Malignant pleural mesothelioma: The role of computed tomography

CT: THE JOURNAL OF COMPUTED

TOMOGRAPHY

1984;8:15-20

MALIGNANT PLEURAL MESOTHELIOMA: THE ROLE OF COMPUTED TOMOGRAPHY HERMAN I. LJBSHITZ, M.D.

Computed tomography is believed to have a definite role in the evaluation of malignant pleural mesothelioma based on a review of computed tomography findings in 23 of our patients and previous reports. Twelve patients had a single computed tomography examination., and 11 had two or more studies. Computed tomography permits better appreciation of the extent of the tumor. This permits appropriate selection of therapy and may demonstrate that surgery or radiotherapy is not indicated. computed tomography often permits more accurate evaluation following chemotherapy and may be the only means by which to follow a patient after radical surgery. Computed tomography also has a role in differential diagnosis. It facilitates distinction of malignant pleural mesothelioma from rounded atelectasis, pleural changes of asbestosis, and pleural involvement with lymphoma and thymoma. It aids, but may not be diagnostic, in separating malignant pleural mesothelioma from metastases to the pleura.

KEY WORDS:

Malignant

pleural mesothelioma;

Computed

tomography

The role of computed tomography (CT) in the evaluation of malignant pleural mesothelioma (MPM) has not been entirely clarified. Some authors have

concluded CT offers little advantage over conventional radiology [l]. Others feel that though CT contributes little to making the diagnosis, it has a role in determining the extent of the disease, the selection therapy [2, 31, and in following the progression of disease and results of therapy [a]. Suggestions as to the role of CT in MPM are made based on our experience and that reported by others.

MATERIALS

AND METHODS

The CT examinations of the chest were available in 23 patients with proved MPM seen from 1977 to July 1982. The earlier examinations in the series were performed with an 18-second body scanner, and more recent examinations were performed with newer faster scanners. Several patients also had examinations performed with a variety of scanners at other institutions, either initially or as follow-up. Twelve patients had only one CT examination, and 11 had multiple examinations (2-5). The duration of follow-up was generally relatively short (3.5 to 11 months), with only one patient seen at more than 1 year (4 years). There was a documented history of asbestos exposure in seven patients and a questionable exposure history in three. The patients averaged 57-years old, with a range from 31 to 72 years. Only two patients were women. FINDINGS

ON COMPUTED

TOMOGRAPHY

Initial Examination From the Department of Diagnostic Radiology, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas. Address reprint requests to: Herman I. Libshitz, MD, Department of Diagnostic Radiology, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, 6723 Bertner, Houston, Texas 77030. Received July 1983. 0 1984 by Elsevier Science Publishing Co., Inc. 52 Vanderbilt

Ave., New York,

0149-936X/84/$3.00

NY

10017

In virtually all cases, CT afforded better appreciation of the extent of the disease in the thorax. Even when there was no difficulty in reaching the correct diagnosis on conventional studies, CT portrayed the extent of the disease more graphically, particularly at the lung bases, in the mediastinum, and in evaluating diaphragmatic involvement. The findings on CT have been described, and most of those noted

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LIBSHITZ

CT: THE JOURNAL OF COMPUTED TOMOGRAPHY VOL. 8, NO. 1

FIGURE 2. Marked pleural thickening, with irregular nodules. The pericardium is invaded. The left diaphragmatic crus is thickened. There is also what appears to be a discrete intrapulmonary nodule (arrowhead). On close inspection a very thin pedicle could be seen extending to the anterior margin of the nodule.

and was seen once in our series (Figure 1).Direct extension to the pericardium may occur and was seen in three of our patients (Figure 2). Similarly, direct extension to the abdomen has been noted [3] and was believed to be present in one of our patients. Invasion of the chest wall can also be present and was seen in one of our patients (Figure 3). Direct bony destruction has been reported [4].

B FIGURE 1. Mediastinal involvement. (A) Markedly thickened and nodular pleural at the level of the aortic arch. The superior vena cava (arrow) is almost enveloped by tumor. (B) A CT scan at the lower level than in A showing even more pleural thickening with only large bronchi still air-filled. The tumor has crossed the midline poste-

riorly [arrow).

previously were represented in this series [l-5]. Pleural thickening of varying extent is present in all cases. It may range from minimal to markedly thickened and nodular pleura. Any pleural surface can be involved, including the fissures, and particularly the medial portion of the pleura, where marked involvement of mediastinal structures can be present (Figure 1). The hemithorax is frequently contracted as a result of the pleural disease. Extension to the contralateral chest has been reported [3]

FIGURE 3. Malignant pleural mesothelioma chest wall (arrow).

invading the

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1984

FIGURE 4. Large pleural effusion associated with malignant pleural mesothelioma. The lung is contracted. A thickened irregular pleural surface is seen. Fissural involvement is present [arrow). Note there is no mediastinal shift. Pleural effusion is frequently present and cannot be distinguished from effusions due to other causes (Figure 41. The CT permitted evaluation of the extent of pleural disease when it was obscured by effusion. Discrete intrapulmonary nodules have also been reported (4), but were not seen in our series. Similar lesions were noted to be attached to the pleura by pedicles of varying thickness (Figure 2) by Rabinowitz et al [B]. ‘This agrees with our experience. Calcification may be seen, either those of associated asbestosis-related plaques or small areas of calcification in association with the tumor itself (Figure 5). Kreel believes these are due to partially absorbed calcified pleural plaques [4]. Because most patients require thoracotomy for diagnosis (6, 7), surgical changes are frequently superimposed on those of the disease when they are seen at a referral institution such as ours for definitive therapy. These may be difficult to distinguish from effects of the disease itself. FIGURE 5. Progression of malignant pleural mesothelioma. [A) Some thickening is seen of the right diaphragmatic crus. A small amount of calcium is present (arrow). This is felt to represent a partially resorbed calcified pleural plaque of the associated asbestosis. (B) Further pleural thickening after 6 months of chemotherapy. (C) Even more pleural thickening, with marked irregularity, and marked thickening of the diaphragmatic crus 5 months after B.

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PLEURAL

MESOTHELIOMA

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LIBSHITZ

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Follow-Up Progression of disease was followed more easily with CT than with conventional radiography. Unfortunately, none of the patients treated with chemotherapy showed improvement. That progression was occurring often could be appreciated on conventional chest radiographs, manifested by an increase in the thickness of the pleura laterally. Frequently, disease at the bases and medially was better evaluated by CT due to location or superimposed pleural effusions [Figure 5). In those patients treated with surgery, CT was of great value in evaluating the postoperative hemithorax. Curative surgery is extensive. It generally includes pneumonectomy and total pleurectomy, including any involved pericardium, as well as resection of all but a peripheral rim of the diaphragm [8]. This, of course, results in an opacified hemithorax on chest radiographs. The postoperative hemithorax can be evaluated with CT and residual or recurrent disease demonstrated (Figure 6). In one patient, a stable postoperative appearance that could not be distinguished from persistent disease on individual examination was noted on repeat examinations 4 months apart. Only one patient was treated exclusively with radiotherapy. The extent of the MPM was determined using CT and the radiotherapy fields planned accordingly. This patient is alive and well 4 years after treatment. Virtual total opacification of the

FIGURE 6. A CT scan demonstrating significant pleural disease (arrows) and effusion after radical surgery. The extent of pleural disease could not be appreciated with conventional examinations.

FIGURE 7. Postradiotherapy appearance. A CT scan through an area of the thorax that was irradiated 4 years earlier for malignant pleural mesothelioma that was limited in extent.

treated area was seen with focal areas of decreased density (Figure 7). Pleural thickening was also noted. To what extent this was due to sterilized tumor and to what extent to effects of radiotherapy in the lung and pleura could not be determined. Because the patient is doing well, no surgical intervention is planned. DISCUSSION Malignant pleural mesothelioma is rare. There are only approximately two cases per million population yearly in the United States [9]. Recent articles by Antman [6, 71 and Brenner et al [9] review the natural history and therapy of the disease, as well as the now-established association with asbestos exposure. It must be appreciated that only 16 of 123 (13%) patients in the review by Brenner et al. had a history of asbestos exposure. Thus, no exposure history is present in many patients, as was the case in our series. Variation in the appearance and extent of the findings in MPM is to be expected. Tumor histology is quite variable [6, 71. Only 20% are purely sarcomatous. In approximately 50% the histology is epithelial or tubulopapillary, and the remainder are of mixed epithelial and sarcomatous histology. Additionally, the findings are also dependent on when in the course of the disease the patient is seen (Figure 5). For example, chest wall invasion, local bony involvement, and pericardial invasion are not uncommon.

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1984

Chest wall involvement was seen in 11% of the patients of Brenner et al. [9] at diagnosis, and increased to 30% during the course of the disease. Involvement of the bony thorax was present in 8% at diagnosis, and this increased to 14% during the course of the disease. Pericardial and diaphragmatic invasion were both seen in 5% of patients at diagnosis, increasing to 7% and 12%, respectively, during the course of the disease. These figures may be somewhat underestimated, as CT would have been available only in the later part of the series reported by Brenner et al. (Patients included were seen from 1949 through 1980.) Because of the rarity and variability of MPM, no uniform or satisfactory approach to therapy is available. Thus no significant numbers of patients treated in the same manner have had CT findings reported. Several points, however, are reasonably clear in review of the literature and of our material. Whereas CT does not establish the diagnosis, it does offer a better appreciation of the extent of disease and can be helpful in choosing therapy. Demonstration of significant mediastinal disease or disease extending beyond the thorax can exclude a surgical approach. Similarly, accurately demonstrating the extent of disease can rule against radiotherapy as the therapy of choice or indicate that it can be used and give more accurate information for the radiotherapy portals to be used. Kreel [4] has suggested CT “may be very useful” in evaluating the progression of disease and effect of therapy. It is our feeling that CT is, indeed, very helpful in this regard. When chemotherapy is the chosen therapy, CT can often give a better picture of the effect of therapy. Unfortunately, this frequently is a demonstration of progression of disease not evaluable or not as well evaluated on conventional studies. Progression in the medial pleura or mediastinum and progression posteriorly in the thorax and diaphragm are often better displayed. The pleural effusions frequently present often make conventional radiology less than ideal in evaluation of therapy. When the patient has undergone radical surgery (pneumonectomy, pleurectomy, and partial diaphragmectomy), the resultant opacification of the hemithorax precludes most conventional studies being used in following the patient. Here CT can play a significant role in following the patient and evaluating residual and/or recurrent disease. We do not have sufficient experience with CT following radiotherapy of MPM to offer suggestions in evaluating such studies. Indeed, there is little information regarding computed tomographic find-

MALIGNANT

PLEURAL

MESOTHELIOMA

19

ings in the therapeutically irradiated thorax for any disease process [lo]. Computed tomography has a role in differential diagnosis of some pleural lesions. Rabinowitz et al [5] suggest that nodular involvement of the pleural fissures (Figure 4), pleural effusion, and ipsilateral volume loss with a fixed mediastinum indicates that MPM is more likely than changes of advanced asbestosis. In their review of CT in pulmonary asbestosis, Katz and Kreel [ll]suggest that CT may afford the opportunity to detect malignant transformation of pleural plaques seen in asbestosis into mesothelioma. Rabinowitz et al [5], however, have suggested that the development of irregular plaques in the presence of smooth plaques may not be sufficient evidence for malignant degeneration. The plaque is not a static structure and may grow and alter its configuration. They do suggest the development of fissural involvement may be ominous. Computed tomography affords the means of distinguishing between rounded atelectasis and mesothelioma. Rounded atelectasis is a recently described pseudotumor frequently associated with asbestosis [12-151. It often is thought to represent either a bronchogenic carcinoma or mesothelioma on conventional radiographs because of the association with asbestosis. The lesion of rounded atelectasis characteristically consists of marked pleural thickening, which has dense streaks extending into the lung [l5]. The atelectatic lung parenchyma and the pleural thickening present as a tumorlke lesion

FIGLNE 8. Metastatic neurofibrosarcoma to the pleura with a large pleural effusion. The mediastinal shift present speaks against mesothelioma, cally exclude it.

but does not categori-

CT: THE JOURNAL OF COMPUTEDTOMOGRAPHYVOL. 8, NO. 1

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6. Antman

KH. Current concepts: malignant Engl J Med 1980; 303:200-202.

mesothelioma.

N

7. Antman

nign

KH. Clinical presentation and natural history of beand malignant mesothelioma. Semin Oncol 1981;

8:%3-320.

-

8. DeLaria GA, Jensik R, Faber LP, Kittle CF. Surgical manage-

ment of malignant

mesothelioma.

Ann Thorac

Surg 1978;

26:375-381. 9. Brenner J, Sordillo PP, Magi11 GB, Golbey RB. Malignant mesothelioma of the pleura: Review of 123 patients. Cancer

1982; 49:2431-2435. 10. Pagani

JJ, Libshitz HI. CT manifestations of radiation-induced change in chest tissue. J Comput Assist Tomogr 1982; 6:243-248.

11. Katz D, Kreel L. Computed tomography tosis. Clin Radio1 1979; 30:207-213.

in pulmonary

asbes-

12. Hillerdal

G, Hemmingsson A. Pulmonary pseudotumours and asbestos. Acta Radio1 (Diagn) (Stockholm) 1980; 21:615620.

FIGURE 9. Metastatic thymoma to the pleura with a discrete smooth pleural based mass [arrow) and an oval subpleural nodule. Recurrent thymoma is present in the mediastinum.

13. Schneider

HJ, Felson B, Gonzalez LL. Rounded Am J Roentgen01 1980; 134:225-232.

atelectasis.

14. Mintzer

RA, Gore RM, Vogelzang RL, Holz S. Rounded atelectasis and its association with asbestos-induced pleural disease. Radiology 1981; 139:567-570.

15. Tylen

with vessels and bronchi converging toward the lesion. Unfortunately, CT cannot definitely distinguish between mesothelioma and metastatic disease or direct extention of a lung cancer that significantly involves the pleura (Figure 8). History and prior radiographic studies most often point to the answer, but biopsy may be necessary. Fixation of the mediastinum is frequent in MPM, so mediastinal displacement is less likely in MPM than in extensive metastatic disease [5]. Kreel [a] noted that pleural deposits of thymoma and lymphoma are usually more localized and appear as discrete masses on the pleural surface. This has also been our experience (Figure 9).

1. Law MR, Gregor A, Husband JE, Kerr IH. Computedtomography in the assessment of malignant mesothelioma of the pleura. Clin Radio1 1982; 33:67-70. Caron-Poitreau C, Delumeau J, Dabouis G, et al. Apport de la tomodensitometrie a l’etude des tumeurs primitives de la plevre. Ann Radio1 1981; 24:247-253.

3. Alexander

E, Clark RA, Colley DP, Mitchell SE. CT of malignant pleural mesothelioma. Am J Roentgen01 1981; 137:287291.

4. Kreel L. Computed tomography co1 1981; 8:302-312. 5. Rabinowitz

CONTINUING MEDICAL EDUCATIONQUESTIONS

True or False 1. Which of the following statements regarding malignant pleural mesothelioma is (are) true? a. It is a common malignancy. b. A history of prior asbestos exposure is almost invariably present. c. Extension beyond the thorax is extremely rare. d. Pericardial extension is not uncommon. 2. Computed tomography in malignant pleural mesothelioma is of value in which of the following? a. Evaluating extent of the extent of the disease.

b. Evaluating residual or recurrent disease. c. Planning radiotherapy portals.

d. Making a definite

REFERENCES

2.

U, Nilsson U. Computed tomography in pulmonary pseudotumors and their relation to asbestos exposure. J Comput Assist Tomogr 1982; 6:229-237.

in mesothelioma.

Semin On-

JG, Efremidis SC, Cohen B, et al. A comparative study of mesothelioma and asbestosis using computed tomography and conventional chest radiography. Radiology 1982; 144:453-460.

diagnosis.

Computed tomographic findings in malignant pleural mesothelioma commonly include which of the following? a. Pleural thickening. b. Pleural effusion. c. Discrete pulmonary parenchymal nodules. d. Fissural involvement. Differential diagnosis of the computed tomographic findings of malignant pleural mesothelioma includes which of the following? a. Lymphoma. b. Metastatic carcinoma. c. Rounded d. Extensive

atelectasis. pleural plaques

due to asbestos

exposure.