Unusual Histologic Types of High-Grade Prostatic Intraepithelial Neoplasia

Abstract

High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor proliferation of peripheral zone, moderately to poorly differentiated prostatic adenocarcinomas. The usual cell type of the epithelial lining of HGPIN is a glandular epithelial cell with characteristic nuclear abnormalities. Here we report nine cases of unusual types of HGPIN, including three cases of signet-ring cell HGPIN, one case of small cell neuroendocrine HGPIN, and five cases of HGPIN with distinctive mucinous features. The three examples of signet-ring cell PIN were all associated with an invasive primary signet-ring cell carcinoma of the prostate. The HGPIN assumed a classical tufted and micropapillary architectural growth pattern, with the constituent cells exhibiting a morphologic appearance identical to that of the invasive signet-ring cells. The intraepithelial and invasive signet-ring cells were mucin negative and were immunoreactive for prostate-specific antigen (PSA). A fourth case displayed a mixed intraepithelial glandular-small cell neoplastic proliferation, where intraepithelial small cells were histologically identical to surrounding invasive small cell carcinoma cells. The small cell HGPIN and invasive small cell carcinoma cells were positive for the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase. In five cases, mucinous distension of HGPIN glands, producing a flat pattern of the epithelial lining layer, comprised the third unusual pattern of HGPIN. These blue mucinous secretions were readily detected by hematoxylin and eosin staining and were composed of both neutral (periodic acid-Schiff-positive) and acidic (alcian blue-positive) mucins. Herein we document the existence of an intraepithelial proliferation of neoplastic cell types-small cell neuroendocrine and signet-ring cell-that are usually considered as stromal-invasive cells in the prostate. The presence of these rare prostatic cell types in both HGPIN and invasive carcinoma provides further support for a close relationship between HGPIN and invasive carcinoma of the prostate. All three unusual types of HGPIN-signet-ring cell, small cell neuroendocrine, and mucinous-are important to diagnostically recognize because of the strength of association of HGPIN with invasive carcinoma.

Precursor lesions to prostatic adenocarcinoma

“…13), and with paneth cell-like neuroendocrine differentiation (Fig. 14) [13][14][15][16]. Following complete androgen deprivation therapy there is a marked decrease in the prevalence and extent of highgrade PIN.…”

High-grade prostatic intraepithelial neoplasia

“…Other unusual patterns of PIN include the signet ring cell pattern, small-cell neuroendocrine pattern, and foamy gland pattern ( Figures 5-8). 58 There is inversion of the normal orientation of epithelial proliferation with PIN; most proliferation normally occurs in the basal cell compartment, whereas in PIN, the greatest proliferation occurs on the luminal surface, similar to preinvasive lesions in the colon (tubular adenoma) and other sites.…”

Prostatic intraepithelial neoplasia

“…There are no known clinically important differences between the architectural patterns of high-grade PIN, and their recognition appears to be only of diagnostic utility. Other unusual patterns of PIN include the signet ring-cell pattern, the small-cell neuroendocrine pattern, and the mucinous pattern [10].…”