Lung Pathology (Obstructive, Restrictive, Tumors, Infections) MCQs

Pathology · 100 free questions with answers & explanations.

1. A 65-year-old non-smoker woman presents with progressive dyspnea. HRCT shows bilateral basilar honeycombing with traction bronchiectasis. Biopsy shows temporal heterogeneity — areas of fibrosis and honeycombing adjacent to relatively normal parenchyma — with fibroblastic foci at the leading edge. This pattern is:
2. A 60-year-old man with a peripheral lung adenocarcinoma is found to have an EGFR exon 19 deletion by molecular testing. Which IHC marker is most useful to confirm the diagnosis of lung adenocarcinoma (as opposed to squamous cell carcinoma) and direct targeted therapy selection?
3. Panacinar emphysema affects the entire acinus uniformly and is classically associated with alpha-1 antitrypsin deficiency. In contrast, centriacinar (centrilobular) emphysema preferentially affects which part of the acinus and is most strongly associated with:
4. A 65-year-old ex-smoker presents with a peripheral lung mass arising from prior scar tissue. Microscopically it shows glandular structures producing mucin, positive for TTF-1 and CK7, negative for p40 and CK5/6. The diagnosis is:
5. A 55-year-old non-smoker woman presents with progressive dyspnea. HRCT shows bilateral basal predominant honeycombing with traction bronchiectasis but no ground-glass opacity. Surgical lung biopsy shows spatial and temporal heterogeneity with fibroblast foci, honeycombing, normal lung, and fibrosis alternating — predominantly subpleural and basal. This histological pattern is:
6. A 65-year-old heavy smoker develops a centrally located lung mass on CXR. Biopsy shows small blue cells with nuclear molding, scant cytoplasm, 'salt and pepper' chromatin, and neuroendocrine markers (synaptophysin, INSM1, CD56) positive. TTF-1 is positive. SCLC is diagnosed. Which oncogene amplification most frequently drives SCLC and what is the key treatment implication?
7. A 38-year-old immunocompetent woman from Ohio Valley develops progressive dyspnea, cough, bilateral pulmonary infiltrates, and mediastinal lymphadenopathy 3 weeks after excavating soil near a river. Biopsy shows a granulomatous pneumonitis with macrophages containing narrow-based budding yeast 2–4 µm in size within phagosomes. This organism's primary virulence mechanism involves:
8. In usual interstitial pneumonia (UIP), the histological pattern is the substrate for idiopathic pulmonary fibrosis (IPF). The hallmark of UIP that distinguishes it from other fibrotic ILDs is the 'temporal heterogeneity' or 'temporal and spatial heterogeneity.' This means:
9. Carcinoid tumors of the lung are well-differentiated neuroendocrine neoplasms. According to the WHO 2021 classification of thoracic tumors, the distinction between typical carcinoid (TC) and atypical carcinoid (AC) is based primarily on:
10. In pulmonary alveolar proteinosis (PAP), the alveoli fill with PAS-positive, lipid-rich material. The most common pathogenic mechanism of acquired PAP involves:
11. A 60-year-old smoker has a peripheral lung adenocarcinoma with the WHO 2021 classification pattern that shows atypical cells growing along pre-existing alveolar walls without stromal, vascular, or pleural invasion and without central fibrosis. This histological pattern is classified as:
12. A patient with IPF (idiopathic pulmonary fibrosis) has a surgical lung biopsy showing usual interstitial pneumonia (UIP) pattern. The characteristic 'temporal and spatial heterogeneity' of UIP refers to:
13. Idiopathic pulmonary fibrosis (IPF) is associated with which histological pattern that is mandatory for diagnosis in the absence of a confident radiologic UIP pattern?
14. ALK gene rearrangements in non-small cell lung carcinoma are most commonly found in which histological subtype, and what is the characteristic oncogenic mechanism?
15. In alpha-1 antitrypsin (A1AT) deficiency-related emphysema, the panacinar emphysema (involving entire acinus including respiratory bronchioles) is predominantly lower-lobe in distribution. Why does the PiZZ genotype cause both liver disease and lung disease?
16. A 62-year-old non-smoker woman presents with worsening dyspnea and dry cough. HRCT shows bilateral, predominantly basal, subpleural ground-glass opacities with honeycombing and traction bronchiectasis. Lung biopsy shows temporal heterogeneity with areas of normal lung adjacent to fibrosis, fibroblastic foci, and honeycombing without significant inflammation. The diagnosis and histological pattern is:
17. In lung adenocarcinoma, the lepidic growth pattern refers to tumor cells growing along pre-existing alveolar walls without stromal invasion. This pattern has the BEST prognosis. Which molecular profile is MOST likely to be found in a lepidic-predominant adenocarcinoma in a young non-smoking East Asian woman?
18. Silicosis shows progressive massive fibrosis (PMF) with 'eggshell' calcification of hilar lymph nodes on CXR. The key pathological mechanism by which silica particles cause fibrosis involves:
19. A 65-year-old never-smoker woman has a lung adenocarcinoma with a lepidic growth pattern on histology and EGFR exon 19 deletion on molecular testing. The lepidic pattern is defined as:
20. Usual interstitial pneumonia (UIP) is the histological pattern of idiopathic pulmonary fibrosis (IPF). The diagnostic hallmark on lung biopsy is:
21. A 50-year-old man with a history of asbestos exposure presents with a pleural-based mass. Biopsy shows biphasic tumor with epithelioid and sarcomatoid components. The most useful IHC combination for diagnosing malignant mesothelioma versus metastatic adenocarcinoma is:
22. A 55-year-old never-smoker woman has a lung adenocarcinoma with EGFR exon 19 deletion. She receives osimertinib (third-generation EGFR TKI). After 14 months, she progresses with a new EGFR C797S mutation. The C797S mutation causes resistance by:
23. A 68-year-old former asbestos worker develops dyspnea and pleural effusion. CT shows bilateral pleural thickening with calcification and a pleural-based mass. Biopsy shows biphasic tumor with epithelioid and spindle cells, positive for calretinin, WT1, mesothelin, and CK5/6, negative for TTF-1 and CEA. Which pathological finding most reliably confirms a diagnosis of malignant mesothelioma over metastatic adenocarcinoma?
24. In diffuse alveolar damage (DAD), the exudative phase (days 1–7) is characterized by hyaline membrane formation. These hyaline membranes are composed of:
25. Usual interstitial pneumonia (UIP) is the histological pattern underlying idiopathic pulmonary fibrosis (IPF). The hallmark histological feature of UIP that distinguishes it from nonspecific interstitial pneumonia (NSIP) is:
26. WHO 2021 classification of lung tumors reclassified adenocarcinoma-in-situ (AIS) and minimally invasive adenocarcinoma (MIA). Which statement is correct regarding AIS per WHO 2021?
27. A 52-year-old lifelong non-smoker woman is found to have a peripheral lung adenocarcinoma. Molecular testing reveals an EGFR exon 19 deletion. After initial response to osimertinib (3rd-generation EGFR-TKI), the patient progresses. Repeat biopsy shows EGFR T790M mutation is now absent. Which of the following resistance mechanisms is most likely responsible for osimertinib resistance without T790M?
28. In idiopathic pulmonary fibrosis (IPF), the usual interstitial pneumonia (UIP) pattern on HRCT/histology is characterized by basal, subpleural honeycombing with fibroblastic foci. Which molecular pathway is considered central to the pathogenesis of irreversible fibrosis in IPF?
29. On HRCT of the lungs, a 55-year-old woman with progressive dyspnoea shows a 'usual interstitial pneumonia (UIP)' pattern: basal-predominant honeycombing with subpleural, peribronchovascular distribution and traction bronchiectasis, without ground-glass opacity predominantly. The 2022 ATS/ERS/JRS/ALAT guidelines classify this HRCT finding in the appropriate clinical context as:
30. A 62-year-old male ex-smoker is found to have a 2.2 cm pure ground-glass opacity (GGO) nodule in the right upper lobe. CT-guided biopsy shows atypical pneumocyte proliferation along alveolar septa with no stromal, vascular, or pleural invasion. The current WHO 2021 lung tumour classification designation for this lesion, if the lesion is entirely GGO with pure lepidic growth and no invasion, is:
31. A 55-year-old woman non-smoker develops progressive breathlessness and dry cough. HRCT shows bilateral, basal, subpleural reticular opacities with honeycombing and traction bronchiectasis. Surgical lung biopsy shows a heterogeneous pattern with areas of dense fibrosis, fibroblastic foci, and normal lung alternating in a temporal and spatial heterogeneity. What is the WHO histological pattern and associated diagnosis?
32. A 65-year-old smoker with a 3 cm peripheral lung nodule undergoes resection. Histology shows tumour cells forming glands with apical mucin, some with hobnail morphology, growing lepidically along alveolar walls without stromal invasion, vascular invasion or pleural involvement. Maximum invasive component is 4 mm. According to the 2021 WHO lung tumor classification, what is the correct diagnosis?
33. A 70-year-old man with a central lung mass is found to have scattered tumour cells arranged in small clusters in the submucosal layer of the bronchus, with prominent palisading, nuclear moulding, and Azzopardi effect (DNA encrustation of vessel walls). NCAM/CD56 is strongly positive on IHC, along with synaptophysin. What is the most likely diagnosis?
34. A 62-year-old never-smoker woman presents with progressive dyspnea. HRCT shows bilateral basal-predominant subpleural honeycomb changes with traction bronchiectasis. No ground-glass opacity. Surgical biopsy shows temporal heterogeneity, fibroblastic foci adjacent to dense fibrosis, and no granulomas or significant inflammation. Which diagnosis and pattern does this represent, and what is the key molecular driver?
35. A 70-year-old man with a 40 pack-year smoking history has a peripheral lung mass. Biopsy shows cells with abundant pink granular cytoplasm and prominent nucleoli growing in a lepidic pattern along alveolar walls without stromal invasion, vascular invasion, or pleural invasion. The tumor measures 1.8 cm. According to WHO 2021 classification, what is this lesion?
36. In extrinsic allergic alveolitis (hypersensitivity pneumonitis, HP), chronic fibrotic HP resembles UIP/IPF on HRCT. Which histological finding on lung biopsy would strongly favour HP over IPF/UIP?
37. A 62-year-old non-smoker woman presents with progressive dyspnea. HRCT shows bilateral basilar predominant subpleural honeycombing with traction bronchiectasis. Surgical lung biopsy shows a UIP (usual interstitial pneumonia) pattern with temporal and spatial heterogeneity — areas of normal lung, fibroblast foci, and established fibrosis. The current ATS/ERS/JRS/ALAT 2022 guidelines recommend which first-line anti-fibrotic agent?
38. Molecular profiling of a pulmonary adenocarcinoma shows EGFR exon 19 deletion (del19). After initial response to osimertinib (third-generation EGFR TKI), the patient develops progression. The most common resistance mechanism to osimertinib as a first-line agent is:
39. A non-smoker woman with lung adenocarcinoma is found to have an EGFR exon 19 deletion mutation. She is started on a first-generation EGFR TKI (gefitinib). After 12 months, she develops acquired resistance. The most common molecular mechanism of acquired resistance to first/second-generation EGFR TKIs is:
40. A 65-year-old man with a history of asbestos exposure develops a pleural mass. Histology shows biphasic pattern with both epithelioid (tubular) and spindle cell (sarcomatoid) components. Immunohistochemistry: calretinin+, WT1+, CK5/6+, CEA−, TTF-1−. What is this diagnosis and the most relevant oncogenic mechanism?
41. A 40-year-old immunocompromised patient develops bilateral pneumonia with diffuse alveolar damage (DAD) pattern on lung biopsy. Viral inclusions are identified — large eosinophilic intranuclear inclusions surrounded by a clear halo ('owl eye') in enlarged cells. What is the organism and the mechanism of DAD in this setting?
42. A 62-year-old male smoker develops progressive dyspnea. CT shows centrilobular emphysema predominantly in the upper lobes. Histologically, alveolar walls are destroyed. Which protease-antiprotease imbalance is responsible, and why is alpha-1 antitrypsin deficiency a separate but related entity?
43. A 55-year-old non-smoker woman presents with a peripheral lung adenocarcinoma. Molecular profiling reveals an EML4-ALK fusion gene (variant 1, E13:A20). Which pattern of ALK expression is seen on immunohistochemistry, and which targeted therapy is first-line?
44. The WHO 2021 classification of lung adenocarcinoma recognizes lepidic, acinar, papillary, micropapillary, and solid patterns. Which pattern carries the WORST prognosis?
45. A 65-year-old smoker develops a 3 cm peripheral lung mass with pleural puckering. Biopsy shows gland formation, mucin production, and positive TTF-1 and Napsin-A staining. EGFR testing shows exon 19 deletion. Which targeted therapy is preferred?
46. A 30-year-old non-smoker develops panacinar emphysema predominantly in the lower lobes. Serum shows markedly reduced alpha-1 antitrypsin levels. What is the mechanism of emphysema in alpha-1 antitrypsin deficiency?
47. A 65-year-old male smoker develops dyspnea and a peripheral coin lesion in the right upper lobe. Biopsy shows tumor cells growing along the pre-existing alveolar framework without stromal invasion (lepidic growth). CK7+, TTF-1+, napsin A+, CK20-, CDX2-. What is the MOST likely diagnosis?
48. Usual interstitial pneumonia (UIP) on histology shows honeycombing, fibroblastic foci, and patchy fibrosis of varying age ('temporal heterogeneity'). Which feature best explains the poor response to immunosuppressive therapy in UIP/IPF?
49. A 55-year-old non-smoking woman is found to have a peripheral lung adenocarcinoma. Molecular profiling reveals an EGFR exon 19 deletion. Which first-line treatment strategy is MOST appropriate based on current guidelines?
50. A 40-year-old man with restrictive lung disease and dyspnoea on exertion undergoes lung biopsy showing non-necrotising granulomas in a perilymphatic distribution along bronchovascular bundles, interlobular septa, and pleura. Serum ACE is elevated. The diagnosis is sarcoidosis. The perilymphatic distribution of granulomas in sarcoidosis is BEST seen on which imaging modality?
51. A 65-year-old heavy smoker with a central lung mass on imaging undergoes bronchoscopy with biopsy showing large polygonal cells with abundant pale cytoplasm, prominent intercellular bridges, and keratin pearls. This squamous cell carcinoma most commonly causes which paraneoplastic syndrome?
52. The pathogenesis of emphysema in alpha-1 antitrypsin (AAT) deficiency involves loss of protection against which protease, leading to alveolar wall destruction?
53. A 60-year-old male smoker has a peripheral lung mass with pleural puckering. Biopsy shows glandular architecture with mucin production and TTF-1 positive staining. EGFR mutation testing is positive. The MOST likely diagnosis is:
54. Usual interstitial pneumonia (UIP) on CT shows bilateral basal-predominant honeycombing with traction bronchiectasis. On histology, the key distinguishing feature from other interstitial pneumonias is:
55. A 55-year-old man who never smoked presents with lower lobe-predominant ground-glass opacities and honeycombing on HRCT. Lung biopsy shows temporal and spatial heterogeneity with fibroblastic foci, dense fibrosis, and honeycombing adjacent to areas of normal lung — a pattern described as usual interstitial pneumonia (UIP). This histopathological pattern is the hallmark of:
56. A 60-year-old heavy smoker presents with chronic cough and a central cavitating lung mass. Biopsy shows large polygonal cells with intercellular bridges and keratin pearl formation. The most appropriate tumour marker to measure in serum is:
57. In panacinar (panlobular) emphysema, which part of the acinus is primarily and earliest affected?
58. In alpha-1-antitrypsin deficiency causing emphysema, the pathogenic mechanism is primarily:
59. A 65-year-old heavy smoker has a peripheral lung mass with hypercalcaemia. Histology shows large cells with intercellular bridges, keratinisation, and abundant pink cytoplasm. Which receptor mechanism does PTH-rP use to cause hypercalcaemia?
60. Usual interstitial pneumonia (UIP) pattern on high-resolution CT shows honeycombing with basal, subpleural, bilateral distribution. On histology, the hallmark finding that distinguishes UIP from NSIP is:
61. In usual interstitial pneumonia (UIP), the histological pattern that distinguishes it from other forms of ILD is:
62. Small cell lung carcinoma (SCLC) is derived from neuroendocrine cells (Kulchitsky cells) of the bronchial mucosa. Which paraneoplastic syndrome is most characteristic of SCLC due to ectopic ACTH production?
63. A 55-year-old non-smoker woman with progressive dyspnea has a CT showing bilateral basal predominant honeycombing and traction bronchiectasis. Lung biopsy shows temporal heterogeneity with fibroblastic foci adjacent to dense collagen fibrosis and relatively normal lung. The pattern is:
64. A 65-year-old heavy smoker presents with cough, hemoptysis, and a central hilar mass. Biopsy shows tumor cells with intercellular bridges and individual cell keratinization. This histological finding is characteristic of:
65. A 45-year-old coal miner with progressive dyspnea has chest X-ray showing upper lobe nodular opacities and fibrosis. Biopsy shows concentric collagen nodules with a necrotic core and doubly refractile silica particles. The diagnosis and mechanism of fibrosis is best described as:
66. A 55-year-old non-smoker woman develops progressive exertional dyspnea and bibasal fine inspiratory crackles. CT shows bilateral ground-glass opacities with honeycombing predominantly in the subpleural regions. The surgical lung biopsy shows temporally and spatially heterogeneous fibrosis with fibroblastic foci. This pattern is called:
67. A 70-year-old heavy smoker presents with superior vena cava syndrome and Horner's syndrome ipsilateral to a right apical lung mass. This presentation is most consistent with:
68. Which histological finding in pulmonary emphysema differentiates centriacinar (centrilobular) type from panacinar (panlobular) type?
69. Panacinar emphysema is classically associated with alpha-1 antitrypsin (AAT) deficiency and preferentially involves which zone of the lung?
70. A 65-year-old former asbestos worker develops a pleural tumor with epithelioid and sarcomatoid components. Immunohistochemistry shows calretinin+, WT-1+, CK5/6+, CEA- staining. The diagnosis is:
71. A 55-year-old lifetime non-smoker woman has a peripheral lung adenocarcinoma with EGFR exon 19 deletion. This mutation confers sensitivity to which targeted therapy?
72. Usual interstitial pneumonia (UIP) pattern on lung biopsy is characterized by which combination of histological features?
73. A 65-year-old male smoker develops hemoptysis and a right hilar mass. Biopsy shows pleomorphic cells with intercellular bridges (desmosomes), pink cytoplasm, and keratin pearls. Which IHC profile confirms the diagnosis?
74. A 70-year-old non-smoker woman has HRCT showing bilateral basilar-predominant subpleural reticular opacities with honeycombing. Surgical biopsy shows temporal and spatial heterogeneity with fibroblastic foci, dense fibrosis, and honeycomb change adjacent to normal lung. This histological pattern is:
75. In alpha-1 antitrypsin deficiency, panacinar emphysema affecting the lower lobes develops because:
76. A 65-year-old non-smoker woman is found to have a peripheral lung adenocarcinoma growing along existing alveolar walls without destroying the architecture (non-invasive growth pattern). This pattern is termed:
77. A 45-year-old man with a 20-pack-year smoking history has FEV1/FVC ratio of 0.60 and FEV1 42% of predicted. His lung biopsy shows panacinar emphysema predominantly in the lower lobes. This pattern is most characteristic of:
78. In usual interstitial pneumonia (UIP), the pathological hallmark is the 'temporal heterogeneity' of fibrosis. Which specific histological finding distinguishes UIP from other interstitial pneumonias?
79. In usual interstitial pneumonia (UIP), the histological hallmark that distinguishes it from other interstitial pneumonias is:
80. A 60-year-old smoker has a peripheral lung mass. Biopsy shows gland-forming cells with intracellular mucin positivity and TTF-1 positivity. The most likely histological type is:
81. Panacinar emphysema predominantly affecting the lower lobes is classically associated with:
82. A 60-year-old male smoker undergoes lobectomy for a peripheral lung mass. Histology shows malignant cells arranged in acini and glandular structures with mucin production; immunostaining is TTF-1 positive, CK7 positive, and CK20 negative. What is the diagnosis?
83. A 35-year-old non-smoker woman with lung adenocarcinoma is tested for molecular targets. The EGFR mutation most predictive of response to first-generation EGFR tyrosine kinase inhibitors (gefitinib, erlotinib) is:
84. A 45-year-old patient with progressive dyspnea has a chest CT showing bilateral ground-glass opacities and honeycombing in the lower lobes. Surgical lung biopsy shows dense fibrosis with architectural distortion, fibroblastic foci at the advancing fibrotic front, and relative sparing of the upper lobes. The histological pattern is:
85. A 45-year-old male smoker with severe early-onset emphysema is found to have a serum alpha-1 antitrypsin (AAT) level of 20 mg/dL (normal >100 mg/dL) and a Pi*ZZ genotype. The mechanism of emphysema in AAT deficiency is:
86. Usual interstitial pneumonia (UIP) is the histological pattern of idiopathic pulmonary fibrosis (IPF). Which histological feature of UIP is most characteristic and essential for diagnosis, distinguishing it from nonspecific interstitial pneumonia (NSIP)?
87. A 50-year-old male smoker with central lung mass undergoes bronchoscopy; biopsy shows a squamous cell carcinoma. Laboratory reveals serum calcium of 12.8 mg/dL. Which molecule secreted by the squamous cell carcinoma is responsible for the hypercalcaemia?
88. Alpha-1 antitrypsin (A1AT) deficiency causes panacinar emphysema predominating in the lung bases and liver disease. The liver disease results from a specific protein quality control failure. What is the mechanism of hepatocyte injury in A1AT deficiency (PiZZ genotype)?
89. Panacinar emphysema (involving the entire acinus from respiratory bronchiole to alveolar sac) is characteristically associated with:
90. Usual interstitial pneumonia (UIP) is the histological pattern underlying idiopathic pulmonary fibrosis. The hallmark histological feature that distinguishes UIP from other interstitial pneumonias is:
91. Bronchioloalveolar carcinoma (now termed lepidic-predominant adenocarcinoma) shows a characteristic growth pattern that distinguishes it from invasive adenocarcinoma. This pattern is:
92. A 55-year-old miner with 20 years of coal dust exposure has bilateral upper lobe nodules with progressive massive fibrosis (PMF) on CT. Histology shows black pigment deposits with stellate fibrotic nodules. The pathophysiology involves activation of which key cellular pathway?
93. A 62-year-old non-smoker woman presents with a peripheral lung adenocarcinoma showing lepidic growth pattern — tumor cells growing along intact alveolar walls without stromal invasion. What is this histological subtype and its significance?
94. In usual interstitial pneumonia (UIP) — the histological pattern underlying idiopathic pulmonary fibrosis (IPF) — which feature is most characteristic and diagnostic?
95. A 45-year-old non-smoker woman with bilateral hilar lymphadenopathy, elevated serum ACE, hypercalcemia, and erythema nodosum undergoes transbronchial biopsy showing non-caseating epithelioid granulomas with Schaumann bodies and asteroid bodies. The mechanism of hypercalcemia in this condition is:
96. In the pathogenesis of usual interstitial pneumonia (UIP) / idiopathic pulmonary fibrosis (IPF), the central mechanism involves abnormal re-epithelialization after repetitive alveolar injury. The key growth factor released by injured alveolar epithelial cells that drives fibroblast activation and myofibroblast differentiation is:
97. Pancoast tumor (superior sulcus tumor) invades the brachial plexus and stellate ganglion. Which specific neurological finding results from stellate ganglion involvement?
98. Usual interstitial pneumonia (UIP) is the histopathological pattern underlying idiopathic pulmonary fibrosis (IPF). Which combination of features on surgical lung biopsy is DIAGNOSTIC of UIP?
99. In usual interstitial pneumonia (UIP), the histological hallmark distinguishing it from other interstitial lung diseases is:
100. A 60-year-old asbestos-exposed shipyard worker develops a pleural mass. Biopsy shows spindle and epithelioid cells with tubulopapillary architecture; IHC is positive for calretinin, WT-1, and D2-40, and negative for CEA and TTF-1. The diagnosis is: