Inverted (hobnail) high-grade prostatic intraepithelial neoplasia (PIN) - Report of 15 cases of a previously undescribed pattern of high-grade PIN

We report 15 cases of a distinctive and previously unrecognized variant of high-grade prostatic intraepithelial neoplasia (HGPIN) that is characterize d by polarization of enlarged secretory cell nuclei toward the glandular lu men. We designate this lesion inverted or hobnail HGPIN. In all cases inver ted HGPIN was identified on needle biopsy where it merged with typical micr opapillary-tufted HGPIN. Inverted secretory cell nuclei frequently demonstr ated less prominent nucleoli than adjacent noninverted secretory cell nucle i, yielding a sense of maturation that falsely suggested a non-neoplastic p rocess. Inverted HGPIN was associated with concurrent prostatic adenocarcin oma in seven cases and with atypical glands suspicious for carcinoma in two other cases, whereas in six other cases inverted HGPIN was the only lesion identified. In both-radical prostatectomies that followed these biopsies t hat were available for review, inverted HGPIN was localized to the peripher al zone of the prostate where it merged with usual forms of HGPIN and carci noma. Inverted HGPIN is a morphologically distinctive form of HGPIN that sh ares the association with carcinoma and peripheral zone localization with o ther recognized forms of HGPIN.