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Mesothelial Hyperplasia
- 1. Reactive Mesothelial Hyperplasia Rawa Muhsin
- 3. Serosal membranes Layers ◦ Mesothelial cells ◦ Basement membrane ◦ Connective tissue Meso (middle) + thele (nipple)
- 4. Histology Small, flat to cuboidal cells Well-defined cell borders Single central nucleus Homogeneous chromatin No nucleolus
- 7. 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
- 10. 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
- 12. Definition and etiogenesis Proliferation of benign reactive mesothelial cells Reaction to injury, such as recurrent effusions, inflammation, neoplasia, or surgical procedures
- 13. Clinical Asymptomatic Incidental finding Benign Regresses when stimulus is removed
- 15. Macroscopy
- 16. 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
- 22. 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
- 27. 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
- 31. Favors reactive hyperplasia Asymptomatic, incidental Focal distribution with skip lesions Absence of tumor cell necrosis Inflammation common Low Ki-67 (<9%) Special studies
- 32. 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%
- 37. Special studies Mesothelioma ◦ p53, EMA, CD146, GLUT1, IMP-3 Reactive hyperplasia ◦ Desmin Inconsistent results Not to be used in practice for now
Editor's Notes
- Epithelium described covering of nipple alone originally, then the German Henle applied it to all skin and mucosa.
- H&E stain of the pleura shows a single layer of normal, nonreactive mesothelial cells . They appear as small cuboidal or flat cells with eosinophilic cytoplasm and indistinct nuclear features. At times, they are difficult to identify in histologic sections and may appear to be absent.
- H&E stain shows cuboidal mesothelial cells , which are easier to identify than flat mesothelial cells but still show a similar bland cytomorphology.
- Many characteristic features of mesothelial cells are seen here: the peripheral lucent zone, or “lacy skirt” (arrow); the dense perinuclear zone; the occasional binucleation; and the slitlike separation (“window”) between adjacent cells. A few histiocytes (arrowheads) with folded nuclei and vacuolated cytoplasm are also present (Papanicolaou stain).
- Benign mesothelial cells are occasionally seen in percutaneous fine needle aspirates. They are arranged in flat, cohesive sheets. The cells have round or oval nuclei, small nucleoli, and a moderate amount of cytoplasm. Slitlike spaces between the cells (“windows”) can be appreciated (Papanicolaou stain).
- Mesothelial/Monocytic Incidental Cardiac Excrescence (MICE) or Histiocytic nodular mesothelial hyperplasia (HNMH): Mass-like aggregates of benign mesothelial cells, histiocytes (macrophages), and fibrin with entrapped blood and fat
- Reactive mesothelial changes (peritoneal fluid, cirrhosis). Some benign fluids contain a population of moderately enlarged mesothelial cells with large, hyperchromatic, irregular nuclei (Papanicolaou stain).
- Reactive mesothelial cells (ovarian torsion). The mesothelial cells are enlarged, with irregular nuclei and prominent nucleoli. Exploratory laparotomy revealed torsion of the right ovary with intraperitoneal adhesions.
- A distinctive feature of reactive mesothelial cells is an open chromatin pattern with 1 to a few small but prominent basophilic nucleoli . This image also shows the characteristic hobnailing or tombstoning of these cells.
- Diffuse-type mesothelial hyperplasia is seen with thickening of the pleural surface caused by sheets of epithelioid cells in a diffuse, solid pattern. Notice the sharp demarcation from the underlying pleural connective tissue.
- In papillary-type mesothelial hyperplasia, hyperplastic mesothelial cells are forming small papillary fronds lined by a single layer of cells. This process may be confused for malignant mesothelioma or a metastasis from papillary carcinoma.
- Reactive mesothelial cells versus mesothelioma. A, Reactive mesothelial cells can show some variation in nuclear size and nuclear membrane irregularity (Papanicolaou stain). B, Mesotheliomas usually show greater cytomegaly, but this can be difficult to assess on a case-by-case basis (Papanicolaou stain).
- Focus of pleural atypical mesothelial hyperplasia is characterized by focal thickening of the pleural surface by proliferation of atypical round epithelioid cells. Small foci like this can be mistaken for metastatic carcinoma.
- Atypical Hyperplasia: Mitosis Higher magnification shows significant cytologic atypia with enlarged, hyperchromatic nuclei and an abnormal mitosis . The cells show some degree of nuclear pleomorphism with variation in size and shape of the mesothelial cells.
- Atypical mesothelial hyperplasia of the pleura shows densely packed proliferation of epithelioid cells along the pleural surface. The area toward the base is suggestive of a focus of invasion.
- This area of mesothelioma shows exophytic papillary and endophytic invasive growth of tumor cells. The tumor cells lining the papillae are relatively uniform. The nuclei of the invasive component are larger and have prominent nucleoli.
- TMA core of benign reactive mesothelial atypia showing intact BAP1 protein expression (yellow arrows). Note nonmesothelial stromal and inflammatory cells showing positive nuclear BAP1 expression (red and green arrows); these cells serve as positive internal controls.
- TMA cores of malignant mesotheliomas showing loss of nuclear BAP1 expression (yellow arrows). Note nuclear positivity within stromal and inflammatory cells (red and green arrows). When assessing BAP1 status, only nuclear positivity represents a signal of interest; cytoplasmic, membranous and extracellular staining is disregarded.
- TMA core of a benign mesothelial proliferation showing dual nuclear signals, orange dots correspond to the p16 (CDKN2A) locus, green dots correspond to the centromere region of chromosome 9. The majority of cells show both signals in an approximately equal ratio indicating that no loss of p16 has occurred.
- TMA core of mesothelioma showing homozygous loss of p16. Majority of cells show green signal(s) without corresponding orange signal.