Case 4 -

Recurrent or Metastatic Prostate Adenocarcinoma with Treatment Effect Jun Zhang, Mayo Clinic, Rochester, MN

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Clinical History 71-year-old male with dysuria, recently underwent cystoscopy on 9-28-10 and had a transurethral resection of a small bladder tumor. Past medical history significant for metastatic prostate cancer to bone and status post prostatectomy, radiation and hormonal therapy. Pertinent Laboratory Data: Bladder calculi Case 4 - Figure 1 Case 4 - Figure 2 Case 4 - Figure 3 Case 4 - Figure 4 Case 4 - Figure 5 Case 4 - Figure 6 Case 4 - Figure 7 S100 Case 4 - Figure 8 Bone biopsy Case 4 - Figure 9 Bone biopsy - PSA Case 4 - Figure 10 Case 4 - Figure 11 Case 4 - Figure 12 Case 4 - Figure 13 Case 4 - Figure 14 Case 4 - Figure 15 Case 4 - Figure 16 Case 4 - Figure 17 Case 4 - Figure 18 Case 4 - Figure 19 Introduction: A 71 Y male with a past medical history of metastatic prostate cancer to T1 vertebral body, status post prostatectomy, radiation and hormonal therapy. Prostatectomy showed cancer with Gleason score: 4+3. Recently underwent a cystoscopy and had a transurethral resection (TUR) of a small bladder tumor. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The overlying urothelial mucosa is benign. Organoid growth pattern arranged in solid nests and trabeculae with small to intermediate and large cells, relatively abundant pink to faintly granular cytoplasm, round-ovoid and vesicular nuclei with single prominent nucleolus. Nuclear pleomorphism are seen. The immunohistochemistry studies show the neoplastic cells are positive for PSA and PSAP, negative for chromogranin, CK903 and P63, and nonspecific stain for S100. Differential Diagnoses: The differential diagnosis include recurrent or metastatic prostate adenocarcinoma with treatment effect, paraganglioma of bladder, nephrogenic adenoma (metaplasia), florid von Brunn's nest proliferation, nested variant of urothelial carcinoma. Final Diagnosis: Recurrent or metastatic prostate adenocarcinoma with treatment effect. Case Discussion: Based on clinical history of prostate carcinoma with Gleason score of 4+3, the number one differential would be recurrent or metastatic prostate adenocarcinoma with treatment effect. The initial immunostains, positive PSA and PSAP (Case 4-Fig 13 and 14) and negative CK903 (not showing) would confirm the diagnosis. The other differential diagnosis would include paraganglioma of bladder. However, there are two different cell populations within the organoid solid nest growth. One population has relatively abundant pink to granular cytoplasm, round-ovoid and vesicular nuclei with single prominent nucleolus; the other population has infiltrative growth and relatively smaller cells and uniform round nuclei, conspicuous nucleoli, prominent basement membrane, which raises the possibility of nephrogenic adenoma (metaplasia), florid von Brunn's nest proliferation and nested variant of urothelial carcinoma. As seen in case 4-Fig 15 and 16, bladder TUR from 43 Y M, the similar morphology with neoplastic cells are positive for chromogranin, the spindle cells (sustentacular cells)are positive for S100 (not showing), which supports a diagnosis of paraganglioma of urinary bladder. In case 4-Fig 18 and 19, bladder curetting from 84 Y M, the acinar and tubular formations with prominent and thickened basement membrane in the different field of a nephrogenic adenoma case gave away the diagnosis. And the PIN2 cocktail (racemase and P63 in case 4-Fig 18) and the negative PSA and PSAP stains (not showing) would rule out prostate adenocarcinoma, and confirm a diagnosis of nephrogenic adenoma (metaplasia). Review of the Literature/Treatment Options (if applicable): Paraganglioma of bladder is a very rare benign neoplasm of urinary bladder, which is easily mistaken for invasive high grade urothelial carcinoma, especially on a small biopsy specimen, and with possible muscularis propria involvement. The possible treatment options would be between partial vs total cystectomy. The nephrogenic adenoma (metaplasia)is relatively common and benign condition, although can recur, which is always related to physical injury and can be seen in muscularis propria. It has many faces and can be mistaken for invasive urothelial carcinoma and prostate adenocarcinoma. Nested variant of urothelial carcinoma is also a very rare and aggressive type. On a small biopsy specimen, it is often very challenging to tell the difference between florid von Brunn's nest proliferation vs nested variant of urothelial carcinoma(NVUC). So far rare effective or definitive immunomarkers can aid in definitive diagnosis, specially when the biopsies are small and superficial. In our lab, using FISH(UroVysion probes), we have a small number of resection proved cases showed very promising results, in which the most NVUC cases have chromosome abnormality of polysomy and 9p21 loss vs no polysomy or rare 9p21 loss in von Brunn's nest proliferation. Conclusion(s): When the morphologic features show paraganlioma-like growth pattern in a bladder biopsy or TUR or curetting specimen, the top 4 differential would include paraganglioma, von Brunn's nest proliferation, prostate adenocarcinoma and nested variant of urothelial carcinoma, especially when lesion involving muscularis propria. The simpe panel of markers would help clarify the diagnosis. References: Ellis, D. W., Leffers, S., Davies, J. S., and Ng, A. B. (1984). Multiple immunoperoxidase markers in benign hyperplasia and adenocarcinoma of the prostate. Am J Clin Pathol 81, 279-84. Grignon, D. J., Ro, J. Y., Mackay, B., Ordonez, N. G., el-Naggar, A., Molina, T. J., Shum, D. T., and Ayala, A. G. (1991). Paraganglioma of the urinary bladder: immunohistochemical, ultrastructural, and DNA flow cytometric studies. Hum Pathol 22, 1162-9. Gupta, A., Wang, H. L., Policarpio-Nicolas, M. L., Tretiakova, M. S., Papavero, V., Pins, M. R., Jiang, Z., Humphrey, P. A., Cheng, L., and Yang, X. J. (2004). Expression of alpha-methylacyl-coenzyme A racemase in nephrogenic adenoma. Am J Surg Pathol 28, 1224-9. Skinnider, B. F., Oliva, E., Young, R. H., and Amin, M. B. (2004). Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma. Am J Surg Pathol 28, 701-5. Oberg, TN, Kipp, BR, Campion, MB, Voss, JS, Jimenez, RE, Sebo, TJ, Cheville, JC, Halling, KC, Zhou, M, Zhang, J. Utilization of FISH to distinguish nested variant of urothelial carcinoma from von Brunn's Nests. Modern Pathology, 2010, USCAP annual meeting abstracts.