CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.
Pseudomyxoma peritonei of appendiceal origin treated with cytoreductive surgery and chemotherapy
Pseudomyxoma peritonei originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The authors conducted a study to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. A retrospective multi-institutional registry was established through the collaborative efforts of units affiliated with the Peritoneal Surface Oncology Group International. A total of 2,298 patients from 16 specialized units underwent CRS for pseudomyxoma peritonei. Treatment-related mortality was two percent, and major operative complications occurred in 24 percent of patients. The median survival rate was 196 months (16.3 years), and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63 percent and 59 percent, respectively. Multivariate analysis identified the following as independent predictors of a poorer progression-free survival: prior chemotherapy treatment (P<.001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P<.001), major postoperative complications (P=.008), high peritoneal cancer index (P=.013), debulking surgery (completeness of cytoreduction [CCR], two or three; P<.001), and not using HIPEC (P=.030). Independent predictors of poorer overall survival were older age (P=.006), major postoperative complications (P<.001), debulking surgery (CCR, two or three; P<.001), prior chemotherapy treatment (P=.001), and PMCA histopathologic subtype (P<.001). The authors concluded that the combined modality strategy for pseudomyxoma peritonei may be performed safely, with acceptable morbidity and mortality, in a specialized unit setting, with 63 percent of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may improve outcomes with this therapy and boost long-term survival. Optimal cytoreduction generates the best outcomes.
Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30:2449–2456.
Correspondence: Terence Chua at terence.chua@unsw.edu.au
An audit of dermatopathology requisitions: handwritten vs. EMR data-entry accuracy
Dermatopathology case requisitions are sent to the authors’ institution in handwritten form or via electronic medical record. Requisition data entry can be divided into the categories of patient demographics, physician name, and procedure site/date. Systematic data-entry problems potentially cause considerable documentation error, propagate inaccurate patient information, and potentially delay billing/revenue collection. The authors conducted a study in which they compared dermatopathology data-entry errors on handwritten requisitions to data-entry errors using an electronic medical record (EMR). A total of 11,475 requisitions (8,545 handwritten and 2,930 via EMR) were included in the study, which ran from April through September 2011. The authors found that the handwritten requisitions generated 258 data-entry errors on 8,545 specimens (three percent), while the requisitions entered via the EMR generated 113 errors on 2,930 specimens (3.9 percent). Container labeling, which is a handwritten process for both requisition methods, was the most common source of error. The authors concluded that even with an EMR, containers are at least partially hand labeled, and 96 percent of EMR errors occurred during the hand-labeling process. Other EMR data-entry errors are extremely uncommon (four of 2,930 cases). These findings suggest that introducing a labeling process entirely linked to EMR data entry could nearly eliminate data-entry errors. Although this study focused solely on dermatopathology cases, the findings can be extrapolated to all types of specimens.
Kinonen CL, Watkin WG, Gleason BC, et al. An audit of dermatopathology requisitions: hand written vs. electronic medical record data entry accuracy. J Cutan Pathol. 2012;39(9):850–852.
Correspondence: Dr. Thomas Cibull at tcibull@northshore.org
Intratumoral heterogeneity of HER2 gene amplification in breast cancer
Intratumoral heterogeneity of human epidermal growth factor receptor 2 gene amplification has been reported to occur with variable frequencies in breast cancers. However, there have been few studies of its clinicopathological significance. The authors used tissue microarrays to evaluate two aspects of intratumoral heterogeneity of HER2 gene amplification: regional heterogeneity and genetic heterogeneity. They examined 96 invasive breast cancers in which HER2 amplification had been diagnosed in whole sections and determined the clinicopathological characteristics of those tumors. HER2 regional heterogeneity, defined as the existence of amplification-negative or amplification-equivocal patterns in different tissue microarray cores of a tumor, was present in 17 (18 percent) of the 96 cases. HER2 genetic heterogeneity, defined as the presence of tumor cells with a HER2/chromosome enumeration probe 17 ratio higher than 2.2 in five to 50 percent of the tumor cells, was found in 11 (11 percent) cases, all of which showed HER2 regional heterogeneity. The cases with intratumoral heterogeneity of HER2 gene amplification were characterized by low-grade or equivocal HER2 amplification and equivocal (2+) HER2 expression in whole sections. The patients with intratumoral heterogeneity of HER2 gene amplification had significantly shorter disease-free survival times than those with homogeneous HER2 gene amplification. This effect was also evident in subgroup analysis by hormone receptor status. In multivariate analysis, intratumoral HER2 heterogeneity retained its status as an independent prognostic factor for disease-free survival. The authors concluded that intratumoral heterogeneity of HER2 gene amplification is present in a subset of HER2-amplified breast cancers, especially in cases with low-grade HER2 amplification and equivocal HER2 expression, indicating a need for HER2 testing on larger, more representative tumor samples to accurately assess HER2 status in such cases. The patients with this heterogeneity have decreased disease-free survival rates, suggesting that genetic instability and hence aberrant HER2 amplification in subclones of such tumors may be associated with breast cancer progression.
Seol H, Lee HJ, Choi Y, et al. Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol. 2012;25:938–948.
Correspondence: Dr. S. Y. Park at sypmd@snu.ac.kr
An immunohistochemical and JAZF1 rearrangement study of endometrial sarcomas
The World Health Organization classifies endometrial sarcomas as either low-grade endometrial stromal sarcoma or undifferentiated endometrial sarcoma. Studies suggest that undifferentiated endometrial sarcoma is a heterogeneous group, and a subgroup with uniform nuclei is more akin to low-grade endometrial stromal sarcoma in terms of morphologic, immunohistochemical, and genetic features. The authors classified endometrial sarcomas treated at their institution from 1998 to 2011 into low-grade endometrial stromal sarcoma or undifferentiated endometrial sarcoma as well, the latter being further categorized into a group with either uniform or pleomorphic nuclei. Morphological features, immunoprofile, and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome. The authors evaluated 40 cases, comprising 23 low-grade endometrial stromal sarcomas, 10 undifferentiated endometrial sarcomas with nuclear uniformity, and seven undifferentiated endometrial sarcomas with nuclear pleomorphism. Low-grade endometrial stromal sarcomas were more often estrogen and progesterone receptor positive (83 percent) compared with undifferentiated endometrial sarcoma with nuclear uniformity (10 percent) or nuclear pleomorphism (none; P<.001). Positivity for p53 was restricted to undifferentiated endometrial sarcomas, with more frequent expression in the group with nuclear pleomorphism (57 percent) than with nuclear uniformity (10 percent; P=.06). Ki-67 proliferation index in more than 10 percent of tumor cells was more frequent in undifferentiated endometrial sarcoma than in low-grade endometrial stromal sarcoma (P<.001). JAZF1 rearrangement was detected in 32 percent of low-grade endometrial stromal sarcomas and none of the undifferentiated sarcomas. Rearrangement of PHF1 was found in two patients, one with JAZF1–PHF1 fusion. No significant differences in clinical behavior were noted between undifferentiated endometrial sarcoma with nuclear uniformity and nuclear pleomorphism. The authors concluded that undifferentiated endometrial sarcoma subtypes and low-grade endometrial stromal sarcoma have distinct immunohistochemical and cytogenetic profiles. The data do not show any difference in clinical behavior between the subgroups of undifferentiated sarcomas.
Jakate K, Azimi F, Ali RH, et al. Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors. Mod Pathol. 2013;26:95–105.
Correspondence: Dr. M. Rouzbahman at marjan.rouzbahman@uhn.on.ca