Histological characteristics of incidentally-found growing meningiomas

Object. With the wider use of CT and MRI, many meningiomas are discovered as incidental findings during diagnostic work-up for unrelated symptoms. The majority shows no or minimal growth. The purpose of this study was to distinguish pathological features of incidentally-found growing meningiomas by comparing incidentally-found with symptomatic meningiomas. Methods. One hundred and thirty two consecutive nonrecurrent surgically-treated meningiomas treated between 2005 and 2007 were divided into three categories : 19 incidentally-found growing meningiomas (IG), 50 incidentallyfound meningiomas (I), and 63 symptomatic (S) meningiomas. The average follow-up period for the IG meningiomas was 3.7 years. Six out of 19 patients of the IG meningiomas became symptomatic during observation. Results. There is a significant difference of the incidence of WHO grades I, II, and III between all three groups (p=0.035). The incidence of WHO grades II and III in groups IG, I, and S were 26%, 2%, and 10%, respectively. We compare MIB-1 staining index between three groups : an average was 3.8% in IG, 1.3% in I, and 2.4% in S meningiomas. Conclusions. Incidentally-found meningiomas need careful follow-up. One fourth of the meningiomas that showed signs of growing belonged to the atypical or malignant grade

Clinical and radiological features related to the growth potential of meningioma

Clinical and radiological features that help predict the growth potential of meningioma would be beneficial. The purpose of this study is to clarify the characteristics related to proliferating potential using the MIB-1 staining index. We analyzed the relationship of MIB-1 staining indices to characteristics of 342 consecutive patients with meningioma surgically removed between 1995 and 2004 by logistic regression analysis. One hundred and forty-nine of the patients with meningioma were ≥60 in age; 89 male; 48 recurrent; 203 symptomatic; 157 at the skull base; 124 over 20 cm(3); 24 multiple; 136 with edema; 117 with calcification. The MIB-1 staining index in 56 of 296 grade I meningiomas in WHO classification was ≥ 3.0; in 27 of 28 grade II; and in 17 of 18 grade III, respectively. Logistic regression analysis demonstrated that male (odds ratio [OR], 2.374, p=0.003), recurrence (OR, 7.574, p=0.0001), skull base (OR, 0.540, p=0.035), calcification (OR, 0.498, p=0.019) were independent risk factors for a high MIB-1 staining index (≥3.0); age, symptomatic, volume, multiple, edema were not. Male, recurrence, non-skull base, absence of calcification are independent risk factors for a high proliferative potential. These should be taken into consideration when managing meningiomas

A Case of Corticotroph Carcinoma that Caused Multiple Cranial Nerve Palsies, Destructive Petrosal Bone Invasion, and Liver Metastasis

A 52-year-old woman experienced sudden onset of double vision due to a right abducens nerve palsy and was diagnosed as having a pituitary macroadenoma that invaded into the right cavernous sinus. Otherwise, she was asymptomatic despite marked elevation of ACTH (293 pg/ml) and cortisol (24.6 μg/dl) levels. The patient underwent transsphenoidal surgery followed by γ-knife radiosurgery (GKR), which healed the diplopia and ameliorated the hypercortisolemia. The excised tumor was diffusely stained for ACTH with a high (15%) Ki-67 labeling index. Early tumor recurrence occurred twice thereafter, producing right lower cranial nerve palsies with petrosal bone destruction at 8 months and an ipsilateral oculomotor nerve palsy at 12 months after GKR; all palsies resolved completely with the second and third GKRs. Hypercortisolemia worsened rapidly soon after the third GKR, and the patient developed marked weight gain, hypokalemia, and hypertension. Multiple liver lesions were incidentally detected with computer tomography and identified as metastatic pituitary tumor on immunohistochemistry. An ACTH-producing adenoma should be followed carefully for early recurrence and/or metastatic spread when the tumor is an invasive macroadenoma with a high proliferation marker level. The unique aggressive behavior and high potential for malignant transformation of this case are discussed

共焦点レーザー顕微鏡(CLSM)を用いた下垂体腺腫の免疫組織化学的検討

下垂体腺腫のうち成長ホルモンとプロラクチン産生腫瘍は一般的にはpure growth hormone secreting adenoma(PGA), pure prolactin secreting adenoma(PPA)とmixed growth hormoneprolactin secreting adenoma(MGPA)に分類されている.更に詳細に分類するとMGPAはacidophil stem cell adenoma(ASCA), mammosomatotroph adenoma(MSA),およびmixed somatotroph-lactotroph adenoma(MSLA)に分けられている。ASCAとMSAは両ホルモンを持っている細胞からなる腫瘍で,MSLAは両ホルモンをそれぞれ別々の細胞が産生している腫瘍といわれている.今回30例の下垂体腺腫の手術例についてこのような詳細な検討をするため,両ホルモンの細胞内分布について二重標識蛍光抗体法を行い共焦点レーザー顕微鏡(CLSM)で観察し検討した.プロラクチン産生腫瘍とされた10例ではPPAが8例,MSLAが2例であった.成長ホルモン産生腫瘍の10例ではMSLAは3例,MSAは4例,PGAが3例であった.非機能性腫瘍の10例では両ホルモンとも認められぬもの5例,PGAが2例,PPA,MSA,MSLAが1例ずつであった.これらの結果よりプロラクチン産生腫瘍ではPPAが多いが,成長ホルモン産生腫瘍ではMGPAが多く,そのうちでもMSAが大部分を占めていることがわかった.CLSMによる下垂体腺腫の観察の報告は今までなく,分泌穎粒の細胞内分布などもよく見え,二重染色による観察も簡便であり,下垂体腺腫の詳細な分類に役立つことがわかった.We retrospectively studied 30 pituitary adenomas to determine the intracellular distributions of prolactin (PRL) and growth hormone (GH) on the same section by double immunofluorescence staining and subsequent observation by confocal laser scanning microscopy (CLSM). The clinical presentations of these tumors were hyperprolactinemia (10 cases), acromegaly (10 cases), and nonfunctioning (10 cases). Of the 10 cases of hyperprolactinemia, 8 were pure PRL- secreting adenomas and 2 were mixed somatotroph-lactotroph adenomas (MSLA). Of the 10 cases of acromegaly, 3 were MSLA, 4 were mammosomatotroph adenomas (MSA), and 3 were pure GH-secreting adenomas. Among the 10 nonfunctioning tumors, there were 2 pure GH-secreting adenomas, one pure PRL-secreting adenoma, one MSA, one MSLA, and 5 negative cases for both PRL and GH. We conclude that pituitary adenomas with clinical hyperprolactinemia are mostly pure PRL-secreting adenomas, whereas those with acromegaly are mostly mixed PRL-GH-secreting adenoma. In addition, pituitary adenomas without clinical endo-crinopathy have diverse hormonal expressions. The method we used in this study by CLSM is technically easy and thus can be performed on a routine basis for more definite classifications of pituitary adenomas

共焦点レーザー顕微鏡(CLSM)を用いた下垂体腺腫の免疫組織化学的検討

下垂体腺腫のうち成長ホルモンとプロラクチン産生腫瘍は一般的にはpure growth hormone secreting adenoma(PGA), pure prolactin secreting adenoma(PPA)とmixed growth hormoneprolactin secreting adenoma(MGPA)に分類されている.更に詳細に分類するとMGPAはacidophil stem cell adenoma(ASCA), mammosomatotroph adenoma(MSA),およびmixed somatotroph-lactotroph adenoma(MSLA)に分けられている。ASCAとMSAは両ホルモンを持っている細胞からなる腫瘍で,MSLAは両ホルモンをそれぞれ別々の細胞が産生している腫瘍といわれている.今回30例の下垂体腺腫の手術例についてこのような詳細な検討をするため,両ホルモンの細胞内分布について二重標識蛍光抗体法を行い共焦点レーザー顕微鏡(CLSM)で観察し検討した.プロラクチン産生腫瘍とされた10例ではPPAが8例,MSLAが2例であった.成長ホルモン産生腫瘍の10例ではMSLAは3例,MSAは4例,PGAが3例であった.非機能性腫瘍の10例では両ホルモンとも認められぬもの5例,PGAが2例,PPA,MSA,MSLAが1例ずつであった.これらの結果よりプロラクチン産生腫瘍ではPPAが多いが,成長ホルモン産生腫瘍ではMGPAが多く,そのうちでもMSAが大部分を占めていることがわかった.CLSMによる下垂体腺腫の観察の報告は今までなく,分泌穎粒の細胞内分布などもよく見え,二重染色による観察も簡便であり,下垂体腺腫の詳細な分類に役立つことがわかった.We retrospectively studied 30 pituitary adenomas to determine the intracellular distributions of prolactin (PRL) and growth hormone (GH) on the same section by double immunofluorescence staining and subsequent observation by confocal laser scanning microscopy (CLSM). The clinical presentations of these tumors were hyperprolactinemia (10 cases), acromegaly (10 cases), and nonfunctioning (10 cases). Of the 10 cases of hyperprolactinemia, 8 were pure PRL- secreting adenomas and 2 were mixed somatotroph-lactotroph adenomas (MSLA). Of the 10 cases of acromegaly, 3 were MSLA, 4 were mammosomatotroph adenomas (MSA), and 3 were pure GH-secreting adenomas. Among the 10 nonfunctioning tumors, there were 2 pure GH-secreting adenomas, one pure PRL-secreting adenoma, one MSA, one MSLA, and 5 negative cases for both PRL and GH. We conclude that pituitary adenomas with clinical hyperprolactinemia are mostly pure PRL-secreting adenomas, whereas those with acromegaly are mostly mixed PRL-GH-secreting adenoma. In addition, pituitary adenomas without clinical endo-crinopathy have diverse hormonal expressions. The method we used in this study by CLSM is technically easy and thus can be performed on a routine basis for more definite classifications of pituitary adenomas

成人低悪性度星細胞腫の再発・悪性転化の予測に関する組織学的研究 : 再発時にMIB-1とp53遺伝子産物発現について

悪性度の低い星細胞腫が,悪性に転化して,きわめて不良な予後を示すことがあることは臨床的にしばしば経験することである.初回手術時に低悪性度の星細胞腫と判断された腫瘍が悪性化するか否かを予測することは臨床上きわめて重要である.本研究では,この予測を可能にすることができるか否かを明らかにするために,再発なしに良好な経過をたどっている症例と悪性転化して再発した症例について,初回手術,ならびに再発時に得られた腫瘍標本について病理組織学的検討を行った.WHO分類で診断が確定したastrocytoma grade II (low grade astrocytoma)30例のうち,再発20例,非再発10例を検討した.再発例と非再発例の低悪性度星細胞腫(low grade astrocytoma)の手術時に得られた組織を用い,HE染色,MIB-1とp53免疫染色を行った.初発時(手術),再発時(再発手術の行われた例のみ),再再発時の手術で摘出した腫瘍組織切片について,それぞれの組織切片で細胞密度の高い部位5カ所を選んで検鏡し,1mm^2あたりのHE染色による腫瘍細胞数NTC(numbers of tumor cells),およびMIB-1とp53の免疫染色陽性細胞指数SI(staining index)を測定した.HE染色のNTC,MIB-1とp53のSIおよび悪性度G(grade),再発までに要した時聞t(recurrence time)の相互の関連性について検討した.初発時および再発時のHE染色による細胞数と腫瘍の悪性度,再発までの時間には有意差は認められなかった.再発例(π=20)ではMIB-1のSIと再発について分析するとMIB-1 SIの高いほど悪性化して再発しやすく(SI 5.75～21.56%),p53 SIの低いほど再発しやすい(SI 6.20～44.53%).非再発例(π=10)ではMIB-1のSIが似値で(SI 0.98 ± 0.90%,p<0.05),p53のSIが高値であった(SI 28.47 ± 7.14%,p<0.05).腫瘍の悪性化,再発を予知する指標としては,細胞密度,MIB-1およびp53のSI値が重要な指数と考えられた.腫瘍再発を予知するためには,増殖と抑制双方の因子のバランスを検討することが必要である.Low grade astrocytomas generally have a good prognosis and the patients can survive a long time without recurrence. It is, however, well known that some low grade astrocytomas can show malignant transformation and they recur in a rather short period. These tumors demonstrate the characteristics of anaplastic astrocytoma or glioblastoma at the time of recurrence. As it is important to predict whether malignant transformation or recurrence will occur after the first operation, we have studied the histopathological characteristics of nonrecurrent and recurrent adult low grade astrocytomas. The population density of hematoxylin-eosin stained tumor cells and MIB-1 and the p53 immuno-stained index (SI) of parafin embedded surgical samples taken from 20 recurrent and 10 non-recurrent cases of low grade astrocytoma (grade II) were histopathologically studied. The numbers of stained tumor cells per 1 mm^2 (SI) were counted from the average population density per 1 mm^2 in 5 quadratic grids of the microscopic field. Formalin-fixed paraffin-embedded tissue sections were immunohistochemically stained for MIB-1 and p53. No correlation was noted between the age of the patients, the recurrence and the recurrence time. Male patients seemed to be more susceptible to recurrence than females. In the majority of recurrent cases, the SI of MIB-1 was higher and the SI of p53 was lower than that observed in the non-recurrent cases at the time of the initial operation. As a statistically significant difference in the SI of MIB-1 and SI of p53 was found between the non-recurrent and recurrent astrocytomas at the time of the first operation, such analysis might be valuable for prediction of the recurrence of low grade astrocytoma

脳動脈瘤を伴ったラトケ嚢胞5症例の経験

ラトケ嚢胞は,画像診断技術の発達に伴い近年報告例が増加している腫瘍である.しかしラトケ嚢胞と脳動脈瘤の合併の報告例は少なく,我々の渉猟し得た範囲では過去2例の文献報告をみるのみである.1980年より1997年7月までに我々の施設および関連病院においてラトケ嚢胞と診断されたものは38症例である.これらのうち動脈瘤を合併した症例を5例経験したので報告する.2例は下垂体部腫瘍症例に術前検査として脳血管撮影を施行したところ動脈瘤が偶然に発見された症例である.3例はくも膜下出血で発症し,そのクリッピング手術の際に,嚢胞性腫瘍が鞍上部に偶然発見されたものである.全症例について切除標本に対し病理学的検査を施行し,ラトケ嚢胞と診断した.ラトケ嚢胞に対する脳動脈瘤の合併頻度は不明であるが,我々はラトケ嚢胞38症例中5例(13%)と高率に動脈瘤の合併を経験した.下垂体腺腫においては約7%に脳動脈瘤の合併を認めるとの報告がなされているが,ラトケ嚢胞についても脳動脈瘤の合併は稀なものではないと考えられた.我々の経験した症例数は,いまだ十分ではなく今後の症例の積重ねが必要と考えられるが,下垂体部の腫瘍を認めた際には脳動脈瘤の存在を考慮し,脳血管撮影を施行すべきと考えられた.また,近年のMRAや3次元CTの進歩により,より非侵襲的に動脈瘤の合併を検索することが可能となってきセいると考えられる.ラトケ嚢胞は良性腫瘍であるが,視神経障害や下垂体機能低下といつた症候を伴うものは積極的な外科治療の必要性を有するものと考えられる.しかし,正常下垂体と腫瘍の位置関係や合併する動脈瘤の位置などにつき,十分に術前検討を加えることが必要と考える.くも膜下出血で発症し偶然ラトケ嚢胞が発見された場合には,術者の疲労度や時間的余裕を考慮して,可能ならば嚢胞切除を行うことが望ましいと考える.Over the past few decades a considerable numbers of studies have been made on Rathke's cleft cyst. Cerebral aneurysm occurs in approximately 7% of patients with pituitary adenoma, but the factual incidence of Rathke's cleft cyst with cerebral aneurysm remains an open question. To the authors knowledge, only a few reports have been reported in the literature concerning such a combined lesion. From 1980 to July 1997, we have experienced 38 cases of Rathke's cleft cyst. These included 16 males and 22 females with a mean age of 42.5 years (range 11-73 years). They were obtained from the Tokyo Women's Medical College Hospital and its affiliated hospitals to treat Rathke's cleft cyst by surgical procedure and histological verification. We have experienced with five cases (13%) in 38 patients. Our data show that, as compared with pituitary adenoma, incidence of Rathke's cleft cyst associated with cerebral aneurysm was not rare than we have considered previously. Our study documents the necessity and importance of cerebral angiography in patient with tumor of the sellar region prior to the surgical procedure

脳動脈瘤を伴ったラトケ嚢胞5症例の経験

ラトケ嚢胞は,画像診断技術の発達に伴い近年報告例が増加している腫瘍である.しかしラトケ嚢胞と脳動脈瘤の合併の報告例は少なく,我々の渉猟し得た範囲では過去2例の文献報告をみるのみである.1980年より1997年7月までに我々の施設および関連病院においてラトケ嚢胞と診断されたものは38症例である.これらのうち動脈瘤を合併した症例を5例経験したので報告する.2例は下垂体部腫瘍症例に術前検査として脳血管撮影を施行したところ動脈瘤が偶然に発見された症例である.3例はくも膜下出血で発症し,そのクリッピング手術の際に,嚢胞性腫瘍が鞍上部に偶然発見されたものである.全症例について切除標本に対し病理学的検査を施行し,ラトケ嚢胞と診断した.ラトケ嚢胞に対する脳動脈瘤の合併頻度は不明であるが,我々はラトケ嚢胞38症例中5例(13%)と高率に動脈瘤の合併を経験した.下垂体腺腫においては約7%に脳動脈瘤の合併を認めるとの報告がなされているが,ラトケ嚢胞についても脳動脈瘤の合併は稀なものではないと考えられた.我々の経験した症例数は,いまだ十分ではなく今後の症例の積重ねが必要と考えられるが,下垂体部の腫瘍を認めた際には脳動脈瘤の存在を考慮し,脳血管撮影を施行すべきと考えられた.また,近年のMRAや3次元CTの進歩により,より非侵襲的に動脈瘤の合併を検索することが可能となってきセいると考えられる.ラトケ嚢胞は良性腫瘍であるが,視神経障害や下垂体機能低下といつた症候を伴うものは積極的な外科治療の必要性を有するものと考えられる.しかし,正常下垂体と腫瘍の位置関係や合併する動脈瘤の位置などにつき,十分に術前検討を加えることが必要と考える.くも膜下出血で発症し偶然ラトケ嚢胞が発見された場合には,術者の疲労度や時間的余裕を考慮して,可能ならば嚢胞切除を行うことが望ましいと考える.Over the past few decades a considerable numbers of studies have been made on Rathke\u27s cleft cyst. Cerebral aneurysm occurs in approximately 7% of patients with pituitary adenoma, but the factual incidence of Rathke\u27s cleft cyst with cerebral aneurysm remains an open question. To the authors knowledge, only a few reports have been reported in the literature concerning such a combined lesion. From 1980 to July 1997, we have experienced 38 cases of Rathke\u27s cleft cyst. These included 16 males and 22 females with a mean age of 42.5 years (range 11-73 years). They were obtained from the Tokyo Women\u27s Medical College Hospital and its affiliated hospitals to treat Rathke\u27s cleft cyst by surgical procedure and histological verification. We have experienced with five cases (13%) in 38 patients. Our data show that, as compared with pituitary adenoma, incidence of Rathke\u27s cleft cyst associated with cerebral aneurysm was not rare than we have considered previously. Our study documents the necessity and importance of cerebral angiography in patient with tumor of the sellar region prior to the surgical procedure