一例京巴犬广泛性皮肤顶浆汗腺囊瘤病

王帆

A case of generalised cutaneous apocrine cystomatosis in a Pekingese dog

一例京巴犬广泛性皮肤顶浆汗腺囊瘤病

作者：Marica Stazi Serenella Silvestri Luca Mechelli Chiara Brachelente

翻译：王帆

 

Abstract

Clinical, histological and immunohistochemical examination of a 13-year-old male client-owned Pekingese dog revealed an uncommon presentation of apocrine cutaneous cystomatosis. This is a rare non-neoplastic condition of uncertain cause, characterised by multiple cystically dilated apocrine sweat glands. We aimed to describe the features of this unusual case of generalised cutaneous apocrine cystomatosis in the dog, which can be useful to distinguish it from multifocal benign cystic apocrine tumours.

摘要

一例13岁家养雄性京巴犬，一种不常见的皮肤顶浆汗腺囊瘤病的临床表现、组织学和免疫组织化学检查。这是一种罕见的非肿瘤性疾病，病因不明，主要表现为多处顶浆汗腺囊性扩张。我们的目的是描述这种不常见的犬广泛性皮肤顶浆汗腺囊瘤病的特征，这有助于将其与多灶性良性囊性顶浆汗腺肿瘤区鉴别。

 

KEYWORDS

apocrine cystomatosis, cytokeratin, dogs, immunohistochemistry, Ki-67 antigen, smooth muscle actin

关键词

顶浆汗腺囊瘤病，细胞角蛋白，犬，免疫组化，Ki-67抗原，平滑肌肌动蛋白

 

1 INTRODUCTION

1 介绍

Apocrine cystomatosis, also called epitrichial sweat gland cystomatosis, is a rare non-neoplastic condition of middle-aged or older dogs characterised by single or multiple cystically dilated sweat glands. No sex or breed predispositions have been identified and the aetiology remains unknown, even if congenital conditions, gland duct obstruction, glandular hyperplasia with retention of the content of dilated glands or senile degenerative changes are proposed. Macroscopically, skin lesions are often located on the head and neck and are characterised by numerous, solitary or grouped, tense to fluctuant bullae or vesicles with translucent and brownish appearance and a smooth surface. Cysts usually contain clear, watery and acellular fluid and measure up to 3 cm in diameter. Histologically, the cysts show the same morphology as normal apocrine glands, being lined by a double layer of cells composed of low cuboidal epithelial cells with apical blebbing (apocrine secretion), surrounded by myoepithelial cells.

顶浆汗腺囊瘤病，也称为毛上汗腺囊瘤病，是一种罕见的非肿瘤性疾病，发生于中年或老年犬，特征为单个或多个汗腺囊性扩张。已确定没有性别或品种倾向性，病因仍然未知，但已提出先天性疾病，腺管阻塞，腺体增生伴有腺体分泌物滞留导致腺体扩张或老年性退行性改变。从宏观上看，皮肤病变常位于头颈部，其特征为大量、单发或成组、胀满到波动的大疱或水疱，外观呈半透明和褐色，表面光滑。囊肿通常含有透明、水样和无细胞液体，直径可达3厘米。组织学上，囊肿表现出与正常顶浆汗腺相同的形态，由双层细胞组成，由小立方上皮细胞组成，顶端空泡(顶浆分泌)，周围是肌上皮细胞。

 

We aimed to describe an uncommon case of severe cutaneous apocrine cystomatosis with a generalised distribution in a Pekingese dog. The clinical, cytological, histological and immunohistochemical findings described in this case report can be useful in differentiating this rare condition from benign apocrine tumours.

我们的目的是描述一个不常见的严重皮肤顶浆汗腺囊瘤病，在一只京巴犬上呈广泛性分布。本病例报告中描述的临床、细胞学、组织学和免疫组化检查结果，可用于与罕见的良性顶浆腺肿瘤进行鉴别。

 

2 CASE HISTORY

2 病例病史

A 13-year-old male Pekingese dog was referred to the clinician with a 3-year history of multiple cutaneous nodules ranging from 0.2 to 1.5 cm in diameter, non-pruritic and indolent, involving the dorsal area of the trunk, the flank and partially extending to the neck; some solitary cysts were present on the cheeks. Benign multicentric apocrine cystadenoma was considered in the differential diagnoses.

1只13岁雄性京巴犬因出现3年多处皮肤结节病史被临床医生转诊来就诊，皮肤结节直径范围0.2-1.5 cm，无瘙痒，无疼痛，位于躯干背侧、胁腹，部分延伸至颈部，双颊部见一些单发囊肿。鉴别诊断为良性多中心顶浆汗腺囊腺瘤。

 

Macroscopically, the lesions were single or multifocal to coalescent, had a dark brown to purple appearance and a soft elastic consistency (Figure 1).

宏观上，病变为单灶或多灶至合并灶，都表现为外观深棕色至紫色，柔软有弹性(图1)。

 

Fine-needle aspiration from these lesions yielded about 0.3 ml of clear yellow-tinged liquid; cytological examination of the content revealed only a few macrophages and plasma cells with a pale blue amorphous proteinaceous fluid on the background.

这些病变进行细针穿刺抽吸，得到约0.3 ml黄色透明液体;细胞学检查显示只有少量巨噬细胞和浆细胞，背景为淡蓝色无定形蛋白质液体。

 

Ultrasound examination revealed multiple cavitary round lesions, ranging from 0.1 to 0.5 cm in diameter, single or confluent, surrounded by a thin hyperechoic wall, filled with anechoic fluid and characterised by a posterior acoustic reinforcement (Figure 2).

超声检查显示多处圆形空腔病变，直径范围0.1-0.5 cm，单发或汇合，周围有薄的高回声壁，充满无回声液体，后方回声增强(图2)。

 

Skin biopsies from trunk and neck were sampled, fixed in 10% neutral buffered formalin, and the serial sections of each biopsy were submitted for histological and immunohistochemical investigation.

在躯干和颈部进行皮肤活检采样，用10%中性缓冲福尔马林固定，并将每个活检的连续切片提交组织和免疫组织化学研究。

 

Histological examination revealed multiple cysts, varying in size, lined by two layers of cells: an inner single layer of low cuboidal epithelium with dome-shaped apical blebbing (apocrine secretion) without morphological atypia, and an outer layer composed by myoepithelial cells that surrounded the wall. In the surrounding dermis, there was mild subepidermal fibrosis with lymphoplasmacellular inflammation (Figure 3).

组织学检查显示多处大小不同的囊肿，内衬两层细胞:内层为单层小立方上皮细胞，顶端有圆顶状空泡(顶泌分泌)，无形态异型性;外层由肌上皮细胞组成，环绕壁。真皮周围有轻度的表皮下纤维化伴淋巴浆细胞炎症(图3)。

 

Immunohistochemical staining with antibodies against pancytokeratin (epithelial cell marker), smooth muscle actin (α-SMA, smooth muscle marker) and Ki67 (cell proliferation marker) was performed. Briefly, after incubation with the primary antibody, a commercially available HRP detection kit was used (Table 1); as a substrate we used the 3-amino-9-ethylcarbazole (AEC). Immunohistochemistry showed strong cytoplasmic positivity of apocrine secretory cells for pan-cytokeratin and marked cytoplasmic positivity of myoepithelial cells that surrounded the wall for α-SMA (Figure 4); the nuclei of apocrine cells were negative for Ki-67.

用抗全细胞角蛋白(上皮细胞标记物)、平滑肌肌动蛋白(α-SMA，平滑肌标记物)和Ki67(细胞增殖标记物)抗体进行免疫组化染色。简单地说，在一抗孵育后，使用市售HRP检测试剂盒(表1);我们使用3-氨基-9-乙基咔唑(AEC)作为底物。免疫组化显示顶浆汗腺分泌细胞全细胞角蛋白在细胞质中呈强阳性，α-SMA围绕壁的肌上皮细胞在细胞质中呈明显阳性(图4);顶浆汗腺细胞核Ki-67阴性。

 

3 DISCUSSION

3 讨论

Apocrine cutaneous cystomatosis, previously reported as apocrine cystic hyperplasia, is an uncommon cutaneous non-neoplastic condition reported in middle-aged or older dogs with no sex predilections or breed predisposition. The main differential diagnosis is multicentric apocrine cystadenoma, a true neoplasm. In the published literature, a single case of generalised apocrine cystomatosis was suspected in an Old English Sheepdog; however, based on histology, immunohistochemistry and biological behaviour, the authors concluded that the lesion was rather more consistent with a benign apocrine tumour.

皮肤顶浆汗腺囊瘤病，以前被报道为顶浆汗腺囊性增生，是一种不常见的皮肤非肿瘤性疾病，报告在中年或老年犬无性别或品种倾向性。主要的鉴别诊断是多中心顶浆汗腺囊腺瘤，一种真正的肿瘤。在已发表的文献中，在一只古老英国牧羊犬中怀疑有一例广泛性顶浆汗腺囊瘤病。然而，基于组织学、免疫组化和生物学行为，作者得出结论，病变更符合良性顶泌腺肿瘤。

 

A condition known as ceruminous cystomatosis is recognised in the cat and is characterised by similar lesions. A congenital condition, senile degenerative changes and obstruction of glandular ducts are suggested aetiologies also in the cat. However, differently from the canine species, the lesions are predominantly localised on the external ear canal and inner pinna, and a breed predisposition is recognised in Abyssinian and Persian cats. Additionally, otitis externa is often reported in the clinical history of cats with ceruminous cystomatosis and can be considered another possible aetiology. Similar lesions are also described in cats’ eyelids.

已知在猫上有一种耵聍性囊瘤病，有相似的病变特征。一种先天性疾病，老年性退行性改变和腺管阻塞也被认为是猫的病因。然而，与犬不同的是，病变主要集中在外耳道和内耳廓，并且在阿比西尼亚和波斯猫中有品种倾向性。此外，猫耵聍性囊瘤病临床病史常见外耳炎，可以认为是另一种可能的病因。猫的眼睑也有类似的病变。

 

Furthermore, in a recent study apocrine cystomatosis in three young pig was described as an incidental finding at the slaughterhouse. The lesions were macroscopically and microscopically similar to those described in the dog, but the localisation was different, since the cysts were found within the subcutaneous fat of the dorsal region. Although in the swine the possible aetiologies are similar to the other species, due to the young age of the pigs, in this case senile degenerative changes were ruled out.

此外，在最近的一项研究中，屠宰场偶然发现三头年轻猪的顶浆汗腺囊瘤病。病变在宏观和微观上与犬的描述相似，但部位不同，因为囊肿在背侧区域的皮下脂肪中发现。虽然在猪中可能的病因与其他物种相似，但由于猪的年龄较小，在此病例中，排除了老年退行性变化。

 

Similarly, in human beings, the histopathological examination of apocrine cystic lesions can occasionally pose diagnostic challenges in differentiating benign from malignant forms. Furthermore, apocrine hidrocystoma, a retention type cyst, and apocrine cystadenoma, an adenomatous cystic tumour, uncommonly cystic lesions of apocrine glands usually found in the head and neck, are terms often used interchangeably by pathologists resulting in confusion about the nature of the disorders. To facilitate the diagnosis, Sugiyama et al. (2007) classified apocrine cystic lesions in non-proliferative and proliferative types, based on the histological architecture of the cysts’ wall. The non-proliferative group included lesions with a simple cystic architecture, where the wall is lined by flattened epithelium or pseudopapillary/papillary-like projections, with variable degrees of stratification and without fibrovascular core. The proliferative group included lesions characterised by cysts with true papillary projections into the cavity and composed by columnar cells with a well-established fibrovascular core. Immunohistochemistry can be useful in distinguishing the two groups, since the non-neoplastic one shows a low proliferative index and strong positivity for α-SMA in the basal area of the lesion. Conversely, the neoplastic group shows usually a higher proliferative index, and a mild to absent positivity for α-SMA.

同样，在人类中，顶浆汗腺囊性病变的组织病理学检查偶尔会在鉴别良性和恶性方面提出诊断挑战。此外，顶浆汗腺囊瘤(一种保留型囊肿)和顶浆汗腺囊腺瘤(一种腺瘤性囊性肿瘤，通常发现于头部和颈部的顶浆汗腺不常见囊性病变，是病理学家经常互换使用的术语，导致对疾病性质的混淆。为了便于诊断，Sugiyama等人(2007)根据囊肿壁的组织学结构将顶泌腺囊性病变分为非增生性和增生性。非增生性组包括具有简单囊性结构的病变，其壁由扁平上皮或假乳头状/乳头状突起排列，分层程度不同，无纤维血管核心。增生性组包括以囊肿为特征的病变，真正的乳头状突起进入腔内，并由具有稳固的纤维血管核心的柱状细胞组成。免疫组化可用于区分两组，非肿瘤组在病变基底区增殖指数较低，α-SMA阳性较强。相反，肿瘤组通常表现出较高的增殖指数，α-SMA轻度阳性或无阳性。

 

In our case, the cysts were lined by two populations of cells: an inner single layer of pan-cytokeratin positive, low cuboidal epithelium with apical blebbing, and an outer population of α-SMA positive myoepithelial cells. In both cell populations, no Ki-67 expression was observed as a consequence of the low proliferative activity. These results, together with the absence of a clinical progression over 3 years, would confirm the benign nature of the lesion and the diagnosis of apocrine cystomatosis. Due to the age of the dog, we may suspect that senile degenerative changes might be at the origin of the lesions in our case, but other aetiologies cannot be ruled out. Although in humans the presence of multiple apocrine hidrocystomas may be associated with inherited disorders, whether a genetic origin can be recognised also in the dog is unknown.

在我们的病例中，囊内排列着两组细胞:内层单层全细胞角蛋白阳性的小立方上皮细胞，顶端有空泡，外层α-SMA阳性肌上皮细胞。在两个细胞群中，由于增殖活性低，没有观察到Ki-67的表达。这些结果，加上3年以上没有临床进展，将证实病变的良性性质和顶浆汗腺囊瘤病的诊断。由于犬的年龄，我们可能怀疑老年性退行性改变可能是我们病例中病变的起因，但不能排除其他病因。虽然在人类中，多发性顶泌汗腺囊瘤的存在可能与遗传性疾病有关，但在犬中是否也可以识别出遗传起源尚不清楚。

 

Over the years, the treatments of choice for apocrine cysts were considered surgical excision or observation without therapy. More recently other possible options were proposed such as chemical ablation with trichloroacetic acid, laser surgery, cauterisation and cryosurgery. However, the continued formation of new lesions after removal is reported. In our case, due to the generalised distribution of the lesions, the dog was only monitored over time and no treatment was undertaken.

多年来，顶浆汗腺囊肿的治疗选择是手术切除或观察不治疗。最近，其他可能的选择被提出，如三氯乙酸化学消融，激光手术，电疗和冷冻手术。然而，据报道，切除后继续形成新的病变。在我们的病例中，由于病变分布广泛，只对犬进行了一段时间的监测，没有进行任何治疗。

 

In conclusion, the clinical history, the architectural growth pattern of cysts’ wall and the immunohistochemical results support the diagnosis of cutaneous generalised apocrine cystomatosis. To the best of the authors’ knowledge, this is the first confirmed case in a dog. Morphological and immunohistochemical features of histologic lesions can help to distinguish hyperplastic from neoplastic apocrine lesions.

综上所述，临床病史、囊肿壁的结构生长模式和免疫组化结果支持皮肤广泛性顶浆汗腺囊瘤病的诊断。据作者所知，这是第一例在犬上确诊的病例。组织学病变的形态学和免疫组化特征有助于顶浆汗腺的增生病变和肿瘤病变。

 

 

FIGURE 1 Skin, trunk. Bulla with translucent and brownish appearance, smooth surface with tense to fluctuant swellings

图1皮肤，躯干。大疱呈半透明和褐色，表面光滑，有紧张或起伏的肿胀

 

 

FIGURE 2 Skin. Multiple adjacent cystic formations varying in size, with a maximum diameter of 8.60 mm, are present involving different parts of dog’s body. Ultrasonography.

图2皮肤。相邻的多个大小不同的囊性形成，最大直径为8.60毫米，涉及犬机体的不同部位。超声。

 

FIGURE 3 Skin, apocrine cysts. Multiple adjacent cystic lesions lined by a single layer cuboidal epithelium. Pseudopapillary projections protrude into the lumen of some cysts but show no fibrovascular core (arrow). H&E, ×2.5

图3皮肤，顶浆汗腺囊肿。相邻多处囊性病变，内衬单层立方上皮。假乳头状突起伸入囊肿腔内，但未见纤维小管核心(箭头)。HE染色,×2.5

 

 

 

TABLE 1 The antibodies and protocols used for immunohistochemical evaluation

表1用于免疫组化评估的抗体和方案

抗体	稀释	孵化	供应商
全角质形成细胞 (AE1/AE3) α-SMA	1:200	2 h RT	Dako; Golstrup, Denmark
Ki67	1:150	ON 4◦C
小鼠和兔子特异性HRP (ABC)检测IHC试剂盒	制造商说明		Abcam; Cambridge, UK

RT：室温; ON：过夜.

 

 

FIGURE 4 Skin, cyst wall. The outer layer is characterised by myoepithelial cells markedly positive for anti-α-SMA antibody, while the inner layer is lined by negative single-layered low cuboidal epithelial cells. Streptavidin-biotin-peroxidase complex method, Carazzi’s haematoxylin counterstain, ×4

图4皮肤、囊肿壁。外层为抗-α-SMA抗体显著阳性的肌上皮细胞，内层为单层低立方上皮细胞。链霉亲和素-生物素-过氧化物酶络合法，Carazzi’s苏木精反染色，×4

 

 

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