Chylothorax as a Result of Chronic Lymphocytic Leukemia: Case Report and Review of the Literature

Todd W. Rice, MD; Aaron P. Milstone, MD

Disclosures

South Med J. 2004;97(3) 

In This Article

Discussion

The accumulation of chyle in the pleural space is a chylothorax, which accounts for a small percentage of all pleural effusions. Chyle (from the Latin word chylus, or juice) consists of chylomicrons and very-low-density lipoproteins absorbed from the small intestine, secreted into intestinal lymphatics, and accumulated in the cisterna chyli. The thoracic duct arises from the cisterna chyli and carries chyle from the intestinal lymphatics and lacteals to the venous circulation in the left thoracic inlet. The duct travels cephalad through the esophageal hiatus of the diaphragm and along the anterior thoracic vertebral surfaces between the aorta and the azygous vein. Around the fifth thoracic vertebra, the thoracic duct crosses to the left side of the vertebral column, where it continues ascending behind the aortic arch, into the neck above the clavicle and terminates into the venous circulation, where the left subclavian and jugular veins combine to form the brachiocephalic vein.[6] Chylothorax occurs when the thoracic duct is disrupted and chyle accumulates in the pleural space. Chyle can accumulate in either the left or right pleural space, depending on where the thoracic duct is disrupted. If the disruption occurs below the fifth thoracic vertebra, the thoracic duct is on the right side of the vertebral column and right-sided chylothorax occurs. However, if the thoracic duct is disrupted above the fifth thoracic vertebra, the chylothorax occurs in the left pleural space.

The appearance of the pleural fluid often leads to the suspicion of chylothorax. However, less than half of all chylothoraces have a classic milky, white appearance.[7] The diagnosis must be confirmed by the measurement of triglycerides in the pleural fluid. A triglyceride level greater than 110 mg/dl is diagnostic of chylothorax. In addition, a triglyceride level between 50 and 110 mg/dl may also represent a chylothorax. In these cases, lipoprotein electrophoresis can be performed to show the presence of chylomicrons in the pleural fluid, confirming the diagnosis of chylothorax. A pleural fluid cholesterol level should also be obtained because pseudochylothorax may also have elevated triglyceride levels. Cholesterol levels greater than 200 mg/dl are suggestive but not diagnostic of pseudochylothorax. The diagnosis of pseudochylothorax can only be confirmed after the demonstration of the presence of cholesterol and/or triglycerides and the lack of chylomicrons (by lipoprotein electrophoresis) in the pleural fluid.

The most common symptoms of chylothorax include dyspnea and orthopnea. Because chyle is not irritating to the pleura, chest pain is an infrequent finding. Compression of the lung by the chyle in the pleural space leads many patients to experience dyspnea. In addition to respiratory difficulties, the main complications of chylothorax are malnutrition and depressed immune function. Chyle contains fat-soluble vitamins and a significant amount of the dietary calories from fat intake. Lymphocytes, predominantly T-lymphocytes, are also present in chyle. The loss of these vitamins, calories, and lymphocytes from the body as chyle spills into the pleural space leads to malnourished and immunodeficient states.[8,9] Fortunately, chyle is bacteriostatic, and thus chylothorax is rarely complicated by empyema. In addition, chyle is nonirritating to the pleura, and thus chylothoraces rarely develop a pleural rind or peel.

The causes of chylothorax have been divided into four main categories.[6] Malignancy, the most common cause of chylothorax, accounts for over half of all cases. Trauma is the second leading cause, accounting for 25% of cases. Idiopathic chylothorax and miscellaneous causes account for the remaining two categories. Idiopathic causes include congenital (neonatal) chylothorax[10] and cases of minor unrecognized trauma, such as coughing, yawning, and vigorous stretching. Miscellaneous causes range from cirrhosis[11] and congestive heart failure[12] to sarcoidosis[13] and lymphangioleiomyomatosis.[14,15,16]

Many different types of cancers have been reported to cause chylothorax, with lymphoma being the most common, and non-Hodgkin's lymphoma is more likely to cause chylothorax than Hodgkin's lymphoma.[17] Although CLL is often associated with pleural effusion,[18,19] chylothorax from CLL is rare, with only five previous cases identified in the literature.[1,2,3,4,5] Typically, malignancies cause chylothorax through disruption or compression of the thoracic duct from mediastinal adenopathy or mass effect. CLL causes diffuse adenopathy but rarely causes mediastinal adenopathy significant enough to obstruct the thoracic duct,[3] which probably explains the infrequent nature of it causing chylothorax.

In general, initial management of chylothorax usually is conservative, with patients being given nothing by mouth and started on total parenteral nutrition to decrease the amount of fluid traveling in the thoracic duct and to allow the duct time to heal while continuing to provide adequate nutrition through parenteral feeding.[20] If the chylothorax does not resolve with conservative treatment, more aggressive measures must be undertaken in a timely manner to ensure that the patient is adequately nourished and immunocompetent to withstand further treatments. If mediastinal adenopathy is present, either chemotherapy, radiotherapy,[21] or both can be tried as treatment. In addition, many cases often require pleurodesis of the pleural space to resolve the chylothorax.[22] In refractory cases, surgery can be performed to ligate the thoracic duct,[23] either in the thorax or in the abdomen, or to establish a pleuroperitoneal shunt.[24,25] The establishment of a pleuroperitoneal shunt allows the chyle to drain into the abdomen, where it is reabsorbed, maintaining adequate nourishment and immunocompetency.

The mechanism of how CLL causes chylothorax is not well understood and theories about its pathophysiology are lacking. We suggest three possible theories to explain how CLL may cause a chylothorax. The most common manner in which a malignancy causes chylothorax is through mediastinal adenopathy. Although CLL rarely causes significant mediastinal adenopathy,[3] it may be these rare cases that are at risk for developing a chylothorax. Our patient did not demonstrate any mediastinal adenopathy on chest radiography, but it is possible that adenopathy that was not visualized on radiography was indeed present. Another possibility involves the flow of leukemic lymphocytes through the lymphatic system. The presence of an extremely large number of abnormal lymphocytes in CLL may cause sludging in the lymphatic system. The sludging may result in a pseudo-obstruction of either the thoracic duct or lymphatics draining the pleura, resulting in a chylothorax. A third possible mechanism involves traumatic disruption of the thoracic duct. Much like patients who have just finished a high-fat meal, the large number of lymphocytes and sludging in CLL patients may distend the thoracic duct, making it more susceptible to rupture. Then, minor trauma, such as a deep cough or violent sneeze, results in microdisruptions of the thoracic duct and allows chyle to leak into the pleural space.

Unfortunately, the rarity with which CLL causes chylothorax and the lack of an adequate animal model make investigations regarding the pathophysiology difficult. In addition, little evidence exists to guide the clinician in determining which treatment option is best for these patients. Case reports suggest that mediastinal irradiation alone (even in the absence of mediastinal adenopathy),[2] mediastinal irradiation followed by talc pleurodesis,[3] and thoracic duct ligation with concomitant talc pleurodesis[1] may all be reasonable options for the treatment of CLL-induced chylothorax.

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