Neoplasia

Question 1

1. A clinician is reviewing the pathology report of
   a patient with adenocarcinoma of the colon. Of the
   following, which helps determine the grade of the
   tumor?
   A. Number of positive lymph nodes
   B. Size of the tumor
   C. Metastatic spread to another organ
   D. Depth of invasion of wall of colon
   E. Number of mitotic figures per high-power field

Answer 1

1. Correct: Number of mitotic figures per high power
   field (E)
   The grade of a tumor is its degree of histologic differentiation (e.g., well, moderate, or poorly differentiated) and represents a subjective determination by the pathologist as to how closely the tumor resembles the tissue type from which it arose (e.g., in colonic adenocarcinoma, whether the tumor
   cells appear like normal glandular epithelium). In
   determining the grade of the tumor, the histologic
   appearance of the tumor is important, including the
   number of mitotic figures per high-power field (E).
   The other features listed are used to determine the
   stage of a neoplasm (A-D). The exact determination
   of stage depends on the tumor type and characteristics
   specific to that tumor.

Question 2

2. A 60-year-old male presents to his family physician
   because of complaints of blood in his stool and
   intermittent constipation. Fecal occult blood testing
   is positive. A colonoscopy is performed, revealing
   a large adenocarcinoma of the sigmoid colon.
   As the tumor was removed at a teaching hospital, a
   researcher tests the tumor and identifies a mutation
   of ras. Of the following, what was one mechanism by
   which the tumor developed?
   A. Inhibition of apoptosis
   B. Abnormal GTPase activity
   C. Abnormal tyrosine kinase activity
   D. Up-regulation of cytokine receptor
   E. Down-regulation of cytokine receptor

Answer 2

2. Correct: Abnormal GTPase activity (B)
   The ras oncogene is associated with colonic adenocarcinoma, and the gene product of the ras gene is a GTPase. For (A, C-E), see previous information.

Question 3

3. The parents of a 17-year-old female bring her
   to the emergency room after she had a brief seizure
   at home from which she recovered. A CT scan is performed
   in the emergency room, identifying a cortical
   nodule in the left cerebral hemisphere. A CT scan of
   the body is also performed, identifying a 3.0 cm mass
   in the left kidney, which is subsequently biopsied
   and diagnosed as an angiomyolipoma. Of the following,
   which other tumor is this patient at increased
   risk for?
   A. Medulloblastoma
   B. Hepatic neuroblastoma
   C. Ewing sarcoma
   D. Cardiac rhabdomyoma
   E. Retinoblastoma

Answer 3

3. Correct: Cardiac rhabdomyoma (D)
   The cortical mass is a tuber, and, when combined
   with an angiomyolipoma in a young patient, the diagnosis
   is most likely tuberous sclerosis. The tumors associated with tuberous sclerosis also include cardiac rhabdomyomas (D). The other tumors listed are not commonly associated with tuberous sclerosis (A-C, E).

Question 4

4. A 63-year-old female is being evaluated by her
   family physician. Over the past 3 months she has
   developed a velvety hyperpigmentation of the skin
   of the posterior neck and bilateral axilla. She has lost
   15 lbs. since her last visit four months ago and has a
   body mass index of 23 kg/m2. Routine blood work is
   normal except for a hemoglobin level of 8.6 g/dL. Her
   HbA1c is 5.4%, and a plain chest radiograph is normal.
   What is the next step in the evaluation?
   A. Bone scan
   B. CT chest with contrast
   C. Skin biopsy
   D. Upper and lower endoscopy
   E. Bone marrow aspirate

Answer 4

4. Correct: Upper and lower endoscopy (D)
   The changes noted on physical examination are consistent with acanthosis nigricans. In the absence of
   obesity or diabetes, the presence of acanthosis nigricans
   in adult patients often indicates underlying malignancy, warranting the upper and lower endoscopy (D). Gastrointestinal malignancies, particularly gastric adenocarcinoma, are most commonly associated with acanthosis. The other choices (A-C, E) would not be as useful.

Question 5

5. A 46-year-old female presents to her family
   physician because she palpated a nodule in her left
   breast during a breast self-examination. She subsequently
   undergoes a partial mastectomy. The mass is
   examined by a pathologist who makes a diagnosis of
   invasive ductal carcinoma. Subsequent genetic testing
   reveals a mutation of the BRCA2 gene. Of the following,
   what is the location for this mutation?
   A. 17p
   B. 17q
   C. 13q
   D. 13p
   E. 18q
   F. 18p

Answer 5

5. Correct: 13q (C)
   The BRCA2 gene is located on the long arm of chromosome 13 (13q) (C). The BRCA1 gene is located on
   the long arm of chromosome 17 (17q) (B). The gene for the p53 protein, which is mutated in many types of cancer, is located on the short arm of chromosome 17 (17p) (A). 18q is the site of the DPC gene, which can be mutated in pancreatic carcinoma (E). For (D, F), see previous information.

Question 6

6. A 4-year-old boy is evaluated by his pediatrician
   for 1 week of intermittent hematuria. On examination
   he appears well developed and well nourished,
   except a right flank mass is palpable. A biopsy of the
   mass is performed, which reveals primitive looking
   small blue cells with glomeruloid and tubuloid
   structures. What is the diagnosis?
   A. Medulloblastoma
   B. Polycystic kidney disease
   C. Clear cell sarcoma
   D. Rhabdoid tumor
   E. Wilms tumor

Answer 6

6. Correct: Wilms tumor (E)
Wilms tumor (E), the most common renal malignancy
in children, usually presents with a palpable mass or hematuria. This tumor, most often caused by a mutation of the WT1 tumor suppressor gene on 11p13, is characterized histologically by a mixture of blastemal (small blue cell), stromal, and epithelial (primitive glomeruloid and tubuloid) cell types. The other choices are not correct (A-D).

Question 7

7. A 46-year-old male presents to his family physician
   with complaints of a headache. While being evaluated,
   he has a seizure and is subsequently taken to radiology
   for a CT scan, which identifies a mass in his corpus callosum.
   Subsequent biopsy determines the mass to be
   composed of malignant lymphocytes. Of the following,
   what other condition does this patient most likely have?
   A. Hepatitis C infection associated with cirrhosis of
   the liver
   B. Hashimoto’s thyroiditis
   C. HIV infection
   D. HSV encephalitis
   E. Remote head trauma

Answer 7

7. Correct: HIV infection (C)
   Of the listed conditions, primary lymphomas of
   the central nervous system in patients under the
   age of 70 are most commonly associated with HIV
   infection (C). Although Hashimoto’s thyroiditis and
   other autoimmune disorders are associated with
   lymphoma, the lymphoma they are most commonly
   associated with is mucosa-associated lymphoid tissue
   (or, MALTomas), of which the brain has none (B).
   Cirrhosis of the liver is a risk factor for hepatocellular
   carcinoma (A), and HSV encephalitis and remote
   head trauma are not commonly associated with an
   increased incidence of malignancy (D-E).

Question 8

8. A 31-year-old female has fecal blood identified
   during a physical examination. A colonoscopy reveals
   an ulcerated mass in her proximal rectum. In the past,
   she has had a ductal carcinoma of her left breast and
   a malignant thyroid tumor, both excised and treated.
   Of the following, what is the most likely mutation if
   she is diagnosed with Cowden’s syndrome?
   A. Mutation of the PTEN gene
   B. Mutation of the CDKN2 gene
   C. Mutation of RB gene
   D. Mutation of the WT gene
   E. Mutation of the TP53 gene

Answer 8

8. Correct: A
   Patients with Cowden’s syndrome develop colorectal,
   thyroid, and breast neoplasms. The underlying
   mutation is that of PTEN (A). Mutations of CDKN2 are
   associated with malignant melanoma (B), RB with
   retinoblastoma (C), WT with Wilms tumor (D), and
   TP53 with breast cancer, brain tumors, and leukemia
   (E).

Question 9

9. In the same family, four individuals are diagnosed
with malignant melanoma. Of the following,
which mutation is most likely?
A. Mutation of the RET gene
B. Mutation of the CDKN2 gene
C. Mutation of APC gene
D. Mutation of the WT gene
E. Mutation of the PTEN gene

Answer 9

9. Correct: B
   Familial malignant melanoma is associated with
   mutations of CDKN2 (p16) (B). Mutations of RET
   are associated with thyroid medullary carcinoma
   and pheochromocytomas (A), mutations of APC are
   associated with colonic adenocarcinoma (C), mutations
   of WT are associated with Wilms tumor (D), and mutations of the PTEN gene are associated with
   colonic adenocarcinoma, breast cancer, and thyroid
   cancer.

Question 10

10. A 35-year-old male presents to his family care
    physician because of balance problems. A CT scan
    of his head reveals a mass near the pontomedullary
    junction. The mass is excised and diagnosed as
    a schwannoma. Four years later, he presents with
    headaches and is found to have two meningiomas.
    Of the following, what is the most likely mutation
    that he possesses?
    A. Mutation of the PTEN
    B. Mutation of the CDKN2 gene
    C. Mutation of the NF2 gene
    D. Mutation of the WT
    E. Mutation of the TP53

Answer 10

10. Correct: C
    Multiple meningiomas and schwannomas are characteristic of neurofibromatosis type II, so the patient most likely has a mutation of the NF2 gene (C). Mutations
    of PTEN are associated with colonic adenocarcinoma
    and breast and thyroid tumors (A), mutations of CDKN2 are associated with familial melanoma (B), mutations of WT are associated with Wilms tumor (D), and mutations of TP53 are associated with a variety of tumors including breast cancer, soft tissue sarcomas, leukemia, and brain tumors (E).

Question 11

11. A 5-year-old male is brought to his pediatrician
    by his parents for an annual examination.
    Palpation of his abdomen reveals a mass, which is
    subsequently resected. The pathologist examining
    the mass identifies three components: blastemal,
    stromal, and epithelial. His sister had the same type
    of tumor. Of the following, what gene mutation do
    the siblings most likely have?
    A. Mutation of the RB gene
    B. Mutation of the CDKN2 gene
    C. Mutation of the VHL gene
    D. Mutation of the WT gene
    E. Mutation of the APC gene

Answer 11

11. Correct: D
    The tumor description fits that of a Wilms tumor.
    Wilms tumors are associated with mutations of the
    WT gene (D). Mutations of the RB gene are associated
    with retinoblastoma (A), mutations of the CDKN2
    gene are associated with familial melanoma (B),
    mutations of the VHL gene are associated with renal
    cell carcinoma (C), and mutations of the APC gene are
    associated with colonic adenocarcinoma.

Question 12

12. A 41-year-old female has had an invasive ductal
    carcinoma, a low grade astrocytoma, a leiomyosarcoma,
    and a rhabdomyosarcoma. She is diagnosed
    with a facial neoplasia syndrome. Of the following,
    which gene mutation is most likely present?
    A. Mutation of the MET gene
    B. Mutation of the CDKN2 gene
    C. Mutation of the ATM gene
    D. Mutation of the TP53 gene
    E. Mutation of the TSC1 gene

Answer 12

12. Correct: D
    The constellation of breast cancer, brain tumors, and
    soft tissue sarcomas is consistent with Li-Fraumeni’s
    syndrome, which is caused by a mutation of the TP53
    gene (D). Mutations of the MET gene are associated
    with papillary renal cell carcinoma (A), mutations of the CDKN2 gene are associated with malignant melanoma
    (B), mutations of the ATM gene are associated
    with leukemia and lymphoma (C), and mutations of
    the TSC1 gene are associated with tuberous sclerosis
    and a variety of tumors including renal cell carcinoma,
    angiomyolipomas, and astrocytomas.

Question 13

13. A 42-year-old male undergoes a colectomy.
    The pathologist identifies more than 100 polyps in
    the resected specimen as well as a focus of invasive
    adenocarcinoma. Of the following, what is the functional
    mechanism for the gene mutation causing his
    disease process?
    A. Decreased breakdown of β-catenin
    B. Increased breakdown of β-catenin
    C. Increased activity of β-catenin
    D. Decreased activity of β-catenin
    E. Lack of production of β-catenin

Answer 13

13. Correct: Decreased breakdown of β-catenin (A)
    This patient suffers from familial adenomatous polyposis,
    one of the genetic colon cancer syndromes. In this disorder, patients have a germline loss of function
    mutation in the APC tumor suppressor gene, which usually functions to break down β-catenin, a protein involved in the signal cascade of APC (A). The subsequent increased amount of β-catenin appears to prevent cell differentiation and apoptosis. (B-E) are incorrect, see previous information.