- Email: [email protected]
Solitary cerebellar metastasis of malignant pleural mesothelioma: case report
Neoplasm
Solitary Cerebellar Metastasis of Malignant Pleural Mesothelioma: Case Report Christopher J. Winfree, M.D., William J. Mack, M.D., and Michael B. Sisti, M.D. Department of Neurological Surgery, The Neurological Institute, Columbia University, College of Physicians and Surgeons, New York, New York
Winfree CJ, Mack WJ, Sisti MB. Solitary cerebellar metastasis of malignant pleural mesothelioma: case report. Surg Neurol 2004; 61:174 –9. BACKGROUND
Malignant pleural mesothelioma is an uncommon malignancy that rarely metastasizes to the central nervous system and even less frequently occurs as a solitary lesion. CASE DESCRIPTION
We present a 71-year-old white female, nonsmoker, with no occupational exposure to asbestos. She presented with a 15-lb. weight loss over several months and persistent right subscapular pain radiating to her anterior chest. Imaging studies revealed a pleural mass, and biopsy confirmed fibrous type malignant pleural mesothelioma. During a metastatic workup, computed tomography (CT) and magnetic resonance imaging (MRI) of the head demonstrated a 1 cm subcortical, contrastenhancing lesion without surrounding edema in the right posterior cerebellum. Surgical resection of the solitary cerebellar mass revealed fibrous-type metastatic malignant mesothelioma. Postoperatively, the patient received a combined chemotherapy regimen of Adriamycin and Cisplatin and underwent whole brain radiation therapy. CONCLUSIONS
We report the first resection of a solitary cerebellar metastasis of malignant pleural mesothelioma. We also review past cases of intracranial metastasis of this malignancy, its histologic subtypes, outcome, and recent treatment modalities. © 2004 Elsevier Inc. All rights reserved. KEY WORDS
Malignant pleural mesothelioma, metastasis, cerebellum, surgery, tumor.
alignant pleural mesothelioma (MPM) is an uncommon malignancy with a high rate of mortality [12]. Reported incidences in the United States
M
Address reprint requests to: Christopher J. Winfree, M.D., Department of Neurological Surgery, 710 West 168th Street, Box 64, New York, NY 10032. Received April 11, 2002; accepted April 4, 2003. 0090-3019/04/$–see front matter doi:10.1016/S0090-3019(03)00448-8
during the 1970s and 1980s range from 9 to 10 cases/ million in males and from 2 to 3 cases/million in females [14,42]. Its association with occupational asbestos exposure is well documented [35,44,45,52], but it may occur in other clinical settings as well [38]. Metastasis to the central nervous system is rare, as MPM typically invades locally or spreads regionally by lymphatics [10]. Few operative cases of intracranial metastasis have been documented (Table 1). We report here the first operative case of a solitary cerebellar metastasis of malignant pleural mesothelioma.
Case Report CLINICAL PRESENTATION A.M. was a 71-year-old white female, nonsmoker, with no occupational exposure to asbestos. Her father, however, was a shipbuilder at a local dockyard. She initially presented following a 15-lb. weight loss over several months and persistent right subscapular pain radiating to her anterior chest that was somewhat relieved by NSAIDs. Physical examination showed decreased breath sounds over the right upper lung field. Chest X-ray and spiral computed tomography (CT) revealed a right pleural mass and anterior chest wall calcifications on the left. The patient underwent a right thoracotomy, during which biopsy specimens from masses in the right upper lobe, chest wall, and pleura were consistent with fibrous malignant pleural mesothelioma. During a metastatic workup, CT and magnetic resonance imaging (MRI) of the head demonstrated a 1 cm subcortical, contrast-enhancing lesion without surrounding edema in the right posterior cerebellum (Figure 1). The patient had no neurologic symptoms, and her neurologic examination was normal. © 2004 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010 –1710
Malignant Pleural Mesothelioma
1
Surg Neurol 175 2004;61:174 –9
Brain Metastases From Malignant Mesotheliomas
CASE REPORT
# OF PATIENTS
CASE REPORT
# OF PATIENTS
Urschel et al (48) Billinghurst et al (6) Oels et al (37) Grumme et al (21) Walters et al (53) Janish et al (29) Elmes et al (18) Roberts et al (40) Brenner et al (10) Gordon et al (20) Schwechheimer et al (43) Law et al (28) Vogelzang et al (50) Harrison et al (22) Bianchi et al (5) Kaye et al (30) Adams et al (1) Kobayashi et al (31)
2 1 1 2 1 3 1 2 7 2 1 7 1 1 1 1 3 1
Huncharek et al (24) Ruffie et al (41) Sridhar et al (46) Ball et al (4) Nielson et al (36) Lewis et al (32) Asoh et al (2) McNaughton et al (34) Falconieri et al (19) Chahinian et al (11) Henderson et al (23) Wronski et al (55) Bohn et al (7) Kitai et al (27) Davies et al (15) Kawai et al (26) Cheeseman et al (12) Losi et al (33)
1 3 1 1 1 1 1 3 2 1 1 1 1 1 1 1 1 2
INTERVENTION The patient underwent uncomplicated suboccipital craniectomy for gross total resection of the solitary cerebellar mass. When compared with her previous biopsy slides (Figure 2), the lesion proved to be metastatic fibrous malignant pleural mesothelioma.
1
Postoperatively, the patient remained neurologically intact. Follow-up MRI demonstrated no residual tumor enhancement. She underwent several courses of chemotherapy with Adriamycin and Cisplatin in addition to postoperative whole brain radiation therapy. She expired from cardiopulmonary
Postcontrast sagittal (left) and axial (right) T1-weighted MRI demonstrating an enhancing right subcortical cerebellar lesion at the base of a cleft.
176 Surg Neurol 2004;61:174 –9
2
Winfree et al
Hematoxylin and eosin-stained sections of the patient’s primary (A) and the cerebellar metastasis (B). Note the typical fibrous appearance characteristic of sarcomatous malignant mesothelioma.
arrest secondary to intrathoracic disease 8 months after the onset of her initial symptoms.
Discussion ETIOLOGY AND EPIDEMIOLOGY Mesotheliomas are membrane-based neoplasms that arise most commonly from the pleura but also from pericardium, peritoneum, tunica vaginalis, and ovaries. Males are affected about twice as frequently as females [10]. Radiation, nonasbestos minerals, organic compounds, and chronic inflammation have all been implicated in the etiology of nonasbestos-related MPM [38]. However, exposure to asbestos is likely to be the most important predisposing factor to the development of MPM. The asbestos fibers crocidolite, tremolite, and chrysotile are thought to be the causative agents [39,51,56]. Clinical disease often occurs between 20 and 30 years following initial exposure to asbestos [15] but sometimes occurs after more than 60 years [54]. Case-control studies have estimated that almost 90% of males with MPM have reported prior exposure to asbestos, whereas only 20% of females have reported prior exposure [45]. Though our patient never worked directly with asbestos, her father was a pipefitter at a shipyard. Women family members of asbestos workers have been shown to be at increased risk for developing malignant mesothelioma [49]. CLINICAL COURSE Patients typically present with chest pain and dyspnea [17]. Tumor usually invades locally, extending to the chest wall and thoracic viscera. Malignant pleural effusions are often present [13]. Lymphatic
and hematogenous dissemination to a variety of sites can occur; however, central nervous system (CNS) metastasis remains rare [34]. The disease is characteristically relentlessly progressive regardless of treatment, with a median survival of 9 months from the time of diagnosis [9]. HISTOPATHOLOGY There are four primary histologic types of MPM: (1) fibrous or sarcomatous, (2) epithelial, (3) undifferentiated, and (4) mixed. The fibrous type typically consists of spindle-shaped cells and bundles of collagenous fibers arranged in sheets. Epithelial tumors consist of small or large epithelium-like cells, often demonstrating secretory vacuoles, arranged in acinar or papillary structures. The undifferentiated type displays polygonal cells arranged in palisading sheets. Mixed tumors show a combination of these three histologic types [17,37,54]. TREATMENT OPTIONS No widely accepted curative approaches exist for MPM. Mesothelioma is unresponsive to most chemotherapy regimens; in fact, there are no standardized, non-experimental protocols. Because of the diffuse nature of the disease, large radiation fields are required to achieve adequate palliation. Therefore, side effects following radiation therapy can be quite extensive and limit the ability of radiotherapy to prolong survival [47]. Radiation, however, can be quite effective at controlling pain associated with tumor invasion of osseous and visceral structures [16]. Surgical treatment of intrathoracic mesotheliomas can consist of local tumor resection, pleurectomy, and pleuropneumonectomy. Survival in these cases averages roughly 1 year. Treatments combining surgical cytoreduction with radiation and chemotherapy have demonstrated varied success in
Malignant Pleural Mesothelioma
different subgroups of mesothelioma patients [47]. Recent advances in photodynamic therapy [3], immunotherapy [8], and gene therapy [25] have shown promise in clinical trials but remain experimental. In the aforementioned case, suboccipital craniectomy was performed for diagnosis and treatment of the CNS lesion. This treatment option was possible due to the solitary nature and surgical accessibility of the mass coupled with the patient’s stable systemic disease. Surgery was followed by systemic chemotherapy and whole brain radiation. Another reasonable treatment option would be stereotactic radiosurgery. The up-front risk of this procedure in a 71-year-old patient with a small tumor is probably less than that of open surgery. This approach, however, does not allow for tissue diagnosis and does not prevent the potentially devastating short-term sequelae, such as bleeding, that are present with such a lesion
Surg Neurol 177 2004;61:174 –9
9. 10. 11.
12. 13. 14. 15.
16.
Conclusion In our review of the literature, brain metastases from malignant pleural mesotheliomas were uncommon but more frequent than generally recognized. None of the reported lesions, however, occurred in the posterior fossa. Our case represents the first surgical resection of a solitary cerebellar metastasis from malignant pleural mesothelioma.
17. 18. 19.
20.
REFERENCES 1. Adams VI, Unni KK, Muhm JR, Jett JR, Ilstrup DM, Bernatz PE. Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 patients. Cancer 1986;58:1540 –51. 2. Asoh Y, Nakamura M, Shiogai T, et al. Brain metastasis from primary pericardial mesothelioma. Case report. Neurol Med Chir (Tokyo) 1990;30:884 –7. 3. Baas P, Murrer L, Zoetmulder FA, et al. Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies. Br J Cancer 1997;76:819 –26. 4. Ball DL, Cruickshank DG. The treatment of malignant mesothelioma of the pleura: review of a 5-year experience, with special reference to radiotherapy. Am J Clin Oncol 1990;13:4 –9. 5. Bianchi, C, Grandi, G, DiBonito, L. Metastasi cerebrali da mesothelioma della pleura. Proceedings XXI Meeting of the Italy-Spain Neuropathologists. Sienna, Italy, 29 June 1985. 6. Billinghurst JR. Intracranial space-occupying lesions in African patients at Mulago Hospital, Kampala. East African Med J 1966;9:385–93. 7. Bohn U, Gonzalez JL, Martin LM, Casado A, DiazRubio E, Aragoncillo P. Meningeal and brain metastases in primary malignant pericardial mesothelioma. Ann Oncol 1994;5:660 –1. 8. Boutin C, Nussbaum E, Monnet I, et al. Intrapleural
21. 22. 23.
24. 25.
26. 27.
treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma. Cancer 1994;74:2460 –7. Boylan AM. Mesothelioma: new concepts in diagnosis and management. Curr Opin Pulm Med 2000;6:157–63. Brenner J, Sordillo PP, Magill GB, Golbey RB. Malignant mesothelioma of the pleura: review of 123 patients. Cancer 1982;49:2431–5. Chahinian AP, Kirschner PA, Gordon RE, Szrajer L, Holland JF. Usefulness of the nude mouse model in mesothelioma based on a direct patient-xenograft comparison. Cancer 1991;68:558 –60. Cheeseman SL, Ranson MR. Cerebral metastases in malignant mesothelioma: a case report. Eur J Cancer Care (Engl) 1999;2:104 –6. Cheng W-F, Berkman AW. Malignant mesothelioma with bone metastases. Med Ped Oncol 1990;18:165–8. Connelly RR, Spirtas R, Myers MH, Percy CL, Fraumeni JF Jr. Demographic patterns for mesothelioma in the United States. JNCI 1987;78:1053–60. Davies MJ, Ahmedzai S, Arsiwala SS, Leverment JN. Intracranial metastases from malignant pleural mesothelioma. Scand J Thorac Cardiovasc Surg 1995;29: 97–9. Davis SR, Tan L, Ball DL. Radiotherapy in the treatment of malignant mesothelioma of the pleura, with special reference to its use in palliation. Australas Radiol 1994;38:212–4. Dunnill MS. Pleural mesothelioma. Eur J Respir Dis 1984;65:159 –61. Elmes PC, Simpson MJC. The clinical aspects of mesothelioma. Q J Med 1976;45:427–49. 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 literature. Arch Pathol Lab Med 1991; 115:591–5. Gordon W, Antman KH, Greenberger JS, Weichselbaum RR, Chaffey JT. Radiation therapy in the management of patients with mesothelioma. Int J Radiat Oncol Biol Phys 1982;8:19 –25. Grumme von Th, Bingas B. Die intrakranielle metastasierung des diffusen pleuramesotheliomens. Zbl Neurochir 1973;34:41–8. Harrison RN. Sarcomatous pleural mesothelioma and cerebral metastases: case report and review of eight cases. Eur J Respir Dis 1984;65:185–8. Henderson DW, Shilkin KB, Whitaker D, et al. The pathology of malignant mesothelioma, including immunohistology and ultrastructure. In: Henderson DW, Shilkin KB, Langlois S, Le P, Whitiker D, eds. Malignant mesothelioma. New York: Hemisphere Publishing Corporation, 1992:127–39. Huncharek M, Muscat J, Capotorto J. Pleural mesothelioma in a lift mechanic. Br J Ind Med 1989;46: 500 –1. Hwang HC, Smythe WR, Elshami AA, et al. Gene therapy using adenovirus carrying the herpes simplexthymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer. Am J Respir Cell Mol Biol 1995;13:7–16. Kawai A, Nagasaka Y, Muraki M, Fukuoka M, Satou T, Kimura M, Hashimoto S. Brain metasatasis in malignant pleural mesothelioma. Intern Med 1997;36:591–4. Kitai R, Kabuto M, Kawano H, Uno H, Kobayashi H,
178 Surg Neurol 2004;61:174 –9
28.
29.
30.
31.
32. 33.
34.
35. 36. 37. 38. 39. 40. 41.
42. 43.
44. 45. 46.
Kubota T. Brain metastasis from malignant mesothelioma-case report. Neurol Med Chir (Tokyo) 1995; 35:172–4. Law MR, Hodson ME, Turner-Warwick M. Malignant mesothelioma of the pleura: clinical aspects and symptomatic treatment. Eur J Respir Dis 1984;65: 162–8. Janisch W, Zimmerman K. Haufigkeit von metastasen im zentralnervensystem bei pleuramesotheliomen ung Lungenkarzinomen. Zbl Neurochir 1975;36:37–9. Kaye JA, Wang AM, Juachim CL, et al. Malignant mesothelioma with brain metastases. Am J Med 1986;80: 95–7. Kobayashi S, Ida M, Matsui O, Kuroda E, Isobe T, Matsubara F. Lipomatous change in a brain metastasis from malignant pleural mesothelioma. Neuroradiology 2001;43:159 –61. Lewis RA. Antemortem recognition of brain metastases in malignant mesothelioma (Letter). Thorax 1990; 45:983–4. Losi L, Cocchi R, Calbucci F, Eusebi V. Metastasis of pleural malignant mesothelioma to the brain and upper maxilla: description of 2 cases. Pathologica 2000; 92:273–7. McNaughton WM, Broughton ME, Toner GC, Schwartz MA. Presentation of malignant pleural mesothelioma with cerebral metastases. J Royal Soc Med 1990;83: 466 –7. Newhouse ML, Thompson H. Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area. Br J Indust Med 1965;22:261. Nielson C, Hansen IM. Sarcomatous mesothelioma of the pleura with cerebral metastases. Med J Austr 1990;153:625–6. Oels HC, Harrison EG, Carr DT, Bernatz PE. Diffuse malignant mesothelioma of the pleura: a review of 37 cases. Chest 1971;60:564 –70. Peterson JT Jr, Greenberg SD, Buffler PA. Nonasbestos-related malignant mesothelioma: a review. Cancer 1984;54:951–60. Pooley FD. Asbestos fibre in the lung and mesothelioma: a re-examination of the Malmo ¨ material. Acta Pathol Microbiol Scand 1973;81A:390 –400. Roberts GH. Distant visceral metastases in pleural mesothelioma. Br J Dis Chest 1976;70:246 –50. Ruffie P, Feld R, Minkin S, et al. Diffuse malignant mesotheliuoma of the pleura in Ontario and Quebec: a retrospective study of 322 patients. J Clin Oncol 1989;7:1157–68. Schottenfeld D, Fraumeni JF Jr. Cancer Epidemiology and Prevention. Philadelphia: W. B. Saunders & Co., 1982:576. Schwechheimer K, Butzengeiger M. Brain metastases in malignant fibrous mesothelioma. Case report and review of literature. Acta Neuropathol (Berl) 1975;33: 173–7. Selikoff IJ, Churg J, Hammond EC. The occurrence of asbestosis amongst insulation workers in the U.S. Ann NY Acad Sci 1965;132:139 –55. Spirtas R, Heineman EF, Bernstein L, et al. Malignant mesothelioma. Attributable risk of asbestos exposure. Occup Environ Med 1994;51:804 –11. Sridhar KS, Hussein AM, Ganjei P, Thurer RJ, Raskin N, Beattie EJ. Brain metastases in malignant pleural
Winfree et al
47. 48. 49. 50. 51. 52. 53. 54. 55. 56.
mesothelioma. Case report and review of the literature. Am J Clin Oncol 1989;12:222–8. Sterman DH, Kaiser LR, Albelda SM. Advances in the treatment of malignant pleural mesothelioma. Chest 1999;116:504 –20. Urschel HC, Paulson DP. Mesotheliomas of the pleura. Ann Thorac Surg 1965;1:559 –73. Vianna NJ, Polan AK. Non-occupational exposure to asbestos and malignant mesothelioma in females. Lancet 1978;1:1061–3. Vogelzang NJ. Malignant mesothelioma: diagnostic and management strategies for 1992. Semin Oncol 1992;19(Suppl 11):64 –71. Wagner JC, Berry G. Mesotheliomas in rats following inoculation with asbestos. Br J Cancer 1969;23:567–81. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Indust Med 1960;17:260 –71. Walters KL, Martinez J. Malignant fibrous mesothelioma metastatic to brain and liver. Acta Neuropathol (Berl) 1975;33:173–7. Whitwell F, Rawcliffe RM. Diffuse malignant pleural mesothelioma and asbestos exposure. Thorax 1971;26:6–22. Wronski M, Burt M. Cerebral metastases in pleural mesothelioma: case report and review of the literature. J Neuro Onc 1993;17:21–6. Yazicioglu S, Ilcayto R, Balci K, Sayli BS, Yorulmaz B. Pleural calcification, pleural mesotheliomas, and bronchial cancers caused by tremolite dust. Thorax 1980;35:564 –9.
COMMENTARY
Winfree et al report a rare case of a patient who developed a malignant mesothelioma cerebellar metastasis. The unusual features of this case are the histology of the tumor type that uncommonly metastasizes to the brain. In a review of 729 patients with brain metastases seen at our institution over 20 years, we did not identify a single case of metastatic mesothelioma [2]. Single lesions in the cerebellum are uncommon and occurred in only 10% of our patients [2]. The management strategy for a single brain metastasis is undergoing evolution. Surgical resection followed by radiotherapy for single brain metastases appears to be just as effective as stereotactic radiosurgery combined with radiotherapy [1]. Although this patient had surgical resection of the cerebellar lesion, an appropriate and acceptable treatment option for this patient might have been stereotactic radiosurgery. An issue that is undecided at present is whether the radiosurgery should be combined with radiotherapy or whether it is sufficient by itself for local control, since there is no mechanical seeding of the adjacent neural tissue that can occur with open surgical resection. As clinicians strive to arrest the rising costs of medical care, stereotactic radiosurgery becomes an attractive treatment option because it could carry a lower risk of morbidity to an elderly patient than would open surgery, thereby preventing
Solitary Cerebellar Metastasis of Malignant Pleural Mesothelioma: Case Report Christopher J. Winfree, M.D., William J. Mack, M.D., and Michael B. Sisti, M.D. Department of Neurological Surgery, The Neurological Institute, Columbia University, College of Physicians and Surgeons, New York, New York
Winfree CJ, Mack WJ, Sisti MB. Solitary cerebellar metastasis of malignant pleural mesothelioma: case report. Surg Neurol 2004; 61:174 –9. BACKGROUND
Malignant pleural mesothelioma is an uncommon malignancy that rarely metastasizes to the central nervous system and even less frequently occurs as a solitary lesion. CASE DESCRIPTION
We present a 71-year-old white female, nonsmoker, with no occupational exposure to asbestos. She presented with a 15-lb. weight loss over several months and persistent right subscapular pain radiating to her anterior chest. Imaging studies revealed a pleural mass, and biopsy confirmed fibrous type malignant pleural mesothelioma. During a metastatic workup, computed tomography (CT) and magnetic resonance imaging (MRI) of the head demonstrated a 1 cm subcortical, contrastenhancing lesion without surrounding edema in the right posterior cerebellum. Surgical resection of the solitary cerebellar mass revealed fibrous-type metastatic malignant mesothelioma. Postoperatively, the patient received a combined chemotherapy regimen of Adriamycin and Cisplatin and underwent whole brain radiation therapy. CONCLUSIONS
We report the first resection of a solitary cerebellar metastasis of malignant pleural mesothelioma. We also review past cases of intracranial metastasis of this malignancy, its histologic subtypes, outcome, and recent treatment modalities. © 2004 Elsevier Inc. All rights reserved. KEY WORDS
Malignant pleural mesothelioma, metastasis, cerebellum, surgery, tumor.
alignant pleural mesothelioma (MPM) is an uncommon malignancy with a high rate of mortality [12]. Reported incidences in the United States
M
Address reprint requests to: Christopher J. Winfree, M.D., Department of Neurological Surgery, 710 West 168th Street, Box 64, New York, NY 10032. Received April 11, 2002; accepted April 4, 2003. 0090-3019/04/$–see front matter doi:10.1016/S0090-3019(03)00448-8
during the 1970s and 1980s range from 9 to 10 cases/ million in males and from 2 to 3 cases/million in females [14,42]. Its association with occupational asbestos exposure is well documented [35,44,45,52], but it may occur in other clinical settings as well [38]. Metastasis to the central nervous system is rare, as MPM typically invades locally or spreads regionally by lymphatics [10]. Few operative cases of intracranial metastasis have been documented (Table 1). We report here the first operative case of a solitary cerebellar metastasis of malignant pleural mesothelioma.
Case Report CLINICAL PRESENTATION A.M. was a 71-year-old white female, nonsmoker, with no occupational exposure to asbestos. Her father, however, was a shipbuilder at a local dockyard. She initially presented following a 15-lb. weight loss over several months and persistent right subscapular pain radiating to her anterior chest that was somewhat relieved by NSAIDs. Physical examination showed decreased breath sounds over the right upper lung field. Chest X-ray and spiral computed tomography (CT) revealed a right pleural mass and anterior chest wall calcifications on the left. The patient underwent a right thoracotomy, during which biopsy specimens from masses in the right upper lobe, chest wall, and pleura were consistent with fibrous malignant pleural mesothelioma. During a metastatic workup, CT and magnetic resonance imaging (MRI) of the head demonstrated a 1 cm subcortical, contrast-enhancing lesion without surrounding edema in the right posterior cerebellum (Figure 1). The patient had no neurologic symptoms, and her neurologic examination was normal. © 2004 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010 –1710
Malignant Pleural Mesothelioma
1
Surg Neurol 175 2004;61:174 –9
Brain Metastases From Malignant Mesotheliomas
CASE REPORT
# OF PATIENTS
CASE REPORT
# OF PATIENTS
Urschel et al (48) Billinghurst et al (6) Oels et al (37) Grumme et al (21) Walters et al (53) Janish et al (29) Elmes et al (18) Roberts et al (40) Brenner et al (10) Gordon et al (20) Schwechheimer et al (43) Law et al (28) Vogelzang et al (50) Harrison et al (22) Bianchi et al (5) Kaye et al (30) Adams et al (1) Kobayashi et al (31)
2 1 1 2 1 3 1 2 7 2 1 7 1 1 1 1 3 1
Huncharek et al (24) Ruffie et al (41) Sridhar et al (46) Ball et al (4) Nielson et al (36) Lewis et al (32) Asoh et al (2) McNaughton et al (34) Falconieri et al (19) Chahinian et al (11) Henderson et al (23) Wronski et al (55) Bohn et al (7) Kitai et al (27) Davies et al (15) Kawai et al (26) Cheeseman et al (12) Losi et al (33)
1 3 1 1 1 1 1 3 2 1 1 1 1 1 1 1 1 2
INTERVENTION The patient underwent uncomplicated suboccipital craniectomy for gross total resection of the solitary cerebellar mass. When compared with her previous biopsy slides (Figure 2), the lesion proved to be metastatic fibrous malignant pleural mesothelioma.
1
Postoperatively, the patient remained neurologically intact. Follow-up MRI demonstrated no residual tumor enhancement. She underwent several courses of chemotherapy with Adriamycin and Cisplatin in addition to postoperative whole brain radiation therapy. She expired from cardiopulmonary
Postcontrast sagittal (left) and axial (right) T1-weighted MRI demonstrating an enhancing right subcortical cerebellar lesion at the base of a cleft.
176 Surg Neurol 2004;61:174 –9
2
Winfree et al
Hematoxylin and eosin-stained sections of the patient’s primary (A) and the cerebellar metastasis (B). Note the typical fibrous appearance characteristic of sarcomatous malignant mesothelioma.
arrest secondary to intrathoracic disease 8 months after the onset of her initial symptoms.
Discussion ETIOLOGY AND EPIDEMIOLOGY Mesotheliomas are membrane-based neoplasms that arise most commonly from the pleura but also from pericardium, peritoneum, tunica vaginalis, and ovaries. Males are affected about twice as frequently as females [10]. Radiation, nonasbestos minerals, organic compounds, and chronic inflammation have all been implicated in the etiology of nonasbestos-related MPM [38]. However, exposure to asbestos is likely to be the most important predisposing factor to the development of MPM. The asbestos fibers crocidolite, tremolite, and chrysotile are thought to be the causative agents [39,51,56]. Clinical disease often occurs between 20 and 30 years following initial exposure to asbestos [15] but sometimes occurs after more than 60 years [54]. Case-control studies have estimated that almost 90% of males with MPM have reported prior exposure to asbestos, whereas only 20% of females have reported prior exposure [45]. Though our patient never worked directly with asbestos, her father was a pipefitter at a shipyard. Women family members of asbestos workers have been shown to be at increased risk for developing malignant mesothelioma [49]. CLINICAL COURSE Patients typically present with chest pain and dyspnea [17]. Tumor usually invades locally, extending to the chest wall and thoracic viscera. Malignant pleural effusions are often present [13]. Lymphatic
and hematogenous dissemination to a variety of sites can occur; however, central nervous system (CNS) metastasis remains rare [34]. The disease is characteristically relentlessly progressive regardless of treatment, with a median survival of 9 months from the time of diagnosis [9]. HISTOPATHOLOGY There are four primary histologic types of MPM: (1) fibrous or sarcomatous, (2) epithelial, (3) undifferentiated, and (4) mixed. The fibrous type typically consists of spindle-shaped cells and bundles of collagenous fibers arranged in sheets. Epithelial tumors consist of small or large epithelium-like cells, often demonstrating secretory vacuoles, arranged in acinar or papillary structures. The undifferentiated type displays polygonal cells arranged in palisading sheets. Mixed tumors show a combination of these three histologic types [17,37,54]. TREATMENT OPTIONS No widely accepted curative approaches exist for MPM. Mesothelioma is unresponsive to most chemotherapy regimens; in fact, there are no standardized, non-experimental protocols. Because of the diffuse nature of the disease, large radiation fields are required to achieve adequate palliation. Therefore, side effects following radiation therapy can be quite extensive and limit the ability of radiotherapy to prolong survival [47]. Radiation, however, can be quite effective at controlling pain associated with tumor invasion of osseous and visceral structures [16]. Surgical treatment of intrathoracic mesotheliomas can consist of local tumor resection, pleurectomy, and pleuropneumonectomy. Survival in these cases averages roughly 1 year. Treatments combining surgical cytoreduction with radiation and chemotherapy have demonstrated varied success in
Malignant Pleural Mesothelioma
different subgroups of mesothelioma patients [47]. Recent advances in photodynamic therapy [3], immunotherapy [8], and gene therapy [25] have shown promise in clinical trials but remain experimental. In the aforementioned case, suboccipital craniectomy was performed for diagnosis and treatment of the CNS lesion. This treatment option was possible due to the solitary nature and surgical accessibility of the mass coupled with the patient’s stable systemic disease. Surgery was followed by systemic chemotherapy and whole brain radiation. Another reasonable treatment option would be stereotactic radiosurgery. The up-front risk of this procedure in a 71-year-old patient with a small tumor is probably less than that of open surgery. This approach, however, does not allow for tissue diagnosis and does not prevent the potentially devastating short-term sequelae, such as bleeding, that are present with such a lesion
Surg Neurol 177 2004;61:174 –9
9. 10. 11.
12. 13. 14. 15.
16.
Conclusion In our review of the literature, brain metastases from malignant pleural mesotheliomas were uncommon but more frequent than generally recognized. None of the reported lesions, however, occurred in the posterior fossa. Our case represents the first surgical resection of a solitary cerebellar metastasis from malignant pleural mesothelioma.
17. 18. 19.
20.
REFERENCES 1. Adams VI, Unni KK, Muhm JR, Jett JR, Ilstrup DM, Bernatz PE. Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 patients. Cancer 1986;58:1540 –51. 2. Asoh Y, Nakamura M, Shiogai T, et al. Brain metastasis from primary pericardial mesothelioma. Case report. Neurol Med Chir (Tokyo) 1990;30:884 –7. 3. Baas P, Murrer L, Zoetmulder FA, et al. Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies. Br J Cancer 1997;76:819 –26. 4. Ball DL, Cruickshank DG. The treatment of malignant mesothelioma of the pleura: review of a 5-year experience, with special reference to radiotherapy. Am J Clin Oncol 1990;13:4 –9. 5. Bianchi, C, Grandi, G, DiBonito, L. Metastasi cerebrali da mesothelioma della pleura. Proceedings XXI Meeting of the Italy-Spain Neuropathologists. Sienna, Italy, 29 June 1985. 6. Billinghurst JR. Intracranial space-occupying lesions in African patients at Mulago Hospital, Kampala. East African Med J 1966;9:385–93. 7. Bohn U, Gonzalez JL, Martin LM, Casado A, DiazRubio E, Aragoncillo P. Meningeal and brain metastases in primary malignant pericardial mesothelioma. Ann Oncol 1994;5:660 –1. 8. Boutin C, Nussbaum E, Monnet I, et al. Intrapleural
21. 22. 23.
24. 25.
26. 27.
treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma. Cancer 1994;74:2460 –7. Boylan AM. Mesothelioma: new concepts in diagnosis and management. Curr Opin Pulm Med 2000;6:157–63. Brenner J, Sordillo PP, Magill GB, Golbey RB. Malignant mesothelioma of the pleura: review of 123 patients. Cancer 1982;49:2431–5. Chahinian AP, Kirschner PA, Gordon RE, Szrajer L, Holland JF. Usefulness of the nude mouse model in mesothelioma based on a direct patient-xenograft comparison. Cancer 1991;68:558 –60. Cheeseman SL, Ranson MR. Cerebral metastases in malignant mesothelioma: a case report. Eur J Cancer Care (Engl) 1999;2:104 –6. Cheng W-F, Berkman AW. Malignant mesothelioma with bone metastases. Med Ped Oncol 1990;18:165–8. Connelly RR, Spirtas R, Myers MH, Percy CL, Fraumeni JF Jr. Demographic patterns for mesothelioma in the United States. JNCI 1987;78:1053–60. Davies MJ, Ahmedzai S, Arsiwala SS, Leverment JN. Intracranial metastases from malignant pleural mesothelioma. Scand J Thorac Cardiovasc Surg 1995;29: 97–9. Davis SR, Tan L, Ball DL. Radiotherapy in the treatment of malignant mesothelioma of the pleura, with special reference to its use in palliation. Australas Radiol 1994;38:212–4. Dunnill MS. Pleural mesothelioma. Eur J Respir Dis 1984;65:159 –61. Elmes PC, Simpson MJC. The clinical aspects of mesothelioma. Q J Med 1976;45:427–49. 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 literature. Arch Pathol Lab Med 1991; 115:591–5. Gordon W, Antman KH, Greenberger JS, Weichselbaum RR, Chaffey JT. Radiation therapy in the management of patients with mesothelioma. Int J Radiat Oncol Biol Phys 1982;8:19 –25. Grumme von Th, Bingas B. Die intrakranielle metastasierung des diffusen pleuramesotheliomens. Zbl Neurochir 1973;34:41–8. Harrison RN. Sarcomatous pleural mesothelioma and cerebral metastases: case report and review of eight cases. Eur J Respir Dis 1984;65:185–8. Henderson DW, Shilkin KB, Whitaker D, et al. The pathology of malignant mesothelioma, including immunohistology and ultrastructure. In: Henderson DW, Shilkin KB, Langlois S, Le P, Whitiker D, eds. Malignant mesothelioma. New York: Hemisphere Publishing Corporation, 1992:127–39. Huncharek M, Muscat J, Capotorto J. Pleural mesothelioma in a lift mechanic. Br J Ind Med 1989;46: 500 –1. Hwang HC, Smythe WR, Elshami AA, et al. Gene therapy using adenovirus carrying the herpes simplexthymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer. Am J Respir Cell Mol Biol 1995;13:7–16. Kawai A, Nagasaka Y, Muraki M, Fukuoka M, Satou T, Kimura M, Hashimoto S. Brain metasatasis in malignant pleural mesothelioma. Intern Med 1997;36:591–4. Kitai R, Kabuto M, Kawano H, Uno H, Kobayashi H,
178 Surg Neurol 2004;61:174 –9
28.
29.
30.
31.
32. 33.
34.
35. 36. 37. 38. 39. 40. 41.
42. 43.
44. 45. 46.
Kubota T. Brain metastasis from malignant mesothelioma-case report. Neurol Med Chir (Tokyo) 1995; 35:172–4. Law MR, Hodson ME, Turner-Warwick M. Malignant mesothelioma of the pleura: clinical aspects and symptomatic treatment. Eur J Respir Dis 1984;65: 162–8. Janisch W, Zimmerman K. Haufigkeit von metastasen im zentralnervensystem bei pleuramesotheliomen ung Lungenkarzinomen. Zbl Neurochir 1975;36:37–9. Kaye JA, Wang AM, Juachim CL, et al. Malignant mesothelioma with brain metastases. Am J Med 1986;80: 95–7. Kobayashi S, Ida M, Matsui O, Kuroda E, Isobe T, Matsubara F. Lipomatous change in a brain metastasis from malignant pleural mesothelioma. Neuroradiology 2001;43:159 –61. Lewis RA. Antemortem recognition of brain metastases in malignant mesothelioma (Letter). Thorax 1990; 45:983–4. Losi L, Cocchi R, Calbucci F, Eusebi V. Metastasis of pleural malignant mesothelioma to the brain and upper maxilla: description of 2 cases. Pathologica 2000; 92:273–7. McNaughton WM, Broughton ME, Toner GC, Schwartz MA. Presentation of malignant pleural mesothelioma with cerebral metastases. J Royal Soc Med 1990;83: 466 –7. Newhouse ML, Thompson H. Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area. Br J Indust Med 1965;22:261. Nielson C, Hansen IM. Sarcomatous mesothelioma of the pleura with cerebral metastases. Med J Austr 1990;153:625–6. Oels HC, Harrison EG, Carr DT, Bernatz PE. Diffuse malignant mesothelioma of the pleura: a review of 37 cases. Chest 1971;60:564 –70. Peterson JT Jr, Greenberg SD, Buffler PA. Nonasbestos-related malignant mesothelioma: a review. Cancer 1984;54:951–60. Pooley FD. Asbestos fibre in the lung and mesothelioma: a re-examination of the Malmo ¨ material. Acta Pathol Microbiol Scand 1973;81A:390 –400. Roberts GH. Distant visceral metastases in pleural mesothelioma. Br J Dis Chest 1976;70:246 –50. Ruffie P, Feld R, Minkin S, et al. Diffuse malignant mesotheliuoma of the pleura in Ontario and Quebec: a retrospective study of 322 patients. J Clin Oncol 1989;7:1157–68. Schottenfeld D, Fraumeni JF Jr. Cancer Epidemiology and Prevention. Philadelphia: W. B. Saunders & Co., 1982:576. Schwechheimer K, Butzengeiger M. Brain metastases in malignant fibrous mesothelioma. Case report and review of literature. Acta Neuropathol (Berl) 1975;33: 173–7. Selikoff IJ, Churg J, Hammond EC. The occurrence of asbestosis amongst insulation workers in the U.S. Ann NY Acad Sci 1965;132:139 –55. Spirtas R, Heineman EF, Bernstein L, et al. Malignant mesothelioma. Attributable risk of asbestos exposure. Occup Environ Med 1994;51:804 –11. Sridhar KS, Hussein AM, Ganjei P, Thurer RJ, Raskin N, Beattie EJ. Brain metastases in malignant pleural
Winfree et al
47. 48. 49. 50. 51. 52. 53. 54. 55. 56.
mesothelioma. Case report and review of the literature. Am J Clin Oncol 1989;12:222–8. Sterman DH, Kaiser LR, Albelda SM. Advances in the treatment of malignant pleural mesothelioma. Chest 1999;116:504 –20. Urschel HC, Paulson DP. Mesotheliomas of the pleura. Ann Thorac Surg 1965;1:559 –73. Vianna NJ, Polan AK. Non-occupational exposure to asbestos and malignant mesothelioma in females. Lancet 1978;1:1061–3. Vogelzang NJ. Malignant mesothelioma: diagnostic and management strategies for 1992. Semin Oncol 1992;19(Suppl 11):64 –71. Wagner JC, Berry G. Mesotheliomas in rats following inoculation with asbestos. Br J Cancer 1969;23:567–81. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Indust Med 1960;17:260 –71. Walters KL, Martinez J. Malignant fibrous mesothelioma metastatic to brain and liver. Acta Neuropathol (Berl) 1975;33:173–7. Whitwell F, Rawcliffe RM. Diffuse malignant pleural mesothelioma and asbestos exposure. Thorax 1971;26:6–22. Wronski M, Burt M. Cerebral metastases in pleural mesothelioma: case report and review of the literature. J Neuro Onc 1993;17:21–6. Yazicioglu S, Ilcayto R, Balci K, Sayli BS, Yorulmaz B. Pleural calcification, pleural mesotheliomas, and bronchial cancers caused by tremolite dust. Thorax 1980;35:564 –9.
COMMENTARY
Winfree et al report a rare case of a patient who developed a malignant mesothelioma cerebellar metastasis. The unusual features of this case are the histology of the tumor type that uncommonly metastasizes to the brain. In a review of 729 patients with brain metastases seen at our institution over 20 years, we did not identify a single case of metastatic mesothelioma [2]. Single lesions in the cerebellum are uncommon and occurred in only 10% of our patients [2]. The management strategy for a single brain metastasis is undergoing evolution. Surgical resection followed by radiotherapy for single brain metastases appears to be just as effective as stereotactic radiosurgery combined with radiotherapy [1]. Although this patient had surgical resection of the cerebellar lesion, an appropriate and acceptable treatment option for this patient might have been stereotactic radiosurgery. An issue that is undecided at present is whether the radiosurgery should be combined with radiotherapy or whether it is sufficient by itself for local control, since there is no mechanical seeding of the adjacent neural tissue that can occur with open surgical resection. As clinicians strive to arrest the rising costs of medical care, stereotactic radiosurgery becomes an attractive treatment option because it could carry a lower risk of morbidity to an elderly patient than would open surgery, thereby preventing