2021 WHO Classification of Tumors of the Pleura: ICD-O Coding and Terminology
Mesothelial tumors
Benign and preinvasive mesothelial tumors
Adenomatoid tumor 9054/0
Well-differentiated papillary mesothelial tumor 9052/1b
Mesothelioma in situ 9050/2c
Mesothelioma
Localized mesothelioma 9050/3b
Diffuse mesothelioma, NOS 9050/3b
Sarcomatoid mesothelioma 9051/3
Epithelioid mesothelioma 9052/3
Mesothelioma, biphasic 9053/3
2021 WHO Classification of Tumors of the Pleura: Essential and Desirable Diagnostic Criteria
Benign and preinvasive mesothelial tumors
Adenomatoid tumor - Focal proliferation of tubular spaces or vacuoles lined by flattened or cuboidal mesothelial cells in a fibrous stroma
- Lack of diffuse or multifocal spread along pleura and absence of malignant histologic features, such as invasive growth into underlying stroma, cytologic atypia, necrosis, or sarcomatoid patterns
- Immunohistochemistry for mesothelial markers, if needed
- Immunohistochemical staining for L1CAM, a marker of TRAF7 mutation, may be useful
- BAP1 expression retained and absence of homozygous deletion of CDKN2A
高分化乳头状间皮肿瘤（Well-differentiated papillary mesothelial tumor）
- Papillary stromal formations covered by bland mesothelium
- No stromal invasion
- Immunohistochemical staining for mesothelial markers
- BAP1 expression retained
原位间皮瘤（Mesothelioma in situ，MIS）
- Pleural effusions (nonresolving)
- No thoracoscopic or imaging evidence of tumor
- Single layer of mesothelial cells (with or without atypia) on pleural surface
- No histologic features of invasive growth
- Loss of BAP1 and/or MTAP by immunohistochemistry and/or CDKN2A homozygous deletion by FISH
- Multidisciplinary discussion of diagnosis
- Papillary stromal formations covered by bland mesothelium
- No stromal invasion
Mesothelioma
Localized pleural mesothelioma
- Presentation as a solitary localized mass by imaging, surgical findings, and histology
- Examination of a surgical resection specimen revealing lack of invasion beyond the circumscribed borders of the tumor
- Histologic features of diffuse mesothelioma
- Immunohistochemical evidence of mesothelial origin
- Multidisciplinary discussion to confirm the diagnosis
Diffuse pleural mesothelioma
- Diffuse pleural thickening by a malignant neoplasm with epithelioid, sarcomatoid, or biphasic histology•
- Invasion of adjacent structures (i.e., adipose tissue, skeletal muscle, and/or lung parenchyma), tumor necrosis, or formation of unequivocal malignant tumor nodules
- Desmoplastic mesothelioma is characterized by dense collagenized tissue separated by malignant mesothelial cells arranged in a storiform or so-called patternless pattern, which must be present in ≥50% of the tumor in definitive resection specimens
- Biphasic mesothelioma is mesothelioma revealing ≥10% each of epithelioid and sarcomatoid patterns in definitive resection specimens or any percentage of each component in smaller biopsy and cytology specimens
- Immunohistochemistry confirming mesothelial origin
Loss of BAP1 and/or MTAP by immunohistochemistry, and/or CDKN2A loss by FISH Or mutations in BAP1 or CDKN2A demonstrated by next-generation sequencing
The 2015 WHO classification6 recognized promising advances in the field of mesothelioma pathology, including histologic features with prognostic significance, nuclear grading of epithelioid diffuse pleural mesothelioma, and the use of BAP1 immunohistochemistry (IHC) and homozygous deletion of CDKN2A (9p21; encoding p16) by fluorescence in situ hybridization (FISH) in the separation of mesothelioma from reactive mesothelial proliferations, but these advances were not thoroughly incorporated into the classification until 2021.1 Recent advances in the understanding of genomics of mesothelioma have led to increased recognition of a new entity, mesothelioma in situ (MIS), which was not formally recognized previously. Criteria for MIS have now been established and are included in the 2021 WHO classification.
Mesenchymal tumors of the pleura have been moved to a new chapter titled “Mesenchymal tumours of the thorax.” An additional section in the “Metastases” chapter titled “Metastasis to the pleura” was added to the 2021 classification. The 2021 WHO Classification of Thoracic Tumors also includes a new chapter “Genetic tumour syndromes involving the thorax,” which includes a section titled “BAP1 tumour predisposition syndrome.” A review to address updates in hematolymphoid tumors of the pleura and pericardium will be published separately.
FISH, fluorescence in situ hybridization. ICD-O, International Classification of Diseases for Oncology.
- Morphology codes are taken from the ICD-O, third edition, second revision (ICD-O-3.2) (REF 1256).
- Behavior is coded
- /0 for benign tumors;
- /1 for unspecified, borderline, or uncertain behavior;
- /2 for carcinoma in situ and grade III intraepithelial neoplasia; and /3 for malignant tumors.
所有间皮瘤现在都被认为是恶性的。
三种组织学亚型（即上皮样、肉瘤样和双相型）
在切除标本中，双相型间皮瘤的诊断标准仍然是上皮样和肉瘤样成分均至少10%，但在小标本中则不再要求占比阈值。
MPM常使用calretinin、CK5/6、WT-1、mesothelin和D2-40等生物标志物进行分子诊断。
原位间皮瘤（mesothelioma in situ，MIS）是2021年新添加分类，可通过免疫组化的BAP1和/或MTAP缺失和/或通过荧光原位杂交技术（fluorescence in situ hybridization，FISH）方法测定CDKN2A的纯合缺失来识别。MPM常涉及TP53、BAP1、CDKN2A、LATS1/2、NF2和SETD2等基因变异。特别是对于那些年轻、没有石棉暴露史且肿瘤无家族聚集的患者，建议进行BAP1基因的检测。值得关注的是，CDKN2A基因的突变与不良预后密切相关，在肉瘤样型的间皮瘤患者中，这一基因的阳性检出率几乎达到100%。
参考文献：
The 2021 WHO Classification of Tumors of the Pleura: Advances Since the 2015 Classification - PubMed (nih.gov)
WHO Classification of Tumours, 5th edition; volume 5, Tumours of the pleura and pericardium (2021).
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