0
ONLINE EXCLUSIVES
Chest Imaging and Pathology for Clinicians |

A 70-Year-Old Woman With Dyspnea and Chest PainOlder Woman With Dyspnea and Chest Pain FREE TO VIEW

Aarthi Ganesh, MD; Michael Flores, MD; Isabel Oliva, MD; Gordon E. Carr, MD
Author and Funding Information

From the Departments of Pulmonary and Critical Care (Drs Ganesh and Carr), Pathology (Dr Flores) and Radiology (Dr Oliva), University of Arizona, Tucson, AZ.

Correspondence to: Aarthi Ganesh, MD, Department of Pulmonary and Critical Care, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85721; e-mail: ganesh_rti@yahoo.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(1):e14-e18. doi:10.1378/chest.13-1871
Text Size: A A A
Published online

A 70-year-old white woman presented to the hospital for evaluation of shortness of breath and chest pain. Her dyspnea began 10 months ago and progressively worsened in the last 2 months. In the 48 h prior to admission, she also had right-sided pleuritic chest pain. She complained of cough with clear sputum for approximately 1 month, but denied hemoptysis, voice changes, or dysphagia. She reported weight loss of 15 pounds over the prior 3 months, as well as fatigue and occasional night sweats. She denied fever or chills. She smoked one pack of cigarettes a day for 15 years, until she quit smoking 30 years ago. She consumed two to three glasses of wine daily, until she quit 6 months ago. Her past medical history was significant only for hypertension. She had worked as a nurse, but denied any occupational exposures to animals, fumes, metals, or dusts.

On examination, the patient was in moderate respiratory distress. Vital signs were as follows: temperature, 36.9°C; heart rate, 117 beats/min; BP, 180/99 mm Hg; respiratory rate, 25 breaths/min; and arterial oxygen saturation, 98% to 99% while breathing 5 L/min supplemental oxygen by nasal cannula. On chest examination, air entry and breath sounds were diminished on the right side but normal on the left. There was dullness to percussion on the right. Cardiovascular examination showed tachycardia with a regular rhythm but no jugular venous distention or abnormal heart sounds. The neck had no masses, and there was no cervical or supraclavicular lymphadenopathy. The abdominal examination showed no hepatosplenomegaly. The skin showed no rashes or jaundice, and the extremities were warm with no edema.

CBC count with differential showed a WBC count of 16.7 × 103/μL with 91% neutrophils, hemoglobin level of 15.2 g/dL, and platelet count of 797 × 103/μL. Her renal function was normal. Her alkaline phosphatase level was 339 IU/L, alanine aminotransferase level was 25 IU/L, aspartate aminotransferase level was 35 IU/L, albumin level was 2.6 g/dL, and lactate level was 1.4 mM. The coagulation profile was within normal limits. The patient’s D-dimer level was elevated at 2.87 μg/mL. Blood cultures were negative. Her calcium level was 8.8 mg/dL.

An initial chest radiograph (Fig 1A) showed complete opacification of the hemithorax on the right side, with leftward shift of the mediastinum, indicative of a large pleural effusion. A CT scan of the chest showed a large, right-sided pleural effusion with leftward shift of the mediastinum and smooth thickening of the parietal pleura (Figs 1B, 1C). There were no visible endobronchial lesions or mediastinal masses.

Figure Jump LinkFigure 1. A, Complete opacification of right-side lung. B, CT scan showing large right-sided pleural effusion and pleural thickening (white arrows). C, Coronal section with large right-sided pleural effusion and mediastinal shift toward the left. White arrows point to areas of pleural thickening. D, Persistent pneumothorax with collapsed lung.Grahic Jump Location

A thoracentesis was performed and showed a cloudy yellow pleural fluid (Table 1). Due to progressive respiratory distress and concern for a possible empyema, the pleural space was drained with a 14F pigtail catheter. Chest CT scan performed after the placement of the pleural pigtail catheter demonstrated a decrease in the pleural effusion, a new pneumothorax, and persistent pleural thickening. Because of the failure of the right lung to reexpand, and the concerning findings on pleural fluid analysis, lung decortication and pleurectomy were performed via video-assisted thoracoscopic surgery (VATS). A chest radiograph taken after the VATS showed a marked decrease in the pleural effusion and persistent pneumothorax, but the right lung failed to reexpand, raising the concern of an unexpandable lung (Fig 1D). The left lung demonstrated pulmonary edema on this follow-up chest radiograph, likely due to the development of renal insufficiency.

Table Graphic Jump Location
Table 1 —Pleural Fluid Analysis

LDH = lactate dehydrogenase.

During the VATS, a parietal pleural biopsy specimen was obtained. Grossly, the pleural surface of the biopsy specimen was thickened, approximately 0.6 to 1.2 cm, and was tan-gray. Histologic examination revealed dense fibrous tissue with irregular islands of pleomorphic epithelioid cells, which imparted a pseudoglandular appearance but no clear glandular pattern. The preliminary reading favored mesothelioma; however, on immunohistochemical staining, the specimen was positive for thyroid transcription factor-1, cytokeratin (CK)-7, and carcinoembryonic antigen, but negative for CK 5/6, calretinin, and antipodoplanin (D2-40) (Fig 2).

Figure Jump LinkFigure 2. A, Histologic examination reveals large atypical cells (black arrow) forming glands (blue arrow) (Hematoxylin and Eosin; original magnification × 400). B, Positive stain for thyroid transcription factor-1 (original magnification × 100). C, Positive stain for CD15 (original magnification × 400). D, Positive stain for carcinoembryonic antigen by immunohistochemistry (original magnification × 400).Grahic Jump Location
What is the diagnosis?
Diagnosis: Pseudomesotheliomatous adenocarcinoma
Clinical Discussion

In this patient, the pleural effusion and collapsed lung resulted from pseudomesotheliomatous adenocarcinoma (PMA). Patients with PMA generally present with cough, dyspnea, and chest pain. This malignancy typically occurs in heavy smokers in the fifth and sixth decades of life and has male preponderance.1-3 Association of this tumor with asbestos has not been clearly determined. Earlier case reports and series negated the association.4 However, certain others found some of their patients had a positive exposure to asbestos.1,2,5,6 Lung tissue analysis for the presence of asbestos fibers has been inconclusive, thus the association is uncertain. This patient had significant smoking history but no exposure to asbestos. Due to the presence of a dense peel of malignant tissue encasing the visceral pleura, lung collapse is a known complication of PMA. Sclerosis attempts are rarely successful, and management of these patients has proved challenging. In the setting of PMA, treatment options for entrapped lung include decortication and pleurectomy, serial thoracentesis, or long-term thoracostomy drainage and chemotherapy.

When remote or active pleural disease causes visceral pleural restriction, drainage of pleural fluid may not result in the normal reapposition of the visceral and parietal pleural surfaces. This phenomenon occurs as two related but distinct clinical entities.7,8 “Trapped lung” refers to the consequence of remote pleural space inflammation. In this setting, the initial inflammation causes the development of a mature, fibrous membrane over the visceral pleura that impedes lung reexpansion. The inflammation must have resolved before the diagnosis of trapped lung can be made. On the other hand, “lung entrapment” refers to an unexpandable lung in the setting of active pleural disease. Common causes of lung entrapment include infection (eg, empyema, parapneumonic effusion, or infected hepatic hydrothorax), malignancy, or hemothorax. Other conditions associated with the development of lung entrapment include coronary artery bypass graft surgery, postcardiac injury syndrome, uremia, radiation therapy, and rheumatoid pleurisy.7,8 In clinical practice, it can be difficult to distinguish between trapped lung and lung entrapment.

Although not performed in this case, pleural manometry may be useful to help distinguish between trapped lung and lung entrapment. In the normal thorax, at functional residual capacity, pleural pressure is slightly subatmospheric (approximately −3 to −5 cm H2O). As fluid accumulates in the pleural space, the pleural pressure typically rises. Normally, lung reexpansion after pleural fluid drainage is accompanied by reestablishment of this normal negative pleural pressure. In contrast, pleural manometry in cases of lung entrapment shows that the initial pressure is generally positive, but as pleural fluid is removed, pleural pressure becomes progressively negative. Finally, in cases of trapped lung, the pleural pressures are highly negative throughout the thoracentesis.9,10

PMA are advanced adenocarcinomas, representing stage IV disease, and carry a rather poor prognosis.5,11 The treatment options for locally advanced adenocarcinoma include chemotherapy, most commonly with platinum-based agents. PMA appears to be resistant to both chemotherapy and radiation in most cases.

Radiologic Discussion

Chest imaging in PMA shows the presence of pleural effusion in the majority of cases, with pleural nodules, plaques, or mesothelioma-like pleural thickening. The effusion is generally unilateral. It is difficult to differentiate between PMA and malignant pleural mesothelioma on the basis of the uptake patterns obtained by 18F-fluorodeoxyglucose PET/CT imaging. However, this type of imaging may be helpful in identifying the primary focus and in staging the disease.12

When chest radiography shows persistent lung collapse after drainage of pleural fluid, PMA should be considered in the differential diagnosis. In the setting of lung entrapment, chest radiography may reveal contralateral mediastinal shift due to a large pleural effusion. CT scans in patients with trapped lung can show abnormal visceral pleural thickening and loculated pleural effusion. The pathognomonic radiographic sign of trapped lung is the pneumothorax ex vacuo, or suction pneumothorax.13 This finding refers to a small to moderate-sized air collection in the pleural space after evacuation of the effusion, often seen in association with a visibly thickened visceral pleural surface. Chest CT scan better depicts the thickened pleura, which usually involves the pleural surface in a circumferential manner encasing the adjacent lung. IV contrast administration for the CT examination allows better characterization of the pleural abnormality and can show enhancement of the visceral and parietal pleura, known as “split pleura” sign.14

Pathologic Discussion

To our knowledge, PMA was first described by Harwood et al4 in 1976. It is a malignant epithelial neoplasm with features similar to those of diffuse malignant pleural mesothelioma.1,4 Gross examination shows extensive pleural thickening with nodules encasing the entire lung and extending into pulmonary septa. The surgical specimens are generally firm, rubbery, or indurated tissues. The tumor generally involves the chest wall and diaphragm. Microscopically, the tumor resembles the epithelioid variant of malignant mesothelioma. It shows areas of glandular, tubular, or papillary features embedded in collagenous stroma. The stroma, in some cases, may show a desmoplastic reaction, mimicking a biphasic mesothelioma.

PMA, a variant of adenocarcinoma, shares multiple common histologic features with mesothelioma. Accordingly, accurate diagnosis requires immunohistochemistry or electron microscopy. Histochemical staining with periodic acid-Schiff, with or without diastase digestion and use of muciramine, maybe useful for diagnosis of adenocarcinoma, but it is not positive in all cases. Also 5% of mesothelioma can show diastase-resistant, periodic acid-Schiff-positive mucin. Pulmonary adenocarcinoma, including PMA, is usually positive for thyroid transcription factor-1; CK-7; the carcinoembryonic antigen, Leu-M1, and BER-EP4 antibodies; and the B72.3 and MOC-31 monoclonal antibodies.2 Usually two or more mesothelial markers and two or more adenocarcinoma markers are necessary to classify the type of malignancy (Table 2).6,15,16 Currently, the most commonly used mesothelial markers include antibodies to CK-5/6, calretinin, and antipodoplanin (D2-40). Other mesothelial markers include Wilms tumor protein-1, mesothelin, Hector Battifora mesothelial-1, and thrombomodulin. Other histologic types of lung carcinoma, including squamous cell carcinoma, can present with pseudomesotheliomatous variants. As such, definitive diagnosis often requires immunohistochemistry.16

Table Graphic Jump Location
Table 2 —Immunohistochemical Markers to Differentiate Between Mesothelioma and Lung Adenocarcinoma

PMA is a specific variant of adenocarcinoma that has a presentation similar to mesothelioma. Definitive diagnosis requires histopathologic analysis with immunohistochemistry. It is important to distinguish between the two tumors due to treatment and medicolegal implications. Treatment is generally palliative and overall prognosis is poor, with mean survival of around 8 months. The patient in this case opted for hospice care.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Saito R, Kasajima A, Taniuchi S, et al. Case reports of primary pulmonary adenocarcinoma with pleural spread: so-called pseudomesotheliomatous adenocarcinoma. Pathol Int. 2012;62(10):709-715. [CrossRef] [PubMed]
 
Attanoos RL, Gibbs AR. ‘Pseudomesotheliomatous’ carcinomas of the pleura: a 10-year analysis of cases from the Environmental Lung Disease Research Group, Cardiff. Histopathology. 2003;43(5):444-452. [CrossRef] [PubMed]
 
Weissferdt A, Moran CA. Diagnostic Pathology of Pleuropulmonary Neoplasia. New York, NY: Springer; 2012:366.
 
Harwood TR, Gracey DR, Yokoo H. Pseudomesotheliomatous carcinoma of the lung. A variant of peripheral lung cancer. Am J Clin Pathol. 1976;65(2):159-167. [PubMed]
 
Koss M, Travis W, Moran C, Hochholzer L. Pseudomesotheliomatous adenocarcinoma: a reappraisal. Semin Diagn Pathol. 1992;9(2):117-123. [PubMed]
 
Koss MN, Fleming M, Przygodzki RM, Sherrod A, Travis W, Hochholzer L. Adenocarcinoma simulating mesothelioma: a clinicopathologic and immunohistochemical study of 29 cases. Ann Diagn Pathol. 1998;2(2):93-102. [CrossRef] [PubMed]
 
Huggins JT, Doelken P, Sahn SA. The unexpandable lung. F1000 Med Rep. 2010;2:77. [PubMed]
 
Pereyra MF, Ferreiro L, Valdés L. Unexpandable lung. Arch Bronconeumol. 2013;49(2):63-69. [CrossRef] [PubMed]
 
Feller-Kopman D, Parker MJ, Schwartzstein RM. Assessment of pleural pressure in the evaluation of pleural effusions. Chest. 2009;135(1):201-209. [CrossRef] [PubMed]
 
Huggins JT, Doelken P. Pleural manometry. Clin Chest Med. 2006;27(2):229-240. [CrossRef] [PubMed]
 
Kobashi Y, Matsushima T, Irei T. Clinicopathological analysis of lung cancer resembling malignant pleural mesothelioma. Respirology. 2005;10(5):660-665. [CrossRef] [PubMed]
 
Nakamori T, Kosuda S, Kyoto Y, Fujikawa A, Naoi Y, Nakamori Y. Pseudomesotheliomatous lung cancer mimicking mesothelioma on F-FDG PET/CT images: report of 2 cases. Jpn J Radiol. 2013;31(8):542-545. [CrossRef] [PubMed]
 
Huggins JT, Sahn SA, Heidecker J, Ravenel JG, Doelken P. Characteristics of trapped lung: pleural fluid analysis, manometry, and air-contrast chest CT. Chest. 2007;131(1):206-213. [CrossRef] [PubMed]
 
Kraus GJ. The split pleura sign. Radiology. 2007;243(1):297-298. [CrossRef] [PubMed]
 
Mani H, Zander DS. Immunohistochemistry: applications to the evaluation of lung and pleural neoplasms: part 2. Chest. 2012;142(5):1324-1333. [CrossRef] [PubMed]
 
Husain AN, Colby T, Ordonez N, et al; International Mesothelioma Interest Group. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013;137(5):647-667. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. A, Complete opacification of right-side lung. B, CT scan showing large right-sided pleural effusion and pleural thickening (white arrows). C, Coronal section with large right-sided pleural effusion and mediastinal shift toward the left. White arrows point to areas of pleural thickening. D, Persistent pneumothorax with collapsed lung.Grahic Jump Location
Figure Jump LinkFigure 2. A, Histologic examination reveals large atypical cells (black arrow) forming glands (blue arrow) (Hematoxylin and Eosin; original magnification × 400). B, Positive stain for thyroid transcription factor-1 (original magnification × 100). C, Positive stain for CD15 (original magnification × 400). D, Positive stain for carcinoembryonic antigen by immunohistochemistry (original magnification × 400).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Pleural Fluid Analysis

LDH = lactate dehydrogenase.

Table Graphic Jump Location
Table 2 —Immunohistochemical Markers to Differentiate Between Mesothelioma and Lung Adenocarcinoma

References

Saito R, Kasajima A, Taniuchi S, et al. Case reports of primary pulmonary adenocarcinoma with pleural spread: so-called pseudomesotheliomatous adenocarcinoma. Pathol Int. 2012;62(10):709-715. [CrossRef] [PubMed]
 
Attanoos RL, Gibbs AR. ‘Pseudomesotheliomatous’ carcinomas of the pleura: a 10-year analysis of cases from the Environmental Lung Disease Research Group, Cardiff. Histopathology. 2003;43(5):444-452. [CrossRef] [PubMed]
 
Weissferdt A, Moran CA. Diagnostic Pathology of Pleuropulmonary Neoplasia. New York, NY: Springer; 2012:366.
 
Harwood TR, Gracey DR, Yokoo H. Pseudomesotheliomatous carcinoma of the lung. A variant of peripheral lung cancer. Am J Clin Pathol. 1976;65(2):159-167. [PubMed]
 
Koss M, Travis W, Moran C, Hochholzer L. Pseudomesotheliomatous adenocarcinoma: a reappraisal. Semin Diagn Pathol. 1992;9(2):117-123. [PubMed]
 
Koss MN, Fleming M, Przygodzki RM, Sherrod A, Travis W, Hochholzer L. Adenocarcinoma simulating mesothelioma: a clinicopathologic and immunohistochemical study of 29 cases. Ann Diagn Pathol. 1998;2(2):93-102. [CrossRef] [PubMed]
 
Huggins JT, Doelken P, Sahn SA. The unexpandable lung. F1000 Med Rep. 2010;2:77. [PubMed]
 
Pereyra MF, Ferreiro L, Valdés L. Unexpandable lung. Arch Bronconeumol. 2013;49(2):63-69. [CrossRef] [PubMed]
 
Feller-Kopman D, Parker MJ, Schwartzstein RM. Assessment of pleural pressure in the evaluation of pleural effusions. Chest. 2009;135(1):201-209. [CrossRef] [PubMed]
 
Huggins JT, Doelken P. Pleural manometry. Clin Chest Med. 2006;27(2):229-240. [CrossRef] [PubMed]
 
Kobashi Y, Matsushima T, Irei T. Clinicopathological analysis of lung cancer resembling malignant pleural mesothelioma. Respirology. 2005;10(5):660-665. [CrossRef] [PubMed]
 
Nakamori T, Kosuda S, Kyoto Y, Fujikawa A, Naoi Y, Nakamori Y. Pseudomesotheliomatous lung cancer mimicking mesothelioma on F-FDG PET/CT images: report of 2 cases. Jpn J Radiol. 2013;31(8):542-545. [CrossRef] [PubMed]
 
Huggins JT, Sahn SA, Heidecker J, Ravenel JG, Doelken P. Characteristics of trapped lung: pleural fluid analysis, manometry, and air-contrast chest CT. Chest. 2007;131(1):206-213. [CrossRef] [PubMed]
 
Kraus GJ. The split pleura sign. Radiology. 2007;243(1):297-298. [CrossRef] [PubMed]
 
Mani H, Zander DS. Immunohistochemistry: applications to the evaluation of lung and pleural neoplasms: part 2. Chest. 2012;142(5):1324-1333. [CrossRef] [PubMed]
 
Husain AN, Colby T, Ordonez N, et al; International Mesothelioma Interest Group. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013;137(5):647-667. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543