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Surgical Pathology Criteria

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High Grade Prostatic Intraepithelial Neoplasia (PIN)


  • Non-invasive intraductal cytologically malignant epithelial process

Diagnostic Criteria

  • 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

Original posting/updates: 6/1/12


Prostatic Carcinomas

Prostatic Benign Lesions/Patterns Simulating Carcinoma

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