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.     

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.     

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.     

Mammary gland adenocarcinoma in a mandrill (Mandrillus sphinix).

A 22-year-old female mandrill (Mandrillus sphinix) with continuously growing mass at the right mammary gland area was found dead, and a postmortem examination was performed. At necropsy, an elevated firm subcutaneous mass about 5 cm in diameter was present at the right mammary gland area. Axillary, mediastinal, and tracheobronchial lymph nodes were enlarged 2 to 4 times their normal sizes. Numerous metastatic foci 2 to 5 mm in diameter were scattered in the lung. Histologically, the tumor was diagnosed as mammary gland adenocarcinoma. Metastasis to the regional lymph nodes and lung was also confirmed. This is the first reported case of a mammary gland tumor in mandrill in Asia.     

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.     

Mammary adenocarcinoma in a male squirrel monkey (Saimiri sciureus)

A nodule was identified within the right mammary gland of a 16-year-old male squirrel monkey (Saimiri sciureus). The mass was excised and diagnosed as a mammary adenocarcinoma. The monkey developed congestive heart failure 1.5 years later and was euthanatized. At necropsy, a subcutaneous mass was found in the right axillary region. Histologically, the mass was identified as a lymph node whose architecture was effaced by neoplastic cells resembling those of the mammary tumor. Metastasis to internal organs was not observed. This is the first reported case of a mammary tumor in a New World primate and the only known case of mammary cancer in a male nonhuman primate.     

A Spontaneous Epithelial-Myoepithelial Carcinoma of the Submandibular Gland in a Sprague-Dawley Rat

The present report describes a rare case of spontaneous tumor of the salivary gland in a male Sprague-Dawley rat. The clinically confirmed mass rapidly developed in the cervical region between 19 and 21 weeks of age, and the animal was subsequently euthanized. At necropsy, a well-circumscribed nodule approximately 7 × 6 cm in diameter was found at the site of the salivary gland. The cut surface of the nodule was lobulated and soft and had a pinkish tan fish-flesh appearance. One large cyst (approximately 3 × 2 cm in size) containing reddish fluid was also present in the nodule. Histopathologically, the tumor, with a partially lobulated structure, was surrounded by a thin fibrous capsule. The majority of tumor cells formed a diffuse solid sheet structure that mainly consisted of small ovoid or spindle-shaped cells. In the tumor periphery, some cells were arranged in nest-like structures. Small duct-like structures lined with a monolayer of cuboidal epithelial cells resembling an intercalated duct or large polygonal clear cells with a myoepithelial component were also observed. Mitotic figures and necrotic foci were frequently observed in solid areas. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, p63, α-smooth muscle actin and calponin. The cells were negative for calcitonin, synaptophysin and chromogranin A. On the basis of these findings, the tumor was diagnosed as an epithelial-myoepithelial carcinoma originating from the luminal epithelial cells and myoepithelial cells in the submandibular 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.     

A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat

Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies.     

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.     

Invasive ductal carcinoma of the mammary gland in a mare

A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.     

Adenocarcinoma of the parotid salivary gland in a cow

A 6‐year‐old Girolando dairy cow was presented for evaluation of a large subcutaneous facial mass. Fine‐needle aspirates of the mass contained many neoplastic cells with high nuclear:cytoplasmic ratios arranged in sheets and loosely cohesive clusters with streaming erythrocytes and neutrophils in the background. Neoplastic cells were 13–25 μm in diameter and were round to cuboidal with variably distinct borders. Based on the signalment, anatomic location, and cytologic findings, differential diagnoses included salivary adenocarcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma. The cow was euthanized and a necropsy was performed. The primary neoplasm arose from the left parotid salivary gland and meastatic tumor was found in the regional lymph nodes and lung. Histologically, the tumor was composed of anastomosing and irregular solid islets surrounded by scant stroma. Cells were negative for periodic acid‐Schiff (PAS), PAS‐diastase, and Alcian blue pH 2.5 stains, used to detect mucin. On immunohistochemical analysis, neoplastic luminal salivary gland cells expressed cytokeratin, but not S100, α‐smooth muscle actin, or vimentin. Peripheral cells of neoplastic islets were immunoreactive for p63. The final diagnosis was nonsecretory adenocarcinoma of the parotid salivary gland.     

Spontaneous histiocytic sarcoma of the popliteal lymph node in a young sprague-dawley rat

The present report describes a rare case of spontaneous primary histiocytic sarcoma of the popliteal lymph node in a 19-week-old female Sprague-Dawley (SD) rat. At necropsy, a 10 mm-diameter whitish nodule was found at the site of the femoral muscle in the right hindlimb. Histopathologically, the nodule comprised large pleomorphic histiocyte-like cells with abundant eosinophilic or foamy cytoplasm. Multinucleated giant cells, necrotic foci surrounded by palisading arrays of epithelioid histiocyte-like cells and phagocytosis of cell debris or erythrocytes by the neoplastic cells were occasionally observed. Invasion of the tumor cells into the surrounding adipose tissue was found focally, but there were no distal metastases. Immunohistochemically, the neoplastic cells were positive for vimentin, CD68 (ED1) and lysozyme. We concluded that this tumor occurred in the popliteal lymph node, considering the anatomical location of the lesion and the presence of the remnants of lymphoid tissue involved in the tumor.     

Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.     

Tubulopapillary carcinoma with spindle cell metaplasia of the mammary gland in a cat

Sarcomatous proliferation of spindle cells was present in the mammary gland and many metastatic sites in a 10-year-old female domestic cat with tubulopapillary carcinoma in the mammary gland. Transition from neoplastic tubular structures to spindle cells in the primary site and fascicular proliferation of the spindle cells with or without coexistance of tubulopapillary carcinoma in the primary and metastatic sites were observed. Most of spindle cells were positive for cytokeratin CAM5.2 as well as the normal luminal epithelium but not the myoepithelium. From these results, this case was diagnosed as tubulopapillary carcinoma with spindle cell metaplasia and it was clarified that neoplastic luminal epithelial cells can transform to sarcomatous appearence.     

Spontaneous Basal cell carcinoma of the submandibular gland in a rat

At necropsy, a white nodule (about 5 × 3 mm in size) was observed in the right submandibular gland of a 10-week-old female GALAS rat. Histopathologically, oval to spindle-shaped and pale basophilic tumor cells proliferated closely, and formed variably sized foci. The nodule partially spread into or invaded the surrounding normal tissue, and necrotic foci were recognized in the tumor. Immunohistochemically, the nuclei of the tumor cells showed a diffusely positive reaction for p63, and the cytoplasm showed a diffusely positive reaction for cytokeratin and negative reaction for αSMA, vimentin, desmin and S-100. Many tumor cells were positive for PCNA. Ultrastructurally, the tumor cells contained many tonofilaments in the cytoplasm and a few desmosomes at the intercellular portion. Based on these findings, the tumor was diagnosed as a basal cell carcinoma originating from the duct in the rat submandibular gland.     

Orbital adenocarcinoma of lacrimal gland origin in a dog.

A 13-year-old intact female mixed-breed dog was presented for a progressive enlargement of the right eye, which had been treated previously for conjunctivitis. A round, firm mass, approximately 4 cm in diameter, was protruding from the superotemporal aspect of the right orbit, displacing the eyeball anteriorly and ventromedially. The mass was encapsulated, distinct from the eyeball, and not associated with the eyelids. On cut surface, there was a pale multilobulated periphery, with a dark red, soft, and depressed core. Histologically, tumor cells formed cords and tubules, which were stained with mouse anti-human cytokeratin antibody AE1/AE3. Residual glands were serous, and the majority of tumor cells were negative for mucin. The supraorbital location, encapsulation, and residual serous glands suggest that this mass was a low-grade adenocarcinoma of the lacrimal gland.     

Ovarian adenocarcinoma with metastases in a white rhinoceros

A 36-y-old white rhinoceros (Ceratotherium simum) was presented with respiratory distress, sanguineous vaginal exudate, and anorexia. The clinical signs progressed over 40 d, and the rhinoceros died. Autopsy revealed significant ascites; a unilateral, 12.5-cm diameter, polypoid mass in the left ovary; a white, firm transmural mass in the right uterine horn; a white, friable mass in the lung; and white-to-tan, friable small nodules in the diaphragm. Histologic examination revealed similar neoplastic cells in the masses in all 4 locations, composed predominantly of epithelial cells proliferating in a tubulopapillary pattern with significant nuclear atypia and numerous atypical mitotic figures (18–42 per 2.37 mm²). Immunohistochemistry for CK7 (cytokeratin 7) and CK20 (cytokeratin 20) suggest that the ovarian, pulmonary, and diaphragmatic lesions were of ovarian origin and that the ovary was the primary tumor site.     

Carcinosarcoma mimicking a feline injection‐site sarcoma in a cat

A 15‐year‐old spayed female domestic short‐haired cat with cutaneous/subcutaneous well‐circumscribed, alopecic mass approximately 25 × 30 mm in diameter, localized to the left shoulder region was brought to the veterinary surgery department. Despite the suggestive location and macroscopic appearance, feline injection‐site sarcoma was not suspected based on the cytologic examination of fine‐needle aspirates. The tumor was surgically resected, and tissue sections were evaluated microscopically. The tumor was found to be nonencapsulated with a distinct border between the neoplastic parenchyma and surrounding connective tissue. The neoplastic tissue consisted of 2 cell populations: elongated to spindle‐shaped cells arranged in bands and cords and malignant epithelial‐like cells. Both populations showed microscopic features of malignancy. Multinucleate giant cells with irregular cytoplasm were scattered among the neoplastic cells. The spindle‐shaped cells strongly expressed vimentin but did not express α‐smooth muscle actin (α‐SMA) or cytokeratin. Desmin was strongly expressed in about 0‐5% of cells. Epithelial‐like cells expressed cytokeratin, but not vimentin, desmin, or α‐SMA. Multinucleate giant cells expressed vimentin, but did not α‐SMA, desmin, or cytokeratin. Based on microscopic observations and IHC results, the final diagnosis was carcinosarcoma with histologic features compatible with feline injection‐site sarcoma, but without the clinical aggressiveness of this tumor.     

A case of adenocarcinoma of the endometrium extending into the leiomyoma of the uterus in a rabbit

In a pet rabbit, 2 tumor masses one on each horn were macroscopically seen in the wall of the uterus. On light microscopic examination, the right horn mass consisted of an admixture of neoplastic epithelial and mesenchymal element. The epithelial element was composed of neoplastic epithelial cells with numerous mitotic figures and formed varied sizes of acini, glandular, and solid structures. The tumor was diagnosed as an adenocarcinoma of the endometrium. The mesenchymal element was composed of well-differentiated smooth muscle cells and was diagnosed as a leiomyoma. While adenocarcinoma cells formed a protrusive mass in the uterine lumen, they also showed an extension into the leiomyoma of the myometrium. By immunohistochemistry, adenocarcinoma stained positive for cytokeratin (MNF116) and leiomyoma stained positive for smooth muscle actin, showing a substantial difference in the cytological nature of these tumor cells. The results may give a further evidence supporting the narrative of the tumor development that an adenocarcinoma of the endometrium extended into leiomyoma of the uterus. To the author's knowledge, this is the first report describing this type of combination of two independent tumors in a pet rabbit.