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Background: The clinical presentation of Langerhans cell histiocytosis (LCH) as a primary solitary nodule in the thyroid gland is rare. As a result, there are few reports of its cytologic features in thyroid aspirates where it can pose a diagnostic pitfall. CASE AND CONCLUSION: To foster familiarity with its cytomorphology, we report the fine-needle aspiration biopsy (FNAB) findings of 3 specimens from 2 patients with LCH presenting as a solitary thyroid nodule. All aspirates contained numerous dispersed cells with prominent nuclear grooves, and the background showed a mixed pattern of chronic inflammation including scattered eosinophils. The aspirate from patient 1 raised a differential diagnosis that included chronic lymphocytic thyroiditis and a thyroglossal duct cyst, while the aspirate from patient 2 was interpreted as 'suspicious for papillary thyroid carcinoma'. The diagnosis of LCH was confirmed in both patients after lobectomy and immunohistochemical studies that revealed positive reactivity for CD1a and S-100. LCH of the thyroid gland is rare and can pose significant diagnostic challenges, but increased familiarity with its characteristic cytomorphology can help in avoiding diagnostic pitfalls., (Copyright © 2013 S. Karger AG, Basel.)

Harnessing the knowledge we have gained on the cell cycle disruption caused by human papillomaviruses (HPV) will likely lead to improved screening modalities for cervical cancer and its precursors. An easily applied biomarker that has high specificity and sensitivity would represent an attractive alternative or complement to cytology and HPV testing. To date, a number of promising markers have been investigated. These include p16(INK4A), MIB-1, BD-ProEx C, and L1. Newer possibilities involve a variety of gene products associated with aberrations of chromosome 3q, such as telomerase, p63, and PIK3CA, as well the combination of biomarkers such as p16(INK4A) and MIB-1 in the same assay. Although none of them has yet been incorporated into screening algorithms or found its way into routine practice, their performance characteristics remain a focus of current investigations. This review summarizes what we know and where we hope to go in translating basic pathobiology into clinical practice., (Copyright © 2012 S. Karger AG, Basel.)

Objective: Cytopathologists' usage patterns for 'atypia of undetermined significance' (AUS) in thyroid fine-needle aspiration (FNA) are not well understood. AUS rates over a 5-year period were analyzed to quantify variability and identify correlations with experience and histologic outcomes., Study Design: A retrospective review of thyroid FNAs from a tertiary-care hospital from 2005 to 2009 was performed. Results were compiled for individual cytopathologists, stratified by year, and correlated with histologic outcomes., Results: Thyroid FNAs (5,327) were evaluated by 7 cytopathologists, with an overall AUS rate of 11.2%. The annual AUS rate remained relatively constant over this time period, though notable inter- and intrapathologist variability was seen. The AUS rate was significantly lower for those with cytopathology boards (10.3%) compared to those without (14.0%). There was no correlation between the AUS rate and cytopathologist experience or thyroid FNA volume. The AUS rate and malignant outcome were inversely related: the higher an individual's AUS rate was, the lower the rate of malignancy for that AUS cohort was., Conclusions: Individual cytopathologist AUS rates were variable and often exceeded the recommended target of 7%. The application of recently published defined diagnostic criteria, along with directed cytopathologist feedback, may reduce observer variability and appropriately lower AUS utilization., (Copyright © 2011 S. Karger AG, Basel.)

Objective: Serous neoplasms of the female pelvis share a müllerian phenotype. Unlike low-grade serous neoplasms (LGSNs), high-grade serous carcinomas (HGSCs) commonly display p53 mutations. The current study correlates p53 immunoreactivity in peritoneal washings with the cytologic interpretation and histology of the corresponding serous neoplasm., Study Design: Peritoneal washings from consecutive cases of pelvic serous neoplasms were identified (n=45, 31 HGSCs and 14 LGSNs), with a control population selected from benign resections. Immunoreactivity for p53 was scored as a percentage of positive epithelioid cells by blinded manual cell count., Results: Washings from LGSNs and HGSCs were cytomorphologically positive with similar frequency (57 vs. 77%, respectively, p=0.15, Fisher's exact test). Immunoreactivity for p53 was not predictive of morphologic positivity. The percentage of p53-positive cells was higher in HGSCs (47±42%), compared to LGSNs (9±9%) and negative controls (2±2%, n=10). The difference in p53 immunoreactivity was statistically significant (p<0.00009, ANOVA)., Conclusions: The proportion of p53 immunoreactive cells was higher in cases of HGSCs, reflecting the importance of p53 mutations in high-grade serous tumorigenesis. The presence of p53 staining is not diagnostic for neoplastic cells; however, peritoneal washings are potential specimens in the investigation of serous neoplasia., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To study cytotechnologist (CT)-cytopathologist (CP) concordance for evaluating individual CTs' performance and for quality assurance and educational feedback., Study Design: The interpretations of individual CTs were compared with the final interpretations (according to the 2001 Bethesda System) of the CP. Concordance percentages and kappa values were calculated for each CT and correlated with the numbers of dots on each slide, years of experience and percentage of work hours devoted to cytology., Results: A total of 10,453 Pap tests were screened by 9 CTs during one year, out of which 993 (9.5%) were referred to one CP for a final interpretation. Mean concordance between the aggregate CT interpretations and those of the CP was 65.5%. Five CTs had good concordance, 3 had moderately good concordance, and one had surprisingly poor concordance that contrasted with good subjective impressions. No correlation was found between concordance and the average number of dots per slide, screening experience in cervicovaginal cytology or percentage of work hours devoted to cytology., Conclusion: Monitoring CT-CP concordance rates can unveil performance issues not detected by subjective impressions. An excessive number of dots per slide may not reflect poor diagnostic precision so much as a lack of confidence in interpretation.

Background: Ciliation is a normal finding in the endometrium, fallopian tubes and cervix. Because cilia are characteristically lost when malignant tumors arise at these sites, the detection of cilia on light microscopy is frequently used to support a benign diagnosis. Ciliated carcinomas of müllerian duct origin, however, do occur, albeit rarely, and can pose a potential diagnostic difficulty in cytologic specimens., Case: A woman with a histologically confirmed ciliated adenocarcinoma of the cervix had prior liquid-based cervical cytology showing atypical, ciliated glandular cells that initially raised the diagnostic consideration of tubal metaplasia. A concurrent biopsy, however, revealed focally ciliated adenocarcinoma of the cervix., Conclusion: Awareness of the ciliated variant of adenocarcinoma of the cervix is important to avoid overreliance on ciliation as a definitive feature of benignity in cervical cytologic specimens.

Objective: To illustrate the cytomorphologic features of pilocytic astrocytoma (PA) in cerebrospinal fluid (CSF) samples., Study Design: A search of records from 1965 to 2001 was performed to identify all patients with a diagnosis of PA in whom CSF samples were examined. Slides from CSF samples originally reported as atypical, suspicious or positive were reviewed and the cytomorphologic features assessed., Results: Two hundred ninety-three patients with a diagnosis of PA were identified. Of these, 44 had a total of 65 cytologic preparations of CSF. In 34 patients (77.2%) the CSF cytology was negative, in 5 (11.4%) either atypical or suspicious, and in 5 (11.4%) positive for neoplastic cells. The tumors in the 5 positive cases arose in the cerebellar hemispheres (2), cerebellar vermis (1), thalamus (1) and tectum with extension into the fourth ventricle (1). All positive samples were hypercellular, with an average of 5 cell clusters per case (range, 3-11). The clusters were composed of cohesive epithelioid cells with a mean of 8 cells per cluster. In addition, some cases had scattered, isolated, single cells. These single neoplastic cells had prominent, hairlike cytoplasmic processes. The cells in clusters appeared epithelioid, with oval nuclei, mild nuclear pleomorphism, finely or slightly coarsely granular chromatin and cobweblike cytoplasm., Conclusion: The cytomorphologic features of PAs recapitulate their histologic characteristics. The tumor cells are recognizable in CSF samples and readily distinguishable from histiocytes and ependymal cells.

Objective: To evaluate, in a preclinical feasibility study, the efficacy of NMP179, a monoclonal antibody recognizing a cervical tumor-associated nuclear matrix antigen, for the early detection of high and low grade cervical intraepithelial neoplasia., Study Design: In a blind study involving two clinical sites, NMP179 immunocytochemical staining data from 261 cervicovaginal Thin-Prep specimens were evaluated. Assay sensitivity and specificity were calculated based upon a positive threshold of > 10 immunostained cells per case, using cytologic diagnosis as an end point., Results: Based upon the examination of squamous epithelial cells, NMP179 detected 96.7% of cases with cytologically diagnosed high grade squamous intraepithelial lesions (HSIL) and 70.5% of low grade squamous intraepithelial lesions. The antibody also reacted with 29.6% of normal (within normal limits or benign cellular changes) smears., Conclusion: The NMP179 assay detected HSIL with very high accuracy (96.7%). The assay was 79.3% sensitive for the detection of low and high grade cervical intraepithelial neoplasia (grades 1-3), with a specificity of 70.4%. NMP179 may be an effective marker for the early detection of preneoplastic squamous intraepithelial lesions of the cervix and may be useful as an adjunctive tool for better management of cervical intraepithelial neoplasia.

Objective: To determine the prevalence of tumor diathesis (TD) in cervicovaginal smears from patients with squamous cell carcinoma (SQC)., Study Design: We reviewed all the cervical smears obtained no more than one year before a biopsy diagnosis of SQC. Patients who underwent irradiation to the cervix before the smear was taken were excluded from the analysis. The smears were rescreened by both authors, and the presence and extent of TD were recorded., Results: Twenty-eight smears from 19 patients with SQC fulfilled the study criteria. TD was seen in 15 of the 28 smears (54%). There was a positive correlation between the presence of TD and the depth of invasion., Conclusion: Although an important criterion of malignancy, TD is absent from some cases of SQC, particularly those that invade < 5 mm. A definite distinction between an intraepithelial lesion and a shallow invasive cancer may not be possible on cervicovaginal smears.

Objective: To report three cases of idiopathic retroperitoneal fibrosis (IRF) diagnosed by fine needle aspiration (FNA) biopsy and confirmed by histologic examination. To our knowledge, this is the first report on the FNA findings in IRF., Study Design: Specimens were obtained under computed tomographic guidance using the standard technique. Half the smears were ethanol fixed and stained with Papanicolaou stain, and the other half were air dried and stained with Diff-Quik. A cell block was prepared in all cases., Results: Similar findings were seen in all three cases. The predominant elements were fibrous tissue and inflammatory cells, which occasionally occurred together but often were separate. The inflammatory cells were predominantly small lymphocytes, with occasional plasma cells, histiocytes and neutrophils. Smears from one case showed the inflammatory component only, but the cell block in all three cases showed both elements. The diagnosis of IRF was suggested in two of the three cases. All patients underwent laparotomy for diagnostic confirmation, and two had therapeutic resection of the lesion. Histologic material reflected the FNA findings, showing hyalinized fibrous tissue and an inflammatory cell infiltrate consisting of lymphocytes, plasma cells, histiocytes and neutrophils. No infection, arteritis or malignancy was present., Conclusion: Although the FNA picture is nonspecific, in combination with clinical and radiologic findings it is highly suggestive of a diagnosis of IRF. A presumptive diagnosis allows a rational approach to further evaluation and therapy, which, in most cases, is an exploratory laparotomy with ureterolysis.

Most patients with malignant mesothelioma (MM) present with an effusion, but distinguishing malignant from reactive mesothelial cells by conventional cytology may be difficult. We investigated the possibility of identifying clonal cytogenetic aberrations in pleural or peritoneal fluid from 10 patients with a clinical suspicion of MM. Direct metaphase harvests and short-term cultures were performed on fresh fluid. Clonal cytogenetic aberrations indicative of malignancy, with findings previously reported in association with mesothelioma, were found in all patients; these included del(1p), del(3p) and del(22q). Cytologic examination of the effusions showed malignant cells consistent with MM in 5 patients and atypical mesothelial cells suggestive of MM in 4. In one case the cytology of several samples of pleural fluid was within normal limits. Subsequent histology confirmed the diagnosis of MM in 9 of the 10 patients; medical complications precluded tissue biopsy in the 10th. We conclude that the cytogenetic analysis of effusions may be a useful and reliable adjunct to cytology in the diagnosis of MM.

Wegener's granulomatosis (WG) is a potentially fatal disease in which early diagnosis and administration of immunosuppressive agents is essential to successful treatment. The disease is characterized by necrotizing and granulomatous inflammation and vasculitis of the respiratory tract and kidney. The variety of clinical presentations often makes the diagnosis difficult. We present a case of WG in a 24-year-old male in whom the diagnosis was first suggested after cytologic examination of a nasal scrape for sinusitis. The smears showed numerous neutrophils and occasional multinucleate histiocytic giant cells. Reactive epithelial cells from the respiratory mucosa were also present. No organisms were identified on Gram or acid-fast stain. Considering the clinical setting, the diagnosis of WG was suggested. Subsequent renal biopsy revealed necrotizing and crescentic glomerulonephritis, and the patient was successfully treated with cyclophosphamide. This case illustrates a rapid and noninvasive method by which the diagnosis of WG may be suspected early in the course of the disease.

The objective of this study was to compare the sensitivity of a new test method with the smear method for detection of neoplasia of the uterine cervix. The new procedure, the ThinPrep process, is an automated, fluid-based technique for the collection and preparation of exfoliated and aspirated cytologic specimens. A single sample from each patient was split and prepared both with the smear and test methods. The diagnostic results from the two slides were compared in this blind study. Among a total of 2,655 patients, diagnoses concurred in 92% of cases and were within one diagnostic level of each other 98% of the time. The ThinPrep method facilitated the detection of more low-grade lesions (P less than .001, McNemar's test). In addition, the test method decreased the number of ambiguous interpretations. The ThinPrep method appears to improve the cervical cytologic smear quality by the harvest of a random and reproducible sample, with a reduction in artifacts. The new method improves the sensitivity of the cervical cytologic screening test.

An unusual case of Hodgkin's disease (HD) in a 36-year-old woman that was diagnosed by fine needle aspiration (FNA) biopsy of a neck mass believed clinically to be diffuse goiter is reported. The aspirate was composed mainly of dispersed lymphocytes; admixed with these were occasional large mononuclear cells with round-to-oval nuclei and prominent nucleoli. Binucleated variants of the large cells were interpreted as Reed-Sternberg cells, suggesting the diagnosis of HD. Subsequent to the FNA biopsy, radiologic examinations demonstrated an enlarged mediastinum, and incisional biopsy of the neck mass confirmed the diagnosis of HD. This case emphasizes the value of FNA biopsy as a rapid and reliable procedure, even in the unusual but established clinical presentation of HD as a diffuse neck mass.