PDA: Prostatic Ductal Adenocarcinoma; PAA: Prostatic Acinar Adenocarcinoma; AJCC: American Joint Committee on Cancer; TRUS: Transrectal Ultrasound; PSA: Prostate Specific Antigen; RT: Radiotherapy; CK: Cytokeratin; HT: Hormone Therapy; TURP: Transurethral Resection of Prostate; CEA: Carcinoembryonic Antigen; TUR: Transurethral Resection; CT: Computed Tomography; PIN: Prostatic Intraepithelial Neoplasia

PDA, not a unique disease but with approximately 5% of the prostate carcinoma prevalence, diverged clinically from common PAA in recent years and was considered the exact existence despite its longtime origin debates [1-3]. However, it usually progressed more aggressively than PAA in most studies [4]. Supplementary, it drew increasing attention in recent years, attributed to its diverse clinical characteristics which were accordingly inspected herein.

Case 1

In May 2013, an 80-year-old male with weak urine stream medicated for years after antecedently-achieved colon cancer surgery was admitted due to recent acute urinary retention. Consecutively, the findings were: the smooth surface, rubbery consistency and marked enlargement without hard palpable nodule of the prostate in the digital examination; the detrusor nor-moreflexia without detrusor sphincter dysynergia in the urodynamic study. Complementarily, the PSA was 33.23 ng/ml; The CEA (carcinoembryonic antigen), 3.8 ng/ml; the pathologists-assessed TRUS biopsy specimens, benign prostatic tissues. Thus, the TURP was attempted. Anyhow, a large round polyp-like tumor beyond the verumontanum was averred (Figure 1a and 1b) along with multiple papillary growths of the prostatic urethra near the apex (Figure 1c and 1d). Consequently, the schemes were:

Figure 1: A large round polyp-like tumor (“a” and “b”) beyond the verumontanum was averred along with multiple papillary growths (“c” and “d”) of the prostatic urethra near the apex cystoscopically.

(1) The Transurethral Resection (TUR) of urethral tumors and transurethral incision of the prostate were plied instead.

(2) In the final pathological specimens, the PDA (Gleason grade 4+4 =8) was attested with the 90% of tumor volume.

(3) In the microscopic sections, adenocarcinomas in papillary and cribriform growth patterns were composed of tall columnar cells displaying nuclear pseudostratification, and prominent nucleoli (Figure 2).

Figure 2: The prostate glandular cells showed cribriform arrangements composed of tall columnar cells displaying nuclear pseudostratification, and prominent nucleoli (hematoxylin and eosin x400).

(4) Regarding the immunohistochemical stains, they were positive for PSA (Figure 3) and p504s (Figures 3 and 4) but not for cytokeratin (CK) 7 and CK20, supporting the diagnosis before the imaging-staged bone metastases.

Figure 3: The PSA stain was positive (x100).

Figure 4: The p504s stain was positive (x400).

(5) The Computed Tomography (CT) proved nodular sclerotic bone metastases to the left pubis and right iliac wing. The clinical TNM staging was T₃N₁M_1b by imaging.

Resultantly, the Hormone Therapy (HT) with leuprorelin acetate and antiandrogen (Cyproterone) were delivered with palliative radiotherapy (RT) for bone pain. Up to Feb 2015, The PSA dropped to 0.56 ng/ml.

Case 2

In March 2014, an 89-year-old male at our clinic was chiefly complained of: about 1-year discontinuous painless gross hematuria; bony pain; being nearly bedridden recently. The PSA was 366.68 ng/ ml. Four sets of urine cytology all reported as negative for malignancy. The strategies were:

(1) The cystoscopy certified several papillary tumors over almost the apex of the prostatic urethra and the lateral kissing lobes of the enlarged prostate (Figure 5); the cystoscopic tumor biopsies, the PDA.

Figure 5: The cystoscopy certified several papillary tumors over almost the apex of the prostatic urethra and the lateral kissing lobes of the enlarged prostate.

(2) Immunohistochemically, the tumor cells were positive for PSA and p504s, but not CK7, confirming the diagnosis of a ductal adenocarcinoma (Gleason’s score 4+4=8) of prostatic origin.

(3) The CT proved the prostate cancer with invaded capsular and bilateral seminal vesicles; the bone scan, multiple bone metastases. The clinical TNM staging was T_3bN_xM_1b by imaging.

Up to Feb 2015, the multiple bony pains always bothered him because of the RT refusal. Although HT was with leuprorelin acetate and antiandrogen (Cyproterone), the PSA was still 96.02 ng/ml predicative of the hormone-refractory prostate cancer. Nontheless, the abiroterona, an androgen synthesis inhibitor was contraindicated in him in view of severe cardiovascular disease (the abdominal aortic aneurysm; hypertension).

Historically PDA, distinct acinar, was accentuated by:

(1) Growing into the proximal prostatic duct tissue [5]

(2) Deriving from the müllerian remnant tissue.

(3) Being probably in the large primary periurethral prostatic ducts or the peripheral prostatic ducts

4) Extending exophytically into the urethra and most commonly in and around the verumontanum [6]

Respecting our first PDA case, it often had no prostate biopsiesdetected tumor cell and dramatically differed from the PAA pertinent to its typical periurethral location which often resulted in hematuria or obstruction [7]. Thence, the approaches were:

(1) Pathologically distinguishing large prostatic lesions with ductal morphology was mandatory, over and above attentively ruling out a lot of mimicking diseases.

(2) Microscopically, the 2 most common ones were papillary and cribriform. The former mimicked papillary urothelial carcinomas closely.

(3) With PSA and p504s, the papillary urethral tumors from the urothelium or colonic epithelium were excluded [8-10]; so were the prostatic intraepithelial neoplasia (PIN) by the normal duct structure microscopically and the colonic lesion by positive CK 20 in our case 1 [11].

(4) Immunohistochemically for PSA, PAP, CK 7, CK 20, alphamethylacyl- CoA racemase, p63, and CK 34BE12, aypical prostatic lesions could be effectively differentially diagnosed.

Accompanying, it was distinctive about the PDA that:

(1) It was more aggressive than PAA in most studies [4,12] and often diagnosed as an advanced disease with early metastases.

(2) Pure PDA increased local recurrence risk but was pronely clinically weird; therefore, if the surgery patients were of pure ductal prostate cancer, they survived longer than those of mixed ductal prostate cancer and had the longer time metastasis than the latter and might improve clinically with local control.

(3) The first case received only en bloc resection of the urethral tumor whose volume occupied 90% of the specimen. Moreover, the PDA cases diagnosed from transurethral biopsy or TURP might be eradicated by the above surgery only and by no further operation [13].

(4) Its progress was not always hazardous.

(5) Regrettably, our long term survivals could not be properly predicted owing to no complete specimen of radical prostatectomy which most Taiwan urologists did not recommend. The life expectancy (exceeding 65 years) in our patients was expectedly 10 years less than that the averagely in Taiwan [14].

In spite of the vicious cycle of PDA, the current consensus in treatment (RT; HT) also worked well as for PAA [15]. Unfortunately, our two patients were with high risk prostate cancer according to the National Comprehensive Cancer Network classification. Inevitably, long term follow-up is needed notwithstanding the serious outcome.

Overall, the patients with PDA had worse prostate cancer-specific survival and prognosis than those with PAA [16]. The PDA metastasis (25%-40%) was evident during diagnosis which affirmed a 2.2-fold increase in cancer-specific mortality [17]. Concomitantly, the gene fusion might progress the PAA or develop the PDA [18]; the rate in pure PDA cases was significantly lower genetically and biologically than that in PAA cases and incidentally was important for future therapy [19] and appealing in recent years [20,21].

PDA was peculiar in prostate adenocarcinoma. Hence, arresting in our limited cases of high histological grades and advanced stages, longterm follow-up for disease outcomes remained requisite regardless of the failure of early diagnosis and aggressive treatment. Unavoidably, the rate of the gene fusion in the pure PDA was significantly lower genetically and biologically than that in the PAA and will be furthermore investigated.

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