恶性颗粒细胞瘤10例临床病理学观察及文献复习

目的 探讨恶性颗粒细胞瘤的临床病理学特征,评价组织学上诊断恶性的标准。方法 对10例恶性颗粒细胞瘤的临床资料和组织学形态进行回顾性分析,并采用免疫组织化学(LSAB法)和电镜检测研究其免疫表型和超微结构。结果男性4例,女性6例,年龄范围为27～73岁(平均46岁)。临床上,9例表现为皮下或深部软组织内无痛性生长的孤立性肿块,其中1例伴有周围神经症状。肿瘤位于下肢3例,乳腺2例,项部2例,胸壁、右颈部和盆腔者各1例。肿瘤直径2～11cm,平均4．8cm。镜下由成巢或成片的多边形细胞组成,胞质呈嗜伊红色颗粒状,与良性性颗粒细胞瘤极为相似,但仔细观察发现,9例显示至少下述形态中的3种：核增大呈空泡状并可见明显的核仁;多形性瘤细胞;核质比增大;瘤细胞趋向梭形;可见核分裂象;凝固性坏死。除经典性形态外,1例尚可见散在的多核性瘤细胞。余1例除局部区域显示核增大呈空泡状并可见明显的核仁外,其余形态均不明显,但临床上却呈恶性经过。9例均强阳性表达S-100蛋白和神经元特异性烯醇化酶(NSE),7例尚表达CD68。电镜观察显示瘤细胞胞质内充满大量退变的复合性溶酶体。随访7例,5例复发,4例转移,2例死于肿瘤。结论 (1)Fangburg-Smith等的组织学恶性标准具有较高的可重复性,但在少数情形下,最终诊断仍需结合肿瘤的生物学行为;(2)提议将核分裂象的标准修订为＞5／50HPF;(3)广泛性局部切除加上必要的区域淋巴结清扫仍是目前最主要的治疗手段,辅助性化疗和(或)放疗并不能明显改善患者的预后;(4)描述一种尚未见报道的多核性瘤细胞形态亚型。

Malignant granular cell tumor: a clinicopathologic analysis of 10 cases with review of literature

OBJECTIVE: To investigate the clinicopathologic features of malignant granular cell tumor (MGCT) and evaluate the histologic criteria for diagnosis of malignancy. METHODS: The clinical and pathologic profiles of 10 MGCT cases were evaluated. Immunohistochemical study was performed on paraffin sections of 9 cases. Electron microscopy was carried out in 3 cases with available fresh or formalin-fixed tissues. The biologic behavior was analyzed with follow-up data. RESULTS: Four patients were males and six were females. Their age ranged from 27 to 73 years (mean = 46 years). The main presenting symptom was a painless nodule or mass located in the subcutis or deep soft tissue. One case had peripheral nerve symptoms. Three of the tumors occurred in the lower extremity, two in the breast, two in the nuchal region, and one each in the chest wall, neck, and peritoneal cavity. The tumor size ranged from 2 to 11 cm (mean size = 4.8 cm). Microscopically, the tumor was composed of nests or sheets of polygonal cells which possessed abundant eosinophilic granular cytoplasm and closely resembled its benign counterpart. After careful assessment, 9 cases exhibited at least 3 of the following suspicious features: enlarged vesicular nuclei with prominent nucleoli, nuclear pleomorphism, high nuclear-to-cytoplasmic ratio, spindling of tumor cells, appreciable mitotic activity, and tumor necrosis. In addition, a hitherto undescribed feature characterized by multinucleated tumor cells was observed in 1 case. The remaining case demonstrated benign-appearing features but behaved in a malignant fashion. Immunohistochemical study showed positive staining for S-100 protein (9/9), neuron specific enolase (9/9) and CD68 (7/9). Electron microscopy demonstrated abundant intracytoplasmic autophagic vacuoles. Follow-up information available in 7 patients revealed local recurrence in 5, metastasis in 4 and tumor-related deaths in 2 patients. CONCLUSIONS: The histologic criteria for malignancy in GCTs established in 1998 by Fanburg-Smith et al. are reproducible in most instances. In exceptional circumstances, however, the diagnosis relies on clinicopathologic correlation. Based on the current study and literature review, a modified criterion of mitotic count (> 5/50 HPF instead of > 2/10 HPF) is recommended. Wide local excision with regional lymph node dissection remains the mainstay of treatment. Chemotherapy and radiotherapy however have not been shown to significantly improve the clinical course of the disease. The morphologic spectrum of MGCT also includes a rare multinucleated variant.