High Grade Prostatic Intraepithelial Neoplasia (PIN)

Definition

Epithelial nuclei must show features of carcinoma
- Usually this means very large nucleoli
- Marked pleomorphism is not seen
Invasive pattern not seen
- Scattered large ducts involved
  - Ducts retain near normal caliber
- May preserve normal duct-lobule architecture
- Basal cells present on IPOX stains but may be decreased
Most common pattern is pyramidal piles of atypical nuclei projecting into duct lumen
- May have a micropapillary pattern but does not have fibrovascular cores
Cribriform and flat variants are seen rarely
- True papillary pattern with vascular cores is not seen
- Very rare patterns reported include foamy cell, signet ring, neuroendocrine/Paneth cell and small cell
Frequently racemase positive
Clinical significance is not clear
- Originally felt to be predictive of invasive carcinoma on subsequent biopsies
  - Thus considered by some to be an indication for rebiopsy
- Some urologists now feel that with the advent of 12 core biopsy procedures the prostate has already been adequately sampled, and that clinical considerations including PSA should determine the need for additional biopsies instead
- It has absolutely no significance if invasive carcinoma is present in other biopsy cores

Differential diagnosis

Prostatic Intraductal Adenocarcinoma	High Grade PIN
Cribriform pattern common	Cribriform pattern rare
Mitotic figures common	Mitotic figures rare
Basal cells if present are usually patchy	Basal cells widespread but may be fewer than normal
Solid or dense cribriform patterns are definitional	Solid and dense cribriform patterns not allowed
Marked nuclear pleomorphism (6 x normal) or comedonecrosis are definitional	Marked nuclear pleomorphism and comedonecrosis not allowed

Prostatic Ductal Adenocarcinoma	High Grade PIN
Columnar cells with elongated nuclei	Generally cuboidal cells with round nuclei
Invasive large glands with no architectural preservation	May preserve normal duct-lobule architecture
Cribriform pattern common	Cribriform pattern rare
Papillae if present have vascular cores	Tufts of cells, but no papillae
Basal cells if present are usually patchy	Basal cells widespread but may be fewer than normal

PIN-like Carcinoma	High Grade PIN
Crowded grouping of large ducts/glands	HG-PIN involves scattered large ducts separated by benign parenchyma
No basal cells	Basal cell markers positive
May surround nerves	No perineural invasion

Bibliography
- Hameed O, Humphrey PA. Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia. Mod Pathol. 2006 Jul;19(7):899-906.
- Tavora F, Epstein JI. High-grade prostatic intraepithelial neoplasialike ductal adenocarcinoma of the prostate: a clinicopathologic study of 28 cases. Am J Surg Pathol. 2008 Jul;32(7):1060-7.
- Bostwick DG, Cheng L. Precursors of prostate cancer. Histopathology. 2012 Jan;60(1):4-27.
- 2: Montironi R, Mazzucchelli R, Lopez-Beltran A, Scarpelli M, Cheng L. Prostatic intraepithelial neoplasia: its morphological and molecular diagnosis and clinical significance. BJU Int. 2011 Nov;108(9):1394-401.

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342