[Show abstract][Hide abstract] ABSTRACT: Fibroepithelial lesions (FEL) of the breast are notoriously difficult to classify on core needle biopsies. The goal of this study was to evaluate interobserver variability and accuracy of subclassifying difficult FELs into fibroadenoma (FA) and phyllodes tumors (PTs). We identified 50 breast core needle biopsies, initially diagnosed generically as FEL, with subsequent excision and final diagnosis of either FA or benign PT. Five surgical pathologists from one institution independently reviewed these in 3 rounds. The pathologists were blinded to the final excisional diagnosis. Two diagnostic categories were allowed: FA and PT. A set of histologic criteria was provided including the presence of subepithelial condensation, stromal heterogeneity, overgrowth, pleomorphism, fragmentation, cellularity, adipose tissue entrapment, and mitotic count and asked to review the slides for the second round. A third round of interpretations was conducted after each criterion was defined. Interobserver agreement for the diagnosis and each criterion was evaluated using the κ level of agreement. Accuracy of ratings to final diagnosis was calculated using Wilcoxon signed-rank test. κ Values for interobserver agreement were fair for the first and second rounds varying from 0.20 to 0.22, respectively. This increased to 0.27 in round 3. When considering each category, the κ value varied from 0.26 to 0.29 for FA and 0.28 to 0.14 for PT. Overall, there was fair agreement between the pathologists in all categories. The rate of correctly diagnosed cases ranged from 40% in the first round, to 48% in the second round, to 67% in round 3. Overall the pathologists performed better in identifying FA than PT. The accuracy of interpretations was significantly different between the first (40%), second (48%), and third rounds (67%).
[Show abstract][Hide abstract] ABSTRACT: The current International Federation of Gynecology and Obstetrics (FIGO) grade in endometrial carcinomas requires the evaluation of histologic features with proven prognostic value but with questionable reproducibility. This study tests the prognostic power and reproducibility of a new binary grading system.
Specimens from 254 hysterectomies were graded according to the new 3- and 2-tiered FIGO grading systems described by Alkushi et al. The selected morphologic parameters for the new grading system included the presence of predominant solid or papillary architecture pattern, severe nuclear atypia, tumor necrosis, and vascular invasion. The Cox proportional hazards and κ statistics were used for comparisons.
On multivariate analysis, and looking at all tumor cell types, the 4 tested grading systems were independent predictors of survival, with the 3-tiered FIGO grading system being the most predictive (P = 0.005). In the subset of endometrioid tumors, the 3- and 2-tiered FIGO grading systems and the new grading system retained their statistical significance as predictors of survival (P = 0.004, P = 0.03, and P = 0.007, respectively), whereas the grading system of Alkushi et al did not (P = 0.1). In nonendometrioid tumors, the new grading system proved to be the best predictor of survival, reaching near statistical significance (P = 0.06). The new grading system had acceptable intraobserver and interobserver reproducibility assessment (κ = 0.87 and κ = 0.45, respectively).
The 3-tiered FIGO grading system retained its superior prognostic power. However, available binary grading systems remain an attractive option by being highly reproducible and by eliminating the clinical ambiguity of intermediate grades of disease.
No preview · Article · May 2011 · International Journal of Gynecological Cancer
[Show abstract][Hide abstract] ABSTRACT: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers.
Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors.
Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P = .0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P = .029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P = .005).
The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy.
[Show abstract][Hide abstract] ABSTRACT: GLUT-1 is involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between GLUT-1 expression and tumor proliferation and angiogenesis in epithelial ovarian carcinoma.
Specimens from 213 patients with epithelial ovarian carcinoma were evaluated by immunohistochemistry for GLUT-1, Ki-67, and vascular endothelial growth factor. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between GLUT-1 expression and clinicopathologic characteristics, tumor angiogenesis (tumor MVD and vascular endothelial growth factor expression), and tumor proliferation (Ki-67). The effect of GLUT-1 expression on patient survival and on the volume of residual disease after cytoreduction was determined.
There was a significant positive correlation between expression of GLUT-1, Ki-67, and microvessel density. In univariate survival analysis, high GLUT-1 expression, high Ki-67 expression and high tumor microvessel density showed a significant impact on patient survival (p=0.0001). In multivariate analysis including patients with all tumor stages, after controlling for age, race, stage, grade, MVD, and the 3 markers (GLUT-1, Ki-67 and VEGF), only age (HR 1.5; 95% CI 1-2.3), stage (HR 3.6; 95% CI 1.8-7.5) and grade (HR 2.3; 95% CI 1.2-4.5) retained their significance as independent poor prognostic factors. Tumors simultaneously overexpressing GLUT-1 and Ki-67 were less likely to be optimally cytoreduced as compared to tumors overexpressing only one or neither of those two markers (OR: 3.8, p=0.01).
Expression of GLUT-1 correlates with tumor proliferation and microvessel density in epithelial ovarian carcinoma. In addition, patients with rapidly proliferating advanced stage tumors overexpressing GLUT-1 have a lesser chance for optimal cytoreduction.
No preview · Article · Dec 2010 · Gynecologic Oncology
[Show abstract][Hide abstract] ABSTRACT: The objective of the study was to evaluate the prognosis of ovarian cancer arising in endometriosis.
We retrospectively compared 42 cases of endometriosis-associated ovarian cancer (EAOC) with 184 cases of ovarian carcinoma without endometriosis (OC).
The median age in the EAOC group was 52 vs 59 years in OC (P < .05). In comparison with OC, the EAOC patients were more likely to have low-grade (21% vs 8%; P = .04) and early-stage tumors (International Federation of Gynecology and Obstetrics I and II combined) (49% vs 24%; P = .002). Clear cell (21% vs 2%) and endometrioid (14% vs 3%) tumors were more frequent in EAOC, whereas mucinous tumors were more prevalent in OC (P = .001). The median survival (199 vs 62 months) and the 5 year survival (62% vs 51%) were better for EAOC when compared with OC (P = .038). After controlling for age, stage, grade, and treatment, association with endometriosis was not an independent predictor of better survival in ovarian cancer.
As such, EAOC has a much better survival rate than OC. This could be explained by the higher prevalence of early-stage and low-grade tumors in EAOC when compared with OC.
No preview · Article · Nov 2010 · American journal of obstetrics and gynecology
[Show abstract][Hide abstract] ABSTRACT: Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.
Preview · Article · Jan 2010 · Cancer biomarkers: section A of Disease markers
[Show abstract][Hide abstract] ABSTRACT: Fibrolamellar carcinoma (FLC) is a rare malignant hepatocellular tumor of unknown etiology, arising almost exclusively from noninfected, noncirrhotic liver of young adults. FLC has traditionally been considered to have better survival than hepatocellular carcinoma; however, this notion might be highly erroneous. Patients with metastatic disease at presentation have a dismal prognosis with 5-year survival of only 15%. We describe a case of highly aggressive metastatic FLC that presented as hyperammonemic encephalopathy, which has never been previously reported in the literature.
No preview · Article · Dec 2009 · The American Journal of the Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Extragonadal germ cell tumors are uncommon and such tumors originating from the lung parenchyma are extremely rare. This is a case of 68-year-old female who was admitted with complaints of right-sided weakness, inability to maintain her balance, right-sided headache, and bloody sputum. Her workup revealed two enhancing brain lesions and large lung mass involving the left lower lobe. Fine-needle aspiration (FNA) of the lung followed by craniotomy was performed and the patient was initially diagnosed with lung adenocarcinoma metastatic to the brain based on the cytomorphology of the lung FNA and histology of the brain mass. However, retrospective investigation revealed markedly elevated alpha fetoprotein (AFP) of which the cytopathologist was unaware at the time of diagnosis. A review of the cytology and surgical specimen slides, as well as immunohistochemistry (IHC) on the brain tumor and FNA cell block were preformed. On the basis of the slides review, clinical findings, and immunostaining results, a diagnosis of primary pulmonary mixed germ cell tumor, containing choriocarcinoma and yolk sac elements, with brain metastases, was retrospectively made.
No preview · Article · Oct 2009 · Diagnostic Cytopathology
[Show abstract][Hide abstract] ABSTRACT: Although microstellite instability (MSI) is a prognostic marker in colorectal cancer, it's relation with prognosis in the endometrial cancer is controversial. The goal of this study is to identify the correlation between MSI and clinicopathologic markers along with survival in high grade endometrial carcinoma EC.
Between 1995 and 2004, we identified 119 patients (57 type-I, and 62 type-II) diagnosed with high grade EC and underwent hysterectomy. Sections were immunostained using antibodies against MLH1, MSH2, and MSH6. Semi-quantitative scoring of immunoreactivity was based on percentage of tumor staining and staining intensity. Statistical analysis and survival were assessed using the Kaplan-Meier method and Cox regression.
Tumors were considered microsatellite unstable (MSI) when at least 2/3 markers tested negative on IHC. Overall, there was no statistically significant difference in survival between patients with MSI tumors and those with microsatellite stable tumors (MSS) (p value=0.70). However, MSI tumors which tested negative for all three markers had markedly poor survival (median survival 3 months vs 71 months, p=0.04) when compared to MSS tumors. The risk of death was 13.2 times greater among women with MSI tumors (with 3 negative markers) compared to women with MSS tumors (OR=13.20 95% CI 3.50-49.76).
Although this study has its limitation due to the small sample size, it raises the question of the prognostic significance of MSI in high grade endometrial carcinoma. It also points to the importance of evaluating three mismatch repair genes (MLH1, MSH2, and MSH6) as a prognostic indicator.
No preview · Article · Apr 2009 · Gynecologic Oncology
[Show abstract][Hide abstract] ABSTRACT: To sudy the accuracy and value of immediate wet preparation (WP) procedure on effusion and washing cytologic specimens.
Two hundred specimens were identified over 3 months in our cytology laboratory, including 102 pleural effusion, 59 peritoneal effusion, 28 pelvic washing and 11 pericardial fluid specimens. WP slides were prepared, stained with toluidine blue (TB) and .. evaluated. Findings were reported as negative, suspicious or positive for malignant cells. For negative specimens, the remaining prepared slides were stained together. For suspicious or positive interpretation, slides were stained separately. Accuracy and additional benefits from this immediate triage step were studied.
Interpretation ofslides resulted in 152 negative, 34 positive and 14 suspicious for malignancy. Analysis for additional values resulted in immediate interpretation relayed to clinicians, additional fluid centrifuged for adequate sediment in samples with scant cellularity, selection of bloody specimens for acid washing procedures, selection of cases to optimize cell block preparation when pivotal histologic evaluation or immunohistochemistry was anticipated and selection of cases for potentially needed ancillary studies. Accuracy, sensitivity, specificity and positive and negative predictive values were high.
WP using the TB is accurate, sensitive and highly specific and has considerable value beyond segregating potential neoplastic cases.
[Show abstract][Hide abstract] ABSTRACT: Fine needle aspiration (FNA) in the operating room is a convenient optional diagnostic approach. Our objective of this study was to evaluate the accuracy and study the potential benefits of fine needle aspiration in the operating room.
Retrospective review of all intraoperative FNA that were requested and performed by pathologists over 20-month period was carried out. Immediate smears were interpreted by the cytopathology team after staining with Diff Quik stain. All cases were reviewed and correlation with subsequent tissue diagnosis was done. Accuracy was calculated and potential benefits were discussed. The number of aspirates was 32. Adequate material for immediate and final interpretation was achieved in 31 cases (sensitivity 97%). In 20 cases (63%), malignancy was diagnosed while a benign diagnosis was rendered in 12 (37%). All cases had a follow up tissue diagnosis. No false–positive cases were identified (specificity 100%). The information gained from this approach was considered helpful to the surgeons. We concluded that FNA of head and neck masses in the operating room is an accurate and sensitive diagnostic approach. The service provides helpful information to surgeons and is an additional optional diagnostic approach. Diagn. Cytopathol. 2008;36:369–374.
No preview · Article · Jun 2008 · Diagnostic Cytopathology
[Show abstract][Hide abstract] ABSTRACT: The association between human immunodeficiency virus HIV infection and the increased incidence of testicular tumors is a recent well-recognized phenomenon. Testicular tumors in the setting of HIV infection are most frequently of germ cell origin, less commonly lymphomas. We are presenting a unique case of testicular non-Hodgkin's B-cell lymphoma with associated atrial mass and mediastinal lymphadenopathy. The patient was not known to be HIV positive at the time of presentation. The initial clinical, radiological, and gross pathologic impression was that of seminoma. Discussion of the differential diagnosis and appropriate work up is presented.
No preview · Article · Sep 2007 · Saudi medical journal