene(s) alteration(s) such as deletions and amplifications may underlie carcinogenesis. Using millions of SNPs can produce a
virtual karyotype down to the gene level.
15. A 29-year-old woman with a history of multiple sexual partners over the last 15 years has a routine physical examination with no abnormal
findings. On pelvic examination, the cervix shows no abnormalities, but a Pap smear is taken and dysplastic cells are reported to be present. A
cervical biopsy is performed and shows a low grade squamous intraepithelial lesion (LSIL), also known as cervical intraepithelial neoplasia 1 (CIN-
1). Which of the following is the most appropriate therapeutic strategy for this lesion?

a. No further treatment b. Antibiotic therapy c. Chemotherapy d. Colposcopy e. Radiation therapy

(D) CORRECT. Cervical dysplasia is a pre-neoplastic condition that has the potential to develop into a carcinoma if not treated. Epithelia subjected
to initiators and promoters of carcinogenesis tend to undergo progression from metaplasia to dysplasia to carcinoma. Even a carcinoma is
essentially 100% curable when it is limited to the epithelium (in situ). That is why you try to diagnose the lesion as early as possible. Some LSILs
on Pap smear have a more advanced lesion present with colposcopic screening and warrants resection. Just LSIL may be followed with Pap
smears, as some women with HPV infection will clear the virus. High-grade squamous intraepithelial lesions (HSIL) correlate with CIN 2 or 3, which
are less likely to regress and are therefore resected.

16. A 64-year-old man has noted a 5 kg weight loss along with increasing fatigue over the past year. He has experienced dull abdominal pain for
the past week. He has developed abdominal distention with lack of stools in the past two days. On physical examination, bowel sounds are reduced.
An abdominal CT scan reveals a mass involving the descending colon. At laparotomy, a partial resection of the left colon is performed, with removal
of an encircling mass. Microscopically, the mass is found to be a moderately differentiated adenocarcinoma. Which of the following laboratory test
findings is most likely to be present in this man?

a. Microcytic hypochromic anemia b. Positive antinuclear antibody test c. Hyperglycemia d. Elevated alpha-fetoprotein
e. Decreased lactate dehydrogenase

(A) CORRECT. He has an adenocarcinoma of the colon. Such lesions are often associated with blood loss from mucosal erosion and necrosis.
Cancer cells are less differentiated and less functional than their normal cell of origin and thus less functional. With poor construction come many
problems.

17. A 14-year-old healthy girl has a 0.3 cm reddish, slightly raised nodule on the skin of the upper part of her chest found on a routine physical
examination. She states that this lesion has been present for years and has not appreciably changed in size or color. Which of the following
neoplasms is this nodule most likely to be?
a. Hemangioma b. Melanoma c. Carcinoma d. Lymphoma e. Glioma

(A) CORRECT. Hemangiomas, teratomas, and fibromatoses are common pediatric neoplasms that are benign. Benign neoplasms tend to grow
slowly and remain localized. They do not invade or metastasize.

18. A 56-year-old man has had a chronic cough for the past year. He is a non-smoker. He had an episode of hemoptysis 3 days ago. No abnormal
findings are noted on physical examination. A chest x-ray demonstrates a 6 cm perihilar mass. A sputum sample is collected, and the sputum
cytology report reads 'Atypical cells present suggestive of squamous cell carcinoma.' Which of the following environmental exposures is most likely
to be associated with these findings?

a. Asbestos b. Radon c. Silica d. Benzene e. Formaldehyde

(B) CORRECT. Radon gas is considered to be the second most common cause for lung cancer following tobacco smoking. However, most persons
with radon exposure who develop lung cancer are also smokers. A small amount of radon gas naturally seeps up from the soil and may collect in
houses. Commercial buildings tend to be larger and well ventilated so little radon collects in them.

19. A 60-year-old man who has a 90 pack year history of cigarette smoking has had a chronic cough for the past 10 years. He has begun to lose
weight (3 kg) during the past year. No abnormal findings are noted on physical examination. He has a chest radiograph that reveals a right hilar
mass. A sputum cytology shows atypical, hyperchromatic squamous cells. What is the most common initial pathway for metastases from this
lesion?

a. Bloodstream b. Pleural cavity c. Contiguous spread to chest wall d. Lymphatics e. Bronchi

(D) CORRECT. Epithelial malignancies such as a squamous cell carcinoma of the lung often have non-contiguous (metastatic) spread initially to
regional lymph nodes. This is important to determine for staging, because the treatment and prognosis depend upon accurate staging. Lymph
node metastases or hematogenous metastases imply the malignancy is systemic and local excision of the lung mass will not be curative.

20. A 55-year-old man has had malaise and a 4 kg weight loss over the past 6 months. On physical examination his stool is positive for occult
blood. An abdominal CT scan shows his liver contains multiple tumor masses from 2 to 5 cm in size with central necrosis. The surrounding hepatic
parenchyma appears normal. Which of the following characteristics of neoplasia is best illustrated by these findings?

a. Multicentric origin b. High tumor grade c. Primary neoplasm in the stomach d. Exposure to a carcinogen
e. Advanced stage

(E) CORRECT. The most likely possibility is that these masses represent metastases from a primary site elsewhere in the body, likely the colon
because of blood in the stool. Thus, this is a malignant neoplasm that has an advanced stage (M1). The central necrosis is the result of tumor
necrosis with collapse of a tumor nodule.

21. A 59-year-old man has had a worsening cough with chest pain for the past 6 months. On physical examination he has no remarkable findings.
A chest x-ray shows a 3 cm left lung mass. A sputum cytology specimen yields cells diagnosed as a squamous cell carcinoma. A mediastinoscopy
is performed and reveals metastases in a lymph node. He is given radiation therapy, and the mass diminishes in size. Which of the following
cellular mechanisms is most likely to account for this tumor response?

a. Point mutations in DNA b. Generation of free radicals c. Loss of the blood supply
d. Secondary inflammation e. Adenosine triphosphate depletion
(B) CORRECT. The purpose of therapeutic radiotherapy is to try and kill more neoplastic cells than normal cells. This is mediated mainly through
direct damage to the cells and one mechanism is generation of oxidant free radicals. Cancer cells are more vulnerable than normal cells.
Techniques are available to focus the beam of radiation energy on the cancer and reduce collateral damage to normal tissues.

22. A 61-year-old woman has a firm mass with irregular borders felt in her left breast on a routine physical examination. A fine needle aspiration is
performed and microscopic examination shows malignant cells. A left mastectomy with axillary lymph node dissection is performed. A tissue
sample of this neoplasm is submitted for analysis by flow cytometry. Which of the following does flow cytometric analysis most likely provide?

a. Analysis of the karyotype b. Detection of gene mutations c. Determination of aneuploidy

d. Distinguishing carcinoma from sarcoma e. Quantitation of RNA content

(C) CORRECT. Flow cytometry can detect the degree of aneuploidy from the DNA content. Aneuploidy implies that the neoplasm is worse (more
aggressive) than if it were not aneuploid.

23. A 35-year-old healthy woman had a firm nodule palpable on the dome of the uterus six years ago recorded on routine physical examination.
The nodule has slowly increased in size and now appears to be about twice the size it was when first discovered. By ultrasound scan it is solid
and circumscribed. She remains asymptomatic. Which of the following neoplasms is she most likely to have?

a. Adenocarcinoma b. Leiomyosarcoma c. Hemangioma d. Leiomyoma e. Metastasis

D) CORRECT. The slow growth of the nodule, the circumscribed nature of the nodule, and the continuing lack of symptoms suggests a benign
course. Leiomyomas of the uterus are quite common (up to 50% of women have at least one).

24. A 15-year-old boy has felt lumps in his right neck for the past 5 months. On physical examination there is painless lymphadenopathy in the
right cervical region. One of the lymph nodes is biopsied and on microscopic examination shows effacement of the nodal architecture by many
lymphocytes that are large, with clumped chromatin and occasional mitoses. The characterization of this population of lymphocytes as a neoplasm
is best accomplished by which of the following methods?

a. Immunohistochemical stain for leukocyte common antigen b. Gene rearrangement studies demonstrating clonality
c. Flow cytometry indicating high S-phase d. Differential white blood count showing a lymphocytosis
e. Light microscopy demonstrating nodal fibrosis

(B) CORRECT. Clonality is a key characteristic of neoplastic cellular proliferations that distinguishes them from reactive proliferations (such as
inflammation).

25. A previously healthy 42-year-old man has a skin nodule on his right hand that has become larger and darker with more irregular outlines over
the past 3 months. On physical examination this lesion is 1.2 cm diameter, darkly pigmented, and a slightly raised nodule on the dorsum of his
right hand. No other skin lesions are noted. Three nontender enlarged lymph nodes are palpable in the right axilla. The lesion is excised and
microscopic examination shows a neoplasm composed of darkly pigmented polygonal and spindle cells. Which of the following risk factors is most
important for development of this neoplasm?

a. Cigarette smoking b. Allergy to latex gloves c. Inheritance of a faulty RB gene

d. Prior job-related handling of asbestos e. Chronic exposure to ultraviolet radiation

(E) CORRECT. Worldwide, more and more skin cancers, including melanoma, are occurring because of sun exposure. The UV light damages the
skin and damages cellular DNA, leading to mutations that escape cellular repair mechanisms. Depletion of the earth's protective upper atmospheric
ozone layer has not helped, either. The ABC's of malignant melanoma: Asymmetrical shape, irregular Border, abnormal Color.

26. A 27-year-old woman in excellent health has a routine health maintenance examination. A 2 cm firm, rounded mass is palpable beneath the
skin of the left forearm. She has no difficulty using the arm and there is no associated pain with the mass, either in movement or on palpation. The
overlying skin appears normal. The mass does not change in size over the next year. Which of the following neoplasms is she most likely to have?

a. Metastatic carcinoma b. Melanoma c. Rhabdomyosarcoma d. Lipoma e. Leiomyoma

(D) CORRECT. The small size of the lesion, the relatively young age of the patient, and the lack of other findings suggests a benign process.
Lipoma is the most common soft tissue neoplasm. Most of them never reach a size sufficient to produce problems.

27. A 41-year-old woman has noted a foul-smelling vaginal discharge for 3 weeks. On physical examination there is an exophytic 3 cm mass
involving the ectocervix. Pap smear testing is performed; she has never had a previous Pap smear. Cytologic changes are present consistent with
squamous cell carcinoma. She is found to have a positive serologic test for syphilis. Her serum glucose is 157 mg/dL. She has been a commercial
sex worker in the past. Which of the following is the most likely risk factor for her cervical carcinoma?

a. Human papillomavirus infection b. Diabetes mellitus, type II c. Heavy cigarette smoking

d. Pelvic inflammatory disease e. Previous cancer chemotherapy

(A) CORRECT. HPV infection, a sexually transmitted disease (STD), is highly associated with cervical dysplasias and malignancies, particularly
high risk subtypes 16 and 18 that are now covered by the HPV vaccine. Syphilis is not a risk for epithelial dysplasias or carcinomas, but if one STD
is present, others can be present as well.

28. A 62-year-old man with an 80 pack year history of smoking experiences an episode of hemoptysis. On physical examination he has puffiness
as well as plethora of the face, pedal edema, bruises of the skin, and a blood pressure of 165/100 mm Hg. A chest radiograph reveals a 5 cm right
upper lobe lung mass. A fine needle aspirate of this mass yields cells consistent with small cell anaplastic lung carcinoma. A bone scan shows no
metastases. Immunohistochemical staining of the tumor cells is likely to be positive for which of the following hormones?

a. Parathormone related peptide b. Erythropoietin c. ACTH d. Insulin e. Gastrin

(C) CORRECT. He has findings of Cushing syndrome from ectopic ACTH production by the lung tumor, a form of paraneoplastic syndrome
common to small cell carcinomas of the lung, which have neuroendocrine derivation.

29. A 45-year-old woman has noted a lump on her left shoulder that has enlarged over the past 4 months. On physical examination there is a
palpable non-tender supraclavicular lymph node. A biopsy of the node is performed and on microscopic examination there is a metastatic
neoplasm. Which of the following is the most likely primary for this neoplasm?

a. Cerebral glioma b. Adenocarcinoma of the stomach c. Fibroadenoma of the breast

d. Liposarcoma of the retroperitoneum e. Laryngeal papilloma

(B) CORRECT. Lymph node metastases are typical of spread from carcinomas. The first stop along the way is regional nodes, but spread to more
distant lymphatic sites is possible. The right supraclavicular node receives drainage from rmid-section of the chest, esophagus, and lungs.
Described here is classic 'Virchow node' that involves left supraclavicular nodal metastasis from drainage via the thoracic duct, the abdomen, and
thorax.

30. A 59-year-old man has had fatigue for the past year. The only abnormal physical examination finding is a positive stool guaiac test. Laboratory
studies show a CBC with Hgb 10.0 g/dL, Hct 29.8&, MCV 73 fL, platelet count 300,000/microliter, and WBC count 8700/microliter. He is found on
colonoscopy to have a 4 cm mass lesion arising on the mucosal surface of the transverse colon. An abdominal CT scan shows hepatic masses.
He receives therapy with cetuximab directed at vascular endothelial growth factor (VEGF). Which of the following cell signaling pathways is most
affected by this therapy?

a. Hedgehog b. Notch c. JAK/STAT d. TGF-beta e. WNT

(B) CORRECT. Cancers must elaborate growth factors in order to produce an environment for continued growth. VEGF promotes angiogenesis
that will keep the neoplasm supplied with blood. VEGF increases the expression of ligands that active the Notch signaling pathway. Biotherapies
with monoclonal antibodies can specifically target protein components of cancers.

31. Columnar epithelial cells from the colonic mucosa are studied to identify abnormalities in cell signaling pathways. Abnormal epithelial cells from
colonic adenocarcinoma are shown to have a mutation that blocks hydrolysis of GTP-bound active RAS. Normal columnar cells have active RAS
protein that undergoes hydrolysis to the inactive GDP-bound form. Which of the following signaling pathways is most likely abnormally stimulated
in the carcinoma cells?

a. ADP b. BCR-ABL c. Cyclic AMP d. Cyclin D1 e. MAP kinase

(E) CORRECT. The mechanism described is that of RAS oncogene activation in which the active RAS is permanently turned on and through the
MAP kinase pathway activates transcription that drives abnormal, uncontrolled cellular proliferation that leads to neoplasia. Many carcinomas, and
adenocardinomas in particular, have RAS mutations.

32. A 52-year-old woman feels a lump in her right breast. On physical examination there is a 3 cm right breast mass fixed to the chest wall. This
mass is biopsied and on microscopic examination shows nests of cells with marked hyperchromatism and pleomorphism. These cells are estrogen
receptor positive. Flow cytometry is performed. Compared with surrounding non-neoplastic stromal cells, the neoplastic cells are more likely to be
in which of the following phases of the cell cycle?

a. G0 b. G1 c. S d.G2 e. M

(C) CORRECT. A high S-phase, as well as aneuploidy, are features often seen in cancers. The hyperchromatism typical for malignant cells
indicates active DNA synthesis. The estrogen receptor positivity suggests that this breast cancer will respond to hormonal therapy with letrozole
or tamoxifen.

33. A 73-year-old man has an episode of hematemesis. Upper GI endoscopy reveals an irregular 4 cm gastric antral ulceration. Biopsies are
performed and microscopically reveal crowded irregular gland-like collections of cells with hyperchromatism and pleomorphism. Molecular analysis
shows DNA hypermethylation of the CDKN2 complex. Through which of the following mechanisms has this abnormal gene expression most likely
occurred?

a. Amplification b. Epigenetic alteration c. Growth factor binding d. Point mutation e. Reduced miRNA expression

(B) CORRECT. Epigenetic changes are common in cancers, and gastric adenocarcinoma is described here. Though the DNA may not be altered,
methylation can occur to silence DNA expression. If selective hypermethylation of a DNA sequence encoding a tumor suppressor occurred, then
the result would be similar to loss of the tumor suppressor gene itself. Genomic imprinting works the same way.

34. In an experiment, it is observed that chronic, increased exposure to ionizing radiation results in damage to cellular DNA. As a consequence, a
protein is now absent that would arrest the cell in the G1 phase of the cell cycle. Subsequent to this, the cell is transformed to acquire the property
of unregulated growth. The absent protein is most likely the product of which of the following genes?

a. RAS b. TP53 c. MYC d. ABL e. BCL-2

(B) CORRECT. Abnormal TP53 protein has been identified in many carcinomas. This loss of normal wild type TP53 with tumor suppression leads
to loss of tumor suppression driving development of carcinomas.

35. A 50-year-old woman notes a lump in her breast. Her physician's assistant palpates a 2 cm firm mass in her left breast. A fine needle aspiration
biopsy is performed, and on microscopic examination a carcinoma is present. Molecular analysis shows HER2 positivity but estrogen receptor
negativity in these malignant cells. Through which of the following mechanisms has this abnormal expression most likely occurred?

a. Amplification b. Epigenetic alteration c. Growth factor binding d. Point mutation e. Reduced miRNA expression
(A) CORRECT. Amplification of gene expression typically occurs when there is reduplication of DNA sequences, often with hundreds of copies,
greatly increasing the amount of protein produced, which drives cellular proliferation. The mutation in HER2 results in amplification of the epithelial
growth factor receptor, as identified by presence of multiple copies by FISH analysis.

36. An epidemiologic study is performed to find risk factors for development of malignant neoplasms. A statistical analysis of pre-existing medical
conditions is done. Some pre-existing chronic medical conditions are observed to precede development of malignant neoplasms, while others do
not. Which of the following conditions is most likely to be statistically related to development of a malignancy?

a. Essential hypertension b. Coronary artery disease c. Chronic bronchitis d. Ulcerative colitis e. Uterine leiomyomas

(D) CORRECT. Adenocarcinoma of the colon is more frequent in persons with chronic ulcerative colitis, an inflammatory bowel disease that leads
to proliferative changes in which mutations may occur that contribute to colonic carcinogenesis.

37. A 35-year-old man has noted several 1 to 2 cm reddish purple, nodular lesions present on the skin of his right arm which have increased in
size and number over the past 3 months. The lesions do not itch and are not painful. He has had a watery diarrhea for the past month. On physical
examination he has generalized lymphadenopathy and oral thrush. Which of the following infections is most likely to be related to the appearance
of these skin lesions?

a. Candida albicans b. Human herpesvirus 8 c. Mycobacterium tuberculosis d. Pseudomonas aeruginosa

e. Pneumocystis jiroveci

(B) CORRECT. These plaque-like reddish lesions are characteristic for Kaposi sarcoma. HHV8 (KSHV) is the agent that promotes angiogenesis
from which the KS arises in persons with HIV infection. This is an example of viral oncogenesis.

38. A 66-year-old woman has noted increasing abdominal girth for 3 months. On examination there is an abdominal fluid wave. Paracentesis yields
cloudy fluid that cytologically contains clusters of malignant cells. An abdominal CT scan shows bilateral cystic and solid pelvic masses and multiple
peritoneal nodules. She is treated with chemotherapy with an initial response, but a year later there is still residual tumor. Which of the following
parameters of the neoplastic cells best predicts her diminished chemotherapy response?

a. Doubling time b. Extent of apoptosis c. Gene amplification d. Growth fraction e. Telomerase expression

(D) CORRECT. The proportion of cancer cells that are actively proliferating will predict response to chemotherapy. Cells not actively proliferating
are generally unresponsive to chemotherapeutic agents. As cancers increase in size, more cancer cells exit the replicative pool. During the course
of chemotherapy, the cells in replication are selectively killed, leaving behind the cells out of the pool that can continue on. If one were to completely
surgically excise the mass, then that would solve this issue, but even if the mass cannot be removed, then at least one can debulk it, or use
radiation therapy to kill more cells. Chemotherapy protocols can be designed to include more agents, thereby reducing cancer cell resistance, or
by giving cycles of chemotherapy that get more cancer cells into the replicative pool. Ovarian carcinomas often seed to the peritoneal cavity.

39. A 49-year-old man complains of pain in his left thigh for 3 months. On physical examination his thigh is increased in size, compared to the right.
A plain film radiograph reveals the presence of a 15 cm solid mass that does not appear to arise from bone, but it does have infiltrative margins.
A biopsy of this mass is taken, and on microscopic examination the mass is composed of highly pleomorphic spindle cells. Which of the following
immunohistochemical markers is most likely to be demonstrated in the cells of this mass?

a. Cytokeratin b. Factor VIII c. Alpha fetoprotein d. Lambda light chain e. Vimentin

(E) CORRECT. The location and size and histologic characteristics suggest a sarcoma. Vimentin is an intermediate filament often found in
neoplasms of mesenchymal (connective tissue) origin.

40. A clinical study is performed with patients who had a diagnosis of breast cancer. Characteristics of the grade, stage, molecular biology, and
histologic type are analyzed. Of the following characteristics, which is most likely to be associated with the best prognosis for these patients?

a. Increased laminin receptor expression b. Increased cathepsin expression c. Increased aerobic glycolysis
d. Amplification of HER2 e. Decreased cell cycle S phase

(E) CORRECT. An increased S (DNA synthetic) phase is a feature of malignancy, indicating loss of growth control with increased cell proliferation.

41. A 66-year-old man has noted darker urine for the past 2 weeks. A urinalysis shows hematuria. Cystoscopy is performed and there is a 3 cm
mass in the dome of the bladder. Biopsies of the mass are taken and on microscopic examination show a urothelial carcinoma. Cells of this
neoplasm demonstrate a single mutation causing cellular inability to hydrolyze GTP, thus resulting in cellular transformation. Which of the following
oncogenes is most likely implicated in this case?

a. ABL b. ERBB2 c. SIS d. RAS e. N-MYC

(D) CORRECT. Through mutation the RAS gene can be turned on, typically by a point mutation, to make it an oncogene. Such a mutation can
occur in a wide variety of carcinomas.

42. A 44-year-old woman who has had multiple sexual partners for the past 30 years has an abnormal Pap smear with cytologic changes suggesting
human papillomavirus (HPV) infection. Without treatment, she is most likely to develop which of the following lesions?

a. Squamous cell carcinoma b. Non-Hodgkin's lymphoma c. Kaposi sarcoma d. Adenocarcinoma

e. Leiomyoma

(A) CORRECT. HPV infection leads to squamous epithelial dysplasias and carcinomas involving the uterine cervix. HPV is a sexually transmitted
infection. HPV produces an E7 protein that binds to the RB gene product that normally suppresses cell prolferation. It produces an E6 protein that
binds to the p53 protein to degrade it, so that the cell cycle is not stopped. Neoplasia can arise in the setting of abnormal cell proliferation.
43. In an epidemiologic study, 'fallout' from nuclear bomb testing and from nuclear power plant disasters is observed to have released radioactive
isotopes into the environment. One of these isotopes is found to be strontium-90. It is observed that the strontium-90 in soils goes into the food
chain and eventually contaminates milk products. This contamination is most likely to increase the risk for which of the following neoplasms?

a. Kaposi sarcoma of skin b. Small cell anaplastic carcinoma of lung c. Osteosarcoma of bone
d. Nasopharyngeal carcinoma e. Endometrial carcinoma

(C) CORRECT. The fallout includes strontium-90, an isotope that can be taken up into bone just like calcium, but promotes neoplastic
transformation. Science fiction often serves as a vehicle for social commentary, and the creator of 'Star Trek' had an alien remark, 'They irradiated
their own planet?' in disbelief humans would be so stupid to pollute their own planet.

44. A clinical trial of a new chemotherapy protocol is performed involving patients with lung carcinoma. It is observed that a response occurs that
leads to neoplastic cell DNA strand breakage and cell death. The primary carcinomas are initially observed to decrease in size following therapy.
However, after 3 months, the carcinoma is no longer regressing with this therapy. Altered expression of which of the following by the neoplastic
cells has most likely resulted in this reduced response?

a. Vimentin b. Leukocyte common antigen c. Laminin receptor d. Actin e. DNA topoisomerase II

(E) CORRECT. This topo II is a nuclear enzyme which untangles DNA at the end of mitosis. The drugs that target topoisomerase II freeze the
enzyme as it is cutting DNA strands. This leads to DNA strand breakage and cell death. Resistant cells in culture show alterations in the
topoisomerase II protein.

45. In an experiment, biologic characteristics of neoplastic and non-neoplastic cells are analyzed in culture. It is observed that cell division in cells
derived from malignant neoplasms, but not in normal cells, is aided by the presence of an enzyme which repairs progressive chromosomal
shortening. The lack of chromosomal shortening allows the malignant cells to undergo many more divisions than the normal cells. Which of the
following enzymes is most likely to have this effect?

a. Reverse transcriptase b. DNA polymerase c. Telomerase d. Protein kinase e. Topoisomerase

(C) CORRECT. The telomerase synthesizes telomeric chromosomal ends. The so-called 'immortal' neoplastic cell lines may result from the
presence of this enzyme. Interfering with it may promise a new cancer therapy. Of normal human cells, stem cells have significant telomerase
activity, but differentiated somatic cells do not.

46. A 62-year-old man has complained of pain on urination for the past week. He is afebrile. On cystoscopy, a slightly erythematous 1 cm diameter
area is seen on the bladder mucosa. This area is biopsied and on microscopic examination shows cells with marked hyperchromatism and
increased nuclear/cytoplasmic ratio involving the full thickness of the epithelium. However, these changes are confined to the epithelium above
the basement membrane. Which of the following terms best describes these biopsy findings?

a. Metaplasia b. Minimal dysplasia c. Microinvasion d. Hyperplasia e. Carcinoma in situ

(E) CORRECT. Malignancy confined to the epithelium is CIS, and such lesions when excised have essentially a 100% cure rate. Unfortunately,
urothelial carcinomas have a propensity to be multifocal.

47. A 32-year-old woman has noted dull pelvic pain for the last two months. On physical examination there is a mass palpated in the right lower
quadrant. An abdominal ultrasound reveals an 8 cm mass involving the right ovary. The mass is surgically excised. On gross inspection, the
surface of the mass is smooth and is not adherent to surrounding pelvic structure. On sectioning it is cystic and filled with hair. On microscopic
examination there is squamous epithelium, tall columnar glandular epithelium, cartilage, and fibrous connective tissue. Which of the following
neoplasms is she most likely to have?

a. Choristoma b. Hamartoma c. Myxoma d. Teratoma e. Mesothelioma

(D) CORRECT. 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 are all well differentiated, the neoplasm is 'mature' (benign).

48. A 54-year-old woman has an episode of coughing with blood-streaked sputum. On physical examination she appears cachectic. A chest x-ray
shows a mass lesion with indistinct borders in the right lung. A transbronchial biopsy is done and on microscopic examination shows small cell
anaplastic lung carcinoma (SCLC). She is treated with a multidrug chemotherapy regimen and has a partial response. However, metastatic disease
develops eight months later. A second chemotherapy protocol is tried, but no response is noted. Which of the following neoplastic cell
characteristics is the most likely reason for failure of the second protocol to elicit a response?

a. Abnormal p53 protein b. Viral infection c. RAS oncogene activation d. P-glycoprotein expression e. Second primary lung cancer

(D) CORRECT. The increase in P-glycoprotein allows the cells to pump out any toxin, including any chemotherapy agent.

49. A previously healthy 67-year-old man has been feeling tired for 5 months. He goes to his physician, who performs a complete physical
examination, including stool guaiac, which is positive. A colonoscopy is performed, and a large, sessile 4.5 cm mass with surface ulceration is
found in the cecum. A biopsy of this mass microscopically shows irregular glands with crowded, tall columnar cells having marked nuclear
hyperchromatism. Which of the following gene alterations is he most likely to have?

a. Inherited mutant APC gene b. Chromosome translocation with BCR gene c. Acquired TP53 gene mutation
d. Abnormal germline mismatch repair gene e. EBV induction of LMP-1 gene

(C) CORRECT. He has an adenocarcinoma of the colon. At his age, a sporadic colon cancer is more likely, and inherited APC and HNPCC are
very unlikely. It takes many years for multiple sporadic mutations to have occurred that contribute to development of most malignancies. p53
mutations are found in many carcinomas.
50. An 8-year-old boy has complained of difficulty swallowing for the past month. On physical examination he has a palpable, firm mass in the right
neck. A head CT scan reveals a 7 cm solid soft tissue mass lateral to the esophagus on the right. A biopsy of this mass demonstrates pleomorphic
spindle cells that are cytokeratin negative, CD45 negative, and vimentin positive. Which of the following neoplasms is he most likely to have?

a. Wilms tumor b. Rhabdomyosarcoma c. Neuroblastoma d. Ewing sarcoma e. Malignant lymphoma

(E) CORRECT. This is one of the more common childhood tumors of soft tissue. Sarcomas tend to be vimentin positive, while carcinomas are
cytokeratin positive and lymphomas CD45 positive. Overall, childhood malignancies are not frequent, compared with adults, but sarcomas make
up a significant number of those that do occur.

51. A 53-year-old woman feels a lump in her right breast. Her nurse practitioner palpates an irregular 3 cm mass that is not movable because it
appears fixed to the overlying skin, which is retracted. A mastectomy is performed and the pathologist on sectioning the breast finds a 3 x 3.5 cm
ovoid mass that does not have discrete borders, but appears to infiltrate into the surrounding fibrofatty breast stroma. The mass is firm, white, and
has a fibrous consistency. Which of the following features is most likely demonstrated by the gross appearance of this mass?

a. Anaplasia b. Aplasia c. Desmoplasia d. Dysplasia e. Metaplasia

(C) CORRECT. Neoplasms, and malignant neoplasms in particular, can form a fibrous stroma that gives the tumor a characteristic firm or hard
feel on palpation. This connective tissue can fix the tumor to surrounding structures. An infiltrating ductal carcinoma of the breast will often have
this appearance.

52. An 81-year-old man has a routine physical examination and a stool sample is positive for occult blood. He undergoes colonoscopy and a 5 cm
sessile mass is present in the sigmoid colon. Biopsy of the mass yields a diagnosis of adenocarcinoma. A chest x-ray shows multiple 1 to 3 cm
nodules in both lungs. An alteration in which of the following molecular components in the neoplastic cells is most likely to explain the formation of
lung nodules?

a. Vimentin b. Leukocyte common antigen c. Beta-catenin d. Telomerase e. DNA topoisomerase II

(C) CORRECT. Beta-catenin can locate to the nucleus to drive cellular proliferation, Mutations of the beta-catenin gene, or in genes such as APC
that produce proteins that downregulate beta-catenin, will favor carcinogenesis. In addition, there is loss of normal cell surface e-cadherin
expression that maintains attachement of cells to each other. Loss of contact inhibition allows neoplastic cells to invade and metastasize.

53. A healthy 22-year-old woman undergoes a routine physical examination. A discrete, firm, rubbery, movable mass is found in the left breast.
She has no axillary lymphadenopathy. The skin overlying the breast and the nipple appear normal. Which of the following neoplasms is most likely
to be present in this woman?

a. Lipoma b. Intraductal carcinoma c.Malignant lymphoma d. Fibroadenoma e. Leiomyoma

(D) CORRECT. The description is that of a benign neoplasm. Fibroadenoma is the most common benign neoplasm of the breast. As the name
implies, there are glandular and stromal elements in this neoplasm. Benign neoplasms are slow growing, discrete masses that do not invade or
metastasize.

54. An epidemiologic study is performed involving patients of East Asian ancestry with long-standing Epstein-Barr virus (EBV) infection. It is
observed that these patients have an increased risk for development of malignant neoplasms in adulthood. Which of the following neoplasms is
most likely to be found in these patients?

a. Kaposi sarcoma of skin b. Small cell anaplastic carcinoma of lung c. Osteosarcoma of bone d. Nasopharyngeal carcinoma
e. Endometrial carcinoma

(D) CORRECT. EBV infection is most often linked to nasopharyngeal carcinoma in Asia and to Burkitt lymphoma in Africa.

55. A clinical study is performed involving children who have developed skin cancers, including squamous cell carcinomas and basal cell
carcinomas. Molecular analysis of their cancer cells shows defective DNA repair from loss of nucleotide excision repair gene expression. Which
of the following genes is most likely mutated in these chilren?

a. APC b. BRCA2 c. MSH2 d. NF1 e. XPA

(E) CORRECT. There are multiple xeroderma pigmentosa (XP) genes, from XPA to XPG and XPV. Sunlight exposure with ultraviolet radiation
induces pyrimidine dimer formation that is ordinarily countered through the action of excision repair gene products. Mutation greatly increases the
risk for skin cancer formation, and affected persons must avoid sunlight.

56. A 29-year-old woman feels a nodule in her neck. On examination there is a firm 2 cm mass in the right lobe of her thyroid. A fine needle
aspiration shows cells consistent with papillary carcinoma. 2 years ago she had a lobular carcinoma excised from her left breast. Her 31-year-old
sister was recently diagnosed with endometrial carcinoma. A 34-year-old cousin has had colon cancer. Over 3 generations, 6 of 24 close relatives
have had a malignancy, most diagnosed before age 35. Which of the following most likely explains the increased risk for cancer in these people?

a. Autosomal dominant cancer syndrome b. Defective DNA repair syndrome c. Germline mosaicism
d. Multifactorial inheritance e. Teratogen exposure

(D) CORRECT. Cancer that runs in families often does not have a clearly defined pattern of inheritance and does not have a specific genetic
marker. Familial cancers should be suspected when cancers occur at a younger age, multiple family members are involved, and multiple sites are
involved. The sites of involvement (breast, colon, thyroid, kidney, ovary) are similar to those for sporadic cancers.
57. A study of malignant neoplasms reveals that some of them have a greater potential for invasion and metastases. Analysis of the cells of cancers
that have metastasized reveals a mutation which results in decreased cell surface expression of E-cadherin. Which of the following genes is most
likely mutated to produce these findings?
a. Beta-catenin b. BRCA-2 c. Cyclin D d. NF-1 e. RAS

(A) CORRECT. Beta-catenin binds to the intracellular portion of cadherins, which anchor cells together, and the loss of this function results in less
cell adhesiveness that favors tumor cell infiltration and metastases. Beta-catenin also binds to a nuclear transcription factor that increases cell
proliferation, and loss of normal beta-catenin function leads to cell proliferation.

58. A 66-year-old woman has a chronic cough for 3 months. A chest radiograph shows a left lung 4 cm peripheral mass. Fine needle aspiration
biopsy is performed and cytologic examination shows nonsmall cell carcinoma (NSCLC). Molecular analysis of these cells shows upregulation of
a pathway form suppression of anti-tumor lymphocytes. Biotherapy with monoclonal antibody to which of the following is most likely to be effective
in treating this woman's malignancy?

a. BRAF b. MYC c. PD-1 d. RAS e. TP53

(C) CORRECT. The programmed cell death-1 (PD-1) pathway can enable carcinomas to suppress lymphocyte function; antibody blockade of PD-
1 with its ligand PD-L1 have shown effectiveness in treating in NSCLC.

59. A 59-year-old woman has a screening mammogram that identifies a suspicious 3 cm mass in her right breast. Fine needle aspiration biopsy is
performed and malignant cells are present. Excisional biopsy is performed and molecular analysis of the malignant cells shows that they are
estrogen receptor positive. In addition to anti-estrogen therapy, a biotherapy with monoclonal antibody targeting the G1 phase of the cell cycle
involves which of the following targets and may be useful in treating this woman?

a. CDK4 b. BCR-ABL c. HER2 d. TP53 e. WNT

(A) CORRECT. Cyclin-dependent kinases (CDKs) promote transition through the cell cycle, and may neoplastic are dependent upon the G1 phase
of the cell cycle. Many events impact neoplastic cell proliferation via their influence on CDK4 or CDK6 complexes in the G1 phase of the cell cycle.
Multiple genes encode for the CDKs, part of a family of serine/threonine protein kinases. ER+ breast cancers respond to estrogen signaling for
proliferation and survival. ER blockers diminish tumor cell viability and lead to cell cycle arrest in the G1 phase, but not all breast cancers respond
to anti-hormonal therapy.

60. In an experiment carcinoma cells are observed to evade immune destruction by lymphocytes which have been stimulated to proliferate. Which
of the following mechanisms is most likely to provide the tumor cells with the capacity to evade immune destruction by lymphocytes?

a. Downregulation of MHC Class I expression b. Expression of oncofetal antigens c. Formation of blocking antibodies
d. Inhibition of regulatory T cells (Tregs) e. Upregulation of caspase production

(A) CORRECT. Tumor cells may not express normal levels of MHC class I molecules to reduce attack by cytotoxic T cells. However NK cells may
attack tumor cells expressing ligands for NK cell activating receptors.