CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Atypical Spitz tumors with chromosomal copy number aberrations and conventional melanomas in children
Death due to melanoma in childhood (up to 20 years of age) is a rare event, with an average of 18 cases reported annually in the United States. In this study, the authors evaluated two subgroups of high-risk melanocytic neoplasms in childhood, specifically atypical Spitz tumors with chromosomal copy number changes and conventional melanomas. They analyzed the clinical, histologic, and molecular features of all cases and performed the Fisher exact test, logistic regression, and multivariate analysis to evaluate features associated with aggressive clinical behavior in these cases. Among the atypical Spitz tumors, all of which had one or more chromosomal copy number aberrations, the presence of homozygous 9p21 deletions and a positive sentinel lymph node were found to be correlated with tumor extension beyond the sentinel lymph node (P=0.046 and 0.01, respectively). Two patients with atypical Spitz tumors that had homozygous 9p21 deletions developed brain metastasis, and one died of disease. Among the 21 patients with conventional melanomas, three patients developed distant metastasis and died of disease. Chromosomal copy number aberrations evaluated by fluorescence in situ hybridization were present in the majority of the cases (16 of the remaining 18). Among the conventional melanomas, the authors did not identify any clinical, histologic, or molecular features associated with aggressive behavior. The presence of 8q24 gains was seen almost exclusively in six amelanotic small cell melanomas in children, one of whom died of disease. The authors concluded that characteristic chromosomal copy number aberrations may occur in specific subtypes of melanocytic neoplasms in children and may help with the classification and prognostication of these rare tumors.
Gerami P, Cooper C, Bajaj S, et al. Outcomes of atypical Spitz tumors with chromosomal copy number aberrations and conventional melanomas in children. Am J Surg Pathol. 2013; 37:1387–1394.
Correspondence e-mail address not provided.
Value of methylene blue-assisted lymph node dissection technique
in colorectal cancer cases
Lymph node staging is of paramount importance for estimating prognosis and stratifying therapy for colorectal cancer. A high number of harvested lymph nodes is associated with improved outcome. Methylene blue-assisted lymph node dissection improves the lymph node harvest and ensures sufficient staging. The authors investigated the effect of the advanced lymph node dissection technique on node positivity rate and stage-related outcome. The study cohort consisted of 669 colorectal cancer cases of all stages with advanced lymph node dissection collected between 2007 and 2012. A historical collection of 663 cases investigated with conventional techniques between 2002 and 2004 served as the control. The authors found that lymph node harvest was dramatically improved in the study group, with mean lymph node numbers of 34±17 versus 13±5 (P<0.001) and sufficient staging rates of 98 percent versus 62 percent (P<0.001). However, neither the rate of nodal positive cases (37 percent versus 37 percent; P=0.98) nor N2 cases differed between the two groups (14 percent versus 13 percent; P=0.80). Furthermore, no differences in outcome were noted between the groups. The authors concluded that the advanced lymph node dissection technique guarantees adequate histopathological lymph node staging in virtually all cases of colorectal cancer and is, therefore, extremely helpful. However, the hypothesis that it also provides a higher sensitivity in detecting metastases could not be proved.
Märkl B, Schaller T, Krammer I, et al. Methylene blue-assisted lymph node dissection technique is not associated with an increased detection of lymph node metastases in colorectal cancer. Mod Pathol. 2013;26:1246–1254.
Correspondence: Dr. B. Märkl at bruno.maerkl@klinikum-augsburg.de
Use of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors
Low-grade serous carcinomas and serous borderline tumors, jointly referred to as low-grade serous tumors herein, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. Differentiating between low-grade serous tumors and high-grade serous carcinomas using small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease, can be challenging. The authors conducted a study to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors confirmed by contemporary histopathological review were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern, or overexpressed (more than 60 percent). CDKN2A was scored as negative/patchy (fewer than 90 percent) or block expression (more than 90 percent). The combination of TP53 wild-type pattern and CDKN2A patchy expression had sensitivity for low-grade serous tumors of 89 percent, specificity of 93 percent, positive predictive value of 68 percent, and negative predictive value of 98 percent. The authors concluded that these markers can be used on small biopsies or cell blocks to refute a diagnosis of low-grade serous tumors. These findings may influence emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial to future clinical trials on molecular-based therapies.
Altman AD, Nelson GS, Ghatage P, et al. The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors. Mod Pathol. 2013;26(9):1255–1263.
Correspondence: Dr. M. Köbel at martin.koebel@cls.ab.ca
Use of immunohistochemical stains for CD3 and CD8 in detecting gluten-sensitive enteropathy in duodenal biopsies
Patients with gluten-sensitive enteropathy usually have increased numbers of duodenal intraepithelial lymphocytes, even if the villous architecture is normal. Some authors advocate the use of CD8 and CD3 immunohistochemical stains to improve detection of intraepithelial lymphocytosis, yet the added value of immunohistochemistry when biopsies appear normal remains unproven. The authors conducted a study to evaluate the utility of CD3 and CD8 immunostains in detecting intraepithelial lymphocytosis among duodenal biopsies originally interpreted to be normal based on routine evaluation. They identified 200 duodenal biopsies from 172 patients, all of which were accompanied by a clinical question of gluten-sensitive enteropathy. Five well-oriented villi from each biopsy were assessed. Intraepithelial lymphocytes present in hematoxylin-and-eosin–stained slides were counted and compared with the number of CD3 and CD8 immunopositive cells present in the villous epithelium. Results were expressed as the mean number of intraepithelial lymphocytes or immunopositive cells present per 20 villous tip enterocytes. Review of H&E-stained slides revealed a mean of 2.1±0.1 intraepithelial lymphocytes, compared with 3.2±0.1 CD3-positive and 2.1±0.1 CD8-positive intraepithelial cells (P=
Hudacko R, Kathy Zho X, Yantiss RK. Immunohistochemical stains for CD3 and CD8 do not improve detection of gluten-sensitive enteropathy in duodenal biopsies. Mod Pathol. 2013;26:1241–1245.
Correspondence: Dr. R. K. Yantiss at rhy2001@med.cornell.edun