Home >> ALL ISSUES >> 2013 Issues >> Anatomic Pathology Selected Abstracts, 1/13

Anatomic Pathology Selected Abstracts, 1/13

image_pdfCreate PDF

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.

Relationship between PAX2-null secretory cell outgrowths in the oviduct and pelvic serous cancer

With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. The authors recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct increase in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null). They conducted a study in which they examined the relationship of PAX2-null SCOUTs to high-grade serous cancers by comparing oviducts from women with benign gynecologic conditions and high-grade serous cancers. PAX2-null SCOUTs were identified by immunostaining and computed as a function of location, frequency (F) per number of cross-sections examined, and age. The authors examined 639 cross-sections from 35 serous cancers (364) and 35 controls (275). PAX2-null SCOUTs consisted of discrete linear stretches of altered epithelium ranging from cuboidal/columnar to pseudostratified, the latter including ciliated differentiation. They were evenly distributed among proximal and fimbrial tubal sections. A total of 114 (F=.31) and 45 (F=.16) PAX2-null SCOUTs were identified in cases and controls, respectively. Mean individual case-specific frequencies for cases and controls were .39 and .14, respectively. SCOUT frequency increased significantly with age in both groups (P=.01). However, when adjusted for age and the number of sections examined, the differences in frequency between cases and controls remained significant (P=.006). The authors concluded that this study supports a relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer. They propose a unique co-variable in benign oviductal epithelium—the PAX2-null SCOUT—that reflects underlying dysregulation in genes linked to serous neoplasia.

Quick CM, Ning G, Bijron J, et al. PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer. Mod Pathol. 2012;25:449–455.

Correspondence: Dr. C. P. Crum at ccrum@partners.org

Broad range of adverse cutaneous eruptions in patients on tumor necrosis factor-alpha antagonists

Biologic therapies targeting tumor necrosis factor (TNF)-α have become a mainstay in managing a number of autoimmune diseases. The authors reported on a series of adverse skin eruptions in six patients (four female, two male; age, 21–58 years; mean, 39 years) receiving four months to 10 years (mean, 3.1 years) of anti-TNF-α therapies (infliximab, n=4; adalimumab, n=1; or etanercept, n=1). The following drug-associated diagnoses were made in eight skin biopsies performed at Massachusetts General Hospital between March 2007 and October 2010: pustular folliculitis, psoriasis, interface dermatitis, neutrophilic eccrine hidradenitis, Sweet’s syndrome, lupus, vasculitis, and palmoplantar pustulosis. The descriptions of neutrophilic eccrine hidradenitis-like and Sweet’s-like hypersensitivity eruptions induced by anti-TNF-α therapies are the first such cases described in the literature. Each cutaneous eruption improved or resolved by switching to a different TNF-α inhibitor, discontinuing the anti-TNF-α agent, and/or using topical or systemic steroids. There was a clear chronologic relationship with, and clinical remission upon, withdrawal or steroid suppression of the anti-TNF-α agents. The mechanism for such diverse cutaneous eruptions among this class of medications remains poorly understood. The authors concluded that the cutaneous adverse reaction profile of TNF-α inhibitors is broad and should be considered in the histopathologic differential in this clinical setting.

Hawryluk EB, Linskey KR, Duncan LM, et al. Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists. J Cutan Pathol. 2012;39:481–492.

Correspondence: Dr. Rosalynn M. Nazarian at rmnazarian@partners.org

A practical approach to HER2 testing in gastric cancer

Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is approved by the European Medicines Agency to treat patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry 3+ or immunohistochemistry 2+/fluorescence in situ hybridization-positive or immunohistochemistry 2+/silver in situ hybridization-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Approvals are underway in other countries and were recently granted in the United States and Japan. Experience and data from trastuzumab use in breast cancer have highlighted the importance of quality HER2 testing and scoring to ensure accurate identification of patients eligible for treatment. HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology. Gastric cancer more frequently shows HER2 heterogeneity (focal staining) and incomplete membrane staining. Consequently, gastric cancer-specific HER2 testing protocols have been developed and standardized, and it is imperative that these recommendations be followed. Given the predictive value of HER2 protein levels with response in the Trastuzumab for Gastric Cancer (ToGA) study, immunohistochemistry should be the initial testing methodology, and fluorescence in situ hybridization or silver in situ hybridization should be used to retest immunohistochemistry 2+ samples. Bright-field methodologies should be used whenever possible as these are considered superior to fluorescent methodologies for identifying heterogeneous staining. Specific training is required before embarking on HER2 testing in gastric cancer, irrespective of experience with HER2 testing in breast cancer. The authors’ paper provides up-to-date, practical guidance on HER2 testing and scoring in patients with gastric and gastro-esophageal junction cancer, as determined by a panel of expert pathologists with extensive experience in HER2 testing, particularly reflecting the European Medicines Agency-approved indication. It is anticipated that these recommendations will ensure accurate and consistent HER2 testing, which will allow appropriate selection of patients eligible for treatment with trastuzumab.

Rüschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25:637–650.

Correspondence: J. Rüschoff at ruschoff@patho-nordhessen.de

Clinical assessment of PTEN loss in endometrial carcinoma

PTEN (phosphatase and tensin homolog) is a tumor-suppressor gene that negatively regulates the PI3K-AKT signaling pathway, which is implicated in the pathogenesis of endometrial carcinoma. Sanger sequencing has been considered the gold standard for detecting PTEN sequence abnormalities. However, this approach fails to address the epigenetic mechanisms that contribute to functional PTEN protein loss. Using a study cohort of 154 endometrioid and non-endometrioid endometrial carcinomas, the authors performed full-length PTEN sequencing and PTEN immunohistochemistry on each tumor. PTEN sequence abnormalities were detected in a significantly lower proportion of cases (43 percent) than PTEN protein loss (64 percent; P=.0004). Endometrioid tumors had a significantly higher proportion of PTEN sequence abnormalities and PTEN protein loss than non-endometrioid tumors. Within the latter group, PTEN sequence abnormalities and PTEN protein loss were most frequent in undifferentiated carcinomas, followed by mixed carcinomas; they were least frequent in carcinosarcomas. Overall, at least one PTEN sequence abnormality was detected in each exon, and the greatest number of sequence abnormalities was detected in exon 8. Pure-endometrioid tumors had a significantly higher frequency of sequence abnormalities in exon 7 than did non-endometrioid tumors (P=.0199). Importantly, no mutational hotspots were identified. While PTEN protein loss by immunohistochemistry was identified in 89 percent of cases with a PTEN sequence abnormality, PTEN protein loss was detected by immunohistochemistry in 44 percent of cases classified as PTEN wild type by sequencing. For the first time, it was demonstrated that PTEN immunohistochemistry can identify the majority of cases with functional PTEN protein loss. However, PTEN immunohistochemistry also detects additional cases with PTEN protein loss that would otherwise be undetected by gene sequencing. Therefore, for clinical purposes, immunohistochemistry appears to be a preferable technique for identifying endometrial tumors with loss of PTEN function.

Djordjevic B, Hennessy BT, Li J, et al. Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. Mod Pathol. 2012;25:699–708.

Correspondence: Dr. R. R. Broaddus at rbroaddus@mdanderson.org

CAP TODAY
X