A case of spontaneous Zymbal’s gland carcinoma with lung metastasis in an aged Fischer 344 rat

Zymbal’s gland neoplasms are induced in rats through the administration of various carcinogens, but spontaneous neoplasia is rare. This report describes a spontaneous Zymbal’s gland carcinoma with lung metastasis found in an aged male Fischer 344 rat. Macroscopically, the dome-like tumor nodule, approximately 30 mm in diameter with ulceration, was located near the ear canal of the rat. No healthy tissue or structure of Zymbal’s gland was identified on the corresponding side, while the normal salivary glands and a lacrimal gland were observed. Histologically, a large part of the tumor mass was occupied by poorly differentiated neoplastic cells, the shapes of which were oval to polygonal or fusiform. Additionally, clusters of sebaceous-like foamy cells and squamous metaplasia with prominent keratinization were observed. Tumor cells were found to metastasize to the lung; these cells displayed histological similarities, including a sebaceous gland-like pattern, to those in the primary site. The tumor cells were immunohistochemically positive for cytokeratin AE1/AE3 or vimentin but negative for CD68, S100, α-smooth muscle actin, von Willebrand factor, and desmin. Our results indicate that the tumor was a poorly differentiated Zymbal’s gland carcinoma with lung metastasis.     

Spontaneous Mammary Adenocarcinoma in a Twelve-week-old Female Sprague-Dawley Rat

Spontaneous mammary adenocarcinoma was observed in a 12-week-old female SD rat. A movable mass in the right cervical region was found at 11 weeks of age, and the rat was sacrificed the following week. The mass was located in the vicinity of the right salivary gland and measured 38 mm × 26 mm × 16 mm in gross size. It was a firm whitish mass, with a cut surface that was also whitish in appearance. Histopathologically, neoplastic cells formed glandular structures that contained secreted eosinophilic material. Ultrastructurally, similar secreted material and lipid droplets were in the cytoplasm of the neoplastic cells. Immunohistochemically, the neoplastic cells were positive for cytokeratin 8, cytokeratin 18 and estrogen receptor α. Based on these findings, the tumor was diagnosed as a mammary gland adenocarcinoma, and we therefore conclude that this tumor type can occur spontaneously in female SD rats as young as 12 weeks of age.     

A pleomorphic adenoma of the lacrimal gland in a dog

A 13-year-old female mongrel dog had a pleomorphic adenoma of the lacrimal gland in the right upper orbit. The tumor measured 3.8 x 3.0 x 3.3 cm, appeared white, round, and firm, and pressed the right globe and surrounding tissues. Histopathologically, the tumor had a thin connective tissue capsule and was composed of tubules with two cell types, some resembling luminal epithelial cells making up the tubular structures and the other of myoepithelial cells. Epithelial tubules were disposed in an adenomatous fashion and separated from each other by proliferating pleomorphic myoepithelial cells. Immunohistochemically, large numbers of the luminal epithelial cells revealed an immunopositive reaction against keratin/cytokeratin (AE1/AE3), and some epithelial cells reacted against cytokeratin 14. Spindle-shaped myoepithelial cells revealed an immunopositive reaction against cytokeratin 14, alpha-smooth muscle actin, and vimentin. A small number of myoepithelial cells reacted against desmin. S-100 protein immunopositivity was frequently found in luminal epithelial cells and rarely in the pleomorphic myoepithelial cells. Glial fibrillary acidic protein positivity was commonly found in myoepithelial cells, myxoid matrices, and intracystic materials, but not in luminal epithelial cells.     

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.     

A salivary malignant myoepithelioma in a dog

Salivary tumours are uncommon in domestic animals and there are no known previous confirmed reports of salivary tumours of myoepithelial origin in dogs. A 12-year-old female mixed breed dog was presented with a lobulated mass, composed of white-yellowish tissues, extending from soft palate to epiglottis. Histological examination revealed a neoplastic lesion consisting of a dense population of cells showing moderate pleomorphism, with pale cytoplasm and large oval nuclei, arranged in solid lobules. Mitotic activity was very high. Tumoral cells were negative for both periodic acid-Schiff reaction and Alcian blue stain and displayed strong immunohistochemical reactivity for pan-cytokeratin, muscle specific actin and myosin and focal positivity for cytokeratin 14. On the basis of the morphological, histochemical and immunohistochemical findings a diagnosis of malignant tumour of myoepithelial origin (malignant myoepithelioma) was made.     

Complex apocrine carcinoma with dominant myoepithelial proliferation in a dog

A rare case of complex apocrine carcinoma displaying dominant myoepithelial proliferation developed in the right leg subcutis of a 10-year-old male dog. The major cell population consisted of diffusely proliferating p63-expressing neoplastic cells that were largely myoepithelial in origin co-expressing α-smooth muscle actin. A small portion of the cell population consisted of concomitant basal epithelial cells lacking α-smooth muscle actin expression. The minor population consisted of p63-negative apocrine gland cells that expressed cytokeratin 8. The myoepithelial cell population showed a rather stronger proliferation activity than did the apocrine epithelial population. Thus, this tumor might have been derived from basal epithelial cells characterized by more predominant myoepithelial differentiation than luminal apocrine epithelial differentiation.     

Spontaneous extraskeletal osteosarcoma with various histological growth patterns in the abdominal wall of an ICR mouse

Extraskeletal osteosarcoma is extremely rare in mice. This case report demonstrates a spontaneous murine extraskeletal osteosarcoma that exhibited various histological growth patterns in an ICR mouse. At necropsy, the tumor mass was located in the abdominal wall and was 45 × 30 × 25 mm in size. Histopathologically, the tumor showed the following four growth patterns: a solid pattern of polygonal cells embedded in an osteoid eosinophilic matrix with calcification, an irregular sheet pattern of short spindle cells accompanying some eosinophilic multinucleated cells, a fascicular pattern of spindle cells and a cystic pattern lined by short spindle cells. Immunohistochemically, most of the tumor cells were positive for vimentin, proliferating cell nuclear antigen and osterix. The multinucleated cells mentioned above were desmin positive and were regarded as regenerative striated muscles but not tumor cells. Since no clear continuity with normal bone tissues was observed, the tumor was diagnosed as an “extraskeletal osteosarcoma.”     

Malignant fibrous histiocytoma (giant cell type) associated with a malignant mixed tumor in the salivary gland of a dog

A 12-year-old male Boxer dog presented with a 5 x 5 x 7-cm partially encapsulated mass in the right mandibular salivary gland. Histologically, the mass was composed of neoplastic epithelial and mesenchymal cells. The mesenchymal component consisted of two cell populations arranged in different patterns: coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled with neoplastic epithelial cells and containing osteoid and well-formed bone trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis of these histological features, two malignant salivary tumors were diagnosed: a malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor. Immunohistochemical studies demonstrated keratin 5 and 8 expression by the neoplastic epithelial cells, indicating a probable salivary ductal origin, and vimentin expression by all mesenchymal elements, suggesting a fibroblastic line of differentiation.     

In vitro model of parathyroid hormone-related protein secretion from mammary cells isolated from lactating cows

Parathyroid hormone-related protein (PTHrP) is produced by the lactating mammary gland and is present in milk in a biologically active form. The goal of this investigation was to determine if cells cultured from the lactating mammary glands of cows would secrete PTHrP in vitro. Mammary acini were isolated from lactating cows at 1–6 wk after calving, and fresh or cryopreserved mammary acini were cultured for 14 d on Type I collagen. Cultures on thick layers of collagen (2.5 mm) were detached and allowed to contract on Day 6. PTHrP production was measured by N-terminal radioimmunoassay and bioassay (increased cAMP levels in ROS 17/2.8 osteoblast-like cells). The mammary cells reached confluence at Day 6. PTHrP production was low at Day 2 (<0.5 ng/ml) but increased to peak production (2–4 ng/ml) at approximately Day 6 and remained constant until Day 14. Immunoreactive and bioactive PTHrP levels in the culture medium correlated well. The cultures produced lactoferrin (2,000–2,300 ng/ml) and α_s1-casein (14–19 ng/ml). Prolactin stimulated PTHrP production approximately 50% on Days 6–14. PTHrP production was increased approximately 100% by treatment with epidermal growth factor (10 ng/ml) for 2 d. Morphologic evaluation of cultures on thick, contracted collagen at Day 14 revealed an inner layer of mammary epithelial cells overlying myoepithelial cells and an outer layer of collagen containing stromal cells. Immunohistochemistry demonstrated positive staining for PTHrP and cytokeratin in both mammary epithelial and myoepithelial cells and a-smooth muscle actin in myoepithelial cells. These data demonstrated that cryopreserved mammary tissue from lactating cows could be cultured in vitro and secreted PTHrP in a regulated manner. This in vitro model will be useful to investigate the function and regulation of PTHrP in the lactating mammary gland.     

Mammary lipid-rich carcinoma with extensive amyloid deposition in a dog

A 6-year-old female Labrador retriever presented with a mass in the right mammary gland, and swollen right inguinal and axillary lymph nodes. Fine needle aspiration biopsy suggested a malignant lipid-producing tumor, such as liposarcoma. Histopathologically, the neoplasms were solid, lobulated nests of atypical epithelial cells with a large amount of extracellular deposits of amyloid in both mammary gland and lymph nodes. The proliferating cells contained large cytoplasmic vacuoles, positive for oil red-O. These cells were immunopositive for cytokeratin (AE1/AE3) and β-casein and negative for SMA. The amyloid deposits were immunopositive for β-casein. These findings suggested that the proliferating cells secreted β-casein forming amyloid deposits. This is the first report of mammary lipid-rich carcinoma with extensive amyloid deposition derived from β-casein.     

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.     

Cardiac ganglioneuroma in a juvenile pig

A cardiac mass (3 × 5 × 3 cm) was detected at the base between the right auricular wall and right vena cava of a slaughtered 6-month-old female mixed-breed pig during a meat inspection. The tumor comprised infiltrative prominent interweaving fascicles of Schwann cells with Verocay bodies. Moreover, the ganglion cells were scattered or aggregated throughout the neoplastic tissue. The ganglion and Schwann cells had neither cellular atypism nor mitosis. On the basis of the bearing site as well as the morphological and immunohistochemical features, this is the first case of a cardiac ganglioneuroma in a pig.     

Multiple dermoid sinuses of type Vb and IIIb on the head of a Saint Bernard dog

Dermoid sinus, a congenital malformation of neural tube development, has been reported in humans and several animal species including dogs. It is typically found in the dorsal midline and commonly occurs in the Rhodesian Ridgeback breed. A case of multiple dermoid sinuses in the fronto-occipital region is described. An 11-month-old, intact female Saint Bernard dog was presented with a 2 day history of discharge from a large irregular subcutaneous mass in the fronto-occipital region. The dog was otherwise healthy. The dog had two circular skin lesions (approximately 4 × 4 and 4 × 2 cm diameter) surrounded by multiple irregular elevated masses. The masses had multiple small openings on the skin surface with tufts of hair protruding from the apertures. The masses were surgically removed, and the diagnosis of multiple dermoid sinuses was confirmed by histological examination. Histopathological examination showed multiple, variably sized, spherical to tubular cysts expanding the dermis and subcutis. Cysts were filled with hair shafts and lamellar keratin and were lined by a stratified squamous epithelium. Sebaceous and apocrine gland adnexal structures were also observed. To the best of our knowledge, this is the first reported case of multiple dermoid sinuses of two different types in the head of a Saint Bernard dog.     

Ultrastrukturelle und ultrahistochemische Untersuchungen an der Milchdrüse des Hundes: II. Ultrahistochemische Untersuchungen

Ultrastructural and ultrahistochemical examinations on the canine mammary gland II. Ultrahistochemical examinations Mammary glands of mostly oldder bitches were examined ultrahistochemically for the distribution of ATPase, alkaline phosphatase, and acid phosphatase. The reactions for ATPase were found regularly in the walls of the blood vessels and often on the plasma membranes of the myoepithelial and epithelial cells. However, plasma membranes adjacent to lumen and basement membrance did not show the reaction. Alkaline phosphatase was found regularly only on the plasma membranes of the myoepithelial cells. Acid phosphatase was found in the lysosomes of myoepithelial and epithelial cells, and increased in amount during the regression of the gland.     

Expression of bone morphogenetic protein-6 (BMP-6) in myoepithelial cells in canine mammary gland tumors.

Seventy-three mammary tumors and three mammary tissue specimens were examined to elucidate the expression of bone morphogenetic protein (BMP)-6 in the myoepithelial cells of canine mammary gland tumors. Morphologically, the myoepithelial cells were classified into four types: resting and proliferating cells inside the basement membrane, and spindle- and star-shaped cells proliferating in the outer area of the basement membrane. The characteristics of these myoepithelial cells were confirmed by immunohistochemistry using antibodies raised against keratin, cytokeratin 19, alpha-smooth muscle actin, and vimentin. In simple adenoma, a small number of resting myoepithelial cells was immunopositive for BMP-6. In complex adenomas and benign mixed tumors, all types of myoepithelial cells, depending in some cases on their specific location within the tumor, were immunopositive for BMP-6, but almost all of the tubular epithelial cells were immunonegative. Foci consisting of a proliferation of BMP-6-positive star- and spindle-shaped cells had mucinous stroma with marked hyaline and chondroid changes. In contrast, the foci with BMP-6-negative spindle- and star-shaped cells tended to have mucinous stroma without chondroid change. Several types of mesenchymal cells including chondrocytes, osteoblasts, and fibroblastlike cells in the mixed tumors, showed an intense immunopositive reaction for the BMP-6 antibody, and were located close to the ectopic cartilage and bone matrix. No significant immunoreactivity for BMP-6 was observed in most of the malignant mammary tumors; only one malignant mixed tumor was examined. All of these findings indicate that BMP-6 expression in myoepithelial cells may increase in complex adenomas and benign mixed tumors in canine mammary glands, and that BMP-6 expression is most intense in the vicinity of chondroid matrix in these tumors.     

Fractal dimension of canine mammary gland epithelial tumors on cytologic smears

BACKGROUND: Fractal geometry is a tool that can be used for describing, modeling, analyzing, and processing irregular and complex figures. Past investigations in medicine have revealed that fractal analysis could also be applied in tumor pathology to characterize irregular boundaries of the nuclei of tumor cells. OBJECTIVE: The aim of this study was to define whether the fractal dimension parameter could be used on cytologic specimens to differentiate benign from malignant canine mammary gland epithelial tumors. METHODS: The fractal dimension of nuclear surface was determined by computer-assisted morphometry on Hemacolor-stained cytologic smears obtained by fine needle aspiration of normal canine mammary gland epithelial cells, and cells in mammary adenomas, tubulopapillary carcinomas, solid carcinomas, and anaplastic carcinomas. Data were analyzed by Mann-Whitney U test. RESULTS: Significant differences (P <.001) were observed in mean fractal dimension among all tumor types and in comparison with normal canine mammary gland epithelial cells (except for the fractal dimension between solid carcinomas and anaplastic carcinomas). CONCLUSION: The morphometric parameter, fractal dimension, could help in the diagnostic discrimination between benign and malignant canine mammary gland epithelial tumors on cytologic specimens.     

Hepatocellular adenoma in a Eurasian otter (Lutra lutra)

A 7-year-old female Eurasian otter (Lutra lutra) at the Seoul Grand Park, Korea, died after displaying depression, anorexia, weight loss and rough skin for several days. At necropsy, a solitary friable round mass, which was approximately 12 × 9 × 5 cm and mottled dark red and yellow, was found bulging from the right hepatic lobe. Microscopically, the nonencapsulated, poorly circumscribed mass was composed of solid sheets of neoplastic hepatocytes. In addition, numerous small tan foci, ranging from 0.5 to 1.0 cm in diameter, were evenly scattered throughout the pancreatic tissue. These foci were found to be nonencapsulated, well-demarcated hyperplastic nodules of the exocrine pancreatic gland. We observed neither intrahepatic nor extrahepatic metastases. Based on the gross and microscopic changes, we diagnosed the animal as having a hepatocellular adenoma accompanied by exocrine pancreatic nodular hyperplasia.     

Basosquamous carcinoma with systemic metastasis in a miniature Pinscher

Basosquamous carcinoma (BSCC) is a rare malignancy, primarily composed of basal cells with foci of squamous differentiation. It is considered to be histologically an intermediate type between basal cell carcinoma and squamous cell carcinoma, and is known to have aggressive behaviors. BSCC occurred in a 17-year-old female minipin with a history of surgical excision for a mammary tumor. The right upper hindlimb was severely enlarged to 8 x 5 cm. Cross-section showed a homogenous white to yellow-white mass compressing the surrounding muscular tissues. The tumor metastasized also to the lungs, heart, abdominal cavity, liver and salivary gland. Microscopically, basaloid cells were crowded into solid nests or lobules separated by well-developed fibrous tissues with occasional keratinizations. Since there was no skin lesions, the tumor is assumed to be originated from the formerly present tumor in mammary gland. To our literature review, this case is the first BSCC with systemic metastasis in a dog.     

Immunohistochemistry of ultimobranchial thyroid carcinomas in seven slaughtered cows and one bull.

Eight thyroid gland epithelial tumors were found in 7 cows and 1 bull in a retrospective study of thyroid gland lesions in slaughtered cattle. All tumors were classified as ultimobranchial thyroid carcinomas based on morphology and immunohistochemistry. All tumors consisted of solid sheets and nests of polygonal to oval epithelial cells, with more sparsely dispersed colloid-filled follicles. Connective tissue separating nests of epithelial cells varied from delicate fibrovascular stroma to dense collagenous stroma. Fusiform epithelial cells with rare neural fibers and ganglion cells were present in 1 tumor. Cells within solid areas of these tumors were immunoreactive for calcitonin, calcitonin gene-related peptide, neuron-specific enolase, and synaptophysin. Colloid and follicle cells were immunoreactive for thyroglobulin. Few follicle cells also were reactive for calcitonin gene-related peptide. Neoplastic cells invaded the fibrous capsules in all 8 cattle. These tumors represented proliferation of a mixed population of undifferentiated cells, C cells, and thyroid follicular epithelial cells, presumably derived from the thyroid ultimobranchial bodies. These ultimobranchial carcinomas in slaughtered cattle are comparable to ultimobranchial tumors described in dairy bulls and the intermediate type of thyroid gland carcinomas (mixed thyroid medullary carcinomas) described in human beings.