Polyclonal anti-PSA is more sensitive but less specific than monoclonal anti-PSA: Implications for diagnostic prostatic pathology

Prostate-specific antigen (PSA) production by nonprostatic tissues has been reported, casting doubts on its specificity. The immunohistochemical relative specificity and sensitivity of PSA expression using monoclonal and polyclonal anti-PSA was analyzed on 60 prostate carcinomas, 40 normal seminal vesicles, and 310 nonprostatic tumors. All nonprostatic tumors proved negative with both antibodies. However, 13 (32%) seminal vesicles showed immunoreactivity with polyclonal anti-PSA, but none showed immunoreactivity with the monoclonal antibody. The sensitivity of the 2 antibodies for prostate cancer varied with tumor grade. In Gleason pattern 3, both antibodies showed diffuse immunostaining in all cases. In Gleason pattern 5, polyclonal anti-PSA showed diffuse (>95%) tumor cell positivity in 18 cases (90%), while with the monoclonal antibody, 7 cases (35%) showed only focal (<10%) tumor cell immunoreactivity. Thus, monoclonal anti-PSA seems to be useful in small gland proliferations in which the differential diagnosis includes seminal vesicle, while for poorly differentiated neoplasms, polyclonal anti-PSA is considered superior. Sections of high-grade prostate cancer should be included as positive controls for PSA immunostaining.     

Bacillus Calmette-Guerin Granuloma in Seminal Vesicle: Report of the First Case in the English Literature

A 64-year-old man underwent a radical cystoprostatectomy for intravesical bacillus Calmette-Guerin (BCG) therapy-resistant, recurrent muscle invasive transitional cell carcinoma (TCC) of the urinary bladder. He had a history of left radical nephroureterectomy for a papillary TCC of the left ureter 10 months ago. On microscopic examination, not only multifocal residual papillary TCCs in the urinary bladder but also multiple small granulomas in the urinary bladder and prostate were noted. Interestingly, unusually severe granulomatous inflammation accompanying focal central caseating necrosis was identified in the subepithelial tissue of the left seminal vesicle and vas deferens. Neither prostatic adenocarcinoma nor TCC involvement was identified in the prostate and seminal vesicles. A few acid-fast bacilli were identified by the Ziehl-Neelsen staining in the seminal vesicle granulomas, confirming the BCG-induced inflammation. To the best of our knowledge, this is the first case of BCG-induced granuloma involving the seminal vesicle. It is uncertain why only the left seminal vesicle was involved with BCG granulomas and the incidence and mechanism of seminal vesicle BCG granuloma await more cases.     

Phyllodes tumor of the prostate

In this report, we describe a case of phyllodes tumor of the prostate with a high value of prostate-specific antigen (PSA). A 47-year-old man with symptoms of hematospermia presented with a steadily elevated serum PSA value of 60.76 ng/mL (normal range, < 4 ng/mL). A needle biopsy revealed atypical stromal cells without any evidence of malignancy. After radical prostatectomy, the tumor measured 2.9 cm in diameter and consisted of a single nodule composed of irregular, elongated epithelial ducts and atypical stromal cells with enlarged, occasionally multinucleated, pleomorphic, or hyperchromatic nuclei. Immunohistochemistry showed that the atypical stromal cells were positive for vimentin, androgen receptor, estrogen receptor, progesterone, and 5α-reductase, but negative for MIB-1, PSA, SMA, p53, desmin, CD34, c-kit, CD10, S-100, and EGFR. Excess PSA might be secreted by hyperplastic luminal cells driven by 5α-reductase-positive stromal and epithelial cells. Array-comparative genomic hybridization (array CGH) for genomic alterations revealed a gain of 11p13, which includes the WT1 gene, and a loss of 1p36.23 and 12p12.1. After surgery, the serum PSA value rapidly decreased to within the normal range; no recurrence or distant metastasis was noted after 2 years of follow up.     

Primary adenocarcinoma of the seminal vesicle

A rare case of primary adenocarcinoma of the seminal vesicle is examined in an 87-year-old Japanese man. Neoplastic cells, especially poorly differentiated cells, showed a positive reaction with periodic acid-Schiff reagent and anti-carcinoembryonic antigen. Neoplastic cells invaded the bladder wall but not the prostate. No other primary tumor was demonstrated.     

Müllerian adenosarcomalike tumor of the seminal vesicle. A case report with immunohistochemical and ultrastructural observations.

A müllerian adenosarcomalike tumor of the seminal vesicle is described in a 49-year-old man. The tumor occupied the entire right seminal vesicle and adhered to the right lobe of the prostate, in the area adjacent to the seminal vesicle. The tumor was also adherent to the rectum. Microscopically, the cells were seen to invade the prostatic tissue. The tumor consisted of a highly cellular stroma with spindle-shaped pleomorphic cells, suggesting the diagnosis of a low-grade sarcoma. In addition, dilated cystic spaces lined by columnar epithelium were seen. Immunohistochemically, most tumor cells showed positivity for vimentin, desmin, and muscle-specific actin, suggesting smooth-muscle cell differentiation. Furthermore, electron microscopy also demonstrated smooth-muscle differentiation of the tumor cells. The patient has been disease-free for 48 months since undergoing a cystoprostatetectomy.     

Epithelial-stromal tumor of seminal vesicle in a patient with chromophobe renal cell carcinoma and small lymphocytic lymphoma

Biphasic tumors of the seminal vesicle are rare. We report a further case in a 61-year-old man of a seminal vesicle epithelial-stromal tumor with focally atypical epithelial and stromal cells, the latter displaying a smooth muscle immunophenotype. In addition, this was associated with 2 synchronous malignant neoplasms, chromophobe renal cell carcinoma and small lymphocytic lymphoma, both of which were detected incidentally after clinical presentation because of the seminal vesicle mass.     

Primary seminal vesicle carcinoma

Criteria for the very rare diagnosis of primary seminal vesicle carcinoma have traditionally been highly stringent but may be relaxed with the application of immunohistochemistry to the diagnosis of mass lesions that occur in the male pelvis. The authors report a case of disseminated carcinoma with a clinically occult primary site that apparently had its origin in the seminal vesicle. Autopsy revealed a 10-cm tumor enveloping the prostate and seminal vesicles without involvement of colonic or urothelial mucosa. Much smaller tumors were present in other sites outside the pelvis. The tumor was composed of poorly formed glands and sheets of malignant-appearing cells, involved the seminal vesicle, and had the immunohistochemical profile of seminal vesicle carcinoma, notably strong immunoreactivity for CA-125 and no immunoreactivity for cytokeratin-20 or prostate-specific markers.     

Prostate volume has prognostic value only in pathologic T2 radical prostatectomy specimens

The objective of this study was to evaluate the prognostic roles of the prostate volume, tumor volume, and tumor percentage as a function of the pathologic T stage in radical prostatectomy specimens. This study included 259 patients who underwent radical prostatectomy between 2005 and 2010. The mean follow-up period was 41.2 months. In all of the specimens, prostate volume (P = 0.021), the Gleason score (P = 0.035), and seminal vesicle invasion (P = 0.012) were independent predictors of biochemical recurrence (BCR). In the T2 group, multivariate analysis showed that the BCR was significantly associated with prostate specific antigen (PSA) (P = 0.028), a lower prostate volume (P = 0.004), and the Gleason score (P = 0.040). The Kaplan-Meier survival curve showed that a smaller prostate volume was significantly associated with a greater risk of BCR (< 30 vs ≥ 30 mL; P = 0.010). In the T3 group, patients with seminal vesicle invasion had a significantly shorter mean BCR-free survival (P = 0.030). In this study, tumor volume and tumor percentage did not predict BCR. Notably, a lower prostate volume is an independent predictor for BCR only in the organ-confined radical prostatectomy specimens. But, prostate volume could not predict BCR in most locally advanced tumors.     

水通道蛋白1在生后小鼠精囊腺与前列腺发育过程中的表达与分布

目的 探讨水通道蛋白1(AQP1)在雄性小鼠出生后不同发育阶段精囊腺和前列腺的表达与分布.方法 应用RT-PCR、免疫印迹和免疫组织化学染色方法,检测出生后15d、35d、70d 小鼠精囊腺、前列腺AQP1 mRNA、蛋白表达水平及细胞定位.结果 RT-PCR与免疫印迹结果均显示,出生后70d小鼠精囊腺、前列腺AQP1 mRNA及蛋白表达量较出生后15d显著增强(P<0.05);免疫组织化学染色显示,AQP1蛋白仅表达于出生后15d、35d小鼠精囊腺平滑肌细胞、前列腺腺泡上皮细胞基膜及间质细胞,而此时期精囊腺上皮细胞AQP1蛋白表达呈阴性;出生后70d,AQP1蛋白强烈表达于精囊腺和前列腺上皮细胞.结论 AQP1 mRNA及蛋白在雄性小鼠精囊腺、前列腺的表达与分布随年龄增长而改变,此变化可能与雄性附属性腺发育相关.     

Tumor cell transendothelial passage in the absorbing lymphatic vessel of transgenic adenocarcinoma mouse prostate

The distribution and fine structure of the tumor-associated absorbing lymphatic vessel in the tumor mass of prostate adenocarcinoma and of seminal vesicle metastasis in transgenic mice was studied for the purpose of understanding the modality of tumor cell transendothelial passage from the extravasal matrix into the lymphatic vessel. In the tumor mass, two main cell populations were identified: stromal tumor cells and the invasive phenotype tumor (IPT) cells, having characteristics such as a highly electron-dense matrix rich in small granules lacking a dense core and massed nuclear chromatin, which is positive to immunostaining with anti-SV40 large T antigen antibody. Based on the ultrastructural pictures of different moments of the IPT cell transendothelial passage by ultrathin serial sections of the tumor-associated absorbing lymphatic vessel, the manner of its transendothelial passage through the intraendothelial channel, without involving intercellular contacts, was demonstrated. The presence of IPT cells in the parenchyma of satellite lymph node highlights its significant role in metastatic diffusion. The intraendothelial channel is the reply to the lack of knowledge regarding the intravasation of the tumor cell into the lymphatic circulation. The lymphatic endothelium would organize this channel on the basis of tumor cell-endothelial cell-extravasal matrix molecular interactions, which are as yet unidentified.     

A seminal vesicle cyst complicated with a tumor like nodular mass of benign proliferating prostatic tissue: a case report with ultrastructural and immunohistochemical studies

We report a seminal vesicle cyst complicated with a tumor-like nodular mass of benign proliferating prostatic tissue. The patient was a 53-year-old Japanese man. A cyst of approximately 4.5 cm in diameter was discovered at the left seminal vesicle area. In the inner part of the cyst, a papillary nodular mass of 0.7 cm in diameter was seen. Under the clinical diagnosis of a seminal vesicle cyst with a tumorous mural nodule, the patient underwent resection of the seminal vesicle cyst to rule out the possibility that the nodular mass in the cyst was a neoplasm of an especially malignant nature. Microscopic examination of the excised specimen revealed a small dome-like nodular mass on the luminal surface of the cyst consisting of nodular proliferation of benign tubular gland tissue with various configurations. Conventional histologic, immunohistochemical, and ultrastructural analysis showed the proliferating cells in the nodular mass consisted of the benign prostate type. It is extremely important to differentiate between a benign proliferation and a malignant one, when the nodular mass is found in the seminal vesicle cyst.     

Malignant phyllodes tumor of the prostate

Phyllodes tumor of the prostate is rare. We have recently experienced a case of phyllodes tumor of the prostate in a 57-year-old man who complained of urinary retention for 1 year. The epithelial components were positive reactivity for prostate specific antigen. The stromal cells showed nuclear atypia with increased mitotic activity. The tumor was diagnosed as a malignant phyllodes tumor as it invaded into the urinary bladder and rectum, and grew rapidly immediately after operation. We describe the morphological features and immunohistochemical findings of malignant phyllodes tumor and review the literature.     

The relationship between the extent of surgical margin positivity and prostate specific antigen recurrence in radical prostatectomy specimens

The presence of positive surgical margins is a negative prognostic indicator in patients undergoing prostatectomy for prostate cancer; whether the extent of the positive margins affects the clinical outcome with regards to prostate-specific antigen (PSA) recurrence remains uncertain. We evaluated the linear extent of margin positivity as a prognostic indicator in a series of radical prostatectomy specimens. One hundred seventy-four consecutive margin-positive prostatectomy specimens were evaluated. The linear extent of margin positivity was measured with an ocular micrometer and ranged from 0.05 to 75.0 mm (mean, 8.94; median, 5.0). The linear extent of margin positivity was associated with tumor volume (P = .03) but was not associated with patients' age at surgery, preoperative PSA level, prostate weight, pathologic stage, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, high-grade prostatic intraepithelial neoplasia, or PSA recurrence. In the full model multiple Cox regression, significant predictors for PSA recurrence were Gleason score (P = .001) and preoperative PSA (P = .01); extent of margin positivity was not predictive of PSA recurrence (hazard ratio, 1.00; 95% confidence interval, 0.98-1.02; P = .97) nor was tumor volume a significant factor when adjusted for other covariates (P = .27). Preoperative PSA, tumor stage, and Gleason score remained significant prognostic factors in evaluating the likelihood of PSA recurrence in patients with positive surgical margins; the extent of margin positivity, however, is not a prognostic factor for PSA recurrence and should, therefore, not necessarily be included in the final report for radical prostatectomy specimens.     

Monstrous epithelial cell clusters in the seminal vesicle

A 60-year-old man presented with dysuria and elevated PSA (6.95 ng/ml). Needle biopsies of the prostate revealed well differentiated adenocarcinoma of Gleason's score 6. Prostatectomy and bilateral seminal vesiculotomy were performed. The material was totally cut into 16 preparations. The prostate showed well differentiated adenocarcinoma. The left seminal vesicle showed intraluminal monstrous large epithelial cells with acidophilic cytoplasm and hyperchromatic nuclei, simulating carcinoma cells. Lipochrome pigment was present in the monstrous cells, and some monstrous cells showed large bizarre nuclei. Such monstrous cells were also present in the mucosal seminal vesicle epithelium, and gradual merge between the intraluminal and mucosal monstorous epithelium. Immunohistochemically, the monstrous epithelial cells showed the following reactions: pancytokeratin (AE1/3, CAM5.2) +, cytokeratin (CK) 5/6 +, CK34βE12 -, CK7 +, CK8 -, CK14 -, CK18 +, CK19+, CK20 -, Ki-67 0%, p53 -, P63 -, NSE -, CEA -, EMA -, CA19-9 -, ER -, PgR -, HER2 -, HepPar1 -, CD34 -, CD10 +, PSA -, AMACR -, Desmin -, ASMA -, CD68 -, S100 -, CD45 -, synaptopysin -, TTF-1 -, CDX-2 -, MUC1 -, MUC2 -, MUC5AC - MUC6 +, CD56 -, PAS -, dPAS -, and alcian blue +. The immunoprofile of normal seminal vesicle epithelium was as follows: pancytokeratin (AE1/3, CAM5.2) +++, cy-tokeratin (CK) 5/6 +++, CK34βE12 -, CK7 +++, CK8 +, CK14 -, CK18 +++, CK19, +++, CK20 -, KI-67 1%, p53 -, P63 +++, NSE -, CEA - EMA -, CA19-9 -, ER -, PgR -, HER2 +, HepPar1 -, CD34 -, CD10 +, PSA -, AMACR -, Desmin -, ASMA -, CD68 -, S100 - , CD45 -, synaptopysin -, TTF-1 -, CDX-2 -, MUC1 -, MUC2 -, MUC5AC -, MUC6 +++, CD56 -, PAS -, dPAS -, and alcian blue +. That is, the immunophenotype was very similar but much weaker in monstrous cells than in normal seminal vesicle epithelium. These findings suggest that the monstrous seminal vesicle epithelial cells are degenerative changes. The monstrous epithelial cells should not be mistaken for carcinoma.     

Findings in 12-core transrectal ultrasound-guided prostate needle biopsy that predict more advanced cancer at prostatectomy: analysis of 388 biopsy-prostatectomy pairs

We analyzed 5 features on 12-core transrectal ultrasound-guided prostate needle biopsy (TRUS) to predict the extent of cancer at radical prostatectomy (RP). In 388 TRUS-RP pairs, number of positive cores (NPC), percentage of each core involved (%PC), perineural invasion (PNI), Gleason score (GS), distribution of positive cores (DPC), and preoperative prostate-specific antigen (PSA) were correlated with extraprostatic extension (EPE), seminal vesicle invasion (SVI), positive surgical margin (R1), positive lymph nodes (N1), and tumor volume. All features predicted EPE and SVI. NPC, GS, %PC, and PNI strongly predicted R1 status. RP tumor volume was directly proportional to the NPC and %PC. PSA alone and with selected biopsy findings correlated with tumor volume, stage, SVI, and N1 (P < .0001). Contiguous DPC was a significant risk for EPE and SVI (P < .0001) compared with isolated positive cores. Findings at 12-core TRUS along with preoperative PSA reliably predict advanced local disease and have practical value as guides to effective planning for surgical resections.     

Primary carcinoid tumor of the urinary bladder with prominent subnuclear eosinophilic granules

Primary carcinoid tumor of the urinary bladder is a very rare neoplasm. We report here a case of primary carcinoid tumor of the urinary bladder with an unusual cytological feature in a 72-year-old Japanese man. A bladder polypoid mass was incidentally found by ultrasonography during the follow-up of a benign prostate hyperplasia. Histological examination of the transurethrally resected tissue revealed that the upper part of the mass was a tumor showing tubuloglandular anastomosing structures. Most of the tumor cells had peculiar subnuclear eosinophilic granules. The features of the granules were reminiscent of those observed in neuroendocrine cells of the intestine. The tumor cells were immunohistochemically positive for chromogranin A and synaptophysin. The tumor was diagnosed as carcinoid tumor of pure form of the urinary bladder. The lower part of the mass showed the findings of glandular cystitis, as its coexistence with carcinoid tumors of the bladder has often been described in previous reports.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Iocalized amyloidosis of the seminal vesicle: Identification of lactoferrin immunoreactivity in the amyloid material

Three specimens of localized amyloidosis of the seminal vesicle surgically removed for prostatic cancer were immuno-histochemically analyzed to clarify the nature of the permanganate-sensitive congophilic subeplthelial deposition. A variety of known amyloidogenic substances and secretory products in the seminal fluid were screened using the indirect immunoperoxldase method. In addition to reactivities with antibodies to amyloid P component and human seminal plasma, the amyloid material was immunoreactive for lactoferrin using a rabbit antiserum and two of three mouse monoclonal antibodies. All the antibodies labeled some of the normal seminal vesicle epithelial cells for this iron-binding, bacteriostatJc glycoprotein. In the prostate without accompanying amyloid deposition, a considerable proportion of the glandular epithelium and secretory material were positive for lactoferrin. Pre-embedding immunoelectron microscopy showed lactoferrin immunoreactivity on the amyloid fibrils. Focal staining of the amyloid for gross cystic disease fluid protein-15 was also observed in two lesions. These findings strongly suggest that lactoferrin is the major constituent in localized senile amyloidosis of the seminal vesicle.     

Prostate-specific membrane antigen expression as a predictor of prostate cancer progression

Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, because current therapy may lead to overtreatment of men with limited disease. The prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein that is highly restricted to the prostate. Previously, studies analyzing the expression of PSMA have found an up-regulation in correlation with prostate cancer, particularly in advanced cancer. This association is ideal for an application as a prognostic marker. In the current study, we characterized PSMA expression in a high-risk cohort and evaluated its potential use as predictive marker of prostate-specific antigen (PSA) recurrence. PSMA expression was analyzed by immunohistochemistry using tissue microarrays composed of tumor samples from 450 patients. Protein intensity was recorded using a semiautomated quantitative microscope system (ACIS II; Clarient Chromavision Medical Systems, San Juan Capistrano, CA). PSMA expression levels differed significantly (P < .001) between benign prostatic tissue, localized prostate cancer, and lymph node metastases. Dividing the cohort into high- and low-PSMA expressing cancers based on the median area of positive staining, we found that high PSMA levels were associated with significant increase of PSA recurrence (P = .004). This was independent of clinical parameters such as lymph node tumor burden (lymph node density, >20%; P < .001), extraprostatic extension (P = .017), seminal vesicle invasion (P < .001), and high Gleason score (8-10, P = .006). In a multivariate model, PSMA expression and metastases to pelvic lymph nodes were significantly associated with time to PSA recurrence (HR, 1.4; 95% confidence interval, 1.1-2.8, P = .017; and hazard ratio, 5; 95% confidence interval, 2.6-9.7, P < .001, respectively). In summary, PSMA is independently associated with PSA recurrence in a high-risk cohort and thus might provide insight into the additional use of adjuvant therapy. Validation on other cohorts is required.     

Metaplastic Breast Carcinoma Invading Chest Wall

Metaplastic breast carcinoma refers to a heterogeneous group of neoplasms in which the typical glandular growth pattern of the tumor undergoes metaplasia, either epithelial or stromal. A 59-year-old woman presented with a breast mass that recurred in 1 year and showed invasion of the chest wall. Histological sections of both the tumor and the recurrence showed a tumor composed predominantly of stromal spindle cells with neoplastic epithelial ducts. Squamous metaplasia was seen in some ducts. Immunohistochemical staining showed positive cytokeratin and epithelial membrane antigen staining of the epithelial cells. Smooth muscle actin, S100, and vimentin were diffusely positive in the stromal cells. Electron microscopy of the original lesion showed cells with squamous epithelial and smooth muscle characteristics, and other cells that formed lumens into which microvilli projected. Electron microscopy of the recurrent lesion showed primarily spindle-shaped cells with abundant tonofilaments in the perinuclear cytoplasm, desmosomes with associated tonofilaments, filaments with focal densities, often aligned parallel with the cell membranes, surface attachment plaques, and fragments of basement membrane. Pinocytotic vesicles were rare. These metaplastic cells are derived from myoepithelial cells which are multipotential and able to differentiate into epithelial or stromal cells.