A Case of Malignant Pleural Mesothelioma with Metastasis to the Orbit

Kaoru Kubota1, Kiyoyuki Furuse1, Masaaki Kawahara1, Mitsumasa Ogawara1, Sinei Ryu3 and Satoru Yamamoto 2
Departments of internal Medicine and 2Pathology, National Kinki Central Hospital for Chest Diseases, Sakai, Osaka, 'Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Habikino, Osaka
A 58-year-old woman with malignant mesothelioma metastatic to the orbit is reported. Malignant pleural mesothelioma was diagnosed by pleural biopsy. Marked reduction of pleural effusion was obtained with intrapleural interleukin-2 therapy. Systemic chemotherapy failed to elicit a response after the first recurrence of the tumor. Multiple systemic metastasis, including metastasis to the orbit, developed and the patient died one year and 4 months after the initial diagnosis. Although malignant mesothelioma is known to spread hematogenously, sometimes producing brain metastasis, there have been few reports of orbital metastasis, and in fact the present report may be the first clinically documented account of its kind.

(Jpn J Clin Oncol 26: 469-471, 1996) Key words: Malignant mesothelioma—Orbital metastasis—Distant metastasis

Introduction Malignant pleural mesothelioma is an uncommon, but increasingly recognized, malignant neoplasm of the pleura.1-2) It has been reported that exposure to asbestos is the most important risk factor for the development of this cancer. Distant metastasis is not rare at autopsy; the most common sites are the adrenals, brain, bones, kidney, pancreas, thyroid, spleen, skin, and lymph nodes. However, clinically documented distant metastasis is rare. Here, we report a patient with malignant pleural mesothelioma metastatic to the orbit. Case Report A 58-year-old woman presented in November 1988 with general fatigue. She was a non-smoker, and had no history of exposure to asbestos. Radiographs of the chest showed right pleural effusion (Fig. 1). Pleural biopsy was performed and pathologic examination confirmed the presence of a
Received: March 15, 1996 Accepted: June 6, 1996 Present address and address for reprint requests: Kaoru Kubota, Division of Thoracic Oncology, National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa 277

diffuse malignant mesothelioma-_of the epithelial type. In December 1988, intrapleural interleukin-2 therapy was performed, and marked reduction of the pleural effusion was obtained. Subsequently, two cycles of cisplatin, vindesine and mitomycin-c were administered. Seven months later, regrowth of the tumor was observed. The patient was referred to the National Kinki Central Hospital for further evaluation. Physical examination revealed percussion dullness over the right lung. No lymphadenopathy was present. Chest x-ray and computed tomographic scanning (CT) revealed diffuse nodular thickening of the right pleura without effusion. Brain CT showed no abnormalities. She received two cycles of 4'-epidoxorubicin (120mg/m2) at three-week intervals. Chest x-ray showed no response of the pleural nodules, and chemotherapy was discontinued. In December 1989, the patient developed dyspnea, cough, and oppression of the right eye. Physical examination revealed right exophthalmos and subcutaneous tumors on her back and shoulder. Brain CT showed a mass involving the right orbit associated with lateral deviation of the right eyeball (Fig 2). Chest x-ray showed a marked increase in the size of the pleural tumor. The patient died despite supportive care on March 5, 1990, one year and 4 months after the initial diagnosis.
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Fig. 1. Chest roentgenogram taken in November 1988, showing right pleural effusion.

Fig. 2. Brain CT in February 1990, showing a mass involving the right orbit associated with lateral deviation of the right eyeball.

(a)

(b)

Fig. 3. Histology of the primary tumor obtained at autopsy, showing malignant mesothelioma with a biphasic pattern, (a) Low-power figure, (b) High-power figure.

At autopsy, malignant mesothelioma was found to involve both lungs and pleurae, with metastasis to the left atrium, left ventricle, liver, kidney, adrenals, uterus, and mesentery. The right orbit was filled with a soft mass, which was confirmed to be a metastasis of the malignant mesothelioma. The histology of the primary and metastatic tumors showed a biphasic pattern (Fig. 3). Immunohistochemical staining showed positivity for MA902 (cytokeratin low molecule monoclonal antibody, Dako Corp., CA) and negativity for CEA (Dako) and vimentin (Dako). Colloidal Fe staining was
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positive.

Discussion
Malignant pleural mesothelioma is a rare tumor. Its incidence is highest in cities with shipyards and asbestos plants,3) and exposure to asbestos is an important etiologic factor.4' The major mode of spread of this tumor is local invasion. The tumor tends to spread throughout the pleural cavity and to the chest wall, as well as to regional lymph nodes in the axilla and supraclavicular area. Distant
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ORBITAL METASTASIS IN MALIGNANT MESOTHELIOMA

hematogenous metastasis are rare, and usually appears at the late stage.5' The present patient had no distant metastasis at initial staging, and developed distant metastasis about 1 year after the initial diagnosis. In 1891, Schwalbe first reported a case of orbital metastasis of malignant mesothelioma.6) So far, 18 cases with brain metastasis have been reported.7' However, there has been no further report of orbital metastasis from malignant mesothelioma. Metastasis of carcinoma to the orbit occurs much less frequently than metastasis to the eye.8' The most common primary sites of orbital metastasis are the breast and lung. Malignant mesothelioma with sarcomatous-type metastasis affects distant sites more frequently than the epithelial form.9' In the present patient, initial histology revealed by pleural biopsy showed an epithelial form, but post-mortem histology showed a biphasic pattern. This patient received intrapleural IL-2 therapy, which led to complete disappearance of the pleural effusion. However orbital metastasis occurred later. As more effective therapies for the primary tumor are developed, the natural history of the disease may change. It should be borne in mind that malignant mesothelioma can metastasise to any organ hematogenously. Acknowledgments
The study was supported in part by a Grant-in-Aid for cancer research from the Ministry of Health and Welfare of Japan.

References
1) Connelly RR, Spirtas R, Myers MH, Percy CL, Fraumeni JF Jr: Demographic patterns for mesothelioma in the United States. J Natl Cancer Inst 78: 1053-1060, 1987 2) Spirtas R, Beebe GW, Connelly RR, Wright WE, Peters JM, Sherwin RP, Henderson BE, Stark A, Kovasznay BM, Davies JNP, Vianna NJ, Keehn RJ, Ortega LG, Hochholzer L, Wagner JC: Recent trends in mesothelioma incidence in the United States. Am J Ind Med 9: 397-407, 1986 3) McDonald JC, McDonald AD: Epidemiology of mesothelioma from estimated incidence. Prev Med 6: 426-442, 1977 4) Wagner JC, Sleggs CA, Marchand P: Diffuse pleural mesothelioma and asbestosis exposure in North Western Cape Province. Br J Ind Med 17: 260-271, 1960 5) Brenner J, Sordillo PP, Magill GB, Golbey RB: Malignant mesothelioma of the pleura; review of 123 patients. Cancer 49: 2431-2435, 1982 6) Schwalbe J: Zur Lehre von der primaren Lungenund Brustfellgeschwulsten. Dtsch Med Wochenschr 45: 1235-1238, 1891 7) Falconieri G, Grandi G, DiBonito L, Bonifacio-Gori D, Giarelli L: Intracranial metastases from malignant pleural mesothelioma: report of three autopsy cases and review of the literature. Arch Pathol Lab Med 115: 591-595, 1991 8) Ferry AP, Font RL: Carcinoma metastatic to the eye and orbit: I. a clinicopathologic study of 227 cases. Arch Ophthalmol 92: 276-286, 1974-—9) Law MR, Hodson ME, Heard BE: Malignant mesothelioma of the pleura: relation between histological type and clinical behavior. Thorax 37: 810-815, 1982

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