The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and ...histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression ...profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC).
We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n = 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME.
The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P = 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, Plog rank <0.001, Ptrend < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature lymphoma-associated macrophage interaction signature (LAMIS).
SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.
•Content of PD1-, FoxP3- and CD8-positive T cells, as well as vessel density fail to associate with outcome in DLBCL.•Low content of CD68+ macrophages is associated with inferior outcome in DLBCL.•High content of SPARC+ macrophage and stromal cells is associated with favorable outcome in DLBCL.•SPARC+ macrophages/stromal cells prove informative regardless of molecular subtypes, including MYC and double-hit status.•SPARC expression can be assessed easily and reliably by a single IHC stain.
Essentials
Extramedullary hematopoiesis (EMH) represents a pathologic finding in adult life.
We report a mass‐like EMH in the presacral space in a patient with ANKRD26‐related thrombocytopenia.
We ...found possible correlation between EMH and conditions causing lifelong thrombocytopenia.
EMH can cause masses of unknown origin in patients with inherited thrombocytopenias.
Summary
Most commonly located in the liver and spleen, extramedullary hematopoiesis (EMH) is the presence of hematopoietic tissue outside the bone marrow. MYH9‐related thrombocytopenia (MYH9‐RD) and ANKRD26‐related thrombocytopenia (ANKRD26‐RT) are two of the most frequent forms of inherited thrombocytopenia (IT). Until recently, EMH has been associated with neoplastic and non‐neoplastic hematologic conditions in which ITs were not included. We describe a case of mass‐like EMH in the presacral space in a patient affected with ANKRD26‐RT, comparing it with another case of paravertebral EMH we recently described in a subject with MYH9‐RD. The surprisingly similitude of such a finding in the context of a group of rare disorders induces us to speculate about the possible pathogenic relationship between EMH and conditions causing lifelong thrombocytopenia, particularly the entity of ITs. Finally, we suggest that EMH has to be taken into consideration in the diagnostic work‐up of masses of unknown origin in subjects affected with ITs.
Silicon Carbide (SiC) is a relatively new entry in the world of solid-state detectors. Although SiC response to neutrons is more complex than the one obtained with diamonds, the measured energy ...resolution (FWHM/Ed<4%) makes SiC an interesting alternative to diamond and silicon detectors for fast neutrons. The results obtained from the measurements of the response of a 100μm thick SiC detector to neutrons in the energy range between 3 and 20 MeV at the n_TOF spallation source at CERN are presented in this paper.
By selecting the neutron energy by means of the time of flight, the detector response to quasi-mono-energetic neutrons was measured. The main neutron-induced nuclear reactions were identified in the measured pulse height spectrum. Detection efficiency as a function of neutron energy was measured and interpreted based on available neutron cross section and by making use of Monte Carlo simulations.
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