2026 PA Exam Prep: Pathologists' Assistant
Practice Questions, Answer Rationales,
Surgical Pathology, Autopsy, Grossing,
Histology, Specimen Handling & Laboratory
Study Guide
Domain 1: Fundamentals of Pathology – General Pathology (Questions 1–25)
Question 1. Which of the following best describes the primary cellular event that
initiates irreversible hypoxic injury?
A) Decreased ATP production
B) Mitochondrial membrane damage and severe ATP depletion
C) Increased intracellular calcium
D) Reactive oxygen species formation
Rationale: Irreversible hypoxic injury is characterized by severe ATP depletion,
mitochondrial membrane damage, and loss of membrane integrity. While
decreased ATP and calcium influx occur early, the point of no return is marked by
mitochondrial membrane rupture and profound ATP depletion.
Question 2. A pathologists' assistant is grossing a liver specimen from a patient
with chronic alcohol use. Which finding is most characteristic of alcoholic
hepatitis?
A) Mallory-Denk bodies and neutrophilic infiltration
B) Fatty change alone
C) Bridging fibrosis
D) Ground-glass hepatocytes
Rationale: Alcoholic hepatitis is characterized by hepatocyte ballooning, Mallory-
Denk bodies (intracytoplasmic eosinophilic inclusions), and neutrophilic
infiltration. Fatty change is nonspecific, and ground-glass hepatocytes are
characteristic of hepatitis B.
,Question 3. Which type of necrosis is most commonly associated with myocardial
infarction?
A) Liquefactive necrosis
B) Coagulative necrosis
C) Caseous necrosis
D) Fat necrosis
Rationale: Coagulative necrosis is characteristic of ischemic injury in most
organs, including the heart, kidney, and spleen. The basic tissue architecture is
preserved for a time after cell death.
Question 4. A granuloma is best described as:
A) A collection of neutrophils
B) A collection of activated macrophages (epithelioid histiocytes)
C) A collection of plasma cells
D) A collection of eosinophils
Rationale: Granulomas are aggregates of activated macrophages that have
transformed into epithelioid histiocytes, often with multinucleated giant cells. They
are a form of chronic inflammation seen in tuberculosis, sarcoidosis, and fungal
infections.
Question 5. Which of the following is a characteristic feature of apoptosis?
A) Cell shrinkage and chromatin condensation
B) Cell swelling and membrane rupture
C) Inflammatory infiltrate
D) Coagulative necrosis
Rationale: Apoptosis is characterized by cell shrinkage, chromatin condensation,
nuclear fragmentation, and formation of apoptotic bodies without an inflammatory
response. Necrosis, by contrast, involves cell swelling and inflammation.
Question 6. The most common cause of fatty liver disease in the United States is:
,A) Alcohol abuse
B) Non-alcoholic fatty liver disease (NAFLD)
C) Viral hepatitis
D) Drug toxicity
Rationale: Non-alcoholic fatty liver disease (NAFLD) has become the most
common cause of chronic liver disease in the United States, associated with
obesity, diabetes, and metabolic syndrome.
Question 7. Which of the following is a tumor suppressor gene commonly mutated
in human cancers?
A) TP53
B) KRAS
C) MYC
D) BCR-ABL
Rationale: TP53 is the most commonly mutated tumor suppressor gene in human
cancers. It regulates cell cycle arrest, DNA repair, and apoptosis. KRAS and MYC
are oncogenes, and BCR-ABL is a fusion oncogene.
Question 8. A pathologists' assistant receives a colon biopsy showing glandular
structures with nuclear stratification and hyperchromasia extending to the surface.
This is most consistent with:
A) Adenocarcinoma
B) Tubular adenoma
C) Hyperplastic polyp
D) Normal colonic mucosa
Rationale: Adenocarcinoma is characterized by malignant glandular epithelium
with nuclear atypia, hyperchromasia, and invasion. Tubular adenomas show low-
grade dysplasia without invasion, and hyperplastic polyps show serrated
architecture without significant atypia.
Question 9. Which of the following best describes the term "desmoplasia"?
, A) Fibrous connective tissue proliferation induced by tumor cells
B) Tumor cell necrosis
C) Lymphatic invasion
D) Perineural invasion
Rationale: Desmoplasia refers to the proliferation of fibrous connective tissue
(collagen) induced by tumor cells, often seen in carcinomas of the breast, pancreas,
and colon. It contributes to the firm texture of these tumors.
Question 10. A lymph node biopsy shows replacement of normal architecture by a
monotonous population of small, round lymphocytes with a "starry-sky" pattern.
This is most characteristic of:
A) Follicular lymphoma
B) Burkitt lymphoma
C) Hodgkin lymphoma
D) Chronic lymphocytic leukemia/small lymphocytic lymphoma
Rationale: Burkitt lymphoma is characterized by a "starry-sky" pattern due to
tingible body macrophages interspersed among a monotonous population of
medium-sized lymphocytes. Follicular lymphoma shows a follicular pattern, and
SLL/CLL shows small lymphocytes without a starry-sky pattern.
Question 11. Which of the following is a characteristic gross finding of a
teratoma?
A) A tumor containing tissue from multiple germ cell layers
B) A uniformly solid tumor
C) A cystic tumor with clear fluid only
D) A tumor with only ectodermal elements
Rationale: Teratomas are germ cell tumors that contain tissue derived from more
than one germ cell layer (ectoderm, mesoderm, endoderm). They may be mature
(benign) or immature (malignant) and often contain hair, teeth, and sebaceous
material.
Question 12. The most common site of metastasis for colorectal carcinoma is:
Practice Questions, Answer Rationales,
Surgical Pathology, Autopsy, Grossing,
Histology, Specimen Handling & Laboratory
Study Guide
Domain 1: Fundamentals of Pathology – General Pathology (Questions 1–25)
Question 1. Which of the following best describes the primary cellular event that
initiates irreversible hypoxic injury?
A) Decreased ATP production
B) Mitochondrial membrane damage and severe ATP depletion
C) Increased intracellular calcium
D) Reactive oxygen species formation
Rationale: Irreversible hypoxic injury is characterized by severe ATP depletion,
mitochondrial membrane damage, and loss of membrane integrity. While
decreased ATP and calcium influx occur early, the point of no return is marked by
mitochondrial membrane rupture and profound ATP depletion.
Question 2. A pathologists' assistant is grossing a liver specimen from a patient
with chronic alcohol use. Which finding is most characteristic of alcoholic
hepatitis?
A) Mallory-Denk bodies and neutrophilic infiltration
B) Fatty change alone
C) Bridging fibrosis
D) Ground-glass hepatocytes
Rationale: Alcoholic hepatitis is characterized by hepatocyte ballooning, Mallory-
Denk bodies (intracytoplasmic eosinophilic inclusions), and neutrophilic
infiltration. Fatty change is nonspecific, and ground-glass hepatocytes are
characteristic of hepatitis B.
,Question 3. Which type of necrosis is most commonly associated with myocardial
infarction?
A) Liquefactive necrosis
B) Coagulative necrosis
C) Caseous necrosis
D) Fat necrosis
Rationale: Coagulative necrosis is characteristic of ischemic injury in most
organs, including the heart, kidney, and spleen. The basic tissue architecture is
preserved for a time after cell death.
Question 4. A granuloma is best described as:
A) A collection of neutrophils
B) A collection of activated macrophages (epithelioid histiocytes)
C) A collection of plasma cells
D) A collection of eosinophils
Rationale: Granulomas are aggregates of activated macrophages that have
transformed into epithelioid histiocytes, often with multinucleated giant cells. They
are a form of chronic inflammation seen in tuberculosis, sarcoidosis, and fungal
infections.
Question 5. Which of the following is a characteristic feature of apoptosis?
A) Cell shrinkage and chromatin condensation
B) Cell swelling and membrane rupture
C) Inflammatory infiltrate
D) Coagulative necrosis
Rationale: Apoptosis is characterized by cell shrinkage, chromatin condensation,
nuclear fragmentation, and formation of apoptotic bodies without an inflammatory
response. Necrosis, by contrast, involves cell swelling and inflammation.
Question 6. The most common cause of fatty liver disease in the United States is:
,A) Alcohol abuse
B) Non-alcoholic fatty liver disease (NAFLD)
C) Viral hepatitis
D) Drug toxicity
Rationale: Non-alcoholic fatty liver disease (NAFLD) has become the most
common cause of chronic liver disease in the United States, associated with
obesity, diabetes, and metabolic syndrome.
Question 7. Which of the following is a tumor suppressor gene commonly mutated
in human cancers?
A) TP53
B) KRAS
C) MYC
D) BCR-ABL
Rationale: TP53 is the most commonly mutated tumor suppressor gene in human
cancers. It regulates cell cycle arrest, DNA repair, and apoptosis. KRAS and MYC
are oncogenes, and BCR-ABL is a fusion oncogene.
Question 8. A pathologists' assistant receives a colon biopsy showing glandular
structures with nuclear stratification and hyperchromasia extending to the surface.
This is most consistent with:
A) Adenocarcinoma
B) Tubular adenoma
C) Hyperplastic polyp
D) Normal colonic mucosa
Rationale: Adenocarcinoma is characterized by malignant glandular epithelium
with nuclear atypia, hyperchromasia, and invasion. Tubular adenomas show low-
grade dysplasia without invasion, and hyperplastic polyps show serrated
architecture without significant atypia.
Question 9. Which of the following best describes the term "desmoplasia"?
, A) Fibrous connective tissue proliferation induced by tumor cells
B) Tumor cell necrosis
C) Lymphatic invasion
D) Perineural invasion
Rationale: Desmoplasia refers to the proliferation of fibrous connective tissue
(collagen) induced by tumor cells, often seen in carcinomas of the breast, pancreas,
and colon. It contributes to the firm texture of these tumors.
Question 10. A lymph node biopsy shows replacement of normal architecture by a
monotonous population of small, round lymphocytes with a "starry-sky" pattern.
This is most characteristic of:
A) Follicular lymphoma
B) Burkitt lymphoma
C) Hodgkin lymphoma
D) Chronic lymphocytic leukemia/small lymphocytic lymphoma
Rationale: Burkitt lymphoma is characterized by a "starry-sky" pattern due to
tingible body macrophages interspersed among a monotonous population of
medium-sized lymphocytes. Follicular lymphoma shows a follicular pattern, and
SLL/CLL shows small lymphocytes without a starry-sky pattern.
Question 11. Which of the following is a characteristic gross finding of a
teratoma?
A) A tumor containing tissue from multiple germ cell layers
B) A uniformly solid tumor
C) A cystic tumor with clear fluid only
D) A tumor with only ectodermal elements
Rationale: Teratomas are germ cell tumors that contain tissue derived from more
than one germ cell layer (ectoderm, mesoderm, endoderm). They may be mature
(benign) or immature (malignant) and often contain hair, teeth, and sebaceous
material.
Question 12. The most common site of metastasis for colorectal carcinoma is:
