侵袭性曲霉菌及毛霉菌性鼻---鼻窦炎临床病理学分析

Clinicopathologic study of invasive fungal rhinosinusitis caused by AspergiUus and Mucorales

目的观察曲霉菌及毛霉菌侵袭黏膜组织引起侵袭性真菌性鼻一鼻窦炎（IFRS）临床病理学特点的异同，探讨两种真菌组织损伤的致病机制。方法收集经组织学及培养证实为曲霉菌性IFRS19例（Aspergillus，A组）、毛霉菌性IFRS16例（Mucorales，M组）患者的临床资料进行回顾性分析，并对其病理形态进行观察。用HE染色观察真菌侵袭组织的方式及组织损伤的特点，用六胺银（GMS）、过碘酸一雪夫（PAS）染色显示侵入组织内真菌的形态特征。结果A组临床病程为急性4例，慢性15例；有基础疾病患者13例（糖尿病4例，恶性肿瘤5例，外伤史1例，慢性上颌窦炎行上颌窦根治术后3例），无基础疾病6例。随访13例，死亡7例，死于真菌性脑病4例，死于基础疾病3例。M组临床病程为急性14例，慢性2例；有基础疾病14例（糖尿病8例，恶性肿瘤5例，智齿冠周炎行智齿拔除1例），2例患者无基础疾病。随访14例，死亡7例，4例死于真菌性脑病。两组临床病程差异有统计学意义（P=0．01），两组基础疾病分布及病死率差异无统计学意义（P〉0．05）。病理学观察：A组：真菌成团生长，附于黏膜表面，附着处黏膜浅层呈条带状坏死（11／19）；类上细胞肉芽肿明显（13／19），单个多核巨细胞少见；黏膜深部坏死、真菌性肉芽肿（3／19）、血管炎及菌栓少见（4／19）。M组：黏膜大片彻底凝固性坏死（13／16），多呈地图状、可累及黏膜深部，其内可见肿胀变形的真菌（散在、成簇）；单个多核巨细胞多见，也可聚集形成肉芽肿，其内可见真菌（16／16）；血管炎、血栓多见（10／16）。结论IFRS时毛霉菌侵袭力较强，以引起急性侵袭型和组织大片坏死多见；曲霉菌侵袭组织相对较慢，临床多以慢性侵袭型为主，镜下以肉芽肿为多见，但两者长期病死率未见明显差异；其机制可能与菌体成分有关。

Objective To compare the differences in clinicopathologic features of invasive fungal rhinosinusitis caused by Aspergillus and Mucorales, and to discuss the pathogenesis of tissue injury induced by these two kinds of fungi. Methods The clinical and pathologic features of 19 patients with invasive fungal rhinosinusitis due to Aspergillus （group A） and 16 patients with invasive fungal rhinosinusitis due to Mucorales （group M ） were retrospectively reviewed. HE, PAS and GMS stains were performed on all the paraffin-embedded tissues. The diagnosis was confirmed by histologic examination and microbiological culture results. Results Amongst the group A patients, the clinical course was acute in 4 cases and chronic in 15 cases. Thirteen cases had underlying predisposing conditions, including diabetes （number = 4）, malignant tumor （ number = 5 ）, history of trauma （ number = 1 ） and radical maxillary sinus surgery （number =3）. Follow-up information was available in 13 patients. Seven of them died, 4 due to fungal encephalopathy and 3 due to underlying diseases. Amongst the group M patients, the clinical course was acute in 14 cases and chronic in 2 cases. Fourteen cases had underlying predisposing conditions, including diabetes （ number = 8 ）, malignant tumor （ number = 5 ） 1 ）. Follow-up information was available in 14 patients. and history of wisdom tooth extraction （ number = Four of them died of fungal encephalopathy. Therewas significant difference in clinical onset between the two groups （ P = 0. 01 ）. There was however no difference in terms of underlying predisposing conditions and disease mortality. Histologically, the microorganisms in group A patients formed fungal masses and attached to the mucosal surface, resulting in necrotic bands （11/19）. Epithelioid granulomas were conspicuous but multinucleated giant cells were relatively rare. Deep-seated necrosis, granulomatous inflammation against fungal organisms （3/19） and vasculitis with thrombosis （4/19） were not common. On the other hand, large areas of geographic necrosis involving deep-seated tissue could be seen in group M patients （13/16）. Isolated multinucleated giant cells were commonly seen. Granulomatous inflammation against fungal organisms were identified （16/16）. Vasculitis and thrombosis were also observed （ 10/16）. Conclusions The invasiveness of Mucorales is remarkable; and when it causes invasive fungal rhinosinusitis, the clinical course is often acute and large areas of tissue necrosis can be seen. The invasiveness of Aspergillus in tissue is relatively mild. Granulomas are more common and the disease often runs a chronic clinical course. There is however no significant difference in long-term mortality. The pathogenesis may be related to the different components of the fungi.