Ann Thorac Surg 2002;73:1292-1294
© 2002 The Society of Thoracic Surgeons
Case report
Flow cytometric analysis of a localized malignant mesothelioma
José Javier Gómez-Román, MD, PhD*a,
Roberto Mons-Lera, MD, PhDb,
Isabel Seco Olmedo, MDc,
José Fernando Val-Bernal, MD, PhDa
a Department of Anatomical Pathology, University Hospital, "Marqués de Valdecilla," National Health Institute, Medical Faculty, Cantabria University, Santander, Spain
b Thoracic Surgery Service, University Hospital, "Marqués de Valdecilla," National Health Institute, Medical Faculty, Cantabria University, Santander, Spain
c General Surgery Service, University Hospital, "Marqués de Valdecilla," National Health Institute, Medical Faculty, Cantabria University, Santander, Spain
Accepted for publication August 17, 2001.
* Address reprint requests to Dr Gómez-Román, Departamento de Anatomía Patológica, Hospital Universitario "Marqués de Valdecilla," Avda de Valdecilla s/n, 39008 Santander (Cantabria), Spain
e-mail: apagrj{at}humv.es
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Abstract
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Malignant mesothelioma usually presents as a diffuse neoplasm. We report a localized malignant mesothelioma in the parietal pleura of a patient who was not exposed to asbestos. A complete clinical, pathologic, and immunohistochemical description is provided. Flow cytometric analysis showed an aneuploid DNA content in neoplastic cells. The patient is alive and well 8 months after complete surgical resection. Localized malignant mesothelioma must be included in the differential diagnosis in chest wall-based neoplasms.
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Introduction
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Malignant mesothelioma (MM) is a neoplasm that arises from the surface serosal cells of the pleural, peritoneal, and pericardial cavities and the tunica vaginalis testis. It usually shows the clinical and pathologic characteristics of a diffuse aggressive malignant tumor, involving serous membranes multifocally at an early stage of the disease. Prognosis is generally poor and adjuvant therapies are of little help. When a patient is suspected of having a diffuse mesothelial cell proliferation, an accurate diagnosis of MM is then needed, but its attainment generally states many problems to clinicians, radiologists, and surgical pathologists. Otherwise, several kinds of localized mesothelial proliferations are described. Most of them are usually benign, such as solitary fibrous tumor or localized fibrous mesothelioma. However, some localized mesotheliomas have been reported to have malignant characteristics with some biologic differences from diffuse mesotheliomas, such as an aneuploid DNA content [1, 2]. The clinical behavior of these malignant localized mesotheliomas is difficult to predict, and some patients have survived disease-free for a long time after a complete surgical resection [1]. Our aim is to describe the clinical, histopathologic, immunohistochemical, and flow cytometric findings in a case of pleural-localized MM.
A 47-year-old man presented after a car accident with severe pain in the right thoracic region. Physical examination showed a hard and painful mass comprising the seventh and eighth ribs that the general practitioner related to the preceding traumatic history.
After 2 months the mass became larger and more painful. Then, a computed tomographic scan was performed, which showed a locally aggressive neoplasm located in the seventh and eighth ribs that was confirmed by magnetic nuclear resonance (Fig 1).
The radiologic differential diagnosis included malignant peripheral nerve sheath tumor versus a metastatic neoplasm.
One month later, an exploratory thoracotomy was performed that revealed an 8-cm mass affecting the posterior arch of the seventh and eighth ribs. Pleura distant from the main tumor mass was examined and appeared unremarkable. A parietal pleura-based sessile mass and portions of the seventh and eighth ribs were resected with free margins and Prolene prosthesis (Ethicon) was included. Randomized pleural biopsies away from the primary mass were taken, which showed no histopathologic changes. Eight months postoperatively, the patient had no evidence of residual disease and was symptom free.
An 8-cm whitish mass was found attached to the parietal pleura and infiltrating the ribs and intercostal muscles. The surgical resection margins were free of involvement. The neoplasm was formed entirely of spindle and ovoid cells, in a herringbone pattern in some areas and in interlacing bundles in others. Focal areas of necrosis were present in most of the examined fields. The spindle cells had blunt-ended nuclei, and pleomorphic, atypical figures with prominent nucleoli were easily found (Fig 2A). Mitotic count was high (2.07 mitoses/mm2).
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Fig 2. (A) Localized malignant mesothelioma. Note the spindle cell malignant component. (Hematoxylin and eosin stain; original magnification x100.) (B) Immunohistochemical staining with calretinin antibody. (Original magnification x100.)
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Immunohistochemical staining was performed from paraffin-embedded tissue by using the streptavidin-biotin peroxidase method. We tested the following antibodies: cytokeratins (Cam5.2 and 34betaE12), vimentin, epithelial membrane antigen (EMA), BerEP4, carcinoembryonic antigen, LeuM1, CD34, thrombomodulin, and calretinin. Only Cam5.2 cytokeratin, EMA, calretinin (Fig 2B), and thrombomodulin showed strong cytoplasmic reactivity. Vimentin was positive focally.
Paraffin-embedded material was available for DNA nuclear content evaluation by flow cytometry. Forty thousand cells were analyzed with a FacScan flow cytometer (Becton-Dickinson, Mountain View, CA) using the ModFit2.0 cycle analysis software. We found an aneuploid DNA content with a DNA index of 1.20, and 46.91% of cells were in S phase.
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Comment
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Malignant mesothelioma usually appears as either multiple pleura-based nodules, with or without a dominant mass, or as a diffuse tumor that encases at least a portion of the lung. This is the reason why clinicians or radiologists do not consider MM in differential diagnosis of solitary thoracic masses. In fact, the rare published cases emphasize that correct diagnosis was made only after the pathologic study of the surgical specimen.
Malignant localized mesothelioma is extremely rare, and it has been absent from the largest series of MMs [3]. Even among the cases reported in the literature there are a few truly localized, MM-based neoplasms. The largest literature review of these kinds of tumors [1] shows only two cases correctly diagnosed with ancillary techniques like immunohistochemistry or electron microscopy. The rest of the reported cases were, in fact, either solitary fibrous tumors or diffuse mesotheliomas.
As far as we know only 10 reliable pleural-localized MMs have been reported [1, 2, 4, 5], although two more cases are described in the peritoneal surface [6, 7]. A surgical series found four malignant localized mesotheliomas in a 13-year period, but the authors did not provide any pathologic characteristics of them [8].
Differential diagnosis must be made to distinguish from diffuse MM (Table 1).
Both can share morphologic and immunohistochemical characteristics. Flow cytometry can aid in differential diagnosis because diffuse mesotheliomas are most frequently diploid [1]. The presence of an aneuploid population in localized mesotheliomas is a phenomenon well described in the series of Crotty and colleagues (80% of cases) [1]. Our finding of DNA aneuploidy in one more case is a sign of another potential difference between diffuse and localized MM, although their histologic and immunohistochemical properties are similar.
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Table 1. Differential Characteristics of Malignant Diffuse Mesothelioma, Localized Malignant Mesothelioma, and Solitary Fibrous Tumor
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Localized MM must also be differentiated from solitary fibrous tumor, a pure spindle cell tumor without a histologic well-defined pattern (patternless pattern), and without atypical features or necrosis. The mitotic index is generally low, and they have a well-described immunohistochemical marker such as CD34. Most of them are benign, although there are described some local recurrences in not well-resected cases. Our case had many architectural patterns, CD34 was consistently negative, and mesothelial markers such as thrombomodulin and calretinin were both positive. Other important differential diagnoses are synovial sarcoma and other sarcomas that could arise from the chest wall. Synovial sarcomas rarely affect the pleura, and most of them are biphasic, epithelial, and sarcomatous. As for the rest of the sarcomas, they are easily distinguished with immunohistochemical staining.
Prognosis in this kind of localized mesotheliomas is unknown because of the few cases reported. Our patient is alive and well 8 months after operation, and there are many cases described in which complete surgical resection might be curative. The recurrent pattern for localized type of mesotheliomas is diffuse type [8] without distant metastasis, and so a correct diagnosis and surgical treatment in the early stages are essential for long-term survival.
In summary, we describe the case of a localized MM proliferation. Localized MM must be included in differential diagnosis of chest wall-based masses. A complete surgical resection may be curative in some of these cases.
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References
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Abstract
Introduction
