The added value of using mutational profiling in addition to cytology in diagnosing aggressive pancreaticobiliary disease: review of clinical cases at a single center.

BACKGROUND: This study aimed to better understand the supporting role that mutational profiling (MP) of DNA from microdissected cytology slides and supernatant specimens may play in the diagnosis of malignancy in fine-needle aspirates (FNA) and biliary brushing specimens from patients with pancreaticobiliary masses. METHODS: Cytology results were examined in a total of 30 patients with associated surgical (10) or clinical (20) outcomes. MP of DNA from microdissected cytology slides and from discarded supernatant fluid was analyzed in 26 patients with atypical, negative or indeterminate cytology. RESULTS: Cytology correctly diagnosed aggressive disease in 4 patients. Cytological diagnoses for the remaining 26 were as follows: 16 negative (9 false negative), 9 atypical, 1 indeterminate. MP correctly determined aggressive disease in 1 false negative cytology case and confirmed a negative cytology diagnosis in 7 of 7 cases of non-aggressive disease. Of the 9 atypical cytology cases, MP correctly diagnosed 7 as positive and 1 as negative for aggressive disease. One specimen that was indeterminate by cytology was correctly diagnosed as non-aggressive by MP. When first line malignant (positive) cytology results were combined with positive second line MP results, 12/21 cases of aggressive disease were identified, compared to 4/21 cases identified by positive cytology alone. CONCLUSIONS: When first line cytology results were uncertain (atypical), questionable (negative), or not possible (non-diagnostic/indeterminate), MP provided additional information regarding the presence of aggressive disease. When used in conjunction with first line cytology, MP increased detection of aggressive disease without compromising specificity in patients that were difficult to diagnose by cytology alone.

Solid-pseudopapillary neoplasm of the pancreas: awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors.

Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm predominantly reported in young women. It classically presents as a large tumor with cystic and solid components. The major differential diagnosis includes pancreatic neuroendocrine tumor (PanNET). This study presents our experience with this tumor with emphasis on the morphologic features of the clear cell variant of SPN. Fifteen histologically confirmed SPN were identified in our files. Endoscopic ultrasound-guided fine needle aspirations (EUS-guided FNA) were performed in 8/15 cases. Patients' demographics, cytohistologic correlation and tumor characteristics were evaluated. Eleven of the 15 subjects were female and four were male with an age range of 17-73 years. Twelve SPN were located in the pancreatic body/tail, and three in the head. Tumor size ranged from 1.5 to 8.5 cm and 11 were solid. Of the eight EUS-guided FNA, four were diagnosed as SPN, two as SPN vs. PanNET, one as malignant with signet ring features, and one was nondiagnostic. Immunohistochemistry was performed on six/eight FNA cell blocks and 13/15 surgical specimens. Two of the 15 cases were classified as clear cell variants of SPN. Our study shows that SPN may occur in males and older adults, and present as a small or solid tumor. The clear cell variant of SPN, characterized by vacuolated cytoplasm and signet cell morphology, may pose a diagnostic challenge on FNA. Awareness of the wide spectrum of SPN clinical presentations, the morphology of its clear cell variant and the appropriate use of ancillary immunohistochemistry can prevent diagnostic errors.

Does on-site adequacy evaluation reduce the nondiagnostic rate in endoscopic ultrasound-guided fine-needle aspiration of pancreatic lesions?

BACKGROUND: This retrospective study compared the nondiagnostic rate for endoscopic ultrasound-guided (EUS) fine-needle aspiration (FNA) of pancreatic lesions in 2 settings: 1 with and 1 without on-site evaluation. METHODS: The authors reviewed 381 consecutive cases and divided them into groups with and without on-site adequacy evaluation. For the group with on-site evaluation, cytopathology personnel prepared and evaluated Diff-Quik-stained direct smears and rinsed the remaining material in CytoLyt solution (Cytyc Corporation, Marlborough, Mass). The group without on-site evaluation was divided into 2 subgroups: the clinical team either prepared an air-dried smear for each FNA pass and then rinsed the remaining material in CytoLyt, or the entire sample was rinsed in CytoLyt. The cytologic diagnoses were reviewed and the nondiagnostic rates for each group were calculated. RESULTS: On-site evaluation was provided for 167 cases with a nondiagnostic rate of 25.8% (43 of 167 cases). On-site evaluation was not provided for 214 cases with a nondiagnostic rate of 24.3% (52 of 214 cases). The nondiagnostic rate for the subgroup with air-dried smears prepared by the clinical team was 25.6% (43 of 168 cases) and that for the subgroup with the entire sample rinsed in CytoLyt was 19.6% (9 of 46 cases). There were no significant statistical differences in nondiagnostic rates noted among the different groups or subgroups. CONCLUSIONS: The results of the current study indicate that when experienced operators perform EUS FNA of pancreatic lesions, on-site adequacy evaluation offers no benefit in reducing the nondiagnostic rate. Optimizing visualization of the sampled material by omitting the preparation of direct smears and rinsing the entire sample in liquid-based media demonstrated a trend toward improving the diagnostic rate.

Telomere length variation in normal epithelial cells adjacent to tumor: potential biomarker for breast cancer local recurrence.

A better understanding of the risk of local recurrence (LR) will facilitate therapeutic decision making in the management of early breast cancers. In the present study, we investigated whether telomere length in the normal breast epithelial cells surrounding the tumor is predictive of breast cancer LR; 152 women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this nested case-control study. Cases (patients had LR) and controls (patients had no LR) were matched on year of surgery, age at diagnosis and type of surgery. Telomere fluorescent in situ hybridization was used to determine the telomere length using formalin fixed paraffin-embedded breast tissues. Small telomere length variation (TLV), defined as the coefficient variation of telomere lengths among examined cells, in normal epithelial cells adjacent to the tumor was significantly associated with a 5-fold (95% confidence interval = 1.2-22.2) increased risk of breast cancer LR. When the subjects were categorized into quartiles, a significant inverse dose-response relationship was observed with lowest versus highest quartile odds ratio of 15.3 (P(trend) = 0.012). Patients who had large TLV had significantly better 10 year recurrence free survival rate compared with patients who had small TLV (80 versus 33%). The present study revealed that TLV in normal epithelial cells adjacent to tumor is a strong predictor of breast cancer LR. If confirmed by future studies, TLV in normal epithelial cells adjacent to tumor has the potential to become a promising biomarker for predicting breast cancer LR after breast conserving surgery.

Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference.

The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The two-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding diagnostic terminology/classification scheme for thyroid FNA interpretation and cytomorphologic criteria for the diagnosis of various benign and malignant thyroid lesions. (http://thyroidfna.cancer.gov/pages/info/agenda/).

Association of race, age and body mass index with gross pathology of uterine fibroids.

OBJECTIVE: To determine the associations of race, age and body mass index (BMI) with the gross pathology parameters of uterine leiomyomas in premenopausal women undergoing hysterectomy or myomectomy. STUDY DESIGN: Participants (N = 107) were recruited from surgical rosters of the George Washington University (GWU) Medical Center Gynecology Department as part of the National Institute of Environmental Health Sciences Fibroid Study. Tumor data and patient demographics were obtained from clinical reports, pathology forms and interviews. RESULTS: Surgical cases consisted of 78% African Americans, 13% Caucasians and 9% others (non-African American, non-Caucasian or race unknown). This proportion of African Americans was significantly higher than the distribution of GWU health plan participants. Fibroids were localized predominantly within the intramural region. Subserosal tumors were more common in patients with more than 9 tumors. African Americans had the highest mean BMI and mean myomatous uterine weight. CONCLUSION: African Americans were the disproportionate majority coming to surgery for fibroids. The average BMI and uterine weight were greater in African Americans than in Caucasians, although these differences were marginal. Race did not influence the size, location or number of fibroids in these surgical cases. Subserosal tumors were more common in patients with more than 9 tumors.

Real-time imaging and characterization of human breast tissue by reflectance confocal microscopy.

Real-time technologies can increase the efficiency of obtaining informative biopsies and accelerate interpretation of biopsy pathological review. Cellular aberrations inherent to cancer cells, including nuclear size, can currently be detected, but few technologies are available to evaluate adequacy of specimens in real time. The aims of this study are: 1. to determine if near-infrared reflectance confocal microscopy (RCM) can be used to assess epithelial/stromal content of core needle breast biopsy samples in real time, 2. to determine if epithelial cell nuclear size can be measured on RCM images, and 3. to test if RCM images can be accurately read for presence/absence of histologically relevant features of malignancy. Breast biopsies are obtained following a medically indicated breast core needle diagnostic biopsy for RCM examination. Acetic acid is used as a contrast agent to visualize structures within breast tissue. Structures are identified and optically serially sectioned, and digital images are cataloged. Relative amounts of epithelial, fatty, and collagenous tissue are determined. RCM biopsies are formalin-fixed and stained for hematoxylin and eosin (H and E) comparison with RCM images. RCM data are comparable to data from H and E sections. Epithelial cell nuclear size is measured on stored digital RCM images. We compare RCM and H and E images from 16 patients and 25 core needle biopsy samples.