Malignant pleural effusion

Dr. Ahmed Hakim Al.Obaidi

M.B.Ch.B, C.A.B.M.S
3rd year respiratory trainee
Definition

 Malignant pleural effusions (MPEs) are caused by infiltration of cancer cells into pleural tissue that may
result in positive fluid cytology and/or be seen on pleural biopsy.

 Para-malignant pleural effusion ??

Introduction

 MPE is the second most common cause of exudative pleural effusion, after infection.

 In most cases, MPE represents spread of metastatic cancer, and the treatment goal is palliation, not cure.
Survival is generally poor, with a median of 4 months, although significant individual variations exist.

 In the tumor-node-metastasis classification of lung cancer, MPE is considered along with contralateral lung
nodules as intrathoracic metastatic disease (M1a)
 Introduction

 Lung cancer is the most common cause of MPEs and, together

with breast cancer, accounts for more than half of all MPEs.
54.3%

 Of the histologic types of bronchogenic cancers,

adenocarcinomas are most frequently associated with MPEs, but
effusions may be seen with all types.
 Introduction

 Breast cancer is the second most common cause of MPEs.

Ipsilateral
50%

 Effusion often develops within a few years of the initial diagnosis

Breast Ca Contralateral
but can present much later, even after 20 years. MPEs 40%

Bilateral
 Lymphoma is the third most common cause in most series but is 10%
possibly the most common cause in young adults.
Radiology

 The size of MPEs varies from small to complete “whiteout” of the hemithorax.

 In one retrospective series of 766 patients, malignancy was found as the cause of 55% of large (opacifying
two-thirds of the hemithorax) and massive (opacifying the entire hemothorax.

 Interestingly, cytologic examination was no more likely to be positive in these large/massive effusions than
in smaller ones (63% yield from large effusions, 53% from small)
Radiology-Plain chest radiograph

 The size of MPEs varies from small to complete “whiteout” of the hemithorax.

 In one retrospective series of 766 patients, malignancy was found as the cause of 55% of large (opacifying two-thirds of
the hemithorax) and massive (opacifying the entire hemothorax. (ref. Murray).

 Chest X-ray often shows moderate to large pleural effusions (80%), and 10% will have massive pleural effusion and 10%
less than 500 mL (ref. ATS).

 Interestingly, cytologic examination was no more likely to be positive in these large/massive effusions than in smaller ones
(63% yield from large effusions, 53% from small).
Radiology-Pleural ultrasound

 Is useful to detect the presence of pleural fluid, guide thoracentesis, and allow assessment of the parietal and
diaphragmatic pleura and can help direct biopsy.

Pleural thickening >1 cm

 Findings suggestive of malignant disease: Pleural nodularity

Diaphragmatic thickening >7 mm

Radiology-CT

 It is part of routine workup of MPE.

Circumferential or nodular pleural thickening

 Findings suggestive of malignant disease: Parietal pleural thickening >1 cm

Mediastinal pleural involvement

Radiology-CT

 Pleural thickening alone was not as specific and could be seen in many benign conditions.

 When present, pleural nodules were highly specific, but they were evident only in 17% of MPEs.

 Half of the patients with malignant effusions had no pleural abnormalities detected on CT, possibly due to
the relative lack of difference in attenuation between the pleural thickening, nodules, and adjacent pleural
fluid.
Radiology-CT

 Contrast-enhanced thoracic computed tomography is the current gold-standard imaging modality for the
pleura.

 When performing a CT for the workup of a pleural effusion, a cenhancement contrast scan may help to
uncover subtle pleural abnormalities.
Radiology-CT
Radiology-MRI

 It is not advocated for routine evaluation of MPEs. However, its excellent soft tissue contrast may be useful
for a detailed evaluation of tumor invasion, especially of the chest wall and pleura as well as in the apices of
the hemithoraces.
Radiology-Positron emission tomography

 PET with 18F-fluorodeoxyglucose (18FDG), when used appropriately, can add valuable information to the
workup of potential MPEs in several ways:
 In cases of significant pleural thickening, absence of 18FDG uptake favors a benign etiology and may help to
avoid pleural biopsies.

 18FDG-avidity can be due to malignancy but can also represent active pleural inflammation of a benign nature.
For example, 18FDG-avidity can persist (probably indefinitely) after talc pleurodesis55.

 In patients with diffuse pleural thickening (or abnormalities) suitable for image-guided pleural biopsy, a preceding
PET scan may help in the selection of biopsy sites.

 PET may also reveal extrapleural sites (e.g., regional lymphadenopathy) more accessible than the pleura for a
biopsy to provide a diagnosis.
 PLEURAL FLUID ANALYSIS

 Malignancy should be considered and a diagnostic thoracentesis performed in any individual with a
unilateral effusion or bilateral effusion and a normal heart size on chest radiograph.

 It is reasonable to order the following pleural fluid tests when considering malignancy: nucleated cell count
and differential, total protein, lactate dehydrogenase (LDH), glucose, pH, amylase, and cytology.
PLEURAL FLUID ANALYSIS

 The majority of MPEs are exudates (MPE is the second most common cause of exudative pleural effusions).

The primary etiology of fluid formation, in most of

 At least 5% of MPEs are transudates
these cases, is a transudative cause (e.g., congestive
heart failure, superior vena cava syndrome, volume
overload)
PLEURAL FLUID ANALYSIS

 The fluid usually is lymphocyte predominant.

 Malignant disease is the most common cause of bloody effusions. However, about half of malignant
effusions are not bloody in appearance (pleural fluid red blood cell counts < 10,000 cells/μL).

 MPEs are often metabolically active with low pleural fluid pH and glucose concentrations (one third of
patient have a Ph <7.30 associated with glucose value <60mg/dl …ref. ATS)
PLEURAL FLUID ANALYSIS

 Pleural fluid amylase concentration is elevated in 10% of MPEs. A very high amylase concentration in MPE
(>600 IU/L) was a poor prognostic factor.

 Tumor markers such as carcinoembryonic antigen (CEA), Leu-1, and mucin, may be helpful in establishing
the diagnosis, as they are frequently positive in adenocarcinomas (50–90%) but rarely seen with mesothelial
cells or mesothelioma (0–10%) (ref. ATS)
PLEURAL FLUID ANALYSIS

 For mesothelioma, detecting the molecule mesothelin, a product of mesothelial cells, may have diagnostic utility
in certain circumstances.

 However, pleural fluid mesothelin levels are elevated in some patients with malignant effusions other than
mesothelioma, whereas the mesothelin level is not elevated in benign effusions (provided the patient has no renal
impairment).

 A high mesothelin level is therefore strongly suggestive of the presence of pleural malignancy and requires
further workup.
PLEURAL FLUID ANALYSIS

 Cytologic examination is reportedly diagnostic in approximately 60% of patients, but the diagnostic yield
varies with the type of tumor, extent of tumor involvement of the pleura, and the expertise of the cytologist.

 Cytologic results are more likely to be positive in adenocarcinoma than in squamous cell lung cancer, for
example, perhaps because adenocarcinoma is more often located peripherally and has a greater tendency to
invade the pleural space.

 Generally speaking, repeating thoracentesis does not increase the yield of cytology for malignancy unless the
first sample was inadequately processed or was very small in volume.
Biopsy

 Biopsy may be necessary when cytologic examination is negative or indeterminate.

 In the past, closed (or “blind”) pleural biopsy was performed as a next step in cases where cytologic results
were negative.

 However, the patchy involvement of the parietal pleura by malignancy appears to make closed pleural
biopsy a hit-or-Miss technique and, not surprisingly, image-directed biopsies have been shown to be more
accurate.
Biopsy

 Thoracoscopy is a well-tolerated procedure that permits excellent visualization of the entire pleural surface.

 Directed biopsies of suspicious areas lead to a correct identification of metastatic pleural disease in nearly
100% of cases.

 This technique has additional advantages, including the ability to provide large biopsy specimens for
immunohistochemical and genetic analysis for molecular markers (e.g., epidermal growth factor receptor), if
needed, to provide information about the gross appearance of tumor, to provide information for staging, to
lyse adhesions, and to drain the pleural space for talc pleurodesis.
Bronchoscopy

 The diagnostic yield of bronchoscopy is low in patients with undiagnosed pleural effusions and should not be
undertaken routinely.

 However, it is indicated when endobronchial lesions are suspected because of hemoptysis, atelectasis, or
large effusions without contralateral mediastinal shift.

 Bronchoscopy also should be performed to exclude endobronchial obstruction before attempting pleurodesis
when there is absence of lung expansion after therapeutic thoracentesis.
 Sensitivity of different biopsy methods

Closed pleural biopsy Fluid cytology Medical thoracoscopy

44 62 95

74 96

97
Ref. ATS
Treatment

 The major indication for treatment is relief of dyspnea. The degree of dyspnea is dependent on both the

volume of the effusion and the underlying condition of the lungs and pleura.

 Because most patients with MPE have limited life expectancy, the overall goal is to provide the greatest
symptom relief using options that are least invasive and require the fewest days in hospital.

 Therapeutic thoracentesis should be performed in virtually all dyspneic patients with malignant pleural
effusions to determine its effect on breathlessness and rate and degree of recurrence.
Treatment

 Repeated thoracentesis may be used for the occasional patient whose fluid reaccumulates slowly or who has a short
life expectancy. Most MPEs recur rapidly and, to avoid frequent drainages, “definitive” treatment is preferred.

 Radiation therapy is not useful for MPE management because tumor involvement of the underlying pleura is
generally extensive. Irradiation of the entire parietal, pleural, and diaphragmatic pleura is not practical.
Treatment

 Definitive treatment for MPEs at present generally refers to pleurodesis or placement of an indwelling
pleural catheter (IPC), or both. This approaches with an intent to provide long-term control of fluid-related
symptoms without requiring repeated invasive drainage procedures

 Pleurodesis is only feasible if the underlying lung expands sufficiently and comes in contact with the parietal
pleura.

 Non expandable (trapped) lung most commonly results from malignant visceral pleural involvement
prohibiting full expansion. Occasionally central airway obstruction can cause non expandable lung.
MPEs Suspected MPE

diagnosis
algorithm Ultrasound guided thoracentesis

Diagnosis made Yes See management options

No

Image guided pleural biopsy Medical thoracoscopy with pleural

Consider repeat thoracentesis (especially if MT non available) biopsy

Diagnosis made No
 Diagnosed malignant pleural effusion

MPEs
Management Symptomatic No Observe

algorithm
Therapeutic thoracentesis

No Evaluate for other causes

Symptomatic relief
consider repeat thoracentesis

No expandable lung Yes

IPC Pleurodesis, IPC or both

Failed pleurodesis
Prognosis

 The overall prognosis is poor for most patients with MPEs.

 Low risk: lived a median duration of 319 days

 Moderate risk: lived a median duration 130 days

 High risk: lived a median duration 44 days

Finally

THANK YOU