Prostate-specific Antigen Staining Research Articles

Prostate cancer stem cells: molecular characterization for targeted therapy

Prostate cancer stem cells: molecular characterization for targeted therapy

Challenges in Diagnosis and Treatment of a Cervical Spinal Cord Injury Patient with Melanoma, Adenocarcinoma, and Hepatic and Osteolytic Metastases: Need to Implement Strategies for Prevention and Early Detection of Cancer in Spinal Cord Injury Patients

A male tetraplegic patient with, who had been taking warfarin, developed haematuria. Ultrasound scan revealed no masses, stones, or hydronephrosis. Urinary bladder had normal configuration with no evidence of masses or organised haematoma. Urine cytology revealed no malignant cells. Four months later, CT urography revealed an irregular mass at the base of urinary bladder. Cystoscopic biopsy revealed moderately differentiated adenocarcinoma, which contained goblet cells and pools of mucin showing strongly positive immunostaining for prostatic acid hosphatase and patchy staining for prostate specific antigen. Computed Tomography revealed multiple hypodense hepatic lesions and several osteolytic areas in femoral heads and iliac bone. With a presumptive diagnosis of prostatic carcinoma, leuprorelin acetate 3.75 mg was prescribed. This patient expired a month later. Conclusion. (i) Spinal cord injury patient, who passed blood in urine while taking warfarin, requires repeated investigations to look for urinary tract neoplasm. (ii) Anti-androgen therapy should be prescribed for 2 weeks prior to administration of gonadorelin analogue to prevent tumour flare causing bone pain, bladder outlet obstruction, uraemia, and cardiovascular risk due to hypercoagulability associated with a rapid increase in tumour burden. (iii) Spinal cord physicians should adopt a caring and compassionate approach while managing tetraplegic patients with several co-morbidities, as aggressive diagnostic tests and therapeutic procedures may lead to deterioration in the quality of life.

The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters

Background:Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA) is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters.Materials and Methods:100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran) were studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied.Results:No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression (P = 0.015).Conclusion:Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

Foamy gland carcinoma‐like carcinoma of the eyelid with sebaceous differentiation

This case report provides the first description of‘‘FGC-like’’ carcinoma of the skin. Based on the results of immuno-histochemistry and histochemis try, we suggest that this FGC-likecarcinomaaccompaniessebaceous differentiation.A74-year-oldmanwithagraduallygrowingyellow,flatnoduleinthe right upper eyelid visited a lo cal dermatologist, and the lesionwas histopathologically diag nosed as xanthoma. Because thepatient wanted complete resection of the tumor, a local plastic sur-geon removed the tumor with a 1-mm margin. The tumor was closeto the lateral margin of excision, and a recurrence was noted2monthsfollowingsurgery.Eventhoughthepatienthadthesec-ond operation, thetumor was histop athologicallydiagnosed as xan-thoma and recurred 6 months later. The patient left the tumor for10 months, resulting in it having extended all over the right eyelidwhen the patient visited our hospital. The clinical picture from theoriginal dermatologist was of a yellow or pale-reddish, hard, ill-demarcatedsubcutaneoustumorintheuppereyelid(Fig.1a).Histo-pathological examination showed the infiltrative mass of tumor cellswith hyperchromatic nuclei and g ranular to foamy cytoplasm in themid-dermis to subcutaneous tissue. Cellular pleomorphism, nuclearpleomorphism and atypism were rare as the previous reports ofFGChave documented(Fig. 1b–d).Magnetic resonance imaging revealed that tumors had growndiffusely in both upper and lower right eyelids, extending aroundthe superior rectus muscle and optic foramen (Fig. 1e). Computedtomography (CT) revealed no metastasis and no suspicious pri-mary tumor except for the right eyelid; therefore, we performedextended excision of the tumor wi th 3-cm margins along with totalorbital exenteration of the right e ye. However, the positive marginswere confirmed at the deepest end around the optic foramen,and further tumor cells were iden tified in the sentinel lymph nodeof the right submandible. The defect of the right eye was recon-structed by using a free rectus abdominis flap. One year after sur-gery, the patient suffered an abdominal incisional hernia at thedonor site of the free flap. Despite emergency surgical treatment,the patient died of severe acute respiratory distress syndromeafter the operation. It was confirmed that there was no primarytumor by autopsy.In histochemical studies, many Sudan-III-positive droplets wereidentified in the cytoplasm, resembling xanthoma (Fig. 2a). Tumorcells were periodic acid Schiff-positive and diastase-resistant(Fig. 2b). In immunohistochemical studies, tumor cells wereimmunoreactive for AE1 ⁄AE3, CAM 5.2, epithelial membraneantigen (EMA), carcinoembryoni cantigen(CEA),GCDFP-15andadipophilin (Fig. 2c–h, respectively). In contrast, tumor cellsshowed no staining for prostate-specific antigen, cytokeratin(CK)20, S-100, HMB-45 and CD68 (data not shown). The exis-tence of Sudan-III-positive droplets and the reactivity with adipo-philin and EMA strongly suggested sebaceous carcinoma orsebaceous differentiation.

An Unusual Presentation of Prostate Adenocarcinoma Metastatic to the Oral Cavity

The lymph nodes and bones are the most common sites of metastases in advanced prostate cancer. However, an unusual clinical presentation or one that mimics another entity may make diagnosis difficult. We report a male patient with metastatic prostate cancer who presented with a primarily localized buccal tumor. Prostatic origin was highly suspected only after positive results of prostate-specific antigen staining from biopsy pathology. We share our clinical experience and review the literature.

Occult prostate cancer detected by hyoid bone metastasis after resection of thyroglossal duct cyst

Metastatic carcinoma involving the hyoid bone has rarely been mentioned in the literature. The most frequent malignant lesion involving the hyoid bone metastasized from the larynx, followed by the vallecula and pyriform sinus. The authors report a unique case of occult prostate cancer that presented with an anterior midline neck mass diagnosed as a thyroglossal duct cyst. Two foci of metastatic carcinoma lesions in the hyoid bone were detected after Sistrunk's operation and occult prostate cancer was confirmed by immunohistochemical staining of prostate-specific antigen. Prostate cancer with metastasis to hyoid bone has not been described previously in the literature. The authors report this case which raises important pathological considerations for diagnosis. The unique presentation also reiterates the importance of prostate cancer bone metastasis.

Penoscrotal Extramammary Paget's Disease: The University of Texas M. D. Anderson Cancer Center Contemporary Experience

Extramammary Paget's disease is a rare intra-epithelial malignancy that is occasionally associated with an invasive adenocarcinoma component as well as other secondary cancers. We investigated a consecutive series of patients referred for extramammary Paget's disease of the penis or scrotum at a single center in the contemporary era to determine the presence of secondary cancers and treatment outcomes. Between December 1990 and February 2009, 20 patients with extramammary Paget's disease of the scrotum and/or penis were seen. Patients were investigated with computerized tomography of the abdomen/pelvis, chest x-ray, cystoscopy, colonoscopy and serum prostate specific antigen measurement to rule out obvious secondary cancer. Clinical charts were reviewed with institutional review board approval. Mean followup of treated cases was 48 months (range 7 to 208). Patients were 50 to 86 years old with a history of symptoms of between 6 months and 10 years. Eight patients had invasive adenocarcinoma, of whom 2 died of the disease and 3 who had disease at 5, 7 and 40 months, respectively, were undergoing multimodal therapy. No patient with confirmed intra-epidermal disease only died of the disease. Invasive disease predicted nodal and metastatic progression. Surgical resection to achieve tumor-free margins resulted in durable relapse-free survival of patients with intra-epidermal extramammary Paget's disease alone. Extramammary Paget's disease with invasion was associated with regional metastatic progression. The latter scenario as well as failure to treat localized extramammary Paget's disease alone was associated with a fatal outcome. Systemic chemotherapy should be further explored in patients with invasive adenocarcinoma or lymph node positive disease.

Prostate-specific antigen and hormone receptor expression in male and female breast carcinoma

BackgroundProstate carcinoma is among the most common solid tumors to secondarily involve the male breast. Prostate specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are expressed in benign and malignant prostatic tissue, and immunohistochemical staining for these markers is often used to confirm the prostatic origin of metastatic carcinoma. PSA expression has been reported in male and female breast carcinoma and in gynecomastia, raising concerns about the utility of PSA for differentiating prostate carcinoma metastasis to the male breast from primary breast carcinoma. This study examined the frequency of PSA, PSAP, and hormone receptor expression in male breast carcinoma (MBC), female breast carcinoma (FBC), and gynecomastia.MethodsImmunohistochemical staining for PSA, PSAP, AR, ER, and PR was performed on tissue microarrays representing six cases of gynecomastia, thirty MBC, and fifty-six FBC.ResultsPSA was positive in two of fifty-six FBC (3.7%), focally positive in one of thirty MBC (3.3%), and negative in the five examined cases of gynecomastia. PSAP expression was absent in MBC, FBC, and gynecomastia. Hormone receptor expression was similar in males and females (AR 74.1% in MBC vs. 67.9% in FBC, p = 0.62; ER 85.2% vs. 68.5%, p = 0.18; and PR 51.9% vs. 48.2%, p = 0.82).ConclusionsPSA and PSAP are useful markers to distinguish primary breast carcinoma from prostate carcinoma metastatic to the male breast. Although PSA expression appeared to correlate with hormone receptor expression, the incidence of PSA expression in our population was too low to draw significant conclusions about an association between PSA expression and hormone receptor status in breast lesions.

Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients

Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.

Cancer of Unknown Primary Finally Revealed to Be a Metastatic Prostate Cancer: A Case Report

The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.

Editorial Comment on: Post-treatment Prostate Biopsies in the Era of Three-Dimensional Conformal Radiotherapy: What Can They Teach Us?

[9] D’Amico AV, Whittington R, Malkowicz SB, et al. A method for determining a prostate-specific antigen cure after radiation therapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 1995;32:473–7. [10] Vicini FA, Kestin LL, Martinez AA. The importance of adequate follow-up in defining treatment success after external beam irradiation for prostate cancer. Int J Radiat Oncol Biol Phys 1999;45:553–61. [11] Connell PP, Ignacio L, McBride RB, et al. Caution in interpreting biochemical control rates after treatment of prostate cancer: length of follow-up influences results. Urology 1999;54:875–9. [12] Kestin LL, Vicini FA, Martinez AA. Practical application of biochemical failure definitions: what to do and when to do it. Int J Radiat Oncol Biol Phys 2002;53:304–15. [13] Crook JM, Perry GA, Robertson S, et al. Routine prostate biopsies following adiotherapy for prostate cancer: results for 226 patients. Urology 1995;45:624–31. [14] Gaudin PB, Zelefsky MJ, Leibel SA, et al. Histopathologic effects of three-dimensional conformal external beam radiation therapy on benign and malignant prostate tissues. Am J Surg Pathol 1999;23:1021–31. [15] Prestidge BR, Hoak DC, Grimm PD, et al. Posttreatment biopsy results following interstitial brachytherapy in early stage prostate cancer. Int J Radiat Oncol Biol Phys 1997;37:31–9. [16] Crook JM, Bahadur YA, Robertson SJ, et al. Evaluation of radiation effect, tumor differentiation, and prostate specific antigen staining in sequential prostate biopsies after external beam radiotherapy for patients with prostate carcinoma. Cancer 1997;79:81–9.

Utility of Prostatic Markers in the Differential Diagnosis of Adenocarcinomas Not Otherwise Specified from metastatic Tumours of the Oral Cavity

Objectives: The aim of the present study was to evaluate the expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and ( alpha)- methylacyl-CoA racemase gene ( P504S) in normal salivary glands and adenocarcinomas not otherwise specified (NOS). Material & Methods: Tissue specimens of 18 normal salivary glands and 22 cases of adenocarcinomas NOS of the oral cavity, formalin-fixed, and paraffin-embedded were studied by using monoclonal antibodies for PSA, PAP and P504S. Results: Positive staining for PSA was detected with one of the two used monoclonal antibodies in normal salivary glands (89%) and adenocarcinomas NOS ( 45.45%) whereas negative staining was observed for PAP and P504S. Conclusions: Our results suggest that the detection of prostatic markers such as PAP, P504s with the use of monoclonal antibodies may offer an adjunctive aid in the differential diagnosis of adenocarcinomas NOS from metastatic carcinomas, when the origin of the primary tumours is unknown.

Metastatic prostatic adenocarcinoma to the orbit diagnosed by prostate-specific antigen staining

Metastatic prostatic adenocarcinoma to the orbit diagnosed by prostate-specific antigen staining

Immunohistochemical Differentiation of High-grade Prostate Carcinoma From Urothelial Carcinoma

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (<or=2%) weak-moderate positive cells. In summary, PSA can be used as the first screening marker for differentiating high-grade prostate adenocarcinoma from high-grade urothelial carcinoma. Immunohistochemistry for P501S, PSMA, NKX3.1, and pPSA are useful when high-grade prostate cancer is suspected based on the morphology or clinical findings, yet shows negative or equivocal PSA staining. HMWCK and p63 are superior to the novel markers thrombomodulin and S100P.

Immunohistochemical Panel of Undifferentiated Orbital Metastatic Carcinomas

Purpose: To examine the applicability of an immunohistochemical panel of seven monoclonal antibodies to identify the primary site of poorly differentiated orbital metastatic carcinomas. Material and Methods: Immunohistochemistry was performed to detect cytokeratin (CK) 7, CK20, thyroid transcription factor-1 (TTF-1), BRST1, BRST2, carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) in seven cases of poorly differentiated orbital metastases. Of the seven cases, four were female and three male. The youngest patient was thirty-six while the oldest was eighty-eight years of age. Results: The immunohistochemical panel alone was helpful to identify the primary source of the metastatic lesion in three out of the seven cases. Two of them were metastatic breast carcinomas (BRST1, BRST2 positive) and one was a prostate carcinoma (PSA positive). By correlating the immunohistochemical results with the previous clinical history, the primary site could be identified in two more cases. In those metastatic lesions, the positive staining for CK7, CK20, and CEA, associated with negative staining for BRST1, BRST2, PSA and TTF-1, indicated bladder as the probable primary site. In two out of seven cases, the metastatic tumor was only positive for CEA, therefore a primary site could not be identified. Conclusions: An immunohistochemical panel of poorly differentiated orbital metastases is helpful in the identification of the primary tumor site. The association of seven markers with the patient's clinical history allowed for the positive identification of the primary tumor in the majority of these cases.

Pleomorphic Giant Cell Adenocarcinoma of the Prostate

Pleomorphic tumors with giant cells have been described in a variety of primary sites. However, only a few cases have been described among prostatic carcinomas with only 1 on diagnostic biopsy material. Five cases were retrieved from the consultation files of one of the authors. One of the cases was retrieved from the surgical pathology files at our institute. Patient ranged in age from 59 to 76 years (mean=65.8 y). The diagnosis was made on needle biopsy (n=3), urethral biopsy (n=1), transurethral resection (n=1), or radical prostatectomy (n=1). In all cases, giant, bizarre, anaplastic cells were present. In 4 of the cases, marked pleomorphism occupied 5% of the specimen, with 20% and 70% bizarre giant cells in the other 2 cases. In one case, the bizarre cells had atypical mitotic figures, with other cases showing no mitoses in the markedly pleomorphic cells. In addition to the pleomorphic giant cell component, multiple coexistent histologic components were seen including Gleason score 9 conventional prostate cancer (n=6), small cell carcinoma (n=1), squamous carcinoma (n=1), and prominent ductal adenocarcinoma differentiation with intraductal spread (n=1). Immunohistochemically, 4 cases were for negative for prostate-specific antigen in the giant cells, 1 had 5% staining, and the other had 50% positivity in the giant cells. Staining for prostate-specific antigen in the conventional prostate carcinoma component was 1%, 5%, 20%, 50%, 100%, and 100%. The bizarre giant cells were strongly positive for cytokeratins AE1/AE3 and/or Cam 5.2 (n=3). Two cases had a history of conventional prostate cancer 4 years before the giant cell component, 1 treated with Lupron and the other with radiation. Follow-up after diagnosis of the giant cell component: Case 1: dead in 1 year of disease; Case 2: progressive metastases in 2 years; Case 3: alive at 1 year with disease; Case 4: large perineal recurrence after brachytherapy at 3 years; Case 5: radical prostatectomy with extraprostatic extension and seminal vesicle invasion; and Case 6: alive at 3 months, free of disease. Conventional prostate cancer, even when very high grade, typically consists of cells with relatively uniform nuclei. Our study expands the histology described in prostate cancer to include in very rare cases with prominent pleomorphism and bizarre giant cells. This giant cell component heralds a particularly aggressive clinical outcome.

Persistent prostate-specific antigen expression after neoadjuvant androgen depletion: An early predictor of relapse or incomplete androgen suppression

Objectives To analyze post-androgen depletion (AD) primary tumors to identify markers of treatment failure because AD does not reduce the probability of prostate-specific antigen (PSA) failure after prostatectomy. Methods Tumors removed by radical prostatectomy after 3 months of AD from 21 patients were analyzed for gene expression using oligonucleotide arrays. Differences between patients with and without relapse were identified using a conservative significance criteria of a threefold change and delta 0.68, ensuring a false discovery rate of less than 11%. Results At 50 months of follow-up, 7 of the 18 evaluable patients developed a biochemical recurrence. Gleason grade, pretherapy PSA level, T stage, and margin status were similar between the two groups. Patients with recurrence had greater post-AD PSA levels than those without recurrence (0.87 versus 0.19 ng/mL; P = 0.042). Gene expression analysis revealed 35 probe sets overexpressed in tumors from patients who relapsed. Among the highest ranked probe sets were PSA and other androgen-responsive genes. Serum PSA values during AD revealed similar findings. After 40 days of AD, the PSA level in those without recurrence was 1.21 ng/mL versus 4.5 ng/mL in those with recurrence ( P = 0.0034). Immunohistochemistry of post-AD tumors also demonstrated a high PSA staining intensity in many tumors that recurred relative to those that didn’t. Conclusions The results of our study show that early recurrence is associated with expression of androgen-responsive genes. Surprisingly, these could be identified as early as 3 months after the initiation of AD therapy. Whether this represents a failure to abrogate androgen receptor mediated signaling with androgen depletion or early reactivation of signaling is under study.

Distorted Rectal Tissue on Prostate Needle Biopsy

Rectal tissue is often seen in needle biopsies of the prostate gland. On rare occasion distorted rectal glands can mimic prostatic adenocarcinoma, an issue not previously addressed in the peer-reviewed literature. We evaluated 16 prostate needle biopsies received in consultation where the submitting pathologist questioned whether a focus of rectal tissue was prostate cancer. In addition to the distorted architecture, features mimicking prostate cancer included: (1) blue-tinged intraluminal mucinous secretions in 10 cases (63%), (2) prominent nucleoli in 6 cases (37%), (3) mitotic activity in 6 cases (37%), (4) extracellular mucin in 5 cases (31%), and (5) adenomatous changes of the rectal tissue in 1 case (6%). Immunohistochemical results further mimicked prostate cancer with negative stains for the basal cell markers high-molecular weight cytokeratin (n=6) and p63 (n=4), and positive stains for racemase in 4 of 5 biopsies. Diagnostic clues to recognizing that these foci were distorted rectal fragments were the presence of (1) lamina propria in 12 cases (75%), (2) rectal tissue located on a detached fragment of tissue in 10 biopsies (63%), (3) associated inflammation in 10 cases (63%), (4) goblet cells in 7 cases (44%), and (5) muscularis propria in 6 cases (37%). In 2 cases, there was negative staining for prostate specific antigen (PSA) and in 1 case negative staining for cytokeratin 7 and positivity for cytokeratin 20. Rectal glands are associated with many of the classical features of prostate cancer, and immunohistochemistry may be misleading. Recognition of these features mimicking prostate cancer and awareness of other findings that are diagnostic of rectal tissue on biopsy can prevent a misdiagnosis of atypical prostate glands or prostate cancer.

Large Cell Neuroendocrine Carcinoma of Prostate

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.

Tumour markers for managing men who present with metastatic prostate cancer and serum prostate‐specific antigen levels of &lt;10 ng/mL

To define immunohistochemical features of the primary cancers that might help in the differential diagnosis and monitoring of treatment in men presenting with metastatic prostate cancer and low serum levels of prostate-specific antigen (PSA), who can be difficult to diagnose and manage. Paraffin blocks of prostate biopsies were obtained for 33 patients presenting with untreated metastatic prostate cancer and serum PSA levels of <10 ng/mL. Sections were immunostained for PSA, prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), androgen receptor (AR), chromogranin A and CD 56. The combined Gleason scores were 8-10 in 25 men (76%) and 6 or 7 in the other eight (24%). Morphologically, there were no neuroendocrine features. PSA immunostaining was equivocal in 12 (36%) cases and in a further 19 (58%) was strong but focal and could be missed on biopsy sampling. PSMA was expressed in 90% of cases, and staining was widely distributed in nine of the 12 in which PSA staining was equivocal. There was strong AR expression in 30 (91%) cases and it was present in areas where PSA was absent. In this patient group, immunohistochemical assessments of PSMA and AR are potentially useful as diagnostic markers.