Anatomic Abstracts
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April 2012 Editors:
Elective neck dissection is commonly used as a staging and therapeutic procedure for oral squamous cell carcinoma cases at high risk of nodal metastases. The authors conducted a study to determine whether the extent of lymphadenectomy, as defined by nodal yield, is a prognostic factor in this setting. A retrospective database review identified 225 patients undergoing elective neck dissection with curative intent for oral squamous cell carcinoma between 1987 and 2009. Nodal yield was studied as a categorical variable for association with overall, disease-specific, and disease-free survival in univariate and multivariate analyses. Nodal yield of less than 18 was associated with a five-year overall survival rate of 51 percent, compared with 74 percent for those with a nodal yield of 18 or greater (P=0.009). Five-year disease-specific survival rates were 69 percent for those with fewer than 18 nodes and 87 percent for patients with 18 or more nodes (P=0.022). Similar results were obtained for disease-free survival, with five-year rates of 44 percent with fewer than 18 nodes versus 71 percent with 18 or more nodes (P=0.043). After adjusting for the effects of age, nodal status, T stage, and adjuvant radiotherapy on multivariate analysis, nodal yield of less than 18 was associated with reduced overall (hazard ratio [HR], 2.0; 95 percent confidence interval [CI], 1.1–3.6; P=0.020), disease-specific (HR, 2.2; 95 percent CI, 1.1–4.5; P=0.043), and disease-free (HR, 1.7; 95 percent CI, 1.1–2.8; P=0.040) survival rates. Similar results were obtained in the pathologically lymph node-negative subgroup (n=148). The authors concluded that nodal yield is an independent prognostic factor for patients undergoing elective neck dissection for oral squamous cell carcinoma. These results suggest that an adequate lymphadenectomy in this setting should include at least 18 nodes. Ebrahimi A, Zhang WJ, Gao K, et al. Nodal yield and survival in oral squamous cancer: defining the standard of care. Cancer. 2011;117(13):2917–2925. Correspondence: Ardalan Ebrahimi at arda lan100@hotmail.com
The authors conducted a study to evaluate whether the incidence of eosinophilic esophagitis in children had increased and whether the histologic diagnosis of EE had been accurate. They also assessed potential interobserver variability in the counting of intraepithelial eosinophils in esophageal biopsies. A total of 1,215 pediatric endoscopic esophageal biopsies were performed. One pathologist reviewed 289 biopsies based on one of the following original histologic diagnoses: EE, reflux esophagitis (RE), or acute/chronic inflammation. EE was diagnosed when at least one high-power field contained 20 or more intraepithelial eosinophils. According to the first pathologist, 104 biopsies had a histologic diagnosis of EE; the prevalence remained relatively stable, ranging from 5.5 to 11 per 100 biopsies annually. In 36 cases, the reporting pathologist correctly diagnosed EE, and in another 34, EE was included in the differential diagnosis. From January 1997 to December 1998, the pathologist either correctly diagnosed EE or included it in the differential diagnosis in six of 13 cases. In contrast, from January 2004 to December 2005, 32 of 37 cases were included. In 34 of 104 cases, EE was misdiagnosed as RE. No case of RE was misdiagnosed as EE. A total of 58 cases had pathology reports that quantified the densest number of eosinophils per high-power field. The agreement rate was 94.8 percent, with a K-value of 0.888. The incidence of EE in children was stable from January 1997 to December 2005. Overall, pathologists recognized EE in two-thirds of cases. The authors concluded that increased diagnostic accuracy over time suggests pathologists are more aware of EE. Patel NP, Bussler JF, Geisinger KR, et al. Are pathologists accurately diagnosing eosinophilic esophagitis in children? A 9-year single academic institutional experience with interobserver observations. Int J Surg Pathol. 2011;19: 290–296. Correspondence information not available.
The epidermal growth factor receptor is overexpressed in 70 percent to 90 percent of cervical cancers. The authors previously have shown that epidermal growth factor receptor overexpression independently predicts poor prognosis in cervical cancer patients, which makes it a potential therapeutic target. The authors conducted a study to systematically analyze the molecular mechanism leading to epidermal growth factor receptor overexpression in cervical cancer. They performed all experiments on archival paraffin-embedded material. The authors studied cytoplasmic, membrane, and phosphorylated epidermal growth factor receptor protein expression in association with patient survival in 166 cervical cancer patients. Membrane epidermal growth factor receptor overexpression was associated with poor disease-specific survival (P=0.027). This association was particularly prevalent in human papillomavirus 16-positive patients (P=0.029). The authors determined whether epidermal growth factor receptor overexpression was caused by gene amplification using fluorescence in situ hybridization. Epidermal growth factor receptor gene copy number was linked to chromosome 7 ploidy as no gene amplification could be detected when corrected for chromosome 7 centromeric signals. Chromosome 7 aneuploidy was associated with membrane epidermal growth factor receptor overexpression (P=0.013). Additional mutation analysis was performed by sequencing pure, flow-sorted tumor cells, but no mutations were detected. Furthermore, human papillomavirus 16 E5 and E6 oncogene mRNA expression was measured, using quantitative real-time polymerase chain reaction, to determine the association between human papillomavirus and epidermal growth factor receptor overexpression. High human papillomavirus 16 E5 and E6 mRNA expression were associated with decreased survival (P=0.045 and P=0.047, respectively). High human papillomavirus 16 E6 mRNA expression was also associated with membrane epidermal growth factor receptor overexpression (P=0.013). The authors concluded that this is the first study performed on cancer patient material that shows that chromosome 7 aneuploidy and high human papillomavirus 16 E6 mRNA expression lead to membrane epidermal growth factor receptor overexpression in cervical cancer. Schrevel M, Gorter A, Kolkman-Uljee SM, et al. Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer. Mod Pathol. 2011;24:720–728. Correspondence: Dr. Marlies Schrevel at m.schrevel@lumc.nl
The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype with biological behavior that ranges from clinically aggressive to clinically indolent. Tumor size, circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables, including genetic changes and putative biomarkers associated with malignant growth, have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed, or encapsulated and from younger female patients. Aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAFV600E), was detected in three of the nine cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasia-associated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in indolent and aggressive tumors. Expression of β-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was, overall, mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in indolent and aggressive neoplasms but was without gender- or age-related differences. However, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. The authors concluded that recognizing the clinicopathological characteristics and molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Chen JH, Faquin WC, Lloyd RV, et al. Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma. Mod Pathol. 2011;24:739–749. Correspondence: Dr. V. Nosé at vnose@med.miami.edu
Frozen-section analysis is an essential tool for assessing margins intra-operatively to assure complete resection. Many institutions evaluate surgical defect edge tissue provided by the surgeon after the main lesion has been removed. This method is becoming even more prevalent with the increasing use of transoral laser microsurgery. The authors evaluated error rates at their large academic institution and evaluated whether sampling errors could be reduced simply by taking an additional third section from these specimens. All head and neck tumor resection cases from January 2005 through August 2008 with margins evaluated by frozen section were identified by a database search. These cases were analyzed by cutting two levels during frozen section and a third permanent section later. All resection cases from August 2008 through July 2009 were identified as well. These were analyzed by cutting three levels during frozen section (the third a much deeper level) and a fourth permanent section later. The authors determined error rates for both of these periods. They separated errors into sampling and interpretation types. The evaluation involved 4,976 frozen-section specimens from 848 patients. The overall error rate was 2.4 percent for all frozen sections for which two levels were evaluated and 2.5 percent if three levels were evaluated (P=0.67). The sampling error rate was 1.6 percent for two-level sectioning and 1.2 percent for three-level sectioning (P=0.42). However, when considering only the frozen-section cases in which tumor was ultimately identified (either at the time of frozen section or on permanent sections), the sampling error rate for two-level sectioning was 15.3 percent versus 7.4 percent for three-level sectioning. This difference was statistically significant (P=0.006). The authors concluded that cutting a single additional deeper level at the time of frozen section identifies more tumor-bearing specimens and may reduce the number of sampling errors. Olson SM, Hussaini M, Lewis JS Jr. Frozen section analysis of margins for head and neck tumor resections: reduction of sampling errors with a third histologic level. Mod Pathol. 2011;24:665–670. Correspondence: Dr. J. S. Lewis Jr. at jlewis@path.wustl.edu 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, assistant professor of pathology and laboratory medicine, University of Kentucky College of Medicine; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill. |
