Counseling About Cancer
Strategies for Genetic Counseling
Fourth Edition
Katherine A. Schneider, MPH, CGC
Dana-Farber Cancer Institute, Boston, MA
Anu Chittenden, MS, CGC
Dana-Farber Cancer Institute, Boston, MA
Kristen Mahoney Shannon, MS, CGC
Massachusetts General Hospital Cancer Center, Boston, MA
This fourth edition first published 2023
© 2023 by John Wiley & Sons Ltd
Edition History
John Wiley & Sons, Inc. (3e, 2012); John Wiley & Sons, Inc. (2e, 2001)
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Library of Congress Cataloging-in-Publication Data
Names: Schneider, Katherine A, author. | Chittenden, Anu, author. | Shannon, Kristen Mahoney, author.
Title: Counseling about cancer : strategies for genetic counseling / Katherine A Schneider, Anu Chittenden, Kristen Mahoney Shannon.
Description: Fourth edition. | Hoboken, NJ : Wiley-Blackwell, 2023. | Includes bibliographical references and index.
Identifiers: LCCN 2022030098 (print) | LCCN 2022030099 (ebook) | ISBN 9781119466468 (paperback) | ISBN 9781119466482 (adobe pdf) | ISBN 9781119466475 (epub)
Subjects: MESH: Neoplasms–genetics | Genetic Counseling
Classification: LCC RC268.4 (print) | LCC RC268.4 (ebook) | NLM QZ 210 | DDC 616.99/4042–dc23/eng/20220819
LC record available at https://lccn.loc.gov/2022030098
LC ebook record available at https://lccn.loc.gov/2022030099
Cover Design by Wiley
Cover Image: Lindwa/Shutterstock, PASIEKA/Getty Images
Set in 10/12pt and PalatinoLTStd by Straive, Pondicherry, India
We dedicate this book with appreciation and love to our wonderful, supportive parents:
Donald and Patricia Daviau
Ambat and Prema Bhaskar
Donald and Karen Mahoney
Contents
Foreword, xi
Preface, xiii
Acknowledgments, xv
CHAPTER 1: CANCER DIAGNOSIS AND TREATMENT, 1
1.1. The Diagnosis of Cancer, 1
1.2. Tumor Classification, 8
1.3. Cancer Treatment, 14
1.4. Risk Factors for Cancer, 28
1.5. Case Examples, 30
1.6. Discussion Questions, 33
1.7. Further Reading, 33
CHAPTER 2: GASTROINTESTINAL CANCER SYNDROMES, 35
2.1. Anatomy, 36
2.2. Colorectal Cancer, 45
2.3. Gastric (Stomach) Cancer, 47
2.4. Pancreatic Cancer, 49
2.5. Lynch Syndrome, 51
2.6. Familial Adenomatous Polyposis/Attenuated Familial Adenomatous Polyposis, 62
2.7. MUTYH-Associated Polyposis, 68
2.8. NTHL1 Tumor Syndrome, 73
2.9. Polymerase Proofreading-Associated Polyposis Syndrome, 75
2.10. Juvenile Polyposis Syndrome, 79
2.11. Peutz-Jeghers Syndrome, 84
2.12. PTEN Hamartoma Tumor Syndromes, 88
2.13. Hereditary Mixed Polyposis Syndrome, 90
2.14. Serrated Polyposis Syndrome, 92
2.15. Hereditary Diffuse Gastric Cancer Syndrome, 96
2.16. Familial Atypical Multiple Mole Melanoma Syndrome, 101
2.17. Hereditary Pancreatitis/Familial Pancreatitis, 105
2.18. Short Reviews, 111
2.19. Further Reading, 114
CHAPTER 3: BREAST AND GYNECOLOGICAL CANCER SYNDROMES, 129
3.1. Anatomy, 129
3.2. Overview of Counseling Issues, 131
3.3. Selected Breast and Gynecologic Syndromes, 133
3.4. Case Examples, 157
3.5. Discussion Questions, 160
3.6. Further Reading, 160
CHAPTER 4: RARE TUMOR PREDISPOSITION SYNDROMES, 163
4.1. Overview of Rare Tumor Syndromes, 163
4.2. Overview of Counseling Issues with Rare Tumor Syndromes, 171
4.3. Clinical Features of Selected Rare Tumor Syndromes, 173
4.4. Case Examples, 204
4.5. Discussion Questions, 207
4.6. Further Reading, 207
CHAPTER 5: PEDIATRIC TUMOR PREDISPOSITION SYNDROMES, 209
5.1. Counseling Issues, 209
5.2. Pediatric Tumor Predisposition Syndromes, 213
5.3. Case Examples, 262
5.4. Discussion Questions, 265
5.5. Further Reading, 266
CHAPTER 6: CANCER FAMILY HISTORIES (COLLECTION AND INTERPRETATION), 269
6.1. Collecting a Cancer History, 269
6.2. Challenges to Collecting an Accurate History, 289
6.3. Interpreting a Cancer History, 293
6.4. Case Examples, 299
6.5. Discussion Questions, 303
6.6. Further Reading, 304
CHAPTER
7: CANCER RISK ASSESSMENT AND RISK MODELS, 307
7.1. Risk Definitions, 308
7.2. Risk Perception and Cancer Risk, 310
7.3. Risk Factors, 312
7.4. Risk Modeling, 318
7.5. Genetics Criteria, 330
7.6. Case Examples, 333
7.7. Discussion Questions, 334
7.8. Further Reading, 335
CHAPTER 8: GENETIC TESTING TECHNOLOGIES, 337
8.1. Older Technologies, 338
8.2. Newer Technologies, 348
8.3. Clinical Issues, 357
8.4. Case Examples, 363
8.5. Discussion Questions, 365
8.6. Further Reading, 366
CHAPTER 9: PRE- AND POST-TEST GENETIC COUNSELING, 369
9.1. Traditional Pre-Test Genetic Counseling Session, 371
9.2. Pre-Test Strategies for Genetic Counselors, 384
9.3. Other Pre-Test Genetic Counseling Considerations, 387
9.4. Alternative Service Delivery Models for Pre-Test Education, 388
9.5. Traditional Post-Test Genetic Counseling, 390
9.6. Post-Test Genetic Counseling When the Genetic Counselor Was Not Involved in Pre-Test Education, 396
9.7. Possible Patient Reactions to Results, 397
9.8. Follow-Up Genetic Counseling, 399
9.9. Psychological Assessment Throughout the Genetic Testing Process (see also Chapter 11), 401
9.10. Summary and Future Directions, 403
9.11. Case Examples, 404
9.12. Discussion Questions, 405
9.13. Further Reading, 406
CHAPTER 10: SPECIAL POPULATIONS AND SPECIAL SITUATIONS, 409
10.1. Counseling for Special Populations, 409
10.2. Counseling About Unanticipated Results, 417
10.3. Case Examples, 421
10.4. Discussion Questions, 425
10.5. Further Reading, 425
CHAPTER 11: PSYCHOSOCIAL ASPECTS OF CANCER GENETIC COUNSELING, 429
11.1. Contextual Information About Patients, 430
11.2. Patient Reactions, Coping Responses, and Risk Perception, 442
11.3. Strategies for Providing Psychosocial Counseling, 446
11.4. Strategies for Effective Psychosocial Genetic Counseling, 454
11.5. Providing Additional Emotional Support, 461
11.6. Case Examples, 468
11.7. Discussion Questions, 473
11.8. Further Reading, 473
CHAPTER 12: ETHICAL ISSUES IN CANCER GENETIC COUNSELING AND TESTING, 475
12.1. Bioethical Principles and Framework, 476
12.2. Putting Ethics into Practice, 484
12.3. Types of Ethical Dilemmas in Cancer Genetic Counseling, 492
12.4. Case Examples, 501
12.5. Discussion Questions, 504
12.6. Further Reading, 504 Index, 507
Foreword
I was so surprised and pleased when Kathy Schneider asked me to write a foreword to this latest edition of her now iconic cancer genetic counseling text, Counseling About Cancer. Kathy and I have been colleagues and friends since collaborating on the very first National Society of Genetic Counselors (NSGC) Short Course on Cancer Genetics in 1993 and joining with other pioneering counselors to form the Familial Cancer Special Interest Group in 1997. Over the decades, through presentations, publications, and other professional activities I have come to know and admire Kristen Shannon and Anu Chittenden for their caring manner and superb cancer genetic counseling expertise. Their recruitment as co-authors adds special breadth and depth to the text. Genetic counselors are only as good as their sources of information. Families come to us for accurate information about the condition in their family, and to help them process complex information in order to make difficult personal decisions. Trusted resources include reliable research and clinical laboratories, medical genetics, oncology and genetic counseling colleagues, and well-worn texts. From the beginning of the cancer genetic counseling specialty, Counseling About Cancer has been a unique trusted resource to guide our practice, for both novices and experienced counselors alike. Each edition has added to the growing body of information. In the almost a decade since the third edition, breathtaking changes have occurred in cancer diagnosis and treatment, recognition of new inherited cancer susceptibility syndromes, and refinement of familiar diagnoses. Genome-wide association studies and applied biostatistical methods have refined risk modeling and risk assessment. Genetic testing has expanded to include discovery of new cancer predisposing genes, common use of multigene panels, exome, and whole-genome analyses.
Relationships are as essential to the process of genetic counseling as they are to life itself. Our relationships to those who seek our services or who participate in groundbreaking research must be built on mutual trust and respect. Greater consciousness of diversity has led to modifying genetic counseling in addressing communities with unique qualities and particular needs. The chapters on psychosocial and ethical issues provide a critical framework for cancer genetic counselors to build mutually enriching relationships with individuals, couples, and families who seek our care and expertise.
In summary, you can rely on the authors to provide you with the essentials of cancer genetic counseling for a rewarding lifetime practice.
June A. Peters, MS, CGC, LMFT
Retired Genetic Counselor, National Cancer Institute
Recipient of 2021 Natalie Weissberger Paul Award May 2022
Preface
It may seem hard to believe, but there was a time when cancer was not considered a major genetic counseling specialty. Genetic counselors have now become fully integrated into clinical oncology clinics by providing care to at-risk patients, newly diagnosed and advanced cancer patients, and cancer survivors. Somatic and germline genetic test results are routinely requested by oncologists with the expectation that results will help guide surgical and treatment decisions, including clinical trial options. The expanded utility of genetic test results and assessments of family history have given new options and hope to individuals and their medical providers— and has greatly increased the demand for cancer genetic counselors.
In a small way, the various editions of this textbook have marked the exponential growth and sophistication of cancer genetic counseling from the slim self-published first edition sponsored by the Jane Engelberg Fellowship Award in 1992 to the larger second edition and even larger third edition, published by John Wiley & Sons, which included a greater number of cancer syndromes and genetic testing options.
This fourth edition reflects how far (and fast) the specialty continues to grow, by offering a treasure trove of new and updated information about tumor predisposition syndromes, testing options, and the genetic counseling processes and discussion points. Given the large number of publications to cull through and summarize, I wisely enlisted two experienced cancer genetic counselors, Anu Chittenden, MS, CGC, and Kristen Shannon, MS, CGC, to co-author this book with me.
Chapter 1 provides an overview of cancer diagnosis and treatment, including the ways in which many cancers are diagnosed and the various types of treatment plans, from watchful surveillance to stem cell transplants. Becoming familiarized with the medical aspects of the patient’s cancer journey may be useful in terms of practical considerations and when fostering connections with patients.
Chapters 2 through 5 provide detailed information about the currently known hereditary cancer syndromes and includes sections on clinical criteria, associated cancer risks, genetic testing considerations, and screening recommendations. Chapter 2 discusses gastrointestinal cancer syndromes, Chapter 3 discusses breast and gynecological cancers, Chapter 4 discusses rare tumor predisposition syndromes, and Chapter 5 discusses pediatric cancer syndromes. Chapter 5
also includes a discussion of counseling strategies and challenges, which may be unique or intensified in pediatric cancer counseling.
Chapters 6 through 9 shift the focus to the genetic counseling and testing process. The evolving needs of patients and the referring providers, the increased reliance on technology, and the wider availability of multigene panel testing have all contributed to changes in how genetic counselors interact with patients. Strategies for collecting and assessing family histories are covered in Chapter 6, while Chapter 7 focuses on the available risk models with their varying benefits and limitations. Chapters 8 and 9 provide detailed information about the genetic testing process, including descriptions of the various testing technologies and possible types of results (Chapter 8) and and the important components of pre- and post-test discussions (Chapter 9). And because there may be special counseling challenges with certain situations or types of patients, Chapter 10 highlights some of the special populations that cancer counselors may encounter and highlights helpful tips and suggestions to providing effective care.
Chapter 11 continues the focus on the counseling aspect of patient interactions by discussing the relevant psychosocial factors that allow counselors to better “see” their patients and providing strategies to help foster more meaningful connections with patients. There is also a new section on how to recognize and avoid signs of provider burnout, which seems especially relevant as the world emerges from the COVID-19 pandemic. Chapter 12 provides an overview of the types of ethical dilemmas that counselors may come across and offers strategies for how to resolve them.
Tables, figures, and case examples are included throughout the book to further illustrate the points made in the text. In addition, at the end of each chapter, possible discussion questions and additional reading suggestions are included.
Anu, Kristen, and I sincerely hope that this textbook proves to be a comprehensive and valuable resource for practicing genetic counselors and other health care providers as well as for genetic counselors in training. Happy reading!
Katherine A. Schneider, MPH, CGC Dana-Farber Cancer Institute
Acknowledgments
We want to thank the many people who helped and supported us through the process of writing this book, including our wonderful and exceedingly patient editor and publishing staff at Wiley.
First, we are extremely grateful to the colleagues who reviewed one or more chapters of the book. Your feedback was invaluable! Specifically, we want to thank Janice Berliner, Leah Biller, Kasia Bloch, Gayun Chan-Smutko, Tom Chittenden, Dillon Davis, Kayla Hamilton, Elaine Hiller, Diane Koeller, Brandie Leach, Lisa Madlensky, Ellen Matloff, Wendy McKinnon, Bita Nehora, Beth Peshkin, June Peters, Robert Resta, Irene Rainville, Jaclyn Schienda, Sarah Scollon, Morgan Similuk, Jilliane Sotelo, Scott Weismann, and Matt Yurgelin.
In addition, each of us has specific individuals in our lives who we wish to acknowledge.
Katherine Schneider:
I want to thank all of my amazing friends and family who have helped out in so many different ways over the past few years:
• To my three wonderful sons, Nicholas Schneider, Christopher Schneider, and Jordan Schneider, who were young children when I wrote the first edition of this book; my two awesome daughters-in-law, Rachel Schneider and Kayla Schneider, and my incredibly talented grandson, Oliver Schneider. I am so proud of all of you as you follow your dreams.
• To my sister, Julia Daviau, for happily adapting to life here in Boston and for our shared love of puzzles and old movies, with a special shoutout to my sister’s fabulous companion care provider, Jeannie McEleney; and to my two awesome brothers, Thomas Daviau and Robert Daviau.
• To my amazing co-authors, Anu and Kristen - I am so grateful for your friendship. And to Audrey D’Atri, Jill Stopfer, Carmen Tso, Dr. Huma Rana, Dr. Judy Garber, Dr. Lisa Diller, Dr. Junne Kamihara, Dr. Sapna Syngal, Dr. Matthew Yurgelun and all my other wonderful colleagues at the Dana Farber. —thanks for all you do.
• To my dearest friend and hiking/theater companion, Vickie Venne, who is the hardestworking person I know—even after retirement!
• To Daniel Hulub & Dee Towne and Frank & Carolyn Walker—thanks for all your support, laughter, and fun; you truly are my Boston “family.”
• To all my spiritual friends and sisters, especially Brenda Vigue and Kacey O’Donnell.
• And a huge thank you to others who have provided friendship and connection over the years, including Rhoda Berlin, Karen Fassett, Kelly Hatfield, Janine Kakishita, Debbie Lewis, and Rebecca Porter.
• Lastly, in memoriam to my beloved parents and partner, Bradford Kinne—we never truly lose the ones we love.
Anu Chittenden:
• A huge thank you to my good friends and co-authors. Kathy, I am so grateful for all that you have done for me. (However, if you ever want to do this again, I am running in the other direction.) Kristen, thank you for always bringing the laughter into everything we do. Both of you are my role models and amazing people.
• To my husband and favorite human, Tom Chittenden, who put up with me during this (seemingly endless) process. You really are the most patient and supportive person I have ever known, and all of my friends agree.
• To my daughters, Amara and Abby Chittenden, two strong, independent, interesting, caring, and funny young women. I am so lucky and so proud of both of you. I hope you both find the kind of fulfillment in your careers that I have.
• To my two families: To my brothers, Rohit and Ranjit, sisters-in-law, Sunu and Lauren, nieces (Nitya, Divya, and Sandhya), nephews (Morgan and Rilen), cousins (Ramesh, Rahul, and all), and extended family, especially my two aunts, Leela and Krishna (matriarchy rules). And to Kathy, Doug, Johnny, Katherine, Beth, Jim, and the rest of this crazy family—I know you don’t know what I do but thank you for listening.
• To the many genetic counselors I have had the privilege of working with over the years at DFCI. You have left pieces of yourselves and remain unforgettable to me, especially Elaine, Shelley, Kelly, Irene, Emily, and Monica.
• To my Dana-Farber family and Dr. Judy Garber—not many people get to spend their entire careers in one place with such dedicated and wonderful people. And a special thanks to my DFCI BFF, Chinedu Ukaegbu, and the make-it-happen team of Audrey D’Atri, Huma Rana, Sarfaraz Shaikh, and Jill Stopfer.
• To my classmates, Deedy Hamer, Judy Jackson, Susan Estabrooks Hahn, and Kristin Clemenz—you are all incredible people! Who knew that getting off the wait list would lead to a lifelong friendship? I look forward to celebrating another 25 years with all of you. Thank you to Judith and the Brandeis program for bringing us together.
• To Patrick Chittenden—your love of life, personality, and smile will never be forgotten.
• To my in-laws, Ted and Diana Chittenden, who accepted me without checking my citizenship status, made me feel welcome, and respected me for my career.
• And to Prema and Ambat Bhaskar—you gave up everything for a better life for us. We were so lucky to have you as parents.
Kristen Shannon:
• To my incredible husband, Sam. Thank you for dealing with me and all my idiosyncrasies. Your love, support, encouragement, and humor have carried me through. I could not possibly be the woman I am without you by my side. I love you very much and am so grateful to travel through this crazy fun life with you.
• To my four amazing kids, Kevin, Luke, Molly, and Matthew. I’m blessed to have such loving, supportive, and absolutely hilarious children. I’m incredibly proud of each of you and am privileged that you call me Mom.
• To my terrific parents, Karen and Don Mahoney. Your unconditional love, support, and sacrifice have helped make me the person I am today.
• To my awesome sister, Deanna McLaughlin, who is always there for me, and my terrific brother, Don Mahoney. Thanks for being such great friends and always having my back. I’m so thankful we are so close (emotionally and geographically!) and get to raise our families together.
• To my best and dearest friend, Amy Foohey. Our friendship has truly stood the test of time! Your generosity, love, and support are unparalleled. I am honored to call you my best friend and can’t imagine life without you by my side.
• To my “Carlin Girls”: Christine Bryson, Kathleen Eaton, Madeleine Friend, Donna McAndrews, and Jennifer Tschirch Phillips. Your love and support throughout the years have been endless. I’m truly grateful.
• To Devanshi Patel and Meredith Seidel, who make my work life manageable and (more importantly) fun, and all my amazing coworkers at the Mass General Cancer Center Genetics Program. Our team is truly a family, and I am very grateful for each of you. Thank you for all your tireless work over the years to make our program so successful.
• And lastly, to my inspirational co-authors, Kathy Schneider and Anu Chittenden. We certainly have had lots of fun over the past decades. I’m humbled to be involved in this project. Thank you for being such wonderful mentors and friends.
Finally, we are so appreciative and grateful for the wonderful patients and families who have taught us so much over the years.
Cancer Diagnosis and Treatment
Doctors have always recognized that every patient is unique, and doctors have always tried to tailor their treatments as best they can to individuals. You can match a blood transfusion to a blood type. That was an important discovery. What if matching a cancer cure to our genetic code was just as easy, just as standard?
President Barack Obama (January 30, 2015; Precision Medicine Initiative)
A cancer genetic counseling session often begins with hearing the patient’s cancer story: the symptoms that led to the suspicion of cancer, the way in which the diagnosis was made, and the subsequent treatment regimen. This chapter describes the process of making a cancer diagnosis, the systems used to classify tumors, and the current strategies for cancer treatment. The chapter will also briefly touch on the risk factors for cancer as context for a genetic counseling session.
1.1. The Diagnosis of Cancer
This section provides the information necessary to understanding a cancer diagnosis, from how cancer is diagnosed to the nomenclature used to describe the tumor and the treatment options that are available.
1.1.1. Cancer Detection
A diagnosis of cancer often begins with a worrisome symptom or problem on a medical intake or screening test. For example, a physical exam may reveal swollen lymph glands or unusual tenderness. A routine screening test, such as a colonoscopy, cervical Pap smear, or blood test,
Counseling About Cancer: Strategies for Genetic Counseling, Fourth Edition. Katherine A. Schneider, Anu Chittenden, and Kristen Mahoney Shannon. © 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
may identify the presence of atypical cells or an unusually high number of cells. A blood specimen that shows a dramatically high count of “blasts” (immature white blood cells) in a young child may point to the presence of acute lymphoblastic leukemia.
In many cases, patients have noticed warning signs of cancer (see Table 1.1). They may note a new physical finding, such as a breast lump, or they have health problems that are not abating over time (such as a persistent cough) or even getting worse (such as bleeding after a bowel movement).
People are more likely to experience symptoms or warning signs if their tumor:
• Is pressing on neighboring tissue and causes pain
• Is interfering with the functioning of normal tissue
• Has invaded the blood vessels to cause abnormal bleeding
• Has grown large enough to be palpated
A malignant tumor can be present for months, even years, before it is detected. The reasons why cancer detection can be so difficult are presented in the following sections.
1.1.1.1. Lack of Warning Signs
There may be no physical symptoms that signal the presence of early-stage cancer. Observable signs of cancer are more likely to be noticed as the cancer progresses. Sometimes, this means that the hallmarks of cancer, such as a lump, bleeding, or pain, indicate a malignancy that is already in an intermediate or advanced stage. However, most of the time, common symptoms are unrelated to cancer. If symptoms persist, they should be evaluated.
TABLE 1.1. General Signs and Symptoms of Cancer
• Fatigue or extreme tiredness that doesn’t get better with rest
• Weight loss or gain of 10 pounds or more for no known reason
• Eating problems such as not feeling hungry, trouble swallowing, belly pain, or nausea and vomiting
• Swelling or lumps anywhere in the body
• Thickening or lump in the breast or other part of the body
• Pain, especially new or with no known reason, that doesn’t go away or gets worse
• Skin changes such as a lump that bleeds or turns scaly, a new mole or a change in a mole, a sore that does not heal, or a yellowish color to the skin or eyes (jaundice)
• Cough or hoarseness that does not go away
• Unusual bleeding or bruising for no known reason
• Change in bowel habits, such as constipation or diarrhea, that doesn’t go away or a change in how stools look
• Bladder changes such as pain when passing urine, blood in the urine, or needing to pass urine more or less often
• Fever or night sweats
• Headaches
• Vision or hearing problems
• Mouth changes such as sores, bleeding, pain, or numbness
Source: American Cancer Society (accessed 2021).
1.1.1.2. Imperfect or Lack of Screening Methods
To be effective, screening tests need to be easily performed, affordable, and accurate in detecting disease cases while limiting the number of false positive tests. The cancers must be detectable at earlier, more curable, stages and must occur at a frequency that justifies population screening. For example, a Pap smear is an effective screening test for cervical cancer, because it is a fairly common disease and early diagnosis has been shown to make a significant difference in survival. Cancers such as ovarian cancer have no known effective screening methods in detecting cancer reliably, although much work is being done in this area. Screening tests for less common forms of cancer are generally offered only to those known to be at high risk.
1.1.1.3. Elusive Premalignant Cells
Few organs can be readily and repeatedly sampled, which makes it difficult to monitor the organs for malignant or (even better) premalignant cells. At this point, only a few screening tests reliably detect premalignant cells, with colonoscopies being one of the best examples.
Cutting edge research is looking into the development of tests for very early markers of cancer through blood tests (see Chapter 8).
1.1.2. Making the Diagnosis of Cancer
The workup for cancer typically begins when other more likely explanations have been ruled out. For example, the differential diagnosis of frequent headaches includes vision problems, allergies, and stress. More serious possibilities, such as a brain tumor or neurological problem, are less likely to be entertained at the outset because of their relative rarity. Because of this, a common theme among members of families with hereditary cancer syndromes is that signs of cancer were initially ignored or downplayed by their providers.
The method by which the cancer will be identified depends on the tumor type (see Table 1.2). The presence of cancer may be suggested by physical exam, imaging studies, specialized blood
TABLE 1.2.
• Lab tests
How Cancer is Diagnosed
• Blood, urine, body fluid
• Imaging tests
• CT scan
• MRI
• Nuclear scan
• PET scan
• Ultrasound
• X-rays
• Biopsy
• With a needle
• With endoscopy
• With surgery
Source: Adapted from National Cancer Institute, How Cancer Is Diagnosed.
TABLE 1.3. Some Common Tumor Markers Used in Diagnosis and Assessment of cancer
Tumor Marker
CA 19-9
CA-125
Calcitonin
CEA
Chromogranin A
Prostate-specific antigen (PSA)
Type of Sample Cancer
Blood Pancreatic, gallbladder, bile duct, and gastric cancers
Blood Ovarian cancers
Blood Medullary thyroid cancer
Blood Colorectal and other cancers
Blood Neuroendocrine tumor
Blood Prostate cancer
Source: Adapted from National Cancer Institute, Tumor Markers in Common Use.
tests (see Table 1.3 for some common tumor markers detected in blood), or invasive procedures. Except in rare cases, biopsy is required to make a definitive diagnosis. For example, the diagnosis of pancreatic cancer may start with a symptom of weight loss and subsequent imaging, but it is the biopsy and subsequent pathologic analysis that will confirm the diagnosis.
Individuals will be referred to a medical oncologist either when the suspicion of cancer has been raised or following the initial diagnosis. As with most medical specialties, clinical oncology is divided into many subspecialties. Other members of the cancer care team include surgeons, radiologists, radiation oncologists, pathologists, and mental health professionals; the care of individuals with cancer requires a multidisciplinary team.
Cancer can be a high-burden disease on both patients and their families. Learning that one has cancer can engender feelings of shock, anger, intense sadness, and extreme anxiety. As patients enter cancer treatment, they may need to make major adjustments in their family responsibilities and workload. At many cancer centers, patients and their families have the opportunity to meet with a social worker or psychologist. Patient support groups may also be helpful.
1.1.3.
Cancer Terminology
Hippocrates named the hard gray tumor tissue that extends into normal tissue “Carcinoma” for its crablike appearance. The Latin word for crab is cancer
The terminology used to describe specific tumors can be daunting and it may be helpful to consider how these names are derived. Tumor nomenclature provides information about where in the body and in what type of tissue and cell the cancer originated. Cancer is currently still classified by the type of tissue and the primary site it originates in. However, with the advent of genomic analysis of tumors, classification systems may rely more heavily on mutational signatures.
1.1.3.1. Site of Origin
The medical term for a tumor is a neoplasm, which literally means new growth. Neoplasms can develop in almost every tissue of the body. The name of a neoplasm will usually first indicate the site in the body where the tumor has originated. As examples, a hepatocellular carcinoma is a liver cancer, and a rhabdomyosarcoma is a tumor of the striated muscle. Cancers of unknown primary are tumors that are metastatic at diagnosis and have unidentifiable sites of origin.
1.1.3.2. Tissue Type
The rationale underlying the name and classification of tumors can be found in embryology (see Table 1.4). In the early embryo there are three layers of germ cells: the ectoderm, the mesoderm, and the endoderm.
The type of tissue in which the neoplasm has occurred—as well as its embryological origin— will typically be indicated within the name of the tumor. There are several major categories of cancers: carcinoma, sarcoma, hematologic malignancies, mixed types, neuroectodermal.
• Carcinomas—Carcinomas occur in the epithelial cells covering the surface of the body and lining the internal organs. Carcinomas account for about 80–90% of all cancers. Carcinomas are divided into two major types: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas arise mostly in organs with glands and occur in mucus membranes, and squamous cell carcinomas arise from cells lining body cavities. The most common sites of carcinomas are in the skin, lungs, female breast, prostate, colon and rectum, cervix, and uterus.
• Sarcomas—Sarcomas occur in tissues of mesodermal origin and are the rarest form of neoplasm. Sarcomas are solid tumors occurring in connective and supporting tissues, such as muscle, bone, or fat (see Table 1.5). Roughly, they can be classified into soft-tissue
Embryonic Tissue
Derivation of Tissue Types
Tissue
Ectoderm Some epithelial (skin, lining for most hollow organs), nerve tissue, salivary glands, and mucous glands
Endoderm Some epithelial, including the lining of the digestive tract (except at open ends) as well as the epithelial lining of hollow structures formed as outpockets in the digestive tract
Mesoderm Endothelium, bone and cartilage, muscle, fat, blood and lymph vessels, blood cells, also epithelial lining of uterus (endometrium), vaginal epithelium, and mucosa of the bladder
Source: Adapted from SEER Training Modules.
TABLE 1.4.
TABLE 1.5. Soft Tissue Sarcomas by Tissue Type
Name of Sarcoma
Angiosarcoma
Desmoid tumor, also called deep fibromatosis
Ewing family of tumors
Fibrosarcoma
Gastrointestinal stromal tumor (GIST)
Kaposi sarcoma
Leiomyosarcoma
Liposarcoma
Myxofibrosarcoma
Malignant peripheral nerve sheath tumor (MPNST), also known as neurofibrosarcoma
Rhabdomyosarcoma
Synovial sarcoma
Undifferentiated pleomorphic sarcoma (UPS), previously called malignant fibrous histiocytoma (MFH)
Source: Cancer.net (ASCO) (2020).
Related Normal Tissue Type
Blood or lymph vessels
Fibroblasts, which are the most common type of cells in connective tissue
No obvious related normal tissue; may be a tumor of stem cells
Fibroblasts, which are the most common type of cells in connective tissue
Specialized neuromuscular cells of the digestive tract
Blood vessels
Smooth muscle
Fat tissue
Connective tissue
Cells that wrap around nerve endings, similar to the way insulation wraps around a wire
Skeletal muscle
No obvious related normal tissue; may be a tumor of stem cells
No obvious related normal tissue; may be a tumor of stem cells or a distant relative of rhabdomyosarcoma
tumors and bone tumors (chondrogenic and osteogenic). There are other rare categories of sarcomas as well.
• Leukemias, lymphomas, and myeloma—Leukemia, lymphomas, and myeloma are cancers occurring in the lymph glands or bone marrow, which generates all of the cells of the circulatory system (see Figure 1.1 for an illustration of the complex blood cell lineage). Leukemias and lymphomas comprise about 10% of all cancers. Leukemias (which literally mean “white blood”) and lymphomas are sometimes referred to as liquid tumors in order to differentiate them from carcinomas, sarcomas, and melanomas, which are collectively termed solid tumors. Myeloma is a disorder of plasma cells that are a normal part of the immune system. Myeloproliferative neoplasms constitute a category of conditions that vary in severity (see Table 1.6).
• Mixed types The presence of more than one category of cancer can be reflected by the name such as carcinosarcoma.
• Neuroectodermal tumors—As the name implies, neuroectodermal tumors arise from ectodermal cells in the central and peripheral nervous system. Examples include gliomas, neuroblastomas, and schwannomas.
TABLE 1.6. List of Some Myeloproliferative Neoplasms
Disorder
Polycythemia vera
Essential thrombocythemia
Primary myelofibrosis
1.1.3.3. Cell Type
Cells Affected
Red blood cells mainly, white blood cells, platelets
Platelets
Red blood cells, white blood cells, platelets
The name of a tumor will often describe the type of cell that has transformed into a cancer cell. Solid tumors can arise from adenomatous cells that are glandular or ductal, or from squamous cells that are flat. Tumors containing cells with features of both glandular and squamous cells may be called adeno-squamous carcinomas. Leukemias can arise from any of the various cells derived from myeloid or lymphoid lineages. Organs of the body are generally composed of more than one type of cell. Therefore, it is important to realize that more than one type of tumor can arise within the same organ.
1.1.3.4. Exceptions
Not all tumors are classified by these cell and tissue types. For example, cancers that resemble embryonic tissue are called blastomas; examples include neuroblastomas and retinoblastomas. Another exception are teratomas, which arise in tissues derived from all three germ cell layers.
Blood stem cell
Lymphoid stem cell
Lymphoblast
Natural killer cell T lymphocyte
White blood cells B lymphocyte
Granulocytes
Myeloblast
Platelets
Red blood cells Neutrophil
Eosinophil Basophil
Myeloid stem cell
FIGURE 1.1. Blood cell development. Source: Terese Winslow.
To further complicate matters, some tumors have been named after the physicians who first described them. These include Ewing sarcoma, Hodgkin lymphoma, Kaposi sarcoma, and Wilms tumor.
1.1.4. Primary Cancer or Recurrence
Your patient explains that her mother was successfully treated for osteosarcoma at age 9 and was well until age 53 when she was diagnosed and treated for invasive breast cancer. Two years later she was found to have brain cancer and died at 56. In deciphering a pattern of cancer in the family, it is important to determine whether a malignancy represents a primary cancer or a recurrence of the initial tumor. In this scenario, the mother’s primary cancer is osteosarcoma, her breast cancer is a second primary, and the brain cancer may represent metastatic breast cancer.
1.1.4.1.
Primary Cancer
A newly arisen tumor from a specific organ is considered a primary tumor. Individuals can develop more than one primary cancer, although this is uncommon. These second (or third) primaries may occur as a consequence of treating the initial cancer. As an example of this, women with Hodgkin lymphoma (previously called Hodgkin disease) who are treated with radiation to the chest have higher rates of breast cancer. Multiple primary cancers are also more likely in those with hereditary cancer syndromes.
1.1.4.2. Recurrence
A recurrence is the reappearance of cancer cells, either in the site of origin (local recurrence) or elsewhere in the body (systemic recurrence or distant metastasis). Recurrent cancer cells will demonstrate features that are consistent with the original tumor.
1.2. Tumor Classification
The tumor classification system helps dictate treatment regimens, predict prognosis, and provide a systematic approach that can be universally recognized and understood. Tumors are assessed for malignant properties or potential and, if malignant, are graded and staged. However, while benign tumors do not undergo the same classification process, properties of the tumor are still important.
1.2.1. Benign Tumors
The word “tumor” conjures up an image of cancer, yet not all tumors are cancerous. Thus, a lipoma (benign tumor of fat cells) may not be clinically significant, while a liposarcoma (malignant tumor of fat cells) represents a serious cancerous tumor. One of the initial steps in cancer
diagnosis is to send a tumor specimen to a pathologist, who will determine if the tumor has any malignant properties.
There are several differences between benign and malignant tumors. The most significant difference is that benign tumors do not spread to other sites of the body, whereas all malignant tumors have at least some metastatic potential. Benign tumors tend to be slow-growing. They are usually enclosed in a fibrous capsule and do not metastasize. Malignant tumors, in contrast, can proliferate rapidly and will, over time, spread to neighboring or distant tissues.
Despite the name, “benign” tumors are not always innocuous and can in fact cause significant risks of morbidity and mortality due to the following factors presented in the succeeding sections.
1.2.1.1.
Location and Size
As a benign tumor grows, it may press against the normal surrounding tissue. This compression of the normal cell parenchyma can cause the normal cells to atrophy due to insufficient blood supply. In some sites of the body, there is sufficient space to tolerate a benign tumor. One example is the female uterus, in which fibroid tumors can grow to be quite large. In other sites, notably the brain and spine, there is little room for expansion and even moderately sized tumors can cause significant morbidity and mortality. Another example of a slow-growing tumor that can cause problems because of location is an abdominal desmoid tumor, which is a type of sarcoma. These types of tumors can lead to complications and even death due to sepsis, obstruction, ischemia, pulmonary embolism, and other factors. One part of diagnosis is determining the site of origin.
1.2.1.2. Excretion of Hormones
Benign tumors typically resemble their normal cell counterparts, which can be problematic if the cell type is hormone-secreting. The benign tumor, not constrained by normal cell regulatory systems, may begin to produce additional amounts of hormones. Although benign tumors are generally less efficient at hormone production than normal cells, the sheer volume of tumor cells can result in massive—and toxic—levels of hormone being produced. For example, most pheochromocytomas are benign tumors of the adrenal gland that produce the hormone epinephrine, which triggers the “fight or flight” response. Excess levels of epinephrine caused by the pheochromocytoma can result in alarmingly high blood pressure and, if untreated, can increase the risk of stroke or myocardial infarction.
In some cases, a benign tumor can be considered a precancerous tumor, that is, a tumor with malignant potential. Cells proceed through multiple steps before reaching a malignant state and some benign tumors may actually be malignant precursors. This has been shown to be the case for several types of cancer, such as certain pigmented moles (nevi) that can evolve into malignant melanoma, and adenomas of the colon, which can eventually transform into adenocarcinomas. Note that benign tumors typically end in the suffix -oma, which means “a tumor of” without the preceding “carcin” or “sarc.” Examples are meningioma and glioma (two types of brain tumors). There are exceptions to this nomenclature, notably melanoma, which is a highly malignant skin cancer. In situ tumors are early-stage malignant tumors. The following sections address the classification of malignant tumors.
1.2.2. Tumor Grading
Tumor grading involves analyzing the histological appearances and biological properties of the tumor in order to determine the extent to which the tumor resembles normal tissue. Histology is the study of the structure and composition of cells, tissues, and organs. A tumor that shows only subtle differences from normal tissue will be considered low grade (well-differentiated), while a tumor that bears little or no resemblance to its normal counterpart is of high grade (poorly differentiated). (See Table 1.7.)
Tumor grading is also based on the degree of cell differentiation that is present. Cell differentiation is the process by which newly formed (immature) cells evolve into different kinds of mature cells. Tumors are graded on whether their cells appear well differentiated, moderately differentiated, or poorly differentiated. (See example in Figure 1.2.)
TABLE 1.7. Histological Grades of Tumors
GX Grade cannot be assessed
G1 Well differentiated (low grade)
G2 Moderately differentiated (intermediate grade)
G3 Poorly differentiated (high grade)
G4 Undifferentiated (high grade)
Source: National Cancer Institute, FactSheet: Tumor Grade. Public domain.
Well Differentiated Moderately Differentiated Poorly Differentiated
FIGURE 1.2. Cellular differentiation. The differences between a well-differentiated tumor cell (left), a moderately differentiated cell (middle), and a poorly differentiated cell (right) are shown. Adapted from Pfeifer and Wick (1991), John Wiley & Sons.
