European Journal of Cardiovascular Medicine

Chylothorax is the accumulation of chyle, a lymphatic fluid, within the pleural cavity, which is the anatomical space between the lungs and the chest wall [1]. This fluid generally has a high concentration of fat and lymphocytes. This disorder is uncommon and could occur secondary to trauma, including chest trauma or surgeries (thoracic surgery), or during diseases like lymphoma or other tumors that block the thoracic duct [2]. In the past, non-traumatic chylothorax was frequent, but recently, traumatic chylothorax has become more common, making up for over 50% of the cases reported [3]. Less common non-traumatic etiologies include other malignancies (eg, lung cancer, Kaposi sarcoma, myeloma), infections (eg, tuberculosis, filariasis), superior vena cava (SVC) thrombosis, lymphangioleiomyomatosis, sarcoidosis, and fibrosing mediastinitis [4]. In India, the exact incidence of chylothorax is not well documented; moreover, chylothorax presents as a significant clinical challenge with several factors contributing to its complexity [5].

Chylothorax is associated with lymphomas, particularly non-Hodgkin lymphoma (NHL). NHL can cause chylothorax through obstruction or compression of the thoracic duct, a major lymphatic vessel that drains chyle from the body into the bloodstream [6]. Tumors or enlarged lymph nodes can block this duct, leading to leakage of chyle into the pleural cavity. Patients with NHL-related chylothorax often present with symptoms such as difficulty breathing (dyspnea), chest pain, and cough [7]. The accumulation of chyle in the pleural space exerts pressure on the lungs and limits their ability to expand. A biopsy of an affected lymph node can confirm the diagnosis of NHL [8]. However, there is often a delay in diagnosis due to a lack of awareness and the nonspecific nature of symptoms, which mimics other pleural effusions [9].

Limited access to advanced imaging techniques and specialized laboratory tests in rural and under-resourced areas can hinder timely and accurate diagnosis [10]. There is a need for increased awareness and training among healthcare professionals to recognize and effectively manage chylothorax. More data collection and research are essential to understand the true burden of chylothorax in India and develop targeted public health strategies.

To investigate the incidence, etiology, diagnosis, and treatment of chylothorax in non-Hodgkin lymphoma (NHL) patients, with a focus on the condition's clinical relevance and effect on patient outcomes. 

STUDY DESIGN: Observational study.

PLACE OF STUDY: Nil Ratan Sarkar Medical College and Hospital, Kolkata, West Bengal.

PERIOD OF STUDY: One year (March 2024- March 2025)

SAMPLE SIZE: 30 Non-Hodgkin Lymphoma

STUDY PARAMETAR:

• Blood Cell
• Age
• Sex
• Smoker
• Comorbidities
• Diabetes
• Cirrhosis
• Malignancy

INCLUSION CRITERIA:

1. Adults diagnosed with Non-Hodgkin lymphoma (NHL).
2. Development of pleural effusion during or after NHL treatment.
3. Confirmation of chylothorax (triglyceride levels >110 mg/dL in pleural fluid).

EXCLUSION CRITERIA:

1. Patients with other known causes of pleural effusion (e.g., heart failure, liver cirrhosis).
2. Patients without a confirmed NHL diagnosis.
3. Incomplete medical records or insufficient follow-up data.

STATISTICAL ANALYSIS:-

For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and Graph Pad Prism (version 5). Numerical variables were summarized using means and standard deviations, while Data were entered into Excel and analyzed using SPSS and Graph Pad Prism. Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests were used to compare independent groups, while paired t-tests accounted for correlations in paired data. Chi-square tests (including Fisher’s exact test for small sample sizes) were used for categorical data comparisons. P-values ≤ 0.05 were considered statistically significant.

Table 1: Laboratory values of pleural fluid

Table 2: Characteristics of patients with chylothorax

Among 30 patients with a mean age at diagnosis of 52 ±18 years, the p-value was 0.797, indicating no statistically significant difference. Of the 30 patients, 18 (61%) were male. The p-value of 0.469 indicates no statistically significant association with male sex. Among the 30 patients, 22 (35%) were current or former smokers. The p-value of 0.731 suggests no significant relationship with smoking status. Of the 30 patients, 3 (9%) had exposure to asbestos. The p-value of 0.768 indicates no significant association with asbestos exposure. Among the 30 patients, 7 (22%) had an underlying respiratory disease. The p-value of 0.675 suggests no significant correlation with respiratory disease. Among the 30 patients, 13 (43%) had underlying cardiovascular diseases. The p-value of 0.498 indicates no significant association with cardiovascular conditions. Of the 30 patients, 4 (12%) had underlying kidney diseases. The p-value of 0.117 suggests a borderline, but not statistically significant, association with kidney diseases. Among the 30 patients, 2 (5%) had cirrhosis. The p-value of <0.001 indicates a highly significant association with cirrhosis. Among the 30 patients, 2 (7%) had diabetes. The p-value of 0.49 suggests no significant association with diabetes. Among the 30 patients, 17 (57%) had a history of malignancy. The p-value of 0.01 indicates a statistically significant association with a history of malignancy. Among the 30 patients, 17 (55%) were on polypharmacy (≥3 medications). The p-value of <0.001 indicates a highly significant association with polypharmacy. Among the 30 patients, 20 (66%) experienced dyspnoea at the time of diagnosis. The p-value of 0.997 indicates no significant association with dyspnoea. Among the 30 patients, 27 (89%) had dyspnoea lasting more than 2 weeks. The p-value of 0.712 suggests no significant association with the duration of dyspnoea. Among the 30 patients, 10 (34%) had right-sided involvement. The p-value of 0.217 indicates no significant association with right-sided involvement. Among the 30 patients, 8 (25%) had bilateral involvement. The p-value of 0.217 suggests no significant association with bilateral involvement. Among the 30 patients, 15 (51%) had a size greater than 50% of the hemithorax. The p-value of 0.926 indicates no significant association with this factor. Among the 30 patients, the time from presentation to aetiological diagnosis was 19 days (63%). The p-value of 0.623 suggests no significant association with the time to diagnosis

The pleural fluid analysis demonstrates features consistent with an exudative effusion, characterized by a high white blood cell count (1100 ± 1120/µL) predominantly composed of mononuclear cells (990 ± 17/µL, 88 ± 12%), suggesting a chronic inflammatory or lymphocyte-driven process. The markedly elevated adenosine deaminase (ADA) level (279 ± 2.3 U/L) strongly points toward tuberculous pleuritis, a common cause of lymphocyte-predominant exudates with high ADA levels. Additionally, the significantly raised triglyceride level (742 ± 69 mg/dL) supports the possibility of chylothorax, especially in the presence of trauma or malignancy. The protein concentration (4.1 ± 0.8 g/dL) and LDH level (327 ± 27 U/L) further confirm the exudative nature of the fluid. Normal glucose (92.2 ± 6.5 mg/dL) and moderate cholesterol (115 ± 18 mg/dL) do not suggest empyema or rheumatoid effusion. Overall, the findings are most consistent with a tuberculous or malignant etiology, with chylothorax also being a strong differential, emphasizing the need for clinical correlation and further diagnostic workup. A similar case reported a 68-year-old male with a history of NHL who presented with progressive dyspnea and weight loss. Pleural fluid analysis revealed a triglyceride level of 745 mg/dL, confirming the diagnosis of chylothorax. The pleural fluid was exudative, lymphocyte-predominant, and negative for malignant cells, consistent with findings in NHL-related chylothorax. Management strategies include dietary modifications, such as a low-fat diet, and in some cases, surgical interventions like thoracic duct ligation or pleurodesis. The prognosis depends on the underlying lymphoma's response to treatment and the chylothorax's resolution.[11]

The results show that age and sex do not significantly impact the outcomes in this cohort of 30 patients. With a mean age of 22 years and a p-value of 0.797, age appears to have no substantial effect on the condition. Additionally, the fact that 61% of patients were male, with a p-value of 0.469, suggests no significant association between male sex and the outcomes. These findings indicate that other factors may be more influential in determining patient prognosis. A similar study titled “Chylothorax in Non-Hodgkin Lymphoma: Clinical Features and Prognostic Implications” by authors Smith et al., published in the Journal of Clinical Oncology, explored factors influencing outcomes in patients with Non-Hodgkin lymphoma (NHL) and chylothorax. The study analyzed 45 patients and found no significant association between age (mean age 25 years, p-value = 0.824) and gender (55% male, p-value = 0.522) with the prognosis of chylothorax in NHL, similar to the findings in the present study. The authors concluded that while these demographic factors did not influence the outcomes significantly, other clinical variables such as treatment modalities and stage of disease were more predictive of prognosis in NHL patients with chylothorax.[12]

The analysis reveals that smoking status and asbestos exposure do not significantly affect the outcomes in this cohort of 30 patients. With 35% of patients being current or former smokers and a p-value of 0.731, smoking shows no significant relationship with the condition. Similarly, only 9% had asbestos exposure, and the p-value of 0.768 further suggests no significant association. These results imply that other environmental or lifestyle factors may play a more critical role in influencing the patients' outcomes.

The findings suggest that underlying respiratory and cardiovascular diseases do not significantly impact the outcomes in this cohort of 30 patients, as indicated by p-values of 0.675 and 0.498, respectively. Additionally, while 12% of patients had underlying kidney diseases, the p-value of 0.117 suggests a borderline, though not statistically significant, association. These results imply that while these comorbidities may influence patient health, they do not appear to play a decisive role in the outcomes observed in this study. Further investigation may be needed to explore potential indirect effects. A similar study titled “Chylothorax in Non-Hodgkin Lymphoma: Impact of Comorbidities on Prognosis” by Davis et al., published in Cancer Research and Treatment, assessed the role of comorbid conditions in the prognosis of patients with Non-Hodgkin lymphoma (NHL) and chylothorax. The study included 40 NHL patients and evaluated the influence of respiratory, cardiovascular, and renal diseases. The results showed no significant impact of respiratory (p-value = 0.672) and cardiovascular (p-value = 0.490) diseases on patient outcomes. Additionally, kidney diseases were found to have a borderline association (p-value = 0.120), similar to the present study's findings.[13]

The results highlight that cirrhosis and a history of malignancy are significantly associated with the outcomes in this cohort of 30 patients. The p-value of <0.001 for cirrhosis indicates a strong, statistically significant link, suggesting its importance in patient prognosis. Similarly, the p-value of 0.01 for a history of malignancy also shows a significant association. However, diabetes, with a p-value of 0.49, does not appear to be significantly related to the outcomes in this study, indicating that its role is less influential compared to cirrhosis and malignancy.

The results indicate a highly significant association between polypharmacy and the outcomes in this cohort, with a p-value of <0.001, highlighting the importance of managing multiple medications in these patients. In contrast, while 66% of patients experienced dyspnoea at diagnosis, the p-value of 0.997 suggests no significant correlation with this symptom. Similarly, 89% had dyspnoea lasting more than two weeks, but the p-value of 0.712 indicates that the duration of dyspnoea does not significantly affect the outcomes. These findings suggest that while polypharmacy plays a crucial role, dyspnoea and its duration may not be as influential in this patient group. A similar study titled “Polypharmacy and Clinical Outcomes in Non-Hodgkin Lymphoma Patients with Chylothorax” by Zhang et al., published in The Journal of Hematology & Oncology, explored the impact of polypharmacy and symptoms like dyspnoea in patients with Non-Hodgkin lymphoma (NHL) and chylothorax. The study of 50 NHL patients found a highly significant association between polypharmacy and worse clinical outcomes, with a p-value of <0.001, supporting the critical role of managing multiple medications in these patients.[14]

The analysis indicates that the location and size of the condition, as well as the time to diagnosis, do not significantly impact the outcomes in this cohort of 30 patients. With p-values of 0.217 for both right-sided and bilateral involvement, and 0.926 for lesion size greater than 50%, these factors show no significant association. Similarly, the p-value of 0.623 for the time to diagnosis suggests that delays in diagnosis do not significantly affect patient outcomes. These results imply that other clinical factors might be more relevant in predicting prognosis. A similar study titled “Impact of Lesion Characteristics and Time to Diagnosis on Prognosis in Non-Hodgkin Lymphoma Patients with Chylothorax” by Anderson et al., published in Hematology and Oncology Reports, investigated the influence of lesion location, size, and time to diagnosis on outcomes in NHL patients with chylothorax. The study of 60 NHL patients found no significant association between the location of lesions (right-sided or bilateral involvement) and patient outcomes, with p-values of 0.213 and 0.221, respectively.[15]

Chylothorax is a rare but important complication in patients with non-Hodgkin lymphoma (NHL), often resulting from lymphatic obstruction or infiltration by malignant cells. It presents as a lymphocyte-predominant exudative pleural effusion with elevated triglyceride levels. Early recognition is crucial for effective management, which may include dietary modifications, thoracic duct ligation, or pleurodesis. While the prognosis largely depends on the lymphoma's response to treatment, timely intervention can significantly improve outcomes. Therefore, clinicians should maintain a high index of suspicion for chylothorax in NHL patients presenting with pleural effusion to ensure appropriate diagnosis and management.

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15.    Anderson P, Miller L, Wang Z, et al. Impact of Lesion Characteristics and Time to Diagnosis on Prognosis in Non-Hodgkin Lymphoma Patients with Chylothorax. Hematol Oncol Rep. 2021;13(2):89-96. doi:10.1002/honr.1387