7-year-old Maltese bitch (Canis familiaris).
A 7-year-old Maltese bitch that had been ovariohysteretomized at age 6 years was found by the owner to bear a nodular mass at the right 2nd mammary gland in the past two weeks. Upon clinical examination, the mass was subcutaneous, solid, firm, and movable near the right second mammary gland. Malignant mammary tumor was suspected and lumpectomy was recommended. The tumor mass was removed one week later.
Grossly, the mass was approximately 3.0 x 3.0 cm and appeared light red on the cut surfaces.
Mammary gland: Within the interlobular connective tissue, separating and surrounding pre-existing and mildly hyperplastic ducts, there is a poorly cellular, infiltrative, unencapsulated, poorly demarcated neoplasm.Â In a large portion of the neoplasm, neoplastic cells line mammary ducts, proliferating up to 5 cells deep and expanding the ductal lumen.Â Neoplastic cells are polygonal with distinct cell borders and a moderate amount of eosinophilic cytoplasm.Â Nuclei are irregularly round with finely stippled chromatin and 1-2 large eosinophilic nucleoli.Â There is moderate anisocytosis and anisokaryosis.Â Mitotic figures average 1/400x field.Â Apoptotic cells are common within ducts, and many ducts lined with neoplastic cells contain low numbers of neutrophils admixed with cellular debris, and ducts are surrounded by low to moderate numbers of lymphocytes, with fewer plasma cells, histiocytes, and hemosiderin-laden macrophages.Â Within the superficial dermis, neoplastic cells have escaped ducts, and are distributed in an individualized fashion, rarely forming nests and acini on a dense fibrous stroma.Â In this area, neoplastic cells range up to 50 Î¼m in diameter, exhibit marked anisokaryosis, and are often separated and surrounded by dense bands of fibrous connective tissue, and in some areas, plump myofibroblasts.Â They often fill and expand lymphatics, and surrounding tissue is often edematous.Â
Canine mammary anaplastic carcinoma.
Canine mammary tumors are the most common neoplasm in female dogs, and anaplastic carcinoma is the most malignant form.Â The occurrence of anaplastic carcinomas is uncommon; no case has ever been reported in Taiwan.Â
The present case is a 7-year-old Maltese bitch with a history of ovariohysterectomy performed a year before the tumor occurrence.Â No other external abnormalities were observed.Â Lumpectomy rather than mastectomy was performed.Â This bitch was still alive at the time this manuscript was prepared (8 months post-surgery) despite the malignant features observed on histopathology.Â Continuous follow up for two year survival will be interesting.
Classification of canine mammary tumors has been complicated and debatable.Â The earliest classification scheme for canine and feline mammary tumors was seen in 1961, in Moultons Tumor in Domestic Animals.Â The classification at that time was fairly simple; however, over the years, the classification scheme has further advanced to more detailed and complex ones, including the 1974 WHO edition of International Histological Classification of Tumors of Domestic Animals, and the 1999 Armed Forces Institute of Pathologys classification.Â In 2011, a new classification scheme was proposed.(2)
Mammary gland: Anaplastic mammary carcinoma.
Of the canine mammary tumors, anaplastic carcinomas are the most malignant, and thus carry the worst prognosis.Â As illustrated so well in this case, anaplastic carcinomas often exhibit diffuse invasion of interlobular connective tissue and elicit a marked desmoplastic response with concomitant proliferation of myofibroblasts.Â Lymphatic invasion and metastasis to regional lymph nodes and lung is also common.Â Interestingly, pulmonary metastasis appears radiographically as an interstitial pattern, rather than a nodular one.Â
As the name implies, neoplastic cells are pleomorphic, round to polygonal, with moderate to abundant eosinophilic cytoplasm, and round to oval nuclei which are sometimes indented.Â Neoplastic cells are often individualized or grouped in small nests.Â Features of malignancy include frequent multiple prominent nuclei, severe anisokaryosis and anisocytosis and a high mitotic rate; occasional multinucleated neoplastic cells are also present.(1)
Conference participants discussed use of the term inflammatory carcinoma, which should not be used as a morphologic diagnosis, as it refers to a clinical entity that can be associated with several types of malignant mammary carcinomas, including anaplastic carcinomas.Â The hallmark histologic lesion for this condition is invasion of neoplastic emboli into dermal lymphatics2 and despite the name, and the clinical appearance of a reddened mammary neoplasm, which is warm to the touch, there is often little to no microscopic inflammation associated with the neoplasm.Â
In addition, inflammatory carcinomas are highly angiogenic.(1) Tumor angiogenesis can be accomplished via several mechanisms, including production of vessels through endothelial precursor cells from the bone marrow or from endothelial cells in preexisting vessels, by sprouting angiogenesis, by intussusceptive angiogenesis, and by vessel co-option.Â More recently, a new mechanism, vasculogenic mimicry (VM) has been identified.Â Vasculogenic mimicry consists of the de novo generation of microvascular channels by genetically deregulated aggressive tumors cells without participation of endothelial cells.Â The resulting channels are not true blood vessels, although they function to distribute plasma and blood cells to the neoplasm, and are thought to play a role in metastasis.Â VM has been identified in several types of malignant tumors in humans, including inflammatory breast carcinoma and ductal breast carcinoma, as well as in several types of inflammatory mammary carcinomas in dogs, with its occurrence seen most frequently in anaplastic carcinomas.Â Highly malignant neoplastic cells in canine mammary cancer have been observed to resemble endothelial cells that histologically, immunohistochemically, and ultrastructurally resembled VM as described in human tumors.Â Specifically, the endothelial-like cells (ELCs) in VM are positive for epithelial markers and for the same markers used for the rest of the tumor cells may be positive for vimentin, but negative for smooth muscle actin and desmin, and show absence of specific immunoreaction with endothelial markers.Â Ultrastructurally, ELCs lack Weibel-Palade bodies (which are characteristic of endothelial cells) and have desmosomes (the type of junctions between epithelial cells) instead of fascia occludens (endothelial cell- to-cell junctions).Â Tumor and/or blood cells contained in the channels formed by ELCs are not inside a vacuole as in emperipolesis or phagocytosis; instead, they are inside an actual space formed by the cytoplasmic membranes of ECLs.Â It is thought that ECLs can also form channels that mimic lymph vessels rather than blood vessels; however, further studies are needed to identify the mechanisms of cancer cells developing channels of VM as well as confirm the presence of lymphatic VM.(1)
1.Â Clemente M, Perez-Alenza MD, Illera JC, Pen+ï¿½-ï¿½a L.Â Histologic, immunologic and ultrastructural description of vasculogenic mimicry in canine mammary cancer.Â Vet Pathol. 2010;47(2):265274.Â
2.Â Goldschmidt M, Pen+ï¿½-ï¿½a L, Rasotto R, Zappulli V.Â Classification and grading of canine mammary tumors.Â Vet Pathol. 2011:48(1):117-131.Â