The value of molecular testing in the evaluation and management of patients with pancreatic cysts.

BACKGROUND: Molecular testing aids in the work up and management of patients with pancreatic cysts. This study reports on the value of PancreaSeq® in the evaluation of pancreatic cyst aspirates. METHODS: PancreaSeq® testing at our institution was implemented June 1, 2022. Over a 7-month period (June 1, 2022 through December 31, 2022) 50 cyst aspirates of which 26 (52%) were non-diagnostic 4 (8%) negative 1 (2%) atypical, 17 (34%) suspicious for a mucinous cystic neoplasm (MCN) and 2 (4%) positive for a MCN on cytology were sent for testing. RESULTS: KRAS/GNAS gene mutations were present in 15 non-diagnostic cases and 5 cases suspicious for an MCN. The type of cyst was interpreted as mucinous (IPMN) and the risk of progression to high grade dysplasia/adenocarcinoma as low. KRAS mutations were present in 8 non-diagnostic cases, 1 atypical case, 8 cases suspicious for a MCN and one case positive for an MCN; findings interpreted as a mucinous cyst (IPMN/MCN) with a low risk of progression. BRAF mutations were present in 2 cases; one suspicious and the second positive for an MCN; both interpreted as a mucinous cyst (IPMN) with a low risk of progression. One non-diagnostic case was positive for several gene mutations and copy number alterations; findings interpreted as a mucinous (IPMN) cyst with an elevated risk of progression. VHL mutations were present in 2 negative cases interpreted as serous cystadenomas. Two non-diagnostic, 2 negative and 2 cases suspicious for a MCN were negative for gene mutations. CONCLUSION: Implementation of PancreaSeq® has led to improvements in clinical management of patients with pancreatic cysts.

A simplified molecular method to detect high-risk HPV using the Aptima HPV assay on head and neck FNA smears.

BACKGROUND: Fine-needle aspiration is used as a diagnostic tool in head and neck oropharyngeal squamous cell carcinoma and its metastases. Prognosis and treatment rely on the presence or absence of the human papilloma virus. The purpose of this study was to validate the performance of the Aptima HPV assay using Hema-Diff stained fine-needle aspiration smears in the diagnosis of human papilloma virus-related oropharyngeal squamous cell carcinoma using a simplified method to obtain tumor cells for testing. METHODS: Patients with a diagnosis of squamous cell carcinoma and positive p16 immunohistochemical staining were identified. Aptima Specimen Transport Media was used to remove tumor cells from the Hema-Diff stained slides using a moistened swab. The selected cells were tested for high risk-human papilloma virus using the Aptima HPV assay and Aptima HPV 16 18/45 genotype assay. The results were compared with the p16 immunohistochemical staining of the related cell block and surgical specimens. RESULTS: Twenty-one of the 21 (100%) p16-positive cases were found to be positive for high risk-human papilloma virus, whereas 20 of 21 (95%) negative cases were found to be negative for high risk-human papilloma virus using the Aptima HPV assay. CONCLUSION: The Aptima HPV assay can be used to detect high-risk human papilloma virus in Hema-Diff stained fine-needle aspiration smears of oropharyngeal squamous cell carcinoma with a sensitivity of 100% and a specificity of 95%. This provides a valuable alternative to p16 immunohistochemical staining of cell block sections that often lack appropriate numbers of tumor cells.

Diagnostic pitfalls and the value of fluorescence in situ hybridization as an adjunct to cytologic evaluation of bile duct brushings in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) can present diagnostic difficulties on bile duct brushings as cytologic features mimicking adenocarcinoma may exist. This study evaluates the role of fluorescence in-situ hybridization (FISH) as an adjunct to cytologic evaluation. METHODS: From January 1, 2020, through December 31, 2021, 308 bile duct brushings were processed of which 34 (11%) were malignant, 25 (8%) were suspicious, 36 (12%) were atypical, 204 (66%) were negative and 10 (3%) were nondiagnostic. Follow-up biopsies/resections were performed in the 95 cases with diagnostic cytology (atypical/suspicious/malignant) of which 12 (13%) showed primary sclerosing cholangitis and form the basis of this study. Cytologic, histologic and FISH findings are presented and discussed. RESULTS: Of the 12 bile duct brushings 4 (34%) were positive/suspicious for adenocarcinoma and 8 (66%) showed atypical epithelial cells. FISH was positive in 2/4 positive/suspicious brushings and negative in the remaining 2 brushings. Histologic findings confirmed the FISH results. The cytologic features of the 2 false positive cases overlapped those of adenocarcinoma. Two of the 8 bile duct brushings with atypical epithelial cells were positive/suspicious for adenocarcinoma on FISH analysis; findings confirmed on histologic follow-up. The remaining 8 patients underwent surveillance for the development of adenocarcinoma with repeat bile duct brushings, FISH analysis and biopsies, each of which has been negative to date. CONCLUSION: FISH, as an adjunct to the cytologic evaluation of bile duct brushings from patients with PSC, plays a role in improving diagnostic accuracy and serves as a surveillance tool for the potential development of adenocarcinoma.

Busulfan associated pulmonary toxicity: A benign mimic of squamous cell carcinoma diagnosed in a bronchoalveolar lavage specimen.

An uncommon case of iatrogenic cellular changes associated with busulfan therapy in a bronchoalveolar lavage of a 65-year-old woman who underwent bone marrow transplantation is presented and discussed. Chemotherapeutic changes are presented, and pitfalls discussed.

The value of concurrent endoscopic ultrasound-guided fine needle aspirates and needle core biopsies in the diagnosis of pancreatic neoplasms.

BACKGROUND: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) is highly sensitive and specific in the detection and diagnosis of pancreatic neoplasms. EUS-guided needle core biopsy has been used alone or as an adjunct to maximize diagnostic yield. This study compared the use of FNA versus needle core biopsy in the diagnosis of pancreatic neoplasms. METHODS: From January 1, 2018 through December 21, 2020, the Cytopathology Laboratory processed 374 FNAs from solid pancreatic masses of which 332 (89%) had concurrent pancreatic biopsies and form the basis of this study. RESULTS: Of the 332 FNAs, 173 (52%) were positive/suspicious for pancreatic adenocarcinoma, 33 (10%) were positive for a neoplasm, 20 (6%) were atypical 19 (6%) were negative and 87 (26%) were non-diagnostic. Biopsies were concordant in 248 (75%) cases and discordant in 84 (25%) cases. Of the 84 discordant cases, 29 (35%) had neoplastic cells on FNA of which 14 were atypical, 11 were negative and 4 were nondiagnostic on core biopsy. Of the 18 (21%) FNAs with atypical cells, 8 showed adenocarcinoma on core biopsy. Thirty-seven nondiagnostic FNAs showed adenocarcinoma on 25 (70%) core biopsies. If nondiagnostic FNAs were included, FNA sensitivity was 89% and specificity; 100%, and both were 100%, if the nondiagnostic cases were excluded. The needle core biopsy sensitivity was 91% and specificity; 100%. CONCLUSION: Both FNAs and core biopsies show high sensitivity and specificity in the detection of pancreatic neoplasms. However, combining the techniques enhances cellular yields and provides material for ancillary tests.

The association of atypical squamous cells, cannot exclude a high grade squamous intraepithelial lesion, hyperchromatic crowded groups and high grade squamous intraepithelial lesions involving endocervical glands.

BACKGROUND: Hyperchromatic crowded groups (HCGs) are often classified as atypical squamous cells, cannot exclude a high grade squamous intraepithelial lesion (ASC-H) on ThinPrep Pap tests. This study reports on the association of HCG's with high grade squamous intraepithelial lesions (HSIL) involving endocervical glands. METHODS: Over a 3-year period (January 1, 2018-December 31, 2020), 115 (0.2%) of 63,817 Pap tests were diagnosed as ASC-H. Histologic follow-up was available in 76 (66%) cases; 42 (55%) cervical biopsies; and 34 (45%) cervical cones/LEEPs. RESULTS: Based on the histologic results, 49 ASC-H cases showed HSIL/CIN 3 and form the basis of this study. ThinPrep Pap tests showed two cell patterns; atypical immature squamous metaplastic cells and HCGs, each of which was difficult to distinguish from HSIL. On histologic correlation all 10 ASC-H Pap Tests with individual atypical immature squamous metaplastic cells showed HSIL/CIN 3 without endocervical gland involvement and 37 (95%) of the 39 Pap Tests with HCGs showed HSIL/CIN 3 with endocervical gland involvement. CONCLUSION: The results of this study support the premise that a subset of HCGs represent endocervical gland involvement by HSIL as opposed to a glandular lesion; in particular endocervical adenocarcinoma in-situ.

The role of ThyroSeq V3 testing in the management of patients with indeterminate thyroid nodules on fine needle aspiration.

BACKGROUND: The multigene genomic classifier ThyroSeq V3 has proven to be an effective triage modality in the management of indeterminate thyroid nodules. This study reports on the clinical management of patients with indeterminate thyroid nodules. METHODS: ThyroSeq V3 testing at our institution was implemented April 1, 2019. Over a 17-month period (1 April 2019 through 31 August 2020). Thirty five indeterminate thyroid nodules were sent for testing; diagnoses included FLUS, suspicious for a follicular/Hurthle cell neoplasm (SFN/SHCN) and suspicious for papillary thyroid carcinoma (SPTC). There were 26 females, nine males; mean age 56 years. Aspirated nodules, mean size of 2 cm, were evaluated by rapid on site evaluation with adequacy assessed by the cytopathologist via telecytology. RESULTS: Of the 35 nodules, 17 (49%) were positive and 18 (51%) were negative on ThyroSeq Testing. All of the 17 positive nodules (four FLUS, 10 SFN/SHCN, three SPTC) showed neoplastic lesions; five adenomas, one NIFTP and 11 carcinomas on surgical resection. Only 4 (22%) of the 18 nodules that were negative were resected and showed two colloid/adenomatous nodules, one NIFTP and one follicular variant of papillary thyroid carcinoma. As FLUS FNAs were the majority of the indeterminate nodules, a comparison was made pre-and post ThyroSeq testing. Prior to ThyroSeq testing the majority (69%) of the nodules were resected as compared to 36% post implementation; a statistically significant value (P < .005). Surgical resection yielded a majority of benign nodules pre-ThyroSeq testing, 68%, as compared to post-ThyroSeq testing, 25%. CONCLUSION: Implementation of ThyroSeq V3 testing has led to improvements in clinical management of patients with indeterminate thyroid nodules.

The presence of multinucleated giant cells: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features vs the follicular variant of papillary thyroid carcinoma.

BACKGROUND: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly described entity with an indolent clinical course as compared to the follicular variant of papillary thyroid carcinoma (FVPTC). As the cytologic features of NIFTP overlap those of the FVPTC, distinction between the two on FNA cytology poses diagnostic difficulties. This study analyzes the presence of multinucleated giant cells (MGCs). METHODS: Twenty histologically confirmed NIFTP cases and 17 FVPTC cases each with a prior FNA and performed over a 2-year period were reviewed, the cytologic diagnoses compared and the number of MGCs counted. RESULTS: Of the 20 NIFTP cases, 55% were diagnoses as FLUS on FNA, 25% as FN/SFN and 10% as SPTC. Of the 17 FVPTC cases, 12% were diagnosed as FLUS, 53% as FN/SFN and 35% as SPTC. Fifteen (88%) FVTPC cases contained MGCs, whereas none of the 20 NIFTP cases contained MGCs. CONCLUSION: The presence or absence of MGCs may serve as an additional finding to differentiate NIFTP cases from FVTPC cases.

On the job training: an educational program in ROSE of fine needle aspirates and telecytology for cytotechnologists.

INTRODUCTION: As the demand for rapid on-site evaluation (ROSE) of fine needle aspirates (FNAs) has continued to increase, the provision of service requires a creative approach to maximize efficiency without compromising patient care. We describe the educational process used to train cytotechnologists in ROSE of FNAs using telecytology. MATERIALS AND METHODS: In 2005, the cytopathology division of the University of Wisconsin pathology department developed an on the job training program for cytotechnologists in ROSE of FNAs using telecytology. Training includes education in assistance on FNA procedures, proficiency and competency in specimen adequacy assessments, and proper usage of the telecytology work station. Trainees are monitored by a trainer through all the steps of the process, including the checklists and examination. RESULTS: Eight cytotechnologists successfully completed the program, with test scores ranging from 90% to 95%, and were deemed competent by all measures to provide ROSE of FNAs via telecytology. CONCLUSIONS: Cytotechnologists play a pivotal role in the provision of an FNA service. Schools of cytotechnology should educate students (future cytotechnologists) in ROSE of FNAs and video streaming via telecytology to prepare them for clinical work, enhance their scope of practice, and improve their job satisfaction.

FNA smears of pancreatic ductal adenocarcinoma are superior to formalin-fixed paraffin-embedded tissue as a source of DNA: Comparison of targeted KRAS amplification and genotyping in matched preresection and postresection samples.

BACKGROUND: The current study was conducted to compare DNA yield, including normalization to nuclear area, DNA amplification functionality, and detection of KRAS mutations between matched fine-needle aspiration (FNA) specimens and pancreatic resections diagnostic of pancreatic ductal adenocarcinoma. METHODS: A retrospective sample of 30 matched single FNA smears and macrodissected formalin-fixed, paraffin-embedded (FFPE) curls (2 5-µm curls) were compared by measuring the following: nuclear area (via digital image analysis), DNA yield (via NanoDrop spectrophotometry and Quantus fluorometry), and polymerase chain reaction threshold cycles for KRAS amplifications. Variants in KRAS codons 12/13 and 61 were detected by fluorescent melt curve analyses, followed by Sanger DNA sequencing. RESULTS: Despite a similar nuclear area, FNA smears yielded greater DNA per nuclear area via 2 DNA quantification methods. KRAS codon 12 mutations were detected in 23 of 30 FNA specimens (77%) compared with 17 of 30 matched FFPE specimens (57%), for a concordance rate of 74%. No KRAS codon 13 or 61 mutations were detected. CONCLUSIONS: FNA specimens are a more optimal source of DNA, and represent an important resource in the preresection and postresection molecular analysis of pancreatic ductal adenocarcinoma. Cancer Cytopathol 2017;125:838-47. © 2017 American Cancer Society.

The role of ancillary tests in the evaluation and management of patients with negative and non-diagnostic pancreatic cyst aspirates.

BACKGROUND: Fine needle aspiration of pancreatic cystic lesions has its limitations as the cytology is often paucicellular to acellular. This study reports on the value of ancillary tests, amylase and carcinoembryonic, in the evaluation and management of patients with negative and non-diagnostic pancreatic cysts. METHODS: From January 1, 2010 through December 31, 2015, the Cytopathology Laboratory processed 119 pancreatic cyst aspirates of which 51(43%) were negative and 52(44%) were non-diagnostic and form the basis of this study. The 103 patients, 66 men and 37 women underwent endoscopic ultrasound with fine needle aspiration and biochemical and biomarker analysis; amylase and carcinoembryonic antigen, of cyst contents. In this study, the cytologic findings were interpreted independent of the cyst fluid analysis. RESULTS: Of the 51 patients with negative pancreatic cyst aspirates, combined endoscopic ultrasound/cytology/cyst fluid analysis findings were compatible with 37 (72%) pseudocysts, 11 (22%) serous cystadenomas, and 3 (6%) intraductal papillary mucinous neoplasms. Of the 52 patients with non-diagnostic pancreatic cyst aspirates, combined endoscopic ultrasound/cyst fluid analysis findings were compatible with 17 (33%) pseudocysts, 17 (33%) serous cystadenomas, 14 (27%) intraductal papillary mucinous neoplasms, and 4 (7%) mucinous cystic neoplasms. Eight patients underwent surgical resection and the remaining 95 patients were managed medically with repeat imaging. CONCLUSION: Ancillary tests are of added benefit in the evaluation and management of patients with negative and non-diagnostic pancreatic cyst aspirates. Diagn. Cytopathol. 2017;45:303-307. © 2016 Wiley Periodicals, Inc.

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

BACKGROUND: Although the incidence of glandular epithelial abnormalities on cervical cytology is low, the clinical and histologic findings are often significant. The laboratory's 12-year experience is reported. METHODS: from January 1, 2003 to December 31, 2014, the Cytopathology Laboratory of the University of Wisconsin Hospital and Clinics processed 191,087 ThinPrep(®) Pap Tests of which 184 (0.1%) were reported as glandular epithelial abnormalities. One hundred forty-three (78%) of these cases had histologic follow-up and form the basis of this study. Of the 143 women (mean age, 52; median, 50), 45% presented with vaginal bleeding and 55% were asymptomatic. The cytologic groups included atypical glandular cells, atypical glandular cells; favor a neoplastic process, atypical endocervical cells, atypical endocervical cells; favor a neoplastic process, endocervical adenocarcinoma in situ, atypical endometrial cells and adenocarcinoma, NOS. RESULTS: Overall, the histologic follow-up showed epithelial abnormalities including endometrial and endocervical carcinoma, endocervical adenocarcinoma in situ, CIN 3 involving endocervical glands and metastatic carcinoma in 78% of the cases. The diagnoses were age-dependent and influenced by clinical symptomatology. CONCLUSION: Glandular epithelial abnormalities on Pap tests warrant further clinical investigation.

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

BACKGROUND: 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. METHODS: Prior to GAA treatment, 2.5 ml of the cervical sample was prealiquoted from 102 bloody ThinPrep(®) vials. Both GAA treated and nontreated samples were analyzed for hr-HPV using the Cervista(®) HPV HR assay. The levels of genomic DNA were measured and compared between these samples. In addition, ThinPrep(®) Pap Test adequacy rates were calculated and compared on aliquoted and nonaliquoted cervical samples. RESULTS: Of the 102 cervical samples, 95 (93%) nontreated aliquots contained satisfactory levels of genomic DNA as compared to 36 (35%) GAA-treated samples (p < 0.00001). Ninety-nine (97%) aliquoted cervical samples were satisfactory for cytologic evaluation as compared to 1,326 (96%) GAA treated samples from 2013 (nonaliquoted); not statistically significant (p = 0.7968). CONCLUSION: The levels of genomic DNA were significantly decreased in GAA treated vs non-treated TP samples. Aliquoting from the TP sample prior to treatment with GAA enables accurate measurement of DNA without affecting the adequacy of the TP cytology slide.

Bile duct brushing cytology: Cytohistologic/fine-needle aspiration correlation and diagnostic pitfalls.

INTRODUCTION: Bile duct brushings are a mainstay in the work-up of patients who present with clinical findings of pancreaticobiliary disease. This study presents the University of Wisconsin Hospital and Clinics Cytopathology Laboratory's experience over a 10.5-year period with histologic and fine-needle aspiration (FNA) correlation. MATERIALS AND METHODS: From January 1, 2005, through June 30, 2015, 676 bile duct brushings were processed, of which 408 (60%) were negative, 84 (12%) were atypical, 65 (10%) were suspicious, and 119 (18%) were malignant. Histologic and FNA follow-up was available in 285 (42%) of the cases and forms the basis of this study. RESULTS: There were 59 (21%) positive, 38 (13%) suspicious, 54 (19%) atypical, and 134 (47%) negative bile duct brushings with follow-up. Of the 59 positive cases, 57 (97%) were malignant and 2 (3%) were negative on histologic/FNA follow-up. Thirty-three (87%) of the suspicious brushing were malignant on follow-up and 5 (13%) were negative; 43 (80%) of the atypical brushings were malignant and 11 (20%) were negative; and 94 (70%) of the negative brushings were malignant and 40 (30%) were negative on histologic/FNA follow-up. The sensitivity was 38%; specificity, 95%; positive predictive value, 97%; negative predictive value, 30%. CONCLUSIONS: Bile duct brushing cytology is highly specific in the detection of malignant pancreatobiliary lesions with few false positives, but has low sensitivity with many false negatives.

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

BACKGROUND: 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. METHODS: From January 1-December 31, 2011, 12,853 ThinPrep® Pap Tests were processed on a ThinPrep® 3000 Processor, stained by the Papanicolaou method and screened manually by the cytotechnologists. In 2012, 26,581 Pap Tests were processed on a ThinPrep® 3000 Processor, stained with the ThinPrep® Stain, screened on the Image Processor, and reviewed on a Review Scope by the cytotechnologists. All cases interpreted as ASCUS were sent to the cytopathologist for final review. RESULTS: Overall, 52% of the ASCUS Pap Tests were overcalled by the cytotechnologists on manual screening and 56% were overcalled by the cytotechnologists with use of the ThinPrep® Imaging System, as addressed by the cytopathologist as the final arbitrator. CONCLUSION: In this study, initial use of a new technology resulted in over interpretation of negative cases as ASCUS. Increased usage and familiarity with the System should lead to pre-Imager rates.

The utility of high-risk HPV testing in the management of women 30 to 64 years of age with low-grade squamous intraepithelial lesions on cervical cytology.

INTRODUCTION: The current American Society for Colposcopy and Cervical Pathology guidelines recommend high risk-human papillomavirus testing for patients 30 to 64 years of age with a low-grade squamous intraepithelial lesion on Papanicolaou (Pap) tests. This study presents our experience since the introduction of the new guidelines. MATERIALS AND METHODS: From September 1, 2013 through August 31, 2014, 20,014 ThinPrep Pap tests were processed, of which 17,989 (90%) were negative, 863 (4.3%) were atypical squamous cells of undetermined significance (ASCUS), and 540 (2.7%) were low-grade squamous intraepithelial lesions (LSIL). Thirty-eight percent of the negative cases, 87% of the ASCUS cases, and 76% of the LSIL cases were processed for high risk-human papillomavirus genotypes. Of the 1,163 patients with a Pap test diagnosis of ASCUS and LSIL, 656 (56%) underwent colposcopic examination and, of those, 240 (37%) had cervical biopsies performed. RESULTS: In our cohort, 247 (33%) of the 754 ASCUS Pap tests were hr-HPV-positive and 507 (67%) were hr-HPV-negative. Of the 409 LSIL Pap tests, 245 (60%) were hr-HPV-positive and 164 (40%) were hr-HPV-negative. Colposcopy/biopsy follow-up within 3-months of the ThinPrep Pap test showed cervical intraepithelial lesion grade 2/3 lesions in 16% of the hr-HPV-positive ASCUS cases, in 15% of the hr-HPV-positive LSIL cases and in 9% of the hr-HPV-negative LSIL cases. CONCLUSIONS: This study supports the current management guidelines of colposcopy for women 30 to 64 years of age with hr-HPV-positive ASCUS and LSIL on Pap tests and repeat Pap test with cotesting for women with hr-HPV-negative LSIL.

Factors contributing to high ThinPrep® Pap test unsatisfactory rates in an academic medical center laboratory.

Specimen adequacy is a key component in the cytologic evaluation of cervical Pap tests. At our institution, yearly unsatisfactory rates continue to be high, placing our laboratory in the 95th percentile for CAP benchmark data for unsatisfactory Pap test rates. Using the 2001 Bethesda System criteria, unsatisfactory Pap test rates were calculated over a ten year period (January 2002 to December 2011) and contributing factors were analyzed. Of the 124,457 ThinPrep Pap tests performed, 4,163 (3.3%) were unsatisfactory for evaluation, the majority (90%) due to too few squamous epithelial cells. Peri/postmenopausal women and those who had received radiation/chemotherapy had the highest unsatisfactory rates; 55% and 25%, respectively. Higher unsatisfactory Pap test rates are related to the patient population served. Defined, reproducible adequacy criteria need to be defined for Pap tests from patients in certain clinical conditions.

Anal-rectal cytology as a screening tool for the detection of anal intraepithelial neoplasia in HIV-positive men.

INTRODUCTION: Use of anal-rectal cytology is on the rise as a screening tool for the detection of anal squamous lesions in human immunodeficiency virus (HIV)-positive individuals. The purpose of this 5-year retrospective study was to determine the utility of routine anal-rectal screening for the detection of squamous lesions in HIV-positive patients with histology correlation. MATERIALS AND METHODS: From January 1, 2008 through December 31, 2012, 448 anal-rectal Papanicolaou tests were performed on HIV-positive men, of which 133 were referred for high-resolution anoscopy. RESULTS: Of the 448 cases, 184 (41%) were classified as atypical squamous cells of undetermined significance or above, of which 133 (72%) had histologic correlation. Nine (7%) were negative, 64 (48%) were anal intraepithelial neoplasia (AIN) 1, 36 (27%) were AIN 2, 21 (16%) were AIN 3, and 3 (2%) were squamous cell carcinoma. CONCLUSIONS: The results of this study support the use of anal-rectal cytology as a screening tool in the detection of anal intraepithelial neoplasia, particularly in high-risk populations.

Kaposi sarcoma herpesvirus/human herpesvirus-8-negative effusion-based lymphoma: report of 3 cases and review of the literature.

BACKGROUND: Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma that arises in body cavities without detectable tumor masses. PEL is universally associated with Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV8). Despite overlapping features, KSHV/HHV8-negative effusion-based lymphoma is a distinct entity from PEL. To date, 52 cases have been reported. The authors report 3 additional cases received in their laboratory from 2007 to 2012. METHODS: Clinical data, cytomorphologic features, and immunophenotypic features of the 3 cases were described and compared with those reported in the literature. RESULTS: The cells in HHV8-negative effusion lymphoma commonly revealed large cell, immunoblastic morphology and B-cell immunophenotype. The 3 cases demonstrated cytomorphologic and immunophenotypic variability. Cytomorphologically, 1 case contained large, highly atypical cells with a moderate amount of cytoplasm, round nucleus, coarsely granular chromatin, and a single macronucleolus. The other 2 cases had medium to large atypical cells with high nuclear-to-cytoplasmic ratios, slightly irregular to cleaved nuclei, and multiple conspicuous nucleoli. One case had a null phenotype with aberrant cytokeratin expression. B-cell phenotype was established by clonal immunoglobulin heavy-chain rearrangement using polymerase chain reaction, whereas the other 2 cases demonstrated a B-cell phenotype by flow cytometry and immunohistochemical staining. All 3 cases were negative for both HHV8 and Epstein-Barr virus. CONCLUSIONS: HHV8-negative effusion lymphoma exhibits clinical, cytomorphologic, and immunophenotypic variability. Cases with a null-phenotype can be particularly challenging. When effusion lymphoma is suspected, ancillary tests are helpful. Moreover, HHV8 detection is critical in differentiating PEL and HHV8-negative effusion lymphoma, because they have overlapping features yet different prognoses.

Clinical significance of atypical squamous cells cannot exclude high grade squamous intraepithelial lesion with histologic correlation-: a 9-year experience.

Atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H) is a recognized category in the 2001 Bethesda Nomenclature System for cervical cytology. Although current ASCCP guidelines recommend colposcopic follow-up, more recent studies are suggesting prior triage for HPV-DNA analysis. We report on our experience at the University of Wisconsin Hospital and Clinics. From January 1, 2003 through December 31, 2011 (9-y), the cytopathology laboratory processed 109,424 Pap Tests, of which 281 (0.26%) were diagnosed as ASC-H. Tissue follow-up was available in 181 (64%) of these cases, of which 45 (25%) were negative/cervicitis, 41 (23%) were CIN 1, 36 (20%) were CIN 2 and 59 (32%) were CIN 3. Stratification by age groups showed a higher percentage of high grade (CIN 2+) lesions (65%) in the premenopausal age group as compared with high grade lesion (35%) in the postmenopausal age group, whereas negative/CIN1 biopsies were more common in postmenopausal (65%) as compared to premenopausal (44%) women. Our data support the use of colposcopy in the management of women with ASC-H on Pap Tests. However, in the older age group, prior HPV-DNA testing may be of benefit to better identify those women at risk for high grade lesions.