Conference 18 - 2012 Case: 04 20130313

Signalment:

A 16-month-old male Sprague-Dawley rat (Rattus norvegicus).Shortly after arrival from the vendor, this aged male rat began T-maze training on a memory task to test cognitive loss with aging. Two weeks later the laboratory notified the veterinary staff of a mass on the ventral surface of the rats neck. Physical examination of the ventral neck revealed, a 2 x 2 firm, non-mobile mass. A fine needle aspirate (FNA) collected from the mass consisted of neutrophils and macrophages. Two weeks treatment with oral enrofloxacin resulted in no change in the size of the mass; therefore, the rat was anesthetized for surgical excision of the mass. The right submandibular lymph node was removed with the mass. Excision was incomplete due to the location of the mass and approximation to the trachea, etc. The biopsy revealed that the tumor was a high grade, poorly-differentiated adenocarcinoma and the rat was euthanized and submitted for necropsy.

Gross Description:

Lung: There are numerous, multifocal, white, firm neoplastic masses encompassing approximately 50% of the lung lobes. Complete atelectasis of one lung lobe is observed and the distal surface of the right caudal lung lobe is adhered to the diaphragm.

Histopathologic Description:

Submandibular salivary gland: The specimen consists of multiple lobules of submandibular salivary glands that are partially effaced and replaced by 2.5 cm unencapsulated irregular mass which extends into the surrounding soft tissues and to the limits of the section. The mass is comprised of irregular epithelial cells that infrequently form irregular ducts or acini. Density of tumor cells varies throughout the mass. Many anaplastic spindle-shaped tumor cells are also present. The neoplastic epithelial cells have marked nuclear pleomorphism, frequent prominent nucleoli and indistinct cell borders. Large foci of necrosis, scattered foci of hemorrhage and variable numbers of mitotic figures vary by field. Excision does not appear to be complete.

Review of a Massons trichrome-stained section of tumor revealed that the neoplastic epithelial cells were negative for collagen while the desmoplastic tissue response was positive for collagen.

Morphologic Diagnosis:

Submandibular salivary gland: Adenocarcinoma: high grade, poorly- differentiated.

Other significant microscopic findings (not submitted): Haired Skin, Incision Site of Tumor Removal: There are numerous small clusters to large foci (0.4 CM) of neoplastic cells similar in appearance to the primary tumor described in the biopsy report above scattered within the dermis and subcutis.

Lung, Thymus (none visible): There is a metastatic neoplastic process admixed with hemorrhage and inflammation that effaces and replaces at least 50% of the lung. The neoplastic cells are similar in appearance to those described for the salivary gland mass above, with the exception of a greater epithelial cell component. Clusters and islands of neoplastic cells are frequent within alveoli. Hemorrhage, fibrin and inflammatory cells (macrophages) predominate within adjacent alveolar spaces.

Liver, Kidney, Adrenal Gland, Spleen, Pancreas: Within the one visible adrenal gland, 75% of the cortex and medulla are effaced and replaced by neoplastic cells similar in appearance to those described for the salivary gland above. There is bilateral mild to moderate chronic progressive glomerulonephropathy.

Condition:

Salivary gland adenocarcinoma

Contributor Comment:

Primary tumors of the major salivary glands are rare in humans, and the majority (>85%) are benign.(1,2,4,8,10,20,22,24) The incidence rate for both malignant and benign tumors is most common in patients between 50-70 years of age, but can occur at any age. There is also a wide geographic diversity of salivary gland tumor prevalence and frequency.(2,11,21) For example, it is reported that Canadian Eskimos have a greater prevalence (14/11,500/9years) of developing salivary gland carcinomas as compared to any other geographic group and they have a 100% mortality rate.(11) The majority of these tumors are undifferentiated lymphoepithelioma-like tumors found in mixed salivary glands.(21) Whereas in Denmark, they have a low prevalence of salivary gland carcinomas with an average of 1.1/100,000/year and the most common type is a parotid gland carcinoma.(2)

Benign salivary gland tumors tend to occur more commonly in females, whereas malignant tumors are more prevalent in males.(10) Malignant salivary gland tumors can be diagnosed using the World Health Organization (WHO) classification system.(22) In general, mucoepidermoid carcinomas account for over 50% of malignant salivary gland tumors in humans, while adenocarcinomas were reported in only 12% of the cases. Tumors have been documented in all three major salivary glands, as well as in minor salivary glands; however, the most common site in humans is the parotid gland and the second most common being the submaxillary gland.(2,4,10,20,22)

In humans, submandibular gland tumors account for 5-15% of all salivary gland tumors and less than 1% of all malignant head and neck tumors, however, over 50% are malignant.(1) Malignant submandibular adenocarcinomas in humans tend to have areas of necrosis and hemorrhage with irregular and ill-defined margins that infiltrate growth into surrounding tissues. They tend to form nests or islands of tumor cells and have a widespread ductal differentiation. Clinically, over 20% of patients have reported pain and facial weakness associated with the mass.(14) Most tumors have progressed to high grade by the time they are diagnosed; therefore, these malignant submandibular salivary adenocarcinomas have a poor prognosis in humans.

Primary salivary gland tumors are also rare in domestic animals and have been reported in dogs(9,17), cats(13), lions(5), and cows.(3) In dogs, the most common salivary gland neoplasms are adenocarcinomas and carcinomas. There are two reports that describe rare cases in dogs, a malignant fibrous histiocytoma in a boxer(9) and another report of an osteosarcoma of the mandibular salivary gland in a collie.(17) Primary salivary gland tumors in cats are commonly carcinomas found in the minor salivary glands, rather than the parotid gland.(13) A single case of a high-grade mucoepidermoid carcinoma of the mandibular salivary gland has been reported in a lion.(5) There have also been three cases of parotid gland carcinomas reported in cows, two of which were pleomorphic carcinomas, and one was a squamous cell carcinoma.(3) Primary salivary gland tumors are also rare in rodents.(6,7,12,15,16,18,19,23) There has also been a single report of a Mongolian Gerbil developing a pleomorphic sarcoma of the salivary gland(18), and a ground squirrel with an adenocarcinoma of a minor salivary gland.(23) Mice very rarely develop salivary gland tumors, but myoepitheliomas have been reported to occur spontaneously in certain inbred strains of mice.

Spontaneous primary salivary gland tumors are also rare in rats, but may be chemically induced.(15,25) A study during carcinogenesis in rat submandibular glands showed that histopathology and immunohistochemistry is a useful tool for tumor histiogenesis.(15) Submandibular salivary gland adenocarcinomas in rats are poorly differentiated, show local invasion, and, in most cases, incite a significant desmoplastic response.(7) They should also exhibit the same characteristics seen in human salivary glands, including nests or islands of tumor cells, and tumor-grade specific nuclear and mitoses characteristics. In this case, the rat demonstrated a significant amount of irregular epithelial cells, marked nuclear pleomorphism, prominent nucleoli, large area of necrosis, scattered foci of hemorrhage, a variable number of mitotic figures, with a desmoplastic tissue response. All of these characteristics are consistent with a diagnosis of a high grade submandibular salivary gland adenocarcinoma. Metastasis to the lungs and adrenal gland also indicates that this was a high-grade tumor with a poor prognosis.

JPC Diagnosis:

Submandibular salivary gland: Carcinoma, poorly-differentiated.

Conference Comment:

The contributor does an excellent job of summarizing salivary gland tumors in humans and animals. We agree that this neoplasm is both a high grade malignancy and poorly-differentiated; however, we prefer a more general diagnosis of poorly-differentiated salivary gland carcinoma. In this case, we considered diagnoses of salivary gland adenocarcinoma and myoepithelial carcinoma, as conference participants discussed whether or not the spindle cells represent either a desmoplastic response to tumor invasion or perhaps, a neoplastic component in itself. Immunophenotyping of the spindle cell population revealed a diffuse, strong cytoplasmic immunoreactivity for vimentin and scattered cytoplasmic immunoreactivity for both smooth muscle actin and calponin, (a myoepithelial cell marker). In addition to the poorly-differentiated tumor cell morphology, additional features of malignancy include local invasion into the surrounding adipose and skeletal muscle, areas of necrosis and neoplastic thrombi within blood vessels. Also present and of descriptive interest are individual and clusters of mast cells within the neoplasm, as well as ductal hyperplasia within the preexisting, entrapped salivary gland.

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