Mrs. A was a 74-year-old African American who presented with a five-month history of progressive fatigue, dyspnea, and cough. She had been admitted to a hospital twice over the past five months alone. Her medical history was significant for hypertension, diabetes mellitus, obesity, supraventricular tachycardia, pulmonary hypertension, peripheral arterial disease, dysthymia, rheumatoid arthritis, fibromyalgia, and stage 3 breast cancer three years ago (treated with four cycles of chemotherapy, radiation, and radical mastectomy). Other surgeries included a laminectomy, total hysterectomy, and three elective abortions.
When asked, Mrs. A stated that she was a lifelong nonsmoker with no history of alcohol or illicit drug abuse. She followed up regularly with her specialty providers (cardiologist, rheumatologist, oncologist, endocrinologist, and internist). Medications included lorazepam (Ativan), docusate sodium (Colace), temazepam (Restoril), aspirin, valsartan, metformin, glimepiride (Amaryl), valsartan (Diovan), and metoprolol.
1. Physical examination
On examination, Mrs. A’s vital signs were BP 114/60 mm Hg, pulse 98 beats per minute, temperature 36.6°C, respiratory rate 22 breaths per minute, and oxygen saturation 93% on 3 L of oxygen via nasal cannula. At a height of 5 ft 5 in and weight of 189.2 lb, she was obese. She appeared not to be in respiratory distress (although she was slightly anxious), and she was alert and oriented to person, place, and time. Carotid arteries were without thrills. Coarse expiratory crackles could be heard at the bases of both lungs. Cardiac auscultation detected a regular heart rate and rhythm without murmurs or heaves. Mrs. A’s right upper extremity had been chronically edematous since her radical mastectomy. Her abdomen was obese, soft, nontender, and without organomegaly. Both lower extremities showed 1+ edema to the knees.
2. Laboratory tests
Mrs. A’s lab values were hemoglobin 10.9 g/dL, platelets 192,000/µL, WBCs 4,400/µL, potassium 4.1 mmol/L, sodium 132 mmol/L, creatinine 0.6 mg/dL, CA 15-3 24 units/mL, carcinoembryonic antigen 1.9 ng/mL, and brain natriuretic peptide (BNP) 93.9 pg/mL. The patient was anemic, and the elevated BNP suggested heart failure. Cardiac enzymes, liver function, blood cultures, urine studies, cocci serology, and
ventilation-perfusion scan were unremarkable.
Given the information we gathered, the differential diagnoses included bronchitis, pneumonia, pneumonitis, anemia, metastatic breast cancer, heart failure, pulmonary embolus, and pleural effusions. A chest x-ray was nondiagnostic. ECG showed abnormal septal motion and mild right ventricular enlargement without intracardiac thrombus or mass.
High-resolution CT scans were done at each of Mrs. A’s three admissions and initially read as probable edema vs. infection. At her first admission, she was treated with oxygen, IV furosemide (Lasix), and levofloxacin (Levaquin), and then switched to oral administration at discharge home on oxygen. Predischarge imaging showed improvement. After her second admission, she was again placed on Lasix. Dexamethasone (Decadron), vancomycin (Vancocin), and fluconazole (Diflucan) were added to cover any atypical pneumonia. Repeat i maging prior to discharge home again showed improvement.
On this, her third admission, three days later, Mrs. A was c ontinued on IV antibiotics, IV steroids, and oxygen. An infectious disease consultation yielded no improvement. Bronchoscop y with cytology was ordered. A repeat CT with contras t showed interlobular septal thickening in the right lung and the left upper lung (Figure 1); mild ground-glass opacifications in both upper lobes; lingual, right paratracheal, and subcarinal adenopathy; bilateral pleural effusions (also seen on c hest x-ray, Figure 2); small pericardial effusion without tamponade; and normal adrenal glands.
Bronchoscopy with tissue biopsy and lavage found adenocarcinoma due to metastasis of Mrs. A’s primary breast cancer. The underlying fatigue, dyspnea, and cough were attributed to pulmonary lymphangitic carcinomatosis (PLC).
Mrs. A’s case was perplexing. Her initial symptoms on her first hospital admission had improved with diuresis and antibiotic therapy even though she had to be discharged home on oxygen. When repeat imaging as an outpatient indicated resolution of previously seen ground-glass opacifications, the lingering adenopathy was thought to be from an inflammatory process. Her second admission showed an elevated WBC count. Decadron, Vancocin, and Diflucan therapy was initiated, which led to improvement of her symptoms. At each hospitalization, chest CTs were done. It was not until her third admission that bronchoscopy was performed and the diagnosis of PLC was reached.
PLC often mimics pneumonia, congestive heart failure (CHF), pulmonary embolism (PE), asthma, and sarcoidosis. Diagnosis is difficult because of limited clinical findings and the fact that these patients often have other underlying lung disease. PLC is a rare finding. The cancers that most commonly cause it are those of the breast, lung, colon, and stomach as well as melanoma.
PLC was first identified in Paris in 1829 in a woman suffering from uterine cancer. It is defined as dissemination of carcinoma through the pulmonary lymphatic system. Most patients are diagnosed on postmortem examination. Antemortem diagnosis is rare because many patients have normal or only atypical chest x-rays.
Chest x-rays often mimic those of other diseases by showing edema, reticulonodular opacifications, septal Kerley lines, pleural effusions, or hilar or mediastinal adenopathy. Hence PLC is missed because other conditions (e.g., pneumonia, CHF, PE, asthma, sarcoidosis) are diagnosed and frequently treated with good outcome, leaving the underlying cause untreated. Clinical diagnosis of PLC is best made with a high-resolution CT scan and tissue obtained through bronchoalveolar lavage.
PLC has a poor prognosis, with long-term survival being only weeks to months at the time of diagnosis. The prudent clinician should include PLC in the differential diagnosis of any patient with a history of cancer, rapidly progressing respiratory impairment, abnormal chest imaging, and pleural effusions.
In patients diagnosed early, chemotherapy may stabilize the PLC as well as slow its progression. Mrs. A was started on inpatient steroids and systemic chemotherapy with albumin-bound paclitaxel (Abraxane) and gemcitabine (Gemzar). Unfortunately, her condition continued to deteriorate, and she died five days after starting chemotherapy.