The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology

Martha Bishop Pitman • Lester James Layfield

The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary CytologyDefinitions, Criteria, and Explanatory Notes

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ISBN 978-3-319-16588-2 ISBN 978-3-319-16589-9 (eBook)DOI 10.1007/978-3-319-16589-9

Library of Congress Control Number: 2015937899

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Martha Bishop PitmanDepartment of PathologyMassachusetts General HospitalHarvard Medical SchoolBoston, MassachusettsUSA

Lester James LayfieldDepartment of Pathology and Anatomical SciencesUniversity of Missouri Medical Center ColumbiaMissouriUSA

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Foreword

“Atypical,” “atypical epithelial cells,” “mucinous epithelial cells,” and “findings consistent with cyst” are a few random examples of interpretations provided in cytopathology reports of fine-needle aspirations (FNAs) of the pancreas. The clini-cian who seeks guidance for patient management finds herself or himself at a loss to interpret this language, and frequently will call the cytopathologist to obtain clarifi-cation. This may or may not be forthcoming, but regardless the report remains, and is not a very effective way to document cytological findings or clearly communicate information to guide patient management.

The recently recommended standardized terminology and nomenclature guide-lines from the Papanicolaou Society of Cytopathology [1] are long overdue. Over the last 20 years, there has been a steep increase in the use of cross-linear imaging. This, coupled with improvements in the resolution of both computed tomography and magnetic resonance imaging, has resulted in an explosion in the incidental dis-covery of lesions throughout the body. The pancreas has not been exempt, and large numbers of solid and cystic lesions are being identified in patients who otherwise have no symptoms related to the pancreas. Because pancreatic malignancies, and in particular ductal adenocarcinoma, are among the deadliest cancers, such a dis-covery may be perceived as a welcome finding. After all, identifying these tumors at an earlier phase should lead to earlier treatment and a better chance of a cure. The problem is that the overall prevalence of these pancreatic “incidentalomas” is approximately 2 % and increases with age to the point that 10 % of the individuals aged > 70 years will have such findings. This prevalence is at least 100 times greater than that of all pancreatic malignancies combined, and therefore the vast majority of these incidental lesions are innocuous. Furthermore, the preemptive removal of these lesions is accomplished with pancreatic resection, which even in expert cen-ters has a mortality rate of 2–5 % and a morbidity rate of 40 % and higher.

Clinical guidelines and algorithms for the management of cystic lesions of the pancreas have helped physicians in the care of these patients (incidentally discov-ered solid lesions are far less common). Initially, these guidelines relied heavily on clinical data and information from imaging studies. After excluding inflamma-tory cysts and some cystic neoplasms with very characteristic epidemiology and/

vi Foreword

or imaging features, the bulk of the remaining cystic lesions of the pancreas are thought to be branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). The management of BD-IPMNs continues to be in a state of flux, but the most re-cent guidelines now recommend the use of endoscopic ultrasound (EUS) and FNA to characterize those lesions measuring > 2 cm in diameter [2]. We and others have for many years used pancreatic cyst cytology coupled with cyst fluid measurements of carcinoembryonic antigen and amylase, and more recently molecular testing for mutations in KRAS and GNAS genes, to refine the differential diagnosis among the different cystic neoplasms and to determine the degree of dysplasia of BD-IPMNs [3]. This is still an imperfect science, but the hope is that this, one day, will lead to more accurate preoperative diagnosis and less overtreatment of these lesions. However, to the best of our knowledge, there is no universal agreement that EUS with cytology and fluid analysis is useful (in Japan and Korea, for example, cyst fluid aspiration is very rarely used), and many centers have used FNA of pancreatic cysts routinely but have found the interpretation of cytology to be inconsistent or unreliable. Because EUS is proliferating, and new guidelines are recommending its use, it is quite likely that it will be used in an increasing number of patients with pancreatic cysts. Having standardized nomenclature will provide a framework for pathologists to follow for the uniform interpretation of cyst fluids that will be more clearly understood by the clinician treating the patient.

Although less of a problem than pancreatic cysts, the incidental detection of small solid lesions in the pancreas has also created a challenge. Even though a small minority are indeed early ductal adenocarcinomas, the vast majority are small, non-functioning neuroendocrine tumors, many of which measure < 1 cm in size. The potential for growth and malignant spread among these lesions is uncertain and, accordingly, their management is also in a state of flux, with some clinicians advo-cating resection and others making a case for observation alone based on the finding that these lesions are observed in 1 % of autopsy studies. EUS-guided FNA is very effective in establishing the diagnosis of a pancreatic neuroendocrine tumor. From a clinician’s standpoint, I am relieved to see that this diagnosis does not by default go into a “malignant” category, but rather into a “neoplastic, other” grouping. Con-vincing a patient that doing nothing is appropriate when a report states a malignant tumor is present is virtually impossible.

Carlos Fernandez-del Castillo, MDProfessor, Harvard Medical SchoolDirector of the Pancreas and Biliary Surgery Program and Codirector of the Tucker Gosnell Center for Gastrointestinal Cancers at the Massachusetts General Hospital,Boston, MA

Reproduced with permission from Fernández-del Castillo C. Standardized cytopathology report-ing for the pancreas: the time is right. Cancer Cytopathol. 2014;122:397–98.

viiForeword

References

1. Pitman MB, Layfield LJ. Guidelines for pancreaticobiliary cytology from the papanicolaou society of cytopathology: a review. Cancer (Cancer Cytopathol). 2014;122:399–411.

2. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pan-creas. Pancreatology. 2012;12:183–97.

3. Pitman MB, Lewandrowski K, Shen J, Sahani D, Brugge W, Fernandez-del Castillo C. Pan-creatic cysts: preoperative diagnosis and clinical management. Cancer (Cancer Cytopathol). 2010;118:1–13.

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Preface

This atlas is a product of the Pancreaticobiliary Guidelines sponsored by the Pa-panicolaou Society of Cytopathology [1–5]. The guidelines are composed of five documents covering indications for endoscopic ultrasound (EUS)-guided fine-nee-dle aspiration (FNA) biopsy, techniques of EUS-FNA, terminology and nomencla-ture of pancreaticobiliary disease, ancillary testing, and post-biopsy treatment and management. The final guidelines resulted from an initial draft document prepared by multidisciplinary committees of physicians with expertise on diagnosis and man-agement of patients with pancreaticobiliary disease (listed below). The documents are published in Diagnostic Cytopathology [1–5] and in the open access journal, Cytojournal [6–10]. A comprehensive review of all the five documents is published in Cancer Cytopathology [11]. All documents are based on the expertise of the au-thors, a review of the literature, discussion of the draft documents at several national and international meetings over an 18-month period, and synthesis of online com-ments of the draft document, which was posted in an online interactive forum on the Papanicolaou Society of Cytopathology Web site [www.papsociety.org].

This atlas focuses on the proposed standardized terminology scheme for pancre-aticobiliary specimens [5] supplemented with cytological criteria, sample interpre-tive reports, succinct ancillary testing recommendations, and management options.

The proposed terminology scheme recommends a six-tiered system: nondiag-nostic, negative, atypical, neoplastic [benign or other], suspicious, and positive. Unique to this scheme is the “neoplastic” category separated into “benign” (primar-ily serous cystadenoma) or “other” (premalignant mucinous cysts, neuroendocrine tumors, and solid-pseudopapillary neoplasms). The positive or malignant category is reserved for high-grade and/or aggressive malignancies including ductal adeno-carcinoma, acinar cell carcinoma, poorly differentiated neuroendocrine carcinomas, pancreatoblastoma, lymphoma, and metastases.

This proposed scheme provides terminology that correlates the diagnostic no-menclature with the 2010 WHO classification of pancreatic tumors [12] and stan-dardizes the categorization of the various diseases of the pancreas, some of which are difficult to diagnose specifically by cytology. In addition, this terminology scheme attempts to provide maximum flexibility for patient management, which has become increasingly conservative for some neoplasms.

x Preface

References

1. Adler D, Max Schmidt C, Al-Haddad M, et al. Clinical evaluation, imaging studies, indications for cytologic study, and preprocedural requirements for duct brushing studies and pancreatic FNA: the papanicolaou society of cytopathology recommendations for pancreatic and biliary cytology. Diagn Cytopathol. 2014;42(4):325–32.

2. Brugge W, Dewitt J, Klapman JB, et al. Techniques for cytologic sampling of pancreatic and bile duct lesions. Diagn Cytopathol. 2014;42(4):333–7.

3. Kurtycz D, Tabatabai L, Michaels C, et al. Postbrushing and fine-needle aspiration biopsy fol-low-up and treatent options for patients with pancreatobiliary lesions: the papanicolaou society of cytopathology guidelines. Diagn Cytopath. 2014;42(4):363–71.

4. Layfield L, Ehya H, Filler AC, et al. Utilization of Ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the papanicolaou society of cytology guidlines of pancreato-biliary cytology. Diagn Cytopath. 2014;42(4):351–62.

5. Pitman MB, Centeno BA, Ali SZ, et al. Standardized terminology and nomenclature for pancreatobiliary cytology: the papanicolaou society of cytopathology guidelines. Diagn Cytopathol. 2014;42(4):338–50.

6. Adler D, Schmidt CM, Al-Haddad M, et al. Clinical evaluation, imaging studies, indications for cytologic study and preprocedural requirements for duct brushing studies and pancreatic fine-needle aspiration: the papanicolaou society of cytopathology guidelines. Cytojournal. 2014;11(Suppl 1):1.

7. Brugge WR, De Witt J, Klapman JB, et al. Techniques for cytologic sampling of pancre-atic and bile duct lesions: the papanicolaou society of cytopathology guidelines. Cytojournal. 2014;11(Suppl 1):2.

8. Kurtycz DF, Field A, Tabatabai L, et al. Post-brushing and fine-needle aspiration biopsy follow-up and treatment options for patients with pancreatobiliary lesions: the papanicolaou society of cytopathology guidelines. Cytojournal. 2014;11(Suppl 1):5.

9. Layfield LJ, Ehya H, Filie AC, et al. Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the papanicolaou society of cytopathology guidelines. Cyto-journal. 2014;11(Suppl 1):4.

10. Pitman MB, Centeno BA, Ali SZ, et al. Standardized terminology and nomenclature for pancreatobiliary cytology: the papanicolaou society of cytopathology guidelines. Cytojournal. 2014;11(Suppl 1):3.

11. Pitman MB, Layfield LJ. Guidelines for pancreaticobiliary cytology from the papanicolaou society of cytopathology: a review. Cancer Cytopathol. Jun 2014;122(6):399–411.

12. Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer; 2010. Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, editors. World Health Organization classification of tumours.

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Papanicolaou Society of Cytopathology Committee Members

Committee 1: Clinical Evaluation, Imaging, Studies, Indications for Cytologic Study, and Preprocedural Requirements for Duct Brushing Studies and Pan-creatic FNA

Douglas Adler, MD, Committee Chair, Department of Medicine, Division of Gastroenterology, University of Utah School of Medicine

C. Max Schmidt, MD, PhD, Department of Surgery, Indiana University

Mohammad Al-Haddad, MD, Department of Medicine, Division of Gastroenterology, Indiana University

James S. Barthel, Florida Digestive Health Specialists, Bradenton, FL

Britt Marie Ljung, MD, Department of Pathology and Laboratory Medicine, UCSF

Nipun B. Merchant, MD, Department of Surgery, Vanderbilt University School of Medicine

Joseph Romagnuolo, MD, Department of Medicine, Division of Gastroenterology, Medical University of South Carolina

Akram Shaaban, M.B.B.Ch., Department of Radiology, University of Utah Medical Center

Diane Simeone, MD, Department of Surgery, University of Michigan Medical Center

Martha B. Pitman, MD, Department of Pathology, Massachusetts General Hospital

Andrew Field, MBBS, Department of Anatomical Pathology, St. Vincent’s Hospital, Sydney

Lester J. Layfield, MD, Department of Pathology and Anatomical Sciences, University of Missouri Medical Center

xii Papanicolaou Society of Cytopathology Committee Members

Committee II: Techniques for Cytologic Sampling of Pancreatic and Bile Duct Lesions

William R. Brugge, MD, Committee Chair, Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital

John DeWitt, MD, Department of Medicine, Division of Gastroenterology, Indiana University

Jason B. Klapman, MD Endoscopic Oncology, Moffitt Cancer Center, Tampa

Raheela Ashfaq, MD, Division of Cytopathology, Caris Life Sciences, Dallas

Vinod Shidham, MD, Department of Pathology, Wayne State University Medical Center, Detroit

David Chhieng, MD, Department of Pathology, Yale University Medical Center

Richard Kwon, MD, Department of Medicine, Division of Gastroenterology, University of Michigan

Zubair Baloch, MD, Department of Pathology and Laboratory Medicine, the Hospital of the University of Pennsylvania

Matthew Zarka, MD, Department of Pathology, Mayo Clinic, Arizona

Gregg Staerkel, MD, Department of Pathology, MD Anderson Cancer Center

Committee III: Standardized Terminology and Nomenclature for Pancreaticobiliary Cytology

Martha B. Pitman, MD, Committee Chair, Department of Pathology, Massachusetts General Hospital

Barbara A. Centeno, MD, Department of Pathology, Moffitt Cancer Center, Tampa

Syed Z. Ali, MD, Department of Pathology, The Johns Hopkins University School of Medicine

Muriel Genevay, MD, Department of Pathology, Hospital de Pathologic Clinique, Geneva, Switzerland

Ed Stelow, MD, Department of Pathology, University of Virginia Medical Center

Mari Mino-Kenudson, MD, Department of Pathology, Massachusetts General Hospital

Carlos Fernandez-del Castillo, Department of Surgery, Massachusetts General Hospital

C. Max Schmidt, MD, PhD, Department of Surgery, Indiana University

William R. Brugge, MD, Chair, Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital

Lester J. Layfield, MD, Department of Pathology and Anatomical Sciences, University of Missouri Medical Center

xiiiPapanicolaou Society of Cytopathology Committee Members

Committee IV: Utilization of Ancillary Studies in the Cytologic Diagnosis of Biliary and Pancreatic Lesions

Lester J. Layfield, MD, Committee Chair, Department of Pathology and Anatomical Sciences, University of Missouri Medical Center

Hormoz Ehya, MD, Department of Pathology, Fox Chase Cancer Center, Philadelphia

Armando C. Filie, MD, Laboratory of Pathology, National Cancer Institute, Bethesda

Ralph H. Hruban, MD, Department of Pathology, The Johns Hopkins University School of Medicine

Nirag Jhala, MD, Department of Pathology and Laboratory Medicine, the Hospital of the University of Pennsylvania

Loren Joseph, MD, Department of Pathology, University of Chicago Medical Center

Philippe Vielh, MD, PhD, Department of Pathology, Institut Gustave Roussy, Paris, France

Martha B. Pitman, MD, Committee Chair, Department of Pathology, Massachusetts General Hospital

Committee V: Post-Brushing and Fine-Needle Aspiration Biopsy Follow-Up and Treatment Options for Patients with Pancreaticobiliary Lesions

Daniel Kurtycz, MD, Committee Chair, Department of Pathology, University of Wisconsin

Laura Tabatabai, MD, Department of Pathology and Laboratory Medicine, UCSF

Claire Michaels, MD, Department of Pathology, Case Western Reserve University

Nancy Young, MD, Department of Pathology, Albert Einstein College of Medicine

C. Max Schmidt, MD, PhD, Department of Surgery, Indiana University

James Farrell, MD, Department of Medicine, UCLA School of Medicine

Deepak Gopal, MD, Department of Medicine, Division of Gastroenterology, University of Wisconsin

Diane Simeone, MD, Department of Surgery, University of Michigan Medical Center

Nipun B. Merchant, MD, Department of Medicine, Vanderbilt University

Andrew Field, MBBS, Department of Anatomical Pathology, St. Vincent’s Hospital, Sydney, Australia

Martha B. Pitman, MD, Department of Pathology, Massachusetts General Hospital

xv

Contents

1 Overview of Diagnostic Terminology and Reporting ������������������������������� 1

2 Category I: Nondiagnostic �������������������������������������������������������������������������� 5

3 Category II: Negative (for Malignancy)����������������������������������������������������� 11

4 Category III: Atypical ���������������������������������������������������������������������������������� 27

5 Category IV: Neoplastic: Benign ���������������������������������������������������������������� 37

6 Category IV: Neoplastic: Other ������������������������������������������������������������������ 45

7 Category V: Suspicious (for Malignancy) �������������������������������������������������� 63

8 Category VI: Positive or Malignant ����������������������������������������������������������� 73

Erratum �������������������������������������������������������������������������������������������������������������� E1

Appendix ������������������������������������������������������������������������������������������������������������� 87

Index �������������������������������������������������������������������������������������������������������������������� 93