A 60-year-old woman presented with complaints of progressive dyspnea on exertion, epigastric pain and low anterior chest pain. She was well until one year ago, when epigastric pain developed. At that time, an abnormality in urinalysis was detected at a local clinic. One month later she underwent an appendectomy with an impression of acute appendicitis. At that time, a chest roentgenogram showed increased interstitial markings in both lower lung fields. Eight months ago, dyspnea on exertion and intermittent edema on her face and dorsum of the hands developed and progressed. For the last three months she was almost in a bed-ridden state due to dyspnea on exertion and weakness. She also felt postural dizziness and a tingling sensation in both hands. So, she was admitted to this hospital.
On physical examination, the blood pressure was 90/60 mmHg, the heart rate 60 beats/minute and respiration rate 24/min. Jugular venous engorgement was noted, and bilateral basal crackles were heard on the chest. The heartbeat was irregular, but a murmur was not heard. Abdominal examination revealed no organomegaly, but epigastric tenderness was noted. Pitting edema was present on both dorsum of the feet, presacral and pretibial areas.
A chest roentgenogram revealed a bilateral diffuse ground-glass density, especially in the lower lung fields, with pleural effusion (Fig. 1). Blood gas analysis showed pH 7.44, PaCO2 33 mmHg, PaO2 67 mmHg, HCO3- 22 mEq/L. The hemoglobin concentration was 11.8 g/dl, leukocyte count 6,300/mm3, platelet count 410,000/mm3 and erythrocyte sedimentation rate was 32 mm/hr. The coagulation profile was normal. The serum calcium level was 7.9 mg/dl, phosphorus 4.5 mg/dl, blood urea nitrogen 19 mg/dl and serum creatinine level 0.9 mg/dl. The serum total protein concentration was 5.0 g/dl, albumin 2.6 g/dl and cholesterol level 388 mg/dl. Urinalysis showed specific gravity 1.025, pH 6.0, albumin 4+, RBC 2-3/high power field (HPF), WBC 7-10/HPF, and 24-hour urine protein was 5,240 mg. Creatinine clearance was 66 ml/minute and the selectivity index of proteinuria was 0.12. In serum protein electrophoresis, albumin was 49.3%, alpha-1 globulin 4.0%, alpha-2 globulin 18.1%, beta globulin 17.5% and gamma globulin 11.3%. Urine protein electrophoresis showed albumin 66.2%, alpha-1 globulin 4.5%, alpha-2 globulin 5.7%, beta globulin 20.6% and gamma globulin 3.0%. In both electrophoresis, there was no M-peak, and urine Bence-Jones protein was negative.
The ECG finding was sinus bradyarrhythmia with sinus pause, junctional escape beats and low voltage QRS complex in the limb leads. A Holter ECG recording showed frequent sinus bradyarrhythmia with junctional escape rhythm, a few episodes of paroxysmal supraventricular tachycardia (sick sinus syndrome) and multiform ventricular premature beats (VPBs) (Fig. 2). In the echocardiogram, the left ventricular posterior wall, interventricular and interatrial septum were thickened, and the myocardium showed a hyperrefractile "granular sparkling" appearance (Fig. 3). A 99m Tc-pyrophosphate myocardial scan revealed no hot uptake.
In an upper gastrointestinal series and colon study, multiple polypoid lesions were suspected in the stomach, ascending colon, splenic flexure of the transverse colon and sigmoid colon.
In a pulmonary function test, the forced vital capacity was 1.54L (68.1% of predicted value), and the forced expiratory volume in one second was 1. 48 L/sec (85.5% of predicted value), showing mainly a restrictive pattern. The carbon monoxide diffusing capacity corrected by alveolar volume (DLCO/VA) was 72.1% of the predicted value. High resolution computed tomography (HRCT) of the lung showed a diffuse thickening of the interlobular septal lines and prominence of bronchovascular core structure, suggesting a diffuse interstitial infiltrative process. Bilateral pleural effusion with mild pleural thickening was observed (Fig. 4).
Because lymphangitic metastasis was suggested on chest CT and gastrointestinal tumor was also suspected, bronchoscopy with transbronchial lung biopsy was done. There was no endobronchial lesion. After the procedure, the patient complained of dyspnea, and inspiratory crackle was heard on the entire lung field. A chest radiograph revealed pulmonary edema and increased pleural effusion. The dyspnea and pulmonary edema was improved by aminophylline and diuretics. Three days later, the patient suddenly experienced dizziness after standing up and loss of consciousness, and cardiac standstill developed. Despite cardiopulmonary resuscitation, the patient expired on the 22nd hospital day.
A transbronchial lung biopsy specimen revealed diffuse hyaline thickening of the alveolar septa and blood vessel walls. Polarizing microscopy following Congo-red stain revealed apple-green birefringence at the vascular walls and along the alveolar septa (Fig. 5). Electron microscopic observation revealed a massive deposit of fibrillar material in the alveolar septum (Fig. 6).
A high resolution CT obtained at right lower lung field (retrospective retargeting, FOV 20 cm, 140KVP, 510 mAs, 512x512 matrix, bone algorithm) shows prominent interlobular septa (white arrowhead) and a central core structure (thin arrow), as well as a diffuse, ill-defined, increased hazy density. Increased density between the rib and the lung (thick black arrows) is due to pleural effusion.