Cancer Overdiagnosis: Pathologists in the Dock.
Pathologists generally submit "background blocks" of macroscopically normal tissue from excision specimens. While this may have clinical utility in some settings, such as assessment of background kidney parenchyma from a nephrectomy specimen for unsuspected glomerular disease, this is often a waste of resources and may significantly contribute to cancer overdiagnosis. (2) The latter is best illustrated by 2 common scenarios.
When a patient with Graves disease with failed medical therapy undergoes total thyroidectomy to control hyperthyroidism, it is recommended that at least 7 sections be submitted for histologic examination if no focal abnormality is identified. (3) It is not rare for microscopic foci of papillary carcinoma to be found in these blocks but these non-mass-forming "tumors" are very unlikely to cause any clinical problems for the patient, who is now burdened with a diagnosis of thyroid cancer. The reported frequency of thyroid cancer in Graves disease varies from 0.5% to 15%. (4) However, this includes grossly identified lesions, so the incidence of macroscopically occult cancers would be lower.
Although rare cases of synchronous distant metastasis from papillary thyroid microcarcinoma have been described, (5) the scientific and clinical rationale behind sampling grossly normal thyroid tissue in this scenario is questionable. Pathologic parameters are for stratifying patients, with different outcomes predicted for those who are positive or negative for the parameter. However, in the scenario described above, identification of focal papillary microcarcinoma is essentially a chance phenomenon in a block randomly selected for histologic examination. Moreover, some cases reported as negative for malignancy would have undetected focal carcinoma deeper in the tissue block. Finally, these patients have already been treated with total thyroidectomy so detection of even multifocal microcarcinomas is unlikely to have any management implications.
An alternative approach could be to examine the slices carefully with a hand lens and sample only grossly abnormal areas. In cases with no focal abnormality, a macrophotograph would be a better record than a few random sections.
A more clinically significant issue relates to tissue sampling of transurethral resection of prostate (TURP) specimens from patients with no clinical suspicion of prostate cancer. The College of American Pathologists recommends submitting 11 sections from a 25-g TURP specimen. (6) As in the previous example, these men have undergone surgery to treat symptoms that could not be controlled by medical therapy. If retention was due to cancer, then most of the chippings would be cancerous and very limited tissue sampling would be sufficient to identify tumor. The more extensive tissue sampling protocol is designed to detect clinically occult cancer and hence it is a form of cancer screening with low-volume, low-grade, generally clinically insignificant cancer detected in about 5% of these specimens. (7) Even if they do not undergo radical therapy, these men are often managed with active surveillance protocols that could have significant impact on their finances and mental health.
The second scenario also raises a significant ethical issue because a man who had declined prostate cancer screening (Prostate-Specific Antigen test) could have his TURP specimen screened for occult cancer without his informed consent!
Random sampling of morphologically normal tissues for histologic examination may pick up a few cancers, but most of these are likely to represent overdiagnosis, and such sampling protocols can have significant resource implications for hardpressed pathology laboratories.
Varsha Shah, FRCPath ; David Scott-Coombes, FRCS ; Murali Varma, FRCPath 
 Department of Cellular Pathology, Royal Gwent Hospital, Newport, United Kingdom;  Departments of Endocrine Surgery and  Cellular Pa thology, University Hospital of Wales, Cardiff, United Kingdom
(1.) Schnadig VJ. Overdiagnosis of thyroid cancer: is this not an ethical issue for pathologists as well as radiologists and clinicians? Arch Pathol Lab Med. 2018;142(9):1018-1020.
(2.) Varma M, Shah V. Potential sources of overdiagnosis in histopathology. BMj. 2012;345: e5722.
(3.) Royal College of Pathologists Australasia. Macroscopic Cut-up Manual: Thyroid. https:// www.rcpa.edu.au/Library/Practising-Pathology/ Macroscopic-Cut-Up/Specimen/Endocrine/Thyroid. Accessed November 14, 2018.
(4.) Pazaitou-Panayiotou K, Michalakis K, Paschke R. Thyroid cancer in patients with hyperthyroidism. Horm Metab Res. 2012;44(4):255-262.
(5.) Bradley NL, Wiseman SM. Papillary thyroid microcarcinoma: the significance of high risk features. BMC Cancer. 2017;17(1):142.
(6.) College of American Pathologists. Cancer Protocol Templates. http://www.cap.org/web/home/ protocols-and-guidel i nes/cancer-reporti ng-tools/ cancer-protocol-templates?_afrLoop = 47010688453105. Accessed November 14, 2018.
(7.) Jones JS, Follis HW, Johnson JR. Probability of finding T1a and T1b (incidental) prostate cancer during TURP has decreased in the PSA era. Prostate Cancer Prostatic Dis. 2009;12(1):57-60.
Accepted for publication February 12, 2019.
The authors have no relevant financial interest in the products or companies described in this article.
In Reply.--While my editorial deals with issues owing to events that occur prior to surgical excision, Shah et al discuss potential overdiagnosis and ethical quandaries generated by evaluation of multiple sections from organs removed for nonneoplastic conditions. As they point out, some consider this practice ipso facto screening for incidental carcinomas, (1) and the subject is worthy of consideration and debate. I am pleased that this issue is being raised and hope that clinicians, surgical pathologists, and patients will continue to address this problem. Radiologists now have to contend with a similar conundrum caused by diagnostic computerized tomograms (CTs) and other imaging examinations that incidentally cut through the thyroid gland or other organs during evaluation of problems unrelated to those organs. (2) This too could be viewed as unsolicited screening. Both histopathologic and radiologic incidentalomas have harmful potential given that most incidentalomas are benign and many that are called malignant are indolent or nonprogressive. The word malignant can be terrifying, and risk of malignancy equally scary.
Clearly, primary care givers, specialists, surgeons, radiologists, and pathologists are now facing dilemmas and controversy regarding how to maximize patient benefit and minimize harm. A potential tool for limiting detection and overtreatment of incidentalomas is shared decision making (SDM). Shared decision making is a 30-year-old idea that is reemerging as a patient-centered technique for discussion of screening test risks and benefits and holds promise despite limitations imposed by physician time constraints and cognitive bias. (3-5) Shared decision making is already proposed for use prior to mammography and CT lung cancer screening. Recently, D'Agostino et al (6) investigated patients' decision-making process in choosing between surgery and active surveillance for thyroid papillary microcarcinoma. This interesting study sets the stage for thyroid cancer SDM. These authors confirmed that, to patients, "Just the word 'cancer' is scary." (6) Can SDM be used to limit detection of incidentalomas? After they have been provided with nonbiased, evidence-based risk/benefit information and an opportunity to ask questions of their physicians, could not this tool be used to allow patients to elect to limit or forego follow-up procedures following detection of incidentalomas via histology or imaging? Also, could not pathologists and radiologists be trained to participate in SDM prior to fine-needle aspiration, surgical procedures for benign conditions, and imaging studies? At least, this is something to ponder.
Vicki J. Schnadig, MD
Department of Pathology, University of Texas Medical Branch, Galveston
(1.) Varma M, Shah V. Potential sources of overdiagnosis in histopathology. BMJ. 2012;345: e5722.
(2.) Berlin L. How do you solve a problem like incidentalomas? Appl Radiol. 2013;42(2):10-12.
(3.) Elwyn G, Frosch D, Thompson R, et al. Shared decision making: a model for clinical practice. J Gen IntMed. 2012;27(10):1361-1367.
(4.) Berger ZD, Brito JP Ospina NS, et al. Patient centered diagnosis: sharing diagnostic decisions in clinical practice. BMJ. 2017;359:j4218. doi:10. 1136/bmj.j4218
(5.) Schrager S, Phillips G, Burnside E. Shared decision making in cancer screening. Fam Bract Manag. 2017;24(3):5-10.
(6.) D'Agostino TA, Shuk E, Maloney EK, Zeuren R, Tuttle rM, Bylund CL. Treatment decision-making in early-stage papillary thyroid cancer. Psychooncology. 2018;27(1):61-68.
Accepted for publication February 27, 2019.
The author has no relevant financial interest in the products or companies described in this article.
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|Author:||Shah, Varsha; Scott-Coombes, David; Varma, Murali|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Article Type:||Letter to the editor|
|Date:||Jul 1, 2019|
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