Conventional Acinar Adenocarcinoma Research Articles

Nomogram for predicting the overall survival and cancer-specific survival of patients with intraductal carcinoma of the prostate

PurposeIntraductal carcinoma of the prostate (IDC-P) is a histological subtype that differs from conventional acinar adenocarcinoma in terms of its origin, appearance, and pathological features. For IDC-P, there is currently no recognized best course of action, and its prognosis is unclear. The goal of this study is to analyze independent prognostic factors in IDC-P patients and to develop and validate a nomogram to predict overall survival (OS) and cancer-specific survival (CSS).MethodsClinical data for IDC-P patients were collected from the Surveillance, Epidemiology, and End Results database. To identify the independent variables influencing prognosis, multivariate Cox regression analysis was performed. A nomogram model was created utilizing these variables after comparing the variations in OS and CSS among various subgroups using Kaplan‒Meier curves. Internal validation of the nomograms was verified using the bootstrap resampling method.ResultsThe study included 280 IDC-P patients in total. Marital status, summary stage, grade, and the presence of lung metastases were significant factors impacting OS, and CSS was significantly influenced by marital status, summary stage, AJCC stage, the presence of lung metastases, the presence of bone metastases, and PSA according to univariate and multivariate Cox regression models (P < 0.05). Nomogram models were created to estimate OS and CSS using these parameters. The OS prediction model’s C-index was 0.744, whereas the CSS prediction model’s C-index was 0.831.ConclusionWe developed and verified nomogram models for the prediction of 1-, 3-, and 5-year OS and CSS in patients with IDC-P. These nomograms serve as a resource for evaluating patient prognosis, therapy, and diagnosis, ultimately improving clinical decision-making accuracy.

Pure Foamy Gland Carcinoma of Prostate - A Series of Rare Cases

Foamy gland carcinoma (FGC) is a distinct histological variant of prostatic acinar adenocarcinomas. It was first described by Epstein and Nelson in 1996. It is characterized by abundant xanthomatous cytoplasm, pyknotic nuclei, and intermediate Gleason grade. However, FGC with a high Gleason grade exists. FGC is found admixed with conventional acinar adenocarcinoma in 17 to 22% of needle biopsies and 13 to 22% of radical prostatectomy specimens and only rarely found in pure form. We report six cases of pure foamy gland carcinoma of prostate. The mean age in our study was 62.83 years and 5 out of the 6 cases presented with an elevated serum PSA level. Histopathological examination of our cases showed tumor cells with abundant foamy cytoplasm and low nucleo-cytoplasmic ratio. This deceptively benign-looking morphology can mimic nonneoplastic prostatic glands, Cowper’s gland, mucinous metaplasia, and xanthomatous prostatitis and hence often pose diagnostic challenges, especially in core needle biopsies. PNI was detected in two of our cases. PSA and AMACR staining was positive in all our cases (100%). p63 Staining was negative in all four cases where it was performed. Three, two, and one of our cases had a Gleason score of 7, 8, and 6 respectively. The prognosis depends on the Gleason score and the presence or absence of PNI or extraprostatic extension. Three of the cases presented with bony metastasis. We report this case series in view of the rarity and also to raise awareness of this entity which is often missed on small biopsies. Keywords: Foamy gland carcinoma, Gleason score, Prostate

P63-expressing Prostate Adenocarcinoma: A Case Study of a Rare Subtype

Abstract Introduction/Objective Prostate acinar adenocarcinoma (PCa) is a well-researched,and often diagnosed entity. A combination of architectural and cytologic characteristics are used in accurately identifying these carcinomas. However, the diagnosis can be challenging when the foci are minute or the cancer presents with unusual features. Ancillary studies aid in these scenarios. The loss of basal cells in adenocarcinoma makes markers targeting these cells desirable. PIN4 cocktail immunohistochemical stain, which combines alpha-methylacyl-coA racemase (AMACR), that is overexpressed in prostate carcinoma, with basal markers high molecular weight cytokeratin and p63, is a popular ancillary study to assist diagnosing demanding cases. Herein, we present a rare, challenging subtype of prostate carcinoma expressing p63. Methods/Case Report A 66-year-old male, with a past medical history of treated HIV and hyperlipidemia, underwent screening biopsies for a PSA of 7.5 ng/mL. Out of 22 parts, three cores showed modest amounts of atypical infiltrating cells. The architecture comprised of ill-defined glands, individual cells and single files of cells. They possessed high nucleocytoplasmic ratio giving a hint of atrophy, with occasional spindling and prominent nucleoli. To add to the challenge, PIN4 immunostaining showed strong nuclear expression of a basal marker with negative AMACR. Due to unusual morphology and basal marker expression, a consideration of basal cell lesion was entertained. However, subsequent staining revealed negative expression of HMWCK, and positive expressions of NKX3.1 and p40. Overall, with this morphology and immunoprofile we diagnosed our case as prostate carcinoma with aberrant expression of p63. Results (if a Case Study enter NA) N/A Conclusion Grading these lesions is controversial as they are considered to carry a better prognosis over conventional acinar adenocarcinoma of similar grade. A distinct etiopathology is suspected as molecular tests for ERG and PTEN are without alterations. Further discussion and characterization of these lesions is warranted as they are infrequently encountered and prone to being overlooked due to their similarities to benign basal cells.

Reporting Trends, Practices, and Resource Utilization in Neuroendocrine Tumors of the Prostate Gland: A Survey among Thirty-Nine Genitourinary Pathologists.

Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin.

BackgroundDuctal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized.ObjectiveTo investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers.Design, Setting, and ParticipantsIn 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis.ResultsIn 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2‐ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549−BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden.ConclusionsDuctal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.

Mixed Small Cell Neuroendocrine Carcinoma and Conventional Acinar Adenocarcinoma of the Prostate: A Case Report

Abstract Prostate cancer with neuroendocrine (NE) differentiation can be classified into six categories: conventional adenocarcinoma with NE differentiation, adenocarcinoma with Paneth cell–like NE differentiation, carcinoid tumor, small cell carcinoma, large cell carcinoma, and mixed NE carcinoma-acinar adenocarcinoma. Mixed NE carcinoma-acinar carcinoma is a biphasic carcinoma characterized by the presence of NE (small or large cell) carcinoma and conventional acinar adenocarcinoma. In rare cases, these two components overlap without discrete classic small cell carcinoma or a usual prostate adenocarcinoma component, making it particularly difficult to determine whether these overlapping cases should be diagnosed as small cell carcinoma or adenocarcinoma with a high Gleason score. Here, we present the case of a 74-year-old man who was diagnosed with mixed small cell NE carcinoma and conventional acinar adenocarcinoma of the prostate.

Atrophic and Microcystic Limited Prostatic Adenocarcinomas.

Atrophic carcinoma and microcystic carcinoma have previously been classified as variants of conventional acinar adenocarcinoma. In this article, we studied 4 cases of atrophic carcinoma and 4 cases of limited microcystic carcinoma. We found an incidence of 0.8% in 250 needle prostatic biopsies and 1.3% of atrophic carcinoma in 150 radical prostatectomies. Microcystic carcinomas were found in 3 prostatectomies (1.2%) and in 1 needle biopsy (0.67%). The useful histological criteria for atrophic carcinoma included the irregular disposition of the glands, infiltrative pattern, "rigid" luminal borders, and intraluminal secretions. Cytological changes included scant cytoplasm, nucleomegaly, hyperchromatic nuclei, and visible nucleoli. The glands of the microcystic carcinoma differ from the benign glands because the malignant ones show a markedly greater dilatation and exhibit rigidity of glandular lumens. In some cases of microcystic carcinoma, the nuclei were flattened, small, and hyperchromatic; therefore, they can be difficult to recognize as malignant.

MP34-10 CHARACTERISING PROSTATE DUCTAL ADENOCARCINOMA: MORPHOMETRY AND CLINICAL OUTCOMES

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2018MP34-10 CHARACTERISING PROSTATE DUCTAL ADENOCARCINOMA: MORPHOMETRY AND CLINICAL OUTCOMES Timothy Harkin, Ashish Chandra, Oussama Elhage, Mark Frydenberg, and Prokar Dasgupta Timothy HarkinTimothy Harkin More articles by this author , Ashish ChandraAshish Chandra More articles by this author , Oussama ElhageOussama Elhage More articles by this author , Mark FrydenbergMark Frydenberg More articles by this author , and Prokar DasguptaProkar Dasgupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1102AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ductal adenocarcinoma is a rare variant of prostate cancer, demonstrating a more aggressive phenotype than conventional acinar adenocarcinoma. Morphometric variables, including distance from the urethra and tumour volume, remain unclear in present literature.This study aimed to examine the relationship between morphometry and clinical outcomes, particularly biochemical recurrence, and to further characterise the morphometry of ductal tumours. METHODS A comparative cohort study of ductal and Gleason 8+ acinar adenocarcinoma patients who had undergone radical prostatectomy between February 2007 and February 2017 was undertaken. Ductal and acinar foci were outlined under direct microscopy and morphometric measurements taken. MRI and clinical data were then compared. RESULTS 68 ductal and 72 acinar adenocarcinomas were included. Ductal tumours were located further from the periphery by 0.3 mm (p = 0.02), and involved 5% more prostate area (p = 0.02). Ductal proportions were reported in 52.7% of cases and identified in another 5% initially labelled as acinar-only. Risk of biochemical recurrence increased per 10% ductal components (HR 1.129, 95%CI 1.023–1.246, p = 0.02), and was substantially higher in tumours with ductal components greater than 50% (HR 2.226, 95%CI 1.110–4.464, p = 0.024). CONCLUSIONS This is the first study to demonstrate a significant relationship between the proportion of ductal components and clinical outcomes, and our findings suggest that more aggressive management strategies are required for patients with higher ductal proportions. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e441 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Timothy Harkin More articles by this author Ashish Chandra More articles by this author Oussama Elhage More articles by this author Mark Frydenberg More articles by this author Prokar Dasgupta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer

BackgroundDuctal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. ObjectiveTo characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Design, setting, and participantsTen patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Outcome measurements and statistical analysisSingle nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Results and limitationsExome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. ConclusionsCoincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. Patient summaryThe aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways.

Minimal (Limited) Pseudohyperplastic Prostatic Adenocarcinoma in Needle Prostatic Biopsy.

Study of minimum adenocarcinoma has been done almost exclusively on conventional acinar adenocarcinoma. Pseudohyperplastic adenocarcinoma can be confused with benign lesions because of its well-differentiated appearance and has not been studied when the biopsy shows few malignant glands (limited carcinoma). We reviewed 94 pseudohyperplastic adenocarcinomas diagnosed in prostatic biopsies for a period of 12 years and selected those measuring less than 1 mm or involving less than 5% of the biopsied tissue. We also reviewed 200 consecutive consultations. Four (4.2%) of the 94 cases were limited pseudohyperplastic adenocarcinomas, and 3 were from consultations. Three of them were mistaken for hyperplastic nodules, prostatic adenosis, or prostatic intraepithelial neoplasm. The number of glands varied between 6 and 50 (average 23). Three nodular histological patterns were identified-nodular, adenosis-like, and pseudohyperplastic carcinoma resembling prostatic intraepithelial neoplasia. The diagnosis of adenocarcinoma was not related to the number of neoplastic glands. Histological criteria that were useful included: crowded medium to large glands, papillary infoldings, branching glands, straight luminal borders, hyperchromatic nuclei, nucleomegaly, and apparent nucleoli. Areas of transition to conventional acinar adenocarcinoma were useful in recognizing four of these neoplasms, but were barely apparent in 2 of them. Hyperchromatic nuclei were found in all cases, whereas apparent nucleoli and nucleomegaly were only present in 4. The architectural and cytological criteria for limited acinar adenocarcinoma are only partially useful in interpreting minimum pseudohyperplastic adenocarcinomas. Knowledge of the criteria for malignancy in both neoplasms is important in order to avoid underdiagnosis of malignancy.

Inverted (hobnail) high-grade prostatic intraepithelial neoplasia and invasive inverted pattern.

High-grade prostatic intraepithelial neoplasia (HGPIN) is considered to be an important precursor for prostatic adenocarcinoma. The present study aimed to investigate the histological features of the uncommon inverted (hobnail) pattern of HGPIN in transrectal ultrasonographic (TRUS) prostatic needle biopsies from 13 cases. These 13 diagnosed cases of inverted HGPIN were identified out of a total of 2,034 TRUS biopsies (0.63%), obtained from patients suspected to have prostate cancer. The hobnail pattern is comprised of secretory cell nuclei, which are histologically localized at the luminal surface of the prostate gland, rather than the periphery, and exhibit reverse polarity. Histological examinations were performed and the results demonstrated that 5 of the 13 cases exhibited pure inverted histology, while HGPIN was observed to be histologically associated with other patterns in the remaining 8 patients. In addition, an association with adenocarcinoma was identified in 7 of the 13 cases. All 7 carcinomas accompanied by inverted HGPIN were conventional acinar adenocarcinoma cases; of note, for these 7 cases, the Gleason score was 7 for each. One acinar adenocarcinoma case accompanying inverted HGPIN demonstrated hobnail characteristics in large areas of the invasive component. It was observed that nuclei were proliferated in the invasive cribriform glands, which was comparable to that of inverted HGPIN, and were located on the cytoplasmic luminal surface; a similar morphology was also observed in individual glands. In conclusion, the results of the present study suggested that the hobnail HGPIN pattern may be of diagnostic importance due to its high association with adenocarcinoma and the high Gleason scores in the accompanying carcinomas.

Small cell–like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive prostatic carcinoma: a study of 7 cases

Small cell carcinoma of the prostate is associated with poor prognosis and different treatment from conventional acinar adenocarcinoma. Given the important clinicopathologic implications of a diagnosis of small cell carcinoma, we report 7 cases showing unusual, extensive small cell-like change in intraductal carcinoma and invasive carcinoma. Prostatic biopsies from 3 patients and radical prostatectomy specimens from 4 patients showed variably extensive small cell-like high-grade prostatic intraepithelial neoplasia and intraductal carcinoma. Five cases were associated with conventional acinar adenocarcinoma (2 cases with Gleason score 4 + 3 = 7; 3 cases with Gleason 3 + 4 = 7). No small cell carcinoma was seen. Small and large ducts with small cell-like change showed solid and cribriform proliferations of atypical cells with abrupt transition between centrally located populations of small cells and more typical large dysplastic cells at the duct periphery. Rosette-like formations were noted within some involved ducts. Small cell-like change was characterized by crowded cells with uniformly bland vesicular nuclei and minimal cytoplasm and no significant mitotic or apoptotic activity. In 3 cases, similar small cell-like morphology was noted focally in invasive carcinoma. The small cell-like areas were negative for synaptophysin and chromogranin, focally positive for TTF-1, and weakly positive for racemase. Ki-67 labeled less than 5% with predominant labeling of the larger atypical cells and minimal reactivity in the small cell-like population. In summary, small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive carcinoma is not associated with small cell carcinoma; shows no immunohistochemical evidence of neuroendocrine differentiation; and likely is not an adverse prognostic feature.

A Primary Signet Ring Cell Carcinoma of the Prostate With Bone Metastasis With Impressive Response to FOLFOX and Cetuximab

Introduction Carcinoma of the prostate gland is the most common visceral malignant tumor that affects men. Conventional acinar adenocarcinoma represents the majority ( 90%) of the tumors derived from the prostate gland. Uncommon variants (5%-10%) of prostatic adenocarcinoma are readily recognizable by their distinctive histologic features and are important because they might signify a worse clinical prognosis. Primary signet ring cell carcinomas (SRCC) of the prostate are extremely rare. As the name implies, the defining characteristic of the variant is the presence of signet ring cells, which are characterized by a crescent-shaped nucleus that is indented, displaced, and compressed against the cell membrane by a large, clear, cytoplasmic vacuole. Fewer than 60 patients with this rare malignancy have been described in the literature. SRCC of the prostate exhibits a median overall survival of 28 months from initial surgery, which implies a worse prognosis compared with standard adenocarcinomas.

Review of Small Cell Carcinomas of the Prostate

Small cell carcinoma of the prostate is a rare neoplasm, with only a few series hitherto reported. A little less than half of the cases are associated with conventional acinar adenocarcinoma, which are usually high grade. Although consensus has not been reached, the majority of patients with small cell neuroendocrine carcinoma of the prostate have advanced disease at diagnosis and disproportionally low PSA levels compared to patients with conventional acinar adenocarcinoma. Treatment consists mainly of chemotherapy associated with surgery. Radiation therapy is reserved for selected cases. This study reviews the most up-to-date information on small cell carcinomas of the prostate.

Intraductal Carcinoma of the Prostate Without Invasive Carcinoma on Needle Biopsy: Emphasis on Radical Prostatectomy Findings

Limited information is available on radical prostatectomy findings in men with intraductal carcinoma of the prostate on needle core biopsy in the absence of invasive prostate cancer. From the consulting files of one of us we identified 83 men in whom biopsy showed only intraductal prostate cancer. Followup was available in 66 cases. We reviewed slides in 21 radical prostatectomy cases. Treatment was radical prostatectomy in 23 men, radiation therapy in 15, hormone therapy in 8 and radiation plus hormone therapy in 15 while 5 underwent no treatment or repeat biopsy. Of the 21 radical prostatectomies available for review findings revealed pathological stage pT3a in 8 (38%), pT3b in 3 (13%), pT2 in 8 (38%) and intraductal carcinoma without identifiable invasive cancer in 2 (10%). One patient with pT3a had a positive lymph node at surgery. Average Gleason score was 7.9. Three patients (14%) experienced post-prostatectomy biochemical failure and another (5%) had bone metastases 2.5 years after prostatectomy. In 15 prostatectomies (71%) there was extensive intraductal carcinoma, defined as greater than 10% of tumor being intraductal, including the 2 cases of intraductal carcinoma only. Of the 19 prostatectomies with invasive adenocarcinoma 16 (84%) were conventional acinar adenocarcinoma, 2 (11%) ductal adenocarcinoma, and 1 (5%) mixed ductal and acinar adenocarcinoma. At radical prostatectomy men in whom prior biopsies showed only intraductal carcinoma of the prostate typically have high grade (Gleason score 7 or greater) invasive adenocarcinoma and most have advanced stage disease (pT3). Definitive therapy is recommended in men with intraductal carcinoma of the prostate on needle biopsy even in the absence of pathologically documented invasive prostate cancer.

Lymphoepithelioma-like carcinoma of the prostate

In this report, we summarized the clinicopathologic features of 5 cases of lymphoepithelioma-like carcinoma of the prostate, a rare variant of prostate cancer characterized by a malignant epithelial component densely infiltrated by lymphoid cells. In all 5 patients, there were obstructive symptoms and elevated prostate-specific antigen; one patient had also hematuria. Their ages ranged from 69 to 82 years (mean age, 76 years). The initial diagnosis of lymphoepithelioma-like carcinoma of the prostate was made on transurethral resection in 3 cases and radical prostatectomy in 2 others. In one case the diagnosis of lymphoepithelioma-like carcinoma admixed with conventional acinar adenocarcinoma was an unexpected finding at time of transurethral resection for benign prostatic hyperplasia. Three patients had clinical stage T3 tumors and another had stage T4 disease; stage T1b was present in the remaining case. Microscopically, all tumors contained lymphoepithelioma-like carcinoma, which comprised 10% to 90% of the entire tumor. All cases were associated with adenocarcinoma, either as the sole pattern in 5 cases or with an additional ductal component in 3 cases. One case had additional features of adenosquamous carcinoma. The lymphoepithelioma-like carcinoma component was characterized by indistinct cytoplasmic borders and a syncytial growth pattern. The stroma was densely infiltrated by lymphoid cells admixed with some plasma cells and neutrophils; one case had a prominent infiltration of eosinophils. Immunohistochemical staining demonstrated that lymphoepithelioma-like carcinoma was positive for prostate-specific antigen, prostate acid phosphatase, alpha-methylacyl coenzyme A racemase, and epithelial membrane antigen; several cytokeratins (AE1/AE3, 7, 8, and 20 [rare cells]) were also immunoreactive. The mean Ki-67 labeling index was 53% (range, 40%-70%), and the p53 expression in all cases was low (10%-20%). The lymphoid component was mainly composed of T with a minor subset of B cells, admixed with some dendritic cells and histiocytes as seen by S100 and CD68 immunoreactivity. Latent membrane protein 1 immunostaining and in situ hybridization for Epstein-Barr virus were negative in all 5 lymphoepithelioma-like carcinoma cases. DNA ploidy of lymphoepithelioma-like carcinoma tumors gave DNA histograms with aneuploid peaks. DNA ploidy of the concurrent adenocarcinoma gave DNA aneuploid peaks except in one DNA diploid case. Four patients died of disease from 8 to 26 months; one patient was lost to follow-up. In summary, lymphoepithelioma-like carcinoma of the prostate arise in aggressive prostate cancers at advanced clinical stage. Morphologic recognition and distinction from other prostatic lesions and tumors with prominent lymphoid stroma is critical for its clinical management.

Pathologic characteristics of pseudohyperplastic prostatic adenocarcinoma

To study the clinicopathologic features of 30 cases of pseudohyperplastic prostatic adenocarcinoma (PHPA). Eight hundred and sixty cases of ultrasound-guided prostatic needle biopsy and 46 cases of radical prostatectomy specimens collected during the period from January 1, 2005 to December 31, 2006 were retrieved from the archival files. The incidence, morphology, pathologic differential diagnosis, tumor volume, preferred location and Gleason's score were studied. The tissue sections suspicious for PHPA were immunohistochemically stained with high-molecular weight cytokeratin (34betaE12) or CK5/6, p63, AMACR, and cocktail antibody of 34betaE12/p63/AMACR. Cases with PHPA component more than 60% in at least one single slide were selected and pathologically analyzed. PHPA was present in 7% of needle biopsy and 15.2% of prostatectomy specimens. Histologically, 66.7% of PHPA demonstrated direct transition with conventional acinar adenocarcinoma; and 76.7% of cases had coexisting conventional acinar adenocarcinoma in the remaining tissue blocks. The tumor volume accounted for 5% to 100% of total carcinoma among core needle biopsy and 1% to 30% of total carcinoma among radical prostatectomy. PHPA resembled benign prostate glands, in which the hyperplastic malignant acini were predominantly of medium to large size. The neoplastic cells were well-differentiated, with basally located nuclei and luminal corpora amylacea. However, amongst the 20 pathologic indices of prostatic malignancy studied, occurrence of 10 or more indices exceeded 66.7%. Although PHPA looked benign morphologically, 66.7% cases had stromal invasion, 6.7% had perineural invasion and 3.3% had bone metastasis. The tumor was primarily located in the peripheral zone. PHPA is not a rare phenomenon in prostatic adenocarcinoma. Majority of cases have concurrent conventional acinar adenocarcinoma. It is different from well-differentiated (with Gleason's score 1 or 2) adenocarcinoma with a relatively indolent clinical course. In contrast, PHPA corresponds to moderately differentiated adenocarcinoma with Gleason's score of 3.

Prostatic ductal adenocarcinoma mimicking villous adenoma of the urethra

Dear Editor, Prostatic ductal adenocarcinoma (PDA) is a rare variant of a prostatic adenocarcinoma, accounting for less than 1% [5]. Usually, PDAs grow in irregular complicated papillary or cribriform pattern, of which nuclear atypia is marked [5]. We report a case of PDA with bland cytological and structural atypia mimicking villous adenoma, suggesting a diagnostic pitfall. A 73-year-old man presented with a complaint of hematuria. A digital rectal examination revealed normal-sized prostate with no nodules, and the serum level of prostatespecific antigen (PSA) was within normal range. Urine cytology showed a few clusters composed of atypical cells with mildly increased N/C ratio and irregular nuclei, suspicious of malignancy. Ultrasonography characterized a tumor in the neck of the urinary bladder, 1.8 cm in maximal diameter (Fig. 1a, arrow), while urethrocystoscopy demonstrated a papillary tumor protruding into the prostatic urethra. Transurethral resection of the tumor was performed. Histologically, the resected specimen showed tumor fragments mainly comprised of simple papillary-growing components associated with a fibrovascular stalk, similar to villous adenoma (Fig. 1b). Serrated and cribriform figures were partially seen. The tumor cells appeared as tall columnar cells with pseudostratified nuclei and abundant cytoplasm (Fig. 1c). Cytological atypia was characteristically minimal. Cytoplasmic mucin was not detected by periodic acid-Schiff or Alcian blue staining. Immunohistochemically, the tumor cells diffusely expressed PSA (Fig. 1d) and androgen receptor and focally expressed prostatic acid phosphatase. Furthermore, α-methylacylCoA racemase (P504S) and prostate-specific membrane antigen were weakly positive, but cytokeratin (CK) 7 and CK20 were negative. Ki-67 (MIB-1) positivity was approximately 20%. Transrectal needle biopsy of the prostate was performed, and one of the six specimens demonstrated conventional acinar adenocarcinoma with a Gleason score of 3+3=6. The patient received hormonal therapy, and there was no evidence of local recurrence or distant metastasis 1 year after the tumor resection. PDA was first described as endometrial carcinoma of the prostatic utricle by Melicow and Pachter in 1967 [4]. The carcinoma has now been confirmed to originate from the prostatic duct, not derived from the Mullerian duct. The tumor growth can be subdivided into two patterns: centrally located papillary tumor protruding into the prostatic urethra such as this case, and peripherally located tumor diffusely involved in the transitional or peripheral zone of the prostate [5]. Histologically, tall columnar epithelium with pseudostratified nuclei and eosinophilic or amphophilic cytoplasm proliferate in a papillary and tubulopapillary fashion, resembling an endometrial carcinoma, and are nominated as type A. Type B shows cribriform patterned or solid growth with frequent comedonecrosis and marked nuclear atypia. Type A almost matches with adenocarcinoma of the primary prostatic ducts, and type B with adenocarVirchows Arch (2006) 449:597–599 DOI 10.1007/s00428-006-0290-6

Simultaneous tumour-like, atypical basal cell hyperplasia and acinar adenocarcinoma of the prostate: a comparative morphological and genetic approach

Basal cell tumours of the prostatic gland are rare, and the classification is difficult. In the present case report, a large, tumour-like proliferation of atypical basaloid cells was found incidentally in a prostatectomy specimen that otherwise contained a conventional acinar adenocarcinoma. The basaloid cells displayed a solid or adenoid-cystic growth pattern and strongly expressed high-molecular-weight cytokeratins and bcl-2. A high Ki-67 index was recorded within the atypical basaloid cells, by far exceeding the one counted in the conventional adenocarcinoma. However, there were no definite criteria for a malignant behaviour of the basal cell tumour. Comparative genomic hybridisation from microdissected tumour cells yielded losses at the short arms of chromosomes 8 and 12 in the conventional adenocarcinoma and a normal karyotype in the basal cell tumour. The pathological findings favoured the diagnosis of an atypical basal cell hyperplasia.