A detailed assessment of LVI is essential to the pathological evaluation of endoscopically resected specimens. An additional surgical resection should be strongly recommended for patients with LVI.

Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We investigated the relationship between chondroid tissue formation and the expression of bone morphogenetic proteins (BMPs), which are strong inducers of ectopic bone and cartilage formation. Fifteen pleomorphic adenomas and seven normal salivary glands were examined genetically and immunohistochemically. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that BMP-1, BMP-2, BMP-3, BMP-4, and BMP-7 mRNAs were overexpressed in 10 (66.7%), 9 (60.0%), 1 (6.7%), 8 (53.3%), and 12 (80.0%), respectively, of the 15 pleomorphic adenomas. Overexpression of BMP-2 mRNA was observed in pleomorphic adenomas. Marked chondroid formation or expression of type II collagen was frequently observed in pleomorphic adenomas that overexpressed BMP-2 mRNA. Immunohistochemically, BMP-2 was detected in modified myoepithelial cells aroud chondroid tissue and basement membranes. These results suggest that BMPs, and expecially BMP-2, have a role in chondroid formation in pleomorphic adenomas.

No abstract

Matrix-producing carcinoma of the breast is a well-established entity in the group of metaplastic carcinoma, which is histologically characterized by myxochondroid matrix formation and is extremely rare. We describe here four additional cases of matrix-producing carcinoma of the breast. All cases of matrix-producing carcinoma show nest-like, sheet-like, and cord-like growth of tumor cells with cellular atypia, in addition to scattered cancer cells within myxoid or myxohyalinous stroma. Three of four cases showed an acellular or oligocellular matrix-rich zone in the center of the tumor. Immunohistochemically, cancer cells of all cases were positive for cytokeratins and epithelial membrane antigens and partially positive for sox9 and p63. Aggrecan and type II collagen, which are cartilage-specific matrix molecules, were deposited in the stroma of all cases. Type I and type IV collagens were also deposited on the stroma of all cases. These findings suggest that, although cancer cells of matrix-producing carcinoma of the breast are epithelial, they transdifferentiate to chondrocyte-like cells and produce cartilage-specific matrix molecules, which are useful markers for diagnosing matrix-producing carcinoma. Modern Pathology (2008Pathology ( ) 21, 1282Pathology ( -1292 doi:10.1038/modpathol.2008 published online 11 July 2008 Keywords: aggrecan; collagens; matrix-producing carcinoma; breast; immunohistochemistry; electron-microscopy Matrix-producing carcinoma of the breast is an extremely rare and specialized variant of metaplastic carcinoma of the breast, which is a well-established entity; 1,2 because of its rarity, the features of its stroma have remained unclear.Aggrecan is a cartilage-specific major proteoglycan. 3 This macromolecule deposits in the hypertrophic zones of growth plate cartilage, 4 although it was reported to deposit in the salivary pleomorphic adenoma, which frequently showed mesenchyme-like elements, including myxoid and chondroid tissues. 5,6 Type II collagen, which is a cartilage-specific major collagen, and chondromodulin-I (ChM-I), which is cartilage-specific noncollagenous matrix protein, 4,7,8 are deposited in the normal cartilaginous matrix. These molecules can be useful markers of cartilaginous differentiation. As sox9 is a transcription factor, the expression of which induces cartilaginous differentiation, 9-11 this molecule is also a useful marker of chondroid differentiation in normal and neoplastic tissues. [9][10][11][12] We investigated the deposition of matrix molecules in matrix-producing carcinoma of the breast, histochemically and immunohistochemically.

Chondromodulin-I (ChM-I) is a novel cartilage-specific matrix protein. In the growth plates of the long bones, ChM-I was shown to be expressed in mature to upper hypertrophic chondrocytes, and to be deposited in the cartilage matrix. As ChM-I strongly inhibits angiogenesis, cartilage is avascular. Also, ChM-I has bifunctional activity against chondrocyte proliferation. On the other hand, pleomorphic adenomas of the salivary glands frequently have chondroid elements. To elucidate the relationship between chondroid formation and hypovascularity in salivary pleomorphic adenomas, we immunohistochemically examined the expression and localization of ChM-I in 35 cases of this tumor. ChM-I was immunolocalized to the lacunae in the chondroid elements of pleomorphic adenomas (100%). Type II collagen and aggrecan were immunolocalized throughout the matrix around lacuna cells of the chondroid element (100%, 91.7%), and ChM-I was infrequently immunolocalized to the spindle-shaped myoepithelial cells in the myxoid element (37.5%). Fibroblast growth factor-2 was strongly immunolocalized to the lacuna cells in the chondroid element (100%), among the neoplastic myoepithelial cells in the myxoid elements (96.9%), and on the basement membranes around the solid nests of neoplastic myoepithelial cells (71.4%). Although CD34 is a marker of endothelial cells, CD34 was expressed in the endothelial cells in only a few areas around the epithelial elements and in the fibrous element of pleomorphic adenomas. No signals for CD34 were observed in chondroid elements in pleomorphic adenomas (P < 0.001), but a few signals were seen in the myxoid elements (P < 0.05). These findings suggested that lacuna cells and neoplastic myoepithelial cells expressed ChM-I, and that this molecule may play an important role in hypovascularity and chondroid differentiation in pleomorphic adenoma. In conclusion, pleomorphic adenoma expressed ChM-I, which is involved in hypovascularity and chondroid formation in this type of tumor.