Columnar cell lesions of the breast: morphologic features and role of 16q losses

Columnar cell lesions of the breast are proposed as the earliest recognizable precursor lesions of low grade breast cancer. The lesions are characterized by cystically enlarged terminal duct lobular units with monotonous (monoclonal) columnar type luminal cells. Variants with and without atypia are recognized. In her thesis, Mirthe de Boer discusses the morphological, immunohistochemical and molecular features of columnar cells lesions and other benign and premalignant look-alikes. Morphologically, a new phenomenon of pagetoid “pale cells” is described in columnar cell lesions. These pale cells could potentially serve as a feature of atypia. The role of chromosome 16q losses in breast carcinogenesis is reviewed and the frequency of chromosome 16q losses is studied in columnar cell lesions, columnar cell look-alikes, other members of the low nuclear grade breast neoplasia family and blunt duct adenosis. Based on the lack of chromosome 16q losses, blunt duct adenosis is proposed as a separate entity, falling in the spectrum of the benign lesions. Morphological criteria to discriminate between blunt duct adenosis and columnar cell lesions are presented. Finally, also the overlapping characteristics of columnar cell lesions and intraductal papillomas are discussed and the first papillary atypical columnar cell lesion variants are described. The results of this thesis underline the precursor role of columnar cell lesions and have the potential to improve accuracy and reproducibility of the diagnosis of early precursor breast lesions, which is the basis for researching optimal patient care

Chromosome 16q loss– a genetic key to the understanding of breast carcinogenesis

In the last decade the concepts of breast cancer dedifferentiation and progression have undergone a significant and substantial change. In the past it was widely believed that the detailed associations between genetic and morphological changes defined in the Vogelstein model of colorectal cancer pathogenesis could be transferred to breast carcinogenesis. A multitude of studies seemed to verify this a priori hypothesis. However, with the introduction of global screening techniques, predominantly at the DNA level, it became obvious that this linear model might be oversimplified for breast cancer. It is now widely accepted that losses of chromosomal 16q characterize in-situ and invasive breast cancer tumours with predominantly low tumour grade and estrogen receptor (ER) positivity (luminal breast cancers). In contrast, high grade breast cancers of the HER2, the basal or the non expressor phenotype with 16q-losses are rarely seen and in consequence a concept of multiple, parallel pathways with defined precursor lesions emerged. As a consequence, it became obvious that the hunt for oncogenes/tumour suppressor genes in invasive breast cancer is pathway specific. Whereas high grade breast cancers have been relatively well characterized by several recurrent changes in oncogenes/tumour suppressor genes located on various chromosomal regions (e.g. egfr, p53, HER2), the characterization of a 16q-specific tumour suppressor gene in ER-positive breast cancer is still a tremendous challenge. This review will focus on the role of 16q in breast cancer and aims to give insights into actual research efforts, e.g. alternative explanations in order to unravel the central role of 16q in breast cancer

Challenges in Diagnosing Myelodysplastic Syndromes in the Era of Genetic Testing: Proceedings of the 13th Workshop of the European Bone Marrow Working Group

Contains fulltext : 201060.pdf (publisher's version ) (Open Access

First report of IgG4 related disease primary presenting as vertebral bone marrow lesions

IgG4-related disease is a fibro-inflammatory disorder characterized by swelling of tissues and affected organs accompanied by the development of scar tissue (fibrosis) and infiltration by IgG4 positive plasma cells. Almost any organ can be affected, including, but rarely, bone marrowinvolvement. Here we present a case of a 76-year-old male with IgG4-related disease presenting primarily with vertebral bone marrow lesions. Histopathology showed the typical features of storiform fibrosis, and increased IgG4 positive plasma cells. Treatment with corticosteroids significantly improved wellbeing and resolved lesion size on MRI

Prediction of ultrasound guided fine needle aspiration cytology results by FDG PET-CT for lymph node metastases in head and neck squamous cell carcinoma patients

Introduction: Accurate assessment of cervical lymph node status is essential in patients with head and neck squamous cell carcinoma (HNSCC) as it influences prognosis and treatment decisions. During patient workup, lymph node status is often examined by ultrasound guided fine needle aspiration cytology (USgFNAC). 18F-Fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is frequently used to assess primary tumor and distant metastases but provides information on lymph node status as well. It is possible that FDG PET-CT (if already made for abovementioned indications) can predict the results of USgFNAC in subgroups of lymph nodes based on FDG-uptake and size. The objective of this study is to identify maximum standardized uptake (SUVmax) and short axis diameter cutoff values of lymph nodes at which FDG PET-CT can reliably predict USgFNAC results. Methods: One hundred and seventeen patients with HNSCC were retrospectively analyzed. Patients were included when FDG PET-CT and USgFNAC were available. SUVmax measurements were performed and compared to the USgFNAC results. Results: Using USgFNAC as a reference standard, the area under the curve of the receiver operating curve was 0.91. At an SUVmax cutoff value of 4.9, the accuracy of FDG PET-CT was the highest (85%). Lymph nodes with short axis diameter ≥1.0 cm and SUVmax ≥4.9 were in 91% positive on USgFNAC. If SUVmax was below 2.2, no nodes were positive on USgFNAC. Of all lymph nodes 52% either had a short axis diameter ≥1.0 cm and SUVmax ≥4.9 or an SUVmax <2.2. FDG PET-CT and USgFNAC results were very similar in these nodes. Conclusions: By measuring SUVmax values and minimal axial diameters of lymph nodes and using appropriate cutoff values, FDG PET-CT can predict the results of USgFNAC examinations in half of the examined lymph nodes. This information may lead to a reduction of USgFNAC examinations in HNSCC patients if FDG PET-CT is already performed for other indications

Role of columnar cell lesions in breast carcinogenesis : analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma. Usual ductal hyperplasia and blunt duct adenosis lacked whole-arm losses of 16q. In contrast, columnar cell lesions without atypia, columnar cell lesions with atypia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ and low-grade invasive carcinomas increasingly harboured whole-arm losses of 16q (17%, 27%, 47% and 57%, respectively). However, no recurrent losses in specific genes could be identified. In several patients, columnar cell lesions and atypical ductal hyperplasia harboured similar losses as related ductal carcinoma in situ or invasive carcinomas within the same breast. There were indications for 16q breakpoints near the centromere. Whole-arm gains on 16p were relatively scarce and there was no relation between whole-arm gains of 16p and progression of lesions of the low-grade breast neoplasia family. In conclusion, columnar cell lesions (with and without atypia) often harbour whole-arm losses of 16q, which underlines their role as precursors in low-grade breast carcinogenesis, in contrast with usual ductal hyperplasia and blunt duct adenosis. However, no recurrent losses in specific genes could be identified, pointing to minor events in multiple tumour suppressor genes rather than major events in a single 16q gene contributing to low-grade breast carcinogenesis

Nationwide differences in cytology fixation and processing methods and their impact on interlaboratory variation in PD-L1 positivity

Programmed death ligand-1 (PD-L1) immunostaining, which aids clinicians in decision-making on immunotherapy for non-small cell lung cancer (NSCLC) patients, is sometimes performed on cytological specimens. In this study, differences in cytology fixation and cell block (CB) processing between pathology laboratories were assessed, and the influence of these differences on interlaboratory variation in PD-L1 positivity was investigated. Questionnaires on cytology processing were sent to all Dutch laboratories. Information gathered from the responses was added to data on all Dutch NSCLC patients with a mention of PD-L1 testing in their cytopathology report from July 2017 to December 2018, retrieved from PALGA (the nationwide network and registry of histo- and cytopathology in the Netherlands). Case mix-adjusted PD-L1 positivity rates were determined for laboratories with known fixation and CB method. The influence of differences in cytology processing on interlaboratory variation in PD-L1 positivity was assessed by comparing positivity rates adjusted for differences in the variables fixative and CB method with positivity rates not adjusted for differences in these variables. Twenty-eight laboratories responded to the survey and reported 19 different combinations of fixation and CB method. Interlaboratory variation in PD-L1 positivity was assessed in 19 laboratories. Correcting for differences in the fixative and CB method resulted in a reduction (from eight (42.1%) to five (26.3%)) in the number of laboratories that differed significantly from the mean in PD-L1 positivity. Substantial variation in cytology fixation and CB processing methods was observed between Dutch pathology laboratories, which partially explains the existing considerable interlaboratory variation in PD-L1 positivity

Lymphoblastic lymphoma with a triple-hit profile : a rare but distinct and relevant entity

Follicular lymphoma with progression to a high-grade lymphoma bears a poor prognosis. We describe a case of a 60-year-old man who presented in 2012 with an epidural mass, diagnosed as a diffuse large B-cell lymphoma (DLBCL) with concurrent low-grade follicular lymphoma. Three years later, the patient presented with a cervical mass, diagnosed as a lymphoblastic lymphoma (LBL). Both the DLBCL and LBL contained a “triple hit” with BCL2, BCL6, and cMYC translocations demonstrated by fluorescence in situ hybridization analysis and a complex karyotype by single-nucleotide polymorphism array analysis. Furthermore, the 2 lymphomas were shown to be clonally related by clonality analysis and single-nucleotide polymorphism array analysis. This case report presents a highly unusual case of an LBL with a triple hit, originating from a DLBCL, which has rarely been described in the literature and deserves further exploration