Pleural Mesothelioma

Mayo Clinic Laboratories

23 Jan 202224:05

EducationalLearning

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TLDRIn this update, Dr. Anja Roden from Mayo Clinic discusses the 2021 WHO classification of pleural mesothelioma, a deadly disease with significant global impact. The presentation covers the removal of 'malignant' from the classification, the introduction of 'mesothelioma in situ', and the importance of architectural and cytological features in grading and diagnosis. It also highlights the role of immunostains and FISH in distinguishing mesothelioma from reactive mesothelial proliferations and emphasizes the need for a panel of markers to differentiate mesothelioma from carcinoma.

Takeaways

📚 The 2021 WHO classification for mesothelioma has been updated, emphasizing changes in terminology and diagnostic criteria.
🔬 'Malignant' has been removed from the classification as all mesotheliomas are inherently malignant, and 'well-differentiated papillary mesotheliomas' are now termed 'well-differentiated papillary mesothelial tumors'.
📈 Pleural mesothelioma is a rare but deadly disease with over 30,000 new cases worldwide in 2020, and it is most prevalent in North America, some European countries, South Africa, and Australia.
🧬 The survival rate of mesothelioma is associated with histologic subtypes, with epithelioid mesotheliomas having the best prognosis and sarcomatoid the worst.
🔍 Mesothelioma in situ, a pre-invasive lesion, has been introduced in the 2021 classification, characterized by a single layer of neoplastic mesothelial cells and specific molecular markers.
🏥 Diagnosis of mesothelioma in situ requires multiple biopsies from different areas and cannot be made from small biopsies, cytology, or effusions.
🔬 The 2021 classification recommends grading epithelioid mesotheliomas based on nuclear atypia and mitotic activity, which is predictive of overall survival.
📊 Architectural patterns and cytologic features of mesotheliomas have prognostic relevance and are crucial for differential diagnosis.
🧬 Loss of BAP1 expression, homozygous deletion of CDKN2A, and other molecular markers are important for distinguishing between malignant and reactive mesothelial proliferations.
🛑 The use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are essential for accurate diagnosis and differential diagnosis of mesothelioma.
📝 A panel of immunostains is necessary to differentiate mesothelioma from carcinoma, as no single marker is specific for mesothelioma.

Q & A

What is the purpose of the speaker's presentation?
-The speaker, Anja Roden, is providing an update on the 2021 World Health Organization (WHO) classification of pleural mesothelioma and discussing ancillary testing in mesothelioma.
What is pleural mesothelioma and why is it a significant health concern?
-Pleural mesothelioma is a rare but serious and deadly form of cancer that affects the lining of the lungs. It is significant because, according to 2020 data, over 30,000 new cases were reported worldwide, with almost as many fatalities.
Which regions have the highest rates of mesothelioma according to the data presented?
-The regions with the highest rates of mesothelioma are North America, some European countries, South Africa, and Australia.
What factors are associated with the overall survival of mesothelioma patients?
-Factors associated with overall survival include the histologic subtype of the disease, with epithelioid mesotheliomas having the best survival rates, as well as stage, gender, lymph node dissection, nuclear grading in the epithelioid subtype, and treatment without chemotherapy.
What changes were made to the WHO classification in 2021 regarding mesotheliomas?
-In the 2021 WHO classification, the term 'malignant' was removed for diffuse and localized mesotheliomas since they are all malignant by definition. Also, well-differentiated papillary mesotheliomas are now referred to as well-differentiated papillary mesothelial tumors to distinguish them from other types.
What is mesothelioma in situ and how is it characterized?
-Mesothelioma in situ is a pre-invasive lesion characterized by a single layer of neoplastic mesothelial cells without a mass lesion on imaging studies or thoracoscopy. It is associated with recurrent unexplained pleural effusions and may show lack of expression of BAP1 and/or mTAP or homozygous deletion of CDKN2A.
How is the epithelioid subtype of diffuse mesothelioma graded in the 2021 WHO classification?
-The epithelioid subtype is graded based on the scoring of nuclear atypia and mitotic activity. The scores for both are summed up, and depending on the sum, the nuclear grade is determined. Necrosis is also considered to form the overall tumor grade.
What are the common architectural patterns in epithelioid mesotheliomas?
-The common architectural patterns in epithelioid mesotheliomas include tubulopapillary, trabecular, micropapillary, solid, and adenomatoid patterns.
What is the significance of the transitional cytologic feature in the 2021 WHO classification?
-The transitional cytologic feature, which lies between epithelioid and sarcomatoid mesothelioma cytologic features, is significant because it has been associated with a prognosis similar to sarcomatoid mesotheliomas and is now classified together with the sarcomatoid subtype.
What are some of the emerging biomarkers for mesothelioma?
-Emerging biomarkers for mesothelioma include loss of BAP1 expression, loss of cytoplasmic mTAP expression, homozygous deletion of CDKN2A, and GLUT-1, p53, desmin, EMA, IMP3, and EZH2, although the latter have insufficient specificity for diagnostic use.
How can immunostains and FISH be helpful in distinguishing between reactive and malignant mesothelial proliferations?
-Immunostains and FISH can be helpful by identifying specific biomarkers such as loss of BAP1 expression, loss of mTAP expression, and homozygous deletion of CDKN2A, which are consistent with malignant proliferation and can assist in making a definitive diagnosis.

Outlines

00:00

📚 2021 WHO Pleural Mesothelioma Classification Update

Anja Roden from Mayo Clinic provides an update on the 2021 WHO classification of pleural mesothelioma, discussing changes and focusing on 'in situ' and diffuse mesothelioma. She explains the disease's rarity, global incidence, and association with histologic subtypes affecting survival rates. The 2021 classification removes 'malignant' from mesothelioma types, introduces 'well-differentiated papillary mesothelial tumors,' and emphasizes architectural and cytological features for grading. Mesothelioma 'in situ' is a new classification for pre-invasive lesions identified through multiple biopsies showing loss of BAP1 or mTAP expression or CDKN2A homozygous deletion.

05:04

🔬 Mesothelioma Subtypes and Ancillary Testing

The script delves into the biopsy of a 59-year-old female with metastatic mesothelioma, highlighting the importance of architectural patterns and cytological features in the 2021 WHO classification. It details the TNM staging system and the grading process for epithelioid mesotheliomas, including the scoring of nuclear atypia and mitotic activity. The summary also includes examples of various architectural patterns and cytological features, emphasizing their prognostic relevance and the necessity of accurate reporting in biopsy and resection specimens.

10:05

🔎 Grading and Subtyping of Diffuse Mesothelioma

This paragraph discusses the grading system for diffuse mesothelioma, explaining how to determine nuclear grades and overall tumor grades based on nuclear atypia, mitotic activity, and necrosis. It contrasts low and high tumor grades and provides examples of different grades. The paragraph also introduces the transitional cytologic feature, newly added to the WHO 2021 classification, and its significance in prognosis and differentiation from epithelioid mesothelioma. Studies by Galateau-Salle et al. are mentioned to support the clustering of transitional features with sarcomatoid mesotheliomas.

15:06

🛡️ Emerging Biomarkers and Diagnostic Challenges

The script addresses the complexities of distinguishing between malignant and reactive mesothelial proliferations, emphasizing the utility of biomarkers such as loss of BAP1 and/or mTAP expression, and homozygous deletion of CDKN2A in identifying malignancy. It critiques the use of GLUT-1, p53, desmin, EMA, IMP3, and EZH2 due to insufficient specificity. The paragraph provides clinical examples illustrating the application of these biomarkers, including a case of sarcomatoid mesothelioma and the use of FISH for CDKN2A in identifying homozygous deletion.

20:08

📉 Mesothelioma Diagnosis and Differential Markers

The final paragraph focuses on the practical application of immunohistochemical (IHC) markers in diagnosing mesothelioma, particularly differentiating it from carcinoma. It discusses the use of BAP1 and mTAP together for higher sensitivity and the limitations of individual markers in distinguishing mesothelioma from carcinoma. The summary outlines a panel approach for mesothelioma and carcinoma markers, providing examples of useful markers and those to avoid due to their lack of specificity. The importance of morphology, immunostains, and FISH in the diagnostic process is underscored, concluding with an invitation for questions and references.

Mindmap

Keywords

💡Pleural Mesothelioma

Pleural mesothelioma is a rare and aggressive form of cancer that primarily affects the lining of the lungs. It is often linked to exposure to asbestos. In the video, it is highlighted as a serious and deadly disease with over 30,000 new cases worldwide in 2020. The discussion revolves around the classification and testing of this disease, indicating its central role in the video's theme of medical updates.

💡WHO Classification

The WHO classification refers to the system used by the World Health Organization to categorize diseases, including different types of cancer. In the context of the video, the 2021 WHO classification is updated to reflect changes in the understanding and categorization of mesothelioma, emphasizing the importance of accurate classification for diagnosis and treatment.

💡Mesothelioma in situ

Mesothelioma in situ is a term introduced in the 2021 WHO classification to describe a pre-invasive form of mesothelioma. It is characterized by atypical mesothelial cells lining the lung surface without forming a mass. The video explains that diagnosing this condition requires multiple biopsies and specific molecular markers, reflecting its significance in early detection and treatment strategies.

💡Ancillary Testing

Ancillary testing refers to additional tests used in pathology to support or confirm a diagnosis. In the video, it is mentioned in the context of testing for mesothelioma, including immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). These tests help differentiate mesothelioma from other conditions and are crucial for accurate diagnosis.

💡Epithelioid Mesotheliomas

Epithelioid mesotheliomas are a subtype of mesothelioma characterized by a more favorable prognosis compared to other subtypes. The video discusses their association with the best overall survival among mesothelioma patients and the importance of grading them according to the 2021 WHO classification.

💡Sarcomatoid Mesotheliomas

Sarcomatoid mesotheliomas represent a subtype of mesothelioma with spindle-shaped cells and are associated with the worst survival rates. The video script describes their cytological features and the importance of distinguishing them from epithelioid mesotheliomas for prognostic and therapeutic purposes.

💡Immunostains Lab

The Immunostains Lab is mentioned as the workplace of the speaker, Anja Roden, who is the medical director there. This lab is likely involved in the development and application of immunohistochemical stains, which are vital for the diagnosis and classification of diseases like mesothelioma, as discussed throughout the video.

💡BAP1

BAP1 is a gene that, when mutated or lost, can be associated with the development of certain types of cancer, including mesothelioma. In the video, loss of BAP1 expression is highlighted as a marker for mesothelioma in situ and a potential aid in distinguishing malignant from reactive mesothelial proliferations.

💡CDKN2A

CDKN2A is a gene involved in cell cycle regulation. Homozygous deletion of CDKN2A is mentioned in the video as a feature of mesothelioma in situ and as a potential biomarker for malignant mesothelial proliferation. This genetic alteration is significant for the diagnosis and understanding of mesothelioma pathogenesis.

💡Grading

Grading in the context of cancer refers to the assessment of the severity or aggressiveness of a tumor based on specific characteristics. The video explains that the 2021 WHO classification recommends grading epithelioid mesotheliomas, which involves scoring nuclear atypia and mitotic activity to predict overall survival and guide treatment.

💡Immunohistochemistry (IHC)

Immunohistochemistry is a laboratory technique used to visualize specific proteins within cells of a tissue section. In the video, IHC is discussed as a crucial tool for diagnosing mesothelioma by identifying specific markers that differentiate mesothelial cells from carcinoma cells, aiding in the differential diagnosis.

Highlights

Update on the 2021 WHO classification of pleural mesothelioma.

Introduction of mesothelioma in situ to the 2021 WHO classification.

Mesothelioma in situ is a pre-invasive lesion characterized by recurrent unexplained pleural effusion.

Diagnosis of mesothelioma in situ requires multiple biopsies and specific molecular markers.

Diffuse mesotheliomas often present with unilateral pleural effusion and can invade contiguous structures.

Grading of epithelioid mesotheliomas is now recommended in the 2021 WHO classification.

Architectural patterns and cytologic features of mesotheliomas have prognostic relevance.

The 8th edition of the AJCC/UICC staging system is used for staging mesothelioma.

Transitional cytologic features in mesothelioma are associated with a poor prognosis.

Loss of BAP1 expression and homozygous deletion of CDKN2A are indicative of malignant mesothelial proliferation.

Immunostains and FISH may assist in distinguishing between reactive and malignant mesothelial proliferations.

Pitfalls in using IHC markers to distinguish mesothelioma from carcinoma are discussed.

A panel of immunostains is necessary for differentiating mesothelioma from other malignancies.

Mesothelioma grading is predictive of overall survival and should be reported in biopsies and resection specimens.

The importance of using a combination of BAP1 and mTAP for higher sensitivity in identifying mesothelioma.

The challenges and considerations in diagnosing mesothelioma, including the use of biomarkers and IHC panels.

Conclusion emphasizing the importance of accurate diagnosis and grading in mesothelioma management.

Transcripts

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Mesothelioma WHO Classification Pleural Cancer Thoracic Pathology Malignant Disease Cytological Features Immunostains Lab Grading System Disease Prognosis Medical Oncology Healthcare