Comparison of the Performance of Two Different ALK Antibody Clones (D5F3 and ALK1) in Anaplastic Large Cell Lymphoma (ALCL)

Background:Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma characterized by CD30 expression and subdivided into anaplastic lymphoma kinase (ALK) positive and negative subtypes that show clinically significant differences in outcomes. The current standard for evaluating ALK status is immunohistochemistry using the mouse monoclonal anti-human CD246 (ALK1) or fluorescence in situ hybridization. The novel rabbit monoclonal anti-human CD246 (D5F3) is proposed as an alternative to ALK1 and FDA approved for diagnosis of ALK-rearranged lung adenocarcinoma. However, its performance has not been systematically tested and compared to ALK1 in ALCL. Design: Twenty-seven cases of ALCL were identified from institutional database searches and retrieved. A representative slide from each case was stained using ALK1 and D5F3 in an automated slide stainer. The intensity of cytoplasmic staining (graded 0-3, none, faint, moderate and strong) and percentage of positive cells (0, \u3c5, 5-50%, 50-75% and \u3e75%) were evaluated for each individual clone and subsequently compared between the two clones. Results: Of the twenty-seven cases, nine were previously diagnosed as ALK expression positive by ALK-1 staining. Nine cases were positive for ALK expression by ALK1 staining (34.6%; 1 1+; 0 2+; 8 3+), while fourteen were positive by D5F3 staining (48.1%; 3 1+; 2 2+; 9 3+). There were no cases that were positive by ALK1, but not by D5F3, which had identified the five additional cases. For three of the nine cases (33.3%) positive by both stains, the D5F3 stained slides showed greater percentage of cells stained. The staining intensity was greater by D5F3 in one of nine cases, the other eight cases showed the same (3+) intensity by D5F3 and ALK1. FISH results are available in five cases (19.2%) and demonstrated 100% concordance with ALK expression by both IHC stains (four positive, one negative). Conclusion: These findings support the use of D5F3 as an equivalent and potentially more sensitive alternative to ALK1 for the evaluation of ALK positivity in ALCL

The 1000 Mitoses Project : A Consensus-Based International Collaborative Study on Mitotic Figures Classification

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.Peer reviewe

Intimal sarcoma of the pulmonary artery treated with neoadjuvant radiation prior to pulmonary artery resection and reconstruction

Intimal sarcoma (IS) is a rare malignancy arising in the great vessels or heart, most commonly in the pulmonary artery, primarily treated with surgical intervention. We report a case of IS of the pulmonary artery diagnosed after an endarterectomy to remove a suspected pulmonary embolism. The tumor could not be entirely resected and showed interval growth at post-operative follow up. Neoadjuvant radiotherapy was then delivered to improve resectability. Imaging confirmed decreased tumor size, and a surgical resection with pulmonary artery reconstruction and right upper lobectomy was then successfully performed. Adjuvant gemcitabine and docetaxel was later initiated. Four months post-operatively, the patient is alive without disease recurrence. While prior reports in the literature document use of adjuvant chemotherapy and radiotherapy for treatment of IS of the pulmonary artery, no prior experience has documented utility of neoadjuvant radiotherapy for improvement of resectability. Our experience suggests that neoadjuvant radiation should be considered to improve resectability in cases of borderline resectable IS of the pulmonary artery

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Abstract Background Current interstitial lung disease (ILD) diagnostic guidelines assess criteria across clinical, radiologic and pathologic domains. Significant interobserver variation in histopathologic evaluation has previously been shown but the specific source of these discrepancies is poorly documented. We sought to document specific areas of difficulty and develop improved criteria that would reduce overall interobserver variation. Methods Using an internet-based approach, we reviewed selected images of specific diagnostic features of ILD histopathology and whole slide images of fibrotic ILD. After an initial round of review, we confirmed the presence of interobserver variation among our group. We then developed refined criteria and reviewed a second set of cases. Results The initial round reproduced the existing literature on interobserver variation in diagnosis of ILD. Cases which were pre-selected as inconsistent with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) were confirmed as such by multi-observer review. Cases which were thought to be in the spectrum of chronic fibrotic ILD for which UIP/IPF were in the differential showed marked variation in nearly all aspects of ILD evaluation including extent of inflammation and extent and pattern of fibrosis. A proposed set of more explicit criteria had only modest effects on this outcome. While we were only modestly successful in reducing interobserver variation, we did identify specific reasons that current histopathologic criteria of fibrotic ILD are not well defined in practice. Conclusions Any additional classification scheme must address interobserver variation in histopathologic diagnosis of fibrotic ILD order to remain clinically relevant. Improvements to tissue-based diagnostics may require substantial resources such as larger datasets or novel technologies to improve reproducibility. Benchmarks should be established for expected outcomes among clinically defined subgroups as a quality metric.http://deepblue.lib.umich.edu/bitstream/2027.42/173443/1/12890_2021_Article_1522.pd

Peyronie Disease: Clinicopathologic Study of 71 Cases with Emphasis on Histopathologic Patterns and Prevalent Metaplastic Ossification

Peyronie disease (PD) is a benign, superficial fibromatosis involving the fascial structures of the penis, causing deformity, pain, and loss of function, for which there are few contemporary studies of the histopathology. We performed a multi-institutional review of 74 routine and consultation specimens submitted with clinical concern for PD. Of these, three non-PD lesions were identified and excluded (a myointimoma, a mammary-type myofibroblastoma, and fibrocalcific atherosclerosis). Of the 71 confirmed to be PD, the majority of patients were white (83%) with a median age of 55 years (range: 26-88). The dorsal aspect of the penis was the most common site involved (78%), followed by lateral (12%) and ventral (10%). The median degree of curvature was 70° (range: 20-360°). On review, three overall histologic patterns characterized the lesions resected: dense fibrotic plaque (61%), dense fibrotic plaque with focal or patchy metaplastic ossification (35%), and plaque composed predominantly of metaplastic ossification (4%). The fibrotic component was predominantly nodular (18%), hyalinized/lamellar (46%), or mixed (32%), excepting two cases consisting entirely of metaplastic bone. Chronic inflammation, when present, was most often focal and perivascular in distribution. In one case, an excision post collagenase treatment, showed myxoid change and increased stromal cellularity. Overall, these findings define the range of PD histology, particularly emphasizing that the calcification noted clinically nearly always represents bona fide metaplastic ossification. Such context will be of value in evaluating specimens prospectively, in light of changing practices and the use of new technologies for treatment