Brian J. Hall

A Systematic Review and Meta-Analysis of the Diagnostic Accuracy of Fine-Needle Aspiration Cytology for Parotid Gland Lesions

The clinical usefulness of fine-needle aspiration cytology (FNAC) for the diagnosis of parotid gland lesions is controversial. Many accuracy studies have been published, but the literature has not been adequately summarized. We identified 64 studies on the diagnosis of malignancy (6,169 cases) and 7 studies on the diagnosis of neoplasia (795 cases). The diagnosis of neoplasia (area under the summary receiver operating characteristic [AUSROC] curve, 0.99; 95% confidence interval [CI], 0.97-1.00) had higher accuracy than the diagnosis of malignancy (AUSROC, 0.96; 95% CI, 0.94-0.97). Several sources of bias were identified that could affect study estimates. Studies on the diagnosis of malignancy showed significant heterogeneity (P < .001). The subgroups of American, French, and Turkish studies showed greater homogeneity, but the accuracy of these subgroups was not significantly different from that of the remaining subgroup. It is not possible to provide a general guideline on the clinical usefulness of FNAC for parotid gland lesions owing to the variability in study results. There is a need to improve the quality of reporting and to improve study designs to remove or assess the impact of bias.

A systematic review and meta-analysis of the diagnostic accuracy of ultrasound-guided core needle biopsy for salivary gland lesions.

Core needle biopsy (CNB) of salivary gland lesions is a relatively new technique that may offer benefits for diagnosis of the lesions. We conducted a systematic literature review to identify studies published between January 1, 1985, and March 15, 2011. Summary estimates of sensitivity and specificity were obtained by using a summary receiver-operating characteristic (SROC) curve. Study quality was assessed by using the QUADAS survey. We identified 5 studies (277 cases) for inclusion. The area under the SROC for CNB was 1.00 (95% confidence interval [CI], 0.99-1.00). Based on histologically verified cases, the sensitivity of CNB is 0.92 (95% CI, 0.77-0.98) and the specificity is 1.00 (95% CI, 0.76-1.00). We conclude that CNB has high accuracy and a low (1.2%) inadequacy rate. CNB is more accurate than fine-needle aspiration, at least in some settings, but the best selection of which test to use for an individual patient and setting remains to be defined.

Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome.

Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high associated mortality. Numerous studies have attempted to define characteristics to more accurately predict outcome. Two recent studies have demonstrated that Merkel cell polyomavirus (MCPyV) seropositivity correlated with a better prognosis, while a third study revealed no difference. Expression of p63 by tumor cell nuclei has been shown to be associated with a worse prognosis in a European cohort. To better understand the relationship between prognosis and MCPyV or p63 status, we used immunohistochemistry to evaluate both attributes in 36 US patients with MCC. Our results show that when considered as a binary variable, p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) = ∞) for shortened survival. In addition, our results show that MCPyV status does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates the European observation that p63 immunoexpression is useful as a prognostic tool. Larger studies will need to be performed in order to determine whether p63 status should be included in MCC staging, since our study is limited by its relative small size.

A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Frozen Section for Parotid Gland Lesions

We conducted a systematic literature review using MEDLINE and Embase to identify articles on diagnostic accuracy of frozen section (FS) for salivary gland lesions published between January 1, 1985, and December 31, 2010. We also reviewed the reference lists of all identified articles and conducted a forward search using Scopus to identify all articles citing the reference set. Meta-analysis was used to produce a summary receiver operating characteristic (SROC) curve from which summary estimates of sensitivity and specificity were obtained. Study quality was assessed using the Quality of Diagnostic Accuracy Study (QUADAS) survey. The accuracy of FS was compared with that of fine-needle aspiration cytology using results from an earlier review. A set of 13 studies (1,880 cases) with extractable data met our inclusion criteria. The summary estimates for the area under the SROC curve, FS sensitivity, and FS specificity are 0.99 (95% confidence interval [CI], 0.98-1.00), 0.90 (95% CI, 0.81-0.94), and 0.99 (95% CI, 0.98-1.00), respectively. FS has acceptable accuracy (90% sensitivity, 99% specificity) and is consistently accurate across study centers.

Risk-Benefit Analysis of Sampling Methods for Fine-Needle Aspiration Cytology: A Mathematical Modeling Approach

The effectiveness of fine-needle aspiration (FNA) increases with the number of needle passes, but needle passes are also associated with increased risk of adverse events. The trade-off between needle passes and adequacy has not been well characterized. Clinical studies are limited because of their inherent variability and limited sample size. We developed mathematical models to compare the performance of a variety of sampling protocols under a wide range of conditions. Specifically, we compared the performance of sampling methods using a fixed number of needle passes with sampling methods using a rapid onsite evaluation (ROSE) with a variable number of needle passes. Variable sampling with ROSE generally required fewer needle passes than fixed sample size policies to achieve a desired adequacy rate. Variable sampling policies using ROSE achieve greater per-case adequacy with fewer needle passes than sampling policies using a fixed number of passes if assessor accuracy is high.

Measurement of surgically induced corneal deformations using three-dimensional confocal microscopy.

The goal of this study was to develop and apply a new set of experimental techniques for measuring the local deformations induced by partial-thickness corneal incisions in situ. Eight adult cat eyes were enucleated and cannulated, with corneal viability maintained as close to in vivo conditions as possible and intraocular pressure (IOP) carefully controlled. Experimental measurements were made pre/post radial keratotomy (RK) surgery in situ at IOPs of 15, 30, and 45 mm Hg. Incision depth and crosssectional profiles were measured at the midpoint of selected incisions using three-dimensional (3-D) tandem scanning confocal microscopy (TSCM); central corneal curvature was estimated using a commercial corneal topographical analysis system, and corneal thickness was assessed by both 3-D TSCM and ultrasonic pachymetry. Corneas were then processed for light microscopy and incision depth was measured histologically. Finite element models were developed for comparison with the experimental measurements. There was no significant change in central corneal thickness (-5.3 ± 3.9%, n=8) over the course of the experiments, demonstrating that normal endothelial cell function and normal stromal hydration was maintained. The in situ TSCM incision depth measurements were significantly correlated with the histological measurements (slope=0.95, R=0.854, p<0.01, n=13 incisions). Measured incision gape at the top (anterior) of the stroma was 64.9 ± 13.4, 87.3 ± 12.6, and 108.7 ± 14 (Jim at IOPs of 15, 30, and 45 mm Hg, respectively. The 3-D incision profiles were nonlinear in shape; comparison with the finite element models suggests that the shape of the wound profile may provide unique infor- mation regarding the shear stiffness of the cornea. Overall, the data suggest that TSCM measurements of the cross-sectional profile of the incisions immediately after RK under controlled in situ conditions provide important data regarding the mechanical behavior of the cornea after refractive surgery. These data should provide the foundation for future studies into the relationships between local tissue mechanics and corneal wound healing.

Atypical intradermal smooth muscle neoplasms (formerly cutaneous leiomyosarcomas): case series, immunohistochemical profile and review of the literature.

Atypical intradermal smooth muscle neoplasms (AISMN, formerly known as cutaneous leiomyosarcomas) are uncommon neoplasms, which seem to be remarkable for their excellent prognosis in contrast to their deeper counterparts. The rarity of AISMN has posed a challenge for characterizing the morphologic spectrum, immunohistochemical staining pattern, and behavior. In this study we evaluated the histologic and immunohistochemical features of 20 cases of AISMN. Clinical follow-up was available on 19 out of 20 patients and ranged from 1 to 124 months with an average of 35 months and a median of 20 months with a male predominance (male to female ratio was 2.3:1). Our data show a wide variation in differentiation and atypical features. Among these, the presence of mitotic figures is diagnostically valuable in rendering the final diagnosis. A broad panel of immunohistochemical stains revealed that smooth muscle actin and muscle specific actin, when used in combination, identified smooth muscle differentiation in 100% of the cases. With some caveats, CD34, S100, and CK 5/6 were helpful in ruling out other important cutaneous spindle cell neoplasms. Significantly, loss of phosphatase and tensin homolog (PTEN) staining was seen in the majority of our cases (80%), supporting a role for PTEN loss in the etiology of these lesions. Logistic regression analysis revealed that positive margin status was helpful for predicting recurrence (100% sensitivity and 94% specificity). We conclude that AISMN can have significant morphologic variation and overlap with other spindle cell neoplasms of the skin and that a limited panel of key immunohistochemical stains should be used to distinguish this lesion. The different surgical measures such as wide excision versus Mohs procedure showed a similar clinical outcome. Although the significance of frequent PTEN loss supports a molecular mechanism of tumor genesis, the diagnostic utility of the stain remains to be determined.

Methods specification for diagnostic test accuracy studies in fine-needle aspiration cytology: a survey of reporting practice.

Diagnostic test accuracy (DTA) studies on fine-needle aspiration cytology (FNAC) often show considerable variability in diagnostic accuracy between study centers. Many factors affect the accuracy of FNAC. A complete description of the testing parameters would help make valid comparisons between studies and determine causes of performance variation. We investigated the manner in which test conditions are specified in FNAC DTA studies to determine which parameters are most commonly specified and the frequency with which they are specified and to see whether there is significant variability in reporting practice. We identified 17 frequently reported test parameters and found significant variation in the reporting of these test specifications across studies. On average, studies reported 5 of the 17 items that would be required to specify the test conditions completely. A more complete and standardized reporting of methods, perhaps by means of a checklist, would improve the interpretation of FNAC DTA studies.

The Comparative Effectiveness of Fine-Needle Aspiration Cytology Sampling Policies A Simulation Study

Sample adequacy is an important aspect of overall fine-needle aspiration cytology (FNAC) performance. FNAC effectiveness is augmented by an increasing number of needle passes, but increased needle passes are associated with higher costs and greater risk of adverse events. The objective of this study was to compare the impact of several different sampling policies on FNAC effectiveness and adverse event rates using discrete event simulation. We compared 8 different sampling policies in 12 different sampling environments. All sampling policies were effective when the per-pass accuracy is high (>80%). Rapid on-site evaluation (ROSE) improves FNAC effectiveness when the per-pass adequacy rate is low. ROSE is unlikely to be cost-effective in sampling environments in which the per-pass adequacy is high. Alternative ROSE assessors (eg, cytotechnologists) may be a cost-effective alternative to pathologists when the per-pass adequacy rate is moderate (60%-80%) or when the number of needle passes is limited.

Neural and Neuroendocrine Neoplasms

Clinical: Benign reactive proliferation of nerves and fibroblasts in response to trauma. Often presents as a small, firm painful lesion typically associated with trauma found at any age or body site.