Nazneen Fatima

Thyroid Transcription Factor 1 and Napsin A Double Stain: Utilizing Different Vendor Antibodies for Diagnosing Lung Adenocarcinoma

Objective: A combined thyroid transcription factor 1 (TTF-1) and Napsin A double stain has been shown to be useful in the diagnosis of adenocarcinoma (ADC). This study compares differences in double staining patterns among vendor antibodies (Leica, Dako, and Biocare). Study Design: The cohorts included 35 FNA cell blocks of lung ADC and 24 cell blocks of lung squamous cell carcinoma (SqCCA). Double-staining immunohistochemistry was performed with TTF-1 as a brown nuclear stain and Napsin A as a red cytoplasmic stain, using three sets of double stains. Additionally, FISH expression was performed on SqCCAs with aberrant TTF-1 expression. Results: The sensitivity for the double stains ranged from 40 to 74%, while the specificity ranged from 88 to 96%. Two Leica TTF-1-positive SqCCAs also showed low-level amplification by FISH assay not seen in the TTF-1-negative control SqCCAs. Conclusion: The use of Dako TTF-1 antibody paired with Leica Napsin A antibody as a double stain yielded the best results for diagnosing ADC; additionally, the Leica Napsin A-only staining results had the highest positive predictive value at 97%. Both Dako and Biocare antibodies expressed less staining of SqCCAs than Leica staining.

Controversial role of epstein-barr virus in multiple sclerosis

The role of Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS) is still elusive. In 2007, Serafini et al demonstrated the direct role of EBV in brain lesions of MS patients. They found positive immunohistochemistry (IHC) staining for latency membrane protein 1 (LMP1), and EBV-encoded RNA (EBER) by in-situ hybridization (ISH) within postmortem brains of MS patients. The goal of this study was to attempt to demonstrate LMP1 by IHC and EBER by ISH in brains of patients with MS, to either support or refute their findings. Seventeen MS (16 brain biopsies and 1 autopsy brain) and 12 autopsy brains with no pathologic abnormalities, as normal controls, were studied. To control for the possibility that inflammation owing to other etiologies could result in EBV-positive cell accumulation, 11 brain biopsies of encephalitis and 4 brain biopsies of progressive multifocal leukoencephalopathy were also studied. Known positive (Hodgkins and non-Hodgkins lymphoma) and negative (with antibody primary replaced by buffer) controls were used. All positive and negative controls showed appropriate staining. However, there were no positive LMP1 or EBER results in any of the groups studied. The negative results of IHC and ISH in our study sharply contrast to those previously mentioned by Serafini et al, 2007 and suggest that EBV is not directly related to MS as an etiology.

GATA3 expression in sarcomatoid urothelial carcinoma of the bladder

The current available data on GATA-binding protein 3 (GATA3) expression in sarcomatoid urothelial carcinoma are limited, especially in the non-tissue microarray-based setting. In this study, we analyzed the expression of GATA3 in sarcomatoid urothelial carcinoma of the bladder in cystectomy/cystoprostatectomy specimens. A search was made through our surgical pathology and consultation files for cystectomy/cystoprostatectomy specimens with a diagnosis of sarcomatoid urothelial carcinoma. Only cases with available tissue blocks were selected. Immunohistochemical staining for GATA3 was performed, and staining in adjacent/overlying conventional urothelial carcinoma and/or benign urothelium was also documented. Twenty-two cases were obtained. Of 22 cases, 16 (73%) of sarcomatoid urothelial carcinoma were positive for GATA3. In the 7 (27%) of 22 cases that were negative for GATA3, it was observed that these cases were predominantly composed either of pleomorphic undifferentiated sarcomatoid areas or foci composed of extensive heterologous elements (chondroid, osteoid, or rhabdoid). GATA3 staining was positive in the adjacent/overlying conventional urothelial carcinoma and/or benign urothelium in all cases. This is one of the largest studies to date analyzing the expression of GATA3 in sarcomatoid urothelial carcinoma in cystectomy/cystoprostatectomy specimens. GATA3 is expressed in most cases of sarcomatoid urothelial carcinoma. Negative expression may, however, be observed in cases composed predominantly of pleomorphic undifferentiated sarcomatoid areas or extensive heterologous elements. We recommend including GATA3 in the panel of immunohistochemical stains for sarcomatoid carcinomas of unknown origin, especially if a bladder primary is being considered in the differential diagnosis.

Arginase-1: A Highly Specific Marker Separating Pancreatic Adenocarcinoma from Hepatocellular Carcinoma

Background: Arginase-1 and HepPar-1 are effective immunohistochemical (IHC) markers for hepatocellular carcinoma (HCC). In this study, we explored the possible efficacy of these stains in diagnosing pancreatic adenocarcinoma (PAD). Study Design: Arginase-1 and HepPar-1 IHC was performed on formalin-fixed, paraffin-embedded fine needle aspiration (FNA) cell blocks (CB) of PAD (n = 46), tissue microarray (TMA) of PAD (n = 33), FNA CB of HCC (n = 44) and TMA of HCC (n = 85). Negative controls without carcinoma were also applied (pancreas CB, n = 7; pancreas TMA, n = 3). Results: PAD CB demonstrated arginase-1 positivity in 0 of 46 cases and HepPar-1 positivity in 7 of 46 cases (15%). PAD TMA demonstrated arginase-1 positivity in 0 of 33 cases and HepPar-1 positivity in 4 of 33 cases (12%). HCC CB demonstrated arginase-1 positivity in 37 of 44 cases (84%) and HepPar-1 positivity in 32 of 44 cases (72%). HCC TMA demonstrated arginase-1 positivity in 75 of 85 cases (88%) and HepPar-1 positivity in 80 of 85 cases (94%). Conclusion: Both arginase-1 and HepPar-1 are effective IHC markers of hepatocellular differentiation. Arginase-1 demonstrates superior sensitivity and specificity compared with HepPar-1 in the diagnosis of HCC. However, both arginase-1 and HepPar-1 have a low sensitivity and a very high specificity for PAD.

Automated and manual human papilloma virus in situ hybridization and p16 immunohistochemistry: comparison in metastatic oropharyngeal carcinoma.

Objectives: We compared the efficacy of automated and manual human papilloma virus (HPV) in situ hybridization (ISH) and p16 immunohistochemical staining (IHC) in fine needle aspiration (FNA) of metastatic oropharyngeal carcinoma. Study Design: A total of 41 FNA cell blocks (CB) were evaluated. HPV ISH was interpreted as positive if a minimum of one tumor cell showed punctate dot-like nuclear positivity. p16 was interpreted as positive if ≥70% of tumor cells showed brown nuclear and cytoplasmic staining. Results: Thirty of 41 CB (73%) were positive by automated HPV ISH, 25 of 41 CB (60%) with manual HPV ISH. Eighteen of 41 CB (43%) were positive for p16 IHC. Twelve of 41 CB (29%) with automated HPV ISH and 2 of 41 CB (4%) with the manual method were positive at 10× magnification. Three of 41 CB (7%) with automated HPV ISH and 14 of 41 CB (34%) with the manual method were positive at 20× magnification. Fifteen of 41 CB (36%) with automated HPV ISH and 9 of 41 CB (21%) with the manual method were positive at 40-60× magnification. Conclusion: Automated HPV ISH plays a more significant role in determining the HPV status in CB. However, the failure to use high magnification in the evaluation can give false-negative results.

Contents Vol. 56,2012

R. Marshall Austin, Pittsburgh, Pa. Th omas A. Bonfi glio, Rochester, N.Y. Lukas Bubendorf, Basel Edmund S. Cibas, Boston, Mass. Yener S. Erozan, Baltimore, Md. David B. Kaminsky, Palm Springs, Calif. Robert Y. Osamura, Tokyo Fernando C. Schmitt, Porto Volker Schneider, Freiburg i.B. Mark E. Sherman, Rockville, Md. Diane Solomon, Rockville, Md. Alain P. Verhest, Brussels Philippe Vielh, Villejuif 1 9 5 7 T H E I N T E RN AT IO NA L EMY O F C Y T O L O G Y . . . . . . Official Periodical of the International Academy of Cytology