The patient was diagnosed at the age of 62-year-old, coherent with the reported median age for prostatic SRCC of around 68 years, with a range of 50–85 years [4, 8]. At the time of diagnosis, 75% of patients were seen to have a locally advanced or metastatic disease as per our patient who had a locally advanced T-stage for the prostate even though he had no metastases [4, 5]. Some studies stated that signet ring cells must constitute at least 20–25% of the tumor to be able to have a diagnosis of primary prostatic SRCC, although other studies stated that a certain ratio of cells was not needed for diagnosis [5]. Either way in our patient, all 12 cores of the TRUS biopsy demonstrated this malignancy which strongly suggests a prostatic SRCC in either school of thought.
Since the gastrointestinal tract harbors more common locations for signet ring cells, many tests especially various immunohistochemistry focus on differentiating a primary SRCC from one located in the gastrointestinal tract. The main diagnostic issue in this patient is in the immunohistochemistry aspect which showed a negative PSA staining, as primary prostatic SRCC cases are 87% positive for PSA/PSAP staining [4]. However, a study by Fujita et al. showed that 3 out of the 37 (8%) of patients with primary SRCC of the prostate did not stain positive for PSA [5]. PSA has also been demonstrated to be a prostate tissue-specific marker, but its reactivity may be lost in a significant number of high-grade, poorly differentiated, and metastatic prostatic adenocarcinoma [3, 6]. Clearly, it is crucial to differentiate between gastrointestinal and prostate origin as the treatment modalities vary remarkably. In metastatic gastrointestinal primary tumor, additional intervention would be required especially bowel resection, defunctioning, and/or stenting.
The intestinal marker CDX2, which was positive in this patient, has also recently been found to stain a small percentage of primary prostate adenocarcinomas and can be positive in 30% of SRCC. GATA3, which has been found negative in this patient, is a transcription factor important in the reliable differentiation of breast epithelium, urothelium, and subsets of T-lymphocyte [6, 7]. Another study done by Chang et al. showed that GATA3 is highly specific when differentiating high-grade urothelial carcinoma from high-grade prostatic adenocarcinoma. Eighty percent of the cases of urothelial carcinoma examined were GATA3 positive and all 38 high-grade prostatic adenocarcinomas in the study were GATA3 negative [8]. In addition, certain immunohistochemical markers namely estrogen receptor-beta and Ki67 are reliable prognostic markers in prostate adenocarcinoma [9].
Metastatic SRCC primarily from the gastrointestinal tracts and the urinary bladder must be ruled out by CT scan, cystoscopy, colonoscopy, and upper gastric tract endoscopy [5]. As in our case, in view of negative PSA stain from TRUS biopsy, metastatic SRCC needs to be ruled out. However, positron emission tomography which will be helpful to look for occult primary cancer could not be performed. In view of the histological findings, immunohistochemical study, and negative systemic examination for other possible primary sites, we concluded that it was a case of primary SRCC of the prostate.
Being a primary SRCC, there is no single treatment modality is ideal, however, an aggressive multimodal treatment paradigm should be considered. This includes an early hormonal treatment and aggressive surgical resection as well as adjuvant radiation therapy. Despite that, studies have shown an overall poor prognosis and survival even with aggressive therapy with a combination of all available modalities, with Fujita et al. showing a 5-year survival rate of only 11.7% while Warner et al. showed an average survival time of 29 months [4, 5]. In addition, stromogenic cancers and patterns with extravasated mucin have the worst outcome amongst Gleason 5 prostate cancers [10]. This is also unfortunately true for our patient who passed away 4 months before any treatment could be initiated.
