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.
Preoperative diagnosis of benign thyroid nodules with indeterminate cytology
Approximately 15 percent to 30 percent of thyroid nodules evaluated by fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. The authors performed a 19-month, prospective, multicenter validation study (funded by Veracyte) involving 49 clinical sites, 3,789 patients, and 4,812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. They obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules, and its performance was assessed. The authors found that of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92 percent sensitivity; 95 percent confidence interval [CI], 84–97) with a specificity of 52 percent (95 percent CI, 44–59). The negative predictive values for atypia (or follicular lesion) of undetermined clinical significance, follicular neoplasm or lesion suspicious for follicular neoplasm, and suspicious cytologic findings were 95 percent, 94 percent, and 85 percent, respectively. An analysis of seven aspirates with false-negative results revealed that six had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. The authors concluded that these data support consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results.
Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367(8):705–715.
Correspondence: Dr. E. K. Alexander at ekalexander@partners.org
Stem cell-related markers in primary breast cancers and associated metastatic lesions
It has been reported that normal breast epithelial cells that are CD24-/44+ express higher levels of stem/progenitor cell-associated genes. It has also been reported that cancer cells that have undergone epithelial to mesenchymal transition display CD24-/44+ cell-surface expression, a marker for breast cancer stem cells; that loss of E-cadherin is a preliminary step in epithelial to mesenchymal transition; and that vimentin is a marker of mesenchymal phenotype. The authors hypothesized that stem cell subpopulations would be more frequent in metastatic than in primary tumors. Therefore, they assessed, by immunohistochemical analysis, tissue microarrays containing tissue from primary and associated metastatic breast cancers for expression of CD24, CD44, E-cadherin, and vimentin to evaluate candidate cancer-initiating cell populations in breast cancer subtypes and metastatic lesions. The occurrence of CD24-/44+ and CD24+/44- cells did not differ in primary versus matched lymph node or distant and locoregional metastatic lesions. E-cadherin expression was decreased in primary versus lymph node metastases (P=.018) but not in distant and locoregional metastases relative to primary tumor. Vimentin was more frequently expressed in lymph node and distant and locoregional metastases (P=.013; P=.004) than in matched primary cancers. The authors concluded that the frequency of CD24-/44+ cells does not differ in metastases relative to the primary breast cancer but differs by tumor stage and subtype.
Guler G, Balci S, Costinean S, et al. Stem cell-related markers in primary breast cancers and associated metastatic lesions. Mod Pathol. 2012;25:949–955.
Correspondence: Dr. K. Huebner at kay.huebner@osumc.edu
DOG1: a marker of salivary acinar and intercalated duct differentiation
Anoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel initially described in gastrointestinal stromal tumors but now known to be expressed in a variety of normal and tumor tissues, including salivary tissue in murine models. The authors performed a comprehensive survey of DOG1 expression in 156 cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA levels were significantly higher (eight-fold increase; P<.0001) in normal parotid tissue (n=6) than in squamous mucosa (n=15). By immunohistochemistry, DOG1 showed a diffuse moderate (2+) apical membranous staining pattern in normal serous acini, 1+ apical membranous pattern in mucous acini, and variable 1–2+ apical staining of distal intercalated ducts. Myoepithelial cells and striated and excretory ducts were invariably negative. All acinic cell carcinomas (n=28) were DOG1 positive, demonstrating a complex mixture of intense (3+) apical membranous, cytoplasmic, and complete membranous staining. Most ductal tumor types were negative or showed only a subset of positive cases. Within the biphasic tumor category, adenoid cystic carcinomas (18 of 24 cases) and epithelial-myoepithelial carcinomas (eight of 15 cases) were frequently positive, often showing a distinctive combined apical ductal and membranous/cytoplasmic myoepithelial staining profile. Therefore, DOG1 staining is a marker of salivary acinar and, to a lesser extent, intercalated duct differentiation. Strong staining can be used to support the diagnosis of acinic cell carcinoma. DOG1 may also be a marker of a transformed myoepithelial phenotype in a subset of biphasic salivary gland malignancies.
Chênevert J, Duvvuri U, Chiosea S, et al. DOG1: a novel marker of salivary acinar and intercalated duct differentiation. Mod Pathol. 2012;25:919–929.
Correspondence: Dr. R. R. Seethala at seethalarr@upmc.edu