Atrophy is a common microscopic finding, consisting of small, distorted glands with flattened epithelium, hyperchromatic nuclei, and stromal fibrosis. It is usually idiopathic, and the prevalence increases with advancing age.(23) At low magnification, atrophy may be confused with adenocarcinoma due to the prominent acinar architectural distortion. At high magnification, atrophy usually lacks nuclear and nucleolar enlargement, except in cases of postatrophic hyperplasia.
Clusters of atrophic prostatic acini which display proliferative epithelial changes are referred to as postatrophic hyperplasia (PAH).(50, 51) PAH is at the extreme end of the morphologic continuum of acinar atrophy, which most closely mimics adenocarcinoma. This continuum varies from mild acinar irregularity with a flattened layer of attenuated cells with scant cytoplasm to that of PAH in which the lining cells are low cuboidal with moderate amounts of cytoplasm. There is no sharp division in thiscontinuum between atrophy and PAH, challenging the utility of PAH as a distinct entity. However, the morphologic mimicry of PAH and carcinoma creates the potential for misdiagnosis, sometimes resulting in unnecessary prostatectomy.(51) To avoid this potentially tragic misinterpretation, the pathologist should have an understanding of this extreme morphologic variant of atrophy. We believe that PAH is a diagnostic category for atrophic acini, which most closely mimic adenocarcinoma, recognizing that this is merely a descriptive term.
PAH consists of a microscopic lobular cluster of five to 15 small acini with distorted contours reminiscent of atrophy (Fig. 6.4a). One or more larger dilated acini are usually present within these small round to oval clusters, and the small acini appear to bud off from the dilated acinus, imparting a lobular appearance to the lesion. The small acini are lined by a layer of cuboidal secretory cells with mildly enlarged nuclei with an increased nucleus-to-cytoplasmic ratio when compared with adjacent benign epithelial cells. The nuclei contain finely granular chromatin, and nucleoli are usually small, although mildly enlarged nucleoli are focally present in 39% of cases. The cytoplasm is often basophilic or finely granular to clear, and luminal apocrine-like blebs are present in 33% of cases. Luminal mucin is occasionally present in PAH. Corpora amylacea are present in 75% of cases of PAH, but crystalloids are rarely if ever seen.
The basal cell layer is usually present in PAH, but is often inconspicuous by routine light microscopy. Basal cell hyperplasia is rarely seen in foci of PAH. Immunohistochemical stains for high molecular weight keratin (antibody 34βE12) reveal a focally fragmented basal cell layer in some cases. Adjacent prostatic acini always show at least focal atrophy.
Stromal changes are always present in PAH, ranging from smooth muscle atrophy to dense sclerosis with compression of acini. In cases with sclerosis, the acinar lumens are compressed and showed marked distortion. Subtyping of PAH into the lobular and postsclerotic subtypes is useful only to allow recognition of PAH and distinguish it from mimics such as low-grade adenocarcinoma, and we prefer not to subtype PAH. Also, PAH is often associated with patchy chronic inflammation; infrequently, dilated acini contain luminal neutrophils. PAH is distinguished from carcinoma by its characteristic lobular architecture, intact or fragmented basal cell layer, inconspicuous or mildly enlarged nucleoli, and adjacent acinar atrophy with stromal fibrosis or smooth muscle atrophy. Low-grade adenocarcinoma is the most important differential diagnostic consideration with PAH. PAH usually has a lobular pattern on low power, similar to Gleason pattern 2 and 3 adenocarcinoma. However, the lobular pattern is less distinct in cases with abundant stromal sclerosis, and there may be a pseudoinfiltrative growth pattern with fibrous entrapment of acini. Nucleolar changes are also useful in separating PAH and carcinoma, although some cases of low-grade carcinoma have only patchy large nucleoli or even micronucleoli. Mildly enlarged nucleoli may be present in PAH, but only focally, and the majority of cells have micronucleoli. The separation of PAH from carcinoma is most difficult in needle biopsy specimens in which only a portion of the lesion is sampled, and awareness of this entity assists in this distinction. In about half of the biopsies containing PAH, the lesion extends to the edge of the tissue core, indicating incomplete sampling.