Mai Gu

Cytokeratin immunoreactivity in Ewing's sarcoma: Prevalence in 50 cases confirmed by molecular diagnostic studies

Ewings sarcoma (ES) and primitive neuroectodermal tumor (PNET) are characterized by the presence of the specific t(11;22)(q24;q12) or variants thereof, producing diagnostic EWS fusion transcripts. Cytokeratin has been reported sporadically to be expressed in some cases of ES/PNET. However, its prevalence has not been assessed systematically in a series of cases with confirmatory molecular or cytogenetic evidence of a diagnostic translocation. We present in detail three index patients in whom strong cytokeratin immunoreactivity was a confounding factor in the diagnosis. To establish further the prevalence of cytokeratin immunoreactivity in a series of well-characterized ES/PNET, we then performed immunohistochemical studies with antibodies CAM5.2 and AE1/AE3 on 50 cases of ES/PNET diagnosed at Memorial Sloan-Kettering Cancer Center in which molecular evidence of a specific ES/PNET-associated translocation were available. Immunoreactivity to cytokeratin was present in 10 cases (20%), in five diffusely and five focally. There was no significant association between cytokeratin expression and the following parameters: patient age, sex, skeletal and extraskeletal primary site, and the type of EWS fusion transcript. Cytokeratin expression, a manifestation of epithelial differentiation, is present in as many as 20% of ES/PNET in either a diffuse or focal pattern.

In Vivo Optical Coherence Tomography of the Human Larynx: Normative and Benign Pathology in 82 Patients

Objectives: Optical coherence tomography (OCT) is an emerging imaging modality that combines low‐coherence light with interferometry to produce cross‐sectional images of tissue with resolution about 10 μm. Patients undergoing surgical head and neck endoscopy were examined using a fiberoptic OCT imaging probe to study and characterize microstructural anatomy and features of the larynx and benign laryngeal pathology in vivo.

High single-pass diagnostic yield of a new 25-gauge core biopsy needle for EUS-guided FNA biopsy in solid pancreatic lesions

BACKGROUNDnCurrent limitations of EUS-guided FNA include the need for multiple passes and on-site cytology assessment and lack of core specimen. Recently, a new 25-gauge core biopsy needle (PC25) was developed to overcome these limitations.nnnOBJECTIVEnTo determine the diagnostic yield of EUS-guided FNA aspiration biopsy (FNAB) when using the PC25 needle among patients with solid pancreatic lesions.nnnDESIGNnRetrospective analysis.nnnSETTINGnAcademic tertiary referral center.nnnPATIENTSnFifty consecutive patients with a solid pancreatic lesion underwent EUS-guided FNAB with PC25.nnnINTERVENTIONSnEUS-guided FNAB with PC25.nnnMAIN OUTCOME MEASUREMENTSnThe primary outcome was the diagnostic yield in single and overall passes of EUS-guided FNAB when using the PC25 needle for pancreatic solid lesions.nnnRESULTSnCytologic analysis showed malignancy in 38 patients on the first pass, with a cumulative sensitivity of 83%, 91%, and 96% on passes 1, 2, and 3, respectively. Although visible core was reported in 46 patients (92%), histologic core was seen in 16 patients (32%). Histologic analysis showed malignancy in 29 patients on the first pass, with a cumulative sensitivity of 63% and 87% on pass 1 and passes 1 to 4, respectively. The sensitivity, specificity, and accuracy in combined cytologic and histologic results were 85%, 100%, and 86% for single pass and 96%, 100%, and 96% on multiple passes, respectively. No complications were seen.nnnLIMITATIONSnA retrospective study design at a single center using a single arm.nnnCONCLUSIONnEUS-guided FNAB with the PC25 needle showed excellent single-pass and overall diagnostic yields. This needle appears to maintain a high cytologic yield, similar to standard 25-gauge FNA needles, while also providing some histologic core tissue.

Optical coherence tomography of laryngeal cancer.

Objectives: Optical coherence tomography (OCT) is a high‐resolution optical imaging technique that produces cross‐sectional images of living tissues using light in a manner similar to ultrasound. This prospective study evaluated the ability of OCT to identify the characteristics of laryngeal cancer and measure changes in the basement membrane, tissue microstructure, and the transition zone at the edge of tumors.

Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering “Green” chemoprevention. Cancer Prev Res; 6(5); 410–8. ©2013 AACR.

Fluorescence in Situ Hybridization for HER-2/neu Amplification of Breast Carcinoma in Archival Fine Needle Aspiration Biopsy Specimens

OBJECTIVEnTo assess the usefulness of fluorescence in situ hybridization (FISH) for HER-2/neu amplification of breast carcinoma in archival fine needle aspiration biopsy (FNAB) specimens.nnnSTUDY DESIGNnAll FISH performed on formalin-fixed, paraffin-embedded surgical specimens during January 2003-August 2003 at the University of California Irvine Medical Center were selected. Prior FNABs were retrieved. One cytologic slide was destained in each case. The results were compared with those obtained on histologic specimens using the paired t test.nnnRESULTSnFISH was performed on 41 surgical specimens of breast carcinoma. Thirteen patients had prior FNABs that were positive for adenocarcinoma. After hybridization on destained fine needle aspiration slides, no cells were found in 2 cases, and the results were not readable in 2 cases. In the remaining 9 cases, the results, expressed as the ratio of copies of the HER-2/neu gene to copies of the chromosome 17 centromere, were 5.10, 1.14, 1.21, 1.12, 0.74, 1.11, 1.21, 9.87 and 2.4. Results on the corresponding histologic specimens were 5.25, 1.05, 1.13, 1.22, 1.13, 1.12, 1.21, 9.35 and 2.61, respectively. No significant difference was found (p = 0.23).nnnCONCLUSIONnHER-2/neu amplification status by FISH can be accurately and reliably evaluated in existing archival cytologic slides.

Diagnosis of gastric glomus tumor by endoscopic ultrasound-guided fine needle aspiration biopsy: A case report with cytologic, histologic and immunohistochemical studies

BACKGROUNDnThe majority of glomus tumor are small, benign neoplasms that arise from modified smooth muscle cells. They usually occur in the dermis or subcutis of the extremities. However, rare cases have been reported in the visceral locations, most often in the stomach.nnnCASEnA 32-year-old woman presented with episodes of right upper quadrant pain. She was found to have a gastric tumor that was biopsied at another hospital, where the diagnosis of gastrointestinal stromal tumor (GIST) was made. Endoscopic ultrasound (EUS) performed at our institution revealed a gastric submucosal tumor that was then biopsied by fine needle aspiration (FNA). Cytology revealed cohesive clusters of uniform, round, small cells with ill-defined cytoplasmic borders and scanty, amphophilic cytoplasm. Nuclei were round, with smooth nuclear membranes and evenly distributed, dusty chromatin. Intermingled with those epithelioid cells were small, short, spindled, normal endothelial cells. Immunohistochemical studies performed on cell block showed that the tumor cells were negative for CD34, CD117, chromogranin, synaptophysin, desmin and AE1/AE3 and were strongly positive for SMA, HHF-35 and collagen type IV. Glomus tumor was diagnosed and later confirmed by histology.nnnCONCLUSIONnEUS-guided FNA biopsy is efficient and permits adequate sampling for accurate diagnosis of gastric glomus tumor. Although rare, glomus tumor should be in the differential diagnosis among other gastric lesions, such as well-differentiated adenocarcinoma, epithelioid GIST and carcinoid tumor.

Laryngeal epithelial thickness: a comparison between optical coherence tomography and histology

Objectives:u2002 Optical coherence tomography, an imaging modality using near‐infrared light, produces cross‐sectional tissue images with a lateral pixel resolution of 10u2003μm. However, normative data is first needed on epithelial thickness for lesion characterisation, and, to date, little exists. The purpose of our study is to measure normal laryngeal epithelial thickness by in vivo optical coherence tomography, and compare these values to those obtained from fixed ex‐vivo laryngectomy specimens.

Early but not delayed continuous arteriovenous hemofiltration improves cardiovascular function in sepsis in dogs

Objective: Continuous arteriovenous hemofiltration (CAVH) has been advocated as treatment to remove inflammatory mediators and thereby to improve hemodynamic parameters in sepsis. However, the results obtained with CAVH have been inconsistent. In a canine model of bacteremic Pseudomonas aeruginosa pneumonia, we tested the hypothesis that the time course of the institution of CAVH may be important in obtaining a beneficial treatment effect. Methods: Two protocols were performed in phenobarbital-anesthetized dogs. In the early hemofiltration study (EHS), CAVH for 3 h was initiated 2 h post-pneumonia before mean arterial pressure (MAP) fell. In the late hemofiltration study (LHS), CAVH for 3 h was initiated at 5 h post-pneomonia when a decrease in MAP had already occurred. Hemodynamic measurements included cardiac output (CO), stroke volume (SV), and stroke work (SW). Myocardial depressant activity [filterable cardiodepressant substance (FCS)] found in plasma was assessed by bioassay at each measurement interval. Results: In EHS, after 5 h of sepsis, SW, CO, and SV in the hemofiltered pneumonia group were higher as compared with the nonhemofiltered pneumonia group. In contrast, in LHS, no differences in hemodynamic parameters were found between the two pneumonia groups. In both EHS and LHS, plasma FCS activity was decreased to similar extents by CAVH. Conclusion: These results suggest the time course of institution of CAVH may be important in obtaining a beneficial treatment effect in sepsis.

Efficacy of Cone Biopsy of the Uterine Cervix During Frozen Section for the Evaluation of Cervical Intraepithelial Neoplasia Grade 3

We retrospectively selected 22 cases in which patients with a biopsy-proven diagnosis of cervical intraepithelial neoplasia grade 3 underwent cervical conization for frozen section (FS) evaluation followed by hysterectomy at the University of California Irvine Medical Center, Orange, during the August 1995 to September 9, 2001. All slides from FS and permanent section (PS) and hysterectomy specimens were reviewed. FS diagnoses were compared with those of previous biopsies, PS, and hysterectomy specimens. The PS correlated with FS in all cases but 1. Appropriate surgery was performed for all patients based on FS diagnosis. The McNemar test was used to compare the results of FS and PS, with a 2-sided P value of 1.0 and a c coefficient of 0.7755 with a 95% confidence level, indicating that the 2 groups were not significantly different. FS evaluation of cervical conization is as efficacious and accurate as evaluation of regular specimens in providing information for the appropriateness of same-day surgery. We recommend that entire tissue be submitted for FS to avoid sampling errors and to increase diagnostic accuracy.