11 to 12-month-old, male and female, Balb/c transgenic mice (HSP70, TLR2) (Mus musculus).Three Balb/c mice weighing about 35 gm were submitted with a large submandibular swelling.
Incision of the skin in the submandibular region revealed a large, smooth, soft, round, bloodfilled,
multi-lobulated mass measuring about 1.5 to 2 cm in diameter.
Salivary gland: Expanding and infiltrating the salivary gland (submandibular,
parotid or sublingual gland, varying depending on mouse and section), there is a large, variably encapsulated mass
with multiple large cystic spaces filled with pale eosinophilic mucinous material and blood. Multifocally, irregular,
variably-sized necrotic areas may be filled with amorphous eosinophilic cellular debris intermixed with pyknotic
nuclear debris, or may form pseudocysts with no lining epithelium. Adjacent to blood vessels, the neoplastic cells
tend to form palisades and have a predominant epithelioid morphology. The mass consists of variably distinct foci
composed of spindle cell and polygonal epithelioid cell populations. The neoplastic spindloid cells have scant to
moderate amounts of pale eosinophilic fibrillar cytoplasm and vesicular nuclei with 1-2 distinct nucleoli. There is
moderate to marked nuclear atypia and numerous mitoses. The epithelioid cells have abundant pale eosinophilic
fibrillar cytoplasm and round to oval basophilic stippled nuclei. There are rare misshaped and attenuated ducts and
tubules entrapped within the neoplastic cell population, especially at the periphery of the mass. In addition, there are
multifocal lymphoid cell infiltrates near the periphery of the neoplasm. Surrounding the neoplastic tissue, there are
multifocal areas of a variable amount of granulation tissue intermixed with hemorrhage and inflammatory cells
(neutrophils and large foamy macrophages) that often extends into the dermis.
Salivary gland: Myoepithelioma.
These are very rare neoplasms seen most commonly in BALB/c, A, C58 strains. (3,5)
Clinically, the neoplasm presents as fluctuant swelling in the ventral aspect of the neck. Macroscopically, the
neoplasms are dark red to yellow, solid to cystic masses filled with mucus, blood and necrotic cellular debris. They
are presumed to arise from the myoepithelial cells of the salivary glands (mainly parotid and submandibular and less
commonly the sublingual gland). Histologically, these neoplasms are biphasic and are comprised of varying
proportions of mesenchymal (spindle) cells and large epithelioid cells; either of these cell types may be the
predominant population in a given tumor. Areas of degeneration and necrosis are relatively common. A majority of
myoepitheliomas are circumscribed with a thin capsule and variable degree of invasion into adjacent tissues.
However, metastasis to regional lymph nodes and lungs may be seen in rare cases.
The characteristic absence of formation of acini or ducts by the neoplastic cells aids in differentiating these tumors from adenomas and carcinomas. The presence of a single solitary mass on the ventral aspect of the neck helps to differentiate these neoplasms from polyoma virus-induced pleomorphic tumors that are multicentric in origin and not limited to the salivary glands.(3) Myoepitheliomas can also occur within mammary glands, Harderian glands, and clitoral glands and preputial glands.
In humans, salivary gland myoepitheliomas are classified based on morphology (plasmacytoid, spindle, stellate, clear or epithelioid) of the neoplastic cells into spindle cell myoepithelioma, clear cell myoepithelioma, etc. Due to the histologic heterogeneity, no single immunostain is diagnostic. For human salivary myoepitheliomas, a panel of markers consisting of AE1/AE3 (PAN-K), S-100, P63, GFAP, calponin and vimentin is commonly used for diagnosis.(4) A panel of markers, such as vimentin and cytokeratin (especially k5 and k14), may be used for immunohistochemical diagnosis of these tumors in mice. Also, PTAH staining will aid in confirmation of the presence of intracytoplasmic fibrils within the neoplastic epithelioid cells. Ultrastructurally, these fibrils are composed of abundant microfilaments in parallel orientation with periodic focal densities, characteristic of smooth muscle fibrils, and are arranged in dense parallel bundles around the nucleus.(3) These tumors are usually negative for smooth muscle actin and desmin.
Acknowledgements: We appreciate the help of Drs. Terry Blankenship-Paris, Mark Hoenerhoff, and Steven Kleeberger at NIEHS, RTP, NC for graciously sharing the case material.
Salivary gland: Myoepithelioma, malignant.
Conference participants agreed the histomorphologic features are consistent with the
diagnosis of myoepithelioma. As indicated by the contributor, myoepitheliomas can have a diverse
histomorphology. From personal experience, the moderator mentioned that the presence of spindle cells which
palisade around the outer edge of the tumor and forming a dark rim is a common histologic feature of the neoplasm.
Additionally, neoplastic cells adjacent to vessels often take on an epithelial-type arrangement.(1) In addition to the
features described by the contributor and the moderator, myoepithelioma also can occur histologically as a
squamous form, both with keratin pearl formation or without the presence of keratinization.(1)
Participants discussed the differential diagnosis, which included poorly differentiated carcinoma/adenocarcinoma, carcinosarcoma, and sarcoma arising or metastatic to glandular organs, such as the salivary, mammary, lacrimal, and Harderian glands. All participants interpreted the tumor as arising from the salivary gland, and thus considered a neoplasm of other regional glandular tissues less likely, including mammary, lacrimal, or Harderian origin. Based on the absence of desmoplasia and glandular or squamous differentiation, participants considered a tumor of epithelial origin less likely; the glandular or ductular profiles occasionally found in the neoplasm were interpreted as preexisting salivary structures entrapped by neoplastic cells. Participants did observe the large pseudocystic structures in the neoplasm described by the contributor, which were not interpreted as evidence of glandular differentiation.
Finally, participants discussed the difficulty in the histologic differentiation of salivary myoepithelioma from polyoma virus-induced salivary neoplasms. Polyoma virus inoculated into neonatal mice of susceptible strains induces tumors in multiple organs, in particular the parotid salivary gland.(2) Histologically, polyoma virus-induced salivary neoplasia most commonly occurs as mixed mesenchymal and epithelioid populations, although neoplasms composed of pure mesenchymal or epithelioid populations may be observed.(2) In contrast to polyoma virus-induced salivary tumors, myoepitheliomas typically are not infiltrated by lymphocytes and plasma cells.(1)
The use of tissue from multiple animals in this case contributed to slide variation, with some slides having one type of salivary gland and others having more than one type present.
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2. Botts S, Jokinen M, Gaillard ET, Elwell MR, Mann PC: Salivary, Harderian, and lacrimal gland glands. In: Maronpot RR, ed. Pathology of the Mouse. Vienna, IL: Cache Valley Press; 1999:56-60.
3. Burger GT, Frith CH, Townsend JW. Myoepithelioma, Salivary glands, mouse. In: Jones TC, Popp JA, Mohr U, eds. Digestive system. Monographs on Pathology of Laboratory Animals. Berlin, Germany: Springer-Verlag; 1997:231-235
4. Hunt JL, Barnes L. Immunohistology of head and neck neoplasms. In: Dabbs D, ed. Diagnostic Immunohistochemistry. 2nd ed. Philadelphia, PA: Churchill Livingstone (Elsevier Inc.); 2006:245-247.
5. Sundberg JP, Hanson CA, Roop DR, Brown KS, Bedigian HG. Myoepitheliomas in inbred laboratory mice. Vet Pathol. 1991;28:313-323.