NBME PATHOLOGY FINAL EXAM 2026
Exam Questions with Answers and Rationales
Cellular Injury, Adaptation, and Neoplasia
1. What is a hypertrophic scar?
• A. Scar tissue that extends beyond the boundaries of the original wound
• B. Excess scar tissue confined within the original wound boundaries
• C. Scar tissue that undergoes malignant transformation
• D. Complete absence of scar tissue formation
Answer: B. Excess scar tissue confined within the original wound boundaries
Rationale: A hypertrophic scar is characterized by excess collagen deposition that
remains within the confines of the original wound. Unlike keloids, hypertrophic
scars do not extend beyond the wound margins and often regress over time.
2. What is a keloid?
• A. Scar tissue confined to the wound boundaries
• B. Excess scar tissue out of proportion to the wound itself
• C. A benign tumor of adipose tissue
• D. A malignant transformation of scar tissue
Answer: B. Excess scar tissue out of proportion to the wound itself
Rationale: Keloids are characterized by excessive scar tissue that extends beyond
the boundaries of the original wound. They are composed primarily of type III
collagen and tend to recur after excision. Keloids do not regress spontaneously and
are more common in individuals with darker skin pigmentation.
3. What is neoplasia?
• A. Controlled, reversible cell proliferation
, • B. Unregulated, irreversible, and monoclonal cell proliferation
• C. Physiologic response to tissue injury
• D. Reversible cellular adaptation to stress
Answer: B. Unregulated, irreversible, and monoclonal cell proliferation
Rationale: Neoplasia is defined as unregulated, irreversible, and monoclonal
proliferation of cells. Unlike hyperplasia, which is a controlled and reversible
response to stimuli, neoplastic growth continues despite the absence of the original
stimulus and results from genetic alterations.
4. How was clonality of a neoplastic mass determined historically?
• A. By microscopic examination of cell morphology
• B. By the presence of G-6P-D isoforms
• C. By measuring tumor size and growth rate
• D. By immunohistochemical staining
Answer: B. By the presence of G-6P-D isoforms
Rationale: Clonality of neoplastic masses was historically determined using
glucose-6-phosphate dehydrogenase (G-6P-D) isoforms. A 1:1 ratio indicates
hyperplasia (polyclonal), while a 1:0 ratio indicates neoplasia (monoclonal). This
method takes advantage of X-chromosome inactivation patterns.
5. How is clonality of B lymphocytes determined?
• A. By CD4/CD8 ratio
• B. By immunoglobulin light chain phenotype
• C. By T-cell receptor rearrangement
• D. By B-cell surface marker expression
Answer: B. By immunoglobulin light chain phenotype
Rationale: B lymphocyte clonality is determined by assessing kappa and lambda
light chain expression. A normal 3:1 kappa:lambda ratio is preserved in reactive
,hyperplasia but distorted in neoplasia (e.g., 6:1 ratio indicates lymphoma). This
reflects the monoclonal nature of neoplastic B-cell populations.
6. Which cancers are most common in order of incidence?
• A. Lung, Colorectal, Breast/Prostate
• B. Breast/Prostate, Lung, Colorectal
• C. Colorectal, Breast/Prostate, Lung
• D. Lung, Breast/Prostate, Colorectal
Answer: B. Breast/Prostate, Lung, Colorectal
Rationale: In order of incidence, the most common cancers are breast/prostate
cancer, followed by lung cancer, and then colorectal cancer. This ranking reflects
the prevalence of these malignancies in the general population, with breast and
prostate cancers being the most frequently diagnosed.
7. Which cancers cause the most deaths in order of mortality?
• A. Breast/Prostate, Colorectal, Lung
• B. Colorectal, Lung, Breast/Prostate
• C. Lung, Breast/Prostate, Colorectal
• D. Lung, Colorectal, Breast/Prostate
Answer: C. Lung, Breast/Prostate, Colorectal
Rationale: Lung cancer is the leading cause of cancer-related death, followed by
breast/prostate cancer, and then colorectal cancer. This mortality ranking differs
from incidence because lung cancer has a particularly poor prognosis and high
case-fatality rate.
8. Describe carcinogenesis at the cellular level.
• A. Lethal DNA damage that causes immediate cell death
, • B. DNA damage that bypasses DNA repair mechanisms but is not lethal
to the cell
• C. Reversible DNA methylation changes
• D. Complete loss of all cellular DNA
Answer: B. DNA damage that bypasses DNA repair mechanisms but is not
lethal to the cell
Rationale: Carcinogenesis involves DNA damage that successfully evades DNA
repair mechanisms while remaining non-lethal to the cell. This allows the damaged
cell to survive and proliferate, accumulating additional mutations that drive
malignant transformation.
9. Describe oncogenes.
• A. Genes that stimulate cell growth and cause cancer when continuously
activated; require only 1 copy to be turned on
• B. Genes that inhibit cell growth and require both copies to be inactivated
• C. Genes that have no role in cancer development
• D. Genes that are always tumor suppressive
Answer: A. Genes that stimulate cell growth and cause cancer when
continuously activated; require only 1 copy to be turned on
Rationale: Oncogenes are gain-of-function mutations of proto-oncogenes that
stimulate cell growth. They are dominant at the cellular level, meaning only one
copy of the gene needs to be activated (mutated) to contribute to cancer
development.
10. Describe tumor suppressor genes.
• A. Genes that stimulate cell growth and require only 1 copy to be inactivated
• B. Genes that normally inhibit cell growth (P53, RB); both copies need
to be knocked out for cancer to occur (2-hit hypothesis)
• C. Genes that have no role in cell cycle regulation
Exam Questions with Answers and Rationales
Cellular Injury, Adaptation, and Neoplasia
1. What is a hypertrophic scar?
• A. Scar tissue that extends beyond the boundaries of the original wound
• B. Excess scar tissue confined within the original wound boundaries
• C. Scar tissue that undergoes malignant transformation
• D. Complete absence of scar tissue formation
Answer: B. Excess scar tissue confined within the original wound boundaries
Rationale: A hypertrophic scar is characterized by excess collagen deposition that
remains within the confines of the original wound. Unlike keloids, hypertrophic
scars do not extend beyond the wound margins and often regress over time.
2. What is a keloid?
• A. Scar tissue confined to the wound boundaries
• B. Excess scar tissue out of proportion to the wound itself
• C. A benign tumor of adipose tissue
• D. A malignant transformation of scar tissue
Answer: B. Excess scar tissue out of proportion to the wound itself
Rationale: Keloids are characterized by excessive scar tissue that extends beyond
the boundaries of the original wound. They are composed primarily of type III
collagen and tend to recur after excision. Keloids do not regress spontaneously and
are more common in individuals with darker skin pigmentation.
3. What is neoplasia?
• A. Controlled, reversible cell proliferation
, • B. Unregulated, irreversible, and monoclonal cell proliferation
• C. Physiologic response to tissue injury
• D. Reversible cellular adaptation to stress
Answer: B. Unregulated, irreversible, and monoclonal cell proliferation
Rationale: Neoplasia is defined as unregulated, irreversible, and monoclonal
proliferation of cells. Unlike hyperplasia, which is a controlled and reversible
response to stimuli, neoplastic growth continues despite the absence of the original
stimulus and results from genetic alterations.
4. How was clonality of a neoplastic mass determined historically?
• A. By microscopic examination of cell morphology
• B. By the presence of G-6P-D isoforms
• C. By measuring tumor size and growth rate
• D. By immunohistochemical staining
Answer: B. By the presence of G-6P-D isoforms
Rationale: Clonality of neoplastic masses was historically determined using
glucose-6-phosphate dehydrogenase (G-6P-D) isoforms. A 1:1 ratio indicates
hyperplasia (polyclonal), while a 1:0 ratio indicates neoplasia (monoclonal). This
method takes advantage of X-chromosome inactivation patterns.
5. How is clonality of B lymphocytes determined?
• A. By CD4/CD8 ratio
• B. By immunoglobulin light chain phenotype
• C. By T-cell receptor rearrangement
• D. By B-cell surface marker expression
Answer: B. By immunoglobulin light chain phenotype
Rationale: B lymphocyte clonality is determined by assessing kappa and lambda
light chain expression. A normal 3:1 kappa:lambda ratio is preserved in reactive
,hyperplasia but distorted in neoplasia (e.g., 6:1 ratio indicates lymphoma). This
reflects the monoclonal nature of neoplastic B-cell populations.
6. Which cancers are most common in order of incidence?
• A. Lung, Colorectal, Breast/Prostate
• B. Breast/Prostate, Lung, Colorectal
• C. Colorectal, Breast/Prostate, Lung
• D. Lung, Breast/Prostate, Colorectal
Answer: B. Breast/Prostate, Lung, Colorectal
Rationale: In order of incidence, the most common cancers are breast/prostate
cancer, followed by lung cancer, and then colorectal cancer. This ranking reflects
the prevalence of these malignancies in the general population, with breast and
prostate cancers being the most frequently diagnosed.
7. Which cancers cause the most deaths in order of mortality?
• A. Breast/Prostate, Colorectal, Lung
• B. Colorectal, Lung, Breast/Prostate
• C. Lung, Breast/Prostate, Colorectal
• D. Lung, Colorectal, Breast/Prostate
Answer: C. Lung, Breast/Prostate, Colorectal
Rationale: Lung cancer is the leading cause of cancer-related death, followed by
breast/prostate cancer, and then colorectal cancer. This mortality ranking differs
from incidence because lung cancer has a particularly poor prognosis and high
case-fatality rate.
8. Describe carcinogenesis at the cellular level.
• A. Lethal DNA damage that causes immediate cell death
, • B. DNA damage that bypasses DNA repair mechanisms but is not lethal
to the cell
• C. Reversible DNA methylation changes
• D. Complete loss of all cellular DNA
Answer: B. DNA damage that bypasses DNA repair mechanisms but is not
lethal to the cell
Rationale: Carcinogenesis involves DNA damage that successfully evades DNA
repair mechanisms while remaining non-lethal to the cell. This allows the damaged
cell to survive and proliferate, accumulating additional mutations that drive
malignant transformation.
9. Describe oncogenes.
• A. Genes that stimulate cell growth and cause cancer when continuously
activated; require only 1 copy to be turned on
• B. Genes that inhibit cell growth and require both copies to be inactivated
• C. Genes that have no role in cancer development
• D. Genes that are always tumor suppressive
Answer: A. Genes that stimulate cell growth and cause cancer when
continuously activated; require only 1 copy to be turned on
Rationale: Oncogenes are gain-of-function mutations of proto-oncogenes that
stimulate cell growth. They are dominant at the cellular level, meaning only one
copy of the gene needs to be activated (mutated) to contribute to cancer
development.
10. Describe tumor suppressor genes.
• A. Genes that stimulate cell growth and require only 1 copy to be inactivated
• B. Genes that normally inhibit cell growth (P53, RB); both copies need
to be knocked out for cancer to occur (2-hit hypothesis)
• C. Genes that have no role in cell cycle regulation
