An ultrastructural and immunohistochemical study of a combined submucosal granular cell tumor and lipoma of the colon showing a unique nodule-in-nodule structure: putative implication of CD34 or prominin-2-positive stromal cells in its histopathogenesis
An ultrastructural and immunohistochemical study of a combined submucosal granular cell tumor and lipoma of the colon showing a unique nodule-in-nodule structure: putative implication of CD34 or prominin-2-positive stromal cells in its histopathogenesis
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结肠黏膜下颗粒细胞瘤和脂肪瘤联合的超微结构和免疫组织化学研究显示独特的结节中结节结构：CD34 或 prominin-2 阳性基质细胞在其组织病理学中的推定意义
DOI：
10.1007/s00428-006-0210-9
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发表时间：
2006
期刊：
影响因子：
3.5
通讯作者：
K. Yamazaki
中科院分区：
文献类型：
--
作者：
Taisuke Mori;H. Orikasa;T. Shigematsu;K. Yamazaki
我们的患者是一名 55 岁的日本男性，作为常规健康检查的一部分，他接受了结肠镜检查。在盲肠中发现白色息肉样病变（图 1a，插图）。怀疑良性粘膜下肿瘤，例如类癌瘤或脂肪瘤，并通过内窥镜切除病变。切除的标本尺寸为 9×6 毫米（图 1a，插图）。肿瘤的低倍光学显微镜检查显示结肠粘膜下层成熟脂肪细胞呈结节状增殖（图1a），没有明确的纤维包膜。在增生性粘膜下脂肪瘤结节中，一簇小纤维状颗粒细胞瘤位于稍增厚的粘膜肌层下方的脂肪瘤结节上（图1a），形成结节中结节（脂肪瘤结节中的颗粒细胞瘤结节）结构（图1a）。在较小的颗粒细胞瘤结节中，具有丰富、细颗粒、透明细胞质的肿瘤细胞以肺泡状或束状形式形成细胞巢，有时靠近周围神经纤维束（图1b）。颗粒细胞瘤的细胞外间质组织中可见致密的纤维状胶原、梭形或星状间质细胞和一些小脉管血管（图1b）。颗粒细胞瘤和脂肪瘤组织之间的界限不明确，由混合的纤维间质组成，其中含有丰富的梭形或星状间质细胞（图1b）。大多数免疫组织化学特征与许多先前对颗粒细胞瘤和脂肪瘤免疫组织化学特征的文字描述一致。简而言之，通过用非免疫性免疫球蛋白G替代一抗来制备阴性对照。外部器官作为阳性对照。 CD34在内皮细胞中表达，prominin-2在成人肾脏和消化道的正常上皮细胞中表达。颗粒细胞肿瘤细胞表达雪旺细胞的各种神经源性标志物，包括 S-100、神经元特异性烯醇化酶和 CD56。神经元或神经内分泌细胞的其他神经源性标志物特征也呈弱阳性，例如突触素和嗜铬粒蛋白。在颗粒细胞瘤成分的细胞中也检测到吞噬体或吞噬细胞标记物（CD68）的强表达。 CD34的阳性表达不仅在小脉管系统的内皮细胞中观察到，而且在梭形或星状基质细胞中也观察到。 CD34 和/或 prominin-2 免疫组织化学染色呈阳性的纺锤形或星状基质细胞在肿瘤结节中比结肠壁其他非肿瘤区域更明显。（图 1a）。然而，在纺锤形或星形基质细胞中未观察到c-kit、肌源性细胞标记物（例如α平滑肌肌动蛋白、HHF35的肌动蛋白、结蛋白和MEF-2）和CD10的表达。颗粒细胞瘤细胞巢中的一些纺锤形或星状基质细胞被抗prominin-2抗体标记（图1c）。透射电镜对颗粒细胞瘤组织标本进行超微结构检查，可见颗粒细胞瘤细胞呈肺泡状聚集，胞质较清晰，有薄层界限。
Our patient, a 55-year-old Japanese man, underwent colonoscopic examination as part of a routine health check. A whitish, polypoid lesion was found in the cecum (Fig. 1 a, inset). Benign, submucosal tumor, such as a carcinoid tumor or a lipoma, was suspected and the lesion was resected endoscopically. The excised specimen measured 9× 6 mm in size (Fig. 1 a, inset). Low-power light microscopic examination of the tumor revealed nodular proliferation of mature fat cells in the submucosal layer of the colon (Fig. 1 a) without a definitive fibrous capsule. In the proliferative submucosal lipomatous nodule, a cluster of small fibrous granular cell tumors was sitting upon the lipoma nodule beneath the slightly thickened layer of the muscularis mucosa (Fig. 1 a), forming a nodule-in-nodule (a granular cell tumor nodule in a lipoma nodule) structure (Fig. 1 a). In the smaller granular cell tumor nodule, tumor cells with rich, finely granulated, clear cytoplasm formed cell nests in an alveolar or fasciculated pattern, sometimes in proximity to bundles of peripheral nerve fibers (Fig. 1 b). Dense fibrous collagen, spindle-shaped or stellate stromal cells, and some small vasculature blood vessels were seen in the extracellular stromal tissue of the granular cell tumor (Fig. 1 b). The boundary between the granular cell tumor and the lipoma tissue was not well defined, which consisted of mixed intervening fibrous stroma containing abundant spindleshaped or stellate stromal cells (Fig. 1 b). Most of the immunohistochemical characteristics were consistent with many previous literal descriptions of the immunohistochemical characteristics of granular cell tumors and lipomas. Briefly, negative controls were prepared by substituting the primary antibodies with nonimmunune immunoglobulin G. External organs served as positive controls. CD34 was expressed in endothelial cells, and prominin-2 was expressed in normal epithelial cells of the adult kidney and digestive tract. The granular cell tumor cells expressed various neurogenic markers of Schwann cells, including S-100, neuron-specific enolase, and CD56. Other neurogenic markers characteristic of neurons or neuroendocrine cells were also faintly positive, eg, synaptophysin and chromogranins. Strong expression of markers of phagosomes or phagocytes (CD68) was also detected in the cells of the granular cell tumor component. Positive expression of CD34 was observed not only in the endothelial cells of the small vasculature, but also in the spindle-shaped or stellate stromal cells. Spindle-shaped or stellate stromal cells showing positive immunohistochemical staining for CD34 and/or prominin-2 were more conspicuous in the tumor nodules than other nontumorous areas of the colonic wall.(Fig. 1 a). However, no expression of c-kit, myogenic cell markers (eg alpha smooth muscle actin, muscle actin of HHF35, desmin, and MEF-2), and CD10 was observed in the spindle-shaped or stellate stromal cells. A few spindle-shaped or stellate stromal cells among the cell nests of granular cell tumor were labeled by the antiprominin-2 antibody (Fig. 1 c). Ultrastructual examination of the granular cell tumor tissue specimens by transmission electron microscope revealed alveolar aggregations of granular cell tumor cells with rather clear cytoplasm demarcated by thin