Editors: Francesca Khani ( and Mahmut Akgul (

2022-04/January 24
Contributors: Daniel Athanazio, Maiara Ferreira de Souza, Maria Estela Pompeu do Amaral

A patient in his early 60s underwent prostatectomy, which showed a Grade Group 2 (Gleason 3+4=7) tumor, stage pT3a. The following images show focal areas of the tumor.


1. In the particular areas shown, what is the diagnosis?

a) invasive adenocarcinoma of the prostate, pseudohyperplastic variant

b) high-grade prostatic intraepithelial neoplasia, hobnail / inverted type

c) invasive adenocarcinoma, ductal PIN (prostatic intraepithelial neoplasia)-like

d) ductal adenocarcinoma

e) intraductal carcinoma

Invasive adenocarcinoma of the prostate, pseudohyperplastic variant

Twenty years ago, Argani and Epstein described the inverted (hobnail) variant of high-grade prostatic intraepithelial neoplasia. These lesions were characterized by the arrangement of nuclei polarized towards the lumen. Among 15 cases reported, seven showed association with invasive acinar adenocarcinoma (usual type). In 2015, Öznur and colleagues described additional 13 cases of inverted variant of HGPIN, seven associated with invasive adenocarcinoma – and one of them with inverted polarity also in the invasive component.

In current practice, an invasive prostatic adenocarcinoma that resembles high-grade prostatic intraepithelial neoplasia is better designated as the pseudohyperplastic variant (and graded as Gleason pattern 3). The pseudohyperplastic variant shows dilated glands with papillary infoldings which may be very reminiscent of benign glands. These glands are lined by a single layer of cells that show vesicular/round nuclei or bland nuclei with deceptively benign appearance. An infiltrative pattern of growth, a high index of suspicious and awareness of this variant, and ancillary investigation of basal cells by immunohistochemistry is often critical for the diagnosis, particularly on core biopsy specimens. In contrast, ductal PIN-like adenocarcinoma is characterized by the same architectural changes but shows a pseudostratified columnar epithelial lining. By definition, ductal adenocarcinoma of the prostate is composed by columnar/tall cells with papillary architecture and/or cribriform architecture and graded as Gleason pattern 4. Recent data suggest that ductal adenocarcinomas with PIN-like architecture (PIN-like ductal adenocarcinoma) show a more indolent behavior and, therefore, should be also graded as Gleason pattern 3.

1. Argani P, Epstein JI. Inverted (Hobnail) high-grade prostatic intraepithelial neoplasia (PIN): Report of 15 cases of a previously undescribed pattern of high-grade PIN. Am J Surg Pathol. 2001;25:1534–1539.

2. Öznur M, Koca SB, Yildiz P, Bahadir B, Behzatoğlu K. Inverted (hobnail) high-grade prostatic intraepithelial neoplasia and invasive inverted pattern. Oncol Lett. 2015 Oct;10(4):2395-2399.

3. Zhou M. High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate. Mod Pathol. 2018 Jan;31(S1):S71-79.

4. Paulk A, Giannico G, Epstein JI. PIN-like (Ductal) Adenocarcinoma of the Prostate. Am J Surg Pathol. 2018 Dec;42(12):1693-1700.

Daniel Athanazio, Maiara Ferreira de Souza, Maria Estela Pompeu do Amaral
Imagepat, Laboratory of Pathology
Salvador, Bahia, Brazil


Prostate; Adenocarcinoma; Prostatic Intraepithelial Neoplasia; pseudohyperplastic