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Background: Microphthalmia transcription factor (MiTF) is a sensitive and specific immunohistochemistry (IHC) marker for malignant melanoma (MM) in surgical resections, but its utility in cytology specimens has not been extensively studied., Methods: A search of the pathology database identified fine-needle aspiration biopsies signed out as MM or suspicious for MM (1998-2012). The final diagnosis and the IHC results were recorded, and all slides were re-reviewed. MiTF IHC (C5/D5 cocktail) was performed on alcohol-fixed, Papanicolaou-stained direct smears. Any amount of nuclear staining was considered positive. Staining was scored on a scale of 1 to 4 (1, 1%-24%; 2, 25%-49%; 3, 50%-74%; 4, 75%-100%)., Results: Two hundred seventy-four cases were diagnosed as MM, and 24 were diagnosed as suspicious for MM. IHC staining was performed for 25% (69 of 274) of the MM cases and for 33% (8 of 24) of the cases suspicious for MM. MiTF IHC of Papanicolaou slides was performed for 37% (101 of 274) of the MM cases (positive, 82% [83 of 101]; negative, 4% [4 of 101]; noncontributory, 14% [14 of 101]) and for 33% (8 of 24) of the cases suspicious for MM (positive, 38% [3 of 8]; noncontributory, 62% [5 of 8]). The majority of positive staining was scored as 3 or 4. The sensitivity of MiTF on Papanicolaou-stained slides was 95%., Conclusions: MiTF is a useful IHC stain for the evaluation of ocular MM, and it is effective when it is performed on alcohol-fixed, Papanicolaou-stained aspirate smears., (© 2015 American Cancer Society.)

Background: Cytopathologic interpretation of endobronchial ultrasound with fine needle aspiration (EBUS-FNA) samples by a pathologist can be time-consuming and costly, and an onsite cytopathologist may not always be readily available. A telecytopathology system was instituted and evaluated to examine the effect on operative time for EBUS., Methods: A prospective study was performed of sequential patients undergoing EBUS-FNA for the evaluation of mediastinal lymphadenopathy. Specimens for the control group were transported to the pathology laboratory, followed by remote cytologic interpretation. In a subsequent cohort, a telecytopathology system was used with intraoperative transmission of real-time live video microscopy to a remote cytopathologist (TCP group). The primary outcome was time to confirmation of cytology results., Results: Of 46 patients entered into the study, 23 underwent traditional analysis (control group), and 20 were analyzed using telecytopathology (TCP group). Lung cancer was the most common malignancy in both groups (12 TCP, 12 control). There was no difference in mean number of lymph node stations sampled (1.3 TCP vs 1.8 control, p = 0.76). Use of TCP was associated with fewer needle passes (4.9 vs 7.3, p = 0.02) and fewer slides for interpretation (8.4 vs 13.5, p = 0.01) per procedure. Time to result confirmation was significantly shorter in the TCP group (19.0 vs 46.7 minutes, p < 0.001). A diagnostic specimen was obtained in 70% of patients in the TCP group compared with 65% in the control group (p = 0.5). False-negative rates in patients undergoing EBUS-FNA and mediastinoscopy were similar between the two groups (0 in TCP vs 2 in control, p = 0.49). Mean procedural costs (excluding cost of the telecytology system and operating room time) were equivalent between the two groups ($888 TCP vs $887 control)., Conclusions: Telecytopathology provides rapid interpretation of EBUS-FNA samples with diagnostic accuracy comparable to traditional methods, shortens procedure time, and is a more efficient model for delivery of on-site EBUS-FNA interpretation., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Adult Wilms' tumor (WT) is a rare entity with less than 300 cases reported to date in the medical literature. Histologic and cytologic features of adult WT of the kidney are similar to findings in pediatric WT. While the lungs are noted to be the most frequent site of metastatic disease in the pediatric population, the incidence of lung metastases remains unknown for adult WT. A search revealed 38 cases of adult WT with lung metastases published to date in the English literature. Amongst these cases only two have utilized cytology of the lung lesions as a means to arrive at a final diagnosis. We report a case of adult WT metastatic to the lung that was initially diagnosed using endobronchial ultrasound-guided fine needle aspiration biopsy. The aim is to compare the current cytologic and immunohistochemical findings with those cases previously published, to outline the cytologic features of adult WT metastatic to the lung, and to emphasize the significance of cytologic diagnosis in the work-up of adult WT., (© 2013 Wiley Periodicals, Inc.)

Background: Molecular markers that can discriminate indolent cancers from aggressive ones may improve the management of prostate cancer and minimize unnecessary treatment.Aberrant DNA methylation is a common epigenetic event in cancers and HOXD3 promoter hypermethylation (H3PH) has been found in prostate cancer. Our objective was to evaluate the relationship between H3PH and clinicopathologic features in screening prostate biopsies., Methods: Ninety-two patients who underwent a prostate biopsy at our institution between October 2011 and May 2012 were included in this study. The core with the greatest percentage of the highest grade disease was analyzed for H3PH by methylation-specific PCR. Correlational analysis was used to analyze the relationship between H3PH and various clinical parameters. Chi-square analysis was used to compare H3PH status between benign and malignant disease., Results: Of the 80 biopsies with HOXD3 methylation status assessable, 66 sets were confirmed to have cancer. In the 14 biopsies with benign disease there was minimal H3PH with the mean percentage of methylation reference (PMR) of 0.7%. In contrast, the HOXD3 promoter was hypermethylated in 16.7% of all cancers and in 50% of high risk tumors with an average PMR of 4.3% (P=0.008). H3PH was significantly correlated with age (P=0.013), Gleason score (P=0.031) and the maximum involvement of the biopsy core (P=0.035)., Conclusions: H3PH is associated with clinicopathologic features. The data indicate that H3PH is more common in older higher risk patients. More research is needed to determine the role of this marker in optimizing management strategies in men with newly diagnosed prostate cancer.

Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors. This study evaluated outcomes after SBRT to identify prognostic variables and to develop a novel scoring system predictive of survival., Methods: The medical records of 52 patients with a total of 85 liver lesions treated with SBRT from 2003 to 2010 were retrospectively reviewed. Twenty-four patients had 1 lesion; 27 had 2 or more. Thirteen lesions were primary tumors; 72 were metastases. Fiducials were placed in all patients prior to SBRT. The median prescribed dose was 30 Gy (range, 16 - 50 Gy) in a median of 3 fractions (range, 1-5)., Results: With median follow-up of 11.3 months, median overall survival (OS) was 12.5 months, and 1 year OS was 50.8%. In 42 patients with radiographic follow up, 1 year local control was 74.8%. On univariate analysis, number of lesions (p = 0.0243) and active extralesional disease (p < 0.0001) were predictive of OS; Karnofsky Performance Status (KPS) approached statistical significance (p = 0.0606). A scoring system for predicting survival was developed by allocating 1 point for each of the three following factors: active extralesional disease, 2 or more lesions, and KPS ≤ 80%. Score was associated with OS (p < 0.0001). For scores of 0, 1, 2 and 3, median survival intervals were 34, 12.5, 7.6, and 2.8 months, respectively., Conclusions: SBRT offers a safe and feasible treatment option for liver tumors. A prognostic scoring system based on the number of liver lesions, activity of extralesional disease, and KPS predicts survival following SBRT and can be used as a guide for prospective validation and ultimately for treatment decision-making.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive tumor of the central nervous system. It is primarily seen in younger age-groups, and the cytomorphology has only been infrequently described., Case: We present a case of AT/RT arising in the cervical spine of a 6-month-old boy. The cerebrospinal fluid (CSF) cytology and correlating findings are described. The CSF cytomorphologic findings of the AT/RT cells are most notably large cells, eccentrically placed pleomorphic nuclei, prominent nucleoli and, commonly, cytoplasmic inclusions, as well as a second population of smaller mononuclear cells with minimal cytoplasm., Conclusion: The cervical spine is a rare site for AT/RT to arise. It is important for pathologists to recognize the cytomorphologic features of AT/RT in the CSF of patients with this tumor to help determine prognosis and disease progression.

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP.

Background: Tumors of the skull base pose unique challenges to radiosurgical treatment because of their irregular shapes, proximity to critical structures and variable tumor volumes. In this study, we investigate whether acceptable treatment plans with excellent conformity and homogeneity can be generated for complex skull base tumors using the Cyberknife radiosurgical system., Methods: At Georgetown University Hospital from March 2002 through May 2005, the CyberKnife was used to treat 80 patients with 82 base of skull lesions. Tumors were classified as simple or complex based on their proximity to adjacent critical structures. All planning and treatments were performed by the same radiosurgery team with the goal of minimizing dosage to adjacent critical structures and maximizing target coverage. Treatments were fractionated to allow for safer delivery of radiation to both large tumors and tumors in close proximity to critical structures., Results: The CyberKnife treatment planning system was capable of generating highly conformal and homogeneous plans for complex skull base tumors. The treatment planning parameters did not significantly vary between spherical and non-spherical target volumes. The treatment parameters obtained from the plans of the complex base of skull group, including new conformity index, homogeneity index and percentage tumor coverage, were not significantly different from those of the simple group., Conclusion: Our data indicate that CyberKnife treatment plans with excellent homogeneity, conformity and percent target coverage can be obtained for complex skull base tumors. Longer follow-up will be required to determine the safety and efficacy of fractionated treatment of these lesions with this radiosurgical system.

Background: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare, low grade, malignant vascular tumor that typically presents with multiple pulmonary nodules in young women. This report details the cytopathologic and pathologic findings in an unusual case presenting in an older male with a pleural effusion, dominant nodule and multiple bilateral infiltrates., Case: A 62-year-old, male nonsmoker was referred due to increasing dyspnea. Chest radiography revealed a pleural effusion and nodular infiltrate in the right upper lobe of the bronchus. Thoracocentesis and thoracoscopy were performed, with a pleural drain inserted. Bronchoscopy revealed a right upper lobe bronchus occluded by a greyish, necrotic mass. Various cytopathologic sampling techniques, including fine needle aspiration biopsy, as well as traditional histopathologic biopsies were performed. Cytologic specimens showed loosely cohesive, epithelioid cells that were binucleated and multinucleated. Chromatin was granular, with scattered, small, multiple nucleoli with occasional, variably sized cytoplasmic vacuoles. The patient's condition deteriorated, and he died 3 weeks after admission., Conclusion: Pulmonary epithelioid hemangioendotheliomas are unusual neoplasms with a epithelioid, discohesive cellular appearance. It can mimic other, more commonly seen pulmonary neoplasms. Careful attention to cytomorphologic features and application of ancillary studies assist in making the diagnosis.