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Malignant Mesothelioma with Heterologous Elements: Clinicopathological Correlation of 27 Cases and Literature Review

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Malignant Mesothelioma with Heterologous Elements: Clinicopathological Correlation of 27 Cases and Literature Review Modern Pathology (2008) 21, 1084–1094 & 2008 USCAP, Inc All rights reserved 0893-3952/08 $30.00 www.modernpathology.org Malignant mesothelioma with heterologous elements: clinicopathological correlation of 27 cases and literature review Sonja Klebe1, Annabelle Mahar2, Douglas W Henderson1 and Victor L Roggli2 1Department of Anatomical Pathology, Flinders University of South Australia, Adelaide, SA, Australia and 2Department of Pathology, Duke University Medical Center, Durham, NC, USA Only a small number of malignant mesotheliomas with heterologous elements have been described. There are currently no criteria for diagnosis and little data regarding prognosis. We suggest that the term heterologous mesothelioma should be reserved for tumours that show malignant heterologous elements, notably osteosarcomatous, chondrosarcomatous, or rhabdomyoblastic elements but have immunohistochemical and clinical characteristics of mesothelioma. We identified 27 such cases and characterized the clinical and pathological characteristics of these tumours. In our series, 89% originated in the pleura, and 11% from the peritoneal cavity. The median age at diagnosis was 68 years, ranging from 27 to 85 years. Of these cases, 93% occurred in males and 7% in women. Of the 27 mesothelioma cases 16 (59%) were sarcomatoid, 10 (37%) were biphasic, and one was reported as epithelioid; 40% (11 cases) showed osteosarcomatous elements only, 19% showed areas of rhabdomyosarcoma only, 19% contained areas of chondrosarcoma only, and 22% exhibited osteochondromatous elements. Immunohistochemical labelling for cytokeratins was present in the majority of cases. Exposure to asbestos was identified in all the 17 cases for which an exposure history was available (63%). Median survival was 6 months after diagnosis, similar to the survival seen in sarcomatoid mesotheliomas. The differential diagnosis includes primary and secondary pleural sarcomas, including osteosarcomas and chondrosarcomas. Immunohistochemical labelling for cytokeratins is helpful in the distinction, but lack of labelling for cytokeratins in a spindle cell/sarcomatoid tumour does not exclude the diagnosis of mesothelioma, irrespective of the presence of heterologous elements. We suggest that if the anatomical distribution conforms to that of mesothelioma, a diagnosis of heterologous mesothelioma should be made in preference to a diagnosis of primary pleural osteosarcoma or chondrosarcoma, regardless of cytokeratin positivity, as for conventional non-heterologous sarcomatoid mesothelioma. Modern Pathology (2008) 21, 1084–1094; doi:10.1038/modpathol.2008.125; published online 27 June 2008 Keywords: malignant mesothelioma; pleura; peritoneum; heterologous differentiation; asbestos According to the 2004 WHO classification, malig- ized by even shorter survival compared with nant mesotheliomas can be broadly classified as epithelial and sarcomatoid mesothelioma without epithelial, biphasic, and sarcomatoid.1 These groups desmoplastic features.5 For most of these subgroups, show significant differences in histological and criteria for diagnosis are well defined; for example, clinical features. In addition, there are several to qualify for a diagnosis of biphasic mesothelioma, further subtypes, including desmoplastic2 and lym- the International Mesothelioma Panel specifies that phohistiocytoid mesothelioma,3 with some of these each component must occupy at least 10% of the subtypes carrying a particularly adverse prognosis; tumour in an adequate tissue sample.6 To qualify for for example, sarcomatoid mesotheliomas are typi- a diagnosis of desmoplastic sarcomatoid mesothe- cally more rapidly lethal than epithelial meso- lioma, the paucicellular collagen-rich tissue must theliomas,4 and desmoplastic mesotheliomas, as occupy at least 50% of a tissue specimen, and other subtype of sarcomatoid mesothelioma, is character- diagnostic features include invasion, foci of overtly malignant (sarcomatoid) tissue, and areas of ‘bland’ necrosis. In contrast, the criteria for diagnosis of Correspondence: Dr S Klebe, MD, PhD, FRCPD, Department of heterologous mesothelioma are less well defined. Anatomical Pathology, Flinders Medical Centre, Bedford Drive, Only a handful of cases of mesothelioma contain- Bedford Park, Adelaide, SA 5042, Australia. 7–20 E-mail: [email protected] ing heterologous elements have been described. Received 06 May 2008; revised and accepted 05 June 2008; Amongst the heterologous elements that have been published online 27 June 2008 recorded, osseous and chondroid elements are most Heterologous mesothelioma S Klebe et al 1085 commonly seen, with liposarcomatous differentia- with two earlier cases from the files of one of the tion representing an extremely rare finding.20,21 No authors (DWH). We did not specify any particular case showing leiomyosarcomatous elements in iso- proportion of the heterologous elements for inclu- lation has been described in the literature, and sion into this series (specifically, we did not require smooth muscle elements in this location are thought the heterologous elements to account for 10% or to arise from submesothelial cells rather than the more of the tumour), but to be classified as a mesothelium itself.22 Endothelial differentiation is heterologous mesothelioma we required the hetero- regarded as inconsistent with a diagnosis of me- logous elements to show sarcomatoid features sothelioma.23 It is worth noting that because cur- (osteosarcomatous, chondrosarcomatous, or rhabdo- rently no clear definition of the term ‘mesothelioma myosarcomatous). In particular, small foci of benign with heterologous elements’ or ‘heterologous me- osseous metaplasia were considered insufficient for sothelioma’ exists in the literature, some of the the diagnosis, because these may be seen in benign reported cases or case series do not distinguish calcified pleural plaques and may simply represent between benign mesenchymal metaplasia and ‘true’ involvement of plaque by tumour. We also excluded histologically malignant heterologous elements.17 In mesothelioma with stromal osteoclast-like giant addition, there are no criteria as to the types of cells unless more definite evidence of osteoid/bone ‘heterologous’ elements that should be included in production was evident. Taking into account the this diagnostic subgroup, for example, whether clinical information regarding the anatomical dis- smooth muscle differentiation and liposarcomatous tribution, a diagnosis of heterologous mesothelioma elements are acceptable. Mesotheliomas with ‘rhab- was made regardless of cytokeratin positivity, as for doid’ features have been reported separately in a sarcomatoid mesothelioma. single large series,12 with only two additional cases that have been reported.10,13 The true incidence of mesothelioma with heterologous differentiation is Immunohistochemical Studies therefore difficult to ascertain. Also, some cases are reported in radiology or surgery literature,7,18,24–26 As many of the cases were received in consultation, sometimes without histopathologic correlation. only limited immunohistochemical studies were Little data has been collected with regards to available for much of the material. In addition, epidemiologic features and with relationship to some of the immunohistochemical assessment was previous asbestos exposure. To the best of our based on immunohistochemical stains that had been knowledge, only two cases of peritoneal mesothe- performed in other laboratories. All tissues had been lioma with malignant heterologous elements have fixed in 10% buffered formalin and had undergone been reported to date.9 standard processing and embedding in paraffin wax. Finally, there are currently conflicting data on Sections were cut 4 mm thick, deparaffinized, and survival for these tumours. Some authors describe rehydrated, if blocks had been received. For all of unusually long survival of up to 3 years for what is the cases received at Duke University and the most often a subtype of sarcomatoid mesothelio- majority of cases reviewed at Flinders Medical ma—highly unusual when one keeps in mind that Center, the streptavidin-biotin-peroxidase complex the mean survival for patients with mesothelioma method was used (Ultra Strepatavidin Detection overall is in the order of 9 months.4 System, Signet Laboratories) as a detection system, This paper represents the largest series of such whereas for one of the cases the DakoCytomation tumours of which we are aware, consisting of 27 EnVision þ Dual Link System (Dako) was used. cases of mesothelioma with heterologous elements, including three arising within the peritoneal cavity. The aims of the series were to propose a definition Results that provides clear criteria for the recognition of The salient case information for the tumours heterologous mesothelioma, based on clinical, radio- included in this study are summarized in Tables 1 logical, histologic, and immunohistochemical and 2. characteristics; to discuss the differential diagnosis; and to ascertain whether the prognosis for hetero- logous mesothelioma differs significantly from Incidence conventional mesothelioma. Among 2694 mesothelioma cases at Duke University Medical Center between 1982 and 2008, 19 (0.6%) Materials and methods cases were identified, and 6 cases were identified Selection of Cases among 594 consecutive malignant mesotheliomas accessioned at the Flinders Medical Centre (1%) Cases were obtained from the departmental over a 10-year period. These consecutive Flinders archives,
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