Le Brian H, Boyer Philip J, Lewis Jean E, Kapadia Silloo B
Department of Pathology, Penn State University College of Medicine, Hershey, Pa, USA.
Arch Pathol Lab Med. 2004 Jul;128(7):771-5. doi: 10.5858/2004-128-771-GCTIAO.
Granular cell tumor (GCT) is a rare tumor of nerve sheath origin with a predilection for upper aerodigestive tract, skin, and soft tissue. The neoplastic cells typically express S100 and CD68 (KP-1), the latter due to cytoplasmic lysosome content. However, the histogenesis of this tumor is unknown. Additionally, distinction between benign and malignant GCT is difficult because of histologic similarity and lack of reliable criteria that can predict clinical behavior.
To perform a comparative, side-by-side immunohistochemical assessment of the traditional immunohistochemical markers for GCTs (S100, CD68), along with the newer markers (inhibin-alpha, protein gene product 9.5) for these tumors.
To address diagnostic and prognostic issues, we studied 30 specimens of GCT (27 primary and 3 recurrent tumors, 2 of which occurred consecutively in the same patient) for (1) nuclear pleomorphism, prominent nucleoli, necrosis, spindling, high nuclear-cytoplasmic ratio, and mitoses; (2) immunohistochemical expression of inhibin-alpha, protein gene product 9.5, S100, CD68 (KP-1), and Ki-67 using the avidin-biotin complex method on formalin-fixed, paraffin-embedded sections; and (3) correlation between tumor grade, proliferative fraction, and clinical data.
Twenty-seven of 27 primary GCTs and 1 of 3 recurrent GCTs had typical histologic features, while the 2 consecutive recurrent GCT specimens from the same patient were atypical (moderate nuclear atypia and prominent nucleoli alone). The mean age for primary GCT was 37.3 years (range, 5-67 years), and mean size was 1.89 cm. None of the cases metastasized. All 30 specimens showed diffuse (2+ to 3+) staining for S100, CD68, and inhibin-alpha, and 3+ staining for protein gene product 9.5; pseudoepitheliomatous hyperplasia was nonreactive. The Ki-67 proliferative index was less than 1% to 20% in typical nonrecurrent cases, 1% in the typical recurrent case, and 1% and 10% in 2 sequential recurrences of the atypical case.
Our study expands the immunophenotype of GCT (S100, CD68, protein gene product 9.5, and inhibin-alpha) regardless of location and supports a neural origin. Intensity of immunohistochemical staining had no prognostic significance. Although 1 of the 2 recurrent GCTs had atypical features, the Ki-67 proliferative index did not distinguish reliably between typical (nonrecurrent) and atypical or recurrent GCTs. The significance of inhibin expression with regard to cell differentiation and pathogenesis is unclear and warrants further investigation.
颗粒细胞瘤（GCT）是一种罕见的神经鞘源性肿瘤，好发于上呼吸消化道、皮肤和软组织。肿瘤细胞通常表达S100和CD68（KP-1），后者因细胞质溶酶体含量而表达。然而，该肿瘤的组织发生尚不清楚。此外，由于组织学相似且缺乏可预测临床行为的可靠标准，良性和恶性GCT的鉴别较为困难。
对GCT的传统免疫组化标志物（S100、CD68）以及这些肿瘤的新标志物（抑制素α、蛋白基因产物9.5）进行对比的、并列的免疫组化评估。
为解决诊断和预后问题，我们研究了30例GCT标本（27例原发性和3例复发性肿瘤，其中2例在同一患者中连续发生），观察（1）核多形性、明显核仁、坏死、梭形化、高核质比和有丝分裂；（2）使用抗生物素蛋白-生物素复合物法对福尔马林固定、石蜡包埋切片进行抑制素α、蛋白基因产物9.5、S100、CD68（KP-1）和Ki-67的免疫组化表达检测；（3）肿瘤分级、增殖分数与临床数据之间的相关性。
27例原发性GCT中的27例和3例复发性GCT中的1例具有典型组织学特征，而同一患者的2例连续复发性GCT标本不典型（仅中度核异型性和明显核仁）。原发性GCT的平均年龄为37.3岁（范围5 - 67岁），平均大小为1.89 cm。所有病例均未发生转移。所有30例标本S100、CD68和抑制素α呈弥漫性（2 +至3 +）染色，蛋白基因产物9.5呈3 +染色；假上皮瘤样增生无反应。典型非复发病例的Ki-67增殖指数为1%至20%，典型复发病例为1%，非典型病例的2次连续复发分别为1%和10%。
我们的研究扩展了GCT的免疫表型（S100、CD68、蛋白基因产物9.5和抑制素α），无论其位置如何，并支持其神经起源。免疫组化染色强度无预后意义。尽管2例复发性GCT中有1例具有非典型特征，但Ki-67增殖指数并不能可靠地区分典型（非复发）与非典型或复发性GCT。抑制素表达在细胞分化和发病机制方面的意义尚不清楚，值得进一步研究。
