Case 8 -

Benign Mimics of Prostate Cancer and Unusual Cancer Morphologies which Mimic Benign Conditions Rajal Shah and Ming Zhou

Case 8: A 50 year-old male patient with family history of prostate cancer and PSA of 4.5 ng/ml. The patient underwent 12 core extended biopsy. Diagnosis: Adenocarcinoma of the prostate, Gleason score of 3+3=6 with pseudohyperplastic and foamy features involving 60% of one core. Prostate Carcinomas Mimicking as Benign Process As there are many benign conditions, which can mimic cancer, some carcinomas may resemble benign prostate process due to their bland cytology or architectural pattern. A careful correlation of several morphological features along with adjunctive immunohistochemistry stains is necessary to arrive at the correct diagnosis. Table 1 Prostate Carcinomas mimicking benign lesions Histological pattern of cancer Benign condition they may mimic Foamy carcinoma Benign/Cowper's glands or Xanthoma cells Atrophic carcinoma Atrophy Pseudohyperplastic carcinoma Hyperplasia or HGPIN Low grade Gleason score 2-5 carcinomas Adenosis 1) Foamy gland carcinoma Foamy gland carcinoma is relatively common differentiation seen in needle biopsies. Conventional carcinoma component is usually present. When it is well differentiated it may mimic benign glands such as cowper's glands or xanthomatous infiltrate when it is of higher grade, due to its relatively bland cytology [1, 2]. Key histological features: 1) Architectural pattern of crowded and/or infiltrative glands lined by abundant foamy cytoplasm. Due to abundant foamy cytoplasm nucleus to cytoplasm ratio is very low, simulating benign condition. The cytoplasm has similar appearance to seen in xanthoma cells; however it does not contain lipid, but rather empty vacuoles. 2) More typical features of adenocarcinoma such as nuclear enlargement and prominent nucleoli are usually not conspicuous. Nuclei in the foamy gland cancer are typically rounder than oval nuclei seen in benign glands. 3) Basal cell markers are typically negative and useful to provide an objective support to the diagnosis. AMACR may demonstrate low sensitivity (68-70%) for this type of cancer [3]. Despite the bland cytology of the foamy gland carcinoma, biologically they appear to behave as an intermediate to aggressive cancers [4]. Many of the foamy cancers, when associated with non-foamy cancer represent Gleason pattern 4. In a recent Gleason grading consensus conference it was adopted that foamy gland cancer should be graded based on its underlying architecture rather than foamy appearance. 2) Atrophic cancer Pure atrophic cancer unassociated with hormonal therapy is rare in needle biopsy. The diagnosis can be challenging and one has to rely on several important architectural and cytological features. Key histological features helpful to differentiate it from benign atrophy [5]: 1) A truly infiltrative process with small atrophic glands situated between larger benign glands 2) Usual concomitant presence of conventional adenocarcinoma of the prostate is typically present and very helpful to facilitate its recognition. 3) Greater cytological atypia than seen in typical benign atrophic glands. The cytoplasm is relatively scant but still more than typical atrophic glands giving them less basophilic appearance then conventional atrophic glands. 4) Basal cell markers are typically negative and similar to foamy cancers AMACR may demonstrate low sensitivity for this cancer [6]. Most atrophic cancers represent Gleason pattern 3 carcinomas. 3) Pseudohyperplastic cancer Pseudohyperplastic cancer typically resemble to hyperpastic/PIN glands due to glands of large size, complex undulating architecture and papillary infolding. Key histological features helpful to separate them from hyperplasia or HGPIN [7, 8]: 1) Architectural pattern of numerous closely packed glands with complex and undulating architecture and frequent papillary infolding. This diagnosis should be made with extreme caution when the focus of concern is small as the diagnosis of HGPIN cannot be excluded with certainty. Immunohistochemical markers may not be very helpful in this circumstance. 2) Nuclear features are usually typical of conventional adenocarcinoma with enlarged nuclei and prominent nucleoli. 3) The cytoplasm is amphophilic with frequent amorphous secretions and blue mucin. 4) The conventional basal cell markers provide an objective support to the diagnosis. AMACR has lower sensitivity for this type of cancer than conventional adenocarcinoma [3]. Majority of pseudohyperplastic carcinomas represent Gleason 3 pattern. Bibliography Sebo, T. J., Bostwick, D. G., Farrow, G. M. et al. prostatic xanthoma: a mimic of prostatic adenocarcinoma. Hum Pathol.25: 386-9, 1994. Nelson, R. S. & Epstein, J. I. Prostatic carcinoma with abundant xanthomatous cytoplasm. Foamy gland carcinoma. Am J Surg Pathol. 20: 419-26, 1996. Zhou, M., Jiang, Z. & Epstein, J. I. Expression and diagnostic utility of alpha-methylacyl-CoA-racemase (P504S) in foamy gland and pseudohyperplastic prostate cancer. 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