Pathogenesis and significance of collagenous micronodules of the prostate

Collagenous micronodules, also known as mucinous fibroplasia, are microscopic structures characterized by the presence of small eosinophilic nodules in areas immediately adjacent to prostatic glandular epithelium. The pathogenesis of collagenous micronodules is unknown, although their relation with mucin has been suggested. The objective of our study was to analyze the structural characteristics of collagenous micronodules by using histochemistry, immunohistochemistry, and electron microscopy to elucidate the pathogenesis of this lesion. We analyzed 15 cases of prostate adenocarcinoma (12 prostatectomy specimens and 3 biopsy specimens) with collagenous micronodules. The collagenous micronodules were closely associated with well-formed malignant glands, where tumor cells exhibited basophilic to amphophilic cytoplasm. Occasionally, intraluminal collagen fragments were observed within malignant but not benign glands. Collagenous micronodules were not associated with mucin, confirmed by negative stainings of mucicarmin or alcian blue in all the collagenous micronodules analyzed in this study. Therefore, the term "mucinous fibroplasia" may not be accurate. Collagenous micronodules stained weakly positive for periodic acid-Schiff. Trichrome stain highlighted the presence of collagenous micronodules as distinct blue structures. Collagen IV and laminin immunostaining performed in 12 cases outlined the micronodules with minimal staining in the center. These findings indicated that collagenous micronodules consisted of predominantly collagen fragments admixed with basement membrane material. Ultrastructurally, they were composed of fragmented banded collagen fibrils surrounded by the basement membrane material. Collagenous micronodules are formed by subepithelial accumulations of fragmented collagen fibers, possibly related to the digestion by collagenase produced by prostatic adenocarcinoma cells.