Suzanne M. Selvaggi

Cytologic features of high‐grade squamous intraepithelial lesions involving endocervical glands on ThinPrep® cytology

Usage of liquid-based cytology has resulted in better cellular preservation with enhancement of nuclear features. The purpose of this retrospective 2-yr study (January 1999 through December 2000) was to evaluate the cellular features of endocervical gland involvement by a high-grade squamous intraepithelial lesion (HSIL) vs. endocervical adenocarcinoma in situ (AIS) on cell samples processed by the ThinPrep method as compared to conventional smears. Of the 97 cases of CIN III diagnosed on cytology, 52 (54%) showed surface endocervical gland involvement by CIN III and form the basis of this study. There were also six cases of endocervical AIS diagnosed on histology with prior cytology. The architectural features of HSIL involving endocervical glands and AIS were similar to those previously reported on conventional smears. A consistent finding of HSIL involving endocervical glands was the loss of central cell polarity and piling within cell groups, a finding not present in AIS. Central cell polarity was maintained in cellular groupings of AIS. In addition to the cellular feature present on conventional smears, micronucleoli were clearly visualized in cells of HSIL involving endocervical glands and prominent nucleoli were present in AIS. Apoptosis and mitoses were clearly visualized in both entities. Endocervical gland involvement by HSIL has characteristic cell patterns and features on liquid-based/thin-layer cytology that permit their distinction from AIS.

Morphologic features of prostatic adenocarcinoma on ThinPrep® urinary cytology

Malignant cells of prostatic adenocarcinoma are rarely identified in urine. In most cases, this finding is associated with high stage tumor. Numerous descriptions of the morphology of prostatic adenocarcinoma have been reported using cytocentrifugated specimens. However, no specific morphologic description of prostatic adenocarcinoma in urine using liquid‐based cytology has been previously described. Four cases of prostatic adenocarcinoma in urine using ThinPrep® liquid‐based preparations were identified between 2002 and 2009 at the University of Wisconsin Hospital and Clinics. Three patients had either high stage tumor or metastatic disease at the time of diagnosis, while the remaining patient had low stage tumor. The morphology of each case was evaluated with specific attention to cell size, nuclear characteristics, nuclear to cytoplasmic ratio, and cytoplasmic characteristics. The resulting key features for prostatic adenocarcinoma in urine are clustering, increased nuclear to cytoplasmic ratio, and prominent nucleoli. Though typically the presence of prostatic adenocarcinoma in urine implies high stage tumor, cells of lower stage tumors may be seen in urine as well. Diagn. Cytopathol. 2011;39:101–104.

Cytologic detection of concurrent infectious agents in urines from renal transplant patients

Cytology is a well recognized and utilized method for the detection of polyomavirus in urine specimens from renal transplant patients. The purpose of this 5 year 6 month retrospective study (January 1, 2003–June 30, 2008) was to report on the additional infectious agents detected in these specimens. Of the 7,116 urine samples from renal transplant patients that were processed for the detection of polyoma (BK) virus, 1,399 (19.7%) were positive for BK viral inclusions and 5,717 (80.3%) were negative. In addition, 347 specimens (4.8%) contained infectious agents including HPV (1.6%), Candida (3.2%), Herpes virocytes (0.03%), cytomegalovirus (CMV; 0.03%), and trichomonads (0.03%) either alone or in combination. Follow‐up cervical, vaginal, and/or vulvar biopsies were available in six (5%) of the 115 specimens with cellular changes consistent with low‐grade HPV infection: three showed high‐grade squamous intraepithelial lesions, two showed low‐grade squamous intraepithelial lesions, and one showed both types of lesions. Urinary cytology plays a role not only in the detection of BK virus but also other infectious agents, which have an impact on follow‐up patient management. Diagn. Cytopathol. 2010;38:549–550.

Small cell variant of malignant melanoma masquerading as lymphoma on fine‐needle aspiration cytology: A case report

The morphologic and immunohistochemical diversity of malignant melanoma is well known to pathologists but despite this widespread awareness the diagnosis remains a constant challenge, particularly when a noncutaneous or metastatic tumor is evaluated by fine‐needle aspiration cytology. We present a case of the small cell variant of malignant melanoma mimicking lymphoma in a 78‐year‐old previously healthy male who presented with multiple pulmonary masses and a right‐sided pleural effusion. This particular case was also immunoreactive for the hematopoietic marker CD43, a feature not previously reported in malignant melanoma. Cytologic, histologic, and immunohistochemical features of this case are presented and discussed. Diagn. Cytopathol. 2012.

Comparison of cytotechnologists' and cytopathologists' ASCUS rates preimplementation and postimplementation of the ThinPrep® imaging system

The automated ThinPrep® Imaging System assists the cytotechnologists in the primary screening of ThinPrep® Pap Tests. This study compares the concordance of the cytotechnologists and cytopathologists in the interpretation of Pap Tests as Atypical Squamous Cells of Undetermined Significance (ASCUS) before and after implementation of the Imager in our laboratory.

Glandular epithelial abnormalities on thinprep® pap tests: Clinical and cytohistologic correlation

Although the incidence of glandular epithelial abnormalities on cervical cytology is low, the clinical and histologic findings are often significant. The laboratorys 12‐year experience is reported.

Maximizing the adequacy of Hologic(®) Cervista(®) HPV HR results on ThinPrep(®) Pap samples treated with glacial acetic acid.

Although glacial acetic acid (GAA) treatment of bloody cervical samples has reduced the rate of unsatisfactory Pap Tests, recent studies suggest that it may negatively impact high‐risk (hr)‐HPV test results. The objectives of this study were to compare the levels of genomic DNA between GAA treated and nontreated ThinPrep® samples using the Hologic® Cervista® HPV‐HR assay and to compare the adequacy of the ThinPrep® Pap Test between aliquoted and nonaliquoted samples.

The equivocal Pap test: Its past, present, and future

Literally hundreds of articles have been published on the Bethesda System Category ‘‘Atypical Squamous Cells’’ (ASC), in particular, those of ‘‘Undetermined Significance’’ (ASC-US). Numerous text books, monographs, atlases, journal articles, and societal websites describe and depict their cytomorphologic features and characteristics. The timely review by Howell and colleagues provides an accurate history of the evolution of ASC terminology from its published description by Papanicolaou in 1928 and his Atlas of Exfoliative Cytology in 1943 to modern times. As noted, not only has the terminology to report ASC changed over time but also follow-up and management strategies have changed as well. Systematic revisions to the category stemmed predominantly from the application of new tests/technologies to the study of cervicovaginal disease, and ease of implementation was the outcome of organized workshops with a wide representation of health care providers. Yet from the first Bethesda workshop in 1988 to the present time, the term ASC continues to cause diagnostic consternation for practicing pathologists and management issues for health care providers. Despite our best efforts, ASC still remains the most common abnormality reported by cervical cytology. A recent study in 2003 by the College of American Pathologists (CAP) Interlaboratory Comparison Program in Cervicovaginal Cytology (Pap) reported a median ASC rate of 4.0% as compared with a rate of 4.5% in 1996 despite wide-spread acceptance of Bethesda 2001 terminology, increased utilization of liquid-based preparations, HPV testing, and in many laboratories, automated screening. If the category of ASC is a cause of such consternation for the profession, why do we continue to use it? Continued use of the term ASC is as uncertain as the certainty it provides. Pitman et al. conducted a study to investigate the impact of reducing or eliminating the ASC-US category on the sensitivity and predictive values for detecting squamous intraepithelial lesions (SILs). The results showed a marked reduction in the sensitivity of the Pap smear for both SIL and HSIL (P < 0.002 for all cases) and was not found to be associated with a significant increase in the positive predictive value of an abnormal diagnosis for either SIL or HSIL (P > 0.46 for all cases). They concluded that reducing or eliminating the diagnosis of ASC-US lead to a statistically significant decrease in the sensitivity of the Pap smear. In addition, there was not a significant increase in the positive predictive value, rather elimination of the category would lead to a decrease in the overall accuracy of the test; findings born out in the literature. However, the forces that continue to drive the profession go well beyond the issue of sensitivity and specificity, not but least, the medical legal climate of the times. To the diagnostician, there is some comfort in rendering an interpretation of ASC-US in equivocal cases, knowing that the current management guidelines include close follow-up with repeat Pap tests, HPV testing, or colposcopy and biopsy. As our understanding of cervical disease evolved over time, the focus of cervical cancer screening was on the detection of HSILs, particularly CIN III and its association with potential progression to invasive carcinoma. Past experience showed us that CIN III was discovered in a small percentage of women with ASC-US on Pap testing. In an effort to detect the subpopulation of women more likely to harbor CIN II, III lesions and to address concerns on overuse of ASC-US, the ASC-US working group at the 2001 Bethesda conference introduced the new term ASC—Cannot exclude a high-grade squamous intraepithelial lesion (ASC-H); dividing the ASC category Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin *Correspondence to: Suzanne M. Selvaggi, M.D., Cytology/Clinical Labs/D4/259, Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, Madison, WI 53792-2472. E-mail: sselvaggi@uwhealth.org Received 7 October 2009; Accepted 19 October 2009 DOI 10.1002/dc.21277 Published online 25 November 2009 in Wiley InterScience (www. interscience.wiley.com).