WGU D115 ADVANCED PATHOPHYSIOLOGY FOR THE APRN
COMPREHENSIVE EXAMINATION TEST BANK WITH VERIFIED ANSWERS AND DETAILED RATIONALES
150 Questions | 8 Sections | 25% Knowledge | 55% Application | 20% Analysis
Section 1: Cellular Adaptation, Injury, and Neoplasia
Questions 1-20
Q1: A 62-year-old man with a 40-pack-year smoking history presents with chronic cough and weight loss. A lung biopsy
reveals squamous cell carcinoma. Pathology notes show keratin pearls and intercellular bridges. The tumor cells have
undergone which of the following adaptive cellular changes before malignant transformation?
A. Metaplasia of bronchial epithelium from columnar to squamous [CORRECT]
B. Hyperplasia of existing squamous cells
C. Dysplasia of the alveolar type II pneumocytes
D. Hypertrophy of the bronchial smooth muscle
Correct Answer: A
Rationale: Chronic cigarette smoke irritation causes the normal ciliated columnar epithelium of the bronchi to undergo metaplasia to
squamous epithelium as an adaptive protective response. However, this metaplastic epithelium is more susceptible to further genetic
damage and can progress to dysplasia and then squamous cell carcinoma. Hyperplasia (B) is an increase in cell number, not the
primary change seen here. Dysplasia of alveolar cells (C) is not the pathway to squamous cell carcinoma. Bronchial smooth muscle
hypertrophy (D) is seen in asthma, not carcinogenesis.
Q2: A 45-year-old woman presents with increasing fatigue, pallor, and splenomegaly. Laboratory studies reveal a
hemoglobin of 8.2 g/dL, WBC count of 3,200/mcL, and platelet count of 95,000/mcL. A bone marrow biopsy demonstrates
hypercellularity with markedly increased myeloid precursors and the presence of the Philadelphia chromosome t(9;22).
Which of the following best describes the initial cellular adaptation that leads to this condition?
A. Apoptosis of megakaryocytes leading to thrombocytopenia
B. Unregulated proliferation of a single hematopoietic stem cell clone [CORRECT]
C. Metaplasia of bone marrow stromal cells
D. Hypertrophy of erythroid precursors
Correct Answer: B
Rationale: Chronic myeloid leukemia (CML) is caused by the BCR-ABL fusion protein resulting from the Philadelphia chromosome
t(9;22). This oncogene drives unregulated proliferation of a single pluripotent hematopoietic stem cell clone, leading to overproduction
of myeloid cells. The pancytopenia described is more consistent with CML in blast crisis or with myelofibrosis. The key concept is
clonal proliferation driven by an acquired genetic mutation, not metaplasia (C) or hypertrophy (D).
Q3: A patient with a p53 gene mutation is being evaluated for cancer risk. The p53 protein normally functions to halt the
cell cycle at which checkpoint to allow DNA repair or trigger apoptosis if repair fails?
A. G1/S checkpoint [CORRECT]
B. G2/M checkpoint
C. M checkpoint (spindle assembly)
D. Restriction point in early G1
Correct Answer: A
Rationale: The p53 tumor suppressor protein acts primarily at the G1/S checkpoint. When DNA damage is detected, p53 activates p21
which inhibits cyclin-dependent kinases, arresting the cell at G1/S to allow DNA repair. If damage is too extensive, p53 triggers
apoptosis via Bax activation. While p53 can also influence the G2/M checkpoint (B), its primary and most critical role is at the G1/S
transition. The M checkpoint (C) is monitored by the anaphase-promoting complex. The restriction point (D) is regulated by Rb, not
p53.
1
,Q4: A 28-year-old nulligravid woman presents with a 3-month history of irregular vaginal bleeding and pelvic pain. An
ultrasound reveals a 6-cm uterine mass. Histopathology after hysterectomy shows spiral arterioles with fibrinoid necrosis,
trophoblastic proliferation, and abnormal villi. Karyotype analysis of the tissue reveals a 46,XX genotype, but all
chromosomes are of paternal origin. What is the most likely diagnosis?
A. Complete hydatidiform mole [CORRECT]
B. Partial hydatidiform mole
C. Choriocarcinoma
D. Placenta accreta
Correct Answer: A
Rationale: A complete hydatidiform mole is characterized by villous swelling (hydropic degeneration), trophoblastic hyperplasia, and
absence of fetal tissue. The karyotype is typically 46,XX with all chromosomes of paternal origin (androgenesis) resulting from
fertilization of an empty egg by a single sperm that duplicates. A partial mole (B) is triploid (69,XXY) with some fetal tissue present.
Choriocarcinoma (C) is a malignant gestational trophoblastic neoplasm with invasive trophoblastic proliferation but no villi. Placenta
accreta (D) involves abnormal placental attachment, not trophoblastic proliferation.
Q5: A researcher is studying the Bcl-2 family of proteins in the context of follicular lymphoma, which is characterized by
the t(14;18) translocation. How does overexpression of Bcl-2 contribute to lymphomagenesis?
A. By increasing the rate of cell proliferation through cyclin D upregulation
B. By inhibiting apoptosis, allowing survival of cells with DNA damage [CORRECT]
C. By promoting angiogenesis through VEGF secretion
D. By disabling DNA mismatch repair mechanisms
Correct Answer: B
Rationale: Bcl-2 is an anti-apoptotic protein that resides on the outer mitochondrial membrane and prevents cytochrome c release,
thereby inhibiting the intrinsic apoptotic pathway. The t(14;18) translocation places the BCL2 gene under the control of the
immunoglobulin heavy chain enhancer, causing constitutive overexpression. This does not increase proliferation rate (A), promote
angiogenesis (C), or disable DNA repair (D). Instead, it allows cells with oncogenic mutations to survive when they would normally
undergo programmed cell death.
Q6: A 55-year-old man with chronic alcohol use presents with ascites, spider angiomas, and palmar erythema. A liver
biopsy demonstrates bridging fibrosis and regenerative nodules. Which of the following best describes the cellular
adaptation occurring in the hepatocytes surrounding the regenerative nodules?
A. Metaplasia of hepatocytes to biliary epithelium
B. Hyperplasia of remaining hepatocytes to restore liver mass [CORRECT]
C. Hypertrophy of hepatocytes with subsequent dysplastic changes
D. Apoptosis mediated by TGF-beta from stellate cells
Correct Answer: B
Rationale: The liver has remarkable regenerative capacity. In cirrhosis, hepatocytes that survive injury undergo compensatory
hyperplasia (increased cell division) to restore functional liver mass, forming regenerative nodules. While individual hepatocytes may
also hypertrophy, the dominant adaptive response is hyperplastic regeneration. Metaplasia (A) does not occur in hepatocytes.
Dysplasia (C) is a pre-malignant change not characteristic of the regenerative process itself. TGF-beta-mediated apoptosis (D) does
occur but is not the adaptive response of the surviving hepatocytes.
Q7: A 70-year-old woman presents with a painless breast lump detected on screening mammography. Core needle biopsy
reveals infiltrating ductal carcinoma. Immunohistochemistry is positive for HER2/neu (ERBB2) amplification. The HER2
receptor belongs to which family of cell surface receptors?
A. G-protein coupled receptors
B. Ion channel receptors
C. Receptor tyrosine kinases [CORRECT]
D. Intracellular steroid hormone receptors
2
, Correct Answer: C
Rationale: HER2/neu (ERBB2) is a member of the epidermal growth factor receptor (EGFR/ERBB) family, which are receptor
tyrosine kinases (RTKs). These receptors have an extracellular ligand-binding domain, a transmembrane domain, and an intracellular
tyrosine kinase domain. HER2 amplification leads to constitutive dimerization and activation of downstream signaling pathways
(RAS/MAPK, PI3K/AKT) promoting cell growth and survival. HER2 is not a GPCR (A), ion channel (B), or intracellular steroid
receptor (D).
Q8: A 40-year-old man who is an avid long-distance runner presents with a 2-cm firm, nontender mass on the lateral aspect
of his right thigh. An MRI reveals a well-circumscribed mass within the skeletal muscle. Biopsy reveals elongated
spindle-shaped cells with hyperchromatic nuclei and occasional mitotic figures. Cytogenetic analysis shows a
t(X;18)(p11;q11) translocation. What is the most likely diagnosis?
A. Rhabdomyosarcoma
B. Liposarcoma
C. Synovial sarcoma [CORRECT]
D. Leiomyosarcoma
Correct Answer: C
Rationale: Synovial sarcoma is characterized by the t(X;18)(p11;q11) translocation, which creates the SYT-SSX fusion gene. Despite
its name, it does not arise from synovial tissue but rather from pluripotent mesenchymal cells. It commonly occurs in young adults near
large joints, particularly the knee. Rhabdomyosarcoma (A) is associated with PAX3-FOXO1 or PAX7-FOXO1 fusions. Liposarcoma
(B) often shows MDM2 and CDK4 amplification. Leiomyosarcoma (D) does not have a specific characteristic translocation.
Q9: Which of the following cellular changes is considered potentially reversible and represents an adaptive response to
increased workload rather than a neoplastic or pre-neoplastic process?
A. Endometrial hyperplasia with atypia
B. Left ventricular hypertrophy in a patient with untreated hypertension [CORRECT]
C. Barrett esophagus with columnar metaplasia
D. Leukoplakia of the oral mucosa with dysplasia
Correct Answer: B
Rationale: Left ventricular hypertrophy (LVH) is a reversible adaptive response to increased afterload from hypertension. The
myocardial cells increase in size (hypertrophy) to generate more force and normalize wall stress according to Laplace's law. If the
hypertension is treated, LVH can regress. In contrast, endometrial hyperplasia with atypia (A), Barrett esophagus (C), and oral
leukoplakia with dysplasia (D) are all pre-neoplastic conditions with significant risk of progression to malignancy.
Q10: A 50-year-old man presents with painless jaundice, weight loss, and a palpable gallbladder (Courvoisier sign). CT scan
reveals a mass in the head of the pancreas. Which of the following tumor markers is most likely to be elevated and useful
for monitoring disease progression in this patient?
A. Alpha-fetoprotein (AFP)
B. Carcinoembryonic antigen (CEA)
C. Cancer antigen 19-9 (CA 19-9) [CORRECT]
D. Prostate-specific antigen (PSA)
Correct Answer: C
Rationale: CA 19-9 is the most commonly used tumor marker for pancreatic adenocarcinoma. It is a sialylated Lewis blood group
antigen expressed on mucin glycoproteins. While not useful for screening due to limited sensitivity and specificity, it is valuable for
monitoring treatment response and detecting recurrence. AFP (A) is associated with hepatocellular carcinoma and germ cell tumors.
CEA (B) is used for colorectal cancer monitoring. PSA (D) is specific to prostate cancer.
Q11: A pathologist examines a biopsy from a colorectal adenocarcinoma and notes that the tumor has invaded through the
muscularis propria into the subserosal fat but has not involved adjacent organs or lymph nodes. According to the TNM
staging system, what is the T stage of this tumor?
A. T1
3
, B. T2
C. T3 [CORRECT]
D. T4
Correct Answer: C
Rationale: In the TNM system for colorectal cancer: T1 is invasion into submucosa, T2 is invasion into muscularis propria, T3 is
invasion through the muscularis propria into the subserosa or mesenteric fat (pericolorectal tissues), and T4 is invasion into adjacent
organs or structures or perforation of the visceral peritoneum. Since this tumor has invaded through the muscularis propria into
subserosal fat without involving adjacent organs, it is classified as T3.
Q12: A 35-year-old woman presents with recurrent episodes of spontaneous pneumothorax. CT scan reveals multiple
thin-walled cysts throughout both lung fields. A lung biopsy demonstrates nests of cuboidal epithelial cells with clear
cytoplasm surrounded by a thin fibrous stroma. The cells are positive for HMB-45 on immunohistochemistry. What is the
most likely diagnosis?
A. Bronchioloalveolar carcinoma
B. Lymphangioleiomyomatosis (LAM) [CORRECT]
C. Tuberous sclerosis complex with pulmonary involvement
D. Pulmonary Langerhans cell histiocytosis
Correct Answer: B
Rationale: LAM is a rare neoplastic proliferation of perivascular epithelioid cells (PECs) that occurs almost exclusively in
premenopausal women. It is characterized by cystic destruction of the lung parenchyma, recurrent pneumothorax, chylous effusions,
and angiomyolipomas. The neoplastic cells are HMB-45 positive and show melanocytic and smooth muscle differentiation. While
LAM can occur sporadically or in association with tuberous sclerosis complex (C), the clinical presentation with isolated pulmonary
cysts and pneumothorax in a woman is classic for sporadic LAM.
Q13: A 60-year-old man presents with a rapidly enlarging, violaceous nodule on his forearm. Biopsy reveals a proliferation
of irregular vascular channels lined by atypical endothelial cells with mitotic figures. The patient is HIV-positive with a CD4
count of 85 cells/mcL. Which virus is most directly implicated in the pathogenesis of this malignancy?
A. Epstein-Barr virus (EBV)
B. Human papillomavirus (HPV)
C. Human herpesvirus 8 (HHV-8) [CORRECT]
D. Hepatitis C virus (HCV)
Correct Answer: C
Rationale: This patient has Kaposi sarcoma (KS), a vascular tumor associated with HHV-8 (also called KSHV, Kaposi
sarcoma-associated herpesvirus). HHV-8 encodes viral homologs of cytokines and cell cycle regulatory proteins that promote
angiogenesis and cell proliferation. KS is an AIDS-defining illness and typically occurs with advanced immunosuppression (CD4 <
200). EBV (A) is associated with Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. HPV (B) causes cervical,
anal, and oropharyngeal carcinomas. HCV (D) is linked to hepatocellular carcinoma and lymphoplasmacytic lymphoma.
Q14: A 22-year-old man presents with a testicular mass. Serum alpha-fetoprotein (AFP) is markedly elevated, and
beta-hCG is within normal limits. Orchiectomy reveals a mixture of embryonal carcinoma and yolk sac tumor elements. The
elevated AFP in this patient is produced by which tumor component?
A. Embryonal carcinoma cells
B. Yolk sac tumor (endodermal sinus tumor) cells [CORRECT]
C. Choriocarcinoma cells
D. Seminoma cells
Correct Answer: B
Rationale: AFP is primarily produced by yolk sac tumor (endodermal sinus tumor) elements. Yolk sac tumor is the most common
testicular germ cell tumor in children and frequently occurs as a component of mixed germ cell tumors in adults. Embryonal
carcinoma (A) does not secrete specific tumor markers. Choriocarcinoma (C) secretes beta-hCG. Seminoma (D) may produce modest
elevations of beta-hCG (from syncytiotrophoblastic giant cells) but does not produce AFP.
4
COMPREHENSIVE EXAMINATION TEST BANK WITH VERIFIED ANSWERS AND DETAILED RATIONALES
150 Questions | 8 Sections | 25% Knowledge | 55% Application | 20% Analysis
Section 1: Cellular Adaptation, Injury, and Neoplasia
Questions 1-20
Q1: A 62-year-old man with a 40-pack-year smoking history presents with chronic cough and weight loss. A lung biopsy
reveals squamous cell carcinoma. Pathology notes show keratin pearls and intercellular bridges. The tumor cells have
undergone which of the following adaptive cellular changes before malignant transformation?
A. Metaplasia of bronchial epithelium from columnar to squamous [CORRECT]
B. Hyperplasia of existing squamous cells
C. Dysplasia of the alveolar type II pneumocytes
D. Hypertrophy of the bronchial smooth muscle
Correct Answer: A
Rationale: Chronic cigarette smoke irritation causes the normal ciliated columnar epithelium of the bronchi to undergo metaplasia to
squamous epithelium as an adaptive protective response. However, this metaplastic epithelium is more susceptible to further genetic
damage and can progress to dysplasia and then squamous cell carcinoma. Hyperplasia (B) is an increase in cell number, not the
primary change seen here. Dysplasia of alveolar cells (C) is not the pathway to squamous cell carcinoma. Bronchial smooth muscle
hypertrophy (D) is seen in asthma, not carcinogenesis.
Q2: A 45-year-old woman presents with increasing fatigue, pallor, and splenomegaly. Laboratory studies reveal a
hemoglobin of 8.2 g/dL, WBC count of 3,200/mcL, and platelet count of 95,000/mcL. A bone marrow biopsy demonstrates
hypercellularity with markedly increased myeloid precursors and the presence of the Philadelphia chromosome t(9;22).
Which of the following best describes the initial cellular adaptation that leads to this condition?
A. Apoptosis of megakaryocytes leading to thrombocytopenia
B. Unregulated proliferation of a single hematopoietic stem cell clone [CORRECT]
C. Metaplasia of bone marrow stromal cells
D. Hypertrophy of erythroid precursors
Correct Answer: B
Rationale: Chronic myeloid leukemia (CML) is caused by the BCR-ABL fusion protein resulting from the Philadelphia chromosome
t(9;22). This oncogene drives unregulated proliferation of a single pluripotent hematopoietic stem cell clone, leading to overproduction
of myeloid cells. The pancytopenia described is more consistent with CML in blast crisis or with myelofibrosis. The key concept is
clonal proliferation driven by an acquired genetic mutation, not metaplasia (C) or hypertrophy (D).
Q3: A patient with a p53 gene mutation is being evaluated for cancer risk. The p53 protein normally functions to halt the
cell cycle at which checkpoint to allow DNA repair or trigger apoptosis if repair fails?
A. G1/S checkpoint [CORRECT]
B. G2/M checkpoint
C. M checkpoint (spindle assembly)
D. Restriction point in early G1
Correct Answer: A
Rationale: The p53 tumor suppressor protein acts primarily at the G1/S checkpoint. When DNA damage is detected, p53 activates p21
which inhibits cyclin-dependent kinases, arresting the cell at G1/S to allow DNA repair. If damage is too extensive, p53 triggers
apoptosis via Bax activation. While p53 can also influence the G2/M checkpoint (B), its primary and most critical role is at the G1/S
transition. The M checkpoint (C) is monitored by the anaphase-promoting complex. The restriction point (D) is regulated by Rb, not
p53.
1
,Q4: A 28-year-old nulligravid woman presents with a 3-month history of irregular vaginal bleeding and pelvic pain. An
ultrasound reveals a 6-cm uterine mass. Histopathology after hysterectomy shows spiral arterioles with fibrinoid necrosis,
trophoblastic proliferation, and abnormal villi. Karyotype analysis of the tissue reveals a 46,XX genotype, but all
chromosomes are of paternal origin. What is the most likely diagnosis?
A. Complete hydatidiform mole [CORRECT]
B. Partial hydatidiform mole
C. Choriocarcinoma
D. Placenta accreta
Correct Answer: A
Rationale: A complete hydatidiform mole is characterized by villous swelling (hydropic degeneration), trophoblastic hyperplasia, and
absence of fetal tissue. The karyotype is typically 46,XX with all chromosomes of paternal origin (androgenesis) resulting from
fertilization of an empty egg by a single sperm that duplicates. A partial mole (B) is triploid (69,XXY) with some fetal tissue present.
Choriocarcinoma (C) is a malignant gestational trophoblastic neoplasm with invasive trophoblastic proliferation but no villi. Placenta
accreta (D) involves abnormal placental attachment, not trophoblastic proliferation.
Q5: A researcher is studying the Bcl-2 family of proteins in the context of follicular lymphoma, which is characterized by
the t(14;18) translocation. How does overexpression of Bcl-2 contribute to lymphomagenesis?
A. By increasing the rate of cell proliferation through cyclin D upregulation
B. By inhibiting apoptosis, allowing survival of cells with DNA damage [CORRECT]
C. By promoting angiogenesis through VEGF secretion
D. By disabling DNA mismatch repair mechanisms
Correct Answer: B
Rationale: Bcl-2 is an anti-apoptotic protein that resides on the outer mitochondrial membrane and prevents cytochrome c release,
thereby inhibiting the intrinsic apoptotic pathway. The t(14;18) translocation places the BCL2 gene under the control of the
immunoglobulin heavy chain enhancer, causing constitutive overexpression. This does not increase proliferation rate (A), promote
angiogenesis (C), or disable DNA repair (D). Instead, it allows cells with oncogenic mutations to survive when they would normally
undergo programmed cell death.
Q6: A 55-year-old man with chronic alcohol use presents with ascites, spider angiomas, and palmar erythema. A liver
biopsy demonstrates bridging fibrosis and regenerative nodules. Which of the following best describes the cellular
adaptation occurring in the hepatocytes surrounding the regenerative nodules?
A. Metaplasia of hepatocytes to biliary epithelium
B. Hyperplasia of remaining hepatocytes to restore liver mass [CORRECT]
C. Hypertrophy of hepatocytes with subsequent dysplastic changes
D. Apoptosis mediated by TGF-beta from stellate cells
Correct Answer: B
Rationale: The liver has remarkable regenerative capacity. In cirrhosis, hepatocytes that survive injury undergo compensatory
hyperplasia (increased cell division) to restore functional liver mass, forming regenerative nodules. While individual hepatocytes may
also hypertrophy, the dominant adaptive response is hyperplastic regeneration. Metaplasia (A) does not occur in hepatocytes.
Dysplasia (C) is a pre-malignant change not characteristic of the regenerative process itself. TGF-beta-mediated apoptosis (D) does
occur but is not the adaptive response of the surviving hepatocytes.
Q7: A 70-year-old woman presents with a painless breast lump detected on screening mammography. Core needle biopsy
reveals infiltrating ductal carcinoma. Immunohistochemistry is positive for HER2/neu (ERBB2) amplification. The HER2
receptor belongs to which family of cell surface receptors?
A. G-protein coupled receptors
B. Ion channel receptors
C. Receptor tyrosine kinases [CORRECT]
D. Intracellular steroid hormone receptors
2
, Correct Answer: C
Rationale: HER2/neu (ERBB2) is a member of the epidermal growth factor receptor (EGFR/ERBB) family, which are receptor
tyrosine kinases (RTKs). These receptors have an extracellular ligand-binding domain, a transmembrane domain, and an intracellular
tyrosine kinase domain. HER2 amplification leads to constitutive dimerization and activation of downstream signaling pathways
(RAS/MAPK, PI3K/AKT) promoting cell growth and survival. HER2 is not a GPCR (A), ion channel (B), or intracellular steroid
receptor (D).
Q8: A 40-year-old man who is an avid long-distance runner presents with a 2-cm firm, nontender mass on the lateral aspect
of his right thigh. An MRI reveals a well-circumscribed mass within the skeletal muscle. Biopsy reveals elongated
spindle-shaped cells with hyperchromatic nuclei and occasional mitotic figures. Cytogenetic analysis shows a
t(X;18)(p11;q11) translocation. What is the most likely diagnosis?
A. Rhabdomyosarcoma
B. Liposarcoma
C. Synovial sarcoma [CORRECT]
D. Leiomyosarcoma
Correct Answer: C
Rationale: Synovial sarcoma is characterized by the t(X;18)(p11;q11) translocation, which creates the SYT-SSX fusion gene. Despite
its name, it does not arise from synovial tissue but rather from pluripotent mesenchymal cells. It commonly occurs in young adults near
large joints, particularly the knee. Rhabdomyosarcoma (A) is associated with PAX3-FOXO1 or PAX7-FOXO1 fusions. Liposarcoma
(B) often shows MDM2 and CDK4 amplification. Leiomyosarcoma (D) does not have a specific characteristic translocation.
Q9: Which of the following cellular changes is considered potentially reversible and represents an adaptive response to
increased workload rather than a neoplastic or pre-neoplastic process?
A. Endometrial hyperplasia with atypia
B. Left ventricular hypertrophy in a patient with untreated hypertension [CORRECT]
C. Barrett esophagus with columnar metaplasia
D. Leukoplakia of the oral mucosa with dysplasia
Correct Answer: B
Rationale: Left ventricular hypertrophy (LVH) is a reversible adaptive response to increased afterload from hypertension. The
myocardial cells increase in size (hypertrophy) to generate more force and normalize wall stress according to Laplace's law. If the
hypertension is treated, LVH can regress. In contrast, endometrial hyperplasia with atypia (A), Barrett esophagus (C), and oral
leukoplakia with dysplasia (D) are all pre-neoplastic conditions with significant risk of progression to malignancy.
Q10: A 50-year-old man presents with painless jaundice, weight loss, and a palpable gallbladder (Courvoisier sign). CT scan
reveals a mass in the head of the pancreas. Which of the following tumor markers is most likely to be elevated and useful
for monitoring disease progression in this patient?
A. Alpha-fetoprotein (AFP)
B. Carcinoembryonic antigen (CEA)
C. Cancer antigen 19-9 (CA 19-9) [CORRECT]
D. Prostate-specific antigen (PSA)
Correct Answer: C
Rationale: CA 19-9 is the most commonly used tumor marker for pancreatic adenocarcinoma. It is a sialylated Lewis blood group
antigen expressed on mucin glycoproteins. While not useful for screening due to limited sensitivity and specificity, it is valuable for
monitoring treatment response and detecting recurrence. AFP (A) is associated with hepatocellular carcinoma and germ cell tumors.
CEA (B) is used for colorectal cancer monitoring. PSA (D) is specific to prostate cancer.
Q11: A pathologist examines a biopsy from a colorectal adenocarcinoma and notes that the tumor has invaded through the
muscularis propria into the subserosal fat but has not involved adjacent organs or lymph nodes. According to the TNM
staging system, what is the T stage of this tumor?
A. T1
3
, B. T2
C. T3 [CORRECT]
D. T4
Correct Answer: C
Rationale: In the TNM system for colorectal cancer: T1 is invasion into submucosa, T2 is invasion into muscularis propria, T3 is
invasion through the muscularis propria into the subserosa or mesenteric fat (pericolorectal tissues), and T4 is invasion into adjacent
organs or structures or perforation of the visceral peritoneum. Since this tumor has invaded through the muscularis propria into
subserosal fat without involving adjacent organs, it is classified as T3.
Q12: A 35-year-old woman presents with recurrent episodes of spontaneous pneumothorax. CT scan reveals multiple
thin-walled cysts throughout both lung fields. A lung biopsy demonstrates nests of cuboidal epithelial cells with clear
cytoplasm surrounded by a thin fibrous stroma. The cells are positive for HMB-45 on immunohistochemistry. What is the
most likely diagnosis?
A. Bronchioloalveolar carcinoma
B. Lymphangioleiomyomatosis (LAM) [CORRECT]
C. Tuberous sclerosis complex with pulmonary involvement
D. Pulmonary Langerhans cell histiocytosis
Correct Answer: B
Rationale: LAM is a rare neoplastic proliferation of perivascular epithelioid cells (PECs) that occurs almost exclusively in
premenopausal women. It is characterized by cystic destruction of the lung parenchyma, recurrent pneumothorax, chylous effusions,
and angiomyolipomas. The neoplastic cells are HMB-45 positive and show melanocytic and smooth muscle differentiation. While
LAM can occur sporadically or in association with tuberous sclerosis complex (C), the clinical presentation with isolated pulmonary
cysts and pneumothorax in a woman is classic for sporadic LAM.
Q13: A 60-year-old man presents with a rapidly enlarging, violaceous nodule on his forearm. Biopsy reveals a proliferation
of irregular vascular channels lined by atypical endothelial cells with mitotic figures. The patient is HIV-positive with a CD4
count of 85 cells/mcL. Which virus is most directly implicated in the pathogenesis of this malignancy?
A. Epstein-Barr virus (EBV)
B. Human papillomavirus (HPV)
C. Human herpesvirus 8 (HHV-8) [CORRECT]
D. Hepatitis C virus (HCV)
Correct Answer: C
Rationale: This patient has Kaposi sarcoma (KS), a vascular tumor associated with HHV-8 (also called KSHV, Kaposi
sarcoma-associated herpesvirus). HHV-8 encodes viral homologs of cytokines and cell cycle regulatory proteins that promote
angiogenesis and cell proliferation. KS is an AIDS-defining illness and typically occurs with advanced immunosuppression (CD4 <
200). EBV (A) is associated with Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. HPV (B) causes cervical,
anal, and oropharyngeal carcinomas. HCV (D) is linked to hepatocellular carcinoma and lymphoplasmacytic lymphoma.
Q14: A 22-year-old man presents with a testicular mass. Serum alpha-fetoprotein (AFP) is markedly elevated, and
beta-hCG is within normal limits. Orchiectomy reveals a mixture of embryonal carcinoma and yolk sac tumor elements. The
elevated AFP in this patient is produced by which tumor component?
A. Embryonal carcinoma cells
B. Yolk sac tumor (endodermal sinus tumor) cells [CORRECT]
C. Choriocarcinoma cells
D. Seminoma cells
Correct Answer: B
Rationale: AFP is primarily produced by yolk sac tumor (endodermal sinus tumor) elements. Yolk sac tumor is the most common
testicular germ cell tumor in children and frequently occurs as a component of mixed germ cell tumors in adults. Embryonal
carcinoma (A) does not secrete specific tumor markers. Choriocarcinoma (C) secretes beta-hCG. Seminoma (D) may produce modest
elevations of beta-hCG (from syncytiotrophoblastic giant cells) but does not produce AFP.
4
