Answer: Adenosis

Histology: Within the TUR, there is a focus of crowded glands. The focus has a relatively lobular appearance. At medium magnification, there is an admixture of medium to small glands, some of which have papillary infolding. Some contain crystalloids. At higher magnification, the smaller crowded glands and the larger more recognizable benign glands with papillary infolding have identical pale cytoplasm and uniform bland nuclei lacking prominent nucleoli. Many of the glands have clefting between the stroma and glands. A PIN4 cocktail shows patchy basal cell staining in some of the glands, with others appearing to lack a basal cell layer.

Discussion: One of the most common lesions that may be confused with carcinoma is adenosis. The other commonly used term for adenosis is “atypical adenomatous hyperplasia (AAH).” I prefer the term “adenosis,” as prefacing “adenomatous hyperplasia” with “atypical” can worry clinicians and patients and there is no association between adenosis and carcinoma. At scanning magnification, adenosis is characterized by a lobular proliferation of small glands. In contrast, low-grade carcinoma has a haphazard, irregular, infiltrative growth pattern. Probably the most important differentiating feature of adenosis seen on hematoxylin and eosin stain is that within a nodule of adenosis there are elongated glands with papillary infolding and branching lumina typical of more benign glands, yet in their nuclear and cytoplasmic features they look similar to the adjacent small glands suspicious for carcinoma. Glands of adenocarcinoma, even in the unusual case when the tumor is fairly lobular, shows a pure population of small crowded glands without benign architectural or cytological features that do not merge in with adjacent larger benign glands. Usually, adenosis has been described as having totally bland appearing nuclei without nucleoli, yet occasional visible nucleoli can be seen. The luminal contents also may be useful in this differential diagnosis. Corpora amylacea are commonly seen in adenosis, and are rare in carcinoma. Crystalloids should not be used to differentiate adenosis and carcinoma as can be seen in both. As few as 10% of the glands in a nodule of adenosis may be labeled with antibodies to basal cell markers, although usually more than half of the glands will show some staining. The stain is also patchy within a given gland, with sometimes only one to two basal cells identified. If some glands suspicious for adenosis lack high molecular weight cytokeratin or p63 immunoreactivity, yet are otherwise indistinguishable from adjacent glands which demonstrate basal cell immunoreactivity, the absence of a basal cell layer in some glands should not be used to diagnose the lesion as carcinoma. Clefting between glands and surrounding stroma which has been proposed to be a feature helpful to diagnose prostate cancer is not specific and as the current case illustrates can be misleading.