一只犬的不常见耳部肿瘤-病例报告

王帆

Uncommon ear tumor in a dog 

一只犬的不常见耳部肿瘤

作者：Sara Soto, Leonore Kuchler and Sylvie Wilhelm

 

翻译：许晓鸥

 

Case history 病史

A 13-year-old intact female Welsh springer spaniel was examined with a two month history of severe pruritus and strong odour from the right ear. Previous treatment for bacterial otitis with doxycyclin (doxycycline 50 g（商品名）, 50 g（商品）/kg per os, twice daily for 26 days) based on bacterial culture and susceptibility testing (Staphylococcus spp. And Corynebacterium spp.) and a routine ear cleanser failed to resolve the clinical signs. On physical examination, the right external ear canal was erythematous with light grey malodorous exudate. Routinely stained ear swabs revealed few neutrophils and numerous extracellular and intracellular coccoid bacteria. On video-otoscopic examination, the vertical canal showed an erythematous and friable mass filling the lumen at the transition to the horizontal canal up to the tympanic membrane (Figure 1).

一只13岁未绝育雌性威尔士史宾格犬，因有两个月的严重瘙痒和右耳强烈异味就诊。既往治疗史，根据细菌培养和药敏试验（葡萄球菌属和棒状杆菌属）使用多西环素（5mg/kg，口服，每日两次，持续26天）治疗细菌性耳炎，常规洗耳液未能解决临床症状。体格检查：右外耳道发红，伴有浅灰色恶臭分泌物。耳拭子常规染色显示少量中性粒细胞和大量细胞外和细胞内球菌。视频耳镜检查：垂直耳道可见一个发红和质脆的肿物，充满水平耳道直至鼓膜（图1）。

 

Questions提问：

What are your clinical differential diagnoses?

您的临床鉴别诊断是什么？

What diagnostic tests would you recommend?

您会推荐什么诊断检查？

Discussion讨论

The clinical findings were compatible with otitis externa (Staphylococcus spp. and Corynebacterium spp. infection) together with a suspected malignant tumour. Excision of the mass was attempted but not completely achieved. Two tissue samples were submitted for histopathological examination in order to confirm the clinical suspicion and to establish a prognosis and further treatment plan.

临床结果符合外耳炎（葡萄球菌属和棒状杆菌属感染）以及疑似恶性肿瘤。尝试切除肿块，但未能完全切除。提交2份组织样本进行组织病理学检查，以便证实临床诊断，并确立预后和进一步治疗方案。

 

Histologically (Figure 2), the dermis was infiltrated by an unencapsulated neoplasm reaching the samples’ surgical borders. The tumour was composed of two different cellular components. The main component consisted of spindle cells arranged in sheets in a moderate fibrovascular stroma. These cells had poorly demarcated cell borders, eosinophilic cytoplasm, an ovoid nucleus with finely stippled chromatin and moderate anisokaryosis. One mitosis was counted in ten 40 high-power fields [HPF; field number of the ocular (FN) 22 mm (0.237 mm2 )]. The second component consisted of epithelial polygonal cells arranged in variably sized tubules and papillae. These cells had eosinophilic cytoplasm and a rounded nucleus with one nucleolus and moderate-to-high anisokaryosis. Two mitoses were counted in ten 40 HPF [FN 22 mm (0.237 mm2 )] in this second cellular component.

组织学检查（图2），真皮被无包膜的肿瘤浸润，到达样本的手术边界。肿瘤由两种不同的细胞成份组成。主要成份由梭形细胞组成，成片排列于中度纤维血管间质中。这些细胞的细胞边界分界不清，细胞质嗜酸性，细胞核呈卵圆形，染色质呈细点状，核大小中度不等。在10个40倍高倍视野[HPF；视野计数(FN)22 mm(0.237 mm2)]中有1个有丝分裂。第二种成份由多边形上皮细胞组成，排列成大小不等的管型结构和乳头状结构。这些细胞具有嗜酸性细胞质和圆形细胞核，具有一个核仁和中度至高度核大小不均。在第二种细胞成份中，10个40倍HPF[FN 22 mm(0.237 mm2)]中有2个有丝分裂。

 

These microscopic features were compatible with a complex ceruminous adenocarcinoma (a ceruminous adenocarcinoma with a myoepithelial component) or, less likely, a spindle cell carcinoma. To the best of our knowledge, spindle cell carcinomas have been reported rarely in the skin of animals and not reported in the external ear. In order to assess the myoepithelial nature of the spindle cells, immunohistochemical analysis for the p63 antibody (Biocare-Medical, CM163C) together with the marker MNF-116 (pan-cytokeratin, Dako, M0821 01) was performed (Figure 3). The spindle neoplastic cells displayed strong cytoplasmic positivity for pan-cytokeratin and strong nuclear positive staining for p63, confirming a myoepithelial origin. The polygonal neoplastic cells were positive for pan-cytokeratin and negative for p63, as expected for epithelial cells. Although some carcinomas can display positivity with p63, a spindle cell carcinoma was excluded based on the presence of two components in the tumour with different morphologies and different immunohistochemical patterns. Based on these results, a complex ceruminous adenocarcinoma was diagnosed. Complex ceruminous adenocarcinomas have been reported uncommonly in dogs and rarely in other species. The benign or malignant nature of the myoepithelial cells in the present tumour was not clear based on morphology alone. Therefore, we assessed its proliferative capacity using immunohistochemical analysis for Ki-67 (Cell Marque, 275R-16). Our subjective impression was that the myoepithelial cells did not display remarkable proliferation and would most probably display benign behaviour. Complex and mixed (mixed: in addition to the epithelial and myoepithelial components, cartilage or bone also is present) ceruminous and apocrine adenocarcinomas have a better prognosis than the simple form of these tumours, although the prognosis is still guarded.

这些显微镜下特征符合复杂性耵聍腺癌（具有肌上皮成分的耵聍腺癌）或可能性较小的梭形细胞癌。据我们所知，梭形细胞癌在动物皮肤中罕有报道，在外耳中未见报道。为了评估梭形细胞的肌上皮性质，用p63抗体和标记物MNF-116（全角蛋白）进行了免疫组织化学分析（图3）。梭形肿瘤细胞对全角蛋白显示强细胞质阳性，对p63显示强细胞核阳性，证实为肌上皮来源。多边形肿瘤细胞为全角蛋白阳性，p63阴性，与上皮细胞预期一致。虽然一些肿瘤可以显示p63阳性，但根据肿瘤中存在两种不同形态和不同免疫组织化学模式的成分，排除了梭形细胞癌。根据这些结果，诊断为复杂性耵聍腺癌。复杂性耵聍腺癌在犬中报告不常见，在其他物种中罕见。仅根据形态学，本肿瘤中肌上皮细胞的良性或恶性性质尚不明确。因此，我们使用Ki-67的免疫组织化学分析评估其增殖能力。我们的主观印象是肌上皮细胞没有表现出明显的增殖，很可能表现出良性行为。复杂和混合性（混合性：除上皮和肌上皮成分外，还存在软骨或骨）耵聍腺癌和大汗腺腺癌，比这些肿瘤的简单形式有更好的预后，但预后仍然需要谨慎。

 

Ceruminous and apocrine gland adenocarcinomas arising on haired skin display similar behaviour in the dog. They are locally invasive and destructive, and metastases beyond the regional lymph nodes are rare. Ceruminous adenocarcinomas typically spare the auricular cartilage, but can infiltrate adjacent tissues. Surgical excision is the main treatment, while radiotherapy may be useful when ceruminous tumours cannot be completely removed. In our case the tumour reached the surgical margins, so a relapse was expected. Computer tomography of the head and thorax, and fine needle aspiration of the regional lymph nodes were recommended in order to evaluate if total ear canal ablation with lateral bulla osteotomy could be a therapeutic option for this case and to assess the existence of metastases. Unfortunately, the owner declined any further work-up and opted for palliative topical treatment (1.5 mL TrisEDTA, dexamethasone and enrofloxacin solution, once daily). The secondary infection was controlled and for approximately four months the dog did not show discomfort and enjoyed a good quality of life. However, afterwards its condition deteriorated (more detailed clinical information could not be achieved) and the dog was euthanised. A necropsy could not be performed.

犬耵聍腺癌和有毛皮肤的顶浆腺腺癌，呈现相似的特性。它们具有局部侵袭性和破坏性，罕见转移到区域淋巴结以外区域。耵聍腺癌通常不伤及耳软骨，但可浸润邻近组织。手术切除是主要的治疗方法，而当耵聍腺肿瘤不能完全切除时，放疗可能有用。在我们的病例中，肿瘤达到了手术切除边缘，因此复发是可预期的。建议进行头部和胸部计算机断层扫描以及局部淋巴结细针抽吸，以评价全耳道消融联合外侧鼓疱截骨术是否可作为该病例的治疗选择，并评估是否存在转移。不幸的是，宠主拒绝进一步检查，并选择姑息性外部治疗（1.5 mL TrisEDTA、地塞米松和恩诺沙星溶液，每日一次）。继发感染得到控制，约4个月内，犬未出现不适，并享受了良好的生活质量。然而，随后其病情恶化（无法获得更详细的临床信息），患犬进行安乐死。无法进行尸检。

 

 

 

 

Figure 1. Video-otoscopy of the right ear of a 13-year-old female Welsh springer spaniel dog.

图1，视频耳镜下一只13岁雌性威尔士史宾格犬的右耳

(a) A mass partly covered with whitish material was found at the transition between the vertical and the horizontal canal, filling its lumen. (b) After cleaning the area, the mass was erythematous and friable, bleeding easily.

(a) 在垂直耳道与水平耳道过度处发现被白色物质覆盖的肿块，填充整个耳道。（b）清理后肿物整体泛红、易碎、易出血。

 

Figure 2. Histopathological evaluation of the mass at the right ear canal of a 13-year-old female Welsh springer spaniel dog.

图2，一只13岁雌性威尔士史宾格犬右耳耳内肿物的组织病理学评估。

(a) Overview of the mass, consisting of an infiltrative neoplastic proliferation replacing most of the dermis and reaching all margins of the sample.

(a)肿块概述，包括浸润性肿瘤增生，取代了大部分真皮层，并延伸到样本的所有边缘。

Haematoxylin & eosin, 20. (b) Closer view of the tumour, composed of two different cellular components: spindle cells arranged in sheet (main component, star) together with epithelial cells forming scattered irregular tubular structures partly displaying intraluminal papillary growing (arrows). H&E, 200.

苏木精和伊红，20倍。(b)肿瘤放大图，由两种不同的细胞成份组成:梭形细胞呈片状排列(主成分星形)与上皮细胞形成分散的不规则管状结构，部分显示腔内乳头状生长(箭头)。),苏木精和伊红，200倍

 

 

 

Figure 3. Immunohistochemical staining of the mass at the right ear canal of a 13-year old female Welsh Springer Spaniel dog.

图3，一只13岁雌性威尔士史宾格右耳道肿物免疫组化染色

(a, c) Both the spindle (star) and the epithelial (arrows) components of the tumour display marked positive cytoplasmic signal for the MNF-116 antibody. The overlying epidermis is also positive, as expected. Unstained areas correspond with the empty lumens of the neoplastic tubules and with the noninfiltrated dermis versus the neoplastic stroma. MNF-116 (pan-cytokeratin antibody, 20 (a), 200 (c). (b, d) Neoplastic spindle cells also display a strong positive nuclear signal for the p63 antibody confirming its myoepithelial nature, while the epithelial neoplastic cells are negative.

Normal p63 positive staining of the keratinocytes of the deep half of the stratum spinosum and the stratum basale in the epidermis is subtly evident in (b). p63 antibody, 20 (b), 200 (d).

(a, c)肿瘤的梭形细胞(星形)和上皮细胞(箭头)均显示MNF-116抗体的阳性细胞质信号。上面的表皮也是阳性的，如预期的那样。未染色区域对应的是肿瘤小管的空腔，而非浸润的真皮层对应的是肿瘤间质。MNF-116(全角蛋白抗体，20倍 (a)， 200倍 (c). (b, d)肿瘤梭形细胞也显示p63抗体的强阳性核信号，证实其肌上皮性质，而上皮肿瘤细胞为阴性。

表皮棘层深半部分和基底层的角质细胞p63阳性染色在(b)中隐约可见。p63抗体，20倍 (b)， 200倍 (d)。

 

 

南海

！！！！