Chordomas commonly express RTKs and activated signal transduction molecules. Although there were no statistically significant correlations between the expression of any of the markers studied and disease-free survival or tumour location, the results nonetheless indicate that chordomas may respond to RTK inhibitors or modulators of other downstream signalling molecules.

Summary Despite reports of sex steroid receptor and COX2 expression in desmoid-type fibromatosis, responses to single agent therapy with anti-estrogens and nonsteroidal anti-inflammatory drugs are unpredictable. Perhaps combination pharmacotherapy might be more effective in desmoid tumors that co-express these targets. Clearly, a further understanding of the signaling pathways deregulated in desmoid tumors is essential for development of targeted molecular therapy. Transforming growth factor-β (TGFβ) and bone morphogenetic proteins (BMPs) are important regulators of fibroblast proliferation and matrix deposition, but little is known about the TGFβ superfamily in fibromatosis. A tissue microarray representing 27 desmoid tumors was constructed; 14 samples of healing scar and 6 samples of normal fibrous tissue were included for comparison. Expression of selected receptors and activated downstream transcription factors of TGFβ family signaling pathways, β-catenin, sex steroid hormone receptors and COX2 were assessed by immunohistochemistry; patterns of co-expression were explored via correlational statistical analyses. In addition to β-catenin, immunoreactivity for phosphorylated SMAD2/3 (indicative of active TGFβ signaling) and COX2 was significantly increased in desmoid tumors compared to healing scar and quiescent fibrous tissue. Low levels of phosphorylated SMAD1/5/8 were detected in only a minority of cases. TGFβ receptor type 1 and androgen receptor were expressed in both desmoid tumors and scar, but not in fibrous tissue. Estrogen receptor-β was present in all cases studied. TGFβ signaling appears to be activated in desmoid-type fibromatosis and phosphorylated SMAD2/3 and COX2 immunoreactivity may be of diagnostic utility in these tumors. Given the frequency of androgen receptor, estrogen receptor-β and COX2 co-expression in desmoid tumors, further assessment of the efficacy of combination pharmacotherapy using hormonal agonists/antagonists together with COX2 inhibitors should be considered.

The distinction between sarcomatoid carcinoma (SC) and bona fide sarcoma can be difficult using conventional immunohistochemical markers. Epithelial-mesenchymal transition (EMT) has been proposed as a histogenetic mechanism for the development of SC. Expression of selected markers of EMT (Twist and Slug) was compared with other markers of epithelial differentiation in SC and spindle cell sarcoma to determine the utility of these antigens in this differential diagnosis. Twenty-seven cases of SC (excluding those of gynecologic origin) were stained by immunohistochemistry for cytokeratins (AE1/AE3, 5D3, CK5/6, and 34betaE12), p63, claudin-1, claudin-7, epithelial cadherin, placental cadherin, epithelial cell adhesion molecule/epithelial-specific antigen, 14-3-3sigma, Twist, and Slug. A comparison group of 21 spindle or pleomorphic spindle cell sarcomas was also studied. Immunohistochemical stains were scored in a semiquantitative manner and subsequent exploratory analyses were performed using logistic regression and chi2 tests. Only cytokeratin AE1/AE3 specifically labeled SC in a statistically significant manner. Other epithelial-specific markers tested did not distinguish SC from sarcoma primarily owing to low sensitivity. However, when positive, immunostains such as CK5/6, membranous epithelial cadherin, and nuclear p63 may aid in the distinction of SC from sarcoma. EMT markers were expressed in most cases of both SC and sarcoma, and were not useful in making a differential diagnosis between these neoplasms.

Summary Despite reports of receptor tyrosine kinase activation in desmoid-type fibromatosis, therapeutic benefits of kinase inhibitor therapy are unpredictable. Variability in signal transduction or cellular kinases heretofore unevaluated in desmoid tumors may be responsible for these inconsistent responses. In either case, a better understanding of growth regulatory signaling pathways is necessary to assess the theoretical potential of inhibitor therapy. Immunohistochemical analysis of tyrosine kinases and activated isoforms of downstream signal transduction proteins was performed on a tissue microarray containing 27 cases of desmoid-type fibromatosis and 14 samples of scar; 6 whole sections of normal fibrous tissue were studied for comparison. Platelet-derived growth factor receptor, β type, and focal adhesion kinase 1 were expressed in all desmoid tumors and healing scars but only 80% and 50% of nonproliferative fibrous tissue samples, respectively. Hepatocyte growth factor receptor was detected in 89% of desmoids and all scars tested, but not in any of the fibrous tissue samples. Epidermal growth factor receptor was detected in only 12% of desmoids and not in scar or fibrous tissue. Mast/stem cell growth factor receptor, receptor tyrosine–protein kinase erbB-2, and phosphorylated insulin-like growth factor 1 receptor/insulin receptor were negative in all study cases. Variable levels of phosphorylated downstream signal transduction molecules RAC-α/β/γ serine/threonine-protein kinase, mitogenactivated protein kinase, and signal transducer and activator of transcription-3 were observed in desmoids (58%, 62%, and 67%), scar tissues (100%, 86%, and 86%), and fibrous tissue (33%, 17%, and 17%). These results indicate that tyrosine kinase signaling is active in both fibromatosis and healing scar, but not in most nonproliferating fibrous tissues. Although platelet-derived growth factor receptor, β type, is expressed ubiquitously in desmoids, the kinases driving cell proliferation in desmoids remain unresolved.

A 47-year-old man presented to the otolaryngologist with a 7-year history of a mass of the cheek. Fine-needle aspiration revealed foci of spindled cells admixed with abundant fat and myxoid material. A diagnosis of spindle cell lipoma was rendered on the resected specimen. The cytologic findings of spindle cell lipoma of the parotid gland as seen by fine-needle aspiration are presented along with the histologic correlates.