Final Diagnosis -- Signet ring cell carcinoma of the prostate



Poorly differentiated prostatic adenocarcinoma, Gleason 4+5=9 with high grade prostatic intraepithelial neoplasia and chronic prostatitis.



Worldwide, prostate cancer is the sixth most common cancer in the world (1). According to SEER data in 2007, it is now the most common cancer in men in the United States (3). It is generally a less considerable cause of death from cancer, comprising 3.2% of all cancer deaths (1). This cancer is among the most prevalent form in men, as many live beyond the initial diagnosis, and approximately 2.2 million men in the US were alive with prostate cancer in 2007 (1,3). The WHO does note that both the increased incidence and prolonged survival, particularly in developed countries, may be due to greater detection of latent cancers by active screening programs. Nevertheless, the risk of prostate cancer increases with age and, worldwide, the vast majority occurs in men older than 65 years (1).

Widespread screening with serum Prostate-Specific Antigen (PSA) has lead to smaller tumors at the time of detection and fewer patients presenting symptomatically. Symptoms may include bladder outlet obstruction and other urinary symptoms. While transrectal ultrasound is helpful in determining the size of the prostate and any specific lesions, computed tomography and magnetic resonance imaging have proven less useful except in staging advanced disease (1).

There are several histologic patterns of prostatic adenocarcinoma besides the typical acinar pattern, including atrophic, pseudohyperplastic, foamy gland, colloid and signet ring cell, oncocytic, lymphoepithelioma-like, and sarcomatoid variants (1). Signet ring cell carcinoma of the prostate is a rare variant; a 2004 review noted only 42 cases in the English literature and a PubMed search revealed very few additional recently reported cases (4). Signet ring cells with large cytoplasmic vacuoles displacing the nucleus should comprise at least 20-25% of the tumor (2-7).

As signet ring cell carcinomas (SRCCs) are well known to occur in the breast, pancreas, stomach, colon, and urinary bladder and similar non-mucin producing cells can be seen in lymphomas, thyroid tumors, oligodendrogliomas, and smooth muscle tumors, alternative primary tumors must also be considered. Artifactual mimickers of smooth muscle cells and lymphocytes with signet-ring morphology, not infrequently seen following transurethral resection or biopsy, must also be excluded. Often this is achieved by a combination of extensive clinical radiologic and endoscopic examination and immunhistochemical staining of biopsy or resection material. These tumors tend to express both PSA and PSAP (prostate specific acid phosphatase), and may also express pancytokeratin but do not stain for carcinoembryonic antigen, cytokeratins 7, cytokeratin 20, synaptophysin, other lymphocytic or smooth muscle markers (5,7). The vacuoles may not contain mucin and, as such, fail to stain with mucicarmine, PAS, PASD, or Alcian Blue. Adjacent adenocarcinoma of a more typical prostatic acinar type may also support diagnosis of primary prostatic SRCC.

In the 2004 review, the mean age of patients was 68.2 years, with a range of 50-84 years, and 41.2% of the patients had stage IV disease at the time of diagnosis (4). These tumors are generally considered to be poorly responsive to hormone therapy and to convey a poor prognosis, although a few reported cases followed less aggressive courses (6,7).


  1. Eble JN, Sauter G, Epstein JI, Sesterhenn IA (Eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press, 2004, 162-192.
  2. Humphrey PA. The Prostate Gland. In Silverberg's Principles and Practice of Surgical Pathology and Cytopathology. Silverberg SG, Delellis RA, Frable WJ, LiVolsi VA, Wick MR (Eds). 4th edition. Philadelphia: Elsevier Churchill Livingstone, 2006, 1791-1930.
  3. Altekruse SF, Kosary CL, Krapcho M, et al (Eds). SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD,, based on November 2009 SEER data submission, posted to the SEER website, 2010.
  4. Fujita K, Sugao H, Gotoh T, Yokomizo S, Itoh Y. Primary signet ring cell carcinoma of the prostate: report and review of 42 cases. Int J Urol 2004; 11: 178-181.
  5. Lilleby W, Axcrona K, Alfsen GC, Urnes T, Hole KH. Diagnosis and Treatment of primary signet ring cell carcinoma of the prostate. Acta Oncol 2007; 46: 1195-1197.
  6. Akagashi K, Tanda H, Kato S, et al. Signet-ring cell carcinoma of the prostate effectively treated with maximal androgen blockade. Int J Urol 2003; 10: 456-458.
  7. Kuroda N, Yamasaki I, Nakayama H, et al. Prostatic signet-ring cell carcinoma: case report and literature review. Pathol Int 1999; 49:457-461.

Contributed by Hannah Kastenbaum, MD and Agnes K. Liman, MD

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