Mesothelial Hyperplasia

A brief presentation on mesothelial hyperplasia and how to distinguish it from mesothelioma

1. Reactive Mesothelial Hyperplasia Rawa Muhsin

2. Serosal membranes Layers Mesothelial cells Basement membrane Connective tissue Meso (middle) + thele (nipple)

3. Histology Small, flat to cuboidal cells Well-defined cell borders Single central nucleus Homogeneous chromatin No nucleolus

4. Cytology Architecture Single cells, sheets, or small clusters with scalloped periphery (<10-15 cells per group) Cytology Foamy or dense cytoplasm ± vacuoles Peripheral clear outer rim Empty spaces between cells Binucleation is common

5. Immunohistochemistry Positive markers Keratins Including AE1/AE3, CK7, CK 5/6, CK 8/18 Calretinin WT1 D2-40 ( podoplanin ) HBME-1, thrombomodulin (CD141), N- cadherin Negative markers CK20 MOC-31 BER-EP4 CEA CD15 TTF-1

6. Reactive mesothelial hyperplasia

7. Definition and etiogenesis Proliferation of benign reactive mesothelial cells Reaction to injury, such as recurrent effusions, inflammation, neoplasia , or surgical procedures

8. Clinical Asymptomatic Incidental finding Benign Regresses when stimulus is removed

9. Macroscopy None!

10. Macroscopy

11. Microscopy Architecture Thickened mesothelial layer Papillae Psammoma bodies No invasion Cytology Larger cells (than normal) Enlarged nucleus with open chromatin Prominent central nucleoli Variable mitotic activity and atypia Multinucleation

12. Differential diagnosis Malignant mesothelioma (early stage) Metastatic papillary carcinoma Clinical history Symptomatic IHC (TTF-1, ER/PR) Müllerian rests Rare, in young women Glands without atypia or mitotic activity Dense spindle cell stroma

13. Reactive vs Mesothelioma

14. Definitive for mesothelioma Stromal invasion with fibroblastic response Sampling entire lesion is critical Highlight with keratin stains Infiltration of underlying fat, muscle, or adjacent tissues

15. Favors reactive hyperplasia Asymptomatic, incidental Focal distribution with skip lesions Absence of tumor cell necrosis Inflammation common Low Ki-67 (<9%) Special studies

16. Special studies Loss of BAP1 (by IHC) 40% in mesothelioma (more in epithelioid ) Loss of p16 (by FISH) 60% in mesothelioma (more in sarcomatoid ) IHC doesn’t count; IHC for loss of MTAP Each 100% specific Combined sensitivity 80%

17. Special studies Mesothelioma p53, EMA, CD146, GLUT1, IMP-3 Reactive hyperplasia Desmin Inconsistent results Not to be used in practice for now