Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD
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.
Reprints: Dr. Stephen S. Raab, Dept. of Pathology, University of Pittsburgh
School of Medicine, 5150 Centre Ave., Pittsburgh, PA 15232; email@example.com
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.
Reprints: Dr. Mark Redston, Brigham and Women’s Hospital, 75 Francis
St., Boston, MA 02115; firstname.lastname@example.org
Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Lele is assistant professor of pathology and laboratory medicine, University of Kentucky Medical Center. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.