Anatomic Abstracts

March 2006

Editors:
Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD

Impact and frequency of anatomic pathology errors in cancer diagnoses

To assess the frequency and clinical impact of errors in the anatomic pathology diagnosis of cancer, the authors examined errors for patients from four hospitals who underwent anatomic pathology tests to determine the presence or absence of cancerous or precancerous lesions. They analyzed one year of retrospective errors detected through a standardized cytologic-histologic correlation process in which patient samesite cytologic and histology specimens were compared. The authors performed medical record reviews to determine patient outcomes. They also measured the institutional frequency, cause—that is, pathologist interpretation or sampling, and clinical impact of diagnostic cancer errors. The authors determined that the frequency of errors in cancer diagnosis was dependent on the institution (P<0.001) and ranged from 1.79 percent to 9.42 percent and from 4.87 percent to 11.8 percent for all correlated gynecologic and nongynecologic cases, respectively. A statistically significant association was found between institution and error cause (P<0.001); the cause of errors resulting from pathologic misinterpretation ranged from 5.0 percent to 50.7 percent. (The remainder were due to clinical sampling.) A statistically significant association was also found between institution and assignment of the clinical impact of error (P<0.001). The aggregated data demonstrated that for gynecologic and nongynecologic errors, 45 percent and 39 percent, respectively, were associated with harm. The pairwise kappa statistic for interobserver agreement on cause of error ranged from 0.118 to 0.737. The authors concluded that errors in cancer diagnosis are reported to occur in up to 11.8 percent of all reviewed cytologic-histologic specimen pairs. To the authors’ knowledge, there is little agreement regarding whether pathology errors are secondary to misinterpretation or poor clinical sampling of tissues and whether pathology errors result in serious harm.

Raab SS, Grzybicki DM, Janosky JE, et al. Clinical impact and frequency of anatomic pathology errors in cancer diagnoses. Cancer. 2005;104:2205–2213.

Reprints: Dr. Stephen S. Raab, Dept. of Pathology, University of Pittsburgh School of Medicine, 5150 Centre Ave., Pittsburgh, PA 15232; raabss@upmc.edu

Cytokeratin 20 expression identifies a subtype of pancreatic adenocarcinoma with decreased overall survival

Cytokeratins are markers of epithelial cell differentiation useful in determining histogenesis for malignancies with an unknown primary. Applying this principle to a single malignancy may identify cancer subtypes with altered developmental pathways. The authors investigated the relevance of two widely used cytokeratins (CKs)—7 and 20—to subtype cancer of the pancreas and identify associations with clinical features. Atissue microarray was constructed using tumor specimens from 103 patients who underwent resection for pancreatic adenocarcinoma with curative intent. Asubset of resection specimens was evaluated for pancreatic intraepithelial neoplasia (PanIN) lesions. Tissues were immunostained using specific anticytokeratin 7 and 20 monoclonal antibodies. CK 7 and 20 expression was present in 96 percent and 63 percent of cases of pancreatic adenocarcinoma, respectively. Ubiquitous CK 7 expression precluded further analysis. Tumoral CK 20 expression was not associated with any histopathologic parameter but correlated with worse prognosis when considered a dichotomous (P=0.0098) or continuous (P=0.007) variable. In a multivariate model, tumoral CK 20 expression remained a significant independent prognosticator. CK 20 expression was absent in all PanIN lesions from the eight resection specimens in which the tumor component was negative for CK 20. In contrast, the presence of tumoral CK 20 was highly concordant with its expression in corresponding PanINs. The authors concluded that CK 20 expression defines a subtype of pancreas cancer with important biologic properties. When present, CK 20 expression is an early event in pancreatic carcinogenesis identifiable in precursor lesions. Additional studies are needed to identify the underlying genetic changes associated with this altered developmental pathway.

Matros E, Bailey G, Clancy T, et al. Cytokeratin 20 expression identifies a subtype of pancreatic adenocarcinoma with decreased overall survival. Cancer. 2006;160:693–702.

Reprints: Dr. Mark Redston, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115; mredston@partners.org