Editor: Mahmut Akgul (

2022-13/March 28
Contributors: Maiara Ferreira de Souza, Daniel Athanazio

This is a prostatectomy specimen from a patient in his early 80s (GG5, pT3b; with 10% involvement of the gland).


1. what would be your diagnosis?

a) small cell neuroendocrine carcinoma

b) high-grade prostaticintraepithelial neoplasia, hobnail / inverted type

c) small cell-like change in intraepithelial lesions and in invasive adenocarcinoma

d) ductal adenocarcinoma

e) crushing artifacts

1. small cell-like change in intraepithelial lesions and in invasive adenocarcinoma (not listed)

In 1997, Reyes and colleagues described unusual variants of high-grade intraepithelial prostatic neoplasia (HGPIN). One of them was a dense cribriform intraductal lesion that was more akin to the current diagnosis of intraductal carcinoma of the prostate: “small cell neuroendocrine HGPIN”. The center of the intraductal proliferation showed bland and monotonous proliferation of small cells.The reported case showed expression of neuroendocrine markers (chromogranin, synaptophysin, and neuron-specific enolase) by immunohistochemistry and had neuroendocrine-type granules at electron microscopy.

In 2013, Lee and colleagues described seven cases of what they named small cell-like change(SCLC) in high-grade intraepithelial prostatic neoplasia and intraductal carcinoma. Five cases had coexisting prostatic invasive adenocarcinoma and four showed small cell-like change in the invasive tumor. Rosette-like formations (as seen in the present case) were noted within some involved ducts in three cases. Despite resemblance of small cell carcinoma, no lesion expressed commonly used neuroendocrine markers such as chromogranin and synaptophysin. Focal expression of TTF1 was focal in three out of four tested cases.

These findings were expanded in a series of 11 eleven cases by Kryvenko and colleagues. All had HGPIN or intraductal carcinoma with small cell-like change. And, again, rosette formation was also a consistent feature. In nine cases with high-grade invasive carcinoma, SCLC was observed in invasive component or intraductal carcinoma. In two cases, it has observed in intraductal lesions away from low-volume GG1 adenocarcinoma. Expression of synaptophysin, chromogranin, and serotonin were seen in only 2/11 cases, but at least focal expression of TTF1 was documented in 6/11 cases. In four cases, electron microscopy was performed and did not show any evidence of neuroendocrine granules.

To date, no cases of small cell-like change showed association with concurrent or subsequent neuroendocrine carcinoma. This finding is believed not to be associated with any relevant prognostic information.

1. Reyes AO, Swanson PE, Carbone JM, Humphrey PA. Unusual histologic types of high-grade prostatic intraepithelial neoplasia. Am J Surg Pathol. 1997 Oct;21(10):1215-22.

2. Lee S, Han JS, Chang A, Ross HM, Montironi R, Yorukoglu K, Lane Z, Epstein JI. Small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive prostatic carcinoma: a study of 7 cases. Hum Pathol. 2013 Mar;44(3):427-31.

3. Kryvenko ON, Williamson SR, TrpkovK, Gupta NS, Athanazio D, Selig MK, Smith PT, Magi-Galluzzi C, Jorda M. Small cell-like glandular proliferation of prostate: a rare lesion not related to small cell prostate cancer. Virchows Arch. 2017 Jan;470(1):47-54.

MaiaraFerreira de Souza
Imagepat, Laboratory of Pathology
Salvador, Bahia, Brazil

Daniel Athanazio
Professor of Medicine, Federal University of Bahia
Imagepat, Laboratory of Pathology
Salvador, Bahia, Brazil


Prostate; Adenocarcinoma; Neuroendocrine Tumors