The changing face of paranasal sinus fungus balls.

OBJECTIVES: We describe the clinical, radiographic, and histopathologic characteristics of fungus balls. METHODS: We performed a retrospective review of 24 consecutive patients with the diagnosis of a paranasal sinus fungus ball (mycetoma) from 2001 to 2008. RESULTS: We found that 18 of the 24 primarily involved sinuses had bony thickening, and 13 of the 24 had notable dilatation of the ostium. Eleven of the 24 patients were found to have some degree of immunocompromise (from organ transplantation, diabetes, etc). The patient's immune status correlated with the type of fungus involved. (Mucor-like fungi were more common in immunocompetent patients, and aspergillus-like fungi were more common in immunocompromised patients.) Also, there was a predilection for immunocompetent patients to have dilatated ostia, whereas immunocompromised patients were more likely to have a nondilatated ostium (p = 0.019). CONCLUSIONS: Our series of paranasal sinus fungus balls defines a group of patients heretofore poorly described in the literature. Our data reveal an increased incidence in immunocompromised patients. We also found consistent radiographic patterns, correlations between immune status and the fungal pathogen, correlations between ostial enlargement and immune status, and the presence of cranial nerve pareses. These represent new findings that merit further study.

Aberrant expression of E-cadherin and beta-catenin in human prostate cancer.

Cadherin-catenin complexes play a key role in embryonic development, and are associated with carcinogenesis and metastasis. We studied the expression of the major members of the family, including E-cadherin and beta-catenin in prostate cancer (PC), and correlated with Gleason grade and pathologic stage. Immunohistochemistry was performed on serial sections of paraffinized radical prostatectomy specimens to evaluate E-cadherin (n = 16) and beta-catenin (n = 17) expression using heat induced epitope retrieval. Benign appearing prostate epithelium was used as an internal control in each specimen. Two pathologists independently reviewed and scored the intensity and extent of immunostaining using a semiquantitative scale. The Mantel-Haenszel method, stratified by reviewer, was used to test for an association among Gleason score, pathologic stage, and the expression of E-cadherin or beta-catenin in PC. Gleason grade > or =7 cancers showed significantly lower expression of E-cadherin and beta-catenin compared to Gleason grade < 7 PC, P = 0.015 and 0.025, respectively. In addition, beta-catenin was down regulated in 4 of 5 (80%) specimens with identifiable high-grade prostatic intraepithelial neoplasia and had demonstrable nuclear staining in higher grade PC (P = 0.0001). However, E-cadherin and beta-catenin membranous or nuclear expressions were not significantly associated with final pathologic stage of the specimens (P values >0.05). Overall, the expression of E-cadherin and beta-catenin is significantly down regulated in PC compared to surrounding benign appearing prostate, which correlates with increasing Gleason grade. Furthermore, nuclear localization of beta-catenin in high grade PC may be a useful biomarker for aggressive PC.

Investigation of scanning parameters for thyroid fine needle aspiration cytology specimens: A pilot study.

BACKGROUND: Interest in developing more feasible and affordable applications of virtual microscopy in the field of cytology continues to grow. AIMS: The aim of this study was to investigate the scanning parameters for the thyroid fine needle aspiration (FNA) cytology specimens. SUBJECTS AND METHODS: A total of twelve glass slides from thyroid FNA cytology specimens were digitized at ×40 with 1 micron (µ) interval using seven focal plane (FP) levels (Group 1), five FP levels (Group 2), and three FP levels (Group 3) using iScan Coreo Au scanner (Ventana, AZ, USA) producing 36 virtual images (VI). With an average wash out period of 2 days, three participants diagnosed the preannotated cells of Groups 1, 2, and 3 using BioImagene's Image Viewer (version 3.1) (Ventana, Inc., Tucson, AZ, USA), and the corresponding 12 glass slides (Group 4) using conventional light microscopy. RESULTS: All three raters correctly identified and showed complete agreement on the glass and VI for: 86% of the cases at FP Level 3, 83% of the cases at both the FP Levels 5 and 7. The intra-observer concordance between the glass slides and VI for all three raters was highest (97%) for Level 3 and glass, same (94%) for Level 5 and glass; and Level 7 and glass. The inter-rater reliability was found to be highest for the glass slides, and three FP levels (77%), followed by five FP levels (69.5%), and seven FP levels (69.1%). CONCLUSIONS: This pilot study found that among the three different FP levels, the VI digitized using three FP levels had slightly higher concordance, intra-observer concordance, and inter-rater reliability. Scanning additional levels above three FP levels did not improve concordance. We believe that there is no added benefit of acquiring five FP levels or more especially when considering the file size, and storage costs. Hence, this study reports that FP level three and 1 µ could be the potential scanning parameters for the thyroid FNA cytology specimens.

Visual memory effects on intraoperator study design: determining a minimum time gap between case reviews to reduce recall bias.

OBJECTIVES: The objective of this research was to determine test intervals between intraoperator case reviews to minimize the impact of recall. METHODS: Three pathologists were presented with a group of 120 slides and subsequently challenged with a study set of 120 slides after 2-week and 4-week intervals. The challenge set consisted of 60 slides seen during the initial review and 60 slides previously unseen within the study. Pathologists rendered a diagnosis for each slide and indicated whether they recalled seeing the slide previously (yes/no). RESULTS: Two weeks after having been shown 60 cases from a challenge set of 120 cases, the pathologists correctly remembered 26, 22, and 24 cases or 40% overall. After 4 weeks, the pathologists correctly recalled 31% of cases previously seen. CONCLUSIONS: Pathologists were capable of recalling from memory cases seen previously at 2 and 4 weeks. Recall rates may be sufficiently high to affect intraobserver study design.

Conventional and liquid-based cervicovaginal cytology: a comparison study with clinical and histologic follow-up.

Increased rates of squamous intraepithelial lesion (SIL) diagnosis with liquid-based cervicovaginal cytology (CVC) methods are well documented. This retrospective study compares the ability of the ThinPrep Pap Test (TP) and the conventional Pap smear (CP) to detect biopsy-proven SIL and to exclude nonneoplastic disease. All CVC reports from January 1999 through December 2000 from seven community Family Medicine clinics affiliated with the University of Nebraska were reviewed. For women with at least one CVC diagnosis of epithelial cell abnormality (ECA), follow-up histology, cytology, and clinical data were obtained. Statistical analysis was performed using the chi-square method. SIL was diagnosed in 166 of 3,286 patients by TP (5.1%) and in 169 of 4,872 patients by CP (3.5%) (P < 0.001); 32 of the TP diagnoses (1.0%) and 34 of the CP diagnoses (0.7%) were high-grade SIL (HSIL). Atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) was the most severe abnormality diagnosed by TP in 218 patients (6.6%) and by CP in 279 patients (5.7%). Follow-up histology data on CVC SIL diagnoses showed evidence of cervical intraepithelial neoplasia in 94 patients screened by TP (2.9%) and in 79 patients screened by CP (1.6%) (P < 0.001); the biopsy diagnoses were CIN 2 or CIN 3 in 34 patients in the TP group (1.0%) and in 28 patients in the CP group (0.6%) (P < 0.025). Follow-up of patients in whom the first ECA CVC diagnosis was ASCUS or AGUS disclosed a positive predictive value for CIN of 22.8% for TP ASCUS/AGUS diagnoses and 11.9% for CP ASCUS/AGUS diagnoses (P < 0.005). In this population, TP was significantly better than CP in detecting biopsy- proven disease and in screening out benign abnormalities.

Whole slide imaging diagnostic concordance with light microscopy for breast needle biopsies.

This study investigated the diagnostic accuracy of whole slide imaging (WSI) in breast needle biopsy diagnosis in comparison with standard light microscopy (LM). The study examined the effects of image capture magnification and computer monitor quality on diagnostic concordance of WSI and LM. Four pathologists rendered diagnoses using WSI to examine 85 breast biopsies (92 parts; 786 slides) consisting of benign and malignant cases. Each WSI case was evaluated using images captured at either ×20 or ×40 magnifications and viewed using a Digital Imaging and Communication in Medicine (DICOM) grade, color-calibrated monitor or a standard, desktop liquid-crystal display (LCD) monitor. For each combination, the WSI result was compared with the original, LM diagnosis. The overall concordance rate observed between WSI and LM was 97.1% (95% confidence intervals [CI]: 94.3%-98.5%). After a washout period, all cases were reviewed a second time by each pathologist after using LM, and the second LM diagnosis was compared with the WSI diagnosis rendered by the same pathologist. Intraobserver concordance between WSI and LM was 95.4% (95% CI: 92.2%-97.4%). The second LM diagnoses were also compared with the original LM diagnoses, and the observed interobserver LM concordance rate was 97.3% (95% CI: 93.1%-99.0%). The study data demonstrated that breast needle biopsy diagnoses rendered by WSI were equivalent to diagnoses rendered by LM. No diagnostic differences were detected between the underlying viewing system parameters of monitor quality and image capture resolution. The results of this study demonstrated that WSI can be effectively used in subspecialty diagnostic cases where a minimum amount of tissue is available.

Salivary duct carcinoma responding to trastuzumab-based therapy: case report and review of the literature.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare malignancy with a poor prognosis. Human epidermal growth factor receptor-2 (Her-2/neu) is overexpressed in SDC and, hence, HER-2/neu targeted therapy could be an option. METHODS: A 72-year-old man presented with parotid swelling and cervical lymphadenopathy. He underwent a parotidectomy, modified radical neck dissection, and postoperative chemoradiation with cisplatin. A year later, he developed metastatic disease in the contralateral neck that was treated surgically with right axillary lymphadenopathy. He received radiation to both sites, concurrent with carboplatin. Two years later, he underwent resection of a lung metastasis. He then had progression in the axillary and mediastinal lymph nodes and received 5 cycles of docetaxel and trastuzumab followed by maintenance trastuzumab. RESULTS: The patient had a partial response and restaging studies 9 months after therapy discontinuation did not show progression. CONCLUSION: Trastuzumab-based therapy is a potential therapeutic option for patients with SDC.

N-cadherin switching occurs in high Gleason grade prostate cancer.

BACKGROUND: The inappropriate expression of non-epithelial N-(neural) cadherin by epithelial cells, called cadherin switching, has been suggested to play a role in prostate cancer (PC) progression. We explored the role of N-cadherin as a biomarker in PC by correlating the expression with clinical parameters. METHODS: Two pathologists blinded to patients' history independently reviewed and scored the intensity and extent of staining of N-cadherin expression in 44 randomly selected radical prostatectomy specimens. The expression was correlated with total Gleason grade, individual Gleason patterns, tumor stage, and preoperative serum prostate specific antigen (PSA) levels and P-values < 0.05 were considered statistically significant. RESULTS: Of the 44 PC specimens, 14 (32%), 23 (52%), 7 (16%) consisted of Gleason grade 5-6, 7, and 8-10, respectively and 20/44 (45%) demonstrated N-cadherin expression. N-cadherin was expressed in 1/14 (7%) of Gleason 5-6 compared to 15/23 (65%) of Gleason grade 7, and 4/7 (57%) of Gleason grade 8-10, demonstrating a significant correlation between N-cadherin switching and higher Gleason grade (P = 0.001). While only about a third of primary or secondary Gleason pattern 3 demonstrated N-cadherin expression, a majority of Gleason patterns of > or = 4 expressed N-cadherin (P > 0.05), further suggesting that N-cadherin switching occurs with higher Gleason pattern. However, N-cadherin expression did not significantly correlate with preoperative serum PSA levels or tumor stage in our study cohort. CONCLUSIONS: We have demonstrated for the first time that N-cadherin switching occurs in higher grade PC and correlates significantly with increasing Gleason patterns. N-cadherin may be as a useful biomarker of aggressive PC.

Conservative management of a myxoid endometrial stromal sarcoma in a 16-year-old nulliparous woman.

BACKGROUND: Sarcomas comprise less than 1% of all gynecological cancers and 2% to 5% of all uterine malignancies, of which endometrial stromal sarcoma accounts for approximately 15%. Surgery is fundamental in sarcoma management and a total hysterectomy is performed in the majority of cases. CASE: Presented is a case of low-grade myxoid endometrial stromal sarcoma in a nulliparous adolescent female managed by local resection and uterine reconstruction. CONCLUSION: In selected cases, the initial management of a localized and well defined low-grade endometrial stromal sarcoma could potentially be conservative (uterine-sparing) surgical resection.