Proposed Working Group Histological Classification of Prostate Atrophy Lesions


Note: This page and its links represent the static "training" web site used by the pathologists for the manuscript entitiled:

A Working Group Classification of Focal Prostate Atrophy Lesions. Am. J.  Surg. Pathol. 30:1281-, 2006

Classification of Normal Epithelium.  Epithelium is classified as histologically normal when glands contain two epithelial cell layers lined by luminal cells that are tall and columnar. These luminal cells contain pale-to-clear cytoplasm (using standard H&E sections of formalin fixed paraffin embedded tissues) and nuclei that are generally round, mostly basally located and nearly even in size and shape and show either no evidence of nucleoli or only very small nucleoli (< 1 μm). These normal appearing glands contain abundant papillary infoldings and are generally lined by a continuous or mostly continuous basal cell layer.

Classification of Focal Prostatic Atrophy Lesions. Although focal atrophy lesions can occupy a very large portion of the prostate, they are distinguished from diffuse or hormonal atrophy. Hormonal atrophy occurs relatively uniformly throughout the entire prostate and occurs in response to castration or other forms of androgen withdrawal (e.g. luprolide treatment).

Most Focal Atrophy lesions can be sub-classified into the following types: simple atrophy, simple atrophy with cyst formation, post-atrophic hyperplasia, or mixed lesions.  A category for mixed lesions is used since there is often more than one pattern found in the same region, at times with the patterns apparently merging together. The epithelium in all types of atrophy is composed of two layers consisting of basal cells and luminal cells.  The luminal cells in atrophic regions often contain scant basophilic cytoplasm (producing a characteristic dark appearance to the lesions at low magnification), although at times the cytoplasm can be clear and somewhat more abundant. At times, luminal cells can be nearly flat and without apparent cytoplasm. The basal layer is often attenuated with many gaps. It can be effectively demonstrated by staining against p63, or basal specific cytokeratins. 

 
Architectural Patterns/Subtypes of Prostate Atrophy

To highlight the fact that these atrophic foci generally harbor associated inflammation and show increased proliferation,  it was proposed to refer to most simple atrophy and PAH lesions as “proliferative inflammatory atrophy” (PIA) as a descriptive umbrella term that would be useful to reflect known and emerging morphological and biological findings. Lesions in which the same prostate atrophy patterns do not contain increased inflammation are referred to as "proliferative atrophy", since these atrophy lesions also generally contain an increased proliferative fraction compared to normal appearing epithelium (De Marzo unpublished observations).  The use of the terms PIA and PA are considered optional depending upon the preference of the individual pathologists. Whether there is increased proliferation in simple atrophy with cyst formation and partial atrophy remains undetermined. Thus, these are not currently considered PIA or PA.

The following table demonstrates how the current classification schema compares to that proposed by L.M. Franks in 1954.

L.M. Franks:  Atrophy and hyperplasia of the prostate proper.  Journal of Pathology and Bacteriology. 68:617-621, 1954.


Franks Designation

Franks Description

Notes (from Franks)

New Classification

Simple atrophy, with or without cyst formation    

Atrophy of epithelium, but usually clear cytoplasm, similar to castrate

No good images shown

Same as Franks

Sclerotic Atrophy

Atrophy of epithelium, with thickening of peri-acinar collagen.

“in early stages” often large collections of lymphocytes and histocytes surrounding affected ducts and acini

Considered simple atrophy in new classification

Post-atrophic hyperplasia

 

 

    1. Lobular hyperplasia

 

 

 

 

 

 

 

    1. Sclerotic atrophy with hyperplasia

Atrophic epithelium undergoes “hyperplastic change”

 

A central duct or alveolus, generally elongated is surrounded by newly formed acini. Acini are small, regular and closely packed.

 

 

 

Resembles lobular hyperplasia described above but is much more irregular. Contain acini of low cuboidal cells with larger hyperchromatic nuclei, with prominent “nuclear dots”

 

 

 

 

Similar to lobular hyperplasia of the breast. May be some increase in fibrous stroma and scattered lymphocytic infiltration is often present.

 

Cytoplasm is scanty and opaque. Stroma is commonly infiltrated with lymphoid cells. Small foci of clear cell small-acinar carcinoma often seen at the margin of these areas.

Considered post-atrophic hyperplasia in new classification

 

 

 

Secondary hyperplasia

 

Relatively common. Stroma is atrophic but epithelium in some areas is quite active, with tall columnar cells with eosinophilic cytoplasm and large nuclei

 

Indicates a similar type of hyperplasia described by Andrews, which appears most consistent with PIN