Overview of nongynecological samples prepared with liquid-based cytology medium.

OBJECTIVE: Liquid-based cytology of nongynecological specimens is commonly used in cytology laboratories throughout the world and various processing methods, such as ThinPrep and SurePath, have been reported. The cytological features and performance of liquid-based cytology for various cytology specimens, including body cavity fluids, urine, brushing specimens and fine-needle aspiration of various lesions, were reviewed and compared with the experience of our laboratory and the literature published in PubMed. STUDY DESIGN: The parameters for the evaluation of liquid-based cytology and conventional smears were described in the various types of specimens. Criteria for the interpretation of nongynecological liquid-based cytology were highlighted to show differences in cell morphology, background and artifacts. RESULTS: The interpretation requires familiarity with the appearance of liquid-based cytology in the various types of preparations to avoid misdiagnosis. CONCLUSIONS: Cell blocks can be prepared with specimens preserved in a liquid-based cytology medium and immunocytochemical stains and molecular testing can be successfully performed. These are important adjuncts in order to reach a definitive diagnosis.

Ureteroscopic management of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (hereditary nonpolyposis colorectal cancer syndrome).

OBJECTIVES: To report our experience with ureteroscopic laser ablation of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (LS), as defined by a documented germline mutation in the MSH-2 gene. To increase awareness among urologists about UTUC in this unique patient population and refer to genetic counselling when appropriate. PATIENTS AND METHODS: Demographic, clinical and pathological data on 13 consecutive patients with UTUC and documented MSH-2 mutation comprising 15 involved renal units were retrospectively collected. Ureteroscopic evaluations involved biopsy and laser treatment with combination holmium/neodymium yttrium aluminum garnet (YAG) lasers. Tumours were graded from 1 to 3 according to the 1973 World Health Organisation classification by a single pathologist evaluating cell block preparations. RESULTS: The mean patient age at initial presentation was 56.5 years, with six of 13 patients having metachronous bilateral UT disease. The mean follow-up was 59 months with a mean number of surveillances of 12. Of 15 affected renal units, 10/15 (67%) of initial tumours involved the ureter with mean lesion size of 17.5 mm, while five of 15 (33%) involved the intrarenal collecting system with mean lesion size of 25 mm. Ureteroscopy cleared 13/15 (87%) lesions and four of those 13 (31%) needed staged procedures. Renal preservation rate was 14/15 (93%) with one nephroureterectomy and one segmental ureterectomy performed. One patient developed metastatic UTUC after 40 months surveillance. No patient presented with bladder tumours but seven of the 13 (54%) developed them within 10 months of the initial ureteroscopy. CONCLUSIONS: Patients with LS who develop UTUC present at younger ages and appear to be more likely to have bilateral UT disease over their lifetimes vs sporadic UTUC patients. Ureteroscopic laser ablation offers a good renal preservation rate with reasonable cancer control in patients willing to undergo endoscopic surveillance. Development of new bladder tumours is common.

The potential value of phosphohistone-h3 mitotic index determined by digital image analysis in the assessment of pancreatic endocrine tumors in fine-needle aspiration cytology specimens.

OBJECTIVE: According to the World Health Organization, pancreatic endocrine tumors are graded by assessment of the Ki67 proliferation index and/or mitotic count. The objective was to find comparable grading on the basis of the novel mitotic marker phosphohistone-H3 (PHH3). STUDY DESIGN: A computer-assisted system was used to assess 23 cell blocks stained with PHH3 and Ki67 antibodies. We investigated possible cut-points for PHH3 and computed percent agreement between the PHH3- and Ki67-based grading. RESULTS: The Spearman correlation between percent Ki67 positive and percent PHH3 positive was 0.76 (p = 0.001). A value of 0.3% for the lower cut-point ('cut-point 1', differentiating between grades 1 and 2) and values of about 1.8-1.9% for the higher cut-point ('cut-point 2', differentiating between grades 2 and 3) shows optimal agreement between PHH3 and Ki67 grading. The percentage of positive cells was much higher for Ki67 than for PHH3 (mean 10.6 vs. 3.0%). CONCLUSIONS: PHH3 has good correlation with Ki67, but the range of PHH3 positivity is much narrower than that of Ki67 (range 0-4% for PHH3 vs. 0-50% for Ki67). Therefore, to be as accurate, grading on the basis of PHH3 requires evaluation of a larger number of tumor cells for a precise determination of percent PHH3-positive nuclei.

Thyroglobulin wash testing in the surveillance of patients with thyroid carcinoma: proposal for a reflex test.

OBJECTIVE: Fine needle aspiration (FNA) cytology with thyroglobulin wash (TG-W) testing is recommended for follow-up of patients with differentiated thyroid carcinoma (DTC). The goal of this retrospective study was to determine if TG-W results contributed to the management of cases with positive FNA cytology. STUDY DESIGN: We reviewed data on patients with positive and suspicious cytology results, undergoing lymph node or thyroid bed FNA with TG-W testing as part of the preoperative or follow-up investigation of histologically proven DTC in our institution and from the literature. RESULTS: Of 30 positive/suspicious lymph node and thyroid bed FNAs in our institution, 22 (73%) had an elevated (>1 ng/ml) TG-W level. Seven of 8 TG-W-negative cases had DTC on follow-up. Of 577 cytology-positive/suspicious FNAs in the literature, 557 (97%) showed TG-W-positive results. Fourteen of 20 TG-W-negative cases had DTC on follow-up. All patients in retrospective and literature review groups with positive and suspicious FNA cytology and available follow-up were treated for recurrent or metastatic disease regardless of TG-W results. CONCLUSION: Observations of both our and other institutions support a recommendation of reflex FNA TG-W testing only for cases with negative or indeterminate cytology results.

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

PURPOSE: T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer. METHODS: PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors. RESULTS: Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001). CONCLUSION: Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.

Targeted cyst wall puncture and aspiration during EUS-FNA increases the diagnostic yield of premalignant and malignant pancreatic cysts.

BACKGROUND: Characterization of pancreatic cysts by using EUS-FNA includes chemical and cytologic analysis. OBJECTIVE: To evaluate whether material obtained from FNA of the cyst wall increases diagnostic yield. DESIGN: Prospective series. SETTING: Tertiary referral center. PATIENTS: Consecutive patients with pancreatic cysts referred for EUS-FNA between March 2010 and March 2011. INTERVENTION: FNA was performed with aspiration of cyst fluid for carcinoembryonic antigen (CEA) and cytology, followed by cyst wall puncture (CWP). CWP is defined as puncturing the far wall of the cyst and moving the needle back and forth through the wall to sample the wall epithelium. MAIN OUTCOME MEASUREMENTS: The diagnostic yield for mucinous cystic pancreatic neoplasms by CEA and cytology obtained from cyst fluid compared with cytology obtained from CWP. CEA ≥192 ng/mL was considered mucinous. RESULTS: A total of 69 pancreatic cysts from 66 patients were included. Adequate amounts of fluid were aspirated for CEA, amylase, and cytology in 60 cysts (81%). Cellular material adequate for cytologic assessment from CWP was obtained in 56 cysts (81%). Ten (30%) of 33 cysts with CEA <192 ng/mL and negative results of cyst fluid cytology had a mucinous diagnosis from CWP; 6 of 9 (67%) cysts with an insufficient amount of fluid for CEA analysis and cyst fluid cytology had a mucinous diagnosis from CWP. Furthermore, 4 malignant cysts were independently diagnosed by CWP cytology. The incremental diagnostic yield of CWP for mucinous or malignant cysts was therefore 29% (20 of 69 cysts, P = .0001). An episode of pancreatitis (1.45%) occurred. LIMITATION: Lack of surgical criterion standard. CONCLUSIONS: CWP during EUS-FNA is a safe and effective technique for improving the diagnostic yield for premalignant and malignant pancreatic cysts.

Assessment of fine needle aspiration specimen adequacy for high-risk HPV detection and genotyping in oropharyngeal squamous cell carcinoma.

OBJECTIVE: The aim of this study was to determine the adequacy of archived and fresh fine needle aspiration (FNA) specimens from metastatic head and neck squamous cell carcinoma (SCC) for the molecular detection and genotyping of high-risk (HR) HPV. STUDY DESIGN: Thirty-seven specimens from 26 patients diagnosed by FNA with metastatic SCC were included as retrospective specimens [19 slides stained with Papanicolaou (Pap) and 18 with Diff-Quik® (DQ)]. Twenty fresh FNA specimens from 18 patients were included as prospective specimens. These specimens were analyzed using the standard protocol for ThinPrep® cervical specimens, with a Cervista HR HPV detection kit. The positive specimens were tested for the HPV 16 and 18 genotypes. RESULTS: Forty-four of 57 specimens (77%) had sufficient cells to yield a valid HPV result. The adequacy rate for Pap-stained slides was 15/19 (79%), for DQ-stained slides it was 13/18 (72%), and for fresh needle aspirates it was 16/20 (80%). HR HPV was detected in 23/44 (52%) specimens. Among the 23 HPV-positive specimens, 19 were genotyped as HPV 16 and 1 as HPV 18. CONCLUSIONS: HR HPV detection and genotyping can be performed on FNA specimens of head and neck SCC prospectively collected in PreservCyt as well as on archival slides with either Pap or DQ stain.

Does mitosis-specific marker phosphohistone H3 help the grading of upper tract urothelial carcinomas in cell blocks?

BACKGROUND: Grading upper tract urothelial carcinomas (UTUC) in cell blocks with small distorted tissue fragments can be challenging; interobserver agreement is poor among pathologists. Mitotic figure (MF) counting along with nuclear features is important in grading these tumors. We evaluated the use of the mitotic-specific marker phosphohistone H3 (PHH3) as an adjunct to hematoxylin and eosin (H&E) stain for grading UTUC in cell blocks. METHODS: Formalin-fixed, paraffin-embedded tissues from the cell blocks of 61 UTUC were stained with H&E and PHH3 antibody. The grading of tumors was performed independently by 3 pathologists, on both H&E-stained and PHH3 plus H&E-stained slides. The grading system used was the 1973 WHO 3-point grading system. Gradings were compared by all the pathologists for H&E staining versus PHH3 plus H&E staining with the Stuart-Maxwell test of marginal homogeneity that accounts for the matched data. RESULTS: The average pairwise agreement by H&E alone was 55%, and 80% by PHH3 plus H&E. CONCLUSION: By adding PHH3 immunostain to the H&E, the agreement in grading the carcinomas among the 3 pathologists improved dramatically. PHH3 immunostain may play an important role in grading UTUC in small cell block samples.

Molecular analysis of centrifugation supernatant fluid from pancreaticobiliary duct samples can improve cancer detection.

OBJECTIVE: We aimed to supplement microscopic examination of biliary cytobrush specimens to improve sensitivity by mutational profiling of: (1) selected cells microdissected from cytology slides and (2) corresponding cell-free DNA in residual supernatant fluid. STUDY DESIGN: From 43 patients with brushings of bile or pancreatic duct strictures, DNA was extracted from microdissected cells and 1-2 ml of cytocentrifugation supernatant fluid. Mutational analysis targeted 17 genomic sites associated with pancreaticobiliary cancer, including sequencing for KRAS point mutation and loss of heterozygosity (LOH) analysis of microsatellites located at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, and 22q. RESULTS: Mutations were found in 25/28 patients with malignancy, and no mutations were found in 5/5 patients with benign surgical results. The cell-free supernatant fluid generally contained higher levels and quality of DNA, resulting in increased detection of mutations in most patients. KRAS mutations only occurred in patients with pancreatic cancer. Mutational profiling of supernatant fluid specimens resulted in high sensitivity and specificity for malignancy, improving the detection of malignancy over cytology alone. CONCLUSION: Brush cytology specimens yielded supernatant fluid enriched with DNA, probably from actively proliferating cells. Mutational profiling can enhance the cytologic evaluation and characterization of specimens suspected to contain pancreatic or bile duct cancer.

Voided urine fluorescence in situ hybridization testing for upper tract urothelial carcinoma surveillance.

PURPOSE: Fluorescence in situ hybridization is gaining popularity for transitional cell carcinoma screening. We determined the accuracy of fluorescence in situ hybridization for identifying upper tract transitional cell carcinoma. MATERIALS AND METHODS: A retrospective review of our upper tract transitional cell carcinoma database from 2005 to 2008 identified 35 patients with upper tract transitional cell carcinoma who submitted voided urine specimens for fluorescence in situ hybridization at commercial laboratory during a routine office visit. Each patient was evaluated endoscopically in the operating room within 3 months of sampling. Suspicious lesions were biopsied and treated. Transitional cell carcinoma in the lower or upper tract was proved by direct visualization, positive biopsy or upper tract cytology read as positive or highly suspicious for malignancy. RESULTS: Of the patients 35 satisfied study inclusion criteria. A total of 67 fluorescence in situ hybridization specimens were submitted. Upper tract transitional cell carcinoma was identified on 51 operative evaluations, of which 23 showed concurrent bladder tumor. For all encounters the sensitivity of fluorescence in situ hybridization was 56% and specificity was 80%. Sensitivity for low and high grade lesions was 68% and 67%, respectively. Only upper tract tumors were noted in 28 patients, in whom there were 2 false-positive and 13 false-negative voided fluorescence in situ hybridization results. In these cases sensitivity was 54% and specificity was 78% compared to the 18% sensitivity and 100% specificity of bladder cytology. Sensitivity for low and high grade upper tract transitional cell carcinoma was 60% and 50%, respectively. CONCLUSIONS: Voided fluorescence in situ hybridization has become an adjunct for bladder transitional cell carcinoma surveillance. However, it has limited value for upper tract tumor surveillance.

The added value of molecular testing in small pancreatic cysts.

CONTEXT: Recent studies have shown high amplitude K-ras gene mutation and allelic imbalances are predictive of malignancy in pancreatic cysts. OBJECTIVE: Our purpose is to determine the added benefit of molecular testing in diagnosing small pancreatic cysts. DESIGN: Retrospective, single-institution study. PATIENTS: Patients with pancreatic cysts (less than, or equal to, 3 cm) who presented for EUS evaluation. INTERVENTION: EUS-guided pancreatic cyst aspiration cytology, carcinoembryonic antigen (CEA) level determination, and detailed DNA analysis including K-ras gene mutation and allelic imbalance. MAIN OUTCOME MEASUREMENTS: Ability of cyst fluid DNA analysis to render a diagnosis compared with cytology and CEA level determination. RESULTS: Diagnostic agreement was seen in 55.6% (35/63) of cases. In 10 cases (15.9%), there was disagreement between cytology and molecular. Molecular testing provided a diagnosis in 20 cases (31.7%) when either cytology was unsatisfactory, or CEA not elevated (less than 192 ng/mL). Elevated CEA levels were seen in 16 cases (25.4%), each diagnosed as a mucinous lesion with molecular analysis. CONCLUSIONS: Molecular analysis of pancreatic cyst fluid adds diagnostic value in scant specimens when cytology may be unsatisfactory and CEA unreliable.

Identification of gastrointestinal contamination in endoscopic ultrasound-guided pancreatic fine needle aspiration.

OBJECTIVE: To evaluate whether B72.3 and CEA could identify duodenal and gastric contamination in cell blocks of clinically proven cases of pancreatic ductal carcinoma, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). STUDY DESIGN: Cell blocks of pancreatic fine needle aspirates from 19 ductal adenocarcinomas, 9 IPMNs, 5 MCNs, and 22 cases containing gastrointestinal epithelial contamination (GIC) (7 gastric, 15 duodenal) were stained with antibody to carcinoembryonic antigen (CEA) and B72.3. RESULTS: CEA was positive in 89% of adenocarcinomas and 92% of mucinous lesions. It was never expressed in gastric contamination and was positive in 2/15 (13%) duodenal contaminants. B72.3 was positive in 95% of adenocarcinomas and 85% of mucinous lesions. It was positive in 2/7 (28%) gastric and 7/15 (47%) duodenal contaminants. CONCLUSION: In contrast to previous work, our preliminary results indicate that B72.3 expression cannot be reliably used to identify GIC. A lack of CEA expression, however, can be used to identify both gastric and duodenal contamination. This represents an important diagnostic aid in the evaluation of suspected low grade mucinous lesions.

Correlation of positron emission tomography with fine needle aspiration biopsies in head and neck malignancy.

OBJECTIVE: To investigate whether a correlation between fine needle aspiration cytology and positron emission tomography (PET) exists in the preoperative screening, staging and diagnosis of head and neck cancer. STUDY DESIGN: We retrospectively correlated fine needle aspiration biopsy (FNAB) and PET scan in patients with head and neck lesions. RESULTS: There were 92 FNABs with corresponding PET scan in 83 patients. Mean standard uptake value (SUV) for benign lymph nodes was 5.05 (SD, 5.79), and 13.56 (SD, 6.38) and 16.99 (SD, 19.04) for squamous carcinoma and other malignancies, respectively. Ideal SUV cutoff value was determined to be 6.0. Of 66 malignant FNABs, 52 had an SUV > or = 6, 8 had an SUV < 6, and 6 were interpreted as "hypermetabolic." Of 26 benign FNAB (SUV was available for 17), 8 were interpreted as "hypermetabolic" and 1 as "not hypermetabolic." Of those with SUVs reported, 15 were < 6 while 2 were > or = 6. CONCLUSION: Lesions with SUV 6 are more likely to harbor malignancy, while lesions with repeatedly negative FNAB in the context of SUV > 6 should be considered for open biopsy. Further, lesions with SUV < 6 may harbor malignancy and therefore fine needle aspiration biopsy is also recommended.

Expression of K homology domain containing protein (KOC) in pancreatic cytology with corresponding histology.

OBJECTIVE: To evaluate if immunocytochemical expression of K homology domain containing protein overexpresssed in cancer (KOC) in biliary brushings and fine needle aspiration improves the diagnostic capability of cytology for intraductal papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDA). STUDY DESIGN: Fourteen PDAs, 15 IPMNs and 7 chronic pancreatitis cases were obtained. The cytology smears and surgical specimens were stained with antibody to KOC (1:500). The intensity (scale 0-3+) and per centage of cells staining were evaluated in pathologic lesions, and diffuse (>75% of cells) staining of 3+ intensity was considered positive. RESULTS: There was 100% specificity for diagnosing PDA. The sensitivity was greater in histology (79%) than cytology (71%). All chronic pancreatitis and IPMN cases, including IPMN with high grade dysplasia, were negative. Benign epithelium adjacent to PDA or IPMN was also negative. CONCLUSION: This study demonstrated that PDA can be differentiated from IPMN and benign ductal epithelium using KOC expression. This could be useful in cytologic cases where atypical features preclude a definitive diagnosis of malignancy.

Cytologic accuracy of samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration at Thomas Jefferson University Hospital.

OBJECTIVE: To evaluate the diagnostic yield and cytologic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in cases of clinically suspected epithelial malignancy, sarcoidosis and lymphoma. STUDY DESIGN: Over a 9-month period from inception at Thomas Jefferson University Hospital, a retrospective analysis of the cytologic diagnoses of all EBUS-TBNA procedures performed in 48 patients was undertaken. The patients were divided into 2 groups, those with clinical suspicion of an epithelial malignancy and those with clinical suspicion of sarcoidosis or lymphoma. RESULTS: Of the 48 patients who underwent EBUS-TBNA, 39 had adequate fine needle aspiration biopsy samples (60 of 78) with a diagnostic yield of 77%; the pre-EBUS yield was 58%. For the group with malignant disease the calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were all 100%. For the group with benign disease the calculated sensitivity, specificity, PPV and NPV were also 100%. CONCLUSION: Preliminary results show that cytologic samples obtained via BUS-TBNA are accurate and specific in making a diagnosis of an epithelial malignancy or benign disease.

Loss of Nuclear Localized Parathyroid Hormone-Related Protein in Primary Breast Cancer Predicts Poor Clinical Outcome and Correlates with Suppressed Stat5 Signaling.

PURPOSE: Parathyroid hormone-related protein (PTHrP) is required for normal mammary gland development and biology. A PTHLH gene polymorphism is associated with breast cancer risk, and PTHrP promotes growth of osteolytic breast cancer bone metastases. Accordingly, current dogma holds that PTHrP is upregulated in malignant primary breast tumors, but solid evidence for this assumption is missing. EXPERIMENTAL DESIGN: We used quantitative IHC to measure PTHrP in normal and malignant breast epithelia, and correlated PTHrP levels in primary breast cancer with clinical outcome. RESULTS: PTHrP levels were markedly downregulated in malignant compared with normal breast epithelia. Moreover, low levels of nuclear localized PTHrP in cancer cells correlated with unfavorable clinical outcome in a test and a validation cohort of breast cancer treated at different institutions totaling nearly 800 cases. PTHrP mRNA levels in tumors of a third cohort of 737 patients corroborated this association, also after multivariable adjustment for standard clinicopathologic parameters. Breast cancer PTHrP levels correlated strongly with transcription factors Stat5a/b, which are established markers of favorable prognosis and key mediators of prolactin signaling. Prolactin stimulated PTHrP transcript and protein in breast cancer cell lines in vitro and in vivo, effects mediated by Stat5 through the P2 gene promoter, producing transcript AT6 encoding the PTHrP 1-173 isoform. Low levels of AT6, but not two alternative transcripts, correlated with poor clinical outcome. CONCLUSIONS: This study overturns the prevailing view that PTHrP is upregulated in primary breast cancers and identifies a direct prolactin-Stat5-PTHrP axis that is progressively lost in more aggressive tumors.

Intraoperative pathologic examination: cost effectiveness and clinical value in patients with cytologic diagnosis of cellular follicular thyroid lesion.

OBJECTIVE: Routine use of intraoperative pathologic examination (IOPE), including frozen section (FS) and scrape preparation cytology (SPC), during diagnostic thyroid lobectomy continues to be a source of controversy. We sought to better delineate the usefulness and cost-benefit ratio of IOPE in the context of cytologically diagnosed cellular follicular lesion (CFL) or follicular neoplasm (FN). DESIGN: Records of 205 patients who underwent thyroidectomy for cytologically diagnosed FN or CFL between 1997 and 2005 were retrospectively reviewed. IOPE results, patient demographics, and tumor characteristics were correlated to final histopathologic diagnoses. Sensitivity, specificity, predictive values, accuracy, and costs of IOPE were calculated. MAIN OUTCOME: IOPE correctly identified 3 of 16 follicular carcinomas and 9 of 36 papillary carcinomas. Sensitivity, specificity, and accuracy were 23%, 99%, and 78%, respectively. On univariate analysis, malignancy risk among follicular nodules did not correlate with age, gender, or nodule size. On multivariate analysis, nodule size was predictive of malignancy (p < 0.05). Over the entire patient series, routine IOPE resulted in a net cost savings of $74,304.33. CONCLUSIONS: IOPE reduced costs and limited the number of completion thyroidectomies necessary. IOPE is specific, cost effective, and of minimal additional risk when performed routinely for patients with CFL or FN.

Weeding atypical glandular cell look-alikes from the true atypical lesions in liquid-based Pap tests: a review.

The purpose of this review is to identify features that separate atypical glandular cells (AGC) associated with glandular neoplasia from its mimickers, both benign and neoplastic. We reviewed cases of AGC diagnosed on liquid-based Pap tests (LBP) for which corresponding histological follow-up was available. A review of the literature for similar studies in LBP tests was also conducted. We find that certain benign mimics can be reliably separated from AGC, but recommend caution in attempting to increase specificity at the risk of losing sensitivity. Although accounting for only a small percentage of diagnoses AGC require a thorough clinical evaluation, including colposcopy. Most cases are ultimately found to be benign. When evaluating smears suspicious for AGC, it is important to examine the subtle features which make truly atypical cells discernible from their numerous benign mimickers.

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' answers follow.