SAGE-Hindawi Access to Research Pathology Research International Volume 2011, Article ID 636495, 4 pages doi:10.4061/2011/636495 Clinical Study Base-Rate Error in the Interpretation of Immunohistochemistry Malcolm Galloway Department of Cellular Pathology, Royal Free Hospital, Royal Free Hampstead NHS Trust, Pond Street, Hampstead, London, NW3 2QG, UK Correspondence should be addressed to Malcolm Galloway, malcolm.galloway@nhs.net Received 10 February 2011; Revised 21 March 2011; Accepted 23 March 2011 Academic Editor: Pablo A. Bejarano Copyright © 2011 Malcolm Galloway. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Failure to appreciate the importance of the frequency of a disorder in the appropriate population (the base rate) may lead to the misinterpretation of the diagnostic signiﬁcance of unexpected test results (unexpected test result deﬁned in this context as a test result that is positive in a higher proportion of cases of an alternative diagnosis than in the diagnosis considered most likely before the test). This study aimed to determine whether pathologists are vulnerable to this error. Pathologists were asked to estimate the probability of tumour B in a scenario in which, prior to the immunostaining result, an experienced pathologist considers there to be a 99% chance that the patient has tumour A and a 1% chance that they have tumour B. Antibody X is positive in 80% of cases of tumour B and negative in 90% of cases of tumour A and is positive in the case described in the scenario. The estimates made by consultant pathologists ranged from 0 to 100% (mean 29.7%). The Bayesian answer would be 7.5%. These ﬁndings suggest that base-rate error may lead some pathologists to overestimate the implications for the likelihood of a diagnosis in the light of an unexpected immunohistochemical result. 1. Introduction Base-rate error in medical diagnosis refers to the cognitive bias in which doctors may underestimate the importance of the frequency of the relevant disorder in the appropriate population (the pretest probability) when considering the implications for the diagnosis of the result of tests which have less than 100% sensitivity and speciﬁcity. An underappre- ciation of the importance of the base rate has been shown outside medical practice, for example, in the interpretation of fallible witness evidence [1], and has also been shown in relation to the interpretation of diagnostic test results by physicians [1–3]. In the ﬁeld of base-rate errors in diagnostic interpre- tation, the most closely studied area thus far has been in relation to mammography. Eddy has previously reported base-rate error in the interpretation of the diagnostic con- tribution of mammogram results by physicians [3]. In his scenario, 79.2% of patients with breast cancer are assumed to have a malignant result on mammography (sensitivity) and 90.4% of patients without cancer to have a benign mammogram result (speciﬁcity). He asked what he described as “an informal group of approximately 100 physicians” what the probability of a patient having breast cancer would be if they had a 1% risk of the disease prior to the mammogram but had a malignant diagnosis on mammography. In this scenario, the mathematically correct answer (by Bayesian analysis) would by 7.7%. He reported that approximately 95% of physicians estimated the risk as approximately 75% (almost 10 times the actual risk). A similar study in which physicians were asked to predict the probability of a malignant lesion in a patient with a positive mammogram result demonstrated that even when providing their own individual estimates for the sensitivity and speciﬁcity of mammography in a breast mass scenario, physicians consistently overestimated the impact of a positive test result on the likelihood of the disease [4]. Pathologists are regularly formulating diﬀerential diag- noses and using further investigations, particularly immuno- histochemistry, to assist in the selection of the ﬁnal diagnosis. This process could be regarded as cognitively equivalent to the processes involved in making a clinical diﬀerential diagnosis of a breast mass, further investigating with mam- mography, and then deciding whether to proceed to biopsy. As with mammography, immunohistochemistry will rarely