The histologic section of one needle biopsy was characterized at low-power examination by the replacement of normal prostatic tissue by a proliferation of haphazardly arranged glands, partially arranged in an ill-defined nodule. The lesions had an infiltrative aspect at their edge, but the glands were not admixed with normal prostatic acini. At medium power, the proliferating glands were often slit-like, variably sized and shaped, alternating small and rounded acini with elongated and branching ones (Figure ​(Figure1A1A &1B). Occasional solid nests and cords could be seen. The atypical acini were lined by epithelial secretory cells with clear eosinophilic cytoplasm (Figure ​(Figure1C).1C). The nuclei were regular, rounded to oval, and slightly larger than those of the adjacent normal prostatic acini. There were inconspicuous nucleoli. There were a few focally prominent basally located cells with dense amphophilic cytoplasm. Eosinophilic crystalloids were present within some acinar lumina (Figure ​(Figure1C1C &1D).

Immunohistochemical (IHC) stains revealed strong reactivity for alpha-methylacyl-coenzyme A-racemase (AMACR) in both small and large glands (Figure ​(Figure2A2A &2B), patchy reactivity for p63 (Figure ​(Figure2C)2C) and patchy reactivity for high-molecular-weight cytokeratin CK903/34βE12 (Figure ​(Figure2D2D).

Microscopically, AAH is a localized proliferative lesion consisting of small amounts of atypical epithelial cells arranged in irregular glandular patterns, often within or adjacent to typical hyperplastic nodules [8]. At low magnification, it is usually partially circumscribed with a pushing rather than infiltrating border, although the small acini may show a limited degree of infiltrative features at the margins. The individual glands are closely packed but separate and show no evidence of fusion. The glands show some variation in size and shape and are lined by cuboidal to low columnar cells with moderate to abundant clear or lightly eosinophilic cytoplasm [6,9]. The basal cells are usually recognized at least focally. The luminal borders are often irregular and somewhat serrated in contrast to the rigid borders that typify small acinar carcinoma. The lumens are often empty but may contain corpora amylacea and in some instances luminal eosinophilic crystalloids [5,9]. The nuclei are round to oval, slightly enlarged, and with uniform fine chromatin and inconspicuous or small nucleoli [9]. AAH can be difficult to distinguish from low-grade prostatic adenocarcinoma (Gleason pattern 1 or 2) because both are located in the transition zone and show small acinar proliferation and intraluminal crystalloids [9]. The two distinguishing features of AAH are the lack of significant cytological atypia and the presence of patchy basal cells, which can be demonstrated by patchy immunostaining for high molecular-weight cytokeratin (CK903/34βE12) or p63 [7-9]. In contrast, prostatic adenocarcinoma usually shows notable nuclear atypia, lacks basal cells, and rarely expresses high molecular weight cytokeratin [10]. Yang and colleagues [11] found that AMACR was focally expressed in 10% of cases and diffusely positive in only 7.5% of cases of AAH. The biological significance of AMACR expression in a small subset of AAH remains to be determined. AAH differs from sclerosing adenosis, another benign mimicker of prostate adenocarcinoma, since sclerosing adenosis displays myoepithelial features of the basal cells and an exuberant stroma of fibroblasts and loose ground substance [12].

While circumstantial evidence exists, there is lack of proof of a relationship between AAH and adenocarcinoma. It has been suggested that AAH is a precursor of some low-grade transition zone carcinomas but the lack of an increased prevalence of AAH in prostate glands with transition zone carcinoma argues against this hypothesis. Clearly, there is less evidence linking AAH to carcinoma than there is for high-grade PIN and cancer. Therefore, the major importance of AAH is its potential for being misdiagnosed as adenocarcinoma. Biochemical and molecular analyses of AAH have generated inconclusive results. There is limited data that AAH has a proliferation rate higher than hyperplasia but lower than adenocarcinoma [1,7,8,13]. By the use of fluorescent in situ hybridization analysis, chromosomal anomalies were seen in only 9% of AAH cases, compared with 55% of prostatic adenocarcinoma cases [13]. Two independent studies showed that AAH contains genetic alterations commonly found in early prostatic carcinoma, with changes being reported in 47% or 12% of AAH cases, respectively [8,14]. Recent cytogenetic analyses have detected abnormalities of chromosome 8 in a very small proportion (4–7%) of AAH cases [7,8]. The recent finding of molecular alterations in AAH including immunoreactivity for AMACR, a marker linked to prostate adenocarcinoma, suggests that at least a subset of AAH cases might be related to prostate carcinoma of the transition zone [11,13,14].