Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

CONTEXT.­: Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications. OBJECTIVES.­: To determine how IPDA for pathologists' diagnoses of non-small cell lung carcinoma (NSCLC) is affected by the addition of a set of mucin and immunohistochemical (IHC) stains to hematoxylin-eosin (H&E) alone, by recent NSCLC reclassifications, by simplification of these classifications, and by pathologists' practice location, pulmonary pathology expertise, practice duration, and lung carcinoma case exposure. DESIGN.­: We used a Web-based survey to present core images of 54 NSCLC cases to 22 practicing pathologists for diagnosis, initially as H&E only, then as H&E plus mucin and 4 IHC stains. Each case was diagnosed according to published 2004, 2011, and 2015 NSCLC classifications. Cohen's kappa was calculated for the 231 pathologist pairs as a measure of IPDA. RESULTS.­: Twenty-two pathologists diagnosed 54 NSCLC cases by using 4 published classifications. IPDA is significantly higher for H&E/mucin/IHC diagnoses than for H&E-only diagnoses. IPDA for H&E/mucin/IHC diagnoses is highest with the 2015 classification. IPDA is estimated higher after collapse of stated diagnoses into subhead or dichotomized classes. IPDA for H&E/mucin/IHC diagnoses with the 2015 World Health Organization classification is similar for community and academic pathologists, and is higher when pathologists have pulmonary pathology expertise, have more than 6 years of practice experience, or diagnose more than 100 new lung carcinoma cases per year. CONCLUSIONS.­: Higher IPDA is associated with use of mucin and IHC stains, with the 2015 NSCLC classification, and with pathologists' pulmonary pathology expertise, practice duration, and frequency of lung carcinoma cases.

Validation of interobserver agreement in lung cancer assessment: hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World Health Organization classification and therapeutically relevant subsets.

CONTEXT: Precise subtype diagnosis of non-small cell lung carcinoma is increasingly relevant, based on the availability of subtype-specific therapies, such as bevacizumab and pemetrexed, and based on the subtype-specific prevalence of activating epidermal growth factor receptor mutations. OBJECTIVES: To establish a baseline measure of interobserver reproducibility for non-small cell lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health Organization classification, to estimate interobserver reproducibility for the therapeutically relevant squamous/nonsquamous subsets, and to examine characteristics that improve interobserver reproducibility. DESIGN: Primary, resected lung cancer specimens were converted to digital (virtual) slides. Based on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a diagnosis using the 2004 World Health Organization classification. Kappa statistics were calculated for each pathologist-pair for each slide and were summarized by classification scheme, pulmonary pathology expertise, diagnostic confidence, and neoplastic grade. RESULTS: The 12 pulmonary pathology experts and the 12 community pathologists each independently diagnosed 48 to 96 single hematoxylin-eosin digital slides derived from 96 cases of non-small cell lung carcinoma resection. Overall agreement improved with simplification from the comprehensive 44 World Health Organization diagnoses (κ  =  0.25) to their 10 major header subtypes (κ  =  0.48) and improved again with simplification into the therapeutically relevant squamous/nonsquamous dichotomy (κ  =  0.55). Multivariate analysis showed that higher diagnostic agreement was associated with better differentiation, better slide quality, higher diagnostic confidence, similar years of pathology experience, and pulmonary pathology expertise. CONCLUSIONS: These data define the baseline diagnostic agreement for hematoxylin-eosin diagnosis of non-small cell lung carcinoma, allowing future studies to test for improved diagnostic agreement with reflex ancillary tests.

Trefoil factor 3 immunohistochemical characterization of follicular thyroid lesions from tissue microarray.

OBJECTIVES: To characterize trefoil factor 3 (TFF3) expression in normal thyroid tissue samples compared with that in follicular adenoma, follicular carcinoma, and follicular variant of papillary thyroid carcinoma using immunohistochemistry on tissue microarrays. DESIGN: Immunohistochemical analysis of 83 normal thyroid tissue and of 83 follicular neoplasms (26 follicular adenomas, 25 follicular variant of papillary thyroid carcinoma, 23 follicular thyroid carcinomas, and 9 papillary thyroid carcinomas) was performed using an antibody to TFF3 on tissue microarray sections composed of formalin-fixed, paraffin-embedded tissue samples. SETTING: Academic research. PATIENTS: Thyroid tissue samples collected from patients over a 15-year period were obtained from the University of North Carolina Hospitals Division of Surgical Pathology archives. MAIN OUTCOME MEASURES: Thyroid tissue samples were graded by a pathologist based on intensity of antibody staining and on percentage of cells stained. Localization of TFF3 antibody was noted. Data were analyzed for semiquantitative differences in immunohistochemical intensity of antibody staining and in percentage of cells stained among normal thyroid tissue samples, follicular adenoma, follicular thyroid carcinoma, follicular variant of papillary thyroid carcinoma, and papillary thyroid carcinoma. RESULTS: Semiquantitative analysis demonstrated that immunohistochemistry detects significant levels of TFF3 expression in normal thyroid tissue samples compared with that in follicular lesions based on intensity of antibody staining (P < .05). Only follicular thyroid carcinoma demonstrated a significant reduction in percentage of cells stained compared with that in normal thyroid tissue samples (P = .03). No significant differences in intensity of antibody staining or in the percentage of cells stained were noted among follicular adenoma, follicular thyroid carcinoma, follicular variant of papillary thyroid carcinoma, or papillary thyroid carcinoma. Trefoil factor 3 staining localized to the cytoplasm. CONCLUSIONS: Protein expression data validate gene expression findings that follicular neoplastic lesions have decreased expression of TFF3 compared with that in normal thyroid tissue samples. These findings contribute to evidence suggesting that TFF3 may have a role in normal thyroid tissue function and that thyroid carcinomas may have reduced expression of TFF3, in contradistinction to other carcinomas that overexpress TFF3.

Recurrent infantile myofibromatosis: a report of conservative management and discussion of treatment strategies.

Infantile myofibromatosis is a rare proliferative mesenchymal disorder that has a potential for rapid growth and recurrence. Approximately 30% of infantile myofibromatosis lesions present in the head and neck, and some of these can cause significant morbidity. We report a case of recurrent infantile myofibromatosis that persisted after surgery and chemotherapy and was managed conservatively. Treatment of infantile myofibromatosis varies according to the size, location, and extent of disease. Solitary lesions may be simply observed in view of their potential for regression, but surgical excision, radiotherapy, and/or chemotherapy should be considered on a case-by-case basis, especially for nonresectable, rapidly progressive, or symptomatic lesions.

Clear cell odontogenic carcinoma: a comprehensive analysis of treatment strategies.

BACKGROUND: Odontogenic neoplasms of predominately clear cells are unusual. They represent a diagnostic dilemma, and as a result, treatment strategies are diverse. Our goal is to present two new cases, summarize reported cases of clear cell odontogenic carcinoma (CCOC), assess potential risk factors for recurrence, and propose definitive surgical and therapeutic strategies. METHODS: A literature search and analysis was performed. Regression models were used to predict risk factors for recurrence. RESULTS: Forty-three cases of CCOC were reviewed, including two reported here. The overall rate of recurrent disease was 55%. Local recurrence rates were higher for curettage (80%) than for resection alone (43%). Age (p = .20), sex (p = .28), and tumor site (p = .50) did not predict risk for recurrence. CONCLUSIONS: CCOC is a potentially aggressive tumor with a tendency for recurrence. Treatment strategies should be directed toward wide surgical resection with confirmation of tumor-free margins. Lymph node dissection and adjuvant radiation therapy should be considered in selected cases.