Histologic features of pseudohyperplastic perineural invasion in prostatic adenocarcinoma: A mimicker of benign hyperplastic glands and high-grade prostatic intraepithelial neoplasia

Perineural invasion (PNI) seen in prostatic adenocarcinoma (PCa) on biopsy has both diagnostic and prognostic implications. On biopsy, PNI is 1 of the 4 pathognomonic features of PCa; it is associated with an increased risk for extraprostatic extension, and its finding can affect therapy. From January 1, 2013 to June 30, 2013, 3120 cases of PCa were seen by the Genitourinary Pathology Consultation Service at the Johns Hopkins Hospital. Of these, 418 (13.4%) had PNI. During this interval, we prospectively identified an unusual pattern of PNI, which we have termed "pseudohyperplastic PNI," which was defined by a "gland-within-gland" morphology, wherein the centrally located gland was wrapped around a nerve. Pseudohyperplastic PNI was found in 9 (2.1%) cases, with an additional 3 cores from 2 patients biopsied at our institution with this finding also included. Of the 12 cores with pseudohyperplastic PNI, the Gleason scores were 6 in 11 cores and 4+3=7 in the remaining core. In 6 cases, the only focus of PNI in the entire case was pseudohyperplastic. In 7 of the 12 foci, the central gland wrapping around the nerve appeared to "float" unattached within the surrounding gland closely resembling a benign hyperplastic gland or high-grade prostatic intraepithelial neoplasia (HGPIN). In the remaining 5 foci, the central PNI was focally attached to the outer gland. In 11 of 12 foci, there was no to mild cytologic atypia. One focus of pseudohyperplastic PNI had prominent nucleoli in a large gland with tufting architecture and foamy cytoplasm. Of the 9 consult cases, pseudohyperplastic PNI was missed in 5, and in all 5 cases PNI was initially not diagnosed in the entire case. In 2 of these cases with missed pseudohyperplastic PNI, PCa was not diagnosed at the outside institution. In 1 of the cases biopsied at our institution, pseudohyperplastic PNI was misdiagnosed as HGPIN. In addition to the morphology of cancer appearing to float within a surrounding gland, other features that contribute to the difficulty of recognizing the focus as cancer are: (1) lack of adjacent cancer in about one half of the foci; (2) larger glands than typical cancer surrounding the PNI in a minority of cases; (3) tufting of the gland surrounding the PNI in a few cases; (4) atrophic or foamy gland features in some cases; and (5) lack of prominent cytologic atypia in most cases. Although this pattern of PNI that mimics either a benign hyperplastic gland or HGPIN is uncommon, accurately recognizing it as carcinoma can have both diagnostic and prognostic implications.