Search

This case report describes the case of a man in his seventies presenting with a nasopharyngeal deposit of myeloid sarcoma associated with acute monomyelocytic leukaemia. He presented with right nasal obstruction associated with unilateral pulsatile tinnitus. CT and MRI scans of sinuses identified a moderately restricting mucosal swelling of the right torus tubarius, and a biopsy of the lesion diagnosed a nasal deposit of myeloid sarcoma. [ABSTRACT FROM AUTHOR]

Summary: The diagnosis of myeloproliferative neoplasms (MPN) requires the integration of clinical, morphological, genetic and immunophenotypic findings. Recently, there has been a transformation in our understanding of the cellular and molecular mechanisms underlying disease initiation and progression in MPN. This has been accompanied by the widespread application of high‐resolution quantitative molecular techniques. By contrast, microscopic interpretation of bone marrow biopsies by haematologists/haematopathologists remains subjective and qualitative. However, advances in tissue image analysis and artificial intelligence (AI) promise to transform haematopathology. Pioneering studies in bone marrow image analysis offer to refine our understanding of the boundaries between reactive samples and MPN subtypes and better capture the morphological correlates of high‐risk disease. They also demonstrate potential to improve the evaluation of current and novel therapeutics for MPN and other blood cancers. With increased therapeutic targeting of diverse molecular, cellular and extra‐cellular components of the marrow, these approaches can address the unmet need for improved objective and quantitative measures of disease modification in the context of clinical trials. This review focuses on the state‐of‐the‐art in image analysis/AI of bone marrow tissue, with an emphasis on its potential to complement and inform future clinical studies and research in MPN. [ABSTRACT FROM AUTHOR]

Keywords: Castleman disease; interleukins; POEMS; KSHV/HHV8; HIV; TAFRO EN Castleman disease interleukins POEMS KSHV/HHV8 HIV TAFRO 328 337 10 11/01/21 20211101 NES 211101 Methodology This "Good Practice Paper" was compiled according to the British Society for Haematology (BSH) process at (http://www.b-s-h.org.uk/guidelines). Despite the success of IL-6-signalling blockade, there remains a significant unmet clinical need not only for patients who are intolerant of anti-IL-6 therapy, but also for a reliable disease-modifying therapy.50 Tocilizumab is a monoclonal antibody that antagonises the IL-6 receptor (IL-6R) to block signal transduction.57 Tocilizumab is licensed in Japan, but not in the UK, for the treatment of iMCD-TAFRO. Survival rates for MCD are not clear given changes in in diagnostic criteria, reporting and therapy.7 Nevertheless, the 5-year OS rate for MCD have been estimated at ˜65%.4 Human herpesvirus 8-associated MCD (HHV8-MCD) A proportion of cases of MCD have been attributed to infection with HHV8. The choice of therapy in MCD depends on the presentation of the patient as well as identification of drivers of disease: HHV8-MCD, POEMS-MCD, iMCD (NOS and TAFRO). [Extracted from the article]

A burgeoning family of p53-related genes have been described recently, including p73 and p63. Both these genes encode proteins with many similarities to p53 but also with the potential for forming a range of related species by alternative promoter usage and alternative splicing. In order to begin the characterization of p63, we generated a polyclonal serum (designated SC1) that recognizes the C-terminus of p63α. We have shown that this reagent recognizes p63α but not p53 nor p73. By western blot analysis both p63α and the N-terminal truncated form of p63α (ΔNp63α) were found in a range of cell lines. Similar immunoblot analysis of tissues reveals considerable complexity with at least four SC1-immunoreactive isoforms being identified. In immunohistological studies SC1 immunoreactivity is widely detectable, being predominantly associated with proliferative compartments in epithelia. However, non-proliferative populations can also show SC1 immunostaining. No simple relationship between the isoforms identified by immunoblotting of tissue lysates and the tissue immunostaining characteristics was identified. A previously unrecognized species intermediate in mobility between p63α and ΔNp63α was found in several tissues, including nerve and peripheral blood lymphocytes. Interestingly, there is suppression of p63α expression in HaCat cells in a time- and concentration-dependent manner after UV and MMS treatment. Our data provide further information about the complexity of p63 and the SC1 serum will prove to be a useful tool in further studies of this p53 homologue. [ABSTRACT FROM PUBLISHER]

Summary Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with ‘triple‐negative thrombocytosis’, we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology (‘myeloproliferative neoplasm‐definite/probable’, 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real‐world ‘triple‐negative’ ET diagnosis currently depends heavily on histology; we advocate caution in MGP‐negative cases and that specific guidelines are needed. [ABSTRACT FROM AUTHOR]

We present a multi-scale graphical network that can capture the relevant representations of individual cell morphology, topological structure of cell communities in a tissue image, as well as whole slide level attributes. This helps to effectively merge the disease relevant cell morphology to the overall topological context within the sample, within one unified deep framework. From the explainability point of view, instead of empirical design, the graphs are designed with biomedical considerations in mind in order to have translational validity. We also provide a clinically interpretable visualisation of the cells and their micro- and macro-environment by leveraging label noise reduction. We demonstrate the efficacy of our methodology on myeloproliferative neoplasms (MPN), a haematopoietic stem cell disorder as an exemplar test case. The proposed method achieves an encouraging performance in the robust separation of different MPN subtypes in this exciting new dataset as part of this work.

Image-based cell phenotyping is an important and open problem in computational pathology. The two principal challenges are: 1) making the cell cluster properties insensitive to experimental settings (like seed point and feature selection) and 2) ensuring that the phenotypes emerging are biologically relevant and support clinical reporting. To gauge robustness, we first compare the consistency of the phenotypes using self-supervised and supervised features. Through case classification, we analyse the relevance of the self-supervised and supervised feature sets with respect to the clinical diagnosis. In addition, we demonstrate how we can add model explainability through Shapley values to identify more disease relevant cellular phenotypes and measure their importance in context of the disease. Here, myeloproliferative neoplasms, a haematopoietic stem cell disorder, where one particular cell type is of diagnostic relevance is used as an exemplar. The experiments conducted on a set of bone marrow trephines demonstrate an improvement of 7.4 % in accuracy for case classification using cellular phenotypes derived from the supervised scenario.

The field of lymphatic research has benefited enormously from the discovery of "marker" proteins that permit not only the identification and quantitation of lymphatic vessels in tissue sections for tumor pathology but also the isolation of primary lymphatic endothelial cells for basic research. This chapter focuses on the use of these markers for the immunohistochemical analysis of lymphangiogenesis in both frozen and paraffin-embedded tissue sections and discusses current protocols including newer versions employing biotin tyramide amplification and their associated problems.