Hospital Medicine

Pleural plaques/Mesothelioma

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Pleural plaques/Mesothelioma

I. What every physician needs to know.

Inhalation exposure to asbestos causes malignant as well as non-malignant diseases of the chest. The spectrum of pleural diseases associated with exposure can range from pleural plaques to effusion and malignancy. Despite major awareness and enormous effort to control exposure, asbestos related diseases will continue because of disease latency and ongoing exposure. In this chapter, the focus on two major diseases related to asbestos: pleural plaques and malignant mesothelioma.

II. Diagnostic Confirmation: Are you sure your patient has Pleural plaques/Mesothelioma?

Asbestos refers to a family of naturally occurring minerals found in soil worldwide. They are categorized into two types: serpentine or amphibole. The former is long curly and used in 93% of commercial products while the latter is straight rodlike and used in 7% of commercial products. Both forms have been associated with mesothelioma, pleural plaques, lung cancer as well as non-malignant respiratory disorders.

A. History Part I: Pattern Recognition:

Pleural plaques are the most common pleural changes caused by asbestos. Usually, there is a 20 - 30 years latency period before pleural plaques appear. Although they do not undergo malignant transformation, patients with plaques are at risk for developing pulmonary fibrosis, lung cancer, and malignant mesothelioma. They are asymptomatic.

Malignant pleural mesothelioma is caused by asbestos exposure in 85% of cases. Less commonly radiation, chemical carcinogens, and viruses have been implicated. It usually occurs 30 - 40 years after exposure. Typically, patients present in the fifth to seventh decade, with men accounting for 80% of cases. Clinically, majority of patients will present with insidious onset of nonpleuritic chest pain, dyspnea, and cough. The mass usually involves both the parietal and visceral pleura.

B. History Part 2: Prevalence:

In the past, high exposure to asbestos dust occurred in the manufacturing of asbestos textiles, building construction, shipbuilding industries and as contaminant in vermiculite. In the present day, asbestos can be found in older homes, commercial buildings, automobile brake pads and clutches, roofing material, vinyl tiles, and some cement pipes. The most common occupations associated with asbestos exposure are plumbing, pipefitting, mechanics, insulating, and electrical work. Asbestos is a known carcinogen and the risk of developing lung cancer can be multiplicative with use of cigarette smoking. However, there is no synergistic interaction between asbestos and cigarette smoking affecting the incidence of mesothelioma.

C. History Part 3: Competing diagnoses that can mimic Pleural plaques and Mesothelioma.

Asbestos exposure can cause a variety of respiratory as well as non-respiratory diseases. Respiratory diseases include parenchymal asbestosis, lung carcinoma, and pleural diseases (pleural plaques, benign asbestos pleural effusions, pleural fibrosis, and malignant mesotheliomas). Non-respiratory diseases includes peritoneal mesotheliomas, cor pulmonale and constrictive pericarditis. Metastatic adenocarcinoma from solid organs can mimic mesothelioma and immunohistochemistry staining in biopsy is helpful to distinguish them. Chest imaging including high resolution computed tomography (HRCT) is essential for differentiating among most of asbestos associated diseases.

D. Physical Examination Findings.

Patients with only pleural plaques are often asymptomatic with unremarkable physical examination. Patients with malignant mesothelioma may have dullness to percussion at the base of the affected lung caused by pleural effusion and tumor invading the pleura. Also, metastatic lymph nodes may be palpated as well as digital clubbing observed occasionally.

E. What diagnostic tests should be performed?

Physical examination is non-specific and does not lead to diagnosis.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Thrombocytosis and anemia might be present in patients with mesothelioma. Mesothelin biomarker in serum and/or pleural fluid may serve as adjuvant diagnostic tool with high specificity but low sensitivity. Pleural fluid cytologic examination is positive for malignant cells in one third of cases, however, it is difficult to make definitive diagnosis without histologic proof. Thoracoscopy with direct visualization of the pleura is useful in obtaining adequate sample for diagnosis in 90% of cases.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Chest imaging will help detect pleural plaques. HRCT is more sensitive than chest radiography.

The most common manifestation on chest radiography in patient with mesothelioma is pleural effusion and nodular thickening of the pleura. Pleural plaques indicate past asbestos exposure but are not a precursor to developing mesothelioma. Computed tomography (CT) will provide more information about the extent of the disease such as diaphragmatic, hilar, or mediastinal lymph node involvement. Positron emission tomography (PET) is helpful in differentiating from benign disease and showing distant metastasis.

Pleural plaques are smooth, calcified, white, raised, irregular lesions found on the parietal pleura. They are usually symmetric and bilateral, commonly located in the posterior and lateral midzone between fifth and eighth ribs and over the diaphragms. See Figure 1.

Figure 1.

A computed tomography scan showing bilateral pleural plaques calcifications

CT imaging of the chest most commonly shows pleural thickening, nodularity, interlobar fissure thickening, and less often pleural plaques. Figure 2 shows a CT chest with pleural thickening and nodularity.

Figure 2.

A computed tomography of the chest shows pleural thickening and nodularity

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

NA

III. Default Management.

Pleural plaques are asymptomatic and do not require treatment.

Malignant Pleural Mesothelioma (MPM) is characterized as being highly malignant and aggressive. If left untreated, the median survival time of the patients is about 4-12 months. Most patients die of the local invasion of the tumor or the contralateral metastasis. The benefit of treatment of pleural mesothelioma is controversial. Pleural effusion management and control of active symptoms are the priority in management. Other modalities include surgery, chemotherapy, and radiation therapy.

A. Immediate management.

The majority of patients with mesothelioma have pleural effusion and are often symptomatic and require drainage. Pleuritic and nonpleuritic chest pain should be adequately controlled with early use of analgesic pain medications (such as opiates).

B. Physical Examination Tips to Guide Management.

None.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Mesothelioma histology is mainly divided in three main types: epithelioid, sarcomatoid, and mixed pattern. Epithelioid histology has better survival.

Chest radiography can be used to monitor pleural effusion. WBC 8.3x103/μL or greater, platelets greater than 400,000μL, LDH greater than 500 IU/L indicate poor prognosis. Mesothelin levels are higher in subjects with larger tumor burden and usually decrease in patients undergoing debulking surgery.

D. Long-term management.

The comprehensive treatment of resecting the visible tumor as much as possible, combined with radiotherapy, chemotherapy and immunotherapy is the most promising strategy currently. Unfortunately, the efficacy of treatment is very limited for the tumor is usually diagnosed too late. All of the current therapies are only expected to improve the quality of life and prolong survival time of the patients with MPM. Decortication or extrapleural pneumonectomy (EPP) techniques are used in operable patients. Compared with decortication, EPP does not prolong survival and may increase the postoperative complications for patients with MPM. Epithelial type, early stage, adequate PFT, confined to the pleura, and no positive lymph nodes are only found in few cases and should be done by an experienced thoracic surgeon. Postoperative chemotherapy with subsequent radiation therapy are used with limited success.

The chemotherapy combination of cisplatin and pemetrexed as well as radiation therapy are used as palliation for inoperable disease. Control of pleural effusion with pleural drains (Pleur-X® catheter) or talc pleurodesis is desirable for symptomatic patients.

There is no effective therapy to cure mesothelioma. The combination of conventional therapy with immunotherapy might be a promising treatment modality in the future.

E. Common Pitfalls and Side-Effects of Management.

The threshold of asbestos inhalation below which asbestos related disease will not occur is unknown. Prevention of inhalation is desirable as there is no effective treatment so far. Malignant mesothelioma should be considered in the differential diagnosis of pleural effusion, especially in patients with exposure to asbestos. Detailed occupation history should be done. However, in 30% of cases no significant history of asbestos exposure might be identified. A negative cytologic pleural effusion or closed pleural biopsy should lead the physician to pursue a definitive diagnosis.

Immunohistochemical staining will differentiate mesothelioma from metastatic cancer. Treatment of mesothelioma is still controversial with no therapy showing long term survival. Patients should be encouraged to enrol in clinical therapeutic trials.

Side effects of medications depend on chemotherapy modality used.

IV. Management with Co-Morbidities.

Non epithelial histology, poor performance status, age above 75, and male gender indicate poor prognosis.

Comorbid conditions in addition to factors mentioned above indicate poor prognosis.

A. Renal Insufficiency.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

B. Liver Insufficiency.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

C. Systolic and Diastolic Heart Failure.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

E. Diabetes or other Endocrine issues.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

F. Malignancy.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management; however, multiple comorbidities indicate poor prognosis.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management; however, multiple comorbidities indicate poor prognosis.

I. Gastrointestinal or Nutrition Issues.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

J. Hematologic or Coagulation Issues.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management; however, multiple comorbidities indicate poor prognosis.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Adequate control of pain.

Consider pleural effusion drainage if patient has shortness of breath.

B. Anticipated Length of Stay.

Once diagnosis of mesothelioma is established, patients should be assessed whether surgery is considered. Inoperable patients should be seen by palliative care team. Permanent control of pleural effusion using pleurodesis or pleural catheter should be considered to minimize hospitalization and for symptomatic control of dyspnea. Adequate control of pain using different modalities such as opiates, palliative chemotherapy or radiation therapy should be considered.

C. When is the Patient Ready for Discharge.

For the majority of patients, control symptoms (chest pain, dyspnea from pleural effusion) should be adequate before discharge.

D. Arranging for Clinic Follow-up.

N/A

1. When should clinic follow up be arranged and with whom.

Patients with pleural plaques should be followed in a pulmonary clinic regularly.

Inoperable mesothelioma patients should be referred to palliative clinic to be followed up for adequate control of symptoms. Operable patients should follow up with oncology, pulmonary, radiation therapy, and cardiothoracic clinic.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Chest radiography should be ordered periodically for patients with asbestos exposure. In patients with <10 years exposure, it should be ordered every 3-5 years; every 1-2 years with > 10 years exposure; annually if >20 years of exposure.

E. Placement Considerations.

For patients with inoperable mesothelioma, hospice care, either at home or in a facility, should be arranged.

F. Prognosis and Patient Counseling.

Patients with pleural plaques are often asymptomatic. There is no evidence that pleural plaques increase the risk of developing malignant mesothelioma or lung cancer and, thus, have survival almost the same as that of general population.

If left untreated, the median survival time of the patients is about 4-12 months. Usually cause of death is attributed to respiratory failure from local extension of the disease, congestive heart failure, pericardial constriction, or cardiac arrhythmia.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

The best preventive measure is to minimize inhalational exposure and counsel for smoking cessation.

VII. What's the evidence?

Cugell, DW, Kamp, DW. "Asbestos and the pleura: a review". Chest. vol. 125. 2004. pp. 1103-1117.

Carbone, M, Ly, BH, Dodson, RF. "Malignant mesothelioma: facts, myths and hypotheses". J Cell Physiol. vol. 227. 2012. pp. 44-58.

Weiss, W. "Asbestos-related pleural plaques and lung cancer". Chest. vol. 103. 1993. pp. 1854-1859.

Henderson, DW, Rantanen, J, Barnhart, S. "Asbestos, asbestosis, and cancer: the Helsinki criteria for diagnosis and attribution—a consensus report of an international expert group". Scand J Work Environ Health. vol. 28. 1997. pp. 311-316.

Weiss, W. "Asbestosis: a marker for the increased risk of lung cancer among workers exposed to asbestos". Chest. vol. 115. 1999. pp. 536-549.

Robinson, BW, Lake, RA. "Advances in malignant mesothelioma". N Engl J Med. vol. 353. 2005. pp. 1591-1603.

Peto, J, Doll, R, Herman, C. "Relationship of mortality to measures of environmental asbestos pollution in an asbestos textile factory". Ann Occup Hyg. vol. 29. 1985. pp. 305-355.

Boutin, C, Schlesser, M, Frenay, C. "Malignant pleural mesothelioma". Eur Respir J. vol. 12. 1998. pp. 972-981.

Hollevoet, K, Nackaerts, K, Thimpont, J, Germonpré, P, Bosquée, L, De Vuyst, P. "Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma". Am J Respir Crit Care Med. vol. 181. 2010. pp. 620-5.

Zhang, W, Wu, X, Wu, L, Zhang, W, Zhao, X. "Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma". Ann Transl Med. vol. 3. 2015 Aug. pp. 182.

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