Lymphadenectomy Specimens in a Large Retrospective Cohort of Pediatric Patients Reveal No in situ Lymphomas but a Broad Spectrum of Reactive Changes.

OBJECTIVES While the incidence and prevalence of in situ follicular neoplasia (ISFN) and in situ mantle cell neoplasia (ISMCN) in adults are well documented, little is known about these early (precursor) lesions in pediatric populations. The aim of this study was to analyze so-called 'reactive' lymph nodes harvested for the purpose of staging solid tumors, unexplained lymphadenopathies, or presumed inflammatory processes or in conjunction with other surgical interventions in children and adolescents aged <18 years, with special attention to ISFN and ISMCN. METHODS Formalin-fixed, paraffin-embedded reactive lymph node samples from an unselected pediatric population from two catchment areas in Switzerland were retrospectively analyzed for the presence of ISFN and ISMCN and specific reactive lymph node patterns. RESULTS While a diverse range of histopathological patterns of reactive lymph node changes with a particular periodic increase in mycobacterioses could be observed in this pediatric population, not a single case of ISFN or ISMCN was found. CONCLUSIONS Early histological lymphomagenesis equivalents in the form of in situ lymphomas are exceedingly rare events in children and young adolescents. The spectrum of reactive lymph node changes is large, with differences possibly determined by regional variations in geography, demographics, catchment areas, seasons, and years, respectively

EDITORIAL DOSSIÊ: FORMAÇÃO E PRÁTICAS DOCENTES NA PERSPECTIVA DA EMANCIPAÇÃO HUMANA

É com grande satisfação que apresentamos aos leitores da Revista Divers@!, o dossiê do v. 15, n. 2 (2022), intitulado de “Formação e Práticas Docentes na Perspectiva da Emancipação Humana”. Este é o segundo dossiê que a revista prepara juntamente com editores parceiros, que tem o objetivo de suscitar temáticas de pesquisas atuais, que contribuem com as diversas áreas do conhecimento que perpassam a interdisciplinaridade na relação com processos educacionais. A revista tem a preocupação em trazer artigos que buscam fazer a reflexão dos caminhos trilhados pelos pesquisadores de diferentes áreas na prática articulada com a formação docente

Composite mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic and molecular study

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many features and both arise from CD5+ B-cells, their distinction is critical as MCL is a much more aggressive neoplasm. Rarely, composite MCL and CLL/SLL have been reported. Little is known, about the nature of these cases and in particular the clonal relationship of the two lymphomas. Eleven composite MCL and CLL/SLL cases were identified. The clinical, morphologic and immunophenotypic features of the MCL and CLL/SLL were characterized. Immunoglobulin heavy chain (IGH) gene analysis was performed on microdissected MCL and CLL/SLL components to assess their clonal relationship. Ten patients had lymphadenopathy, and 7 patients had bone marrow involvement. The MCL component had the following growth patterns: in situ (n=1), mantle zone (n=3), nodular and diffuse (n=3), diffuse (n=3), and interstitial in the bone marrow (the only patient without lymphadenopathy) (n=1); 6 MCL had blastoid or pleomorphic and 5 classical cytologic features. The CLL/SLL component was internodular (n=9) or diffuse (n=2). All MCL were CD5+ and cyclin D1+ with t(11;14) translocation. All CLL/SLL were CD5+, CD23+ and negative for cyclin D1 or t(11;14). IGH gene analysis showed that the MCL and CLL/SLL components displayed different sized fragments, indicating that the MCL and CLL/SLL are likely derived from different neoplastic B-cell clones. The lack of a clonal relationship between the MCL and CLL/SLL components suggests that the MCL and CLL/SLL represent distinct disease processes and do not share a common progenitor B-cell

CCR2 Acts as Scavenger for CCL2 during Monocyte Chemotaxis

<div><h3>Background</h3><p>Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces or on matrices along the attracting gradient towards increasing concentrations of agonist. On the other hand agonist-induced desensitization and internalization is a general paradigm for chemokine receptors which is inconsistent with the prolonged migratory capacity.</p> <h3>Methodology/Principal Findings</h3><p>Chemotaxis of monocytes was monitored in response to fluorescent CCL2-mCherry by time-lapse video microscopy. Uptake of the fluorescent agonist was used as indirect measure to follow the endogenous receptor CCR2 expressed on primary human monocytes. During chemotaxis CCL2-mCherry becomes endocytosed as cargo of CCR2, however, the internalization of CCR2 is not accompanied by reduced responsiveness of the cells due to desensitization.</p> <h3>Conclusions/Significance</h3><p>During chemotaxis CCR2 expressed on monocytes internalizes with the bound chemoattractant, but cycles rapidly back to the plasma membrane to maintain high responsiveness. Moreover, following relocation of the source of attractant, monocytes can rapidly reverse their polarization axis organizing a new leading edge along the newly formed gradient, suggesting a uniform distribution of highly receptive CCR2 on the plasma membrane. The present observations further indicate that during chemotaxis CCR2 acts as scavenger consuming the chemokine forming the attracting cue.</p> </div

When and how to test for C - MYC in aggressive B cell lymphomas

C-MYC (MYC) is a regulator gene that plays an important role in cell cycle progression, apoptosis, and cellular transformation. It is believed to regulate expression of up to 15% of all human genes. In recent years, C-MYC has been extensively studied in blastic B cell lymphomas, and currently C-MYC is regarded not only as a diagnostic tool, but also a promising prognostic biomarker. C-MYC testing is therefore no longer simply a confirmational analysis for Burkitt's lymphoma, but also provides important information on prognosis and risk stratification of diffuse large B cell lymphoma patients. This review outlines our approach to integrate this new role of C-MYC in a convenient way in routine diagnostics and discusses the application of different techniques such as immunohistochemistry and FISH for C-MYC testing

Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival

Programmed death-1 (PD-1), a protein that is physiologically expressed by germinal center-associated helper T cells, has an inhibitory function on T-cell activity. The distribution of PD-1+ lymphocytes in the microenvironment of Hodgkin lymphoma is not random and can serve as a diagnostic marker. We measured the number of PD-1+ lymphocytes in Hodgkin lymphoma and correlated it with the remaining background lymphocyte populations and known biological and clinical key data on a tissue microarray platform encompassing 280 cases of classical Hodgkin lymphoma and 3 cases of nodular lymphocyte-predominant Hodgkin lymphoma. Prognostic cutoff scores were determined by receiver operating curve analysis. The number of PD-1+ tumor-infiltrating lymphocytes in 189 evaluable cases was median of 27 and mean of 269 cells/mm(2), being higher in lymphocyte-rich classical Hodgkin lymphoma and lower in the mixed cellularity variant. Rimming of tumor cells by PD-1+ cells was observed in all cases of nodular lymphocyte-predominant Hodgkin lymphoma but only in 1% of classical Hodgkin lymphomas, particularly in lymphocyte-rich and -mixed cellularity variants. Thus, the presence of PD-1+ rosettes around neoplastic cells is typical but not exclusive for nodular lymphocyte-predominant Hodgkin lymphoma because it may be encountered in classical Hodgkin lymphoma. The PD-1+ cell amount was lower in classical Hodgkin lymphoma cases with 9p24 gains (PD-1 ligand 2 locus) and in cases with higher numbers of FOXP3+ regulatory T cells. An increased amount of PD-1+ tumor-infiltrating lymphocytes above the prognostic cutoff score (23 cells/mm(2)) was a stage-independent negative prognostic factor of overall survival as opposed to the number of FOXP3+ regulatory T cells. Along with the latter, PD-1+ cells might represent important lymphoma/host microenvironment modulators

PCM1-JAK2-fusion : a potential treatment target in myelodysplastic-myeloproliferative and other hemato-lymphoid neoplasms

Activating mutations of the JAK2 gene are of tumorigenic significance in myeloproliferative neoplasms. Translocations involving the JAK2 locus are of oncogenic importance in acute leukemias, myelodysplastic/myeloproliferative diseases and T-cell lymphomas. JAK2 locus gains, which are recurrent in Hodgkin's- and primary mediastinal B-cell lymphoma, are also efficient mechanisms of JAK2 activation. Recently, specific drugs blocking JAK2 have been developed and are currently in clinical trials

Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations

In the currently published World Health Organization-Classification, the new entity of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly was introduced largely based on findings from East-Asian populations. Little is known about its frequency or characteristics in the West, especially in European populations. Using a tissue microarray approach, we identified 8 out of 258 diffuse large B-cell lymphoma cases fulfilling the World Health Organization criteria of an Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly, suggesting an incidence of 3.1% in a European population. The median patient age was 65 years. The highest diagnostic sensitivity was only achieved by EBER in situ hybridization. No correlation between Epstein-Barr virus status and outcome was noted except in latency type 3 lymphomas, which had a very poor survival. Sixty-seven percent of Epstein-Barr virus-positive cases showed the presence of necrosis and 50% expressed the activation marker CD30. However, no morphological or immunohistochemical features reliably distinguished all Epstein-Barr virus-positive diffuse large B-cell lymphoma cases. Thus, to identify these Epstein-Barr virus-positive diffuse large B-cell lymphoma in the elderly, EBER in situ hybridization of all de novo diffuse large B-cell lymphoma cases of patients older than 50 years should be considered. In summary, Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is rare in Europeans older than 50 years. It can only be diagnosed by EBER-ISH, and its precise prognostic role is unclear. Whether routine testing of all diffuse large B-cell lymphoma patients older than 50 years can be recommended depends essentially on its clinical relevance. Future studies are needed to address this question