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Chest pain and shortness of breath

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In a lifelong smoker, a tumor in the periphery of the lung and histology showing glandular cells with some neuroendocrine differentiation is most likely large cell carcinoma, a type of non–small cell lung cancer (NSCLC). Although small cell lung cancer is also associated with smoking, histology typically demonstrates highly cellular aspirates with small blue cells with very scant or null cytoplasm, loosely arranged or in a syncytial pattern. Bronchial adenoma is unlikely, given the patient's unintentional weight loss and fatigue over the past few months. Mesothelioma is most associated with asbestos exposure and is found in the lung pleura, which typically presents with pleural effusion.

Lung cancer is the top cause of cancer deaths in the US, second only to prostate cancer in men and breast cancer in women; approximately 85% of all lung cancers are classified as NSCLC. Histologically, NSCLC is further categorized into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (LCC). When a patient presents with intrathoracic symptoms (including cough, chest pain, wheezing, or dyspnea) and a pulmonary nodule on chest radiography, NSCLC is typically suspected as a possible diagnosis. Smoking is the most common cause of this lung cancer (78% in men, 90% in women). 

Several methods confirm the diagnosis of NSCLC, including bronchoscopy, sputum cytology, mediastinoscopy, thoracentesis, thoracoscopy, and transthoracic needle biopsy. Which method is chosen depends on the primary lesion location and accessibility. Histologic evaluation helps differentiate between the various subtypes of NSCLC. LCC is a subset of NSCLC that is a diagnosis of exclusion. Histologically, LCC is poorly differentiated, and 90% of cases will show squamous, glandular, or neuroendocrine differentiation.

When first diagnosed with NSCLC, 20% of patients have cancer confined to a specific area, 25% of patients have cancer that has spread to nearby areas, and 55% of patients have cancer that has spread to distant body parts. The specific symptoms experienced by patients will vary depending on the location of the cancer. The prognosis for NSCLC depends on the staging of the tumor, nodes, and metastases, the patient's performance status, and any existing health conditions. In the US, the 5-year relative survival rate is 61.2% for localized disease, 33.5% for regional disease, and 7.0% for disease with distant metastases. 

Treatment of NSCLC also varies according to the patient's functional status, tumor stage, molecular characteristics, and comorbidities. Generally, patients with stage I, II, or III NSCLC are treated with the intent to cure, which can include surgery, chemotherapy, radiation therapy, or a combined approach. Lobectomy or resection is generally accepted as an approach for surgical intervention on early-stage NSCLC; however, for stages higher than IB (including stage II/III), patients are recommended to undergo adjuvant chemotherapy. Patients with stage IV disease (or recurrence after initial management) are typically treated with systemic therapy or should be considered for palliative treatment to improve quality of life and overall survival.
 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

 

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In a lifelong smoker, a tumor in the periphery of the lung and histology showing glandular cells with some neuroendocrine differentiation is most likely large cell carcinoma, a type of non–small cell lung cancer (NSCLC). Although small cell lung cancer is also associated with smoking, histology typically demonstrates highly cellular aspirates with small blue cells with very scant or null cytoplasm, loosely arranged or in a syncytial pattern. Bronchial adenoma is unlikely, given the patient's unintentional weight loss and fatigue over the past few months. Mesothelioma is most associated with asbestos exposure and is found in the lung pleura, which typically presents with pleural effusion.

Lung cancer is the top cause of cancer deaths in the US, second only to prostate cancer in men and breast cancer in women; approximately 85% of all lung cancers are classified as NSCLC. Histologically, NSCLC is further categorized into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (LCC). When a patient presents with intrathoracic symptoms (including cough, chest pain, wheezing, or dyspnea) and a pulmonary nodule on chest radiography, NSCLC is typically suspected as a possible diagnosis. Smoking is the most common cause of this lung cancer (78% in men, 90% in women). 

Several methods confirm the diagnosis of NSCLC, including bronchoscopy, sputum cytology, mediastinoscopy, thoracentesis, thoracoscopy, and transthoracic needle biopsy. Which method is chosen depends on the primary lesion location and accessibility. Histologic evaluation helps differentiate between the various subtypes of NSCLC. LCC is a subset of NSCLC that is a diagnosis of exclusion. Histologically, LCC is poorly differentiated, and 90% of cases will show squamous, glandular, or neuroendocrine differentiation.

When first diagnosed with NSCLC, 20% of patients have cancer confined to a specific area, 25% of patients have cancer that has spread to nearby areas, and 55% of patients have cancer that has spread to distant body parts. The specific symptoms experienced by patients will vary depending on the location of the cancer. The prognosis for NSCLC depends on the staging of the tumor, nodes, and metastases, the patient's performance status, and any existing health conditions. In the US, the 5-year relative survival rate is 61.2% for localized disease, 33.5% for regional disease, and 7.0% for disease with distant metastases. 

Treatment of NSCLC also varies according to the patient's functional status, tumor stage, molecular characteristics, and comorbidities. Generally, patients with stage I, II, or III NSCLC are treated with the intent to cure, which can include surgery, chemotherapy, radiation therapy, or a combined approach. Lobectomy or resection is generally accepted as an approach for surgical intervention on early-stage NSCLC; however, for stages higher than IB (including stage II/III), patients are recommended to undergo adjuvant chemotherapy. Patients with stage IV disease (or recurrence after initial management) are typically treated with systemic therapy or should be considered for palliative treatment to improve quality of life and overall survival.
 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

In a lifelong smoker, a tumor in the periphery of the lung and histology showing glandular cells with some neuroendocrine differentiation is most likely large cell carcinoma, a type of non–small cell lung cancer (NSCLC). Although small cell lung cancer is also associated with smoking, histology typically demonstrates highly cellular aspirates with small blue cells with very scant or null cytoplasm, loosely arranged or in a syncytial pattern. Bronchial adenoma is unlikely, given the patient's unintentional weight loss and fatigue over the past few months. Mesothelioma is most associated with asbestos exposure and is found in the lung pleura, which typically presents with pleural effusion.

Lung cancer is the top cause of cancer deaths in the US, second only to prostate cancer in men and breast cancer in women; approximately 85% of all lung cancers are classified as NSCLC. Histologically, NSCLC is further categorized into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (LCC). When a patient presents with intrathoracic symptoms (including cough, chest pain, wheezing, or dyspnea) and a pulmonary nodule on chest radiography, NSCLC is typically suspected as a possible diagnosis. Smoking is the most common cause of this lung cancer (78% in men, 90% in women). 

Several methods confirm the diagnosis of NSCLC, including bronchoscopy, sputum cytology, mediastinoscopy, thoracentesis, thoracoscopy, and transthoracic needle biopsy. Which method is chosen depends on the primary lesion location and accessibility. Histologic evaluation helps differentiate between the various subtypes of NSCLC. LCC is a subset of NSCLC that is a diagnosis of exclusion. Histologically, LCC is poorly differentiated, and 90% of cases will show squamous, glandular, or neuroendocrine differentiation.

When first diagnosed with NSCLC, 20% of patients have cancer confined to a specific area, 25% of patients have cancer that has spread to nearby areas, and 55% of patients have cancer that has spread to distant body parts. The specific symptoms experienced by patients will vary depending on the location of the cancer. The prognosis for NSCLC depends on the staging of the tumor, nodes, and metastases, the patient's performance status, and any existing health conditions. In the US, the 5-year relative survival rate is 61.2% for localized disease, 33.5% for regional disease, and 7.0% for disease with distant metastases. 

Treatment of NSCLC also varies according to the patient's functional status, tumor stage, molecular characteristics, and comorbidities. Generally, patients with stage I, II, or III NSCLC are treated with the intent to cure, which can include surgery, chemotherapy, radiation therapy, or a combined approach. Lobectomy or resection is generally accepted as an approach for surgical intervention on early-stage NSCLC; however, for stages higher than IB (including stage II/III), patients are recommended to undergo adjuvant chemotherapy. Patients with stage IV disease (or recurrence after initial management) are typically treated with systemic therapy or should be considered for palliative treatment to improve quality of life and overall survival.
 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

 

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A 62-year-old man presents to his primary care physician with a persistent cough, dyspnea, unintentional weight loss, and fatigue over the past few months. He has a history of smoking for 30 years but quit 5 years ago. He also reports occasional chest pain and shortness of breath during physical activities. Physical examination reveals crackles in the middle lobe of the right lung. The patient occasionally coughs up blood. Chest radiography shows a large mass in the right lung, and a subsequent CT scan confirms a large peripheral mass of solid attenuation with an irregular margin. The patient undergoes thoracoscopy to obtain a biopsy sample from the tumor for further analysis. The biopsy reveals glandular cells with some neuroendocrine differentiation.

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NSCLC- Clinical Presentation

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Complaints of cough and fatigue

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The history and findings in this case are suggestive of non–small cell lung cancer (NSCLC) large cell carcinoma.

Lung cancer is the most common cancer worldwide and has the highest mortality rate of all cancers. It comprises two major subtypes: NSCLC and small cell lung cancer (SCLC). Histologically, NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma with or without neuroendocrine features. Large cell carcinoma accounts for 9% of all cases and is frequently associated with poor prognosis. Most patients with NSCLC large cell carcinoma are older than 60 years and are diagnosed with stage III or IV disease. NSCLC large cell carcinoma appears to occur more commonly in men than in women and in patients with a history of smoking. It often presents as a large mass with central necrosis. 

NSCLC is often asymptomatic in its early stages. The most frequently reported signs and symptoms of lung cancer include:

•    Cough
•    Chest pain
•    Shortness of breath
•    Coughing up blood
•    Wheezing
•    Hoarseness
•    Recurring infections, such as bronchitis and pneumonia
•    Weight loss and loss of appetite
•    Fatigue

Signs and symptoms of metastatic disease may include bone pain, spinal cord impingement, or neurologic problems, such as headache, weakness or numbness of limbs, dizziness, and seizures.

All patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. After physical examination and a complete blood count, a chest radiograph is often the first test performed. Chest radiographs may show a pulmonary nodule, mass, or infiltrate; mediastinal widening; atelectasis; hilar enlargement; and/or pleural effusion.

Various methods are available to confirm the diagnosis, and the method chosen may be determined at least in part by lesion location. These include: 

•    Bronchoscopy
•    Sputum cytology
•    Mediastinoscopy
•    Thoracentesis
•    Thoracoscopy
•    Transthoracic needle biopsy (CT- or fluoroscopy-guided)

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), the diagnosis of NSCLC large cell carcinoma requires a thoroughly sampled resected tumor with immunohistochemical stains that exclude adenocarcinoma (TTF-1, napsin A) and squamous cell (p40, p63) carcinoma. Nonresected specimens or cytology specimens are insufficient for its diagnosis. NSCLC large cell carcinoma lacks the cytologic, architectural, and histochemical features of small cell carcinoma, adenocarcinoma, or squamous cell carcinoma and is undifferentiated. 

When the NSCLC histologic subtype is determined, molecular testing should be performed as part of broad molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available or to appropriately counsel patients regarding the availability of clinical trials. NSCLC diagnostic standards include the detection of EGFR, BRAF, and MET mutations, ERBB2 (HER2) expression, and the analysis of ALK, ROS1, RET, and NTRK translocations. In addition, analysis of programmed death-ligand 1 expression is necessary to identify patients who may benefit from the use of immune checkpoint inhibitors. 

Surgery combined with chemotherapy has been shown to improve the prognosis of patients with NSCLC large cell carcinoma. Preferred regimens in various lines of treatment and according to molecular characteristics can be found in the NCCN guidelines. 

 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

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The history and findings in this case are suggestive of non–small cell lung cancer (NSCLC) large cell carcinoma.

Lung cancer is the most common cancer worldwide and has the highest mortality rate of all cancers. It comprises two major subtypes: NSCLC and small cell lung cancer (SCLC). Histologically, NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma with or without neuroendocrine features. Large cell carcinoma accounts for 9% of all cases and is frequently associated with poor prognosis. Most patients with NSCLC large cell carcinoma are older than 60 years and are diagnosed with stage III or IV disease. NSCLC large cell carcinoma appears to occur more commonly in men than in women and in patients with a history of smoking. It often presents as a large mass with central necrosis. 

NSCLC is often asymptomatic in its early stages. The most frequently reported signs and symptoms of lung cancer include:

•    Cough
•    Chest pain
•    Shortness of breath
•    Coughing up blood
•    Wheezing
•    Hoarseness
•    Recurring infections, such as bronchitis and pneumonia
•    Weight loss and loss of appetite
•    Fatigue

Signs and symptoms of metastatic disease may include bone pain, spinal cord impingement, or neurologic problems, such as headache, weakness or numbness of limbs, dizziness, and seizures.

All patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. After physical examination and a complete blood count, a chest radiograph is often the first test performed. Chest radiographs may show a pulmonary nodule, mass, or infiltrate; mediastinal widening; atelectasis; hilar enlargement; and/or pleural effusion.

Various methods are available to confirm the diagnosis, and the method chosen may be determined at least in part by lesion location. These include: 

•    Bronchoscopy
•    Sputum cytology
•    Mediastinoscopy
•    Thoracentesis
•    Thoracoscopy
•    Transthoracic needle biopsy (CT- or fluoroscopy-guided)

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), the diagnosis of NSCLC large cell carcinoma requires a thoroughly sampled resected tumor with immunohistochemical stains that exclude adenocarcinoma (TTF-1, napsin A) and squamous cell (p40, p63) carcinoma. Nonresected specimens or cytology specimens are insufficient for its diagnosis. NSCLC large cell carcinoma lacks the cytologic, architectural, and histochemical features of small cell carcinoma, adenocarcinoma, or squamous cell carcinoma and is undifferentiated. 

When the NSCLC histologic subtype is determined, molecular testing should be performed as part of broad molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available or to appropriately counsel patients regarding the availability of clinical trials. NSCLC diagnostic standards include the detection of EGFR, BRAF, and MET mutations, ERBB2 (HER2) expression, and the analysis of ALK, ROS1, RET, and NTRK translocations. In addition, analysis of programmed death-ligand 1 expression is necessary to identify patients who may benefit from the use of immune checkpoint inhibitors. 

Surgery combined with chemotherapy has been shown to improve the prognosis of patients with NSCLC large cell carcinoma. Preferred regimens in various lines of treatment and according to molecular characteristics can be found in the NCCN guidelines. 

 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of non–small cell lung cancer (NSCLC) large cell carcinoma.

Lung cancer is the most common cancer worldwide and has the highest mortality rate of all cancers. It comprises two major subtypes: NSCLC and small cell lung cancer (SCLC). Histologically, NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma with or without neuroendocrine features. Large cell carcinoma accounts for 9% of all cases and is frequently associated with poor prognosis. Most patients with NSCLC large cell carcinoma are older than 60 years and are diagnosed with stage III or IV disease. NSCLC large cell carcinoma appears to occur more commonly in men than in women and in patients with a history of smoking. It often presents as a large mass with central necrosis. 

NSCLC is often asymptomatic in its early stages. The most frequently reported signs and symptoms of lung cancer include:

•    Cough
•    Chest pain
•    Shortness of breath
•    Coughing up blood
•    Wheezing
•    Hoarseness
•    Recurring infections, such as bronchitis and pneumonia
•    Weight loss and loss of appetite
•    Fatigue

Signs and symptoms of metastatic disease may include bone pain, spinal cord impingement, or neurologic problems, such as headache, weakness or numbness of limbs, dizziness, and seizures.

All patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. After physical examination and a complete blood count, a chest radiograph is often the first test performed. Chest radiographs may show a pulmonary nodule, mass, or infiltrate; mediastinal widening; atelectasis; hilar enlargement; and/or pleural effusion.

Various methods are available to confirm the diagnosis, and the method chosen may be determined at least in part by lesion location. These include: 

•    Bronchoscopy
•    Sputum cytology
•    Mediastinoscopy
•    Thoracentesis
•    Thoracoscopy
•    Transthoracic needle biopsy (CT- or fluoroscopy-guided)

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), the diagnosis of NSCLC large cell carcinoma requires a thoroughly sampled resected tumor with immunohistochemical stains that exclude adenocarcinoma (TTF-1, napsin A) and squamous cell (p40, p63) carcinoma. Nonresected specimens or cytology specimens are insufficient for its diagnosis. NSCLC large cell carcinoma lacks the cytologic, architectural, and histochemical features of small cell carcinoma, adenocarcinoma, or squamous cell carcinoma and is undifferentiated. 

When the NSCLC histologic subtype is determined, molecular testing should be performed as part of broad molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available or to appropriately counsel patients regarding the availability of clinical trials. NSCLC diagnostic standards include the detection of EGFR, BRAF, and MET mutations, ERBB2 (HER2) expression, and the analysis of ALK, ROS1, RET, and NTRK translocations. In addition, analysis of programmed death-ligand 1 expression is necessary to identify patients who may benefit from the use of immune checkpoint inhibitors. 

Surgery combined with chemotherapy has been shown to improve the prognosis of patients with NSCLC large cell carcinoma. Preferred regimens in various lines of treatment and according to molecular characteristics can be found in the NCCN guidelines. 

 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

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A 67-year-old White man presents to the emergency department with reports of cough, dyspnea, fatigue, hoarseness, and unintentional weight loss. The patient states that his symptoms began approximately 3 weeks earlier and have progressively worsened. In the past year, he has been treated twice for respiratory infections (bronchitis and pneumonia approximately 6 and 9 months before the current presentation, respectively). He has a 45-year history of smoking (45 pack-years). The patient's vital signs include temperature of 100.4 °F, blood pressure of 142/80 mm Hg, and pulse ox of 95%. Physical examination reveals rales in the left side of the chest and decreased breath sounds in bilateral bases of the lungs. The patient appears cachexic. He is 6 ft 2 in and weighs 163 lb. 

A chest radiograph reveals a large mass in the left lung field. A subsequent CT of the chest reveals encasement of the left upper and lower lobe bronchus with extensive mediastinal lymphadenopathy and areas of necrosis. Immunohistochemical analysis of the resected tumor reveals a malignant, poorly differentiated epithelial neoplasm composed of large, atypical cells. There is no morphologic or immunohistochemical evidence of glandular, squamous, or neuroendocrine differentiation.

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NSCLC- The Basics

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Woman presents with cough and bronchorrhea

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Bronchioalveolar cell carcinoma (BAC) is a variant of non–small cell lung cancer (NSCLC) that, in recent years, has received a new identity in some of the literature. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are relatively new entities that in some published literature have replaced the term BAC. The National Comprehensive Cancer Network recognizes these terms. AIS is defined as a localized adenocarcinoma of < 3 cm that exhibits a lepidic growth pattern, with neoplastic cells along the alveolar structures but without stromal, vascular, or pleural invasion. MIA refers to small, solitary adenocarcinomas < 3 cm with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm of stromal invasion. BAC has unique epidemiologic, pathologic, and clinical features compared with other NSCLC subtypes. For example, although it is smoking-related, the relationship of BAC to smoking is less strong than with other types of NSCLC. About a third of patients with BAC are never-smokers. 

There are also some unique radiographic features — its presentation may be confused with pneumonia or other inflammatory conditions in the lung, and only after a patient does not improve after a course of antibiotics should a diagnosis of BAC be considered. Unlike other types of lung cancer where chemotherapy may be the first plan of attack, surgery is often the first choice for treating BAC, particularly when there is no mediastinal node involvement (10%-25% of cases) or distal metastases (5% of cases). BAC usually harbors EGFR mutation. It is responsive to new targeted therapies for lung cancer, particularly osimertinib, afatinib, erlotinib, and gefitinib. Thus, people with BAC are good candidates for genetic testing.


Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

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Bronchioalveolar cell carcinoma (BAC) is a variant of non–small cell lung cancer (NSCLC) that, in recent years, has received a new identity in some of the literature. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are relatively new entities that in some published literature have replaced the term BAC. The National Comprehensive Cancer Network recognizes these terms. AIS is defined as a localized adenocarcinoma of < 3 cm that exhibits a lepidic growth pattern, with neoplastic cells along the alveolar structures but without stromal, vascular, or pleural invasion. MIA refers to small, solitary adenocarcinomas < 3 cm with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm of stromal invasion. BAC has unique epidemiologic, pathologic, and clinical features compared with other NSCLC subtypes. For example, although it is smoking-related, the relationship of BAC to smoking is less strong than with other types of NSCLC. About a third of patients with BAC are never-smokers. 

There are also some unique radiographic features — its presentation may be confused with pneumonia or other inflammatory conditions in the lung, and only after a patient does not improve after a course of antibiotics should a diagnosis of BAC be considered. Unlike other types of lung cancer where chemotherapy may be the first plan of attack, surgery is often the first choice for treating BAC, particularly when there is no mediastinal node involvement (10%-25% of cases) or distal metastases (5% of cases). BAC usually harbors EGFR mutation. It is responsive to new targeted therapies for lung cancer, particularly osimertinib, afatinib, erlotinib, and gefitinib. Thus, people with BAC are good candidates for genetic testing.


Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Bronchioalveolar cell carcinoma (BAC) is a variant of non–small cell lung cancer (NSCLC) that, in recent years, has received a new identity in some of the literature. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are relatively new entities that in some published literature have replaced the term BAC. The National Comprehensive Cancer Network recognizes these terms. AIS is defined as a localized adenocarcinoma of < 3 cm that exhibits a lepidic growth pattern, with neoplastic cells along the alveolar structures but without stromal, vascular, or pleural invasion. MIA refers to small, solitary adenocarcinomas < 3 cm with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm of stromal invasion. BAC has unique epidemiologic, pathologic, and clinical features compared with other NSCLC subtypes. For example, although it is smoking-related, the relationship of BAC to smoking is less strong than with other types of NSCLC. About a third of patients with BAC are never-smokers. 

There are also some unique radiographic features — its presentation may be confused with pneumonia or other inflammatory conditions in the lung, and only after a patient does not improve after a course of antibiotics should a diagnosis of BAC be considered. Unlike other types of lung cancer where chemotherapy may be the first plan of attack, surgery is often the first choice for treating BAC, particularly when there is no mediastinal node involvement (10%-25% of cases) or distal metastases (5% of cases). BAC usually harbors EGFR mutation. It is responsive to new targeted therapies for lung cancer, particularly osimertinib, afatinib, erlotinib, and gefitinib. Thus, people with BAC are good candidates for genetic testing.


Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

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A 50-year-old woman, a never-smoker, presented with complaints of intermittent cough and shortness of breath for 3 months, associated with bronchorrhea (copious watery sputum production). She had lost 15 pounds in the past 2 months and had dyspnea on exertion for 1 month. Her pulse rate was 88/min, respiratory rate 18/min, and oxygen saturation 96% on room air. A chest x-ray (posteroanterior view) showed dense opacity in the right lower zone. Contrast-enhanced CT of the thorax showed diffuse ground-glass opacities around nodules and consolidation involving the apical and basal segments of the right lower lobe. Despite several courses of antimicrobials, bronchodilators, and IV corticosteroid therapy, the patient's condition worsened.  
 

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NSCLC Medications

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Paresthesias along forearm

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On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

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On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

 

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A 54-year-old man presents with shoulder pain and paresthesias along the medial side of the forearm. The patient has a 50–pack-year history of smoking. He reports that the pain began about 6 weeks ago, at which point he scheduled an orthopedic consultation. Physical examination is also notable for facial flushing. Breathing is normal, with no shortness of breath. Chest radiography reveals asymmetry of the apices (right apex is more opaque than the left). Invasion of the ribs is also seen.

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