Spontaneous Adenosquamous Carcinoma with Rapid Growth and EMT-like Changes in the Mammary Gland of a Young Adult Female BALB/c Mouse

This study histopathologically and immunohistochemically investigated a spontaneously occurring single mass subcutaneously located in the left lower abdomen of a female BALB/cAJcl−nu/+ mouse at 10 weeks of age. The mass was about 20 × 15 × 10 mm in size after formalin fixation; nevertheless, it was not detected by clinical observations at 9 weeks of age. H&E staining revealed the tumor origin was epithelial and probably arose from the mammary gland, and the tumor cells demonstrated a squamous, acinar or polyhedral/basal pattern. A cell kinetics analysis revealed that many of the tumor cells of the squamous, acinar or polyhedral/basal component were positive for PCNA and cyclin D1, although there were a few of TUNEL-positive tumor cells in all of the components. An epithelial/mesenchymal analysis demonstrated that most of the tumor cells of the squamous and acinar components contained keratin and E-cadherin; however, most of the tumor cells of the polyhedral/basal component were less or very weakly positive for these markers. The tumor cells of the squamous component were negative for vimentin and SMA; however, many of the tumor cells of the polyhedral/basal component exhibited vimentin. In addition, expression of SMA was confirmed in some tumor cells of the acinar and basal components. Based on the microscopic and immunohistochemical characterizations, the tumor was diagnosed to be adenosquamous carcinoma that originated from the mammary gland with rapid growth, and the tumor cells demonstrated epithelial-mesenchymal transition-like changes.     

The expression of p63 and cytokeratin 5 in mixed tumors of the canine mammary gland provides new insights into the histogenesis of these neoplasms

Cytokeratin 5 and p63 have been described as basal and myoepithelial cell markers in human breast. Mixed tumors of the canine mammary gland have been associated with a myoepithelial origin. Cytokeratin 5 expression has not been evaluated in these tumors. We investigated the relation between cytokeratin 5 and p63 double-immunohistochemical expression in 23 mixed tumors of the canine mammary gland (10 benign mixed tumors and 13 carcinomas arising from benign mixed tumors) and their origin. Cytokeratin 5 and p63 co-expression was observed in myoepithelial cells of benign mixed tumors, as well as in squamous differentiation of carcinoma arising from benign mixed tumors. Though a few interstitial spindle cells of the mesenchymal components expressed both p63 and cytokeratin 5, the basal epithelial cells were labeled only by cytokeratin 5. The co-expression of p63 and cytokeratin 5 in myoepithelial cells and squamous differentiation suggest that, like in human breast, cytokeratin 5 can also be considered a myoepithelial- and squamous-cell differentiating marker in canine tumors. The presence of some interstitial spindle cells stained for p63 and cytokeratin 5 might be associated with a myoepithelial origin of the mesenchymal component of mixed tumors of the canine mammary gland. Moreover, contrary to p63, basal epithelial cells were labeled by cytokeratin 5, indicating that cytokeratin 5 may not represent an exclusive myoepithelial cell marker but also a basal epithelial cell marker in canine mixed tumors. According to these data, basal epithelial cells may be related to the origin of the epithelial component of mixed tumors of the canine mammary gland.     

Lectin histochemistry on squamous metaplasia in different epithelial tumors of dogs.

Biotinylated lectins and avidin-biotin-peroxidase complex were used to study the correlation between cellular glycoconjugates' expression and squamous maturation in normal canine skin and in various epithelial neoplasms. Normal skin tissue was obtained from five, male, random-source dogs, 5 to 7 years old. The tumors tested, selected from the files of our Department, were fifteen squamous cell carcinomas from different tissue origin, five hepatoid perianal gland adenocarcinomas with squamous metaplasia, and fourteen solid mammary carcinomas with and without histologic evidence of squamous metaplasia. Except for mammary gland carcinomas, all tumors had been surgically excised from male dogs. Intermediate filament aggregation of twelve solid mammary gland carcinomas were studied electron microscopically. The basal and the lower spinous cells in normal skin and the less differentiated cells in squamous cell carcinomas stained moderately with Griffonia simplicifolia agglutinin-I. Spinous and granular cell layers stained strongly with Phytolacca americana mitogen and Arachis hypogaea agglutinin. Both lectins stained well-differentiated cells in squamous cell carcinomas. The electron microscopic study carried out in solid carcinomas of mammary glands revealed some relationship between the presence of intracytoplasmic tonofibrils and the binding of Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen to the tumors tested. Our results suggest that the glycosylation pattern occurring during normal keratinocyte differentiation is conserved in squamous cell carcinomas and that Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen may represent useful tools in distinguishing poorly differentiated squamous cell carcinomas from other poorly differentiated mammary epithelial tumors.     

24例20种犬肿瘤的病理组织学观察

对犬的皮脂腺瘤、肛周腺腺瘤、肛周腺癌、毛基质瘤、间叶性软骨肉瘤、腺样型基底细胞上皮瘤、囊样型基底细胞上皮瘤、水母样型基底细胞上皮瘤、混合型基底细胞上皮瘤、基底鳞状细胞上皮瘤、甲状腺腺瘤、肥大细胞瘤、组织细胞瘤、乳腺良性混合瘤(软骨腺瘤)、乳腺良性混合瘤(肌上皮腺瘤)、恶性肌上皮细胞瘤、乳腺恶性混合瘤(癌肉瘤)、汗腺囊性增生、汗腺腺瘤、汗腺癌等20种24例肿瘤(良性肿瘤14种,恶性肿瘤6种)作了详细的病理组织学描述。     

Mammary carcinoma with sebaceous differentiation in a dog

This report describes an invasive mammary carcinoma with a rare distinctive feature characterized by sebaceous differentiation of tumor cells. This tumor occurred in a 10-year-old female mixed breed dog. The patient had two masses in the left fifth mammary gland. Grossly, the masses were firm, whitish to light brown, and superficially ulcerated. On cut surface, they were multilobulated with foci of necrosis. Microscopically, the tumors were composed of two distinctive neoplastic components, intraductal papillary adenocarcinoma and sebaceous carcinoma. The regions of sebaceous tumor were clumped separately, contained well-developed sebaceous cells and keratinized epithelial cells, and were surrounded by few to several layers of basaloid cells. The cells with abundant foamy cytoplasm that resembled sebaceous cells were also found within the intraductal papillary-like nests of mammary carcinoma, providing evidence of sebaceous metaplasia. Sebaceous differentiation in a mammary gland tumor is possible, because skin appendages and ductal apparatus of the mammary gland share a common anlagen. This tumor had an aggressive behavior with lymphatic metastasis. Consequentially, the dog had a poor prognosis.     

Spontaneous gastric squamous cell carcinomas and other neoplasms in Greenland collared lemmings (Dicrostonyx groenlandicus).

Malignant neoplasms were present in 39/66 Dicrostonyx groenlandicus of varying ages, examined from a laboratory colony. The presence of multiple neoplasms in some resulted in an overall average of 1.15 tumors/affected animal. Gastric squamous papillomas were present in nine, and locally invasive or metastatic gastric squamous cell carcinomas in a further 36 animals. Three mammary adenocarcinomas, one pancreatic islet cell tumor, one probable pancreatic adenocarcinoma and one adrenal cortical adenoma were also seen in lemmings with gastric tumors. Two others had mammary adenocarcinoma alone, and one animal had bilateral Harderian gland adenocarcinoma. Lesions resembling glomerulonephrosis of rats were seen in 23/51 animals whose kidneys were examined. These findings were not considered artefacts of captivity since concurrent gastric squamous cell carcinoma, mammary adenocarcinoma and glomerulonephrosis were present in the single animal examined directly from the wild at Eskimo Point, Northwest Territories.     

Expression of maspin in mammary gland tumors of the dog

Maspin is a serine protease inhibitor that inhibits tumor invasion and metastasis in human breast cancer and is consistently expressed by mammary myoepithelial cells (MECs). To analyze the value of maspin as a marker of the MEC layer of the normal and tumoral canine mammary gland, the immunohistochemical expression of maspin was studied in formalin-fixed tissues from 55 benign and malignant tumors (40 tumors also contained the surrounding normal mammary gland) using a commercially available monoclonal antibody. Periacinar and periductal MECs of all 40 normal mammary glands were stained by the anti-human maspin monoclonal antibody, and immunoreactivity was observed in the nucleus and cytoplasm of these cells. In addition, maspin was found in 53 (98%) of the tumors studied, reacting with the MECs in 100% of benign tumors and 93% of malignant tumors and to the epithelial cells of 16% of benign and 73% of malignant tumors. In the MEC compartment, immunoreactivity was observed in the cytoplasm of hypertrophic MECs, fusiform MECs, stellate MECs, rounded (myoepithelial) cells, and chondroblasts. In the epithelial cell compartment, immunoreactivity was observed in the cytoplasm of cells with and without squamous differentiation. Stromal myofibroblasts were unreactive. Maspin appears to be a very sensitive marker of the normal and neoplastic myoepithelium that, contrary to smooth muscle differentiation markers, does not stain stromal myofibroblasts. In addition, a subset of neoplastic epithelial cells reacted with the maspin antibody. The relationship between maspin expression in different cellular compartments of canine mammary carcinomas and the biologic aggressiveness of the disease remains to be elucidated.     

犬低分化鳞状细胞癌的病理特点

运用病理组织学方法,观察了3例犬低分化鳞癌的病理特点,结果显示,在犬低分化鳞状细胞癌组织中,癌细胞类似于棘细胞、基底细胞,癌组织中形成癌腔,在一些癌腔内可见角化不全细胞,无癌珠形成。癌腔是低分化鳞状细胞癌的病理特点之一,可作为诊断低分化鳞状细胞癌的依据。     

Pseudohyperparathyroidism in a mare associated with squamous cell carcinoma of the vulva

An 18-year-old Appaloosa mare was examined because of squamous cell carcinoma of the vulva, anorexia with pronounced weight loss, and hypercalcemia. The tumor had developed rapidly over a period of 3 months and externally extended ventrally involving the perineum and the dorsal aspect of the udder. Necropsy examination demonstrated a large primary squamous cell carcinoma of the vulva, perineum, and mammary gland with metastases to the supramammary, sublumbar, deep inguinal, and mediastinal lymph nodes. No gross renal lesions were observed and, histologically, there was only mild vacuolation of renal tubular epithelium. Based on the normal concentration of serum parathyroid hormone, the absence of evidence of hypervitaminosis D, and normal renal function, a diagnosis was made of hypercalcemia of malignancy or pseudohyperparathyroidism. The mechanism responsible for hypercalcemia was not determined, but the histologic type of the neoplasm and the clinical course suggested possible production of a humoral hypercalcemic factor by the neoplasm, similar to that demonstrated in certain types of human squamous cell carcinoma.     

动物乳腺干细胞研究进展

乳腺是一个高度活跃的器官,在青春期和生殖周期中,其上皮细胞发生了极大的变化。这些变化是由专门的干细胞和祖细胞推动的。研究乳腺干细胞对动物乳腺发育、哺乳和乳腺癌等方面都有着重大意义。如今,在乳腺干细胞生物学研究方面已经取得了显著进步。乳腺干细胞是组织学上未分化的上皮细胞,可以对称分裂产生两个相同的干细胞,或不对称地产生一个干细胞和一个腔上皮祖细胞或基底/肌上皮祖细胞。通过标记滞留细胞、染料排斥法、干细胞抗原-1标记、细胞表面标记物标记以及谱系示踪等方法可以鉴定出多种不同类型的乳腺干/祖细胞,应用多种不同方法分离鉴定乳腺干细胞有助于深入了解其异质性。乳腺的研究主要分为6个阶段：胚胎期、青春期、性成熟期、妊娠期、泌乳期和退化期。在乳腺不同发育阶段,乳腺干/祖细胞的类型及特性不同。有研究表明,在胚胎期就有基底和管腔谱系的祖细胞产生,静止的乳腺干细胞也可能来自于胚胎期,出生后,静止干细胞可以在卵巢激素的刺激作用下重新进入细胞周期,产生乳腺细胞谱系和自我更新。作者介绍了乳腺干细胞和祖细胞的存在、形态特征、鉴定方法,简述了乳腺干细胞在胚胎期、青春期和妊娠期的特征,分析了目前该领域研究的不足之处以及对未来应用的展望。     

Presence of p53 mutations in feline neoplasms

A region from exon 4 to 8 of the tumour suppressor gene p53 was analysed in 60 feline tumours (30 fibrosarcomas, seven malignant histiocytomas, three lymphosarcomas, five basal cell tumours, five squamous cell carcinomas, two adenocarcinomas of tubular skin glands, one undifferentiated carcinoma of the skin, seven mammary carcinomas). Missense mutations were detected in two fibrosarcomas, one malignant fibrous histiocytoma, the undifferentiated carcinoma of the skin and one mammary carcinoma. One nonsense mutation was detected in one fibrosarcoma and one deletion/frameshift-mutation was observed in one squamous cell carcinoma.     

Histological and electron microscopic studies of endemic ethmoidal carcinomas in cattle.

In five cases of endemic ethmoidal carcinoma in cattle from the Dominican Republic three tumor types could be classified: undifferentiated carcinoma (3), adenocarcinoma (1), and squamous cell carcinoma (1). Electron microscopy showed that the tumor cells in undifferentiated carcinomas closely resembled the cells of the normal olfactory mucosa. This was especially true for the dark cells of Bowman's gland. Ultrastructurally, the lymphoid cells of the undifferentiated bovine carcinoma resembled the lymphoid cells of human nasopharyngeal carcinoma being closely associated with Epstein-Barr Virus. This and epidemiological observations suggested a viral cause of endemic ethmoidal carcinoma.     

犬常见肿瘤流行病学调查及组织病理学诊断

为探讨犬常见肿瘤的发病规律，试验收集哈尔滨地区2016-2017年宠物医院部分犬肿瘤病例71例，采用组织病理学方法对犬肿瘤进行病理学诊断，并对患病动物的品种、性别、年龄、发生部位和饮食情况与肿瘤发生关系进行统计分析。结果显示，71例确诊肿瘤病例中，恶性肿瘤28例，包括鳞状上皮细胞癌3例，基底细胞癌5例，乳腺癌14例，淋巴瘤2例，肾母细胞瘤、精原细胞癌、生殖细胞癌、侵袭性血管黏液瘤各1例；良性肿瘤43例，包括良性乳腺肿瘤15例，纤维瘤10例，平滑肌瘤5例，乳头状瘤和精原细胞瘤各3例，造釉细胞瘤、耵聍腺瘤、脂肪瘤、结节样增生、性索间质细胞瘤、颗粒细胞瘤、肛周腺瘤各1例。上述病例中，乳腺和皮肤是犬肿瘤的高发部位，分别占全部患犬的40.8%和34.0%；患病犬年龄1~16岁不等，平均发病年龄为9.1岁，7岁以后是肿瘤的高发期，中老年犬仍为主要发病群体，但低龄犬发病数量上升；各品种犬均可发生肿瘤，其中杂种犬发病率最高，其次是贵宾犬和京巴犬，且主要为乳腺肿瘤；饮食习惯主要以剩饭剩菜类和肉拌饭类为主，分别占患犬总数的39%和30%；部分肿瘤类型与犬的性别、是否绝育有关，如乳腺肿瘤多发生于未绝育的老年母犬。本研究结果为犬肿瘤的流行病学及诊断提供了参考依据，对犬肿瘤的预防和诊断有一定的借鉴意义。     

Secretory carcinoma of the canine mammary gland

Secretory carcinoma is an uncommon variant of breast cancer, characterized by the presence of intracellular and extracellular eosinophilic secretion. Here, we report the cytologic, histologic, and immunohistochemical findings of a secretory carcinoma diagnosed in the left inguinal mammary gland of a 3-year-old female German Shepherd Dog. The fine-needle aspiration cytology showed numerous large branching sheets of neoplastic cells and isolated cells with cytoplasmic vacuoles. Histologically, the tumor was composed of cells with clear cytoplasm and prominent vacuoles that pushed the nuclei to the periphery, resembling signet ring cells. These cells were arranged in solid or tubular structures with lumenal spaces filled with eosinophilic secretion. Immunohistochemical reactions to cytokeratin (CAM 5.2) and alpha-lactalbumin were strongly positive in all neoplastic cells, and staining for vimentin and S100 protein was negative. The cytomorphologic and immunohistochemical features of this tumor are similar to those seen in tumors in women, hence enabling the diagnosis of a rare case of primary secretory carcinoma of the canine mammary gland.     

荷斯坦奶牛乳腺上皮细胞的分离培养

目的：建立荷斯坦奶牛乳腺上皮细胞的分离培养方法。方法：采用组织块种植法培养奶牛乳腺上皮细胞,利用胰蛋白酶差时消化法分离、纯化上皮细胞。结果：成功培养出奶牛乳腺上皮细胞,显微镜下观察,纯化的乳腺上皮细胞呈典型上皮细胞形态,细胞之间排列紧密,呈鹅卵石铺路样,形态均一,多角形的单层聚集。通过荧光免疫细胞染色方法对细胞骨架蛋白-角蛋白18进行鉴定,呈现阳性反应。乳腺上皮细胞增殖旺盛,经25次以上传代后长势仍然良好。结论：采用组织块种植法结合胰酶差时消化法成功获得纯化的奶牛乳腺上皮细胞。     

Cutaneous metastases of a mammary carcinoma in a llama

An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis.     

Expression of podoplanin in various types of feline tumor tissues

Podoplanin is expressed in various human tumors where it promotes tumor progression, epithelial-mesenchymal transition, and distant metastasis. Podoplanin is also expressed in cancer-associated fibroblasts and induces tumor malignancy. The objective of this study was to evaluate podoplanin expression in various types of feline tumor tissues. Immunohistochemical analysis revealed that podoplanin was expressed in cells of 13/15 (87%) squamous cell carcinomas and 5/19 (26%) fibrosarcomas. Moreover, cancer-associated fibroblasts expressed podoplanin in most tumor types, including 18/21 (86%) mammary adenocarcinoma tissues. Our findings demonstrate that various types of feline tumor tissues expressed podoplanin, indicating the importance of the comparative aspects of podoplanin expression, which may be used as a novel research model for podoplanin biology.     

PTEN 基因在犬乳腺肿瘤组织中的表达及临床意义

有关酪氨酸磷酸酶基因（Phosphatase and tensin homolog deleted on chromosometen,PTEN）在乳腺肿瘤中的检测在人医早有报道。为了研究PTEN基因在犬乳腺肿瘤组织中的表达情况,笔者运用实时荧光PCR定量检测了38例不同的犬乳腺肿瘤组织（包括15例良性乳腺肿瘤和23例恶性乳腺肿瘤）、4例正常犬乳腺组织。结果发现：PTEN基因在犬恶性乳腺肿瘤组织中表达量明显低于其在良性乳腺肿瘤和正常乳腺组织中的表达量,两者差异极显著（P〈0.001）;PTEN在良性乳腺肿瘤组织中的表达与正常犬乳腺组织相比,差异不显著（P〉0.05）;发生了淋巴结转移的乳腺癌PTEN基因的表达量与未发生转移的乳腺癌组织的表达量间差异亦不显著（P〉0.05）,且PTEN的表达量与肿瘤组织的大小和发病动物年龄无关。结论：PTEN蛋白表达异常可能与乳腺肿瘤发生、发展相关,可考虑作为判断犬乳腺肿瘤生物学行为和预测的指标。     

Alteration of somatostatin receptor 2 expression in canine mammary gland tumor

Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.