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

Simple Atrophy: consists of atrophic cells lining acini with relatively normal caliber that lack papillary fronds, where the number of glands per unit area do not appear to be increased relative to normal tissue.
Simple Atrophy with Cyst Formation: This is a subtype of simple atrophy as delineated originally by Franks. Two general patterns are now encompassed: those containing very large diameter glands (> 1 mm) and those containing smaller, rounded glands. The amount of cytoplasm at times may be so attenuated as to be nearly invisible. When there is significant cytoplasm in the luminal cell, it tends to be clear. Atrophy with cyst formation tends to have less inflammation than the other sub-types.
Post-Atrophic Hyperplasia (PAH): The subtype consists of acini that are smaller and round and appear in a lobular distribution, often surrounding a somewhat dilated duct with an apparent increase in the number of small glands compared to normal tissue (thus the term hyperplasia). Some authors tend to refer to some of these lesions as "lobular atrophy" or "lobular hyperplasia".
Partial Atrophy: Prostate acini in which luminal cells contain less cytoplasm than normal, but cytoplasm is mostly clear. This gives the glands a distinct atrophic quality but unlike most other types of focal atrophy, they do not appear basophilic at low magnification. The architectural arrangement of glands can be similar to that of either simple atrophy or post atrophic hyperplasia. These cells frequently show mild to moderate nucleolar enlargement.
Mixed Prostate Atrophy Lesions:

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 Lobular hyperplasia 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