Mesothelial proliferations. An increasing morphologic spectrum.

During the past 2 decades, a great deal has been written about the epidemiology, clinical features, and pathologic characteristics of malignant mesotheliomas (MMs),1,2 as well as the multiple other neoplasms with which they may be confused. This is, in part, because throughout the 1970s and 1980s, the incidence of MMs demonstrated an alarming increase.1 Fortunately, this trend has now reached a plateau; however, MM continues to represent an important tumor entity to recognize accurately because of the grave prognostic import this diagnosis carries. In this issue of the Journal, Khalidi et al3 describe 3 cases of a rare mesothelioma variant, namely, so-called lymphohistiocytoid (lymphoma-like) MM. This lesion was reported for the first time in 1988 by Henderson and colleagues,4 after a survey of cases entered in the Australian Mesothelioma Surveillance Program. As they and Khalidi and colleagues3 documented, the resemblance between lymphohistiocytoid MM and malignant hematopoietic lesions of the pleura can be striking. Because of the large number of lymphocytes and plasma cells in these tumors and the wide dispersion of the malignant keratin-positive epithelioid cells, another potential diagnostic trap would be to consider them “inflammatory pseudotumors.”5 As such, lymphohistiocytoid MM is, perhaps, yet another neoplasm that may assume a “lymphoepithelioma-like” image, reinforcing the notion that the latter appearance is a pattern rather than a singular clinicopathologic entity.6 Like many other groups of neoplasms, mesothelial tumors have undergone considerable nosologic revisionism during the past 25 years ❚Table 1❚. The lesion formerly known as “benign fibrous mesothelioma” is now known to represent solitary fibrous tumor of the pleura,7-10 which is an entirely unrelated proliferation at the cellular and epidemiologic levels. Similarly, adenomatoid tumor is now known to be a benign neoplasm with definite mesothelial differentiation,11 instead of an endothelial lesion as originally thought. “Multicystic” mesothelioma and “well-differentiated papillary mesothelioma” continue to be the subjects of some debate regarding their status as benign or “borderline” mesothelial neoplasms vs complex mesothelial hyperplasias.12-21 Based on the information now extant, we prefer the latter of those interpretations, and there is little doubt that the clinical outcome for patients with those 2 forms of mesothelial proliferation is extremely favorable in the vast majority of cases. In turning attention to overtly malignant mesothelial tumors, a surprising variety of patterns has emerged, aside from lymphohistiocytoid mesothelioma, to expand the traditional categoric outline that simply included “epithelioid,” “biphasic,” and “sarcomatoid” mesotheliomas.22 The epithelioid subgroup now has been expanded to include mesothelial malignant neoplasms that have a wholly clear cell, oncocytoid or granular-cell, tubulopapillary, large polygonal cell, polyhedral stromal mucin-producing, “medullary” epithelioid, or even small-cell appearance.22-26 The differential diagnostic potentialities raised by such images are numerous, including metastatic non–small cell carcinomas of various primary origins, metastatic melanoma, pleural sarcomas with an epithelioid or small round cell appearance, and even metastatic small cell neuroendocrine carcinoma.27-29 In reference to biphasic MM, primary synovial sarcoma of the pleura now has been well-characterized as an important diagnostic alternative.30 Indeed, in the absence of data showing the characteristic t(X;18) chromosomal translocation of synovial sarcoma, which is associated with production of SYT-SSX fusion transcripts,31 its separation