Question Bank Lung (Rosai) PDF

1. A 70-year-old male presents with weight loss, chronic cough, and hemoptysis. He has a history of smoking and asbestos exposure. A chest CT reveals a mass in the superior pulmonary sulcus. Which of the following additional findings is most likely associated with this presentation? A. Horner syndr...

1. A 70-year-old male presents with weight loss, chronic cough, and hemoptysis. He has a history of smoking and asbestos exposure. A chest CT reveals a mass in the superior pulmonary sulcus. Which of the following additional findings is most likely associated with this presentation? A. Horner syndrome due to sympathetic chain involvement B. Pancoast syndrome characterized by shoulder pain radiating down the arm C. Paraneoplastic syndrome involving Cushing’s syndrome D. Coin lesion on chest x-ray Rationale: The mass located in the superior pulmonary sulcus suggests a Pancoast tumor, which is associated with Pancoast syndrome. This syndrome typically involves shoulder pain that radiates down the arm due to the involvement of the brachial plexus and possibly Horner syndrome from sympathetic chain involvement, but the defining characteristic of Pancoast syndrome is shoulder pain radiating to the arm. Therefore, B is the most appropriate answer. Horner syndrome alone would not be as specific without the pain distribution. 2. A 45-year-old non-smoker woman is diagnosed with adenocarcinoma of the lung. She has no history of occupational exposure. Which of the following factors most likely played a role in her cancer development? A. Genetic predisposition, particularly common in women and Asian populations B. Long-term secondhand smoke exposure C. Past exposure to radon gas in her home D. Previous tuberculosis infection causing scar carcinoma Rationale: Among non-smokers, particularly women, adenocarcinoma of the lung is often linked to genetic predisposition rather than environmental factors. This is especially prevalent in Asian populations. Although secondhand smoke and radon exposure are risk factors, genetic factors are the most significant contributor in non-smokers with lung cancer. Previous tuberculosis leading to scar carcinoma is rare and less likely in this scenario. Therefore, A is the correct answer. 3. A 68-year-old male with a significant smoking history is diagnosed with multiple synchronous lung tumors. Despite genetic evidence of a common clonal origin, which of the following statements best reflects his prognosis compared to a patient with a single tumor? A. He is likely to have a worse prognosis due to the presence of multiple tumors. B. His prognosis is better than someone with intrapulmonary metastasis despite the presence of multiple tumors. C. His prognosis is similar to that of someone with extensive small cell lung carcinoma. D. He has the same prognosis as a patient with metastatic lung cancer to distant organs. Rationale: Although the tumors share a common clonal origin, patients with multiple synchronous primary tumors tend to have a better prognosis compared to those with intrapulmonary metastases. This is because these tumors are often treated as separate primaries, which typically behave less aggressively than metastatic tumors. The presence of multiple tumors does not automatically result in a worse prognosis if they are primary rather than metastatic. Thus, B is the correct answer. 1. A 52-year-old man presents with muscle weakness, especially in the proximal muscles, and difficulty swallowing. Neurological examination reveals diminished reflexes. He has a history of heavy smoking. Imaging shows a lung mass. Which paraneoplastic syndrome is most likely in this patient? A. Carcinoid syndrome associated with carcinoid tumor B. Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) secretion in small cell carcinoma C. Myopathic–myasthenia syndrome (Lambert–Eaton syndrome) associated with small cell carcinoma D. Hypercalcemia due to squamous cell carcinoma Rationale: Lambert-Eaton syndrome, a paraneoplastic syndrome, is commonly associated with small cell lung carcinoma. It presents with muscle weakness, particularly in the proximal muscles, and diminished reflexes, which aligns with the symptoms described. The other options, while linked to lung cancers, do not fit the specific clinical presentation as closely as Lambert-Eaton syndrome does. 2. A 65-year-old female with a long history of smoking presents with confusion, lethargy, and a serum sodium level of 120 mEq/L (normal: 135-145 mEq/L). Which tumor type is most likely responsible for her symptoms? A. Squamous cell carcinoma associated with hypercalcemia B. Small cell carcinoma associated with syndrome of inappropriate antidiuretic hormone (SIADH) C. Carcinoid tumor associated with carcinoid syndrome D. Small cell carcinoma associated with myasthenic syndrome Rationale: The patient's hyponatremia (low sodium level) is indicative of SIADH, a condition often caused by small cell carcinoma. This paraneoplastic syndrome leads to excessive water retention, diluting the sodium in the body. The other options, while related to lung cancer, do not directly explain the patient's hyponatremia. 3. A 60-year-old male presents with severe joint pain, digital clubbing, and a chronic cough. Imaging reveals a lung mass near the pleural surface. What is the most likely tumor type associated with his symptoms? A. Any tumor type, with the symptoms being more related to proximity to the pleural surface B. Small cell carcinoma C. Squamous cell carcinoma D. Carcinoid tumor Rationale: The patient’s symptoms suggest hypertrophic pulmonary osteoarthropathy (HPOA), which is associated with digital clubbing and joint pain. HPOA is not strongly tied to a specific tumor type but is more related to the tumor's proximity to the pleural surface. Thus, the correct answer is that it can be related to any tumor type with pleural involvement. 4. A 58-year-old male presents with new-onset confusion, personality changes, and hallucinations. He has a significant smoking history. A lung biopsy reveals small cell carcinoma. Which paraneoplastic syndrome is most likely in this case? A. Hypercalcemia associated with squamous cell carcinoma B. Mental syndromes, including toxic confusional psychosis, associated with small cell carcinoma C. Cushing syndrome associated with small cell carcinoma D. Carcinoid syndrome associated with carcinoid tumor Rationale: Mental syndromes, including toxic confusional psychosis, are known paraneoplastic syndromes associated with small cell carcinoma. This explains the neuropsychiatric symptoms described in the scenario. Hypercalcemia, Cushing syndrome, and carcinoid syndrome are associated with different presentations and would not explain the mental status changes. 5. A 45-year-old woman presents with episodic flushing, diarrhea, and wheezing. She is found to have a lung mass on imaging. What is the most likely diagnosis? A. Small cell carcinoma associated with Cushing syndrome B. Squamous cell carcinoma associated with hypercalcemia C. Small cell carcinoma associated with encephalomyelitis D. Carcinoid tumor causing carcinoid syndrome Rationale: The triad of flushing, diarrhea, and wheezing is characteristic of carcinoid syndrome, which is typically caused by carcinoid tumors. These symptoms result from the secretion of serotonin and other vasoactive substances by the tumor. Small cell carcinoma can cause other paraneoplastic syndromes but not this specific syndrome. 1. A 60-year-old male with a history of heavy smoking presents with a lung mass. Biopsy shows poorly differentiated cells, and immunohistochemistry is positive for TTF-1 and napsin A. What is the most likely diagnosis? A. Squamous cell carcinoma B. Large cell carcinoma C. Adenocarcinoma D. Small cell carcinoma Rationale: TTF-1 and napsin A are markers commonly associated with adenocarcinoma of the lung, with TTF-1 being expressed in over 80% of adenocarcinomas. The positivity for both markers strongly suggests adenocarcinoma. 2. A biopsy from a lung mass in a 65-year-old male reveals cells that are negative for TTF-1 and napsin A but strongly positive for p40. Which subtype of lung carcinoma is most likely? A. Adenocarcinoma B. Small cell carcinoma C. Squamous cell carcinoma D. Sarcomatoid carcinoma Rationale: p40 is a specific marker for squamous cell carcinoma. The negativity for TTF-1 and napsin A, which are markers for adenocarcinoma, further supports the diagnosis of squamous cell carcinoma. 3. A 55-year-old female with no significant smoking history presents with a lung mass. The tumor cells are positive for TTF-1 but negative for p63. What is the most likely diagnosis? A. Squamous cell carcinoma B. Adenocarcinoma C. Large cell carcinoma D. Sarcomatoid carcinoma Rationale: TTF-1 positivity, especially in the absence of p63 expression, is highly suggestive of adenocarcinoma. This is common in non-smokers, particularly women. 4. A lung biopsy in a 70-year-old male reveals a tumor with a mixture of glandular and squamous differentiation. Immunohistochemical stains are positive for both TTF-1 and p40. What is the most appropriate classification? A. Adenosquamous carcinoma B. Large cell carcinoma C. Small cell carcinoma D. Neuroendocrine tumor Rationale: The presence of both glandular (TTF-1 positive) and squamous (p40 positive) differentiation in the tumor indicates adenosquamous carcinoma, which is a mixed type of lung carcinoma. 5. A 62-year-old male with a lung mass has a biopsy that is positive for chromogranin, synaptophysin, and TTF-1. The tumor cells are small, round, and hyperchromatic. What is the most likely diagnosis? A. Adenocarcinoma B. Squamous cell carcinoma C. Large cell carcinoma D. Small cell carcinoma Rationale: The positivity for neuroendocrine markers like chromogranin and synaptophysin, along with TTF-1 positivity and the described morphology, strongly suggests small cell carcinoma, a type of neuroendocrine tumor. 6. A lung tumor in a 68-year-old male shows spindle cell morphology with immunohistochemical positivity for cytokeratins. What is the most appropriate diagnosis? A. Squamous cell carcinoma B. Adenocarcinoma C. Sarcomatoid carcinoma D. Large cell carcinoma Rationale: Spindle cell morphology in the lung, combined with cytokeratin positivity, is characteristic of sarcomatoid carcinoma, which includes tumors with mesenchymal differentiation. 7. A lung biopsy reveals a poorly differentiated tumor with cells that are negative for TTF-1, napsin A, and p40 but positive for CK5/6. Which lung carcinoma subtype is most likely? A. Adenocarcinoma B. Large cell carcinoma C. Squamous cell carcinoma D. Small cell carcinoma Rationale: Large cell carcinoma can present with a lack of specific markers (TTF-1, napsin A, p40) but may still express cytokeratins like CK5/6, making it the most likely diagnosis when other subtypes are ruled out. 8. A lung mass biopsy in a 58-year-old woman shows cells that are positive for napsin A and negative for p40. What is the most likely subtype of lung carcinoma? A. Adenocarcinoma B. Squamous cell carcinoma C. Large cell carcinoma D. Sarcomatoid carcinoma Rationale: Napsin A positivity is highly specific for adenocarcinoma. The absence of p40, which is a marker for squamous cell carcinoma, further supports the diagnosis of adenocarcinoma. 9. A 63-year-old male with a lung mass has a biopsy showing a tumor with neuroendocrine features, including chromogranin positivity and high mitotic rate. Which lung carcinoma subtype is most likely? A. Adenocarcinoma B. Squamous cell carcinoma C. Small cell carcinoma D. Large cell carcinoma Rationale: Neuroendocrine features such as chromogranin positivity and a high mitotic rate are classic findings in small cell carcinoma, a highly aggressive form of lung cancer. 10. A 70-year-old male presents with a lung mass that is biopsied, showing poorly differentiated cells with strong p63 and weak TTF-1 staining. What is the most likely diagnosis? A. Squamous cell carcinoma B. Adenocarcinoma C. Large cell carcinoma D. Small cell carcinoma Rationale: Strong p63 staining with weak or absent TTF-1 suggests squamous cell carcinoma, even in poorly differentiated tumors. TTF-1 positivity is more commonly associated with adenocarcinoma or small cell carcinoma. 1. A 55-year-old female presents with a peripheral lung mass that on gross examination is gelatinous and gray-yellow. Biopsy shows tumor cells with abundant mucin. Which histologic subtype of lung carcinoma is most likely? A. Squamous cell carcinoma B. Adenocarcinoma C. Large cell carcinoma D. Small cell carcinoma Rationale: Adenocarcinomas are often peripheral and can produce abundant mucin, giving them a gelatinous appearance. The other types of lung carcinomas do not typically present with these features. 2. A 60-year-old male with a smoking history presents with a peripheral lung mass and pleural fibrosis. Biopsy reveals a poorly differentiated tumor that is TTF-1 positive. What is the most likely diagnosis? A. Squamous cell carcinoma B. Large cell carcinoma C. Adenocarcinoma D. Small cell carcinoma Rationale: TTF-1 positivity is a strong indicator of adenocarcinoma, particularly in peripheral lung tumors, which often show pleural involvement and fibrosis. 3. A 65-year-old male presents with a peripheral lung tumor that has invaded the pleural space, mimicking diffuse mesothelioma. What is the most likely histologic type of this tumor? A. Large cell carcinoma B. Squamous cell carcinoma C. Adenocarcinoma D. Small cell carcinoma Rationale: Adenocarcinomas can occasionally spread extensively into the pleural space and mimic the appearance of diffuse mesothelioma, a phenomenon known as pseudomesotheliomatous carcinoma. 4. A lung biopsy from a 62-year-old female reveals a tumor with a lepidic growth pattern and minimal invasion. What is the prognosis for this patient? A. Poor B. Intermediate C. Excellent D. Uncertain Rationale: A lepidic growth pattern with minimal invasion in adenocarcinoma is associated with an excellent prognosis, particularly in early-stage, node-negative tumors. 5. A 68-year-old male with a history of smoking presents with a lung mass that is found to be an adenocarcinoma. The tumor has a significant micropapillary component. What does this imply about the tumor's behavior? A. More aggressive with a higher risk of recurrence B. Benign behavior with low recurrence risk C. Excellent prognosis D. No prognostic implications Rationale: A micropapillary component in adenocarcinoma is associated with a more aggressive behavior and a higher risk of recurrence, even if it is a minor component of the tumor. 6. A lung adenocarcinoma in a 70-year-old male is found to have a KRAS mutation. Which of the following is most likely true about this patient's smoking history? A. Never smoked B. Light smoker C. Current or former smoker D. Non-smoker with secondhand smoke exposure Rationale: KRAS mutations are frequently associated with smoking and are commonly found in lung adenocarcinomas from current or former smokers. 7. A 58-year-old woman with lung adenocarcinoma tests positive for an ALK gene translocation. Which of the following characteristics is most likely true for this patient? A. Never-smoker or light smoker B. Heavy smoker C. Older age at diagnosis D. Presence of KRAS mutation Rationale: ALK translocations are typically found in lung adenocarcinomas in younger patients who are never-smokers or light smokers, and they are mutually exclusive with KRAS mutations. 8. A lung biopsy reveals adenocarcinoma cells that are positive for TTF-1 and napsin A, but negative for CDX2. What is the significance of the CDX2 negativity? A. Indicates a high-grade tumor B. Suggests squamous cell carcinoma C. Helps differentiate from metastatic colorectal carcinoma D. Suggests small cell carcinoma Rationale: CDX2 negativity in a lung adenocarcinoma helps differentiate it from metastatic colorectal carcinoma, which typically expresses CDX2. 9. A 64-year-old male presents with a peripheral lung mass, and biopsy reveals adenocarcinoma with signet ring cell morphology. Which molecular feature is this tumor most likely to have? A. ALK translocation B. EGFR mutation C. KRAS mutation D. TP53 mutation Rationale: Signet ring cell morphology in lung adenocarcinoma is often associated with ALK translocations, which have significant implications for targeted therapy. 10. A 58-year-old female with a history of light smoking is diagnosed with lung adenocarcinoma. Molecular testing shows an EGFR mutation. Which of the following is most likely true about the patient's demographics? A. Male and Asian B. Female and Caucasian C. Female and East Asian D. Male and African-American Rationale: EGFR mutations are more common in women, East Asians, and non-smokers or light smokers, making "Female and East Asian" the most likely demographic profile for a patient with this mutation. 1. A 58-year-old male presents with a centrally located lung mass. The biopsy reveals poorly differentiated cells with strong, diffuse staining for CK5/6 and p63, and the presence of keratin pearls. What is the most likely diagnosis? A. Adenocarcinoma B. Squamous cell carcinoma C. Large cell carcinoma D. Small cell carcinoma Rationale: The strong, diffuse staining for CK5/6 and p63, along with the presence of keratin pearls, is characteristic of squamous cell carcinoma (SCC). These features help distinguish SCC from other types of lung cancers. 2. A 65-year-old male with a history of heavy smoking presents with a lung mass. The tumor cells show basaloid features with a lobulated growth pattern and peripheral palisading. Immunohistochemistry is positive for p63 and negative for TTF-1. What is the most likely diagnosis? A. Small cell carcinoma B. Large cell carcinoma C. Basaloid squamous cell carcinoma D. Adenosquamous carcinoma Rationale: Basaloid squamous cell carcinoma is a poorly differentiated variant of SCC that presents with basaloid features, lobulated growth, and peripheral palisading. The immunohistochemical profile (p63 positive, TTF-1 negative) supports this diagnosis. 3. A lung biopsy from a 60-year-old female smoker reveals a tumor with strong p40 staining and occasional intracytoplasmic mucin droplets. However, only 5% of the tumor shows a glandular component. What is the correct classification of this tumor? A. Adenosquamous carcinoma B. Squamous cell carcinoma C. Adenocarcinoma D. Large cell carcinoma Rationale: The presence of occasional mucin droplets in a predominantly squamous tumor does not warrant reclassification as adenosquamous carcinoma. For a tumor to be classified as adenosquamous, at least 10% of the tumor must show a distinct glandular (adenomatous) component. 4. A 63-year-old male with a centrally located lung mass is diagnosed with squamous cell carcinoma. Genetic analysis reveals TP53 mutation and inactivation of CDKN2A. Which of the following is the most likely additional genetic alteration in this tumor? A. ALK translocation B. EGFR mutation C. NOTCH1 mutation D. KRAS mutation Rationale: Squamous cell carcinomas often involve mutations in TP53 and inactivation of CDKN2A. NOTCH1, a gene involved in squamous differentiation, is another gene frequently altered in SCC. 5. A 70-year-old male presents with a lung mass and biopsy shows keratin formation and a giant cell foreign body reaction to keratin. Which lung carcinoma subtype is most likely? A. Adenocarcinoma B. Small cell carcinoma C. Squamous cell carcinoma D. Large cell carcinoma Rationale: The presence of keratin formation and a giant cell foreign body reaction to keratin is characteristic of squamous cell carcinoma. These features are not typically seen in other lung cancer subtypes. 6. A 65-year-old female presents with a centrally located lung mass. Biopsy reveals non-keratinizing carcinoma with focal staining for neuroendocrine markers and strong diffuse p63 positivity. What is the most likely diagnosis? A. Small cell carcinoma B. Large cell neuroendocrine carcinoma C. Basaloid squamous cell carcinoma D. Adenosquamous carcinoma Rationale: Basaloid squamous cell carcinoma is a poorly differentiated variant of SCC that can present with focal staining for neuroendocrine markers, which is unusual for other types of SCC. Despite this focal neuroendocrine marker expression, the strong and diffuse p63 positivity supports the diagnosis of basaloid SCC rather than a purely neuroendocrine tumor like small cell carcinoma or large cell neuroendocrine carcinoma. 7. A 59-year-old male with a history of smoking presents with a lung mass. Histology shows a poorly differentiated carcinoma with strong staining for CK5/6 and absence of TTF-1 staining. Which additional immunohistochemical marker would most likely confirm the diagnosis of squamous cell carcinoma? A. p40 B. Napsin A C. CDX2 D. Chromogranin Rationale: p40 is a specific marker for squamous cell carcinoma. The absence of TTF-1, which is more indicative of adenocarcinoma or small cell carcinoma, along with CK5/6 positivity, further supports the diagnosis of SCC. 8. A lung biopsy reveals a tumor with an oncocytoid appearance, and immunohistochemistry is positive for CK5/6 and p63. Which lung carcinoma subtype is most likely associated with this histologic appearance? A. Squamous cell carcinoma B. Adenocarcinoma C. Large cell carcinoma D. Small cell carcinoma Rationale: The oncocytoid appearance (due to increased mitochondrial density) can be seen in squamous cell carcinoma. The immunohistochemical profile (CK5/6 and p63 positivity) supports the diagnosis of SCC. 9. A 68-year-old male presents with a lung mass, and biopsy reveals a squamous cell carcinoma. Genetic analysis shows mutations in KEAP1 and NFE2L2. Which biological process is most likely affected by these mutations? A. Cell cycle regulation B. Oxidative stress response C. DNA repair mechanisms D. Apoptosis pathways Rationale: KEAP1 and NFE2L2 are genes involved in the oxidative stress response. Mutations in these genes can alter how cancer cells respond to oxidative stress, which can contribute to tumor growth and survival in squamous cell carcinoma. 10. A lung biopsy in a 60-year-old male smoker reveals squamous cell carcinoma with GATA3 positivity. What is the significance of this finding? A. GATA3 positivity is unusual but can occur in lung SCC and may help distinguish it from other malignancies B. Indicates a metastatic origin from the breast C. Confirms primary lung origin D. Suggests coexisting adenocarcinoma Rationale: GATA3 is typically associated with breast and urothelial carcinomas but can be positive in about 10% of lung squamous cell carcinomas. While it's not a primary marker for lung SCC, its positivity should prompt consideration of the differential diagnosis, including the possibility of a metastasis from another site. However, its presence in lung SCC is recognized and should be interpreted with caution, considering the full clinical and histopathological context. 1. A 63-year-old male with a history of heavy smoking presents with a central lung mass. Biopsy reveals small, round cells with scant cytoplasm and finely granular chromatin. The tumor is TTF-1 positive and shows a Ki-67 index of nearly 100%. What is the most likely diagnosis? A. Large cell neuroendocrine carcinoma B. Atypical carcinoid tumor C. Small cell carcinoma D. Basaloid squamous cell carcinoma Rationale: The combination of small, round cells with scant cytoplasm, finely granular chromatin, high Ki-67 index, and TTF-1 positivity strongly suggests small cell carcinoma (SCLC), a highly aggressive neuroendocrine tumor. 2. A lung biopsy from a 58-year-old female reveals large cells with prominent nucleoli, abundant cytoplasm, and a high mitotic rate (>10 mitoses per 2 mm²). The tumor shows neuroendocrine architecture with organoid nests and peripheral palisading. What is the most likely diagnosis? A. Small cell carcinoma B. Large cell neuroendocrine carcinoma C. Typical carcinoid tumor D. Adenocarcinoma Rationale: The presence of large cells with neuroendocrine architecture, prominent nucleoli, and a high mitotic rate is characteristic of large cell neuroendocrine carcinoma (LCNEC), differentiating it from small cell carcinoma (SCLC) which has smaller cells. 3. A 70-year-old male presents with a centrally located lung mass. The biopsy reveals a tumor with high mitotic activity, necrosis, and a solid growth pattern. Immunohistochemistry is positive for synaptophysin and CD56 but negative for chromogranin. What is the most likely diagnosis? A. Atypical carcinoid tumor B. Small cell carcinoma C. Large cell neuroendocrine carcinoma D. Squamous cell carcinoma Rationale: Small cell carcinoma (SCLC) often shows positivity for synaptophysin and CD56, even when chromogranin is negative. The combination of high mitotic activity, necrosis, and solid growth pattern further supports the diagnosis of SCLC. 4. A 64-year-old male with a central lung mass undergoes biopsy. The tumor cells are small, round, and exhibit nuclear molding. There is also extensive necrosis. Immunohistochemistry shows strong TTF-1 positivity but only focal staining for neuroendocrine markers. What is the most likely diagnosis? A. Small cell carcinoma B. Large cell neuroendocrine carcinoma C. Basaloid squamous cell carcinoma D. Atypical carcinoid tumor Rationale: The small, round cells with nuclear molding, extensive necrosis, and strong TTF-1 positivity, along with focal neuroendocrine marker expression, are indicative of small cell carcinoma (SCLC). The presence of neuroendocrine markers supports the diagnosis but is not required for SCLC. 5. A 55-year-old female with a history of smoking presents with a peripheral lung mass. The biopsy reveals a tumor with prominent nucleoli, abundant cytoplasm, and a neuroendocrine growth pattern. The Ki-67 index is high, and immunohistochemistry is positive for synaptophysin and chromogranin. What is the most likely diagnosis? A. Typical carcinoid tumor B. Large cell neuroendocrine carcinoma C. Small cell carcinoma D. Adenocarcinoma Rationale: The large cell size, prominent nucleoli, abundant cytoplasm, neuroendocrine growth pattern, and high Ki-67 index point to large cell neuroendocrine carcinoma (LCNEC), differentiating it from small cell carcinoma which has smaller cells. 6. A lung biopsy in a 62-year-old male smoker reveals small, round tumor cells with a high nuclear-to-cytoplasmic ratio and finely dispersed chromatin. Immunohistochemistry is positive for low-molecular-weight keratins and TTF-1 but negative for CK5/6 and p63. What is the most likely diagnosis? A. Basaloid squamous cell carcinoma B. Large cell neuroendocrine carcinoma C. Small cell carcinoma D. Atypical carcinoid tumor Rationale: The small, round cells with a high nuclear-to-cytoplasmic ratio, finely dispersed chromatin, and positivity for low-molecular-weight keratins and TTF-1 are characteristic of small cell carcinoma (SCLC). The negative staining for CK5/6 and p63 helps exclude basaloid squamous cell carcinoma. 7. A 59-year-old male with a central lung tumor undergoes biopsy. The tumor is composed of cells with abundant cytoplasm, prominent nucleoli, and a neuroendocrine architecture. Immunohistochemistry is positive for TTF-1 and CD56 but shows a lower Ki-67 index compared to typical small cell carcinoma. What is the most likely diagnosis? A. Large cell neuroendocrine carcinoma B. Small cell carcinoma C. Atypical carcinoid tumor D. Typical carcinoid tumor Rationale: The presence of large cells with neuroendocrine architecture, abundant cytoplasm, and a lower Ki-67 index (compared to small cell carcinoma) points to large cell neuroendocrine carcinoma (LCNEC). 8. A 68-year-old female presents with a lung mass. Biopsy reveals tumor cells with an organoid growth pattern, frequent mitoses, and extensive necrosis. Immunohistochemistry is positive for neuroendocrine markers and TTF-1. Molecular testing shows a TP53 mutation. What is the most likely diagnosis? A. Typical carcinoid tumor B. Small cell carcinoma C. Large cell neuroendocrine carcinoma D. Adenocarcinoma Rationale: The organoid growth pattern, frequent mitoses, extensive necrosis, and TTF-1 positivity are characteristic of small cell carcinoma (SCLC). The presence of a TP53 mutation, common in SCLC, further supports this diagnosis. 9. A lung biopsy reveals a tumor with large, polygonal cells, a high mitotic rate, and a neuroendocrine growth pattern. Immunohistochemistry shows positivity for synaptophysin and chromogranin but negativity for CK5/6 and p63. What is the most likely diagnosis? A. Squamous cell carcinoma B. Small cell carcinoma C. Large cell neuroendocrine carcinoma D. Adenocarcinoma Rationale: The presence of large cells with a neuroendocrine growth pattern and positivity for synaptophysin and chromogranin, along with negativity for CK5/6 and p63, points to large cell neuroendocrine carcinoma (LCNEC). 10. A 65-year-old male with a central lung mass has a biopsy that shows small, round cells with nuclear molding and scant cytoplasm. There is focal positivity for synaptophysin and extensive necrosis. Molecular analysis reveals inactivation of the RB1 gene. What is the most likely diagnosis? A. Large cell neuroendocrine carcinoma B. Basaloid squamous cell carcinoma C. Small cell carcinoma D. Atypical carcinoid tumor Rationale: The small, round cells with nuclear molding, scant cytoplasm, and focal synaptophysin positivity are characteristic of small cell carcinoma (SCLC). The inactivation of RB1, a common genetic alteration in SCLC, further supports this diagnosis. 1. A 45-year-old female presents with a centrally located lung mass causing hemoptysis. A biopsy shows a well-circumscribed tumor with uniform cells forming nests and ribbons. The tumor is strongly positive for chromogranin and synaptophysin, and the Ki-67 index is low. What is the most likely diagnosis? A. Small cell carcinoma B. Large cell neuroendocrine carcinoma C. Typical carcinoid tumor D. Atypical carcinoid tumor Rationale: The well-circumscribed tumor with a low Ki-67 index, uniform cells, and positive staining for chromogranin and synaptophysin is characteristic of a typical carcinoid tumor. The central location and symptoms like hemoptysis are also consistent with this diagnosis. 2. A 60-year-old male with a history of smoking presents with a peripheral lung nodule. Biopsy reveals spindle-shaped cells with a paraganglioid growth pattern, positive for S-100 protein. What variant of carcinoid tumor does this most likely represent? A. Oncocytic carcinoid B. Spindle cell carcinoid C. Melanotic carcinoid D. Typical carcinoid Rationale: The presence of spindle-shaped cells and a paraganglioid growth pattern, along with S-100 positivity, suggests a spindle cell carcinoid tumor. This variant can resemble other spindle cell tumors but is still classified under carcinoid tumors due to its neuroendocrine features. 3. A 55-year-old male with a centrally located lung tumor undergoes a biopsy. The tumor cells are uniform with low mitotic activity, and there is no evidence of necrosis. Immunohistochemistry is positive for TTF-1 and negative for CDX2. What is the most likely diagnosis? A. Typical carcinoid tumor B. Atypical carcinoid tumor C. Small cell carcinoma D. Metastatic gastrointestinal neuroendocrine tumor Rationale: The uniform cells with low mitotic activity and absence of necrosis suggest a typical carcinoid tumor. TTF-1 positivity supports a primary lung origin, while CDX2 negativity helps rule out a metastatic gastrointestinal neuroendocrine tumor. 4. A 52-year-old female with a history of Cushing syndrome is found to have a lung mass. Biopsy reveals a well-circumscribed tumor with increased mitotic activity (7 mitoses per 2 mm²) and foci of necrosis. What is the most likely diagnosis? A. Typical carcinoid tumor B. Atypical carcinoid tumor C. Small cell carcinoma D. Large cell neuroendocrine carcinoma Rationale: The increased mitotic activity and presence of necrosis indicate an atypical carcinoid tumor. Atypical carcinoid tumors can cause paraneoplastic syndromes like Cushing syndrome and are more aggressive than typical carcinoid tumors. 5. A lung biopsy from a 70-year-old male smoker reveals a tumor with a low Ki-67 index and prominent vascularity. The tumor cells form nests and ribbons and are positive for chromogranin, synaptophysin, and TTF-1. What is the most appropriate treatment? A. Radiation therapy B. Chemotherapy C. Surgical resection D. Watchful waiting Rationale: The low Ki-67 index, positive neuroendocrine markers, and well-defined growth pattern indicate a typical carcinoid tumor, which is best treated with surgical resection. These tumors are generally slow-growing and have a good prognosis after surgery. 6. A 63-year-old male presents with multiple lung nodules and a history of bronchiectasis. Biopsy of one nodule reveals small spindle cells with neuroendocrine differentiation, less than 0.5 cm in size. What is the most likely diagnosis? A. Carcinoid tumor B. Tumorlet C. Small cell carcinoma D. Metastatic carcinoma Rationale: The small size (less than 0.5 cm), spindle cell morphology, and neuroendocrine differentiation suggest a tumorlet. Tumorlets are often associated with conditions like bronchiectasis and are typically benign, unlike carcinoid tumors, which are larger. 7. A 58-year-old male with a history of gastrointestinal carcinoma is found to have a lung nodule. Biopsy reveals a neuroendocrine tumor that is positive for CDX2 but negative for TTF-1. What is the most likely origin of this tumor? A. Primary lung carcinoid tumor B. Atypical carcinoid tumor C. Metastatic gastrointestinal neuroendocrine tumor D. Large cell neuroendocrine carcinoma Rationale: The CDX2 positivity and TTF-1 negativity indicate that the tumor is most likely of gastrointestinal origin, making it a metastatic gastrointestinal neuroendocrine tumor rather than a primary lung carcinoid. 8. A lung biopsy reveals a well-circumscribed tumor with uniform cells, no necrosis, and low mitotic activity. The tumor is positive for chromogranin, synaptophysin, and TTF-1, and negative for PAX8. What condition can be confidently ruled out? A. Typical carcinoid tumor B. Atypical carcinoid tumor C. Small cell carcinoma D. Metastatic renal cell carcinoma Rationale: The negative PAX8 staining rules out metastatic renal cell carcinoma, which would typically be positive for this marker. The positive neuroendocrine markers and TTF-1 positivity, along with the histologic features, suggest a primary lung typical carcinoid tumor. 9. A 64-year-old female is diagnosed with an atypical carcinoid tumor of the lung. What feature is most likely associated with a poorer prognosis? A. Peripheral location B. Low mitotic rate C. Lymph node involvement D. Presence of necrosis Rationale: Lymph node involvement is a strong predictor of poorer prognosis in atypical carcinoid tumors. While necrosis and a higher mitotic rate are also concerning features, the presence of metastasis to lymph nodes significantly impacts survival. 10. A 55-year-old male with a central lung mass is found to have a tumor with an intact mucosal surface, limited invasion, and a low mutation burden. The tumor is composed of uniform cells with small nucleoli and forms nests. What is the most likely underlying genetic alteration? A. TP53 mutation B. RB1 inactivation C. MEN1 mutation D. KRAS mutation Rationale: Carcinoid tumors, especially typical carcinoid tumors, often have a low mutation burden and are associated with mutations in MEN1, a gene involved in histone methylation. TP53 and RB1 mutations are more characteristic of high-grade neuroendocrine tumors like small cell carcinoma. 1. A 62-year-old male with a history of smoking presents with a large lung mass. Biopsy reveals pleomorphic tumor cells with abundant cytoplasm and marked nuclear variability. Immunohistochemical staining is negative for TTF-1, p40, and synaptophysin. What is the most likely diagnosis? A. Adenocarcinoma B. Squamous cell carcinoma C. Large cell carcinoma D. Small cell carcinoma Rationale: The pleomorphic cells with abundant cytoplasm and lack of specific markers (negative for TTF-1, p40, and synaptophysin) suggest that this tumor does not fit the criteria for adenocarcinoma, squamous cell carcinoma, or small cell carcinoma. Therefore, large cell carcinoma (LCC) is the most likely diagnosis, as LCC is defined by the absence of specific features of other lung cancer subtypes. 2. A lung tumor in a 65-year-old male is initially diagnosed as large cell carcinoma based on a lack of differentiation and the absence of adenocarcinoma and squamous cell carcinoma markers. Further molecular testing reveals mutations typical of poorly differentiated adenocarcinoma. What is the most appropriate reclassification of this tumor? A. Squamous cell carcinoma B. Poorly differentiated adenocarcinoma C. Large cell neuroendocrine carcinoma D. Small cell carcinoma Rationale: The identification of molecular markers characteristic of adenocarcinoma suggests that the tumor should be reclassified as poorly differentiated adenocarcinoma. This reclassification is important because many tumors historically categorized as LCC are now recognized as poorly differentiated forms of other lung cancers, particularly adenocarcinoma. 3. A lung biopsy from a 58-year-old female reveals large, pleomorphic cells with no distinguishing features of squamous cell carcinoma or adenocarcinoma. The tumor is also negative for neuroendocrine markers. Given these findings, what is the most appropriate next step in the diagnostic process? A. Begin chemotherapy for small cell carcinoma B. Confirm diagnosis of large cell carcinoma with additional immunohistochemical stains C. Treat as adenocarcinoma based on the size of the tumor cells D. Reclassify as large cell neuroendocrine carcinoma Rationale: When a lung tumor lacks distinguishing features of squamous cell carcinoma, adenocarcinoma, or neuroendocrine carcinoma, and shows large, pleomorphic cells, the diagnosis of large cell carcinoma should be considered. However, to confirm this diagnosis, additional immunohistochemical stains should be used to ensure that no specific markers were missed, ruling out other potential diagnoses. 1. A 60-year-old male with a history of smoking presents with a peripheral lung mass. Biopsy reveals both squamous cell carcinoma and glandular (adenocarcinoma) components, each comprising more than 10% of the tumor. What is the most accurate diagnosis? A. Squamous cell carcinoma B. Adenocarcinoma C. Adenosquamous carcinoma D. Large cell carcinoma Rationale: The presence of both squamous cell carcinoma and adenocarcinoma components, each constituting more than 10% of the tumor, meets the criteria for diagnosing adenosquamous carcinoma. This is the most accurate diagnosis given the dual histological features. 2. A lung tumor biopsy from a 65-year-old female shows predominantly squamous differentiation with occasional mucin-producing cells. The glandular component makes up less than 5% of the tumor. How should this tumor be classified? A. Adenosquamous carcinoma B. Squamous cell carcinoma C. Adenocarcinoma D. Large cell carcinoma Rationale: Since the glandular (adenocarcinoma) component is less than 10%, the tumor should be classified as squamous cell carcinoma. Adenosquamous carcinoma requires that both components constitute at least 10% of the tumor. 3. A 58-year-old male is diagnosed with a peripheral lung tumor associated with scarring. Biopsy reveals distinct areas of squamous differentiation and glandular structures, each making up approximately 15% of the tumor. What is the most likely type of lung cancer? A. Small cell carcinoma B. Large cell carcinoma C. Adenosquamous carcinoma D. Basaloid squamous cell carcinoma Rationale: The presence of both squamous and glandular components, each constituting at least 10% of the tumor, along with its peripheral location and association with scarring, strongly suggests adenosquamous carcinoma. 4. During the examination of a lung tumor biopsy, a pathologist identifies that 8% of the tumor shows squamous differentiation while the remaining 92% shows glandular features. What is the appropriate classification for this tumor? A. Adenosquamous carcinoma B. Adenocarcinoma C. Squamous cell carcinoma D. Large cell carcinoma Rationale: Since the squamous component is less than 10%, this tumor should be classified as adenocarcinoma. Adenosquamous carcinoma requires both the squamous and glandular components to be at least 10% of the tumor. 5. A 70-year-old patient presents with a peripheral lung mass. Biopsy reveals a tumor with both glandular and squamous cell components, with each comprising about 12% of the tumor. Given the histological findings and location, what additional feature is most commonly associated with this type of tumor? A. Central necrosis B. Association with scarring C. Lymph node metastasis D. Predominant neuroendocrine differentiation Rationale: Adenosquamous carcinoma, especially when located peripherally, is often associated with lung scarring. This association links it more closely to adenocarcinoma, which frequently shows similar peripheral scarring. 1. A 63-year-old male presents with a large, necrotic lung mass. Biopsy reveals both spindle-shaped cells and large tumor giant cells, with some areas showing squamous differentiation. Immunohistochemical staining is positive for pankeratin and p63. What is the most appropriate diagnosis? A. Squamous cell carcinoma B. Adenosquamous carcinoma C. Pleomorphic carcinoma D. Large cell carcinoma Rationale: The presence of both spindle-shaped cells and giant cells, along with squamous differentiation, suggests a pleomorphic carcinoma. The positive staining for pankeratin and p63 supports the epithelial nature of the tumor, which is consistent with a diagnosis of pleomorphic carcinoma, a variant of sarcomatoid carcinoma. 2. A 70-year-old female with a history of smoking is found to have a bulky lung mass. Biopsy shows areas resembling osteosarcoma and adenocarcinoma. Immunohistochemical staining confirms epithelial differentiation in the adenocarcinoma component. What is the most likely diagnosis? A. Spindle cell carcinoma B. Giant cell carcinoma C. Carcinosarcoma D. Squamous cell carcinoma Rationale: The presence of distinct areas resembling osteosarcoma (a type of sarcoma) and adenocarcinoma, along with confirmed epithelial differentiation, suggests a diagnosis of carcinosarcoma. This tumor type contains both carcinomatous and sarcomatous components, making it the most appropriate diagnosis. 3. A 58-year-old male undergoes a lung biopsy for a mass that reveals large pleomorphic cells with no distinct squamous or glandular features. The tumor is negative for TTF-1 but positive for pankeratin and EMA. What is the most likely type of tumor? A. Adenocarcinoma B. Sarcomatoid carcinoma C. Small cell carcinoma D. Large cell neuroendocrine carcinoma Rationale: The presence of large pleomorphic cells and positivity for pankeratin and EMA, along with negativity for TTF-1, suggests that the tumor is of epithelial origin but lacks specific features of more differentiated lung cancers. This is consistent with sarcomatoid carcinoma, a type of poorly differentiated carcinoma with sarcoma-like features. Certainly! Here are three challenging multiple-choice questions based on the text: ### Question 1: Which of the following statements about the alveolar cells in the lungs is correct? A) Type I pneumocytes are the main proliferating cells after alveolar injury. B) Type II pneumocytes are responsible for producing surfactant and have a hobnail appearance. C) Type I pneumocytes are cuboidal cells with a secretory function. D) Type II pneumocytes cover the majority of the alveolar surface in normal lungs. **Answer:** B) Type II pneumocytes are responsible for producing surfactant and have a hobnail appearance. --- ### Question 2: Which of the following structures is NOT typically associated with the bronchial and bronchiolar epithelium? A) Basal cells B) Goblet cells C) Clara cells D) Alveolar macrophages **Answer:** D) Alveolar macrophages --- ### Question 3: Which of the following statements is TRUE regarding the lung vasculature? A) Pulmonary arteries have a single outer elastic membrane, while pulmonary veins have both an internal and external elastic membrane. B) The bronchial arteries belong to the systemic circulation and are the primary source of blood supply to the alveoli. C) The pulmonary arteries have both an internal and external elastic membrane. D) The bronchial veins have a dual elastic membrane structure, similar to the pulmonary arteries. **Answer:** C) The pulmonary arteries have both an internal and external elastic membrane. Here are seven challenging multiple-choice questions based on the text provided: ### Question 1: Which of the following is NOT a commonly recognized type of congenital cystic disease of the lung? A) Congenital lobar overinflation B) Bronchogenic cyst C) Pulmonary sequestration D) Swyer-James syndrome **Answer:** D) Swyer-James syndrome --- ### Question 2: Congenital lobar overinflation most commonly affects which regions of the lung? A) Both lower lobes B) One of the upper lobes or the right middle lobe C) The entire left lung D) The posterior basal segment of the right lower lobe **Answer:** B) One of the upper lobes or the right middle lobe --- ### Question 3: Which feature is LEAST likely to be found in a large cystic congenital cystic adenomatoid malformation (CCAM)? A) Ciliated respiratory epithelium B) Mucinous columnar epithelium resembling gastric mucosa C) Destruction of alveolar walls D) Multilocular cystic spaces **Answer:** C) Destruction of alveolar walls --- ### Question 4: Placental transmogrification, as seen in emphysematous bullae, is best described as: A) A condition where cystic spaces resemble the structure of chorionic villi. B) A type of congenital cystic adenomatoid malformation. C) A form of bronchogenic cyst characterized by cartilaginous islands. D) A variant of pulmonary sequestration with extralobar lesions. **Answer:** A) A condition where cystic spaces resemble the structure of chorionic villi. --- ### Question 5: Which of the following congenital cystic lung diseases is most commonly associated with the development of mucinous adenocarcinoma later in life? A) Congenital lobar overinflation B) Congenital cystic adenomatoid malformation (CCAM) C) Pulmonary sequestration D) Bronchogenic cyst **Answer:** B) Congenital cystic adenomatoid malformation (CCAM) --- ### Question 6: Which of the following is TRUE regarding pulmonary sequestration? A) It is characterized by cystic spaces lined by ciliated epithelium. B) It often involves abnormal lung tissue with its own blood supply disconnected from the bronchial tree. C) It is associated with mucinous columnar epithelium resembling gastric mucosa. D) It typically presents with symptoms of respiratory distress in early infancy. **Answer:** B) It often involves abnormal lung tissue with its own blood supply disconnected from the bronchial tree. --- ### Question 7: Which of the following is a known characteristic of Swyer-James (McLeod) syndrome? A) Formation of large cystic spaces lined by ciliated respiratory epithelium. B) Development of severe emphysema, bronchiectasis, and/or bronchiolitis obliterans. C) Presence of cartilaginous islands in connective tissue septa. D) A congenital defect causing overinflation of the upper lobes. **Answer:** B) Development of severe emphysema, bronchiectasis, and/or bronchiolitis obliterans. Here are three additional challenging multiple-choice questions based on the text: ### Question 8: In the context of congenital cystic adenomatoid malformation (CCAM), which Stocker type is most closely associated with small cysts (