消化管GISTの診断と悪性度の評価―組織分類と予後からみて

Diagnosis and Evaluation of Malignancy of Gsatrointestinal Stromal Tumor (GIST)― From the Aspect of Histological Classification and Prognosis

要旨　GISTの概念・分類に関しては，現在広くWHOの定義，分類が使用されているが，今なおそれにもいくつかの臨床病理学的問題点が指摘されている．われわれはGIST 124例を含むGIMT 262例を，c-kitを含めた免疫染色結果に基づきMuscle cell（M）type97例，Neural cell（N）type0例，Cajal cell（C）type103例，Mixed cell（Mixed）type（M＋C，N＋C，M＋N，M＋N＋C）41例，Undifferentiated cell（U）type21例の5型に分類し，この5型の悪性度と予後，およびGIST（CとU型）の主として腫瘍径，発育形式，細胞密度，核分裂数，Ki-67 labeling indexなどの悪性度の指標につき検索した．その結果，M型は97.9％が良性であるのに対し，C型の78.6％およびU型の95.2％は悪性ないし境界領域であった．また予後ではC型，Mixed型，およびU型はM型と比較し有意に予後不良であった．また，GISTの悪性度の評価に関しては，2cmを超える腫瘍径，Skandalakis分類の壁内型発育以外の発育（管内型，管外型，混合型発育），細胞密度高度，400倍50視野で5個以上の核分裂数，Ki-67 labeling indexなどが悪性度の指標となりうるとの結果であった．このことからわれわれの5型分類はある程度の予後予測にも有用と考えた．そして，これらの因子の多変量解析の結果，独立かつ有意な因子は発育形式と腫瘍径であることが判明したので，GISTの最も重要な悪性度の指標は発育形式と腫瘍径であると結論した．

　Classification of gastrointestinal stromal tumors (GISTs) in a broad sense has undergone a change from the Rosai classification to the WHO classification, but, clinicopathological problems still remain. On the basis of the results of immunostaining, including c-kit, we classified GIST lesions into 5 types, namely, the smooth muscle (M) type, neural cell (N) type, Cajal cell (C) type, Mixed cell (Mixed) type (M＋C, N＋C, M＋N, and M＋N＋C), and undifferentiated cell (U) type. We compared the pathological features (tumor size, growth pattern, cellularity, mitotic rate, and Ki-67 labeling index) in malignancy and C type and U type, and investigated the correlations between the malignancy grade of each type, and the prognosis. A total of 262 lesions that were excised and diagnosed as GIST in a broad sense at our hospital or affiliated institutions between July, 1989 and August 2001 were included in the analysis. The immunohistochemical classification was conducted using 15 types of antibodies, including desmin, α-SMA, calponin, S-100, CD34, and c-kit. With regard to the histological classification of malignancy, 95 (97.9％) of the 97 M-type lesions were benign, while 30 (73.2％) of the 41 mixed-cell type lesions, 81 (78.6％) of the 103 C-type lesions, and 20 (95.2％) of the 21 U-type lesions were borderline or malignant tumors. The 5-year survival rate of the patients with the M type, C type, Mixed type, and U type of tumors was 100％, 87.5％, 80.0％, and 81.8％, respectively. Analysis of the prognosis revealed that there was no significant difference in the prognosis among the C, Mixed type and U type of tumors. On the other hand, the prognosis of the M type was significantly better than that of the C, Mixed and U types of tumors. In addition, as a result of multivariate analysis of the above factors, it was found that growth pattern and tumor size was an independent and significant factor. Thus, it was concluded that the most important malignancy criterion of GIST are growth pattern and tumor size.