Yang Eric J, Mutter George L
Department of Pathology, Division of Women's and Perinatal Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Mod Pathol. 2015 Jun;28(6):830-5. doi: 10.1038/modpathol.2015.35. Epub 2015 Feb 20.
Uterine leiomyosarcomas are rare malignant tumors with a poor prognosis while leiomyomas are common benign tumors unrelated to their malignant counterparts. Diagnostic features commonly present in leiomyosarcoma include cytologic atypia, high mitotic index, and a sarcoma-specific geographic cell death designated 'tumor cell necrosis (TCN)'. TCN has a sharp viable-nonviable boundary lacking inflammation, fibrosis or granulation tissue seen in nonspecific infarction. These characteristics are sometimes difficult to interpret on routine hematoxylin and eosin slides, and can lead to diagnostic errors. In this study, we used extracellular matrix stains to test the hypothesis that the host response which characterizes nonspecific infarction may degrade the matrix in infarcted tumor more than in TCN. A 'honeycomb' pattern of reticulin highlighted individual tumor cells in viable regions of all cases. Nonviable area of reticulin patterns differed significantly by diagnosis (P<0.001), with a honeycomb pattern maintained (91%, 20/22) in leiomyosarcoma and lost (61%, 11/18) in leiomyomas. Retention of honeycomb reticulin in nonviable areas of leiomyosarcoma occurred irrespective of the presence of inflammation, hemorrhage, fibrosis, or diffuse hyalinization. Fibrosis/hyalinization as evidenced by trichrome stain was significantly (P<0.001) more common in nonviable areas of benign leiomyomas (100%, 18/18) compared with leiomyosarcomas (36%, 8/22). In those occasions where viable tissues contained discernable polarization of mitotic activity, these decreased toward the nonviable interface in leiomyosarcoma, and had an opposite pattern in leiomyomas, increasing toward the interface. There is a significant difference in the reticulin and collagen networks of nonviable areas of leiomyosarcoma compared with leiomyoma. At the time of early injury, both retain reticulin; however, this is cleared over time in benign, but not malignant, areas of necrosis. We conclude that proliferative repair of leiomyomas at the viable-nonviable interface includes remodeling of the extracellular matrix, in contrast to the static preservation of extracellular matrix ('mummification') in nonviable areas of leiomyosarcomas.
子宫平滑肌肉瘤是罕见的恶性肿瘤，预后较差，而平滑肌瘤是常见的良性肿瘤，与恶性肿瘤无关。平滑肌肉瘤常见的诊断特征包括细胞异型性、高有丝分裂指数以及一种肉瘤特异性的局灶性细胞死亡，称为“肿瘤细胞坏死（TCN）”。TCN有一个清晰的存活-非存活边界，没有非特异性梗死中所见的炎症、纤维化或肉芽组织。这些特征在常规苏木精和伊红染色切片上有时难以解释，可能导致诊断错误。在本研究中，我们使用细胞外基质染色来检验这一假设，即表征非特异性梗死的宿主反应对梗死肿瘤中基质的降解可能比对TCN中的降解更严重。网状纤维的“蜂窝”模式突出了所有病例存活区域中的单个肿瘤细胞。网状纤维模式的非存活区域在诊断上有显著差异（P<0.001），平滑肌肉瘤中维持“蜂窝”模式（91%，20/22），而平滑肌瘤中则消失（61%，11/18）。平滑肌肉瘤非存活区域中蜂窝状网状纤维的保留与炎症、出血、纤维化或弥漫性玻璃样变的存在无关。与平滑肌肉瘤（36%，8/22）相比，经三色染色证实的纤维化/玻璃样变在良性平滑肌瘤的非存活区域（100%，18/18）中显著更常见（P<0.001）。在那些存活组织中含有可辨别的有丝分裂活性极化的情况下，这些极化在平滑肌肉瘤中朝着非存活界面减少，而在平滑肌瘤中则呈现相反的模式，朝着界面增加。与平滑肌瘤相比，平滑肌肉瘤非存活区域的网状纤维和胶原网络存在显著差异。在早期损伤时，两者都保留网状纤维；然而，随着时间的推移，这种网状纤维在良性坏死区域中被清除，而在恶性坏死区域中则不会。我们得出结论，平滑肌瘤在存活-非存活界面的增殖性修复包括细胞外基质的重塑，这与平滑肌肉瘤非存活区域中细胞外基质的静态保存（“木乃伊化”）形成对比。
