EURACAN/IASLC Proposals for Updating the Histologic Classification of Pleural Mesothelioma: Towards a More Multidisciplinary Approach

Nicholson, Andrew G.; Sauter, Jennifer L.; Nowak, Anna K.; Kindler, Hedy L.; Gill, Ritu R.; Rémy‐Jardin, Martine; Armato, Samuel G.; Fernández-Cuesta, Lynnette; Bueno, Raphael; Alcala, Nicolas; Foll, Matthieu; Pass, Harvey I.; Attanoos, Richard; Baas, Paul; Beasley, Mary Beth; Brčić, Luka; Butnor, Kelly J.; Chirieac, Lucian R.; Churg, Andrew; Courtiol, Pierre; Đačić, Sanja; Perrot, Marc de; Frauenfelder, Thomas; Gibbs, A R; Hirsch, Fred R.; Hiroshima, Kenzo; Husain, Aliya N.; Klebe, Sonja; Lantuéjoul, Sylvie; Moreira, André L.; Opitz, Isabelle; Pérol, Maurice; Roden, Anja C.; Roggli, Victor L.; Scherpereel, Arnaud; Tirode, Franck; Tazelaar, Henry D.; Travis, William D.; Tsao, Ming‐Sound; Schil, Paul Van; Vignaud, J; Weynand, Birgit; Lang-Lazdunski, Loı̈c; Cree, Ian A.; Rusch, Valerie W.; Girard, Nicolas; Galateau-Salle, Françoise

doi:10.1016/j.jtho.2019.08.2506

Cited by 111 publications

(158 citation statements)

References 107 publications

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“…using current histological and immunohistochemical criteria. [1][2][3] Histopathological parameters were assessed and recorded independently, blinded to outcome, by one pathologist. All available haematoxylin & eosin (H&E) sections were reviewed, with an average of 3.9 sections per case (range: 1-47).…”

Section: H I S T O P a T H O L O G I C A L A S S E S S M E N Tmentioning

confidence: 99%

“…Common growth patterns (solid, tubulo-papillary, trabecular, micropapillary, microcystic) and the presence of pleomorphic features were evaluated using the current diagnostic criteria. 1,3 A minimum of 10% of tumour cells exhibiting severe nuclear atypia was required for the diagnosis of E-MPM with pleomorphic features. For the same reason in this study it was not regarded as a growth pattern.…”

Section: H I S T O P a T H O L O G I C A L A S S E S S M E N Tmentioning

confidence: 99%

“…This is defined as cases not having undergone maximal cytoreductive surgery (MCS) and generally comprised a lesser amount of tissue. 1,14 E-MPM with pleomorphic features represented 8.3% (51/614) of the study population.…”

Section: E M O G R a P H I C A N D C L I N I C O P A T H O L O G I mentioning

confidence: 99%

“…Epithelioid malignant pleural mesothelioma (E-MPM), the most common subtype of malignant pleural mesothelioma, morphologically resembles primary thoracic epithelial malignancies with the propensity to form diverse growth patterns. [1][2][3] The prognostic impact of these patterns has been investigated in a limited number of studies [4][5][6] although none fully explored the relationship with nuclear grade, which has only been recently proposed and validated as a robust prognostic tool. 1,[7][8][9] Also yet to be elucidated is the extent of intra-tumoural heterogeneity in terms of growth patterns, and their relation with nuclear grade and prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6]10,11 However, the relatively small number of published cases (103 over the past 10 years) poses challenges to the ongoing discussion within major guideline committees in relation to its classification as a variant of epithelioid or non-epithelioid subtype. 1 The primary aims of this study were (i) external validation of the prognostic impact of pleomorphic features in E-MPM and (ii) evaluation of the prognostic impact of growth patterns both alone and in combination with 2-tier nuclear grade. The secondary aims of the study were (i) characterisation of intra-tumoural heterogeneity of growth patterns by assessing predominant and co-existing secondary (non-predominant) patterns, (ii) investigation of the association of growth patterns with 2-tier nuclear grade 7,8 and (iii) evaluation of the prognostic impact of three growth patterns additional to those currently recommended for routine diagnostic usage 1 and identified during review of the cohort: discohesive, cribriform and well differentiated papillary mesothelioma (WDPM)-like features.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: H I S T O P a T H O L O G I C A L A S S E S S M E N Tmentioning

confidence: 99%

Section: H I S T O P a T H O L O G I C A L A S S E S S M E N Tmentioning

confidence: 99%

Section: E M O G R a P H I C A N D C L I N I C O P A T H O L O G I mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Malignant Pleural Mesothelioma

Carbone¹,

Gomez²,

Tsao³

et al. 2023

Holland‐Frei Cancer Medicine

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Overview Malignant pleural mesothelioma is an aggressive malignancy with an incidence that may be peaking worldwide. While the majority of patients do ultimately die of this disease, there have been substantial treatment and diagnostic shifts over the past decade that may improve long‐term outcomes. These changes include worldwide interest in defining early detection biomarkers for the disease, a debate as to the optimal surgical approach (extrapleural pneumonectomy vs lung‐sparing methods such as pleurectomy/decortication), further refinement of radiation techniques that allow for conformal treatment fields and the delivery of radiation with the involved lung intact, and the emergence of systemic therapies that are targeted in nature and allow for the increased individualization of care. Indeed, prospective clinical trials assessing the safety and efficacy of novel treatment approaches will be essential to the standardization of paradigms that improve outcomes. It is hoped that the maturation of these efforts will lead to an optimal approach in which earlier stage patients will benefit from multiple modalities that will provide synergistic control while limiting toxicity, thereby increasing the number of long‐term survivors over the next one to two decades.

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Testing for BAP1 loss and CDKN2A/p16 homozygous deletion improves the accurate diagnosis of mesothelial proliferations in effusion cytology

Chevrier

Jerome

Galateau-Sallé

et al. 2020

Cancer Cytopathology

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BACKGROUND: A number of ancillary tests have been developed that aid in the diagnosis of mesothelioma in cytology specimens. The aim of this retrospective study was to determine whether testing for BAP1 and CDKN2A/p16 status in effusion specimens preceding the tissue diagnosis of mesothelioma would improve diagnostic accuracy and allow an earlier diagnosis of malignancy. METHODS: The study cohort included 99 matched cytology fluid specimens from 74 patients with a surgical specimen diagnosis of malignant mesothelioma (67 epithelioid, 7 biphasic, 55 pleural, and 19 peritoneal). BAP1 immunohistochemistry and p16 fluorescence in situ hybridization (FISH) were performed retrospectively. RESULTS: BAP1 or p16 FISH testing revealed a loss in 7 of 18 (39%) samples originally categorized as benign/reactive, 20 of 33 (61%) interpretable samples categorized as atypical, and 10 of 14 (71%) cases suspicious for mesothelioma. In some cases, the diagnosis of mesothelioma could have been made up to 9 months before biopsy. Similarly, loss of BAP1 or p16 was found in 28 of 30 (93%) samples categorized as malignant, with some cases diagnosable up to 6 months before biopsy. Overall, loss of BAP1 and/or CDKN2A/p16 homozygous deletion would change the diagnostic interpretation in 37 of 60 (62%) (P = .07) effusion specimens, particularly in pleural effusions (32 of 48 samples) (P = .002). The sensitivity of morphologic interpretation alone was 30.3%; however, adding testing for BAP1 and p16 resulted in an increase in sensitivity to 68.7%. (P < .0001). CONCLUSION: These findings suggest that routine use of BAP1 immunochemistry and p16 FISH as adjunctive tests improves the diagnostic accuracy of cytology specimens and potentially allows an earlier diagnosis of malignant mesothelioma. Cancer Cytopathol

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EURACAN/IASLC Proposals for Updating the Histologic Classification of Pleural Mesothelioma: Towards a More Multidisciplinary Approach

Cited by 111 publications

References 107 publications

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

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

Malignant Pleural Mesothelioma

Testing for BAP1 loss and CDKN2A/p16 homozygous deletion improves the accurate diagnosis of mesothelial proliferations in effusion cytology

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