Cutaneous calcification in patients with end-stage renal disease: a regulated process associated with in situ osteopontin expression.

BACKGROUND: Cutaneous calcification, or calcinosis cutis (CC), is found in approximately 1% of patients with end-stage renal disease (ESRD) undergoing chronic dialysis. While the pathogenesis is not well understood, it may be similar to those for medial and intimal vascular calcifications, which are actively regulated processes. OBSERVATION: In a retrospective study of 9 patients, the role of an active calcification process leading to CC was assessed by the immunohistochemical detection of osteopontin, which is a regulator of osseous and extra-osseous calcification processes. Calcinosis cutis was associated with female sex, vascular comorbidity, inconstant secondary hyperparathyroidism, and elevated levels of plasma calcium-phosphorus product. Six patients had a favorable outcome after the lowering of plasma calcium levels during dialysis or after parathyroidectomy. CONCLUSIONS: Calcinosis of the vascular media of subcutaneous vessels was the most common histologic feature and was always associated with osteopontin staining, suggesting that CC is a regulated process. Moreover, to our knowledge, extravascular staining of osteopontin in sweat glands, nerves, and macrophages was demonstrated for the first time in this study.

Diagnostic utility of a p63/alpha-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate.

Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34betaE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and alpha-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.