长期复发但不恶化的犬爪部病毒性乳头状瘤

王帆

Long-term recurrent, yet nonprogressive, pedal viral papillomas in a dog

长期复发但不恶化的犬爪部病毒性乳头状瘤

作者：John S. Munday, Susan A. Piripi, Alan Julian and Scott J. Martin

翻译：罗雪

Viral papillomas that developed on the toe of a dog, were removed and recurred four times in two years. Despite the papillomas being‘persistent’, they remained small and confined to the toe, and did not spread or progress to severe disease. Not all persistent papillomas will progress, even when these are treated using more conservative therapies.

一只犬的脚趾上发生的病毒性乳头状瘤被切除，并在两年内复发四次。尽管乳头状瘤“持续复发”，但它们仍然很小，并且局限于脚趾，并没有扩散或发展为严重的疾病。即使使用最保守治疗方法，也并非所有持续复发性乳头状瘤都会进一步发展。

Introduction

介绍

Canine viral papillomas (warts) are common hyperplastic lesions caused by papillomavirus infection. There are no large studies reporting the behaviour of cutaneous papillomas in dogs. However, the vast majority of oral papillomas resolve spontaneously within six months. As both cutaneous and oral papillomas often are caused by canine papillomavirus (CPV) type 1, the behaviour of these papillomas is expected to show some similarities. Previous reports have documented ‘persistent’ canine oral or mucocutanous papillomas which progressed to massive numbers of lesions that necessitated euthanasia or transformed to squamous cell carcinoma.

犬病毒乳头状瘤（疣）是乳头瘤病毒感染引起的常见增生性病变。没有关于犬皮肤乳头状瘤特性的大型的研究报告。然而，绝大多数的口腔乳头状瘤会在6个月内自行消退。由于皮肤和口腔乳头状瘤通常是由犬乳头状瘤病毒(CPV)1型引起的，这些乳头状瘤的特性有望表现出一些相似之处。先前的报告记录了“持续复发性”犬口腔或粘膜皮肤乳头状瘤，发展为大面积病变，被迫安乐死或转化为鳞状细胞癌。

Case Report

病例报告

A 2-year-old castrated male Jack Russell terrier developed a 4 mm diameter pedunculated mass on the medial surface of the 3rd digit of the right hind paw. The dog was otherwise healthy. The papilloma was removed by ligation using suture. The mass recurred two weeks later (Figure 1). As a result of concerns that the mass was irritating the dog, surgical excision was performed. The mass was submitted for histological evaluation which revealed markedly hyperplastic folded epidermis and numerous enlarged epidermal cells that had blue-grey cytoplasm consistent with papillomavirus-induced cytopathic change (Figure 2a and b). The papilloma appeared to be completely excised. Ten months later, three exophytic masses developed on the medial surface of the same digit. These were surgically excised and not submitted for histological evaluation. Ten months later, a new papilloma was removed by ligation from the same location, followed by recurrence at the same location three months later. This was surgically excised and histological evaluation again revealed a typical viral papilloma with numerous cells showing papillomavirusinduced cytopathological findings. Blood chemistry was analysed before both surgeries and revealed no abnormalities.

一只2岁已去势雄性杰克罗素㹴，在右后爪部第三趾的内侧长了一个直径4毫米的带蒂肿块。该犬在其他方面都很健康。乳头状瘤用缝线结扎去除。两周后肿块再次复发（图1）。由于担心肿块会刺激犬，所以进行了手术切除。肿块提交组织学评估，发现表皮层明显增生有皱褶，大量增大的表皮细胞，胞浆呈蓝灰色，与乳头瘤病毒诱导的细胞病变一致(图2a和b)。乳头状瘤似乎已经被完全切除了。10个月后，在同一趾的内侧表面出现3个外生性肿块。这些都被手术切除了，没有提交组织学评估。10个月后，一个新的乳头状瘤从同一部位通过结扎去除，3个月后在同一部位复发。手术切除，组织学评估再次显示典型的病毒性乳头状瘤，大量细胞显示乳头状瘤病毒诱导的细胞病理学表现。在两次手术前均进行了血液生化检查，均未发现任何异常。

Total DNA was extracted from shavings of formalin- fixed paraffin-embedded tissue blocks of each of the papillomas that had been submitted for histological evaluation as described previously. The consensus primers FAP59/64 and CP4/5 were used with no template DNA added to the negative controls.Amplicons were purified and sequenced as described previously.Both primer sets amplified DNA sequences from each papilloma that were identical to previously deposited CPV-1 DNA sequences in GenBank (D55633).

如前所述，从每个已提交进行组织学评估的乳头状瘤的福尔马林固定石蜡包埋的组织块中提取总DNA。采用一致引物FAP59/64和CP4/5，在阴性对照中不添加模板DNA。扩增物被纯化和测序。两组引物均扩增了每个乳头状瘤的DNA序列，与之前在GenBank中沉积(D55633)的CPV-1DNA序列相同。

The final surgical excision was performed 25 months after the first papilloma was observed. No other lesions had developed five months after the latest surgical excision.

在观察到第一个乳头状瘤的25个月后进行了最后一次的手术切除。在最后一次手术切除5个月后，未出现其他病变。

Discussion

讨论

Papillomaviruses infect the basal cells of the epidermis with most infections remaining clinically silent. Some papillomavirus types stimulate marked epidermal hyperplasia resulting in papilloma development.Normally, the development of a cell-mediated immune response causes spontaneous resolution of any existing papillomas and prevents additional papillomas from developing.However, some dogs with persistent papillomas appear to never mount an appropriate immune response and subsequently develop massive numbers of papillomas that are predisposed to neoplastic transformation.

乳头状瘤病毒感染表皮的基底细胞，大多数感染在临床上处于静息状态。一些乳头状瘤病毒类型刺激造成明显的表皮增生，导致乳头状瘤的发展。正常情况下，细胞介导的免疫反应的发展会导致任何现有乳头状瘤的自发消退，并防止其他乳头状瘤的发展。然而，一些患有持续复发性乳头状瘤的犬似乎从来没有产生适当的免疫反应，随后发展为大面积的乳头状瘤，倾向于肿瘤化。

Papillomas in the present case recurred at the same site after multiple attempts at removal using ligation and surgery. Both techniques remove the bulk of the hyperplastic mass, yet either can leave infected basal cells within the skin. As the papillomas remained small and confined to one area of the body, it may suggest that the immune response of some dogs can contain the infection without spread to other parts of the body or progression to more severe local disease.

本病例中的乳头状瘤在多次尝试使用结扎和手术切除后在同一部位复发。这两种技术都能去除大量的增生性肿块，但两者都能在皮肤内留下受感染的基底细胞。由于乳头状瘤仍然很小，并且局限于机体的一个区域，这可能表明一些犬的免疫反应可以控制感染，而不会扩散到机体的其他部位或发展为更严重的局灶疾病。

It is unclear why the presently described dog had not developed an appropriate immune response two years after the first papilloma was observed. However, there was no evidence of any underlying disease or immunosuppression and this lack of response may simply be due to interindividual variability in the time taken by the host to mount an immune response. This variability is well-recognized in humans, with warts rapidly resolving in some individuals yet remaining present for many years in others. As papillomas contain massive numbers of viral particles, they are easier to detect by the immune system. The repeated excision of small papillomas in the present case may therefore, paradoxically, have delayed the development of cell-mediated immunity by decreasing the number of viral particles on the dog.

目前尚不清楚为什么在观察到第一个乳头状瘤两年后没有产生适当的免疫反应。然而，没有任何潜在疾病或免疫抑制的证据，这种缺乏反应的原因可能只是由于宿主在产生免疫反应所需的时间有个体差异。这种差异在人中是公认的，疣在某些个体中迅速消失，但在另一些个体中仍然存在多年。由于乳头状瘤含有大量的病毒颗粒，它们更容易被免疫系统检测到。因此，在本病例中，反复切除小乳头状瘤可能会通过减少犬的病毒颗粒数量，反而延迟了进一步细胞介导免疫。

The only papillomavirus amplified from these lesions was CPV-1. As this is a common cause of canine viral papillomas, the unusual repeated recurrence of papillomas does not appear to be due to an unusual type of causative papillomavirus. However, the possibility that these papillomas were caused by a second papillomavirus type that was not amplified by the consensus primers used cannot be definitively excluded.

从这些病变中扩增出的乳头瘤病毒是CPV-1。由于这是犬病毒性乳头状瘤的常见原因，乳头状瘤的不寻常反复复发似乎不是由于一种不寻常的致病乳头状瘤病毒。然而，不能明确排除这些乳头状瘤是由第二种乳头状瘤病毒类型引起的可能性，该类型没有被使用的现有引物扩增。

Figure 1. Cutaneous viral papilloma in the toe of a dog, morphology. The small papilloma appears as a single small polypoid mass on the medial surface of the 3rd digit of the right hind paw. The papilloma has a characteristic roughened surface appearance.

图1，犬脚趾上的皮肤病毒性乳头状瘤，形态学。小乳头状瘤表现为右后肢爪部第三趾内侧表面的一个单一的小息肉样肿块。乳头状瘤具有典型的粗糙的表面外观。

Figure 2. Cutaneous viral papilloma in the toe of a dog, histogical evaluation.

a: The mass consists of thickened epidermis that is arranged in folds supported by thin fibrovascular stalks. Haematoxylin & eosin, x50. b: Higher magnification shows how cells within the epidermis are enlarged by increased quantities of blue-grey cytoplasm, consistent with papillomavirus-induced cytopathic change (arrows). Haematoxylin & eosin, x400.

图2。犬脚趾皮肤病毒乳头状瘤，组织学评估。

a: 肿块由增厚的表皮组成，由薄的纤维血管支撑。苏木精和伊红，50倍。 b: 高倍镜显示表皮内的细胞因蓝灰色的细胞质数量的增加而增大，这与乳头瘤病毒诱导的细胞病变相一致（箭头）。苏木精和伊红，400倍。

zhangenzyme

笼中红细胞

南海

马海军

宠医医宠

曾医生

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