When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines

Abstract

The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. This gap may potentially create problems for patients in sustaining a difficult diagnosis of MPM in clinical practice and during legal disputes. Indeed, the guidelines accidentally tend to favor the job of lawyers and pathologists defending asbestos-producing industries against patients suffering from MPM characterized by uncommon features. The current review is aimed at underlining the wide spectrum of clinical and radiological presentation of MPM, the possibility to consistently use cytology for diagnostic intent, the aberrant immunohistochemical expression using so-called specific negative and positive primary antibodies, and finally proposing some alternative and more unbiased approaches to the diagnosis of MPM.

Unusual Histology in Mesothelioma: A Report of Two Cases with a Brief Review

“…Ultimately, the two cases presented in this paper are merely examples of some diagnostic difficulties encountered in the management of the pathology of malignant epithelioid mesotheliomas, but with some ancillary methods, as discussed before, a correct diagnosis is possible, bearing in mind also the rare histological variations. Furthermore, a diagnostic pitfall is not only related to morpho-architectural features, but we should also keep in mind the clinical, radiological and unusual patterns of immunostaining that sometimes are misleading even if they present with the usual morphological features [23]. Institutional Review Board Statement: Ethical review and approval were waived for this study, due to patients were not directly involved in the design, conduct, reporting or dissemination plans of this research.…”

“…The use of a specific immunohistochemistry panel for detecting these alterations should be performed depending on, and in combination with, cytoarchitectural characteristics, clinical and radiological findings, to address the possible differential diagnosis (i.e., to distinguish an epithelioid mesothelioma with clear cell features from a clear cell renal carcinoma) [ 22 , 23 ].…”

“…The prognosis of signet ring cell mesothelioma is equally poor, with 15 months of median survival starting from diagnosis. This peculiar cytological feature makes the differential diagnosis challenging, especially towards metastatic adenocarcinoma, signet ring type, and more so in peritoneal sites or in the case of aberrant expression of CDX2 or cytokeratin 20, as reported by Rossi et al [ 23 ]. Furthermore, rare cases of ALK rearranged mesotheliomas and signet ring cell adenocarcinoma from the lung ALK-rearranged are also included in differential diagnoses [ 34 ]…”

“…Moreover, unusual clinical–radiological findings and immunostaining patterns could be a diagnostic pitfall, even with the usual morphological features of malignant mesothelioma [ 23 ].…”

Sarcomatoid Mesothelioma With Bland Histologic Features: A Potential Pitfall in Diagnosis

“…It has been recently suggested that the fact that sarcomatoid mesothelioma usually is negative for mesothelioma markers has been little appreciated and ignored by pathologists and lawyers working for industry. It is sometimes argued that a sarcomatoid mesothelioma that is only cytokeratin positive (and negative for a panel of mesothelial markers, such as the case in this report) should be diagnosed as “sarcomatoid malignant neoplasm.” 6 In consulting for a plaintiff's attorney, one of the authors encountered a tumor that the defense expert argued was a sarcoma; even though there was strong cytokeratin positivity, the clinical and imaging were typical of mesothelioma, and after staining several blocks, areas of calretinin and GATA3 positivity were found (Table 1).…”