The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

Multiparameter immunophenotyping by flow cytometry in multiple myeloma. The diagnostic utility of defining ranges of normal antigenic expression in comparison to histology

BACKGROUND: Numerous studies have reported on the immunophenotype of plasma cells (PCs) in monoclonal gammopathy of undetermined significance (MGUS) and in plasma cell myeloma (PCM), but very few have examined the immunophenotype of normal PCs. In this study, an objective definition of normal range of expression for each antigen was found on normal control PCs. Using these new ranges of normal expression (new method) is different from using a static 20% of PCs cut-off for all antigens as described in the literature (traditional method). These newly calculated normal ranges for each antigen were applied to our data, and compared to histologic and immunohistochemical findings. METHODS: Bone marrow samples from 46 patients with PC neoplasms and 15 normal controls were studied. A minimum of 100 PC were analyzed for each patient and control sample. An 8-color staining method was applied to study the immunophenotype of PCs, using a BD FACSCanto II. RESULTS: By the new ranges of normality calculated in this study it was determined that different antigens have different level of expression on polyclonal PCs. CD19 correlated with histology by both the traditional and new methods, but had superior correlation by the new method. CONCLUSIONS: This report is the first 8-color immunophenotypic study of PCM in which a "range of normal expression" for each antigen is defined. This is a critical step to help distinguish between a normal and neoplastic PC immunophenotype and discern which antigens are of diagnostic importance

Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors.

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient's follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development

Telecytology in East Africa: a feasibility study of forty cases using a static imaging system

We conducted a pilot study to assess the feasibility of telecytology as a diagnostic tool in difficult cases originating from a hospital in East Africa. Forty cytology cases considered difficult by a referring pathologist were posted on a telepathology website. Six pathologists independently assessed the static images. Telecytology diagnoses were compared with the consensus diagnoses made on glass slides and also with the histogical diagnoses when available. The diagnostic agreement of the six pathologists was 71–93% and tended to be higher for pathologists with more experience. Reasons for discordance included poor image quality, presence of diagnostic cells in thick areas of smears, sampling bias and screening errors. The consensus diagnoses agreed with histological diagnoses in all 17 cases in which a biopsy was performed. Diagnostic accuracy rates (i.e. telecytology diagnosis vs. histological diagnosis) for individual pathologists were 65–88%. To ensure diagnostic accuracy both referring and consulting pathologists must have adequate training in cytology, image acquisition and image-based diagnosis and the diagnostic questions of importance must be clearly communicated by the referring pathologist when posting a case

MYD88 L265P somatic mutation in Waldenstrom’s Macroglobulinemia

Background: Waldenstrom’s Macroglobulinemia (WM) is an incurable, IgM secreting lymphoplasmacytic lymphoma (LPL) with overlapping clinicopathological features to IgM secreting monoclonal gammopathy of unknown significance (MGUS), marginal zone lymphoma (MZL) and myeloma (MM). The underlying mutation for WM remains to be delineated. Methods: Whole genome sequencing (WGS) of bone marrow (BM) LPL cells was performed for 30 WM patients and included sequencing of paired normal/tumor tissues for 10 patients. Sanger sequencing was used to validate these findings in samples from an expanded cohort of patients with LPL, other overlapping B-cell disorders, and healthy donors. Results: A somatic variant (T→C) in LPL cells was identified at position 38182641 at 3p22.2 in all 10 paired, and 17/20 unpaired WM patients which predicted for an amino acid change (L265) in MYD88, a mutation which triggers IRAK/MAPK/NF-κβ signaling. Sanger sequencing identified MYD88 L265P in tumor samples from 49/54 WM and 3/3 non-IgM secreting LPL patients (91.2% of all LPL patients). MYD88 L265P was absent in normal paired tissues from WM/LPL patients, healthy donor B-cells, and absent or rarely expressed in samples from MM, MZL or IgM MGUS patients. Mutations in ARID1A (5/30; 17%) leading to premature stop or frameshift were also identified, which associated with greater disease burden. Lastly, 2 of 3 WM patients with wild type MYD88 had variants in MLL2. Conclusions: MYD88 L265P is a highly recurring mutation in WM/LPL patients, which can aid in differentiating WM/LPL from overlapping B-cell disorders, and provides a novel target for the development of therapeutics for WM/LPL