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Anatomic Pathology Selected Abstracts, 10/14

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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.

Role of STAT6 immunohistochemistry in diagnosis of solitary fibrous tumors

Solitary fibrous tumor is an uncommon fibroblastic neoplasm. Although histologic characteristics and frequent CD34 expression allow for an accurate diagnosis in the majority of solitary fibrous tumor (SFT) cases, a wide histologic spectrum and occasional unexpected immunophenotype may pose diagnostic challenges. Molecular analyses have shown that almost all SFTs harbor a NAB2-STAT6 fusion gene, which is considered specific to this tumor type. Recent studies have suggested that STAT6 immunohistochemistry is a reliable surrogate for detecting the fusion gene. The authors conducted a study to validate these findings by examining a large number of SFT cases and 30 types of non-SFT tumors. Forty-nine SFTs with a range of histologic characteristics and 159 benign or malignant tumors that can mimic SFTs were retrieved and stained for STAT6. All of the 49 SFTs showed STAT6 expression that was restricted in the nucleus, mostly in a diffuse and strong manner, irrespective of tumor sites and histologic patterns. The staining was uniform in most cases but heterogeneous in about 20 percent of the cases in which zonal staining attenuation was observed, likely reflecting variability in fixation or tissue ischemia. In contrast, only four non-SFT tumors (2.5 percent) exhibited weak nuclear STAT6 expression, whereas the remaining 155 cases showed no staining or often weak reactivity in the cytoplasm and nucleus. The authors concluded that nuclear STAT6 immunoreactivity is a highly sensitive and specific marker of SFTs and can be helpful when diagnosis by conventional methods is inconclusive.

Yoshida A, Tsuta K, Ohno M, et al. STAT6 immunohistochemistry is helpful in the diagnosis of solitary fibrous tumors. Am J Surg Pathol. 2014;38(4):552–559.

Correspondence email not provided.

Incidence and significance of neuroendocrine differentiation in invasive breast carcinoma

The definition of invasive breast carcinoma with neuroendocrine differentiation and its clinical outcomes have been the focus of controversy. The authors investigated the incidence and clinical significance of neuroendocrine (NE) differentiation in patients with invasive breast carcinoma (IBC). They performed immunohistochemistry for NE markers, chromogranin A, and synaptophysin on 1,428 IBC samples using tissue microarrays and classified cases with NE differentiation into two groups: focal (one to 49 percent of tumor cells positive for any NE marker) and diffuse (50 percent or more tumor cells positive for any NE marker). Fifty-nine cases (4.1 percent) showed NE differentiation immunohistochemically, and the majority did not show typical NE morphology. NE differentiation showed a significant association with positive oestrogen receptor (P=0.001) and progesterone receptor (P=0.008) status. Patients with NE differentiation exhibited worse overall survival and disease-free survival than those without NE differentiation in univariate (P

Kwon SY, Bae YK, Gu MJ, et al. Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma. Histopathol. 2014;64:647–659.

Correspondence: Y. K. Bae at ykbae@ynu.ac.kr

Venous invasion in oesophageal adenocarcinoma: enhanced detection using elastic stains

In oesophageal adenocarcinoma, detection rates of venous invasion using H&E and elastic stains have not been compared. The authors conducted a study to investigate whether or not elastic stains facilitate the detection of venous invasion and to determine the prognostic significance of venous invasion following review with elastic stains. The authors examined 103 resection specimens containing oesophageal adenocarcinoma (all originally reported as negative for venous invasion) for the presence of venous invasion using H&E and subsequently Movat pentachrome stains. Venous invasion was detected in eight cases with H&E and an additional 66 cases using Movat pentachrome; overall, 72 percent of cases contained venous invasion. Venous invasion was associated with advanced stage, tumor size, lymphatic and perineural invasion, and subsequent distant metastases. Venous invasion, stage, size, grade, lymphatic invasion, and perineural invasion were prognostically significant on univariate analysis. Only tumor stage was independently prognostic. Two of eight patients with venous invasion but no other indication for adjuvant treatment died of recurrent disease. The authors concluded that elastic stains improve detection of venous invasion significantly in oesophageal adenocarcinoma. Venous invasion is associated with multiple adverse clinicopathological features. Its identification may help stratify patients at risk for visceral metastases and disease-related death.

Castonguay MC, Li-Chang HH, Driman DK. Venous invasion in oesophageal adenocarcinoma: enhanced detection using elastic stain and association with adverse histological features and clinical outcomes. Histopathol. 2014;64:693–700.

Correspondence: Dr. D. K. Driman at ddriman@uwo.ca

A retrospective comparison of HER2 immunohistochemistry and FISH in breast carcinomas

In 2007, the American Society of Clinical Oncology/College of American Pathologists developed new recommendations for HER2 testing and redefined HER2 positivity. The objective of this study was to analyze results from simultaneous HER2 testing with immunohistochemistry and FISH in 2,590 invasive breast carcinomas between 2002 and 2010 using two scoring systems. Cases from between 2002 and 2006 were scored using original Food and Drug Administration criteria (n=1,138), and those from between 2007 and 2010 were evaluated according to American Society of Clinical Oncology/College of American Pathologists criteria (n=1,452). Concordance between testing methods and clinicopathologic associations were determined. Overall concordance between immunohistochemistry/FISH in the nine-year period was 96.2 percent (κ=0.82), and positive concordance was lower. After 2007, the proportion of HER2/neu-positive and HER2/neu-negative cases was not significantly changed when using immunohistochemistry (10.5 versus 8.9 percent, P=0.22; and 69.4 versus 63 percent, P=0.13, respectively), but the number of equivocal cases was higher (19.9 versus 28 percent, P<0.001). While the proportion of negative cases by FISH remained unchanged after 2007 (86.5 versus 88.2 percent, P=0.76), the number of positive cases was lower (13.4 versus 9.2 percent, P<0.001). Furthermore, 38 cases (2.6 percent) were FISH equivocal, 16 of which were also equivocal by immunohistochemistry. Overall, immunohistochemistry/FISH concordance was 95.9 percent between 2002 and 2006 (κ=0.82) and 96.4 percent after 2007 (κ=0.82). However, an approximately 13 percent lower positive assay concordance was noted in the last period. The authors concluded that application of American Society of Clinical Oncology/College of American Pathologists recommendations is associated with comparable overall immunohistochemistry/FISH concordance, reduced positive concordance, and increased equivocal results.

Schalper KA, Kumar S, Hui P, et al. A retrospective population-based comparison of HER2 immunohistochemistry and fluorescence in situ hybridization in breast carcinomas: impact of 2007 American Society of Clinical Oncology/College of American Pathologists criteria. Arch Pathol Lab Med. 2014;138(2):213–219.

Correspondence: Dr. Kurt A. Schalper at kurt.schalper@yale.edu

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