Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer

Radiographic Findings

Plain chest radiography is the most common radiographic means of identifying malignant pleural involvement. There is opacification of various extent of the hemithorax, ranging from blunting of the costophrenic angle on the frontal view and posterior gutter on the lateral view to complete opacification of the hemithorax, with or without a midline shift of the mediastinal structures. Decubitus films to confirm a free-flowing liquid layer may be used to follow up suspicious blunting without the classic meniscus fluid sign. With the ready availability of computed tomography (CT) scans that provide superior discrimination of tissue versus fluid, advanced three-dimensional imaging can help direct diagnosis and treatment. Contrast enhancement of the parietal pleural is useful in separating exudative from transudative effusions. More specific features of malignant pleural involvement include pleural nodularity and irregularity and pleural thickness greater than 1 cm. Pleural surfaces thus assessed with CT scanning have a sensitivity of 87% and specificity of 100% for malignant involvement, although the sensitivity is lower for metastatic cancers versus primary pleural cancers. A large pleural effusion normally shifts the mediastinum toward the contralateral chest, sometimes causing critical compression of vascular and conducting airway structures. Therefore a midline undeviated mediastinum or an ipsilaterally deviated mediastinum in the presence of a large effusion suggests central airway obstruction leading to complete atelectasis of the lung. This should prompt an airway examination to look for endobronchial obstruction resulting from tumor or volume loss resulting from inspissated mucus. Ultrasound can complement chest films and/or CT scans to guide bedside sampling and drainage of fluid pockets, especially when these are small or may have become loculated, or when the patient’s comorbidities such as bullous emphysema or large body habitus may increase the risk of complications from thoracentesis.

Most metastatic pleural effusions from breast cancer are unilateral and arise in the hemithorax ipsilateral to the initial site of disease 50% to 83% of the time. Bilateral pleural effusion could be due to underlying systemic diseases such as left ventricular dysfunction and congestive heart failure, renal failure, hepatic disease, hypoalbuminemia, and other causes; however, up to 10% of patients with MPE may have bilateral malignant effusions. It should be qualified that these studies are from the era before CT scans were routinely used to assess disease progression or to identify pleural pulmonary involvement. The routine use of CT scanning may detect many smaller pleural effusions. Distribution of metastatic implants on the pleural surfaces has been studied in vivo during diagnostic and therapeutic thoracoscopy, and this has demonstrated that a majority of the visible lesions stud the visceral pleura and the parietal pleura. Given the differential blood supply and lymphatic drainage of the visceral and parietal pleural surfaces, this suggests that most pleural metastases occur in combination with and perhaps subsequent to hematogenous and lymphangitic spread of disease to the lungs.

18-Fluorodeoxy glucose positron emission tomography (FDG-PET) is accepted as an effective metabolic imaging adjunct to help characterize abnormal-appearing tissue as likely being neoplastic, inflammatory, or benign. FDG-PET has high sensitivity and specificity rates in the imaging of primary pleural cancers, as in mesothelioma. FDG-PET is superior to CT alone in the detection of pleural metastases in primary bronchogenic carcinoma, with a sensitivity approaching 90% and a specificity and accuracy of 94.1% and 91.4%, respectively. Although not part of the standard staging workup for breast cancer, PET/CT imaging has shown usefulness in staging patients with at least clinical IIB disease, where it may detect intrathoracic metastases.

An example of FDG-PET positive pleural, lung parenchymal, and extra-thoracic soft tissue metastases in a breast cancer patient is presented in Fig. 64.1 . The use of PET-CT scanners with fused PET-CT imaging facilitates the localization of pleural metastases and help distinguish these from metastases to the lung periphery, chest wall osseus, and soft tissue structures.

Tissue Confirmation

Thoracentesis and Studies on the Pleural Fluid

The radiologic advances outlined earlier have greatly improved our ability to detect earlier and characterize the extent of possible pleural metastases from breast cancer. However, the broad differential of a possible malignant effusion generally makes it necessary to obtain a tissue diagnosis for accurate staging before proceeding with appropriate regional and/or systemic therapy.

Since the presentation of malignant pleural metastases from breast cancer is most often a pleural effusion ( Fig. 64.2 ), symptomatic or otherwise, the initial diagnostic step is removal and analysis of fluid for diagnosis and as needed for the relief of symptoms. Thoracentesis can be performed “blind,” without real-time radiologic guidance, after review of a chest film or CT scan; however, beside ultrasonography by physicians can be a valuable tool, especially in patients with smaller or loculated effusions. The diagnostic yield of pleural fluid cytology varies and ranges from 40% to 90%, depending on the tumor type, tumor burden, and number of thoracenteses performed. Breast cancer appears to have a higher pleural cytologic yield than metastatic lung cancer. There is debate as to whether a large volume of fluid improves diagnostic yield; practice currently varies from sending only 10 to 20 mL to more than 1 L. Furthermore, local laboratory practice differs as to whether only a small aliquot is processed as a smear or whether a larger volume is processed into a cell block. There is evidence that the preparation of a cell block increases the diagnostic yield from 11% to 38%. An additional advantage of a cell block is having additional material available for immunostaining. Routine tests performed on the pleural fluid include chemistries to distinguish an exudate from a transudate. Pleural fluid glucose, pH, lactate dehydrogenase (LDH), and cultures may rule differentiate a pleura space infection from a malignant effusion. Table 64.1 highlights some common causes and findings that may be encountered in the workup of a pleural effusion in a patient with a history of breast cancer. A proven malignant effusion with low glucose, low pH, and a high LDH generally portends a worse prognosis, but it should not discourage the clinician from attempting to drain and potentially sclerose the affected space for palliation.

Tissue Biopsies

Pleural needle biopsy with a variety of needles had been performed “blind” after confirming entry into a pocket of pleural fluid with a finder 21-gauge or smaller needle or directly with ultrasound. The yield of pleural needle biopsy is generally lower than that provided by fluid cytology. Because the parietal surface implants may be not diffuse ( Fig. 64.3 ), needle sampling alone of the pleura alone may have low yield unless a clearly thickened area is seen on imaging and can be targeted. Given the potential risk of parenchymal lung puncture, occasional life-threatening bleeding (typically from intercostal arteries), and the availability of more accurate minimally invasive image-guided procedures, blind pleural needle biopsies are generally of historical interest and unwarranted.

Surgical approaches for tissue diagnosis may be required when repeat thoracentesis with or without image-guided pleural biopsy fails to provide a tissue confirmation or when the initial presentation suggests a multiloculated complex malignant effusion. Thoracoscopic approaches, either with video-assisted thoracoscopic surgery (VATS) or robotic-assisted thoracoscopic surgery (RATS), have 86% to 100% diagnostic accuracy in diagnosing a MPE. These procedures are generally performed under general anesthesia, but small single-incision thoracoscopy can also be performed under local anesthetic in the appropriate patient. Confirmation of malignant pleural involvement based on histologic examination of fresh-frozen tissue or the appearance under visual examination may expedite long-term management of the involved pleural space by pleurodesis at the end of the case, either by mechanical or chemical means. If pleural apposition cannot be achieved to allow for successful pleurodesis, pleural drainage catheters—either temporary or tunneled indwelling pleural catheters (IPCs)—can also be optimally positioned at the time of surgery.