Factors Influencing the Recurrence Rate of Intracranial Meningiomas after Surgery

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1 Factors Influencing the Recurrence Rate of Intracranial Meningiomas after Surgery Katsuzo KUNISHIO, Takashi OHMOTO, Tomohisa FURUTA, Kengo MATSUMOTO, and Akira NISHIMOTO* Department of Neurological Surgery, Okayama University Medical School, Okayama, *Department of Neurosurgery, Kagawa Rosai Hospital, Marugame, Kagawa Abstract The postoperative recurrence rate was examined in 242 patients with intracranial meningiomas to identify correlations with age, location, histology, or extent of surgery (Simpson's grade). There was no significant difference in the recurrence rate among the histological subtypes, but malignant me ningiomas and hemangiopericytomas tended to recur earlier. Anterior basal meningiomas demon strated a higher recurrence rate, but this depended on the feasibility of complete surgical removal. The recurrence rates significantly decreased in the order Simpson's grade I surgery, grade II or III surgery, and grade IV surgery (p < 0.001). These results indicate that the most important factor to influence recurrence is the extent of surgical removal. Key words: meningioma, recurrence, Simpson's grade Introduction Meningiomas are generally benign and constitute approximately 15% of intracranial neoplasms." However, clearly malignant subtypes such as hemangiopericytoma and the socalled malignant meningioma are sometimes encountered.",") In complete removal of meningioma frequently results in recurrence, but even total removal of nonmalig nant meningioma is associated with a significantly high incidence of recurrence, varying from 3 to 32% in different series. 1,2,14,19,27,29) This study analyzed a series of 242 intracranial meningioma patients treated at our hospital to iden tify factors associated with recurrence. Patients and Methods 291 patients who underwent surgical treatment for in tracranial meningioma at our hospital between 1966 and 1988 were reviewed. Fortytwo patients were ex cluded because they were lost to followup, and seven died postoperatively during the hospital stay from various causes. Thus, 242 cases were available for further analysis. The extent of surgical removal was determined from the operation report and classified according to Simpson's grading system.25) The histological diagnosis was based on the World Health Organization (WHO) classification.") This study defined malignant meningioma'7,22,28> as a tumor demonstrating necrosis, mitotic figures, high cellularity, brain infiltration, and loss of architec ture. Papillary meningioma21) was also included as malignant meningioma. Recurrence was defined as the necessity for reoperation because of neuroradiological indications of an increase in the tumor size or progressive neurological deficits following partial or total removal. Patients were classified according to age, sex, location, extent of surgery, and histology. The prognostic significance of these factors were assessed by the KaplanMeier method. 16) Significant differences in the length of recurrencefree survival were assessed using the CoxManntel method or Student's ttest. 5~ Received March 29, 1993; Accepted July 5, 1993 Author's present address: K. Kunishio, M.D., Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, New York, U.S.A.

2 Results I. Age and sex Figure 1 shows the distribution of patients accord ing to age and sex at the first operation, peaking in the sixth decade of life. 159 patients were females and 83 were males, with a female to male ratio of 2:1. There was no statistically significant sex difference in the time to recurrence after the first operation. There was also no significant difference in the time to recurrence between patients under 50 years old and those 50 years old or over. II. Histology Histological types of the 242 meningiomas are shown in Table 1. Histologically nonmalignant me Fig. 2 Correlation of recurrence with histological classification. Benign meningiomas show no significant difference in the recurrence rate among the subtypes. However, malignant me ningiomas and hemangiopericytomas tend to recur earlier than benign meningiomas. Fig. 1 Distribution of the 242 patients in this series ac cording to the age and sex. Dotted columns represent females (n = 159) and hatched col umns males (n = 83). Table 1 Histological type and recurrence in 242 me ningiomas ningiomas also showed no significant difference in the recurrence rate among the subtypes. Six of nine (66.7%) malignant meningiomas and two of five (40.0%) hemangiopericytomas recurred, and the time to recurrence tended to be shorter than that for nonmalignant meningiomas, but the number of patients was too small for statistical analysis (Fig. 2). The time to recurrence for malignant meningio mas and hemangiopericytomas ranged from 70 days to 7 years (mean 35.5 mos), while that for non malignant meningiomas ranged from 4 months to 16 years (mean 71.2 mos). III. Operation Table 2 shows the recurrence rates in patients with different extents of removal after various followup periods. The rate of recurrence 20 years after the first surgery was significantly less for grade I than for grade II (p < 0.02) or IV (p < 0.01). In addition, using the KaplanMeier method, the recurrence rate after grade I removal was signifi cantly (p < 0.001) less than that after grade II or III removal, while that after grade IV removal was sig nificantly (p < 0.001) greater than that after grade II or III removal (Fig. 3). IV. Location The recurrence rate was higher in anterior basal meningiomas (olfactory, middle fossa, and tuber culum sellae) as compared to convexity meningio mas, but this was related mainly to the feasibility of complete surgical removal (Table 3).

3 Table 2 Extent of removal and recurrence in 228 meningiomas Table 3 Location and recurrence in 228 menin giomas Fig. 3 Correlation of recurrence with Simpson's grade of surgery.") There are statistically significant differences between grade I and grade II or III, and grade II or III and grade IV (p < 0.001). However, there is no significant difference be tween grades II and III. Discussion The present study agrees with previous works in that the degree of removal is the most important fac tor in recurrence.2,19,25,27) We and others found that age and sex are irrelevant, although Kajiwara et al.") reported that recurrence occurred more often in patients under 40 years old or in males. The location was an important factor in recurrence be cause anterior basal meningiomas can only be re moved subtotally or partially.") Borovich et al.3) suggested that meningiomas lo cally recur as regrowth within the limit of the previous dural flap, so wide resection of the dura around the attachment zone of the meningioma might reduce the recurrence rate. Recently, Goldsher et al.') found that gadoliniumenhanced magnetic resonance imaging of meningiomas show ed a linear enhanced structure, the socalled "me ningeal tail sign," in 18 of 30 cases, and suggested that this is a highly specific feature of meningio mas. Though this sign is frequently found to cor relate with tumor infiltration along the dural sur face, the precise pathological explanation is con troversial. This radiological sign may be important for surgical treatment. The histological malignancy of meningiomas is not always a useful guide to the clinical behavior, and the histological features that indicate malignan cy in meningiomas have long been debated.',",") De la Monte et al.') reported that histological features such as large prominent nucleoli, tumor growth in sheets, individual cell necrosis, and nuclear pleomor phism indicate that subtotally removed nonmalig

4 nant meningiomas will recur. Jaaskelainen et al. 13) found a significant difference in the recurrence rate in their series of 936 tumors, of which 93% were benign, 4.7% atypical, and 1.0% anaplastic accord ing to WHO criteria. Histologically benign tumors recurred in 3% at 5 years; atypical tumors, 38% at 5 years; and anaplastic tumors, 78% at 5 years. The measurement of cell kinetics by bromodeoxyuridine (BrdU) labeling and Ki67 immunoreactivity has been used to estimate the proliferative potential and risk of recurrence of meningiomas, as well as other human brain tumors, and a high BrdU or Ki67 label ing index is thought to be related to recurrence and malignancy.',", ) Recently, the argyrophilic nucleolar organizer region (AgNOR) staining method, apparently a simple and useful method for differentiating between high and low malignancy grades in various tumors 6) has been applied to me ningioma specimens. 11,20) We previously found that the mean number of AgNOR per nucleus may be of value in predicting the recurrence of histolog ically nonmalignant meningiomas.18) This study indicates that a greater extent of surgical removal will reduce the probability of recur rence of meningioma, but histological malignancy may also be important. References 1) Adegbite AB, Kahn MI, Paine KWE, Tan LK: The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58: 5156, ) Beks JWF, de Windt HL: The recurrence of supraten torial meningiomas after surgery. Acta Neurochir (Wien) 95: 35, ) Borovich B, Doron Y, Braun J, Guilburd JN, Zaaroor M, Goldsher D, Lemberger A, Gruszkiewicz J, Feinsod M: Recurrence of intracranial menin giomas: The role played by regional multicentricity. Part 2: Clinical and radiological aspects. J Neurosurg 65: , ) Christensen D, Laursen H, Klinken L: Prediction of recurrence in meningiomas after surgical treatment. A quantitative approach. Acta Neuropathol (Berl ) 61: , ) Cox DR: Regression model and life tables. J R Stat Soc (B) 34: , ) Crocker J, McGovern J: Nucleolar organizer regions in normal, cirrhotic, and carcinomatous livers. J Clin Pathol 41: , ) De la Monte SM, Flickinger J, Linggood RM: Histopathologic features predicting recurrence of meningiomas following subtotal resection. Am J Surg Pathol 10: , ) Goldsher D, Litt AW, Pinto RS, Bannon KR, Kricheff II: Dural tail associated with meningio mas on GdDTPAenhanced MR images: Chracter istics, differential diagnostic value, and possible im plications for treatment. Radiology 176: , ) Hoshino T, Nagashima T, Cho KG, Murovic JA, Hodes JE, Wilson CB, Davis RL: Proliferative poten tial of human meningiomas of the brain: A cell kinetics study with bromodeoxyuridine. Cancer 58: , ) Inoue H, Tamura M, Koizumi H, Nakamura M, Naganuma H, Ohye C: Clinical pathology of malig nant meningiomas. Acta Neurochir (Wien) 73: , ) Iwaki T, Takeshita I, Fukui M, Kitamura K: Cell kinetics of the malignant evolution of meningothelial meningioma. Acta Neuropathol (Berl) 74: , ) Jaaskelainen J, Haltia M, Laasonen E, Wahlstrom T, Valtonen S: The growth rate of intracranial me ningiomas and its relation to histology. An analysis of 43 patients. Surg Neurol 24: , ) Jaaskelainen J, Haltia M, Servo A: Atypical and anaplastic meningiomas: Radiology, surgery, radiotherapy and outcome. Surg Neurol 25: , ) Jellinger K, Slowik F: Histological subtypes and prognostic problems in meningiomas. J Neurol 208: , ) Kajiwara K, Fudaba H, Tsuha M, Ueda H, Mitani T, Nishizaki T, Aoki H: Analysis of recurrences of me ningiomas following neurosurgical resection. No Shinkei Geka 17: , 1989 (in Japanese) 16) Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc 53: , ) Kepes JJ: Meningiomas. Biology and Differential Diagnosis. New York, Masson Publishing U.S.A., 1982, pp ) Kunishio K, Ohmoto T, Matsuhisa T, Maeshiro T, Matsumoto K, Furuta T: The significance of nucleolar organizer region (AgNOR) score in pre dicting meningioma recurrence. Cancer (in press) 19) Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL: Meningioma: Analysis of recurrence and progression following neurosurgi cal resection. J Neurosurg 62: 1824, ) Orita T, Kajiwara K, Nishizaki T, Ikeda N, Kamiryo T, Aoki H: Nucleolar organizer regions in menin gioma. Neurosurgery 26: 4346, ) Pasquier B, Gasnier F, Pasquier D, Keddari E, Morens A, Couderc P: Papillary meningioma. Clinicopathologic study of seven cases and review of the literature. Cancer 58: , ) Rubinstein LJ: Tumors of the central nervous system, in: Atlas of Tumor Pathology. Washington, DC, Armed Forces Institute of Pathology, 1972, pp ) Shibata T, Burger PC, Kleihues P: Cell kinetics of human meningiomas and neurinomas: Ki67 PAP

5 stain. No Shinkei Geka 16: , 1988 (in Japanese) 24) Shibuya M, Hoshino T, Ito S, Wacker MR, Prados MD, Davis RL, Wilson CB: Meningiomas: Clinical implications of a high proliferative potential deter mined by bromodeoxyuridine labeling. Neurosurgery 30: , ) Simpson D: The recurrence of intracranial me ningiomas after surgical treatment. J Neurol Neurosurg Psychiat 20: 2239, ) Skullerud K, Loken AC: The prognosis in menin giomas. Acta Neuropathol (Berl) 29: , ) Tamura M, Kawafuchi J, Inoue H, Takeda F: Prognosis in meningioma after surgical treatment. With special reference to malignant transformation and recurrence. Neurol Med Chir (Tokyo) 19: (in Jananesel 28) Thomas HG, Dolman CL, Berry K: Malignant me ningioma: Clinical and pathological features. J Neurosurg 55: , ) Waga S, Yamashita J, Handa H: Recurrence of me ningiomas. Neurol Med Chir (Tokyo) 17 [Part II]: , 1977 (in Japanese) Address reprint requests to: K. Kunishio, M.D., Depart ment of Neurological Surgery, Okayama University Medical School, 251 Shikatacho, Okayama 700, Japan.