Klebe, Sonja

ABSTRACTThe 2021 WHO classification of thoracic tumours recommends grading pleural mesothelioma to aid prognostication. Robustness of grading and morphological characterisation is key to its clinical utility, though validation of this grading system has largely been conducted by expert thoracic pathologists. We conducted a survey inviting pathologists across a range of practices and expertise to grade digitised images of 50 epithelioid pleural mesotheliomas that had been graded by an expert in thoracic pathology. We included slides that were considered potentially problematic such as small biopsies, focal necrosis, and rare subtypes that may affect grading (small cell and deciduoid features). Using the Sectra Uniview web viewer, participants were asked to score atypia, mitotic count, and necrosis and choose from a list of cytological and architectural features. Seventy‐four pathologists anonymously participated. There was 90% agreement of consensus scores with expert opinion using the WHO 2‐tier grade and 72% for the 3‐tier nuclear grade but only 70% for nuclear atypia, 56% for mitoses, and 84% for necrosis. Both 3‐tier nuclear grade and WHO 2‐tier grading systems were significantly associated with survival. Our study affirms the overall robustness and utility of grading for pleural mesothelioma, reveals variances, and suggests the need for dedicated training.

Context.— Mesothelioma is an uncommon tumor that can be difficult to diagnose. Objective.— To provide updated, practical guidelines for the pathologic diagnosis of mesothelioma. Data Sources.— Pathologists involved in the International Mesothelioma Interest Group and others with expertise in mesothelioma contributed to this update. Reference material includes peer-reviewed publications and textbooks. Conclusions.— There was consensus opinion regarding guidelines for (1) histomorphologic diagnosis of mesothelial tumors, including distinction of epithelioid, biphasic, and sarcomatoid mesothelioma; recognition of morphologic variants and patterns; and recognition of common morphologic pitfalls; (2) molecular pathogenesis of mesothelioma; (3) application of immunohistochemical markers to establish mesothelial lineage and distinguish mesothelioma from common morphologic differentials; (4) application of ancillary studies to distinguish benign from malignant mesothelial proliferations, including BAP1 and MTAP immunostains; novel immunomarkers such as Merlin and p53; fluorescence in situ hybridization (FISH) for homozygous deletion of CDKN2A; and novel molecular assays; (5) practical recommendations for routine reporting of mesothelioma, including grading epithelioid mesothelioma and other prognostic parameters; (6) diagnosis of mesothelioma in situ; (7) cytologic diagnosis of mesothelioma, including use of immunostains and molecular assays; and (8) features of nonmalignant peritoneal mesothelial lesions.

Abstract Objectives Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM. Methods Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions. Results Histologic subtype was concordant in 81% of cases (κ = 0.58). When compared with resection specimens, epithelioid morphology at biopsy had a positive predictive value (PPV) of 78.9% and a negative predictive value (NPV) of 93.5%; sarcomatoid morphology showed high PPV (92.9%) and NPV (99.3%), and biphasic morphology PPV was 89.7% and NPV was 79.7%. Agreement of the percentage of epithelioid morphology was fair (κ = 0.27). Nuclear grade and necrosis were concordant in 75% (κ = 0.59) and 81% (κ = 0.53) of cases, respectively. Nuclear grade showed moderate (κ = 0.53) and substantial (κ = 0.67) agreement from patients with and without neoadjuvant therapy, respectively, and necrosis showed moderate (κ = 0.47 and κ = 0.60) agreement, respectively, in the same subsets of paired specimens. Conclusions Paired biopsy-resection specimens from pleural MM show overall moderate agreement in pathologic parameters. These findings may help guide postbiopsy management and triage of patients with MM.