Patterns of Error in Interpretive Pathology.

OBJECTIVES: To demonstrate how the educational presentation and targeted review of cases with discrepant interpretive findings between pathologists can raise awareness for specific diagnostic errors through identification of common overarching patterns of error in interpretive pathology. METHODS: We performed a review of 147 surgical pathology and cytopathology cases of discordances from 23 PowerPoint presentations presented between 2010 and 2017. Pathologists and pathology residents, blinded from the official interpretations, were presented each case and surveyed for their own diagnostic assessments. Survey results were compared with the final/correct interpretations of the signing pathologists. RESULTS: Of the 134 cases with available survey results, there were 87 (64.9%) for which most survey respondents proposed a diagnostic interpretation concordant with the final/correct diagnosis. There were 37 (27.6%) cases for which most survey responses were either wholly or partially discordant with the final/correct diagnosis. For 10 (7.5%) cases, there were equal numbers of concordant and discordant survey responses. CONCLUSIONS: Our analyses of the cases with frequent erroneous diagnoses reveal common patterns of error that are widely applicable and outline specific error-prone interpretive tendencies. Greater awareness for these tendencies, highlighted by presentation of discordant cases, can improve the quality of diagnostic pathology services.

The role of Dlc1 isoform 2 in K-Ras2(G12D) induced thymic cancer.

The Deleted in liver cancer one (Dlc1) tumor suppressor gene encodes a RhoGTPase activating protein (RhoGAP). The Dlc1 gene has multiple transcriptional isoforms and we have previously established a mouse strain containing a gene trap (gt) insertion, which specifically reduces the expression of the 6.1 kb isoform (isoform 2). This gene trapped allele when homozygous results in embryonic lethality and the heterozygous gene trapped mice do not show an increased incidence of cancers, suggesting that cooperating oncogenic changes may be required for transformation. In the present work, we have studied the in vivo cooperation between oncogenic K-Ras2 and Dlc1 genes in tumourigenesis. We have observed an increase in invasive thymic cancers, including both thymomas and lymphomas, resulting in significantly shortened life spans in mice heterozygous for the gt Dlc1 allele and an inducible LSL-K-Ras2(G12D) allele compared with the LSL-K-Ras2(G12D) only mice. The heterozygous mice showed a high degree of metastasis in the lung. We have found tumour specific selective hypermethylation of the Dlc1 isoform 2 promoter and reduction of the corresponding protein expression in thymic lymphoma (TL) and thymic epithelial carcinoma (TEC) derived from the thymic tumours. The Dlc1 deficient thymic lymphoma cell lines exhibited increased trans-endothelial cell migration. TEC cell lines also exhibited increased stress fiber formation and Rho activity. Introduction of the three Dlc1 isoforms tagged with GFP into these cells resulted in different morphological changes. These results suggest that loss of expression of only isoform 2 may be sufficient for the development of thymic tumors and metastasis.

Intermediate-grade squamous intraepithelial lesion may be a valid diagnostic/interpretive category.

We undertook this study to assess the characteristics of smears with features intermediate between high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (ISIL). We also wanted to determine how these smears correlate with high risk biopsy diagnosis and to compare this with the biopsy correlation of LSIL and HSIL. Seventy-four squamous intraepithelial lesion (SIL) smears were identified as intermediate-grade SIL smears taken at colposcopy in a 1 year period. They were correlated with concurrent colposcopically guided biopsies. Thirty-five percent of cases with intermediate-grade SIL smears had a biopsy diagnosis of moderate dysplasia or higher as compared with 12% for LSIL 74% for HSIL. This confirmed our hypothesis that intermediate-grade SIL smears have a rate of biopsy diagnosis of moderate dysplasia or higher intermediate to that of LSIL and HSIL.

Diagnosis of lymphoma by image-guided needle biopsies: fine needle aspiration biopsy, core biopsy or both?

OBJECTIVE: To determine whether or not concurrent core biopsy adds to results obtained from image-guided fine needle aspiration biopsy (FNAB) in cases of lymphoma. STUDY DESIGN: Twenty-eight FNABs of lymphomas with adjuvant flow cytometry (FC) and concurrent core biopsy were evaluated retrospectively. In each case, completeness of diagnosis by FNAB, including phenotyping and grading, where appropriate, was reviewed. The contribution of core biopsy to the diagnosis in cases where FNAB did not render a complete diagnosis was assessed. Prognostic information not available from the FNAB but obtained from the core biopsy was also evaluated. RESULTS: FNAB with adjuvant FC gave a complete diagnosis, including phenotype and grade, where applicable, in 23 of 28 cases (82%). Core biopsy added to the diagnosis in 3 cases. In 1 case, large B-cell lymphoma was diagnosed on core biopsy when FNAB was unsatisfactory. In the other 2 cases, grade of follicle center cell lymphoma was higher on core biopsy than on FNAB. The addition of the information obtained by core biopsy to that obtained by FNAB raised the diagnostic accuracy to 93%. Core biopsy was used to assess nodularity, which could not be determined on FNAB. Core biopsy was also used to assess prognostic markers by immunohistochemistry (Ki-67 and p53); they were not available with FC. This was done in 11 cases when requested by the oncologist. CONCLUSION: FNAB with adjuvant FC is a useful technique for diagnosing and subtyping lymphomas. However, diagnosis and subclassification are often insufficient. Core biopsy material provides opportunity for obtaining additional diagnostic and prognostic information that may not be easily derived from the FNAB. This allows optimal treatment planning in patients for whom excisional biopsy is contraindicated.

Transmission electron microscopy of fine needle aspiration biopsies of metastases. Accuracy of both techniques as established by biopsy diagnoses.

OBJECTIVE: To determine the accuracy of fine needle aspiration biopsy in establishing the primary on cytology and on cytologic and electron microscopy examinations using tissue biopsy as the gold standard. STUDY DESIGN: A retrospective study of 96 nonrandomly selected cases of metastases with an unknown primary was carried out. Tissue biopsy was performed subsequently for confirmation. Proper clinical correlation was part of the analysis. RESULTS: The accuracy of cytology in identifying the tumor category (e.g., carcinoma, sarcoma) and tumor type (e.g., adenocarcinoma, leiomyosarcoma) was 76% and 78%, respectively, while that of electron microscopy was 95% and 91%, respectively. The primary site was correctly identified by cytology in 59% and by electron microscopy in 88% of cases, provided that clinical parameters were also considered. CONCLUSION: Electron microscopy is an ancillary technique useful in increasing the accuracy of tumor classification of metastatic neoplasms identified by fine needle aspiration biopsy.