The role of P501S and PSA in the diagnosis of metastatic adenocarcinoma of the prostate

BACKGROUND: Adenocarcinoma of the prostate can present as metastatic carcinoma with no known primary. Prostatic origin can be confirmed in most of these cases by immunohistochemistry for prostate-specific antigen (PSA) and prostate-specific acid phosphatase. In a small subset of high-grade prostate carcinomas, both markers are negative and therefore are not helpful for confirming prostatic origin. Recently, novel marker proteins that are preferentially expressed in prostate tissue were identified. One such marker is P501S or prostein, a 553-amino acid protein that is localized to the Golgi complex. It is expressed in both benign and neoplastic prostate tissues, but not in any other normal or malignant tissue examined to date. Owing to its apparent specificity, prostein may be a good marker to demonstrate prostatic origin in metastatic prostate cancer. DESIGN: Five-micron sections of a tissue microarray were subjected to immunohistochemistry with a monoclonal mouse anti-P501S (clone 10E3, Dako, Carpintera, CA) antibody and a monoclonal mouse anti-PSA (clone ER-PR8, Dako, Carpintera, CA) antibody. The tissue microarray contains 78 cases of metastatic prostatic adenocarcinoma, 20 cases of primary prostatic adenocarcinoma, and 20 cases of benign prostate tissue from the peripheral zone as well as samples of benign brain, pancreas, kidney, thyroid, testis, skeletal muscle, and fibroconnective tissue. RESULTS: Similar staining (intensity and extent) was identified for both markers in the majority of metastatic tumors (11 distant sites, 42 pelvic lymph nodes), in all 20 primary tumors and in all benign prostate and nonprostate tissues. The P501S stain had perinuclear cytoplasmic (Golgi) distribution even in poorly differentiated tumors and metastases. Two distant metastases were negative for PSA but retained focal weak positivity for P501S. Two other distant metastases were weakly PSA positive, but strongly P501S positive. Metastases in the pelvic lymph nodes were positive for both markers in 53 cases and 1 lymph node metastasis was strongly PSA positive but P501S negative. In summary, 67 of the 69 cases (97%) of metastatic prostate carcinomas were PSA positive, whereas 68 of the 69 cases showed at least focal weak reactivity for P501S (99%). None of the tumors were negative for both markers. CONCLUSIONS: Immunohistochemistry for P501S is a sensitive and highly specific marker for identifying prostate tissue. The large majority of metastatic prostatic adenocarcinomas are P501S positive (99%). A small subset of metastatic prostatic adenocarcinoma shows significant differences in staining intensity and extent for PSA and P501S and, therefore, combined use of these markers may result in increased sensitivity for detecting prostatic origin.     

Metastatic tumors involving testis

Two cases of metastatic tumors involving the testis are reported: one from an adenocarcinoma of the prostate and the other from an adenocarcinoma of the colon. The first was found incidentally in the orchiectomy specimen done for prostatic cancer while the other was noted clinically as a part of a widely disseminated disease. Although there are numerous pathways through which tumors may metastasize to the testis, the occurrence of testicular metastasis is extremely rare. The reason for this rarity remains unknown.     

Metastasis of the epididymis disclosing cancer of the prostate. Apropos of a case

The authors present a patient who had prostatic carcinoma metastatic to the epididymis. The patient was asymptomatic except for painless swelling in the right epididymis. The laboratory radiographic and physical examination of the patient were normal. The prostate was clearly demarcated, homogeneous and solid. Surgery was performed in two stages. In the first stage semi-castration was performed. Histopathological analysis of the biopsy material showed prostatic carcinoma metastatic to the epididymis. There were no metastases in the testis. In the second stage, TUR of the prostate was performed. To our knowledge prostatic carcinoma metastatic to the epididymis has not been described previously.     

胃低分化腺癌合并印戒细胞癌睾丸转移1例报告并文献复习

目的:探讨我院1例罕见胃印戒细胞癌睾丸转移的临床病理特点,免疫组织化学在睾丸转移瘤与原发肿瘤鉴别诊断中的应用。方法:回顾分析了我院收治1例睾丸肿瘤患者,1年前曾行胃贲门癌根治性全胃切除术,术后病理报告提示低分化印戒细胞癌,术后未予以放化疗,此次外院睾丸穿刺活检病理报告为低分化腺癌浸润或转移,考虑患者的病情及预后,行患侧根治性睾丸切除术。结果:术中见睾丸略增大,约4cm×3cm×2cm,质地硬,颜色呈淡红色,附睾大小、质地无异常。术后病理证实胃低分化腺癌合并印戒细胞癌转移。随访半年,临床症状好转。结论:胃印戒细胞癌睾丸转移非常罕见,特定的免疫组织化学指标可以有助于诊断。     

Testicular metastasis from carcinoma of prostate: report of two cases

Despite the high incidence of prostatic adenocarcinoma and its ability for wide dissemination, metastatic involvement of testis is rather uncommon. We report two cases (aged 76 and 55 years, respectively), where unilateral testicular metastasis was incidentally discovered after bilateral orchiectomy following detection of adenocarcinoma prostate in six-quadrant trucut specimen. Both patients had obstructive voiding symptoms, hard nodular prostate on direct rectal examination and raised serum prostate-specific antigen levels, without associated systemic or testicular symptoms. Extensive evaluation excluded any other possible primary, although axial skeletal metastasis was detected on radionucleotide bone scans, in the first case. These cases highlight the need for proper evaluation of testes and para-testicular structures, for accurate staging of these tumors and to exclude any possible metastasis.     

Testicular metastases from prostate carcinoma

Metastasis of prostate carcinoma to the testis is seldom reported. The tumour may spread from the prostatic urethra by retrograde venous extension, arterial embolism or through direct invasion into the lymphatics and lumen of the vas deferens. Clinical manifestations of secondary testicular tumours from the prostate are most often unsuspected clinically and are instead detected incidentally during orchidectomy. Less frequently, a palpable mass is detected, which may be confused with a primary testicular neoplasm. We report a case of a 66-year-old patient with adenocarcinoma of the prostate, and a left testicular tumour that was diagnosed as metastases from prostate carcinoma after radical orchidectomy.     

Metastatic ductal carcinoma of the prostate: a rare variant responding to a common treatment

Ductal carcinoma of the prostate is a rare histologic subtype of prostate carcinoma. It represents 0.4% to 0.8% of all prostate cancers and is associated with a poor prognosis. Given the paucity of cases reported in the literature on ductal prostate carcinoma, little is known about how this cancer responds to cytotoxic chemotherapy. We report the case of a 56-year-old male who presented to our clinic with hemoptysis, cough and hematuria and was found to have metastatic ductal carcinoma of the prostate. He was initiated on docetaxel chemotherapy, which has been previously shown to improve overall survival in patients with metastatic prostate adenocarcinoma, but has never been studied in this less common subtype of prostate cancer. To the best of our knowledge, the following is the first reported case of a patient with metastatic ductal carcinoma of the prostate responding to docetaxel chemotherapy.     

Ureteric stricture: an unusual presentation of metastatic prostate adenocarcinoma

We describe an unusual case of a prostatic adenocarcinoma presenting with a ureteric stricture secondary to a discrete metastatic lesion. A 76-year-old man presented with a short history of right loin pain. Initial examination was unremarkable, digital rectal examination was normal and prostate specific antigen was within normal range. Computed tomography showed right hydronephrosis and a distal ureteric stricture. A distal ureteric transitional cell carcinoma was thought to be most likely. A nephroureterectomy was carried out and histology revealed a skipped lesion of a metastatic prostate adenocarcinoma. Metastatic lesions to the ureters due to prostate cancer are rare. It was believed to be secondary to a transitional cell carcinoma as there was no evidence initially to suggest prostatic disease as the cause. A prostatic adenocarcinoma should be considered in the differential diagnosis of any lesions in the ureter believed to have a malignant origin.     

Metastatic carcinoma of prostate 23 years after radical prostatectomy

Carcinoma of the prostate may present with metastatic disease many years after treatment. We present a patient with adenocarcinoma of the prostate, "cured" by radical perineal prostatectomy in 1962, with the first signs of metastases presenting in 1985. This emphasizes the importance of long-term follow-up of patients with prostate carcinoma.     

Transdural metastasis from adenocarcinoma of the prostate mimicking subdural hematoma: case report

BACKGROUND: Metastasis of prostatic adenocarcinoma to the nervous system is extremely rare and has been infrequently reported over the last several years. We describe the presentation, evaluation, and surgical intervention of a case of metastatic prostate carcinoma to the dura. CASE DESCRIPTION: This patient presented with symptoms and physical findings consistent with a subacute subdural hematoma in the setting of recently diagnosed adenocarcinoma of the prostate. He underwent a craniotomy for presumed subdural hematoma. The pathologic diagnosis was consistent with metastatic prostatic carcinoma. CONCLUSION: This case report demonstrates the need for broad differential diagnosis in the evaluation and treatment of patients presenting with seemingly straightforward subacute subdural hematomas.     

Testicular metastasis from prostate carcinoma three years after subcapsular orchiectomy. A case-report

Metastatic cancer to the testis is a rare phenomenon of prostate carcinoma with only 80 cases reported in the literature. Most of these secondary testicular tumors were diagnosed on routine pathohistological examination of testicular tissue after plastic orchiectomy. In none of these cases metachronous development of these metastases has been described. For the first time we report on a 75-year old patient who developed a prostate carcinoma metastatis to the right testicle three years after undergoing subcapsular orchiectomy. This case shows that the urologist has to think about a metastatic cancer when he sees a testicular tumor also after plastic orchiectomy.     

Testicular metastasis from prostate carcinoma three years after subcapsular orchiectomy. A case-report A case-report

Metastatic cancer to the testis is a rare phenomenon of prostate carcinoma with only 80 cases reported in the literature. Most of these secundary testicular tumors were diagnosed on routine pathohistological examination of testicular tissue after plastic orchiectomy. In none of these cases metachronous development of these metastases has been described. For the first time we report on a 75-year old patient who developed a prostate carcinoma metastatis to the right testicle three years after undergoing subcapsular orchiectomy. This case shows that the urologist has to think about a metastatic cancer when he sees a testicular tumor also after plastic orchiectomy.     

Sarcomatoid carcinoma of the prostate: a study of 42 cases

Sarcomatoid carcinoma of the prostate is a rare type of prostatic cancer. With the exception of 1 study, the morphologic features and patient outcomes have been reported only in relatively small case series and individual reports. We examined transurethral resection, needle biopsy, and radical prostatectomy specimens from 42 patients with sarcomatoid carcinoma of the prostate, all of which were received in consultation. Clinical information on 32 patients was obtainable. Five patients were lost to follow-up and information on the 5 remaining patients could not be obtained. Prior prostatic adenocarcinoma: The majority of patients (n=21; 66%) had a prior history of acinar adenocarcinoma of the prostate. Of the 14 men with available data, reported Gleason scores were 6 (n=7), 8 (n=4), and 10 (n=3). Of the remaining patients for whom this information was known, 11 patients presented with de novo sarcomatoid carcinoma. The time between the original diagnosis of acinar adenocarcinoma and diagnosis of sarcomatoid carcinoma ranged from 6 months to 16 years (mean 6.8 y). Concurrent adenocarcinoma: The majority of patients demonstrated a concurrent high grade acinar carcinoma of Gleason score 7 (n=3), 8 (n=9), 9 (n=10), and 10 (n=10). A subset of patients contained an admixed ductal adenocarcinoma (n=4), small cell carcinoma (n=3), squamous cell carcinoma (n=3), or other unusual pattern of prostate carcinoma (n=3). In 1 case, the diagnosis was based on immunohistochemical evidence of epithelial differentiation along with the history of prior adenocarcinoma. Morphology of the sarcomatoid component: The percentage of sarcomatoid growth ranged from 5% to 99% (mean 65%). Bizarre atypia with giant cells was present in 55% of cases. Admixed heterologous elements were identified in 10 cases (29%), including osteosarcomatous (n=7), chondrosarcomatous (n=5), and rhabdomyosarcomatous (n=2) elements. Of the 12 cases with received immunostains of the sarcomatoid component, 5/7 cases were at least focally positive for cytokeratin, 1/1 case was focally positive for Cam5.2, and 3/6 cases were focally positive for prostate acid phosphatase. The sarcomatoid component did not demonstrate immunoreactivity for prostate-specific antigen in 8 cases. Prognosis: approximately half of all patients developed metastatic disease either at time of presentation or subsequently. Of patients with meaningful follow-up, 6/7 died within 1 year of the diagnosis of sarcomatoid carcinoma; 20 were alive yet with very short follow-up (median 1 y; mean 2.3 y). Kaplan-Meier analysis revealed that the actuarial risk of death at 1 year after diagnosis of sarcomatoid carcinoma was 20%. No correlation was identified between patient survival and morphologic features, before radiation or hormone therapy, or concurrent high-grade prostate cancer. Sarcomatoid carcinoma demonstrates diverse spindle and epithelial cell morphologies. The sarcomatoid component often has heterologous elements and, in 1 case, no epithelial component was seen on hematoxylin and eosin-stained sections. The epithelial component is typically high-grade acinar adenocarcinoma, yet other aggressive tumor subtypes such as ductal adenocarcinoma and small cell carcinoma may also be seen. Sarcomatoid carcinoma is an aggressive form of prostate cancer, the prognosis of which is dismal regardless of other histologic or clinical findings.     

Delayed cutaneous hypersensitivity in patients with prostatic adenocarcinoma.

Cell-mediated immunocompetence of patients seen for followup of adenocarcinoma of the prostate is evaluated using dinitrochlorobenzene as a contact sensitizing agent. The immune status is correlated with the presence or absence of metastatic disease. A highly significant correlation is found between the lack of immune response and the presence of metastatic carcinoma, suggesting that immunotherapy will be useful in the treatment of carcinoma of the prostate.     

Adenocarcinoma of the prostate involving 2 cell types (prostate specific antigen producing and carcinoembryonic antigen producing) with selective metastatic spread.

Of 3 patients with clinically localized adenocarcinoma of the prostate 2 were treated by radical prostatectomy and 1 was treated with radiation therapy. Serum prostate specific antigen (PSA) values were elevated before therapy. After treatment the PSA levels were decreased to zero. All 3 patients later had evidence of metastatic tumor spread to the liver with elevation of serum carcinoembryonic antigen but not PSA. Immunohistochemical staining of the 2 primary tumors from the prostatectomy specimens identified 2 cell clones, one immunoreactive to PSA and prostatic acid phosphatase (PAP) and nonimmunoreactive to carcinoembryonic antigen, and the other immunoreactive to carcinoembryonic antigen but not PSA or PAP. Biopsy of a hepatic metastasis in 2 patients confirmed anaplastic carcinoma of the carcinoembryonic antigen-producing cell type. Immunohistochemical staining of a lymph node metastasis identified the PSA-producing cell type only. Such results suggest selective metastatic spread of each cell type to its own organ tropic site. Occasional carcinoembryonic antigen-producing prostate cancers may metastasize to the liver. Serum carcinoembryonic antigen measurements occasionally may be useful in the management of certain prostate adenocarcinoma patients.     

Testicular and epididymal metastasis of prostate cancer

Metastatic testicular carcinoma is unusual. A case of carcinoma of the prostate with metastases to the testis and epididymis is reported. Routes of metastatic spread of neoplasm to the testis are discussed. Easily removable cancer may remain in the scrotum when using the socalled subcapsular orchiectomy without complete removal of the scrotal contents.     

Oat cell carcinoma of lung masquerading as prostatic carcinoma

We believe this is the second case of oat cell carcinoma metastatic to the prostate to be reported. The patient was treated for prostatic carcinoma diagnosed by rectal examination. Subsequent biopsy confirmed oat cell carcinoma and led to the discovery of pulmonary carcinoma. Tumors metastatic to the prostate are rare and are identified when they result in urologic symptoms. A review of tumors metastatic to the prostate is presented.     

Adenocarcinoma arising from a mature cystic teratoma of the testis

A 52-year-old male diagnosed pathologically with metastatic adenocarcinoma of the skin was referred to our department. Physical examination revealed a right scrotal mass the size of child's head and several skin tumors. Right high orchiectomy and resection of skin tumors were performed. Histopathological examination revealed a well-differentiated, mucinous adenocarcinoma originating from the gastrointestinal epithelium in a mature cystic teratoma (dermoid cyst) of the testis and metastatic mucinous adenocarcinoma of the skin. We made a diagnosis of teratoma with malignant transformation (TMT) of the testis. Combination chemotherapy with low-dose cisplatin/5'-deoxy-5-fluorouridine (CDDP/5'-DFUR) was initiated, but the patient died 8 months after orchiectomy. At autopsy, similar mucinous adenocarcinoma of the testis and the skin were observed at the metastatic sites.     

Immunohistochemical demonstration of prostatic origin of metastases

An immunoperoxidase technique for prostate specific acid phosphatase was performed on 14 lymph node metastases of prostatic carcinoma and 13 cases of metastatic adenocarcinoma from other primary sites. Eleven metastatic prostate carcinomas showed diffuse strongly positive immunostain and one showed focal weak positivity. Two prostatic and all other metastatic carcinomas were negative. Thus, the method is found to be extremely specific (100 per cent) and to show a high degree of sensitivity (86 per cent) for the demonstration of the prostatic origin of lymph node metastases.     

Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.