Cancer Cytopathology

Cover image for Vol. 122 Issue 8

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Celeste N. Powers, MD, PhD

Impact Factor: 3.807

ISI Journal Citation Reports © Ranking: 2013: 15/76 (Pathology); 58/202 (Oncology)

Online ISSN: 1934-6638

Associated Title(s): Cancer, CA: A Cancer Journal for Clinicians


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  1. Original Articles

    1. Implications of a suspicious afirma test result in thyroid fine-needle aspiration cytology: An institutional experience

      Ricardo R. Lastra, Michelle R. Pramick, Cody J. Crammer, Virginia A. LiVolsi and Zubair W. Baloch

      Article first published online: 13 AUG 2014 | DOI: 10.1002/cncy.21455

      A significant number of thyroid fine-needle aspiration cases are diagnosed as indeterminate by cytomorphologic evaluation. The Afirma gene expression classifier test aids in the characterization of these lesions by diagnosing them as benign or suspicious. Herein, the authors report their experience with the use of suspicious Afirma testing in a group of indeterminate thyroid fine-needle aspiration cases.

  2. Editorials

    1. You have free access to this content
      Lessons from early clinical experience with the Afirma gene expression classifier

      Jeffrey F. Krane

      Article first published online: 13 AUG 2014 | DOI: 10.1002/cncy.21472

      Early clinical experience with the Afirma gene expression classifier indicates potential limitations of the test in everyday practice. The Afirma test may have diminished utility for Hurthle cell lesions. Additional challenges include high test cost relative to repeat fine needle aspiration and the dependence of test performance on highly variable diagnostic thresholds in cytology and surgical pathology specimens.

  3. Original Articles

    1. Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening

      Nicolas Wentzensen, Barbara Fetterman, Diane Tokugawa, Mark Schiffman, Philip E. Castle, Shannon N. Wood, Eric Stiemerling, Nancy Poitras, Thomas Lorey and Walter Kinney

      Article first published online: 12 AUG 2014 | DOI: 10.1002/cncy.21473

      The authors evaluate the reproducibility and accuracy of p16/Ki-67 dual-stain cytology among 10 newly trained evaluators. The results indicate that the evaluation of p16/Ki-67 dual staining on cytology slides can be implemented in routine cytology practice with limited training and good to excellent reproducibility.

    2. Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics

      Lisa A. Radkay, Simion I. Chiosea, Raja R. Seethala, Steven P. Hodak, Shane O. LeBeau, Linwah Yip, Kelly L. McCoy, Sally E. Carty, Karen E. Schoedel, Marina N. Nikiforova, Yuri E. Nikiforov and N. Paul Ohori

      Article first published online: 12 AUG 2014 | DOI: 10.1002/cncy.21474

      RAS mutations are found in approximately 20% to 45% of thyroid neoplasms and are associated with carcinoma in 74% to 87% of cases (most commonly follicular variant papillary thyroid carcinoma). In the current study, the authors report that subclassification of RAS mutations provides better insight into lesional characteristics. In particular, KRAS12/13-mutated thyroid nodules are associated with a lower carcinoma outcome (41.7%) and frequent oncocytic changes.

  4. Review Articles

    1. You have full text access to this OnlineOpen article
      Available resources and challenges for the clinical annotation of somatic variations

      Catherine I. Dumur

      Article first published online: 8 AUG 2014 | DOI: 10.1002/cncy.21471

      This review focuses on the publicly available resources for the annotation of somatic variants found by next-generation sequencing (NGS) technologies applied to mutational analyses of tumor specimens in clinical settings. The characteristics of the existing databases as well as the ideal tools needed to comprehensively annotate mutations for the creation of clinically relevant reports for oncology are discussed.

  5. Original Articles

    1. Cytology specimens offer an effective alternative to formalin-fixed tissue as demonstrated by novel automated detection for ALK break-apart FISH testing and immunohistochemistry in lung adenocarcinoma

      Frida Rosenblum, Lloyd M. Hutchinson, Joann Garver, Bruce Woda, Ediz Cosar and Elizabeth M. Kurian

      Article first published online: 5 AUG 2014 | DOI: 10.1002/cncy.21467

      The results of the current study demonstrate that cytologic material (using ThinPrep/UroCyte, formalin-fixed or alcohol-fixed paraffin-embedded cell blocks) is equivalent to paraffin-embedded tissue for anaplastic lymphoma kinase (ALK) fluorescence in situ hybridization (FISH) testing. The authors conclude that alcohol-fixed and formalin-fixed cytology are suitable for ALK FISH and immunohistochemical testing.

    2. Cytologic characterization of atypical teratoid/rhabdoid tumor in cerebrospinal fluid

      Eric C. Huang, Miguel A. Guzman, Umberto De Girolami and Edmund S. Cibas

      Article first published online: 4 AUG 2014 | DOI: 10.1002/cncy.21470

    3. The impact of atypia/follicular lesion of undetermined significance and repeat fine-needle aspiration: 5 years before and after implementation of the Bethesda System

      Peggy S. Sullivan, Sharon L. Hirschowitz, Po Chu Fung and Sophia K. Apple

      Article first published online: 30 JUL 2014 | DOI: 10.1002/cncy.21468

      In the current study, the authors observe an increase in the percentage of atypia or follicular lesion of undetermined significance (AUS/FLUS) cases and a decrease in nondiagnostic cases with implementation of the Bethesda System for Reporting Thyroid Cytopathology. They also note more repeat fine-needle aspirations in the management of an AUS/FLUS diagnosis and an elevated malignancy risk in benign and AUS/FLUS cases associated with another AUS/FLUS diagnosis.

    4. The usefulness of the cell transfer technique for immunocytochemistry of fine-needle aspirates

      Ann E. Marshall, Harvey M. Cramer and Howard H. Wu

      Article first published online: 30 JUL 2014 | DOI: 10.1002/cncy.21469

      In the authors' experience with performing immunocytochemistry through the cell transfer technique, a total of 118 of 11,259 fine-needle aspiration cases (1%) studied were found to demonstrate useful information that contributed to the final diagnosis.

    5. p16INK4a overexpression is not linked to oncogenic human papillomaviruses in patients with high-grade urothelial cancer cells

      Eric Piaton, Jean-Sébastien Casalegno, Anne-Sophie Advenier, Myriam Decaussin-Petrucci, Florence Mege-Lechevallier, Alain Ruffion and Yahia Mekki

      Article first published online: 28 JUL 2014 | DOI: 10.1002/cncy.21462

      The study shows a low prevalence of oncogenic human papillomaviruses (HPVs) in the urine of patients with high-grade urothelial malignancy. In the tissue sections of tumors, p16(INK4a) overexpression occurs in the absence of demonstrable HPV DNA, contrary to what is noted in gynecopathology.

    6. A minimum fluid volume of 75 mL is needed to ensure adequacy in a pleural effusion: A retrospective analysis of 2540 cases

      Lisa M. Rooper, Syed Z. Ali and Matthew T. Olson

      Article first published online: 24 JUL 2014 | DOI: 10.1002/cncy.21452

      A pleural effusion volume of ≥ 75 mL is required to eliminate the influence of specimen size on diagnostic adequacy. Above 75 mL, larger volumes further decrease the numbers of indeterminate or nondiagnostic results.

    7. The role of SOX11 immunostaining in confirming the diagnosis of mantle cell lymphoma on fine-needle aspiration samples

      Y. Helen Zhang, Joe Liu, Marilyn Dawlett, Ming Guo, Xiaoping Sun and Yun Gong

      Article first published online: 23 JUL 2014 | DOI: 10.1002/cncy.21465

      SOX11 immunostaining on fine-needle aspiration samples is highly accurate for mantle cell lymphoma. The staining can be used as a reliable adjunct to confirm mantle cell lymphoma.

    8. The role of cytopathology and cyst fluid analysis in the preoperative diagnosis and management of pancreatic cysts >3 cm

      Ivan Chebib, Kurt Yaeger, Mari Mino-Kenudson and Martha B. Pitman

      Article first published online: 17 JUL 2014 | DOI: 10.1002/cncy.21460

      Fine needle aspiration of pancreatic cysts >3 cm adds value to imaging studies, especially when compared with computed tomography. Cytology is more specific for the detection of malignancy than imaging for cysts >3 cm.

    9. Lung cancer adrenal gland metastasis: Optimal fine-needle aspirate and touch preparation smear cellularity characteristics for successful theranostic next-generation sequencing

      Ferga C. Gleeson, Benjamin R. Kipp, Michael J. Levy, Jesse S. Voss, Michael B. Campion, Douglas M. Minot, Zheng J. Tu, Eric W. Klee, Konstantinos N. Lazaridis and Sarah E. Kerr

      Article first published online: 15 JUL 2014 | DOI: 10.1002/cncy.21464

      Cellular cytologic smears from adrenal gland metastases are suitable for next-generation sequencing in patients with advanced lung cancer. In the current study, the characteristics of acceptable smears are outlined for use in onsite adequacy evaluation.

    10. The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management

      Julia C. Gage, Hormuzd A. Katki, Mark Schiffman, Philip E. Castle, Barbara Fetterman, Nancy E. Poitras, Thomas Lorey, Li C. Cheung, Catherine Behrens, Abha Sharma, Fang-Hui Zhao, Jack Cuzick, Zi Hua Yang and Walter K. Kinney

      Article first published online: 9 JUL 2014 | DOI: 10.1002/cncy.21463

    11. Pancreatic neuroendocrine tumors: Accurate grading with Ki-67 index on fine-needle aspiration specimens using the WHO 2010/ENETS criteria

      Jessica M. Farrell, Judy C. Pang, Grace E. Kim and Z. Laura Tabatabai

      Article first published online: 9 JUL 2014 | DOI: 10.1002/cncy.21457

      The precise and accurate grading of pancreatic neuroendocrine tumors is critical for predicting biologic behavior patient prognosis, and making informed decisions regarding patient management and treatment. Pancreatic neuroendocrine tumors can be accurately graded by analyzing the Ki-67 proliferation indices in fine-needle aspiration specimens.

    12. A panel of protein markers for the early detection of lung cancer with bronchial brushing specimens

      Yi-Zhen Liu, Yan-Yi Jiang, Bo-Shi Wang, Jia-Jie Hao, Li Shang, Tong-Tong Zhang, Jian Cao, Xin Xu, Qi-Min Zhan and Ming-Rong Wang

      Article first published online: 9 JUL 2014 | DOI: 10.1002/cncy.21461

      The 6-protein panel (TP53, Ki67, MCM6, MCM7, KIAA1522 and KIAA0317) is a potential biomarker for the early detection of lung cancer in bronchial brushings. The combinaion of cytology and the protein panel significantly improved the sensitivity of bronchial brushing examination for lung cancer detection

  6. Cytopathology Help Desk

    1. The patient-centered practice

      David B. Kaminsky

      Article first published online: 1 JUL 2014 | DOI: 10.1002/cncy.21450

  7. Original Articles

    1. Reliability of immunostaining using pan-melanoma cocktail, SOX10, and microphthalmia transcription factor in confirming a diagnosis of melanoma on fine-needle aspiration smears

      Jessica Clevenger, Cicily Joseph, Marilyn Dawlett, Ming Guo and Yun Gong

      Article first published online: 20 JUN 2014 | DOI: 10.1002/cncy.21458

      In the current study, SOX10 was found to have the highest detection rate for melanoma on cytology smears, followed by microphthalmia transcription factor (MITF) and pan-melanoma cocktail. The nuclear staining markers, SOX10 and MITF, appear to be more readily interpreted than pan-melanoma cocktail.

    2. Impact of touch preparations on core needle biopsies

      Leung Chu B. Tong, Dorota Rudomina, Natasha Rekhtman and Oscar Lin

      Article first published online: 19 JUN 2014 | DOI: 10.1002/cncy.21447

      Touch preparations used for rapid on-site assessment have the potential to impact the findings in core biopsies.

    3. Cytologic features of parathyroid fine-needle aspiration on ThinPrep preparations

      Shelley I. Odronic, Jordan P. Reynolds and Deborah J. Chute

      Article first published online: 18 JUN 2014 | DOI: 10.1002/cncy.21453

      The cytologic features of parathyroid tissue on ThinPrep slides differ from those found on smears. ThinPrep cases demonstrate lower cellularity, lack papillary architecture, and show a predominant microfollicular pattern compared with aspirate smears.

  8. Review Articles

    1. Nucleic acid-based assays for the detection of high-risk human papillomavirus: A technical review

      Jane S. Gibson

      Article first published online: 17 JUN 2014 | DOI: 10.1002/cncy.21451

      Nucleic acid-based high-risk human papillomavirus testing is essential to contemporary cervical cancer screening. An understanding of methodologies associated with human papillomavirus testing is important to the practice of laboratory medicine.

  9. Erratum

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  10. Original Articles

    1. Molecular Characterization of 54 cases of false-negative fine-needle aspiration among 1347 papillary thyroid carcinomas

      Agnese Proietti, Nicla Borrelli, Riccardo Giannini, Rossana Romani, Giancarlo Di Coscio, Francesca Quilici, Teresa Rago, Paolo Miccoli, Paolo Vitti and Fulvio Basolo

      Article first published online: 9 JUN 2014 | DOI: 10.1002/cncy.21454

      The rate of false-negative cases on thyroid fine-needle aspiration was 1.3% (18 of 1347 cases) in the referral center. The addition of molecular analysis decreased the false-negative rate to 0.4% (5 of 1347 cases). These data suggest that the addition of BRAF and Ras mutation preoperative assessment may be helpful but the cost benefit must be carefully evaluated.

    2. You have full text access to this OnlineOpen article
      Thyroid fine-needle aspiration cytology: Performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data

      Stan G. Eilers, Paula LaPolice, Perkins Mukunyadzi, Umesh Kapur, Amy Wendel Spiczka, Ajay Shah, Husain Saleh, Adebowale Adeniran, Amberly Nunez, Indra Balachandran, Jennifer J. Clark and Larry Lemon

      Article first published online: 9 JUN 2014 | DOI: 10.1002/cncy.21440

      Data from 1558 responses in the American Society for Clinical Pathology Non-GYN Assessment program for thyroid fine-needle aspirates from thyroid neoplasms and malignancies were evaluated for the correct diagnostic interpretation as well as classifying the incorrect responses into treatment-based groups (nonsurgical benign thyroid nodule, thyroid neoplasm, or malignancy). Participants generally performed well, except for the entities of follicular neoplasm and follicular variant of papillary carcinoma, which were challenging diagnoses to program participants.

    3. The value of the “suspicious for urothelial carcinoma” cytology category: A correlative study of 4 years including 337 patients

      Tuyet Nhung Ton Nu, Wassim Kassouf, Babak Ahmadi-Kaliji, Michele Charbonneau, Manon Auger and Fadi Brimo

      Article first published online: 6 JUN 2014 | DOI: 10.1002/cncy.21449

      A diagnosis of “suspicious for urothelial carcinoma” is likely similar to the recently suggested “atypical urothelial cells, cannot rule out high-grade carcinoma” category. It also carries a significant risk of harboring high-grade urothelial carcinoma.

    4. FNAB of benign thyroid nodules with papillary hyperplasia: A cytological and histological evaluation

      Marc P. Pusztaszeri, Jeffrey F. Krane, Edmund S. Cibas, Gilbert Daniels and William C. Faquin

      Article first published online: 2 JUN 2014 | DOI: 10.1002/cncy.21441

      A subset of benign thyroid nodules with papillary hyperplasia is misinterpreted on fine-needle aspiration biopsy as “suspicious for malignancy” or as “malignant,” potentially resulting in unnecessary surgery. These cases are characterized histologically by a high proportion of papillary hyperplasia and cytologically by papillary structures, variable nuclear atypia, small nuclear size, and cytoplasmic pigment.

    5. Human papillomavirus testing in young women: Clinical outcomes of human papillomavirus triage in a UK cervical screening program

      Michael McKenna and Mary M. McMenamin

      Article first published online: 2 JUN 2014 | DOI: 10.1002/cncy.21444

      Colposcopy referrals increased significantly with the introduction of human papillomavirus triage. In women with borderline cytology or mild dyskaryosis who tested positive for human papillomavirus, there was no significant difference noted in the rate of biopsy-confirmed cases of cervical intraepithelial neoplasia of type 2 or higher or type 3 or higher between women aged < 25 years and those aged ≥ 25 years.

  11. Erratum

    1. You have free access to this content
  12. Original Articles

    1. You have free access to this content
      Factors associated with reduced accuracy in Papanicolaou tests for patients with invasive cervical cancer

      Lichao Zhao, Nicolas Wentzensen, Roy R. Zhang, S. Terence Dunn, Michael A. Gold, Sophia S. Wang, Mark Schiffman, Joan L. Walker and Rosemary E. Zuna

      Article first published online: 28 MAY 2014 | DOI: 10.1002/cncy.21443

      Papanicolaou tests from women with invasive cervical cancer, particularly squamous cancers, have a higher rate of unsatisfactory and limited-quality samples. Human papillomavirus testing of unsatisfactory ThinPrep Pap tests in women aged > 30 years can identify high-risk women in this scenario.

    2. Programmed cell death 4 and microRNA 21 inverse expression is maintained in cells and exosomes from ovarian serous carcinoma effusions

      Rocco Cappellesso, Andrea Tinazzi, Thomas Giurici, Francesca Simonato, Vincenza Guzzardo, Laura Ventura, Marika Crescenzi, Silvia Chiarelli and Ambrogio Fassina

      Article first published online: 28 MAY 2014 | DOI: 10.1002/cncy.21442

      PDCD4 and miR-21 are involved in ovarian serous carcinma oncogenesis. The transfer of miR-21 by exosomes could promote oncogenic transformation in target cells distant from the primary tumor without direct colonization by cancer cells and could be used as diagnostic tool.

    3. Evaluation of intraoperative cytological assessment of bone resection margins in patients with oral squamous cell carcinoma

      Markus Nieberler, Patrick Häusler, Enken Drecoll, Mechthild Stoeckelhuber, Herbert Deppe, Frank Hölzle, Andreas Kolk, Klaus-Dietrich Wolff, Marco Rainer Kesting and Gregor Weirich

      Article first published online: 18 APR 2014 | DOI: 10.1002/cncy.21428

      The current study evaluates the intraoperative cytological assessment of bone resection margins to control resection status in patients with bone-infiltrating oral squamous cell carcinomas. The work demonstrates that intraoperative cytological assessment of bone resection margins could supplement the intraoperative assessment of soft tissue margins through the immediate microscopic control of bony resection margins, enabling a guided reresection of positive bone margins during a surgical intervention to optimize surgical concepts, especially for patients with carcinoma, who receive primary reconstruction with osteo-(myo-)cutaneous microvascular transplants.


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