Lung carcinoma in the era of personalized medicine: the role of cytology.

In 2004, three groups working independently [1–3] , almost simultaneously, reported remarkable findings: that activating mutations in the epidermal growth factor receptor (EGFR) were common in certain lung carcinomas and that these mutations correlated with the response of those lung tumors to therapy with gefitinib and erlotinib, both EGFR tyrosine kinase inhibitors (TKIs). This was the first time driver mutations in lung cancer that responded to targeted therapy had been identified, marking the beginning of a new era of personalized medicine in lung cancer. Prior to the discovery of these mutations, patients had been treated with EGFR TKIs but predicting who would respond and who would not was only imperfectly correlated with the histologic appearance of the tumor and the clinical profile of the patient

The Added Value of Molecular Testing in Small Pancreatic Cysts

Background: Cystic lesions of the pancreas (CLP) represent a relatively common pathologic entity affecting at least 1% of medical patients and represent a spectrum of lesions from inflammatory pseudocyststo malignant neoplasms. A significant percentage of these cysts are found incidentally during imaging work-up for unrelated conditions and require appropriate diagnostic testing to characterize the nature of the CLP. A multi-disciplinary approach to characterize CLP is currently used involving cytology, imaging, and cyst fluid analysis. The most recent international guidelines recommend resection of pancreatic mucinouscysts \u3e3 cm, or smaller cysts with positive cytology, mural nodules, or symptoms. Recent work utilized DNA analysis to characterize CLP as either mucinousor serous, and assess malignant potential. Focusing on k-rasgene point mutation, this group was able to detect mucinousdifferentiation (specificity 96%). Further, high amplitude k-rasmutations combined with allelic loss were 96% specific for malignancy. Correlation of k-rasmutation / allelic imbalances with CEA, however, showed poor agreement in the diagnosis of mucinousCLP. Our aim is to determine the added benefit of molecular testing in diagnosing small (≤3 cm) pancreatic cysts

Scientific issues related to the cytology proficiency testing regulations

The member organizations of the Cytology Education and Technology Consortium believe there are significant flaws in current cytology proficiency testing regulations. The most immediate needed modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme, and changing the focus of the test from the individual to laboratory level testing. Integration of new computer-assisted and located-guided screening technologies into the testing protocols is necessary for the testing protocol to be compliant with the law

Comprehensive cytopathology

https://jdc.jefferson.edu/jeffersonfacultybooks/1010/thumbnail.jp

Cyclin e expression and early cervical neoplasia in thinprep specimens: A feasibility study

To investigate cyclin E expression as a possible marker for early cervical neoplasia using ThinPrep gynecologic specimens from premenopausal women. STUDY DESIGN: Archived ThinPrep liquid-based cervical/endocervical specimens (Cytyc Corporation, Box- borough, Massachusetts, U.S.A.) diagnosed as human papillomavirus infection (HPV) (20), atypical squamous cells of undetermined significance (ASCUS) (48) and within normal limits (WNL)/benign cellular changes (BCC) (21) were resampled in duplicate, fixed in 95% ethanol, subjected to immunocytochemical staining with the cyclin E antibody (clone 13A3, Novocastra Laboratories Ltd., Newcastle upon Tyne, U.K.) and HPV antibody (clone K1H8, Dako Corporation, Carpinteria, California, U.S.A.) and the expression scored by two pathologists and correlated with the cytologic diagnosis. A case was scored as positive if it contained >10 abnormal squamous cells with nuclear immunocytochemical staining. RESULTS: The cylin E antibody assay was positive in 20 (100%) cases cytologically diagnosed as HPV. These cases were also anti-HPV antibody positive. Four cases (19%) cytologically diagnosed as WNL/BCC were cyclin E positive. Of these, two were anti-HPV antibody positive. Thirty-four (73%) cases cytologically diagnosed as ASCUS were positive for the cyclin E assay and for anti-HPV antibody staining. CONCLUSION: Cyclin E expression correlates strongly with morphologic features of HPV in ThinPrep specimens and may serve as a surrogate marker for HPV infection and early cervical preneoplastic lesions

Targeting cytolytic samples for quality control

In the presence of Lactobacillus, intermediate squamous cells often exhibit cytolysis. This lysis of the cytoplasm of glycogen-rich intermediate cells represents a peptolytic process that is rarely encountered in superficial squamous cells and practically never in parabasal cells. The gynecologic specimen exhibits naked nuclei of intermediate cells, cellular debris and abundant bacilli.3 When the cytolytic process is excessive, evaluation of the sample is limited due to partially obscuring debris. Not only the recognition of endocervical cells may be a problem, but also epithelial abnormalities. This may have potential legal implications in disputed cases of sample adequacy in Pap smears. We report quality control (QC) of cervical- vaginal samples interpreted as within normal limits (WNL) with an adequacy score of satisfactory but limited by (SBLB) excessive cytolysis by prospective, random, 10% QC and high-risk (HR) QC for a six-month period in the Cytology Laboratory, Thomas Jefferson University Hospital

Golden anniversary of acta cytologica

Much has changed from when the journal was founded, 50 years ago, in both appearance and content. Acta Cytologica grew along with cytopathology. Over time the journal flourished, and its contents expanded to accommodate new scientific endeavors. With a makeover in 2005, the cover became blue and the contents organized according to original articles in gynecologic and nongynecologic material, fine needle aspiration, molecular techniques, other techniques, case reports and letters to the editor. The masthead shows 85 editorial board members from all continents, and the journal is the official publication of 53 international cytology societies which select their national editors. In contrast to 500 copies of the first issue, we printed in excess of 3,500 copies of the November/December 2006 issue in addition to our online subscribers

How technology is reshaping the practice of nongynecologic cytology: Frontiers of cytology symposium

To pay tribute to the Founders of Acta Cytologica, this Golden Anniversary symposium on nongynecologic cytology revives the written symposium style of the 1950s. Participants from countries throughout the world were asked how new technologies are currently applied in their laboratories and whether future advances and challenges can be predicted. The specific questions and the participants\u92 answers follow

Processing liquid based gynecologic specimens: Comparison of the available techniques

OBJECTIVE: To develop a cytopreparation protocol suitable for satisfactory processing by the AutoCyte(r) PREP System with the gynecologic specimens collected in PreservCyt(r) fluid for the ThinPrep(r) machine. STUDY DESIGN: The resi- due of a number of gynecologic specimens collected in PreservCyt(r) and processed by ThinPrep(r) were pro- cessed by AutoCyte(r) PREP. Some modifications were made in the cytopreparatory protocol in order to obtain satisfactory specimens. RESULTS: The ThinPrep(r) and AutoCyte(r) PREP specimens were examined independently. The results were comparable, with a high degree of concordance between the two techniques. CONCLUSION: Gynecologic specimens collected in PreservCyt(r) and following the ThinPrep(r) specimen collection protocol can be processed using the AutoCyte(r) PREP System. Minor protocol modifications provided comparable diagnostic material. Additional studies are needed to explore the feasibility of this approach and fulfill the various U.S. regulatory agency requirements for the liquid-based Pap test

P53 Immunohistochemistry for distinguishing reactive mesothelium from low grade ovarian carcinoma

To determine the utility of immunohistochemical staining for p53 in cell block material for distinguishing reactive meso-thelium from borderline or low grade ovarian carcinoma. STUDY DESIGN: Paraffin-embedded cell blocks from paracentesis and pelvic wash fluid of 44 cases of ovarian carcinoma and 20 cases containing only reactive mesothelium were immunostained for p53 using monoclonal antibody DO-7. Tumor grades ranged from borderline to high grade and were serous papillary (33), clear cell (3), mucinous (2), endometrioid (2), mixed serous papillary/clear cell (3) and undifferentiated (1). The three authors independently evaluated the staining, including estimation of the percentage and intensity of positive nuclear staining. RESULTS: A separation of positive from negative cases was seen when staining intensity was considered the critical parameter; moderate to strong staining was considered truly positive. Seventy-three percent (8/11) of borderline tumors, 80% (8/10) of low grade tumors and 65% (15/23) of intermediate to high grade tumors showed moderate to strong positivity. Percentage of staining was a less-reliable parameter as 25% of negative cases were positive by this assessment. CONCLUSION: p53 Immunohistochemistry, using monoclonal antibody DO-7 combined with standard morphologic evaluation, may be useful in distinguishing benign reactive mesothelium from borderline or low grade ovarian carcinoma