Pathology Diagnosis: What You Don’t Know Can Hurt You

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(From CancerWire July 2005) For cancer, a pathological diagnosis is the gold standard that indicates the presence or absence of cancer, the type of cancer, and its classification. Unfortunately, medical studies over the last two decades have demonstrated that this gold standard is not consistently reliable. In fact, studies have demonstrated discrepancy rates of up to 30%.

Pathology is the medical specialty that deals with the examination of tissues and cells under the microscope in order to arrive at a diagnosis. When it comes to cancer, a pathological diagnosis is the gold standard that indicates the presence or absence of cancer, the type of cancer, and its classification. Because therapeutic decisions are based on the presumed reliability of the pathology diagnosis, a misdiagnosis can result in unnecessary, harmful and aggressive therapy or inadequate treatment.

Unfortunately, medical studies over the last two decades have demonstrated that this gold standard is not consistently reliable. In fact, multiple studies have demonstrated discrepancy rates of up to 30% with an average of approximately 10%. A “discrepancy” happens when one pathologist renders a diagnosis and another pathologist looks at the same material and renders a different opinion. See for example, Gupta D, Layfield LJ. Am J Surg Pathol. 2000 Feb;24(2):280-4. Prevalence of inter-institutional anatomic pathology slide review: a survey of current practice.

Here are some examples from the medical literature:

  •     Bladder Cancer – Wrong Pathology Would Have Led to Five Unnecessary Cystectomies: The pathology of 97 patients (131 specimens) with suspected urothelial carcinoma of the bladder was reviewed. Twenty-four of the 131 specimens "exhibited significant discrepancies." This included two patients who showed no evidence of tumor. As a result of the review, five radical cystectomies were avoided.

Coblentz TR, Mills SE, Theodorescu D. Cancer. 2001 Apr 1;91(7):1284-90. Impact of second opinion pathology in the definitive management of patients with bladder carcinoma.

  •     Brain Tumors – Pathologists Often Disagree With Themselves or Others Pathologists agreed with their original diagnosis only 51.43% for anaplastic astrocytomas, 74.73% for glioblastoma multiforme, and 65.22% for low-grade astrocytomas. Pathologists agreed with other pathologists only 62.41% for glioblastomas, 36.04% for AA, and 57.14% for low-grade astrocytomas.

Mittler MA, et al., J Neurosurg. 1996 Dec;85(6):1091-4. Observer reliability in histological grading of astrocytoma stereotactic biopsies.

  •     Breast Cancer – Different Treatment Recommendations 43% of the Time: Seventy-five women with a total of 77 breast lesions were examined. The reviewing panel disagreed with the treatment recommendations 43% of the time (32 cases). The disagreements included breast-conservation therapy instead of mastectomy (13 patients) and different treatment based on a "major change in diagnosis on pathology review. (3.9%)."

Chang JH, et al., Cancer. 2001 Apr 1;91(7):1231-7. The impact of a multidisciplinary breast cancer center on recommendations for patient management: the University of Pennsylvania experience.

  •     Ovarian Cancer – 12.7% Did Not Have Ovarian Cancer

The medical records and pathology slides of 339 women diagnosed with ovarian cancer were reviewed. Forty-three women (12.7%) were discovered not to have ovarian cancer. (28 had other types of cancer and 15 had benign tumors.)

McGowan L, Norris HJ. Surg Gynecol Obstet. 1991 Sep;173(3):211-5. The mistaken diagnosis of carcinoma of the ovary.

  •     Prostate Cancer – Wrong Pathology Would Have Led to Six Unnecessary Prostatectomies: A total of 535 men referred for radical prostatectomy were reviewed. Seven (1.3%) of the men were found to have a benign pathology. “Upon subsequent clinical work up, six of seven men were considered not to have adenocarcinoma, and their surgery was cancelled.”

Epstein JI, et al., Am J Surg Pathol. 1996 Jul;20(7):851-7. Clinical and cost impact of second-opinion pathology. Review of prostate biopsies prior to radical prostatectomy.

  •     Soft Tissue Lesions – Benign Considered Malignant and Malignant Considered Benign: In this study 266 cases of soft tissue lesions were reviewed. A major discrepancy was found in 25% of cases. Of these discrepancies, 45% consisted of benign lesions diagnosed as sarcomas, and 23% were sarcomas diagnosed as benign tumors.

Arbiser ZK, Folpe AL, Weiss SW. Am J Clin Pathol. 2001 Oct;116(4):473-6. Consultative (expert) second opinions in soft tissue pathology. Analysis of problem-prone diagnostic situations.

Getting the pathology wrong is not limited to the U.S. Other countries have found similar problems. For example, in the United Kingdom, 413 cases of sarcoma were reviewed and the diagnosis was confirmed only 76% of the time. The study concluded that "second opinion is essential in cases of presumed sarcoma…to ensure that appropriate treatment is selected." Harris M, Hartley AL, et al., Br J Cancer. 1991 Aug;64(2):315-20. Sarcomas in north west England: I. Histopathological peer review

Do You Need a Second Opinion?

The vast majority of pathologists are excellent physicians and that the diagnoses they render are correct. However, a minority of cases benefit from a second opinion. The problem, of course, is accurately identifying which cases should get a second opinion. To read the rest of the story go to


Of course, none of this information in CancerWire is a substitute for professional medical advice, examination, diagnosis or treatment and you should always seek the advice of your physician or other qualified health professional before starting any new treatment or making any changes to an existing treatment. No information contained in Cancer Monthly or CancerWire including the information above, should be used to diagnose, treat cure or prevent any disease without the supervision of a medical doctor.

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Michael Horwin