Image Quizzes

Complaints of cough and fatigue

Reviewed by Karl J. D'Silva, MD

Living Art Enterprises / Science Source

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.

What is the likely diagnosis?

Carcinoid lung tumor

Non–small cell lung cancer large cell carcinoma

Lung adenoma

Small cell lung cancer

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.

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