Foamy Gland Carcinoma of the Prostate in Needle Biopsy Incidence, Gleason Grade, and Comparative α-Methylacyl-CoA Racemase vs. ERG Expression

Foamy gland carcinoma is a variant of prostatic acinar adenocarcinoma characterized by abundant, foamy cytoplasm, frequently showing small, pyknotic nuclei. The incidence and Gleason grade of foamy gland carcinoma in a large prostate needle biopsy series have not been established. Foamy gland carcinoma may be deceptively benign appearing and missed on needle biopsy. Immunohistochemical staining for basal cells and alpha-methylacyl-CoA racemase (AMACR) can support a diagnosis of foamy gland carcinoma, but the sensitivity of AMACR for foamy gland carcinoma has been reported to be lower than that for usual acinar carcinoma. The utility of ERG immunohistochemistry in the diagnosis of foamy gland carcinoma has not been explored. The aim of this study was to characterize the incidence and Gleason grade of foamy gland carcinoma in a large consecutive series of prostate needle biopsy cases. We also assessed ERG expression in foamy gland carcinoma, in comparison with AMACR expression, to determine whether ERG expression provides added diagnostic value beyond AMACR expression. We evaluated a consecutive series of 476 prostatic adenocarcinoma needle core biopsy cases for presence, linear extent, and Gleason grade of foamy gland carcinoma. A selected block from each case containing foamy gland carcinoma was evaluated for AMACR and ERG expression by immunohistochemistry. Of the 476 cases, 17% contained a foamy gland carcinoma component, with 2% of the cases showing pure foamy gland carcinoma. Two cases of pure foamy gland carcinoma had a total linear extent of <3 mm. The majority (80%) of cases had a Gleason score 3+3 = score of 6. Sensitivity of AMACR for foamy gland carcinoma was 92%, and sensitivity of ERG was 42%. No AMACR-negative case was ERG positive. Low AMACR expression was detected in 24 of 72 cases (33%), and of these cases ERG was positive in 5 (21%). In summary, foamy gland carcinoma features are relatively common in prostate needle core biopsies, the foamy gland carcinoma is admixed with usual acinar carcinoma in the majority of cases, and is usually not of high Gleason grade, although 20% are Gleason score 7 or greater. ERG immunohistochemistry did not provide added value beyond AMACR expression in most cases, suggesting that it need not be initially utilized in addition to basal cell markers and AMACR when immunohistochemistry is needed to substantiate a diagnosis of foamy gland malignancy. This is an important consideration in this era of cost-consciousness in application of immunohistochemistry. Sensitivity of AMACR for foamy gland carcinoma was comparable to that seen in studies of usual acinar carcinoma and is an excellent marker for foamy gland carcinoma of the prostate. ERG immunohistochemistry could be considered in a second round of immunostaining of select difficult cases of foamy gland carcinoma with low AMACR expression.