CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anatomic pathology abstracts editors: Michael Cibull, MD, professor of pathology, University of Kentucky, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.; and Rachel Stewart, DO, resident physician, Department of Pathology and Laboratory Medicine, University of Kentucky.
Value of autopsies in the era of high-tech medicine
Although the autopsy is still the gold standard for quality assessment of clinical diagnoses, autopsy rates have declined to less than 10 percent. The authors conducted a study to investigate the value of autopsies in the era of high-tech medicine by determining the frequency of discrepancies between clinical and autopsy diagnoses. The authors classified all adult autopsy cases (n=460) performed at the Symbiant Pathology Expert Centre in Holland, in 2007 and from 2012 to 2013, as having major or minor discrepancy or total concordance. They analyzed the roles of possible contributory factors and assessed the role of microscopic examination in identifying cause of death. Major and minor discrepancies were found in 23.5 percent and 32.6 percent of the classifiable autopsies, respectively. The most commonly observed major discrepancies were myocardial infarction, pulmonary embolism, and pneumonia. Improper imaging and discontinuation of active treatment were significantly associated with a higher and lower frequency of major discrepancies, respectively. Comparing 2007 and 2012 to 2013, the frequency of minor discrepancies significantly increased from 26.8 percent to 39.3 percent. Final admission length of more than two days was significantly associated with a lower frequency of class III minor discrepancies. Microscopic examination contributed to establishing cause of death in 19.6 percent of the cases. The authors concluded that discrepant findings persist at autopsy, even in the era of high-tech medicine. Therefore, autopsies should still serve as an important part of quality control in clinical diagnosis and treatment. Learning from individual and system-related diagnostic errors can help improve patient safety.
Kuijpers CC, Fronczek J, van de Goot FR, et al. The value of autopsies in the era of high-tech medicine: discrepant findings persist. J Clin Pathol. 2014;67:512–519.
Correspondence: Dr. Mehdi Jiwa at m.jiwa@symbiant.nl
Keratin 17 in premalignant and malignant squamous lesions of the cervix safety.
Most previously described immunohistochemical markers of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma may help improve diagnostic accuracy but have minimal prognostic value. The authors conducted a study to identify and validate novel candidate biomarkers that could potentially improve diagnostic and prognostic accuracy for cervical HSIL and squamous cell carcinoma. Microdissected tissue sections from formalin-fixed, paraffin-embedded normal ectocervical squamous mucosa, low-grade squamous intraepithelial lesion (LSIL), HSIL, and squamous cell carcinoma sections were analyzed by mass spectrometry-based shotgun proteomics for biomarker discovery. The diagnostic specificity of candidate biomarkers was subsequently evaluated by immunohistochemical analysis of tissue microarrays. Among 1,750 proteins identified by proteomic analyses, keratin 4 and keratin 17 showed reciprocal patterns of expression in the spectrum of cases ranging from normal ectocervical squamous mucosa to squamous cell carcinoma. Immunohistochemical studies confirmed that keratin 4 expression was significantly decreased in squamous cell carcinoma compared with the other diagnostic categories. By contrast, keratin 17 expression was significantly increased in HSIL and squamous cell carcinoma compared with normal ectocervical squamous mucosa and LSIL. Keratin 17 was also highly expressed in immature squamous metaplasia and endocervical reserve cells but was generally not detected in mature squamous metaplasia. Furthermore, high levels of keratin 17 expression were significantly associated with poor survival of squamous cell carcinoma patients (hazard ratio, 14.76; P=0.01). The authors concluded that the level of keratin 17 in squamous cell carcinoma may help identify patients who are at greatest risk for cervical cancer mortality.
safety.
Escobar-Hoyos LF, Yang J, Zhu J, et al. Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker. Mod Pathol. 2014;27(4):621–630.
safety.
Correspondence: K. R. Shroyer at kenneth.shroyer@stonybrook medicine.edu
Hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer
The clinical behavior of human epidermal growth factor receptor 2-positive breast cancer, including pathologic complete response rate and pattern of relapse and metastasis, differs substantially according to hormone receptor (HR) status. The authors investigated various histopathologic features of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and their correlation with HR status. They retrospectively analyzed tumors from 450 HER2-positive breast cancer patients treated with chemotherapy and one year of trastuzumab. HR-negative/HER2-positive tumors showed higher nuclear grade, less tubule formation, higher histologic grade, frequent apocrine features, diffuse and abundant lymphocytic infiltration, strong HER2 immunohistochemical staining (3+), higher average HER2 copy number and HER2/CEP17 ratio, absence of HER2 genetic heterogeneity, and greater p53 expression than HR-positive/HER2-positive tumors. An inverse correlation was observed between estrogen receptor or progesterone receptor Allred score and average HER2 copy number or HER2/CEP17 ratio. The percentage of ductal carcinoma in situ (DCIS) within the tumor was negatively correlated with estrogen receptor Allred score but positively correlated with average HER2 copy number and HER2/CEP17 ratio. Pathologic tumor size and DCIS percentage also showed a significant inverse correlation. Ratio of metastatic to total examined lymph node number was significantly correlated with average HER2 copy number and HER2/CEP17 ratio. High pT stage (hazard ratio, 2.370; P=0.027), presence of lymphovascular invasion (hazard ratio, 2.806; P=0.005), and HR negativity (hazard ratio, 2.202; 1.074–4.513; P=0.031) were independent prognostic indicators of poor disease-free survival. The authors concluded that HR-positive/HER2-positive and HR-negative/HER2-positive breast cancer showed distinct histopathologic features that may be relevant to their clinical behavior.
Lee HJ, Park IA, Park SY, et al. Two histopathologically different diseases: hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer. Breast Cancer Res Treat. 2014;145(3):615–623.
Correspondence: G. Gong at gygong@amc.seoul.kr