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Lymphoid neoplasms of the urinary tract and male genital organs are relatively rare, comprising less than 5% of all primary extranodal lymphomas; only a handful of small case series and isolated case reports have been published describing their predominant sites and subtypes. We identified 40 patients with lymphoid neoplasms of the urinary tract and male genital organs. Hematoxylin and eosin slides and immunohistochemical stains were reviewed, and follow-up data were also obtained. Twenty-six of 40 cases (65%) were primary genitourinary lymphomas. Mean age at diagnosis was 56 years (range 4-86 years). Among renal, bladder, and ureter lymphomas, a male predominance was noted (1.6:1). The subtypes of the lymphoid neoplasms observed were diffuse large B-cell lymphoma (17 cases, 43%); Burkitt lymphoma, extranodal marginal zone lymphoma, SLL/CLL, and follicular lymphoma (4 cases, or 10% each); B-cell ALL (2 cases, 5%); B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, mantle cell lymphoma, plasmacytoma, polymorphic post-transplant lymphoproliferative disorder, and peripheral T-cell lymphoma NOS (1 case, or 2.5% each). In most cases, the genitourinary tract was the site of initial presentation. Genitourinary tract lymphomas most commonly occurred in the kidney. B-cell non-Hodgkin's lymphomas predominated, with diffuse large B-cell lymphoma being the most common subtype in the entire group. Extranodal marginal zone lymphoma was seen only in the kidney, rather than the bladder, where it is typically thought to be more common. Although this study confirms the predominance of diffuse large B-cell lymphoma in extranodal sites, the findings also highlight the variety of lymphomas that may occur in the genitourinary tract. This diversity of subtypes affirms the importance of fully characterizing lymphomas by immunohistochemistry and other modalities, which are indispensable for accurate diagnosis.

The relationship between tubulocystic carcinoma and collecting duct carcinoma of the kidney remains controversial. Some experts are of the opinion that the tumors are related, considering tubulocystic carcinoma to be synonymous with low-grade collecting duct carcinoma. However, others maintain that the 2 are distinct, unrelated entities on the basis of morphologic features and clinical outcome. To explore the relationship between tubulocystic carcinoma and collecting duct carcinoma, we compared the expression of several gene products at the mRNA level in cohorts of each tumor subtype. Seven cases of tubulocystic carcinoma and 8 cases of collecting duct carcinoma were identified. Total RNA was isolated from formalin-fixed paraffin-embedded tissue from each case. Relative expression levels of vimentin, alpha methylacyl CoA racemase, E-cadherin, p53, CD10 antigen, parvalbumin, cytokeratin 7, and cytokeratin 19 were assessed by quantitative reverse transcription polymerase chain reaction. Tubulocystic carcinoma was characterized by relative overexpression of vimentin, p53, and alpha methylacyl CoA racemase, compared with collecting duct carcinoma (P<0.05 for each gene, t test). In general, tubulocystic carcinoma expressed higher levels of E-cadherin and CD10, whereas collecting duct carcinoma expressed higher levels of cytokeratin 19; however, these trends did not reach statistical significance in this study cohort. Tubulocystic carcinoma and collecting duct carcinoma did not express cytokeratin 7 differentially. Case-to-case variability of gene expression limited the effectiveness of any one marker to distinguish the tumor types. Our study demonstrates that tubulocystic carcinoma and collecting duct carcinoma have different expression profiles of selected genes, including vimentin, p53, and alpha methylacyl CoA racemase. Further analysis of additional cases, using quantitative reverse transcription polymerase chain reaction and immunohistochemistry, will be useful to test the reproducibility of these findings. In addition, larger studies may establish statistical differences in expression of other genes analyzed in this study. Overall, these findings support the view that tubulocystic carcinoma and collecting duct carcinoma should be considered as 2 distinct entities at the molecular level.

The plasmacytoid variant of urothelial carcinoma is rare, of which less than 40 cases have been reported in the English language literature. Herein we report the largest series to date of 17 cases of urothelial carcinoma with plasmacytoid features and report the associated clinicopathologic findings. The architectural pattern of the tumor varied from cells arranged in cords and single cells (35%), small nests (17%), solid sheetlike growth (29%), and diffuse discohesive patternless architecture (23%). The plasmacytoid component varied from 15% to 100% of the specimen analyzed; in 12 cases the plasmacytoid component composed greater than 50% of the tumor. The individual tumor cells had striking morphologic overlap with plasma cells with an eccentrically placed nucleus and abundant amphophilic to eosinophilic cytoplasm. The nuclei were of low to intermediate nuclear grade with minimal nuclear pleomorphism. Thirteen of 17 cases (76%) were associated with conventional high-grade invasive urothelial carcinoma and 9 cases showed very focal intracytoplasmic vacuoles mimicking signet ring cells. One case also showed sarcomatoid dedifferentiation. The tumor cells were positive for cytokeratin 7 (94%) and cytokeratin 20 (31%); CD138 was positive in 94% of cases. All cases were invasive -- 7 into at least the lamina propria, 7 into at least the muscularis propria, and 3 into perivesical fat. Follow-up information was available in 16 cases (range: 2 wk to 43 mo; mean 10 mo; median 5.5 mo). Eleven patients died of disease and 5 patients were alive with disease. Plasmacytoid variant of urothelial carcinoma is an aggressive subtype associated with poor prognosis. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression. Distinction from metastatic carcinoma from other primary sites such as stomach and breast is critical due to differing therapeutic implications.

Pax 2, expressed by metanephric mesenchyme is vital for renal tubule formation and development. Carbonic anhydrase IX (CA IX) is implicated in cell proliferation, adhesion, and invasion. Data regarding expression in renal epithelial tumors other than clear cell renal cell carcinoma (RCC) are limited, conflicting, from tissue microarrays, and do not encompass the entire spectrum or novel uncommon variants. Conventional sections from 200 renal tumors comprising clear cell RCC (n=30), oncocytoma (n=17), papillary RCC (n=30), chromophobe RCC (n=50), urothelial carcinomas (n=30), collecting duct carcinomas (n=5), renal tumors with Xp11.2 translocation (n=15), tubulocystic carcinoma (n=19), and mucinous tubular spindle cell carcinoma (n=4) were immunostained for Pax 2 and CA IX. Clear cell RCC (28/30, 93%), oncocytoma (17/17, 100%), papillary RCC (16/30, 53%), and mucinous tubular spindle cell carcinoma (3/4, 75%) demonstrated nuclear immunoreactivity with Pax 2, whereas the other subtypes were nonreactive. Clear cell RCC (30/30, 100%), urothelial carcinoma (27/30, 90%), papillary RCC (17/30, 57%), and renal tumors with Xp11.2 translocation (6/15, 40%) exhibited membranous immunoreactivity with CA IX, whereas the other subtypes were nonreactive. This suggests potential diagnostic utility of Pax 2 in distinction of (i) oncocytoma (positive) from chromophobe RCC (negative), (ii) clear cell RCC and papillary RCC (positive) from renal tumors with Xp11.2 translocation (negative), and (iii) high-grade clear cell RCC (positive) from urothelial carcinoma (negative). CA IX expression has potential diagnostic implications including (i) clear cell RCC (positive) versus chromophobe RCC (negative) and (ii) urothelial carcinoma (positive) versus collecting duct carcinoma (negative). These antibodies may reliably discriminate between clinically significant subtypes of RCC with overlapping cytoarchitectural features.

Claudin-7 and claudin-8 code for tight junction proteins expressed in distal nephron epithelium. In a recent oligonucleotide microarray study, we identified claudin-7 and claudin-8 as candidate markers to distinguish chromophobe renal cell carcinoma from other renal tumors, including oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because chromophobe renal cell carcinoma has malignant biological potential, whereas renal oncocytoma is benign. Claudin-7 and claudin-8 expression was studied by immunohistochemistry in 11 chromophobe renal cell carcinomas and 17 oncocytomas using formalin-fixed paraffin-embedded tissue sections of tumor with adjacent nonneoplastic kidney. Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon carcinoma and adjacent nonneoplastic kidney). Claudin-7 protein was expressed in a membranous pattern in 10 of 11 chromophobe renal cell carcinomas and 4 of 17 oncocytomas (P < .01). Claudin-8 was expressed in multiple patterns: In oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative claudin-8 was seen in 7 of 11 chromophobe renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for oncocytoma). The distal nephron proteins claudin-7 and claudin-8 have potential use as immunohistochemical biomarkers in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma. Expression of claudin-7 and claudin-8 may reflect the relationship of chromophobe renal cell carcinoma and oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional biomarkers to include with claudin-7 and claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity.

Objectives: To assess the interpretation of modern criteria for evaluating surgical margins (SMs), by examining the incidence of positive SMs (PSMs) and subsequent biochemical recurrence in a single-surgeon series of radical prostatectomy (RP) at two institutions, as the criteria for determining PSMs after RP are subject to individual interpretation, and this might explain some of the variability in biochemical recurrence rates with different rates of PSMs., Patients and Methods: We reviewed 301 consecutive perineal RPs by one surgeon (T.K.) at Emory University Hospital (EUH) and the Medical University of South Carolina (MUSC), with each pathology department using modern criteria to evaluate the SMs. The SM status and biochemical recurrence (BCR) were analysed, the latter defined as a prostate-specific antigen level of > or =0.2 ng/mL., Results: There were 158 perineal RPs at EUH followed by 143 at MUSC. PSMs were reported in 39 patients (24.7%) at EUH, whereas six (4.2%) were positive at MUSC. The overall BCR rates were similar between the groups, but BCR within margin-positive cases was 100% at MUSC vs 25.6% at EUH (P < 0.01). The presence of tumour at <1 mm from the margin did not increase the rate of BCR compared to those with obvious negative SMs (P = 0.731)., Conclusion: In this single-surgeon series, using the same criteria to evaluate the SMs resulted in significantly different PSM rates and margin-positive BCR rates between the institutions. Although the reason for these differences is difficult to determine, the study shows clearly that tumour within 1 mm of the margin should not be classified as margin-positive.

Background and Objectives: Mitochondrial DNA (mtDNA) mutations, inherited and somatically acquired, are common in clinical prostate cancer. We have developed model systems designed to study specific mtDNA mutations in controlled experiments. Because prostate cancer frequently metastasizes to bone we tested the hypothesis that mtDNA mutations enhance prostate cancer growth and survival in the bone microenvironment., Methods: The pathogenic nucleotide position (np) 8993 mDNA mutation was introduced into PC3 prostate cancer cells by cybrid formation. Wild-type and mutant cybrids were grown as nude mouse subcutaneous xenografts with or without bone stromal cell co-inoculation. Cybrids were also grown in the intratibial space. Tumor growth was assayed by direct tumor measurement and luciferase chemiluminescence. Gene expression was assayed using cDNA microarrays confirmed by real time PCR, western blot analysis and immunohistochemistry., Results: Cybrids with the 8,993 mtDNA mutation grew faster than wild-type cybrids. Further growth acceleration was demonstrated in the bone microenvironment. A 37 gene molecular signature characterized the growth advantage conferred by the mtDNA mutation and bone microenvironment. Two genes of known importance in clinical prostate cancer, FGF1 and FAK, were found to be substantially upregulated only when both mtDNA mutation and bone stromal cell were present., Conclusions: The ATP6 np 8,993 mtDNA mutation confers a growth advantage to human prostate cancer that is most fully manifest in the bone microenvironment. The identification of specific molecular alterations associated with mtDNA mutation and growth in bone may allow new understanding of prostate cancer bone metastasis., (Copyright 2008 Wiley-Liss, Inc)

Background: A large percentage of patients with recurrent ovarian cancer develop resistance to the taxane class of chemotherapeutics. While mechanisms of resistance are being discovered, novel treatment options and a better understanding of disease resistance are sorely needed. The mitotic kinase Aurora-A directly regulates cellular processes targeted by the taxanes and is overexpressed in several malignancies, including ovarian cancer. Recent data has shown that overexpression of Aurora-A can confer resistance to the taxane paclitaxel., Methods: We used expression profiling of ovarian tumor samples to determine the most significantly overexpressed genes. In this study we sought to determine if chemical inhibition of the Aurora kinase family using VE-465 could synergize with paclitaxel to induce apoptosis in paclitaxel-resistant and sensitive ovarian cancer cells., Results: Aurora-A kinase and TPX2, an activator of Aurora-A, are two of the most significantly overexpressed genes in ovarian carcinomas. We show that inhibition of the Aurora kinases prevents phosphorylation of a mitotic marker and demonstrate a dose-dependent increase of apoptosis in treated ovarian cancer cells. We demonstrate at low doses that are specific to Aurora-A, VE-465 synergizes with paclitaxel to induce 4.5-fold greater apoptosis than paclitaxel alone in 1A9 cells. Higher doses are needed to induce apoptosis in paclitaxel-resistant PTX10 cells., Conclusion: Our results show that VE-465 is a potent killer of taxane resistant ovarian cancer cells and can synergize with paclitaxel at low doses. These data suggest patients whose tumors exhibit high Aurora-A expression may benefit from a combination therapy of taxanes and Aurora-A inhibition.

Objectives: One would expect cases with small foci of cancer at radical prostatectomy to be associated with correspondingly favorable (Gleason score < or = 6, < 3 positive cores, no core with greater than 50% cancer) biopsy and preoperative clinical findings., Methods: Radical prostatectomies from The Johns Hopkins Hospital (July 2004 to July 2006) with only 1 to 3 slides involved by 3+3=6 adenocarcinoma of the prostate with no focus of cancer measuring greater than 2 mm in dimension were identified., Results: One hundred fifty-one radical prostatectomy specimens were obtained with cancer involving 1 slide in 69 cases (45.7%), 2 slides in 61 cases (40.4%), and 3 slides in 21 cases (13.9%). Predominantly transition zone cancer was present in 1 patient (0.66%). Mean patient age was 57.1 years (41 to 73 years). Twenty-two patients (14.6%) had a suspicious digital rectal examination. Mean serum prostate-specific antigen (PSA) and percentage free PSA were 5.2 ng/dL (0.3 to 16.7 ng/dL) and 15.5% (8% to 36%), respectively. Of 146, 127 (87%) men with available information had PSA density of less than 0.15. Mean number of cores obtained was 12 (4 to 27 cores) and all were Gleason 3+3=6 cancers on biopsy. One hundred fourteen cases (75.5%) had 1 core positive, 28 cases (18.5%) 2 cores, and 9 cases (6%) had 3 or more cores positive. One hundred forty-eight cases (98%) had cancer involving 50% or less of 1 core; 2 of these cases with greater than 50% cancer were discontinuous foci., Conclusions: Although, typically, biopsy and clinical preoperative findings associated with very limited cancer at radical prostatectomy are correspondingly favorable, exceptions occur in terms of biopsy cancer extent, serum PSA measurements, and digital rectal examination findings.

Aims: The diagnosis of prostate carcinoma is based on a constellation of architectural, nuclear, cytoplasmic, and ancillary features. The aim of this study was to determine if the Ventana Symphony H&E protocol can improve on the detection of prominent nucleoli in foci of prostate cancer., Methods: One hundred and twenty cases of Gleason score 3 + 3 = 6 cancers involving 10-30% of one core were retrieved from four academic institutions and two large laboratories (20 cases per institution). The routine H&E and Symphony H&E protocol stained slides from the same case were reviewed centrally in a blinded fashion at the Johns Hopkins Hospital. The mean percentages of prominent nucleoli in malignant and benign glands by visual estimation were recorded for each case. After unblinding, the routine H&E slides were compared in a pair-wise t-test with the corresponding Symphony stained slide., Results: Within all sites, the Symphony slides showed statistically significantly more prominent nucleoli in the malignant glands than the routine slides., Conclusions: The Symphony H&E staining protocol consistently highlights nucleoli in cancer to a greater extent than routine H&E stains and may increase the likelihood of making a diagnosis of limited adenocarcinoma of the prostate in challenging cases.

The expression of mucin (MUC2) in prostate cancer has not been well studied previously and may be of prognostic and pathobiologic significance. It is, however, well known that MUC2 expression in mucinous pancreatic and breast cancer represents an indolent pathway since these tumors have a significantly better outcome than their conventional counterparts. Twenty-five cases each of Gleason pattern 3 and 4 mucinous adenocarcinoma of the prostate defined by greater than 25% mucinous component and nonmucinous adenocarcinoma of the prostate were obtained from the surgical pathology files of the Johns Hopkins Hospital and Emory University Hospital. Immunohistochemical stains were performed for MUC2 on all 50 cases. Mean patient age was 60 years (range 44-72 years). MUC2 was expressed in all 25 cases (100%) of mucinous adenocarcinoma of the prostate, irrespective of the Gleason pattern. The nonmucinous component of these cases was negative for MUC2. In contrast, MUC2 expression was significantly lower in nonmucinous adenocarcinoma of the prostate, detected in only 6/25 cases as a focal finding, while 19/25 (76%) of nonmucinous adenocarcinoma of the prostate were completely negative for MUC2 (P<0.01). In six cases that showed focal positivity, MUC2 was expressed in areas with Gleason pattern 3 cancer with extensive mucinous fibroplasia (one case) and prominent intraluminal mucin (five cases). Other areas of these tumors were negative for MUC2. Mucinous adenocarcinoma of the prostate shows diffuse expression of MUC2, a known tumor suppressor, which is not present in either normal prostate or the majority of conventional adenocarcinomas of this organ. This indicates that mucinous adenocarcinoma of the prostate is indeed of the 'colloid type' akin to those in other exocrine organs. It is highly conceivable that this de novo expression of MUC2 has a role, not only in the mucinous differentiation of these tumors and their colloid pattern, but also in their relatively indolent behavior that has been recently elucidated.

Purpose: We examined contralateral prostate cancer potentially left behind by focal therapy., Materials and Methods: We investigated 100 completely embedded radical prostatectomy specimens in which needle biopsy predicted limited disease (less than 3 positive cores, 50% or less involvement of any positive core, Gleason score 6 or less) and all positive needle cores were unilateral. Clinical stage was T1c in 85 and T2a in 15 cases with the palpable lesion on the positive biopsy side., Results: There was 1 positive core in 66 cases. On average 13.9% of each positive core was involved with tumor. The mean number of separate tumor nodules per radical prostatectomy was 2.9. In 65 radical prostatectomy specimens there was some tumor contralateral to the positive biopsy side. Total tumor volume in the radical prostatectomy contralateral to the positive biopsy side averaged 0.2 cm(3) (largest 1.3). In 23 cases contralateral tumor volume was greater than biopsy positive side tumor volume. There were 13 cases in which more than 0.5 cm(3) cancer was contralateral to the positive biopsy and 7 with predominantly anterior tumor. Volume contralateral to positive biopsy side could not be predicted by the number of positive cores (1 vs 2) or maximum percent of the core involved. Gleason pattern 4, extraprostatic extension or positive margins were seen contralateral to the positive biopsy side in 13, 1 and 2 cases, respectively., Conclusions: In a highly selected population with limited unilateral biopsy cancer, tumor contralateral to the positive biopsy side at radical prostatectomy is typically small. However, 20% of radical prostatectomy specimens had some contralateral adverse pathology in terms of size, extraprostatic extension, grade or margins.

The epithelial-to-mesenchymal transition (EMT) is crucial for the migration and invasion of many epithelial tumors, including prostate cancer. Although it is known that ZEB1 overexpression promotes EMT primarily through down-regulation of E-cadherin in a variety of cancers, the soluble ligands responsible for the activation of ZEB1 have yet to be identified. In the present study, we investigated the role of insulin-like growth factor-I (IGF-I) in the regulation of ZEB1 during EMT associated with prostate tumor cell migration. We found that ZEB1 is expressed in highly aggressive prostate cancer cells and that its expression correlates directly with Gleason grade in human prostate tumors (P < 0.001). IGF-I up-regulates ZEB1 expression in prostate cancer cells exhibiting an epithelial phenotype. In prostate cancer cells displaying a mesenchymal phenotype, ZEB1 inhibition reverses the suppression of E-cadherin protein and down-regulates the expression of the mesenchymal markers N-cadherin and fibronectin. Furthermore, ZEB1 blockade decreases migratory and invasive potential in ARCaP(M) compared with the control. These results identify ZEB1 as a key transcriptional regulator of EMT in prostate cancer and suggest that the aberrant expression of ZEB1 in prostate cancer cells occurs in part in response to IGF-I stimulation.

Mucinous adenocarcinoma of the prostate is one of the least common variants of prostate cancer. The prognosis of this variant of prostate cancer remains controversial. We present 47 cases (1991 to 2006) of mucinous carcinomas treated by radical prostatectomy. Mean patient age at diagnosis was 56 years (range: 44 to 69 y). The mean preoperative prostate-specific antigen (PSA) level was 9.0 ng/mL (range: 1.9 to 34.3 ng/mL). Clinical stages were T1c (34 cases), T2a (7 cases), and T2b (6 cases). The mean percentage of tumor composed of the mucinous component was 52% (range: 25% to 90%). The mean Gleason score was 7 with scores of 6 in 6 cases (12.8%), 7 in 37 cases (78.7%), and 8 in 4 cases (8.5%). Margins were positive in 4 cases of mucinous adenocarcinoma of the prostate. Only 2 cases had isolated margin positivity in the nonmucinous acinar component of cancer. In 12 cases (25.5%), mucinous adenocarcinoma had established extraprostatic extension (EEPE). Eight cases (17.0%) had isolated EEPE of nonmucinous cancer. The 1 lymph node metastasis contained nonmucinous cancer. All together, taking into account both the mucinous and nonmucinous tumor, 20/47 cases (42.5%) had EEPE and 6/47 (12.7%) had positive margins. The 1 lymph node metastasis contained nonmucinous cancer. The mean follow-up for those without progression was 5.6 years (median 6 y, range: 1 to 15 y). One patient (2.1%) progressed 3 years after his radical prostatectomy (5 y actuarial progression-free risk 97.2%). Using the Kattan nomogram, the predicted mean 5-year PSA progression-free risk for nonmucinous prostate cancer with the same PSA and postoperative findings as in the current study was 85.4%. This study confirms that mucinous adenocarcinoma of the prostate treated by radical prostatectomy is not more aggressive, and possibly even less aggressive than nonmucinous prostatic adenocarcinoma.

Aberrant diffuse expression of p63 in prostate carcinoma cells is a rare and poorly understood phenomenon. We studied 19 cases of prostate cancer with aberrant diffuse expression of p63 on needle biopsy and reviewed the subsequent radical prostatectomies in 6 cases. In 19/21 cases, 100% of the cancer nuclei stained intensely for p63, with 70% staining in the remaining 2 cases. Two additional radical prostatectomies with aberrant p63 staining with no needle biopsies available for review were also analyzed. On the hematoxylin and eosin-stained slides, 19/21 cases (90.5%) showed a distinctive morphology composed predominantly of glands, nests, and cords with atrophic cytoplasm, hyperchromatic nuclei, and visible nucleoli. Needle biopsy cases ranged from Gleason patterns 3 to 5 with tumor identified on one or more cores, ranging from a minute focus to 80% of the core. In all 8 radical prostatectomies p63 positive cancer was present, with in 2/8 cases both p63 positive cancer and usual p63 negative acinar prostate cancer. In all 8 cases, the tumors were organ confined with negative margins and there was no seminal vesicle involvement or lymph node metastasis. The presence of p63 positive atypical glands with an infiltrative pattern and perineural invasion on radical prostatectomy confirmed the needle biopsy diagnosis of carcinoma. Rarely, prostate cancer can aberrantly express diffuse p63 staining in a nonbasal cell distribution leading to the erroneous diagnosis of atrophy or atypical basal cell proliferation. The diagnosis of prostate cancer is based on the morphology and confirmed by the absence of high molecular weight cytokeratin staining and positivity for alpha-methylacyl-CoA racemase in the atypical glands. Pathologists need to be aware of this rare and unusual phenomenon, which is a potential pitfall in prostate cancer diagnosis.

Background: Uterine leiomyoma are commonly diagnosed in women of reproductive age. However, these benign tumors may present with clinical signs and symptoms that are consistent with ovarian carcinoma., Case: A 47-year-old gravida 0 presented with a large pelvic mass, ascites, bilateral pleural effusions, and an elevated CA 125 worrisome for ovarian carcinoma. Exploratory laparotomy revealed a 20,120 g pelvic mass, with 2 L ascites, and pelvic and periaortic lymphadenopathy. Final pathology was consistent with a benign giant leiomyoma. Postoperative course was complicated by reaccumulation of pleural effusion requiring therapeutic thoracentesis and diuretics. Patient had return to full activity with 50 pound weight loss at 8 weeks after surgery., Conclusion: Elevated CA 125 levels and ascites are often associated with ovarian carcinoma, but it is also important to keep benign processes in the differential diagnosis when considering malignancy.

We present 9 consult cases, the largest series to date, of colorectal adenocarcinoma involving the prostate. Mean age of patients at diagnosis was 61 years (range, 42-78 years). Six cases were initially diagnosed on needle biopsy and the others by transurethral resection. Three cases were diagnosed before biopsy of the colon, which led to the discovery of a primary colonic tumor. The mean interval between the detection of the primary colonic tumor and prostatic involvement in the other 6 cases was 30 months (range, 1-52 months). At diagnosis, the stages of colorectal carcinomas were pT1 (n=2), pT2 (n=2), pT3 (n=2), and pT4 (n=3). Two cases involved the prostate after the recurrence of rectal adenocarcinoma at the anastomotic site of the previous colonic resection. In most cases, the tumors were typical moderately differentiated with occasional poorly differentiated foci. Other histologic features included desmoplastic stromal reaction (100%, n=9), necrosis (77.8%, n=7), chronic inflammatory response (77.8%, n=7), cribriform pattern (66.7%, n=6), villous architecture (22.2%, n=2), mucin production (22.2%, n=2), signet-ring cells (11.1%, n=1), and perineural invasion (11.1%, n=1). Immunohistochemical stains were positive for beta-catenin in 6 of 6 cases, CDX2 in 6 of 6 cases, carcinoembryonic antigen in 7 of 7 cases, CK20 in 5 of 6 cases, high-molecular-weight cytokeratin in 5 of 6 cases, and alpha-methylacyl-CoA racemase in 3 of 6 cases. Stains were negative in all cases for prostate-specific antigen, P501S (prostein), and CK7. Six patients (66.7%) died of disease within an average of 34 months (range, 8-88 months) after diagnosis of prostatic involvement. There are critical therapeutic and prognostic implications for distinguishing between prostatic adenocarcinoma and colorectal carcinoma involving the prostate. Colorectal adenocarcinoma should be considered on prostate sampling when carcinoma exhibits either "dirty" necrosis, tall columnar epithelium with mucin production, mucin-positive signet-ring cells, villous architecture, or associated inflammation. Immunohistochemical stains for beta-catenin, CDX2, carcinoembryonic antigen, high-molecular-weight cytokeratin, prostate-specific antigen, P501S (prostein), CK20, and CK7 can be helpful in making a definitive diagnosis.

Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional prostate carcinoma. beta-catenin, CDX2, and clinical studies are needed to rule out colonic adenocarcinoma. As prostatic urothelial-type adenocarcinoma is entirely analogous to bladder adenocarcinoma in both, its morphology and immunophenotype, only clinical studies or in some cases pathologic examination of the cystoprostatectomy specimen can exclude infiltration from a primary bladder adenocarcinoma.

Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases, VEGFR-1 and VEGFR-2, are important therapeutic targets for various cancers including AML. Paraffin-embedded bone marrow samples (PE-BM) are, in most cases, the only tissue accessible to perform retrospective analyses of novel targets such as VEGF and/or its receptors. As a result, it limits our options to immunohistochemistry (IHS), or more expensive and less practical techniques such as enzyme-linked immunosorbent assay (ELISA) or fluorescence in situ hybridization (FISH). We analyzed the feasibility of IHS to measure VEGFR-1 and VEGFR-2 expression in 28 AML samples using monoclonal antibodies (moAbs) against Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2). Medical records were reviewed for relevant clinical information. Expression of VEGFR-1 (+) and VEGFR-2 (+) were seen in 25% (7/28) and 43% (12/28) respectively. Forty-six percent (13/28) were dual-negatives for VEGFR-1 and VEGFR-2; 14% (4/28) were dual-positives for VEGFR-1 and VEGFR-2. An inferior survival was observed in patients whose myeloblasts express either VEGFR-1 (+) or VEGFR-2 (+), or both. Determination of expression of VEGF receptors (1 and 2) by IHS in PE-BM tissue is feasible. Prospective comparison of IHC to flow cytometry or other molecular techniques, and assessment of the prognostic significance of VEGF receptors in AML patients is warranted.

Head injury is an important cause of mortality worldwide. The objective of the present study was to analyse the pattern of fatal head injury among patients seen in University College Hospital, Ibadan. The study was based on retrospective investigation of cases of fatal head injury referred by the coroner to the Department of Pathology, University College Hospital, between 1991 and 2000. Pertinent clinical and postmortem findings were extracted from available coroner's autopsy records. There were 529 cases (402 males and 127 females). Their ages ranged from <1 year to 90 years (mean=33 years), the average age of females (27.8) being less than that of males (34.6) (p=0.00003). 83.8% were road traffic accidents, 8.9% falls from a height, 3.8% assault, and 3% gunshot injuries. 79.1% had a GCS of 8 or less at presentation. The mean survival period of children aged less than 15 years was 2 days while that of adolescents and adults aged 15 years and above was 5.6 days (p=0.02). Subdural (62.4%), subarachnoid (24.6%), epidural (10.2%), and intracerebral (10%) haemorrhages were the major causes of death. Skull fractures occurred in 38.2%, while cerebral contusions occurred in 22.1%. Intracranial infection was relatively uncommon in these patients. The present study has shown that young adults, predominantly males in their most productive years of life, are especially prone to fatal head injury.