Prostate gland & seminal vesicles

• First described in 1995, vanishing cancer indicates no residual tumor found in radical prostatectomy specimen despite confirmed tumor in needle biopsy (Am J Surg Pathol 1995;19:1002)
• Sometimes, only high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation suspicious for but not diagnostic of cancer (ASAP) is found

• Contemporary incidence of vanishing cancer is 0.2% of radical prostatectomy specimens; it was higher a decade or two ago when prostatectomy was being performed for smaller / lower grade cancers
• Incidence is higher in large prostates or in preoperatively treated ones
• Resolution of dilemma involves complete tissue submission, cancer specific immunostains, use of second opinion, consider flipping blocks to other surface; some residual cancers simply cannot be detected after the above efforts

• ICD-10: C61 - malignant neoplasm of prostate

• Most recent incidence at prostatectomy is 0.2% of 160,532 with clinically localized cancer based on Surveillance, Epidemiology and End Results (SEER) database (2004 - 2015) (Urol Oncol 2019;37:696)
• This is lower than the incidence of vanishing cancer of 0.6% up to 4.9% of prostatectomy specimens a decade ago (Arch Pathol Lab Med 2011;135:1466, Virchows Arch 2007;450:371, Am J Surg Pathol 2009;33:120, Indian J Cancer 2013;50:170, Pathol Res Pract 2012;208:578)
• Variation in rate is probably due to the institution and time of the study; however, the recent decrease may reflect upward stage and grade migration at prostatectomy, due to increased acceptance of active surveillance for low grade cancer (Eur Urol Oncol 2018;1:160)
• Predictors of vanishing cancer included a prostate weight ≥ 60 g or patients with prostate specific antigen (PSA) < 20 ng/ml, with biopsy GS < 7, patients with < clinical T2 disease and < 2 positive biopsy cores (Am J Surg Pathol 2009;33:120, Urol Oncol 2019;37:696)

• Most often, the phenomenon is attributed to the fact that routine histologic sections cannot evaluate every cubic millimeter of prostate volume, so small cancer foci remain in the paraffin block
• Rarely, prostate cancer may have been ablated by the biopsy or transurethral resection procedure (BJU Int 2004;94:939)
• Currently, more patients are receiving preoperative androgen deprivation, such as enzalutamide, that shrinks the cancer (Urology 2005;65:76, Clin Cancer Res 2017;23:2169)
• It is also proposed that a minute cancer focus at the edge of the prostate may be inadvertently left behind in the overzealous attempt to perform a nerve sparing procedure (Indian J Cancer 2013;50:170)

• Diagnostic resolution should include these steps in the following order (Urol Oncol 2019;37:696):
  • If the prostatectomy tissue has been partially submitted, complete submission should be pursued
  • Get a second pathologist, particularly a urologic pathologist, to reread the resection slides
  • Review the biopsy that was diagnostic of cancer, if slides are available
  • Immunostains (see below)
  • Flip tissue in some or all of the paraffin blocks and have the opposite surfaces of the tissues cut
  • DNA identity analysis can be performed if specimen switching is suspected (see below)

• Vanishing cancer patients typically have lower serum PSA (Urol Oncol 2019;37:696)

• Larger prostates with an average size of 74 g are more likely to exhibit no residual tumor (Am J Surg Pathol 2009;33:120)

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• P504S racemase is positive in cancer; get immunostains on deeper levels, on areas initially suspicious for cancer (ASAP)

• Microsatellite analysis can be performed on the prostatectomy and biopsy specimens to confirm specimen identity; this very rarely shows a specimen switch (1 in 10 cases of vanishing cancer was attributed to specimen mixup) (Am J Surg Pathol 2005;29:467)
• This is particularly indicated if there is high grade or high volume cancer on the biopsy (Am J Surg Pathol 2005;29:467)

A 70 year old man undergoes radical prostatectomy with an organ weight of 90 g. What is the least likely contributor to finding no residual cancer?

1. Partial sampling of every other tissue slice (as is commonly done for > 50 g prostates)
2. Preoperative course of enzalutamide ablated any residual cancer
3. Prior prostate biopsy specimen switch
4. Residual cancer remains in the paraffin, even after flipping the blocks

C. A specimen switch of the prior prostate biopsy is the least likely explanation and could be detected molecularly. If initial partial sampling was done, complete sampling of the tissue should be pursued; if cancer is not found, flipping the blocks is recommended; use of immunostains may help if any foci are suspicious. Finally, it is possible that a preoperative course of enzalutamide has ablated any residual cancer.

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Reference: Vanishing cancer