Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2‐tier nuclear grade

Abstract

Aims Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E‐MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (i) externally validate the prognostic role of pleomorphic features in E‐MPM and (ii) investigate if evaluating growth pattern in addition to 2‐tier nuclear grade improves prognostication. Methods and results 614 consecutive cases of E‐MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E‐MPM with pleomorphic features showed significantly worse overall survival compared to those without (5.4 versus 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo‐papillary (18.6 months). Sub‐classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 versus 18.0 months) but did not predict survival independent of 2‐tier nuclear grade. A composite score comprised of growth pattern and 2‐tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra‐tumoural heterogeneity in growth patterns is ubiquitous. Conclusions Our findings support the incorporation of E‐MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2‐tier nuclear grade. E‐MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2‐tier nuclear grade.

Updates on grading mesothelioma

“…Grading was recommended on all specimens, including biopsies. Subsequent work has shown that grading can be applied to biopsy specimens 18,19 . This two‐tiered grading system is now also recommended by the most recent WHO Classification of Thoracic Tumours book, and is a required element in the College of American Pathologists synoptic report 20–22 .…”

“…We subsequently re‐reviewed the original data from the Rosen study and did find a statistically significant difference when applying the two‐tiered system to the original data set (unpublished data). Some subsequent studies have been published using the two‐tiered grading system and continue to show that there is a prognostic value in this system and that the two‐tiered grading system can be used in both biopsy and resection specimens 18,19 . Second, the grading system was developed and endorsed by experts in pulmonary and thoracic pathology with significant experience in the diagnosis and classification of mesothelioma.…”

“…Subsequent work has shown that grading can be applied to biopsy specimens. 18,19 This two-tiered grading system is now also recommended by the most recent WHO Classification of Thoracic Tumours book, and is a required element in the College of American Pathologists synoptic report. [20][21][22] Grading of epithelioid mesothelioma is also recommended by the updated consensus diagnosis guidelines sponsored by the International Mesothelioma Interest Group (article under review).…”

Updates on the pathologic diagnosis and classification of mesothelioma

“…The ratio of each constituent, especially with regard to the sarcomatoid component, may be prognostic. Data is limited, but it is suggested that sarcomatoid predominant biphasic mesotheliomas have worse outcomes, with prognostic cutoffs reported from 20%-50% sarcomatoid morphology [19,22] . Given that there is some data to suggest a prognostic cutoff around 50% for sarcomatoid morphology, it may be helpful for the patient's treatment team to be aware that 95% of biopsies with pure epithelioid morphology showed at least 50% epithelioid morphology at the time of resection [20] .…”

Grading in Lung Adenocarcinoma: Another New Normal

“…For breast cancer, the grading system is a combination of architectural and nuclear features, and, for pleural epithelioid mesotheliomas, the recently proposed system is based mainly on cytomorphologic features (pleomorphism, mitotic activity, and necrosis), [29][30][31] with architectural patterns not adding significantly to the refinement of prognostication. 32 This is perhaps not unsurprising given that the biology and drivers of carcinogenesis differ so greatly for individual tumors, but it is important for clinicians to realize that, in relation to grading, one size does not fit all. Even within individual organs, taking the lung, grading systems are likely to differ between tumor subtypes as it seems that tumor budding may be the most significant adverse prognostic histologic feature for resected squamous cell carcinoma.…”