“New consult,” said my nurse, “a 78-year-old woman with lung cancer.” Unfortunately, with lung cancer reaching epidemic proportions in American women, such patients are showing up more often. Mrs. P turned out to be a delightful retired rancher with no prior medical conditions and no history of smoking. She had gone to her family physician four months earlier with a complaint of nonproductive cough, and a chest x-ray had shown several pulmonary nodules. At follow-up a few weeks later, all the nodules had resolved except one, but disturbingly, it had enlarged to 4 cm. A subsequent fine-needle biopsy of the nodule by a pathologist showed “undifferentiated malignancy, consistent with adenocarcinoma.”
Mrs. P was not as distraught as most patients facing a cancer diagnosis. “The Lord will take care of me,” she said quietly. Except for the mild, nonproductive cough, she had no complaints. In fact, she looked and felt healthy. Her chest CT showed no mediastinal or hilar adenopathy, and staging studies revealed no additional disease. Her “lung cancer” was potentially curable with surgery. Certainly she could receive chemoradiation. Yet I was uncomfortable initiating toxic therapy. Why had all the other nodules disappeared? If the remaining nodule was truly malignant, it must be quite aggressive to have enlarged so rapidly. Why was there no adenopathy? Fine-needle biopsies are prone to distortion artifact and provide insufficient tissue for staining studies designed to provide a more specific diagnosis.
I explained my concern to Mrs. P and arranged for a thoracoscopic biopsy. Everyone was comfortable with this plan except the pathologist. “You have your diagnosis. What more do you need?” he asked. I reassured him that I simply wanted a bigger tissue specimen so he could make a more specific diagnosis. Imagine our surprise when two weeks later, the “tumor” was reclassified as Wegener’s granulomatosis (WG)!
WG is a systemic vasculitis of unknown cause that preferentially affects small blood vessels. The lungs, upper airway, and kidneys are most commonly involved, although no organ system is spared. More than 90% of patients will have upper respiratory tract disease, with such nonspecific symptoms as ear, nose, or sinus congestion. Pulmonary involvement can cause cough, dyspnea, and hemoptysis. Subtle renal involvement, manifested as hematuria or proteinuria, can occur in up to 80% of patients. Occasionally, there is also rash, neuropathy, or GI bleeds. These nonspecific symptoms explain why the diagnosis of WG is often missed or delayed. Even after the diagnosis, Mrs. P’s only symptom was the persistent cough.
The important histopathologic features of WG are vasculitis and chronic granulomatous inflammation, with underlying parenchymal necrosis. The vasculitis damages capillaries, causing mild epistaxis, hemoptysis, and hematuria. The specific trigger of this immune response is unknown, but an unidentified infectious agent is suspected because some patients respond to treatment with trimethoprim/sulfamethoxazole.
Although pulmonary granulomata are initially microscopic, tissue necrosis can lead to coalescence of lesions and formation of cavitary masses. Chest radiographs sometimes show solitary or multiple pulmonary nodules, leading to a misdiagnosis as primary or metastatic lung disease. In contrast to other systemic vasculitides, active WG can occur without an elevated erythrocyte sedimentation rate. Patients are often positive for antineutrophil cytoplasmic antibodies. This finding, however, is not sensitive or specific enough to be the sole criterion for diagnosis. Biopsy of the lung, sinuses, or kidneys is usually necessary.
The clinical course of WG is variable. Like other autoimmune conditions, there can be relapses, but these respond to retreatment. Patients with limited pulmonary WG enjoy a better prognosis, while those presenting with massive hemoptysis have a rapidly fatal disease. The average WG patient who receives treatment has a 75% chance of surviving for five years.
3. Treatment and resolution
Mrs. P’s limited WG, while no walk in the park, would be amenable to nonsurgical therapy and had a potentially better prognosis than lung cancer. The irony was that she might still need chemotherapy. Standard WG therapy involves steroids in conjunction with cyclophosphamide or methotrexate. A pulmonologist started Mrs. P on oral cyclophosphamide and steroids. Within three months, a chest x-ray showed complete resolution of all nodules. Now off therapy, she remains symptom-free.
Mrs. P’s experience reminded all the physicians who saw her of important factors regarding cancer diagnoses. First, never rely on fine-needle aspirates for a primary cancer diagnosis. Second, if the clinical picture does not fit the pathologic diagnosis, obtain more tissue.
Mrs. P has turned out to be one of my most grateful patients. I still get flowers from her on the anniversary of her rediagnosis.