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ABSTRACT: We report a soft tissue sarcoma from the thigh with morphologic features resembling Ewing sarcoma, clear cell sarcoma, and myoepithelial tumor of soft tissue. In addition, the genetic and immunohistochemical findings do not correspond to any established pattern, so the tumor does not clearly fit into any one classification. The karyotype analysis revealed a rare chromosomal rearrangement, t(6;22)(p22;q12), that previously has been reported in bone and epithelial tumors. Molecular studies confirmed the presence of an EWSR1-POU5F1 fusion creating a chimeric gene with the N-terminal transcriptional activation domain of EWSR1 and the C-terminal POU DNA binding domain of POU5F1. This report is novel in that to our knowledge, it is the first complete molecular characterization of an EWSR1-POU5F1 fusion in a soft tissue sarcoma. Evaluation of existing data on the known EWSR1-POU5F1 tumors suggests that the fusion gene functions in a wide variety of cell types and may modify the differentiation state of cells, resulting in susceptibility to tumorigenesis.
Cancer Genetics 08/2011; 204(8):423-9.
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ABSTRACT: The prostate cancer risk indicator is a validated tool for predicting the chance of a screen detected prostate cancer to be classified as indolent, partially based on lateralized sextant biopsies. Our objective is to extract correction factors for adjustment of the model, addressing contemporary extended biopsy schemes.
Post-mortem 18-core biopsy results of men who died of unrelated causes, but were diagnosed with prostate cancer post-mortem were used to provide details on prostate biopsies and whole mount specimens. For each of the 18-core biopsies showing cancer, Gleason score, number of positive cores, location in the gland and percentage of cancer involvement were determined and correlated to final pathology. Total length of cancer tissue in a 6-core scheme was related to the length in 12 and 18-core schemes to compute correction factors. Furthermore, upgrading on extended biopsies and final pathology was evaluated.
Data from 33 autopsied men were included. The 18 and 12-core biopsies showed 192.72 mm and 143.76 mm of prostate cancer, compared to 70.80 mm with lateralized sextant biopsy, resulting in correction factors of 2.72 and 2.03 for 18 and 12-core schemes respectively. Upgrading in Gleason score on extended biopsy regimens compared to lateralized sextant biopsy occurred in 33% (11/33) of the cases.
Based on autopsy data, the present correction factors provide a support in the adjustment of the prostate cancer risk indicator towards more extended contemporary biopsy schemes, eventually leading to a more accurate prediction of the probability of indolent cancers and assisting patients and clinicians to make appropriate choices in daily practice.
The Canadian Journal of Urology 04/2011; 18(2):5625-9. · 0.64 Impact Factor
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ABSTRACT: From a morphologic standpoint, Ewing sarcoma (EWS) is one of a number of pediatric malignancies that are characterized by sheets of small, round, blue cells. Ewing sarcoma can usually be differentiated from other small round blue cell tumors by the presence of a gene rearrangement having a consistent breakpoint within the Ewing sarcoma gene (EWSR1) at 22q12. Although the most common translocation partner is FLI1, located at 11q24, there is a growing list of alternate rearrangements involving different loci. We describe the first example of a soft-tissue sarcoma morphologically and immunohistochemically similar to Ewing sarcoma, but with a novel t(18;19)(q23;q13.2).
Cancer genetics and cytogenetics 08/2010; 201(1):1-5. · 1.54 Impact Factor
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ABSTRACT: Recent guidelines recommend that men older than 75 years should not be screened for prostate cancer. However, increased life expectancy and the development of less invasive treatments have led to an interest in characterizing prostate cancer in elderly men. We determined how prostate cancer pathological characteristics differ in men older vs younger than 70 years.
We studied differences in prostate cancer pathological characteristics in autopsied glands from men 70 years old or older and compared findings to those in men younger than 70 years. All men died of causes unrelated to prostate cancer. Prostates were whole mounted at 4 mm intervals. Histological analysis was done to identify and characterize each cancer focus observed. Tumor volume was measured by computerized planimetry. Cancer was defined as clinically significant or insignificant based on established histological characteristics.
Of 211 prostates evaluated 74 were from men 70 years old or older. We identified cancer in 33 men (45%) in this age group vs in 26 of 137 (19%) younger than 70 years (p <0.001). Men older than 70 years had significantly larger cancer and more clinically significant cancer (64% vs 23%, p <0.005). Older men had more advanced stage cancer and greater Gleason scores (p <0.001).
In an autopsy study of men with no history of prostate cancer those older than 70 years were more likely to have larger and higher grade prostate cancer than younger men.
The Journal of urology 08/2009; 182(3):927-30. · 4.02 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumors (GISTs) are a rare and heterogeneous group of spindle cell neoplasms that have also been reported outside of gastrointestinal (GI) tract. These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). We report two cases of gastrointestinal stromal tumor identified on prostatic biopsies, where a primary prostatic sarcoma was considered in the differential diagnosis. In one of the cases, there was extensive local disease involving prostate, rectum, and pelvic wall, as well as metastatic disease that quickly lead to the patient's death despite aggressive treatment with imatinib mesylate and conventional chemotherapy. In the other case, the tumor was mostly confined to the rectum but also focally extended into the prostate capsule. The patient underwent resection and was alive without disease 18 months after surgery. In both cases, tissue samples from prostate and the rectum showed a malignant spindle cell neoplasm, which was positive for CD117 (c-kit). Given their unique clinical management, gastrointestinal stromal tumors should be considered in the differential diagnosis of spindle cell lesions on prostatic needle biopsies and CD117 should be added to the immunohistochemical panel in the work-up of such lesions to avoid misinterpreting them as primary prostatic neoplasms.
The Canadian Journal of Urology 03/2009; 16(1):4502-6. · 0.64 Impact Factor
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ABSTRACT: Poorly differentiated synovial sarcomas are diagnostically challenging soft tissue tumors. They can be indistinguishable from other "small blue cell tumors" based on morphology and even immunohistochemical studies. Here we report a rare case of poorly differentiated metastatic synovial sarcoma to lung without known primary, diagnosed with molecular genetic analysis. The tumor was negative for EMA and cytokeratin, previously reported as the most sensitive immunostaining markers for synovial sarcomas. SYT-SSX gene fusion, characteristic for synovial sarcoma, was identified in this case by FISH and RT-PCR assays.
International journal of clinical and experimental pathology 01/2009; 3(2):217-21. · 1.89 Impact Factor
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ABSTRACT: To evaluate a 36-core saturation biopsy scheme on autopsied prostate glands to estimate the detection rate based on the true cancer prevalence, and to compare the cancer features on biopsy with whole-mount pathological analysis, as saturation biopsies have been proposed as a tool to increase the prostate cancer detection rate, and as a staging tool to identify potentially insignificant cancers before surgery.
We took 36-core needle biopsies in 48 autopsied prostates from men who had no history of prostate cancer. The first 18 cores corresponded to an extended biopsy protocol including six cores each in the mid peripheral zone (PZ), lateral PZ and central zone. Six additional cores were then taken in each of these three locations. We compared the histological characteristics of step-sectioned prostates with the biopsy findings. Tumours were considered clinically insignificant if they were organ-confined with an index tumour volume of <0.5 mL and Gleason score of <or=6.
The pathological evaluation identified 12 (25%) cases of prostate cancer and 22 tumour foci; seven prostate cancers were significant. Of the 22 tumour foci, 16 (73%) were in the PZ. The first 18 cores detected seven cancers (58%), of which five were clinically significant. The last 18 cores detected four cancers, all of which were already detected by the first 18 cores. Of the five cancers remaining undetected by biopsies, two were clinically significant and three were insignificant. Comparison of the histological characteristics between biopsies and step-sectioned prostates showed an overestimation of Gleason score by saturation biopsies in three of seven cases.
The evaluation of saturation biopsies based on the true prevalence of prostate cancer showed no increase in detection rate over a less extensive 18-core biopsy. Also, saturation biopsies might overestimate the final Gleason score on whole-mount analysis.
BJU International 09/2008; 103(1):49-54. · 2.84 Impact Factor
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Urology 09/2008; 72(2):241-242. · 2.43 Impact Factor
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ABSTRACT: To investigate whether the inclusion of occult cancer in the control group can influence the association of prostate cancer and the polymorphism of manganese superoxide dismutase (MnSOD).
Prostate specimens and sera were obtained from 194 deceased men who did not have a history of prostate cancer. Eighteen-core biopsy specimens and whole-mount sections were evaluated histologically. The MnSOD genotype of the specimens was determined by polymerase chain reaction restriction fragment length polymorphism analysis.
Tumors were present in 57 of the prostates, and biopsy detected 33 (including 1 false-positive finding). It detected 17 (1 false-positive finding) and missed 14 tumors in the subgroup of 135 specimens with a prostatic-specific antigen <4 ng/mL. The MnSOD AA genotype was associated with prostate cancer found in the step-sectioned specimens vs the control group in whom the absence of occult prostate cancer had been verified. However, no association was found if the control group consisted of subjects with negative biopsy results from the overall group or the subgroup with a prostatic-specific antigen level of <4 ng/mL.
The MnSOD AA genotype was associated with prostate cancer in our study; however, contamination of occult prostate cancer in the control group reduced the power of analysis and might yield seemingly negative results. Epidemiologic studies should strive to include control groups with a verified absence of occult cancer.
Urology 07/2008; 72(2):238-41; discussion 241-2. · 2.43 Impact Factor
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ABSTRACT: Chronic inflammation is associated with prostate cancer and benign prostatic hyperplasia. However, the prevalence of chronic inflammation in malignant and benign glands has not been compared. We evaluated the association of inflammation, benign prostatic hyperplasia and cancer in autopsied prostates.
We prospectively analyzed 167 autopsied prostates. Pathological analysis identified each focus of cancer, benign prostatic hyperplasia nodules and areas of acute or chronic inflammation. Any cancer focus or benign prostatic hyperplasia nodule involved directly with inflammation was recorded. The association of the prevalence of prostate cancer, benign prostatic hyperplasia and inflammation was statistically assessed.
Inflammation was present in 113 (67.6%) of 167 cases. Chronic inflammation was identified in 88 (53%), acute inflammation in 6 (4%), and chronic inflammation and acute inflammation in 19 (11%) glands. In the majority of cases inflammation was present in the transitional zone. A total of 93 glands (56%) were involved with benign prostatic hyperplasia and 49 (29%) with cancer. Of the glands harboring benign prostatic hyperplasia 75% were also involved with chronic inflammation compared to only 50% of those without benign prostatic hyperplasia (p <0.01). Comparatively the glands with or without any evidence of cancer were similarly involved with chronic inflammation (55% vs 58%, p >0.1). Of the 27 glands involved with cancer and benign prostatic hyperplasia, chronic inflammation was more associated with benign prostatic hyperplasia than cancer (p = 0.006). Acute inflammation was not significantly associated with either benign prostatic hyperplasia or cancer.
Chronic inflammation was a common finding in autopsied prostates. It appeared to be directly associated with the presence of benign prostatic hyperplasia but not with cancer.
The Journal of urology 05/2008; 179(5):1736-40. · 4.02 Impact Factor
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ABSTRACT: Chromosomal translocations of t(2;13)(q35;q14) and t(1;13)(p36;q14), resulting in PAX3-FOXO1 (FKHR) and PAX7-FOXO1 (FKHR) gene fusions, have been found to be specific molecular markers for alveolar rhabdomyosarcomas (ARMS) and can be identified in approximately 80% cases. As the prognosis of ARMS is worse than that of embryonal rhabdomyosarcomas (ERMS), it is important to accurately distinguish between these 2 subtypes. This distinction may be difficult on the basis of morphology alone. To detect the genetic alterations, reverse transcriptase polymerase chain reaction (RT-PCR) or dual-color dual-fusion fluorescence in situ hybridization (FISH) have been used in most studies so far. In this study, we used FOXO1 (FKHR) gene break-apart FISH probe, which can detect both of the translocations involving the FOXO1 gene, and tested 20 cases of rhabdomyosarcoma (RMS) including 6 cases of ARMS, 8 ERMS, 1 pleomorphic type, 5 not otherwise specified (RMS-NOS), and 10 non-RMS sarcomas. A home-brew RT-PCR that could detect both PAX3-FOXO1 and PAX7-FOXO1 was also performed. Four pathologists independently reviewed all RMS and a consensus diagnosis was also reached in discrepant cases. Histologic and molecular findings were correlated with clinical outcomes with an average of a 49-month follow-up. FOXO1 break-apart by FISH was positive in 4 of 6 (66%) ARMS and 2 of 5 (40%) RMS-NOS cases. All other cases, including all ERMS, were negative. RT-PCR assay confirmed all FISH results. While 2 of 6 (33%) RMS patients with a FOXO1 break-apart died of the disease, there were no deaths among the patients with negative result. The FOXO1 gene break-apart FISH probe is a simple and accurate tool to detect the translocations associated with ARMS. As characteristic genetic alterations of ARMS can be identified in 40% of RMS-NOS cases in our study, the FISH assay would provide an additional useful tool in the diagnosis and prognosis of ARMS, and an alternative to RT-PCR.
Diagnostic Molecular Pathology 04/2008; 17(1):14-20. · 2.26 Impact Factor
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ABSTRACT: Prostate cancer is the most frequently diagnosed non-skin cancer in the United States and the third leading cause of cancer deaths. International trends in the incidence, mortality and prevalence of prostate cancer are assessed.
Databases from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute and the International Agency for Research on Cancer (IARC), and the literature on autopsy studies on prostate cancer were reviewed and summarized in the article.
Prostate cancer remains an important public health concern in Western countries and an emerging malignancy in developing nations. Prostate cancer incidence is dependent on efforts to detect the disease. Autopsy studies provide accurate and useful information regarding comparative prevalence rates of the disease among regions of interest.
Improved cancer registration is needed in developing nations. The prevalence of prostate cancer must be established to predict the expected incidence of the disease and in order to plan rational detection and treatment strategies. Clinically significant disease should be distinguished from insignificant disease which may pose little or no biological danger to the patient.
The Canadian Journal of Urology 03/2008; 15(1):3866-71. · 0.64 Impact Factor
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Clinical Orthopaedics and Related Research 11/2007; 463:229-36. · 2.53 Impact Factor
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Gabriel P Haas,
Nicolas Barry Delongchamps,
Richard F Jones,
Vishal Chandan,
Angel M Serio,
Andrew J Vickers,
Mary Jumbelic,
Gregory Threatte,
Rus Korets,
Hans Lilja, Gustavo de la Roza
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ABSTRACT: It is difficult to estimate the diagnostic accuracy of biopsy for prostate cancer because men with negative biopsy do not undergo radical prostatectomy and thus have no confirmation of biopsy findings.
We performed 18-core needle biopsies on autopsy prostates from 164 men who had no history of prostate cancer. Six-core biopsies were taken from each of the mid peripheral zone (MPZ), the lateral peripheral zone (LPZ), and the central zone (CZ). We tested associations between age and tumor characteristics and analyzed the sensitivity of biopsies at each site. All statistical tests were two-sided.
Prostate cancer was present in 47 (29%) prostates. Of the 47 cancers detected, 20 were clinically significant according to histologic criteria. Tumor volume was associated with tumor grade (P = .012) and with age (P<.001). The biopsies from the CZ did not detect any cancer that was not present in biopsies of either the MPZ or LPZ. The sensitivity of the biopsies taken from the MPZ and LPZ together (53%, 95% confidence interval [CI] = 38% to 68%) was therefore the same as that of 18-core biopsies and was superior to that of biopsies of the MPZ alone (30%, 95% CI = 17% to 45%) (P = .003). The sensitivities of biopsies from the MPZ for clinically significant and insignificant cancer were 55% (95% CI = 32% to 77%) and 11% (95% CI = 2% to 29%), respectively, compared with 80% (95% CI = 56% to 94%) and 33% (95% CI = 17% to 54%) for those from the MPZ and LPZ combined.
The ability to detect prostate cancer was more related to the biopsy site than to the number of biopsy cores taken. The 12-core biopsies, six cores each from the MPZ and LPZ, were most likely to detect the majority of clinically significant cancers but also detected many insignificant cancers. When the six-core biopsies from the CZ were added, no increase in sensitivity was observed.
CancerSpectrum Knowledge Environment 10/2007; 99(19):1484-9. · 14.07 Impact Factor
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Clinical Orthopaedics and Related Research 09/2007; 463:229-236. · 2.53 Impact Factor
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ABSTRACT: Surface lesions of bone usually present little diagnostic dilemma because the majority are conventional osteochondromas. Other surface bone lesions include periosteal chondroma, periosteal chondrosarcoma, and parosteal osteosarcoma. Mineralized soft tissue lesions such as myositis ossificans, synovial chondroma, and synovial sarcoma may present in a similar fashion when they occur in a juxtaarticular position. The soft tissue osteochondroma or paraarticular osteochondroma may simulate some of these more aggressive tumors, and its recognition is important to avoid overtreatment. A case of an 11-year-old male with a soft tissue osteochondroma is reported to illustrate the characteristic radiographic and histological features of this rare entity. No prior reports have examined soft tissue osteochondroma for expression of parathyroid hormone related protein, an established cartilage tumor proliferative mitogen.
Annals of Diagnostic Pathology 09/2006; 10(4):222-9. · 0.88 Impact Factor
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Archives of pathology & laboratory medicine 11/2005; 129(10):1343-4. · 2.58 Impact Factor
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International Journal of Surgical Pathology 05/2005; 13(2):233. · 1.00 Impact Factor
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ABSTRACT: Liposarcomas of the head and neck region are rare; only a few cases have been reported to arise in the cheek or buccal mucosa. Dedifferentiated liposarcoma has rarely been reported in the head and neck region and, to the best of our knowledge, this is the first reported case of dedifferentiated liposarcoma of the cheek. Dedifferentiated liposarcoma is a mixed histologic subtype defined by the association of an atypical lipomatous tumor or well-differentiated liposarcoma and a nonlipogenic sarcoma. The patient was a 61-year-old man who presented with a soft-tissue mass of the left cheek and a presumptive diagnosis of salivary neoplasm based on a fine needle aspiration. The tumor was excised and consisted histologically of an atypical lipomatous tumor/well-differentiated liposarcoma composed a well-differentiated lipomatous neoplasm with atypical cells and rare lipoblasts. The tumor recurred in the same location 5 months after surgery. The recurrent tumor was primarily composed of a nonlipogenic spindle sarcoma with focal rhabdomyoblastic differentiation associated with areas of an atypical lipomatous tumor/well-differentiated liposarcoma.
Annals of Diagnostic Pathology 01/2005; 8(6):352-7. · 0.88 Impact Factor
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ABSTRACT: Cystic nephroma is a rare and controversial benign multicystic renal tumor. While the clinical, radiologic, and histologic features of cystic nephroma are well described, the immunohistochemical features are not. The role of immunohistochemistry in the differential diagnosis, which includes multicystic renal cell carcinoma, is also unknown.
To define the histologic and immunohistochemical features of cystic nephroma.
Ten cases of cystic nephroma diagnosed at 2 institutions during a period of 10 years were stained with an immunohistochemical panel consisting of 20 immunostains.
Median age at diagnosis was 61 years, with a range from 31 to 79 years. The female-to-male ratio was 9:1. Grossly, the tumors were multicystic masses without solid nodules. Histologic features included cysts lined by flat, cuboidal, or hobnail epithelium and septa variably lined by fibrous (10/10 cases) and/or ovarian-like (7/10 cases) stroma. Corpus albicans-like acellular hyalinized structures were noted in the septa in 9 of 10 cases. The cyst epithelium showed consistent positivity for distal tubule/collecting duct markers (cytokeratin 19, cytokeratin AE1/AE3, epithelial membrane antigen) and variable positivity for proximal tubule markers (alpha1-antitrypsin, lysozyme, CD15, CD10). The ovarian-like stroma (present in 7/10 cases) stained positively for progesterone receptors (6/7 cases) and estrogen receptors (4/7 cases).
Our immunohistochemical findings confirm a previous report of both distal tubule/collecting duct and proximal tubule differentiation in cystic nephroma. Stromal estrogen and/or progesterone receptor positivity in the majority of cases of cystic nephroma is a novel finding.
Archives of pathology & laboratory medicine 01/2005; 128(12):1404-11. · 2.58 Impact Factor
