A Prospective Study of the Volume of Pleural Fluid Required for Accurate Diagnosis of Malignant Pleural Effusion

doi:10.1378/chest.08-2002

Chest

Volume 135, Issue 4, April 2009, Pages 999-1001

https://doi.org/10.1378/chest.08-2002 Get rights and content

Background

This is a prospective study to define the volume of pleural fluid adequate for maximal yield of cytologic analysis of pleural fluid.

Methods

Patients undergoing diagnostic thoracentesis with malignancy in the differential diagnosis were enrolled in the study. The first 50 mL of pleural fluid were put in a specimen cup, and subsequent fluid was collected in a drainage bag. Both samples were sent for cytologic evaluation. The cytologist was blinded as to which specimen was being evaluated.

Results

Forty-four patients (21 men, 23 women; mean [± SD] age, 46 ± 11.1 years) were enrolled in the study. The average volume of the “large-volume” specimen was 890 ± 375 mL (range, 250 to 1,800). Although malignant pleural involvement had never been documented for any patients, 31 patients had received a diagnosis of malignancy prior to undergoing thoracentesis. Cytologic tests were positive for malignancy in 23 of the 44 patients (55%). In the group of patients with an established history of cancer, pleural fluid was positive for malignant cells in 19 of 33 samples (58%). In all 23 patients with malignant pleural effusion, both the 50-mL specimen and the large-volume specimen were cytologically identical. In all 21 patients with negative pleural cytology findings, there was again 100% concordance between the 50-mL samples and the larger samples. The minimum adequate pleural fluid volume for cytologic diagnosis has been a matter of debate. The strongest data to date came from a retrospective study in 2002.

Conclusion

Our prospective study now unequivocally supports the concept that the submission of > 50 mL of pleural fluid for cytologic analysis does not increase diagnostic yield.

Section snippets

Materials and Methods

This study was approved by the institutional review board of our institution. Due to logistical reasons, subjects were accrued during the following two separate intervals: March 4, 2003, to June 3, 2004; and August 7, 2007, to December 1, 2007. During these intervals, patients with suspected malignant pleural effusion undergoing a diagnostic thoracentesis were enrolled prospectively. The skin was sterilized and draped in standard fashion. After injecting the skin with 1% lidocaine, a small 8F

Results

Forty-four patients were included in our study (21 men and 23 women). The mean age was 46 ± 11.1 years. The mean volume of the large-volume specimen was 890 ± 375 mL (range, 250 to 1,800 mL). Thirteen patients had no history of cancer. Thirty-one patients had received a diagnosis of malignancy prior to pleural fluid sampling, although malignant pleural involvement had never been documented for any. Twelve of the patients with previously documented malignancy had lung cancer, 9 patients had

Discussion

Malignant pleural effusion complicates the course of malignancy and is the initial presentation of malignancy in about 13% of patients.⁴ The documentation of malignant cells in pleural fluid has both diagnostic and prognostic value. We are unaware of any prospective study documenting the equivalence of small- and large-volume pleural fluid samples in the diagnosis of malignant pleural effusion; ours appears to be the first such study.

The issue of minimum adequate volume for cytologic diagnosis

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The comparative diagnostic accuracy, efficiency and specificity of cytologic techniques used in the diagnosis of malignant neoplasm in serous effusions of the pleural and pericardial cavities
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Cited by (91)

High Yield of Pleural Cell-Free DNA for Diagnosis of Oncogenic Mutations in Lung Adenocarcinoma
2023, Chest
Pleural cytology is currently used to assess targetable mutations in patients with advanced lung adenocarcinoma. However, it is fraught with low diagnostic yield.
Can pleural cell-free DNA (cfDNA) be used to assess targetable mutations in lung adenocarcinoma patients with malignant pleural effusions (MPE)?
Patients with lung adenocarcinoma MPE were recruited prospectively between January 2017 and September 2021. Oncogenic mutations were assessed by treating providers using pleural fluid cytology or lung cancer biopsies. Pleural and plasma cfDNA were used to assess the mutations using next-generation sequencing (NGS).
Fifty-four pleural fluid samples were collected from 42 patients. The diagnostic yield to detect oncogenic mutations for pleural cfDNA, pleural cytology, biopsy, and plasma cfDNA was 49/54 (90.7%), 16/33 (48.5%), 22/25 (88%), and 24/32 (75%), respectively, P < .001. The agreement of mutations in positive samples between pleural cfDNA and pleural cytology was 100%, whereas the agreement of pleural cfDNA with biopsies was 89.4%. The median concentration (interquartile range) of pleural cfDNA was higher than plasma: 28,444 (4,957-67,051) vs 2,966.5 (2,167-5,025) copies of amplifiable DNA per mL, P < .01. Median of 5 mL (interquartile range, 4.5-5) of pleural fluid supernatant was adequate for cfDNA testing.
The diagnostic yield of pleural cfDNA NGS for oncogenic mutations in lung adenocarcinoma patients is comparable to tumor biopsies and higher than pleural cytology and plasma cfDNA. The pleural cfDNA can be longitudinally collected, can be readily incorporated in clinical workflow, and may decrease the need for additional biopsies.
Malignant Pleural Effusion: Presentation, Diagnosis, and Management
2022, American Journal of Medicine
Citation Excerpt :
The optimal amount of pleural fluid to send for cytology has been subject to debate. Studies have shown optimal volumes ranging from 50 to 150 mL.12,13 Cytology of pleural fluid has a mean sensitivity of approximately 60% in diagnosing metastatic malignancy, and is even lower for mesothelioma.2
Malignant pleural effusions are common in patients with cancer. Most malignant pleural effusions are secondary to metastases to the pleura, most often from lung or breast cancer. The presence of malignant effusion indicates advanced disease and poor survival; in lung cancer, the presence of malignant effusion upstages the cancer to stage 4. Usually presenting as a large, unilateral exudative effusion, most patients with malignant pleural effusion experience dyspnea. Prior to intervention, diagnosis of malignant pleural effusion and exclusion of infection should be made. Thoracic imaging is typically performed, with computed tomography considered by many to be the gold standard. Thoracic ultrasound is also useful, particularly if diaphragmatic or pleural thickening and nodularity can be identified. Cytology should then be obtained; this is typically done via pleural fluid aspiration or pleural biopsy. Treatment focuses on palliation and relief of symptoms. Numerous interventions are available, ranging from drainage with thoracentesis or indwelling pleural catheter to more definitive, invasive options such as pleurodesis. There is no clear best approach, and a patient-centered approach should be taken.
Update on the diagnosis and management of malignant pleural effusions
2022, Respiratory Medicine
Roughly 150,000 malignant pleural effusions (MPE) are diagnosed in the United States each year. The majority of cases are caused by lung and breast cancer, and since MPE represents advanced disease, the prognosis is generally poor. In this article we review the pathophysiology, epidemiology, and prognosis of MPE. We then discuss the approach to diagnosis of MPE including the role of imaging, pleural fluid analysis, and medical thoracoscopy. Current management strategies for symptomatic MPE include repeated thoracentesis for patients with very limited life expectancy as well as more definitive procedures such as chemical pleurodesis, tunneled indwelling pleural catheters, and novel combined approaches. The choice of intervention is guided by the efficacy, local expertise, and risk, as well as patient factors and preferences.
How much is enough: investigation of pleural fluid cytology findings related to sample volume
2022, Journal of the American Society of Cytopathology
Citation Excerpt :
They found no differences in the sensitivity or negative predictive values between any 2 quartiles, with small-volume samples diagnosing pleural malignancies with the same sensitivity and statistical accuracy as the larger volume samples.5 In 2009, Abouzgheib et al6 conducted a prospective study investigating whether 50 mL of pleural fluid was equivalent to a larger extracted volume for cytologic analysis by splitting the same samples into small- and large-volume specimens. They found complete concordance between the <50-mL and >50-mL groups in diagnosing malignant effusions, concluding that the collection of >50 mL of pleural fluid for cytologic analysis did not increase the diagnostic yield.6
Cytologic evaluation of pleural effusion samples plays an invaluable role in patient care. Despite this, only a few robust studies have investigated the optimal specimen volume for cytologic evaluation. It is not unusual for our laboratory to receive low-volume pleural effusion samples. Thus, as a part of ongoing quality assurance studies, we examined the performance of low-volume samples.
All pleural effusion samples received during a 1-year period from January 1, 2020 to December 31, 2020 were reviewed. The case data collected included the clinical indications, diagnostic categorization, cell block performance, and adequacy notations. Follow-up data were also collected. The cases were placed into low-volume (≤10 mL, 11-25 mL, and 26-50 mL) and higher volume (>50 mL) groups for analysis.
A total of 226 samples were included in the present study. Of the 226 samples, 89 had a volume of ≤50 mL, including 32 with a very low volume of ≤10 mL. Significantly fewer positive cases were diagnosed in the ≤10-mL group relative to the >50-mL group (6.3% versus 27.7%) with significantly fewer cell blocks performed (15.6% versus 57.7%). However, only 7 of the ≤10 mL cases (21.9%) had been performed to rule out malignancy, significantly less than that for the >50 mL group (81 of 137; 59.1%). Additionally, none of the very-low-volume cases had an upgraded follow-up effusion sample.
The exact role of the sample volume is not entirely clear as there are many factors are at play beyond volume itself. Although larger specimen volumes might be more optimal for a number of reasons, malignancy can be diagnosed at even low sample volumes. Thus, there is value to examining all samples regardless of the volume received. Insertion of an adequacy comment might be prudent for low-volume cases, especially those with a high clinical concern for malignancy.
Malignant Pleural Effusions
2021, Clinics in Chest Medicine
The international system for reporting serous fluid cytopathology—diagnostic categories and clinical management
2020, Journal of the American Society of Cytopathology
Effusions can develop inside serous cavities in several pathologic states, both neoplastic and non-neoplastic. They are easy to drain and can provide useful diagnostic information. However, the reported diagnostic efficacy of these specimens has not been uniform across different laboratories. To standardize practices, the international system for reporting serous fluid cytology (TIS) was developed in accordance with the best international practices, the most up-to-date reported data, and expert consensus.
TIS has set the basic principles for laboratory handling of serous effusion specimens, defined the adequacy criteria, and set a standardized reporting terminology with well-defined criteria for each diagnostic category. These include nondiagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and malignant. Each can provide useful inherent information for appropriate clinical management and follow-up, with a defined expected diagnostic category incidence and risk of malignancy.
TIS applies to serous fluids collected from the pleura, peritoneal, and pericardial cavities. Using TIS, indeterminate categories are presented as either preliminary or as options of last resource. TIS has emphasized the role of ancillary tests in arriving at the correct interpretation within each category. It also has emphasized the importance of a malignant diagnosis as a definitive diagnosis, comparable to histologic examinations. Because of the well-documented outcomes in the adoption of uniform cytology terminology for other organ systems, we recommend the use of the upcoming TIS and believe its use will be paramount to improving the diagnostic yield in this area of cytology.

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The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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Chest

Original ResearchMalignant DiseaseA Prospective Study of the Volume of Pleural Fluid Required for Accurate Diagnosis of Malignant Pleural Effusion

Background

Methods

Results

Conclusion

Section snippets

Materials and Methods

Results

Discussion

Chest

Chest

The comparative diagnostic accuracy, efficiency and specificity of cytologic techniques used in the diagnosis of malignant neoplasm in serous effusions of the pleural and pericardial cavities

Acta Cytol

Pleural diseases related to metastatic malignancies

Eur Respir J

Pleural effusion from malignancy

Ann Intern Med

Original Research
Malignant Disease
A Prospective Study of the Volume of Pleural Fluid Required for Accurate Diagnosis of Malignant Pleural Effusion