Discussion & Conclusion Predictives of Meningioma Grading Predictive Markers for Meningioma Grading Hussam Abu-Farsakh1 ,Noor Abu-Farsakh2 and, Ibrahim Sbeih 3    1First Medical Lab   2Faculty of Medicine, Jordan University;  3 Neurosurgery center, Ibn Hytham Hospital. Jordan. Replace with logo Abstract Results Material & Methods Discussion & Conclusion Context: Meningiomas are divided into 3 grades according to the WHO 2007 classification: grade I, grade II and grade III. Grading is important to predict survival and plan further therapy. Histomorphology and immunohistochemistry markers are important aids for grading. Design: We studied 244 meningioma cases during the last 10 years at our center. All cases were studied for the following: gender, tumor size, mitotic count, the presence of small cell component (SCC), brain invasion (BRI), bone invasion (BNI), necrosis, and atypia (defined as pleomorphism, prominent nucleoli +/- large hyperchromatic nuclei). Additionally, Immunohistochemistry for the percentage of progesterone receptors(PRG) expresoin, p53 and Ki 67 were calculated. Results: Grade I and II meningiomas were more common in females, but Grade III were equally distributed (p<0.05). See Table for all parameters. Conclusions: Meningioma are more common in females except for Grade III. Grade III are likely to be larger in size than Grade I and Grade II. Grade II and Grade III have higher mitotic counts, a higher chance of having necrosis, are more likely to have a small cell component, and are more likely to have brain or bone invasion. The higher the grade, the higher the Ki67 index, the higher the percentage of p53 expressing cells and the less likely to have progesterone expression. We studied 244 meningioma cases during the last 10 years at our center. All cases were studied for the following: gender, tumor size, mitotic count, the presence of small cell component (SCC), brain invasion (BRI), bone invasion (BNI), necrosis, and atypia (defined as pleomorphism, prominent nucleoli +/- large hyperchromatic nuclei). Additionally, Immunohistochemistry for the percentage of progesterone receptors(PRG) expression, p53 and Ki 67 were calculated. Results: Grade I and II meningiomas were more common in females, but Grade III were equally distributed (p<0.05). See Table for all parameters. Meningioma are more common in females except for Grade III. Grade III are likely to be larger in size than Grade I and Grade II. Grade II and Grade III have higher mitotic counts, a higher chance of having necrosis, are more likely to have a small cell component, and are more likely to have brain or bone invasion. The higher the grade, the higher the Ki67 index, the higher the percentage of p53 expressing cells and the less likely to have progesterone expression.. Predictives of Meningioma Grading Grade I Grade II Grade III P value Size cm, average 3.9 3.8 9.5 <0.0065 Atypia presence in cases 8% 9% 55% <0.001 Mitotic figures/10HPF average in Grade 0.2 1.2 11.6 <0.0001 Necrosis presence in cases 3% 14% SCC presence in cases 4% 27% BRI presence in cases 0% 58% 91% BNI presence in cases 1% 6% PRG% average in grade 65% 32% p53% average in grade 0.9% 3.1% 7% Ki67% average in grade 2.9% 6.4% 23.5% Fig 1: Ki67% in Grade I meningioma 1%, Grade II: 6%, Grade III: 17% Background Meningioma Grading is done by histological examination using 5 histological features into WHO grade I, II (atypical), or III (anaplastic). Meningioma peaks at 65-75 years; with F:M = 2:1. The natural history of Grade I: Grows slowly and compress adjacent structures. Grade II: Variable; some recur or invade brain. Grade III: Sarcoma-like; recur, invade, and may metastasize to extracranial sites: lung, liver, bone, lymph nodes, The Prognosis is Excellent for completely excised WHO grade I and II tumors. But poor for grade III, anaplastic tumors. The Recurrence risk increases with grade and presence of residual tumor. The Skull base meningiomas often recur. Mitotic figures varies according to the grade, in Grade I they are usually ≤ 3 mitoses/10 HPF: Grade II, ≥ 4 mitoses/10 HPF, Grade III ≥ 20 mitoses/10 HPF: Small cell changes occurs in some grade II types. Ki-67 is one of the markers that varies with grading. Grade I lesions usually have ≤ 5% but no defined threshold for grade I vs. II or II vs. III but in general it is high in grade III. WHO Grade I has the following subtypes: Meningothelial, fibrous, transitional, angiomatous, microcystic, secretory, metaplastic, lymphoplasmacyte rich, psammomatous ≤ 3 mitoses per 10 high-power fields. No brain invasion. WHO Grade II has ≥ 4 mitoses/10 high-power fields or 3 of the following High cellularity, Small cells with high N:C ratio, clustered Prominent nucleoli, Uninterrupted growth pattern ("sheeting") Necrosis ± palisading, brain invasion or chordoid or clear cell subtype. WHO Grade III has ≥ 20 mitoses/10 high-power fields or Overt malignant features resembling carcinoma, melanoma, sarcoma or Rhabdoid or papillary subtype, Necrosis frequent but not required Fig 2: Brain invasion and GFAP in atypical meningioma Background Fig 7: A: p53 nuclear staining in malignant meningioma Fig 6::: p63 nuclear staining in atypical meningioma Fig 4: Small cell component in atypical meningioma References Fig 3: Mitotic figure in atypia meningioma Perry A et al: The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas. Cancer. 82(11):2262-9, 1998 Perry A et al: Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. J Neuropathol Exp Neurol. 59(10):872-9, 2000 Fig5: Progesterone level in meningioma Grade I and in grade II