A 60-year-old Saudi woman was admitted through the emergency room for progressively worsening dyspnea, dry cough and mild fever of two weeks duration. The patient had been well until two years earlier, when she presented to another hospital with slowly increasing dyspnea and dry cough. A diagnosis of LIP was established on bronchoscopic biopsy. Since that time she had been on the oral steroids Imuran (azathioprine) and Ventolin (albuterol) inhaler. She denied any history of tuberculosis, exposure to chemicals, organic dust, toxic gas, molds, bird feed or smoking. She was not known to have diabetes, hypertension or heart disease. On physical examination she was mildly febrile and dyspneic, but not hypoxic. There was no finger clubbing or pitting edema. Chest auscultation found inspiratory crackles bilaterally. Cardiac, CNS, abdomen, pelvic, breast and neck examinations were unremarkable.
Initial laboratory work up showed elevated ESR (56 mm/h) and a normal CBC, liver and renal function tests. Rheumatoid factor, anti-DNA, antineutrophil and HIV serology were negative. Admission chest radiographs revealed multiple dense and ill-defined nodules of variable size in both lungs for which the patient was evaluated with CT. A high-resolution and conventional CT (Figure 1) of the chest revealed multiple calcific nodules of 0.3 cm to 5 cm size predominantly distributed in the mid-lower lungs subpleurally and peripherally. The calcification was dense and homogenous in the smaller nodules, while irregular and amorphous or punctate in the larger nodules. Consolidations with a variable degree of amorphous and punctate calcifications were noted at the right upper lobe posterior segment, middle lobe and at lung bases. A cavity with a small fluid level and smooth inner wall was present in the right lower lobe consolidation (Figure 1E). Randomly distributed multiple thin-walled air cysts of varying size (0.3 cm to 6 cm) were present in both lungs. There were a few small and discrete reactive lymph nodes in the superior mediastinum. There was no evidence for calcific lesions in the heart musculature. Pleural, pericardial effusions or thickening were absent.
Given these radiologic findings, the differential diagnoses were limited. We considered metastatic disease, tuberculosis, amyloidosis and Wegener's granulomatosis. A technicium MDP bone scan was requested, revealing no abnormal uptake in the skeleton, but most of the large calcific nodules in the lung did show increased tracer activity mimicking rib metastasis (Figure 2). There was no tracer uptake in the heart and extrathoracic soft tissues. The patient was further evaluated clinically and radiologically for a primary malignancy.
An ultrasound examination of the neck for thyroid and CT scans of the abdomen and pelvis were non-rewarding. We arrived at a diagnosis of metastatic lung disease from an unknown primary tumor or amyloidosis, and a CT-guided transthoracic core biopsy was performed with an 18-gauge needle. A lung core biopsy was fixed in neutral formalin and processed for paraffin embedding. Histologic tissue sections were stained with hematoxylin and eosin stain. After the initial observations, Congo red staining was performed and studied by light and polarized microscopy. Automatized immunohistochemistry was carried out using antigen unmasking and streptavidin peroxidase methods. Commercial antibodies included kappa and lambda. The H&E sections (Figure 3) revealed a variable density of plasma cell infiltration and amorphous interstitial substance with focal microcalcifications. No preserved lung tissue was discernible. Plasma cells showed no atypical features. The amorphous substance showed variable eosinophilic intensity, and stained positive for Congo red, which under polarized light displayed a characteristic "apple-green" color. The vast majority of plasma cells were positive for a kappa light chain (Figure 4). A pathologic diagnosis of amyloidosis with kappa-light-chain restriction was established.