NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
NBME CBSE
ACTUAL TEST QUESTIONS AND ANSWERS
TEST BANK — COMPLETE SOLUTION
RATED A | EDITION
Total Questions 200
Sections 13 Organ-System & Multisystem Blocks
Format Single-Best-Answer (A–D) with Rationales
Cognitive Mix 20% Recall / 50% Application / 30% Analysis
Alignment NBME CBSE Content Outline & USMLE Step 1
25 Case-Based • 15 Pharmacology • 15
Special Inclusions
Biostatistics
Preclinical Medical Education Standards • Comprehensive Basic Science Examination (CBSE) • USMLE
Step 1 Competencies
Page 1
,NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
Section 1: General Principles
Q1: A 58-year-old man with a 30-pack-year smoking history presents with a 3-cm pulmonary mass.
Biopsy reveals sheets of malignant cells with scant cytoplasm, granular "salt-and-pepper" chromatin,
and absent nucleoli. Numerous mitotic figures and apoptotic bodies are present. Which cellular process is
most directly responsible for the apoptotic bodies observed in this tumor?
A. Activation of BCL-2 with inhibition of caspase-9
B. Release of cytochrome c from mitochondria with activation of the apoptosome *[CORRECT]*
C. Activation of macrophage nitric oxide synthase causing oncotic necrosis
D. Inhibition of p53 with failure of G1/S checkpoint arrest
Correct Answer: B
Rationale: Apoptotic bodies are the histologic hallmark of programmed cell death, mediated by cytochrome c release
from mitochondria, apoptosome (Apaf-1 + caspase-9) assembly, and downstream executioner caspases (3, 6, 7). BCL-2
inhibits apoptosis; p53 induces apoptosis via BAX, so its inhibition would reduce, not increase, apoptotic bodies; nitric
oxide mediates oncotic (necrotic) rather than apoptotic death. NBME CBSE/Step 1 content outline: cellular injury,
apoptosis vs. necrosis.
Q2: A 42-year-old woman presents with fatigue and pallor. Laboratory studies show MCV 78 fL, serum
iron low, ferritin low, and TIBC elevated. Which molecular mechanism most directly accounts for the
elevated transferrin (TIBC) in this patient?
A. Hepcidin-mediated ferroportin degradation is increased
B. Liver transferrin synthesis is upregulated in response to low intracellular iron stores *[CORRECT]*
C. Defective DMT1 intestinal iron transport causes iron trapping in enterocytes
D. Heme oxygenase-1 degrades heme in macrophages, releasing free iron
Correct Answer: B
Rationale: In iron-deficiency anemia, low body iron stores stimulate hepatic transferrin synthesis (and thus TIBC rises),
while ferritin (storage iron) is depleted. Hepcidin is decreased (not increased) in iron deficiency, allowing
ferroportin-mediated iron export to continue. DMT1 defects cause iron-refractory iron-deficiency anemia, not classic
IDA. NBME CBSE: iron homeostasis, biochemistry of iron metabolism.
Q3: A 67-year-old man undergoes an uncomplicated total hip replacement. On postoperative day 4 he
develops dyspnea, tachycardia, and hypoxia. A ventilation-perfusion scan shows multiple segmental
perfusion defects with normal ventilation. Which inflammatory mediator is most directly responsible for
the systemic hemodynamic effects (hypotension, tachycardia) seen in this patient within minutes of the
embolic event?
A. Interleukin-6 release from activated T lymphocytes
B. Platelet-activating factor and thromboxane A2 from activated platelets *[CORRECT]*
C. Tumor necrosis factor-alpha from alveolar macrophages
D. Complement C5a-mediated neutrophil chemotaxis
Correct Answer: B
Rationale: Acute pulmonary embolism produces rapid hemodynamic compromise via platelet activation with release of
thromboxane A2 and PAF, causing bronchoconstriction and pulmonary vasoconstriction. IL-6 and TNF-α are later
Page 2
,NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
cytokine responses (hours). C5a mediates neutrophil chemotaxis, not acute hemodynamic compromise. NBME CBSE:
hemostasis, platelet mediators, inflammation.
Q4: A 19-year-old college student is evaluated for recurrent sinopulmonary infections with encapsulated
organisms. Flow cytometry shows absent CD19+ B cells but normal CD3+ T cells. Serum IgG is
markedly reduced. Genetic testing reveals a loss-of-function mutation in BTK. Which of the following
best describes the pathogenic mechanism of his immunodeficiency?
A. Failure of immunoglobulin class-switch recombination due to defective CD40L
B. Failure of B-cell maturation beyond the pro-B cell stage due to blocked signaling through the pre-B
cell receptor *[CORRECT]*
C. Defective somatic hypermutation causing low-affinity antibodies
D. T-cell deficiency with secondary B-cell dysfunction
Correct Answer: B
Rationale: X-linked agammaglobulinemia (Bruton disease) results from BTK mutation, which blocks B-cell maturation
at the pro-B to pre-B transition due to defective pre-BCR signaling; mature B cells and immunoglobulins are absent.
CD40L deficiency causes hyper-IgM with normal/elevated IgM but low IgG/IgA/IgE. NBME CBSE: immunology,
immunodeficiency, B-cell development.
Q5: A 28-year-old African American woman presents with painful red nodules on both shins, bilateral
hilar lymphadenopathy on chest X-ray, and hypercalcemia. Biopsy of a nodular skin lesion shows
non-caseating granulomas. Which cell type is most directly responsible for the hypercalcemia in this
patient?
A. Multinucleated giant cells expressing 1-alpha-hydroxylase *[CORRECT]*
B. CD4+ T-helper-17 cells secreting IL-17
C. Plasma cells producing parathyroid hormone-related peptide
D. Eosinophils releasing major basic protein
Correct Answer: A
Rationale: Sarcoidosis is characterized by non-caseating granulomas whose activated macrophages (including
multinucleated giant cells) express 1-alpha-hydroxylase, converting 25-OH vitamin D to active 1,25-(OH)2 vitamin D,
producing absorptive hypercalcemia. NBME CBSE: granulomatous inflammation, calcium/vitamin D metabolism.
Q6: A 6-month-old boy of Ashkenazi Jewish descent presents with developmental regression,
exaggerated startle response, and a cherry-red macular spot on funduscopic exam. Hexosaminidase A
activity is absent. Which cellular organelle is functionally defective in this disorder?
A. Mitochondrion
B. Peroxisome
C. Lysosome *[CORRECT]*
D. Smooth endoplasmic reticulum
Correct Answer: C
Rationale: Tay-Sachs disease is a lysosomal storage disorder caused by hexosaminidase A deficiency, leading to GM2
ganglioside accumulation in neurons. The cherry-red spot results from ganglioside-laden ganglion cells surrounding the
Page 3
, NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
relatively spared macula. NBME CBSE: cellular pathology, lysosomal storage disorders, genetics (autosomal recessive).
Q7: A 55-year-old man with metastatic melanoma is treated with a monoclonal antibody that blocks the
PD-1 receptor. Two months later he develops fatigue, hypotension, and hyperpigmented skin; labs show
hyponatremia, hyperkalemia, and low morning cortisol. Which immunologic mechanism best explains
this adverse event?
A. Direct cytotoxicity of melanocytes by activated CD8+ T cells
B. Loss of self-tolerance with autoantibody-mediated destruction of the adrenal cortex *[CORRECT]*
C. Cross-reactivity of anti-melanoma antibodies with steroidogenic enzymes
D. Complement-mediated lysis of pituitary corticotrophs
Correct Answer: B
Rationale: Immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4) remove inhibitory signals on T cells, allowing
breakthrough autoimmunity. Adrenalitis with primary adrenal insufficiency is a recognized immune-related adverse
event mediated by T-cell destruction of the adrenal cortex. NBME CBSE: tumor immunology, immunotherapy,
autoimmunity.
Q8: A 30-year-old man with a long-standing history of gastroesophageal reflux develops a distal
esophageal adenocarcinoma. Biopsy of adjacent non-tumor mucosa shows intestinal metaplasia with
goblet cells. Which molecular event is the earliest recognized driver of the
metaplasia-dysplasia-carcinoma sequence in this Barrett esophagus?
A. TP53 loss of heterozygosity
B. CDKN2A promoter hypermethylation
C. Activation of CDX2 expression in squamous epithelium *[CORRECT]*
D. Amplification of ERBB2 (HER2)
Correct Answer: C
Rationale: Barrett intestinal metaplasia is initiated by acid/bile-induced activation of CDX2 (an intestinal lineage
transcription factor) in squamous epithelium, driving columnar metaplasia. TP53 and CDKN2A alterations occur later,
in the dysplasia-carcinoma progression. ERBB2 amplification is variable, late. NBME CBSE: neoplasia, metaplasia,
molecular pathogenesis.
Q9: A 41-year-old HIV-positive man with a CD4 count of 28/μL develops progressive shortness of breath
and a dry cough. Chest X-ray shows bilateral fluffy perihilar infiltrates. Sputum stain reveals cup-shaped
cysts stained by methenamine silver. Which pharmacologic agent specifically targets the enzyme
dihydropteroate synthase in the causative organism?
A. Trimethoprim
B. Sulfamethoxazole *[CORRECT]*
C. Atovaquone
D. Pentamidine
Correct Answer: B
Rationale: The clinical presentation is Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole (TMP-SMX)
is first-line therapy. Sulfamethoxazole inhibits dihydropteroate synthase (DPS) in folate synthesis; trimethoprim inhibits
Page 4
NBME CBSE
ACTUAL TEST QUESTIONS AND ANSWERS
TEST BANK — COMPLETE SOLUTION
RATED A | EDITION
Total Questions 200
Sections 13 Organ-System & Multisystem Blocks
Format Single-Best-Answer (A–D) with Rationales
Cognitive Mix 20% Recall / 50% Application / 30% Analysis
Alignment NBME CBSE Content Outline & USMLE Step 1
25 Case-Based • 15 Pharmacology • 15
Special Inclusions
Biostatistics
Preclinical Medical Education Standards • Comprehensive Basic Science Examination (CBSE) • USMLE
Step 1 Competencies
Page 1
,NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
Section 1: General Principles
Q1: A 58-year-old man with a 30-pack-year smoking history presents with a 3-cm pulmonary mass.
Biopsy reveals sheets of malignant cells with scant cytoplasm, granular "salt-and-pepper" chromatin,
and absent nucleoli. Numerous mitotic figures and apoptotic bodies are present. Which cellular process is
most directly responsible for the apoptotic bodies observed in this tumor?
A. Activation of BCL-2 with inhibition of caspase-9
B. Release of cytochrome c from mitochondria with activation of the apoptosome *[CORRECT]*
C. Activation of macrophage nitric oxide synthase causing oncotic necrosis
D. Inhibition of p53 with failure of G1/S checkpoint arrest
Correct Answer: B
Rationale: Apoptotic bodies are the histologic hallmark of programmed cell death, mediated by cytochrome c release
from mitochondria, apoptosome (Apaf-1 + caspase-9) assembly, and downstream executioner caspases (3, 6, 7). BCL-2
inhibits apoptosis; p53 induces apoptosis via BAX, so its inhibition would reduce, not increase, apoptotic bodies; nitric
oxide mediates oncotic (necrotic) rather than apoptotic death. NBME CBSE/Step 1 content outline: cellular injury,
apoptosis vs. necrosis.
Q2: A 42-year-old woman presents with fatigue and pallor. Laboratory studies show MCV 78 fL, serum
iron low, ferritin low, and TIBC elevated. Which molecular mechanism most directly accounts for the
elevated transferrin (TIBC) in this patient?
A. Hepcidin-mediated ferroportin degradation is increased
B. Liver transferrin synthesis is upregulated in response to low intracellular iron stores *[CORRECT]*
C. Defective DMT1 intestinal iron transport causes iron trapping in enterocytes
D. Heme oxygenase-1 degrades heme in macrophages, releasing free iron
Correct Answer: B
Rationale: In iron-deficiency anemia, low body iron stores stimulate hepatic transferrin synthesis (and thus TIBC rises),
while ferritin (storage iron) is depleted. Hepcidin is decreased (not increased) in iron deficiency, allowing
ferroportin-mediated iron export to continue. DMT1 defects cause iron-refractory iron-deficiency anemia, not classic
IDA. NBME CBSE: iron homeostasis, biochemistry of iron metabolism.
Q3: A 67-year-old man undergoes an uncomplicated total hip replacement. On postoperative day 4 he
develops dyspnea, tachycardia, and hypoxia. A ventilation-perfusion scan shows multiple segmental
perfusion defects with normal ventilation. Which inflammatory mediator is most directly responsible for
the systemic hemodynamic effects (hypotension, tachycardia) seen in this patient within minutes of the
embolic event?
A. Interleukin-6 release from activated T lymphocytes
B. Platelet-activating factor and thromboxane A2 from activated platelets *[CORRECT]*
C. Tumor necrosis factor-alpha from alveolar macrophages
D. Complement C5a-mediated neutrophil chemotaxis
Correct Answer: B
Rationale: Acute pulmonary embolism produces rapid hemodynamic compromise via platelet activation with release of
thromboxane A2 and PAF, causing bronchoconstriction and pulmonary vasoconstriction. IL-6 and TNF-α are later
Page 2
,NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
cytokine responses (hours). C5a mediates neutrophil chemotaxis, not acute hemodynamic compromise. NBME CBSE:
hemostasis, platelet mediators, inflammation.
Q4: A 19-year-old college student is evaluated for recurrent sinopulmonary infections with encapsulated
organisms. Flow cytometry shows absent CD19+ B cells but normal CD3+ T cells. Serum IgG is
markedly reduced. Genetic testing reveals a loss-of-function mutation in BTK. Which of the following
best describes the pathogenic mechanism of his immunodeficiency?
A. Failure of immunoglobulin class-switch recombination due to defective CD40L
B. Failure of B-cell maturation beyond the pro-B cell stage due to blocked signaling through the pre-B
cell receptor *[CORRECT]*
C. Defective somatic hypermutation causing low-affinity antibodies
D. T-cell deficiency with secondary B-cell dysfunction
Correct Answer: B
Rationale: X-linked agammaglobulinemia (Bruton disease) results from BTK mutation, which blocks B-cell maturation
at the pro-B to pre-B transition due to defective pre-BCR signaling; mature B cells and immunoglobulins are absent.
CD40L deficiency causes hyper-IgM with normal/elevated IgM but low IgG/IgA/IgE. NBME CBSE: immunology,
immunodeficiency, B-cell development.
Q5: A 28-year-old African American woman presents with painful red nodules on both shins, bilateral
hilar lymphadenopathy on chest X-ray, and hypercalcemia. Biopsy of a nodular skin lesion shows
non-caseating granulomas. Which cell type is most directly responsible for the hypercalcemia in this
patient?
A. Multinucleated giant cells expressing 1-alpha-hydroxylase *[CORRECT]*
B. CD4+ T-helper-17 cells secreting IL-17
C. Plasma cells producing parathyroid hormone-related peptide
D. Eosinophils releasing major basic protein
Correct Answer: A
Rationale: Sarcoidosis is characterized by non-caseating granulomas whose activated macrophages (including
multinucleated giant cells) express 1-alpha-hydroxylase, converting 25-OH vitamin D to active 1,25-(OH)2 vitamin D,
producing absorptive hypercalcemia. NBME CBSE: granulomatous inflammation, calcium/vitamin D metabolism.
Q6: A 6-month-old boy of Ashkenazi Jewish descent presents with developmental regression,
exaggerated startle response, and a cherry-red macular spot on funduscopic exam. Hexosaminidase A
activity is absent. Which cellular organelle is functionally defective in this disorder?
A. Mitochondrion
B. Peroxisome
C. Lysosome *[CORRECT]*
D. Smooth endoplasmic reticulum
Correct Answer: C
Rationale: Tay-Sachs disease is a lysosomal storage disorder caused by hexosaminidase A deficiency, leading to GM2
ganglioside accumulation in neurons. The cherry-red spot results from ganglioside-laden ganglion cells surrounding the
Page 3
, NBME CBSE Test Bank — Complete Solution (2026/2027) Rated A
relatively spared macula. NBME CBSE: cellular pathology, lysosomal storage disorders, genetics (autosomal recessive).
Q7: A 55-year-old man with metastatic melanoma is treated with a monoclonal antibody that blocks the
PD-1 receptor. Two months later he develops fatigue, hypotension, and hyperpigmented skin; labs show
hyponatremia, hyperkalemia, and low morning cortisol. Which immunologic mechanism best explains
this adverse event?
A. Direct cytotoxicity of melanocytes by activated CD8+ T cells
B. Loss of self-tolerance with autoantibody-mediated destruction of the adrenal cortex *[CORRECT]*
C. Cross-reactivity of anti-melanoma antibodies with steroidogenic enzymes
D. Complement-mediated lysis of pituitary corticotrophs
Correct Answer: B
Rationale: Immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4) remove inhibitory signals on T cells, allowing
breakthrough autoimmunity. Adrenalitis with primary adrenal insufficiency is a recognized immune-related adverse
event mediated by T-cell destruction of the adrenal cortex. NBME CBSE: tumor immunology, immunotherapy,
autoimmunity.
Q8: A 30-year-old man with a long-standing history of gastroesophageal reflux develops a distal
esophageal adenocarcinoma. Biopsy of adjacent non-tumor mucosa shows intestinal metaplasia with
goblet cells. Which molecular event is the earliest recognized driver of the
metaplasia-dysplasia-carcinoma sequence in this Barrett esophagus?
A. TP53 loss of heterozygosity
B. CDKN2A promoter hypermethylation
C. Activation of CDX2 expression in squamous epithelium *[CORRECT]*
D. Amplification of ERBB2 (HER2)
Correct Answer: C
Rationale: Barrett intestinal metaplasia is initiated by acid/bile-induced activation of CDX2 (an intestinal lineage
transcription factor) in squamous epithelium, driving columnar metaplasia. TP53 and CDKN2A alterations occur later,
in the dysplasia-carcinoma progression. ERBB2 amplification is variable, late. NBME CBSE: neoplasia, metaplasia,
molecular pathogenesis.
Q9: A 41-year-old HIV-positive man with a CD4 count of 28/μL develops progressive shortness of breath
and a dry cough. Chest X-ray shows bilateral fluffy perihilar infiltrates. Sputum stain reveals cup-shaped
cysts stained by methenamine silver. Which pharmacologic agent specifically targets the enzyme
dihydropteroate synthase in the causative organism?
A. Trimethoprim
B. Sulfamethoxazole *[CORRECT]*
C. Atovaquone
D. Pentamidine
Correct Answer: B
Rationale: The clinical presentation is Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole (TMP-SMX)
is first-line therapy. Sulfamethoxazole inhibits dihydropteroate synthase (DPS) in folate synthesis; trimethoprim inhibits
Page 4
