Wold, Lester E.

PURPOSE: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio [OR] = 2.2; 95% confidence interval [CI], 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P = .06, Fisher’s exact test). CONCLUSION: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.

A retrospective case review was carried out to report the outcomes in a contemporary case series of Ewing’s sarcoma originating in the hand. We identified five patients treated since 1995. All five had wide surgical excision, one by ray amputation. All were treated with chemotherapy. Four patients also received radiation therapy, two to treat metastases and two as an adjunct to local excision. There were no local recurrences. Two patients developed metastases. Both died of their disease. Neither of these two patients had received local postoperative radiation therapy; one did not receive chemotherapy before definitive surgery. The other three patients were alive and free of disease at last follow-up, 4 to 12 years after initial presentation.

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml of 10% dextrose solution in 1 paw and 0.05 ml of saline in the contralateral paw, to serve as a control. The animals were killed at 1, 2, 4, 8, or 12 weeks. While the saline side showed minimal changes at any time period, the hypertonic dextrose side showed progressive noninflammatory SSCT fibrosis, with vascular proliferation and thickening of collagen bundles. Demyelination of the median nerve developed at 12 weeks after the injection on the dextrose side. These findings are similar to the progression of pathology noted in humans with CTS.

The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were graded and compared to similar tissue from 12 cadaveric spec imens. All studies were done by a single pathologist who had no knowledge of the origin of the specimen. The surgical specimens were interpreted as abnormal in all 11 specimens, and all 12 of the control specimens were reported as being without histologic abnormality. Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens. Neither feature was present in any of the control material (P < 0.001). These data suggest that chronic refractory lateral epicondylitis requiring sur gery is a degenerative rather than inflammatory proc ess. This may account for the lack of response to rest and antiinflammatory medication.