To the Editor:
A chyliform effusion (also described as pseudochylothorax, cholesterol pleurisy, and cholesterol effusion) is usually seen in the context of a chronic pleural collection and a thickened, fibrosed pleura. The effusion has a high cholesterol level, and a low triglyceride level, chylomicrons are absent and if cholesterol crystals are seen on microscopy the diagnosis is certain.
An 88-year-old woman presented with a 6-week history of progressive dyspnea. She had no significant past medical history and was not taking any medications. She was a nonsmoker with no history of asbestos exposure. Baseline hematology and biochemistry blood tests were unremarkable. A plain chest radiograph showed a large right-sided pleural effusion, confirmed on computed tomography (CT). Previous CT colonography a year earlier had not demonstrated any pleural effusion. Both CT scans did not show any pleural thickening.
Thoracocentesis was carried out for diagnostic and therapeutic purposes. The macroscopic appearance of the pleural fluid was unusual; it was golden-yellow, opalescent, glossy, and thick. It was neither milky nor purulent (Fig. 1). A repeat CT scan after drainage showed multiple small pleural-based nodules (Fig. 2). Analysis of the pleural fluid was consistent with an exudate (protein, 54 g/L; lactate dehydrogenase, 630 mmol/L) with a glucose of 5.6 mmol/L. The pleural fluid specimen remained turbid after centrifugation and cultures were negative. No acid fast bacilli were seen and tuberculous cultures were negative after 6 weeks. Cytological examination was consistent with metastatic adenocarcinoma of unknown primary; immunohistochemistry was weakly positive for BerEP4, but with insufficient cells for further analysis. Pleural fluid triglyceride was low (0.25 mmol/L), excluding a chylothorax, while cholesterol was raised (3.78 mmol/L) and with the macroscopic appearance this was considered to be suggestive of a chyliform effusion. Unfortunately the laboratory was unable to look specifically for cholesterol crystals.
The patient’s case was discussed at the Thoracic Cancer Multi-Disciplinary Team Meeting and based on her age and frailty it was decided that she should be managed palliatively. She was subsequently followed-up in the outpatient pleural clinic and remained asymptomatic despite a recurrent and slowly enlarging effusion. However, 18 months after her initial presentation, she was readmitted with worsening dyspnea. Repeat CT showed progression of the pleural nodularity and a large effusion, which was drained again for symptomatic relief. The patient passed away 6 months later without the need for further pleural intervention.
It has been proposed that a pleural fluid cholesterol value >5.18 mmol/L (200 mg/dL) is strongly suggestive of a chyliform effusion.1 However, evidence to support this diagnostic cut-off is limited and can be traced to a single study with a small sample size.1 Garcia-Zamalloa et al2 reviewed 172 published cases of chyliform effusions and found many reported a pleural fluid cholesterol value of <5.18 mmol/L and as low as 3.1 mmol/L (120mg/dL). Lama et al3 performed a systematic review of 62 studies involving 104 patients; 25.7% of the cases had pleural fluid cholesterol values of <5.18 mmol/L. Some authors propose that a cholesterol/triglyceride ratio of >1 is also used as an additional or alternative criterion to establish the diagnosis of chyliform effusion. In the review by Lama et al,3 97.4% (37/38) of patients had a cholesterol/triglyceride ratio of >1. In our case the ratio was indeed >1.
Although opalescent pleural effusions can be seen in both chylothorax and chyliform effusions, the opalescence and satin-like sheen observed in our case is particularly characteristic of chyliform effusions, and is thought to be due to the presence of cholesterol crystals.4 In 1961, Coe and Aikawa4 described the sheen-like appearance of the effusion in a case they reported as resembling “that of the metallic paints used in the automotive industry.” This description can be appreciated from the images of the pleural fluid collected in our patients’ case (Fig. 2).
It has traditionally been thought that chyliform effusions arise in the context of fibrotic and thickened pleura due to a chronic effusion which has been present for at least 5 years.2 This concept has been challenged.5 Lama et al3 also found that pleural thickening was absent in 20.6% of cases. Our case also goes further to challenge this paradigm; the pleural effusion was not chronic and there was an absence of more diffuse or extensive pleural thickening.
The commonest causes of chyliform effusions are tuberculosis, followed by rheumatoid arthritis.2 Malignancy is a rare cause and, to our knowledge, this is only the third reported case of a chyliform effusion associated with malignancy.
The biochemical and macroscopic features of the pleural fluid in our patients’ case were suggestive of a chyliform effusion, highlighting that a chyliform effusion can occur with a lower pleural fluid cholesterol level than that which is often quoted. Furthermore, we propose that chyliform effusions can occur in the absence of pleural thickening and can be associated with malignancy.
Yasser Madani, MBBS*
Robert W. Fowler, MD†
John P. Corcoran, MRCP‡
*Royal Brompton and Harefield NHS Foundation Trust, London
†Barking, Havering, and Redbridge University Hospitals NHS Trust, Romford
‡Plymouth Hospitals NHS Trust Plymouth, UK
1. Hamm H, Pfalzer B, Fabel H. Lipoprotein analysis in a chyliform pleural effusion: implications for pathogenesis and diagnosis. Respiration. 1991;58:294–300.
2. Garcia-Zamalloa A, Ruiz-Irastorza G, Aguayo FJ, et al. Pseudochylothorax. Report of 2 cases and review of the literature. Medicine (Baltimore). 1999;78:200–207.
3. Lama A, Ferreiro L, Toubes ME, et al. Characteristics of patients with pseudochylothorax-a systematic review. J Thorac Dis. 2016;8:2093–2101.
4. Coe JE, Aikawa JK. Cholesterol pleural effusion. Report of 2 cases studied with isotopic techniques and review of the world literature. Arch Intern Med. 1961;108:763–774.
5. Wrightson JM, Stanton AE, Maskell NA, et al. Pseudochylothorax without pleural thickening: time to reconsider pathogenesis? Chest. 2009;136:1144–1147.