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Breast cancer metastases to the head and neck region are very rare and therefore represent a challenge for the clinician in terms of diagnosis and therapy. Recent advances in breast cancer treatment have achieved longer median survival times in affected patients. However, at the same time, the risk of a clinical manifestation of metastasis increases. Here we present the cases of two breast cancer patients who developed filiae into the petrous portion of the temporal bone and one very rare case of metastasis to the larynx. Diagnosis, therapy and distinctive features of metastasis to the head and neck region are discussed.Secondary to long-term endocrine hormone therapy, a reduction in estrogen receptor expression occurred in all three cases. We believe that the loss of steroid receptor expression contributed to tumor resistance to endocrine therapy. Moreover, this receptor loss hindered the pathologist from confirming the diagnosis of metastases at very unusual sites.

STUDY AIM: To assess the accuracy of ultrasound-guided fine-needle aspiration biopsy in the differential diagnosis of gastrointestinal stroma cell tumors (GIST) from other submucosal tumors, using both cytology and histology. PATIENTS AND METHODS: We conducted a prospective study from May 2005 to September 2008 in all patients presenting with upper gastrointestinal submucosal tumors. Only patients in whom surgical resection was carried out were included in the final analysis. In cases of mesenchymal tumor, immunocytochemistry was attempted for further differentiation between GIST and non-GIST. Surgical histopathology served as the gold standard. RESULTS: A total of 47 patients were analyzable, with a final histologic diagnosis of 35 mesenchymal tumors. Sufficient tissue for conventional cytologic diagnosis was obtained only in the 35 patients with mesenchymal tumors; in this subgroup, immunocytochemistry was possible in 46 %. If and only if enough material was available for immunocytochemistry, the sensitivity for (correct recognition of) GIST tumors was 93 %. In all 12 patients with nonmesenchymal tumors and lesions, cytology was nondiagnostic and the diagnosis had to be based on clinical suspicion and the appearance on endoscopy and endoscopic ultrasound (EUS). On an intention-to-diagnose basis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) had a positive predictive value for mesenchymal tumors of 100 %, but no value for the diagnosis of other lesions; using immunocytochemistry, a GIST tumor was recognized among the mesenchymal tumors with a sensitivity of 58 % and a specificity of 8 %. CONCLUSIONS: EUS-FNA-based cytology is safe and has only limited value for the differential diagnosis of submucosal tumors, mainly because insufficient material is harvested. Better tissue acquisition techniques are necessary for better differential diagnosis.

Phytohormones and chemical compounds revealing estrogenic effects are of increasing interest for their possible influence on the physiology of the reproductive tract. The gap junction connexin (Cx) genes Cx26 and Cx43, the plasma glycoprotein clusterin gene and the complement C3 gene are highly regulated by estrogen in rat endometrium. To test the value of these genes as markers for estrogenic responsiveness we analyzed the effects of estradiol, diethylstilbestrol, the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen, the phytoestrogens genistein and daidzein, and the industrial compounds DDT (1,1,1-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl) ethane) and polychlorinated biphenyl (PCB) on the transcription of these genes in rat endometrium in vivo. Enhancement of Cx26 and decrease of clusterin transcripts expression by estradiol was observed at 0.03 micro g/250 g body weight (BW), and induction of C3 expression was observed at 0.05 micro g/250 g BW. A comparable effect was obtained by a tenfold higher concentration of diethylstilbestrol. Tamoxifen had a regulatory effect on this set of genes at about a 300-fold higher concentration, while raloxifen revealed much weaker estrogenic activity. No effect on Cx43 transcripts was observed with any of the compounds at the concentrations used. An effect of genistein was observed only on Cx26 expression, while PCB decreased clusterin transcripts. These results show that Cx26, C3 and clusterin reveal a comparable sensitivity to estrogens and SERMs. With respect to the phytoestrogen genistein, however, Cx26 seems to be the most sensitive gene. The analysis of clusters of estrogen-sensitive endometrial genes could help to identify estrogenic substances, assess their potency, and elucidate their mechanism of action.