A 56-year-old homemaker seen at your office has a 3-month history of chronic, nonproductive cough with chest pain associated with the cough. The cough has recently become unresponsive to over-the-counter liquid cough suppressants.

She denies having

• Shortness of breath,
• Wheezing,
• Hemoptysis,
• Fever,
• Chills,
• Sore throat,
• Hoarseness, or
• Postnasal drip.

Her cough is independent of time of day, physical activity, weather conditions, and exposure to dust or household cleaning agents. Her daughter's cigarette smoke does not seem to aggravate the cough. She notes that she has been feeling fatigued and, without dieting, has lost 18 pounds over the past 6 months.

Her past medical history is noncontributory. She is a nonsmoker and nondrinker. She does not come in contact with any known chemical substances or irritants other than typical household cleaning agents. Her father died at age 65 of a myocardial infarction. Her mother had breast cancer at age 71. Her first husband died of a cerebrovascular accident 3 years ago. Newly remarried to a retired shipyard worker, she and her current husband live with her 28-year-old daughter and 9-year-old grandson in their New Hampshire home. She has not been outside the New England area for the last 5 years.

Results of the physical examination, including head, eye, ear, nose and throat (HEENT) and chest examination are normal. No cyanosis or clubbing of the extremities, and no palpable lymph nodes. Blood tests, including a complete blood count and chemistry panel, are normal, with the exception of a total serum calcium level of 12.7 milligrams per deciliter (mg/dL) (normal range: 9.2 to 11.0 mg/dL). A chest radiograph reveals, however, a noncalcified, noncavitary 3.5 centimeter (cm) mass located within the parenchyma adjacent to the right hilum. No other radiographic abnormalities appear. Results of a purified protein derivative (PPD) skin test for tuberculosis are negative. Urinalysis results are normal.

Choose the one best answer

1. Given the clinical findings to this point, which of the following is most likely part of the differential diagnosis?
   A. Chronic obstructive pulmonary disease (COPD).
   B. Angina.
   C. Pulmonary Tuberculosis.
   D. Primary pulmonary malignancy.
2. What further testing might you order?
   A. Search for previous chest radiographs for comparison.
   B. Low-dose, computerized tomography (LDCT) scan of the lungs.
   C. Lateral chest X-ray.
   D. Sputum studies for cytology and cultures (standard pathogens, fungus, acid-fast bacilli).
   E. All of the above.
3. Which environmental causes have been associated with this patient's probable disorder?
   A. Daughter’s smoking and exposure to increased levels of radon gas.
   B. Persistent organic pollutants.
   C. Exposure to pesticides from the home’s foundation.
   D. Toxic products in the patient’s drinking water.

1. The best choice is D. Primary pulmonary malignancy.

   The differential diagnosis for the patient's radiographic solitary pulmonary nodule would include

   • Primary pulmonary malignancy,
   • Metastatic malignancy,
   • Granulomatous disease (e.g., tuberculosis, coccidioidomycosis, histoplasmosis, nocardiosis),
   • Arteriovenous (av) malformation,
   • Pulmonary hamartoma,
   • Bronchial adenoma,
   • Pulmonary abscess,
   • Pseudonodule (e.g., nipple shadow, superficial skin lesion), and
   • Sarcoidosis.

   The following increase the likelihood of a pulmonary malignancy:

   • Radiographic appearance of the lesion (size and lack of calcification),
   • Age,
   • Sex (current or former women smokers are at higher risk).
   • Symptoms of cough and weight loss,
   • Hypercalcemia,
   • Absence of residence in or travel to an area endemic for coccidioidomycosis (southwest United States) or histoplasmosis (Ohio/Mississippi Valley),
   • Absence of fever or evidence of infectious disease, and
   • Negative ppd skin test. The latter does not rule out tuberculosis, but makes it less likely.

   More information for this answer can be found in the “How Should Patients Potentially Exposed to Increased Levels of Radon Be Treated and Managed?” section.

   
   

2. The best choice is E, All of the above.

   At this point, referral to a specialist such as a pulmonologist with expertise and clinical experience diagnosing, treating, and managing lung disease would be reasonable. Additional testing and care based on the specialist’s assessment and recommended treatment plan may include further testing with additional referral (depending on the findings) to an oncologist, a chest surgeon, or both. Initially, one or more of the following tests might be appropriate:

   • Search for previous chest radiographs for comparison,
   • Sputum studies for cytology and cultures (standard pathogens, fungus, acid-fast bacilli),
   • LDCT scan, or
   • Fiber optic bronchoscopy with bronchial brushings and specimens for cytology and culture.

   If a primary lung cancer is detected, a metastatic workup (scans of the brain, liver, adrenals, and bones) might be indicated. Again, this would be guided by specialist care and recommendations.

   More information for this answer can be found in the “How Should Patients Potentially Exposed to Increased Levels of Radon Be Treated and Managed?” section.

   
   

3. The best choice is A, Daughter’s smoking and exposure to increased levels of radon gas.

   "Environmental causes of lung cancer may include

   • Arsenic http://www.atsdr.cdc.gov/csem/csem.asp?csem=1&po=0,
   • Asbestos,
   • Chloromethyl ethers,
   • Chromium,
   • Ionizing radiation (alpha, beta, gamma, or x-radiation),
   • Nickel,
   • Polycyclic aromatic hydrocarbons,
   • Radon, and
   • Tobacco smoke.

   As previously mentioned, referral to and consultation with a specialist with expertise and experience diagnosing, treating, and managing lung disease should guide treatment options. Referral options might include recommendations for any additional referrals to an oncologist, a chest surgeon, or both. Depending on histologic type, local extension into adjacent anatomical structures, presence of metastases, and the general health of the patient, treatment options might include surgical excision, radiation therapy, chemotherapy, and possibly immunotherapy. Again, specialist care and a recommended treatment plan should guide the choice of options.

   More information for this answer can be found in the “How Should Patients Potentially Exposed to Increased Levels of Radon Be Treated and Managed?” section.