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We retrieved a total of 25 patients from our database who had been affected by either MF or SS. No patients were excluded. Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common cutaneous T-cell lymphomas (CTCL).[1] While the early-stage can be treated with skin-directed therapies, advanced phases require systemic treatments. All patients with a diagnosis either of MF or of SS from January 2015 to January 2022 were retrieved through our cutaneous lymphoma database. [Extracted from the article]

Summary: The prognostic role of TP53 disruption has been established in diffuse large B‐cell lymphoma (DLBCL). Aim of this analysis was to correlate TP53 mutations by Sanger sequencing, cell of origin (COO) profile by Lymph2Cx panel on the NanoString platform and MYC, BCL2 and BCL6 overexpression or re‐arrangements by immunohistochemistry (IHC) and fluorescent in‐situ hybridization (FISH), with outcome in DLBCL patients enrolled into the FIL‐DLCL04 trial (NCT00499018). One hundred and twenty‐five DLBCL patients with tumour block available were analyzed. TP53 was mutated in 11/125 (9%) cases; 60/125 patients received high‐dose chemoimmunotherapy up‐front, as for the randomization arm; COO was reported in 88 patients: 48 germinal centre B‐cell like, 25 activated B‐cell like and 17 unclassified; 26 patients were double expressors in IHC and 11 double hit in FISH. After a median follow‐up of 72 months, five‐year failure‐free survival (FFS) for TP53 mutated versus wild‐type was 24% and 72%, and five‐year overall survival (OS) was 34% and 83%, respectively. Adjusted hazard ratio (HR) was 2·28 [95% confidence interval (CI) 0·89–5·86, p = 0·086] and 4·05 (95% CI 1·37–11·97, p = 0·011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers. [ABSTRACT FROM AUTHOR]

Aims: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. Methods and results: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. Conclusions: Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy. [ABSTRACT FROM AUTHOR]

BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of the mutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long‐term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR. [ABSTRACT FROM AUTHOR]

Aims: A wide range of post‐radiotherapy (RT) vascular lesions can occur, ranging from benign lymphangiomatous papules of the skin (BLAPs), to atypical vascular lesions (AVLs) and post‐RT angiosarcomas (ASs). The relationship between benign and malignant post‐RT breast lesions and their prognostic features are still controversial. The aims of this study were to investigate the relationship between benign and malignant mammary post‐RT vascular lesions and to define post‐RT AS prognostic features. Methods and results: Seventy‐four post‐RT vascular lesion cases were obtained and stained with antibodies against CD34, CD31, D2‐40, Ki67, and c‐Myc. Mutational analysis was performed by deep sequencing for the following genes: KRAS, NRAS, HRAS, BRAF, PIK3CA, TP53, NOTCH1, PTEN, CDKN2A, EGFR, AKT1, CTNNB1, hTERT, and PTPRB. Post‐RT AS cases were graded according to a previously reported breast AS grading system. AVL cases showed a low number of HRAS and hTERT mutations, whereas post‐RT AS cases showed a high frequency of EGFR, TP53, HRAS and hTERT mutations. On follow‐up, all BLAP and AVL patients were alive with no evidence of disease. Post‐RT AS 5‐year overall survival declined with the increase in grade, as follows: 85.7% for grade 1, 83.3% for grade 2, and 40.4% for grade 3. Conclusions: Our findings confirm that BLAP and AVL have a good prognosis, and that post‐RT AS prognosis is strongly related to histological grading. On molecular analysis, AVL and post‐RT AS shared HRAS and hTERT mutations, suggesting a relationship between the two lesions. [ABSTRACT FROM AUTHOR]

In this case, the core biopsy disclosed a diffuse proliferation of CD20-positive mature B cells, leading to a putative diagnosis of indolent non-Hodgkin B-cell lymphoma. Randomized comparison of power Doppler ultrasonography-guided core-needle biopsy with open surgical biopsy for the characterization of lymphadenopathies in patients with suspected lymphoma. Excisional biopsy of the same lymph node disclosed scattered Hodgkin/Reed-Sternberg (HRS) cells (insert), which were not evident on first biopsy. [Extracted from the article]

In 2009, the four laboratories of the Fondazione Italiana Linfomi (FIL) minimal residual disease (MRD) Network started a collaborative effort to harmonize and standardize their methodologies at the national level, performing quality control (QC) rounds for follicular lymphoma (FL) and mantle cell lymphoma (MCL) MRD assessment. In 16 QC rounds between 2010 and 2017, the four laboratories received 208 bone marrow (BM) samples (126 FL; 82 MCL); 187 were analyzed, according to the EuroMRD Consortium guidelines, by both nested (NEST) polymerase chain reaction (PCR) and real-time quantitative (RQ) PCR for BCL2/IGH MBR or IGHV rearrangements. Here, we aimed at analyzing the samples that challenged the interlaboratory reproducibility and data interpretation. Overall, 156/187 BM samples (83%) were concordantly classified as NEST+/RQ+ or NEST-/RQ- by all the four laboratories. The remaining 31 samples (17%) resulted alternatively positive and negative in the interlaboratory evaluations, independently of the method and the type of rearrangement, and were defined "borderline" (brd) samples: 12 proved NEST brd/RQ brd, 7 NEST-/RQ brd, 10 NEST brd/RQ positive not quantifiable (PNQ), and 2 NEST brd/RQ-. Results did not change even increasing the number of replicates/sample. In 6/31 brd samples, droplet digital PCR (ddPCR) was tested and showed no interlaboratory discordance. Despite the high interlaboratory reproducibility in the MRD analysis obtained and maintained by the QC round strategy, samples with the lowest MRD levels can still represent a challenge: 17% (31/187) of our samples showed discordant results in interlaboratory assessments, with 6.4% (12/187) remained brd even applying the two methods. Thus, although representing a minority, brd samples are still problematic, especially when a clinically oriented interpretation of MRD results is required. Alternative, novel methods such as ddPCR and next-generation sequencing have the potential to overcome the current limitations. [ABSTRACT FROM AUTHOR]

The article offers information on analysing public datasets containing whole exome sequencing data from multiple studies on mature lymphoid B cell malignancies using the cBioportal website analysis tool, focusing on genomic alterations of ribosomal protein genes and the TP53 gene; and mentions that genomic alterations of ribosomal proteins (RPs) occurred at low frequency in 4 percent of analysed samples.

Keywords: BPDCN; discriminant analysis; miRNAs; MS EN BPDCN discriminant analysis miRNAs MS 831 833 3 12/31/20 20201201 NES 201201 Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and myeloid sarcoma (MS) are two rare hematological neoplasms, both stemming from a myeloid precursor undergoing divergent malignant transformation.1 They can primarily present in the skin, with or without extramedullary organ involvement and leukemic dissemination, and are characterized by a highly aggressive clinical course with dismal prognosis (overall survival 12-14 months).1 Possibly due to their rareness, BPDCN and MS still show unexplored biological facets and lack a standardized therapeutic approach, thus justifying their inclusion among orphan tumors. To evaluate the impact of these differentially expressed miRNAs on the BPDCN transcriptional program and determine miRNA-genes regulatory pathways potentially contributing to BPDCN pathogenesis, we performed a functional network analysis. Interestingly, we found that in BPDCN respect to MS the I TP53 i signaling may be inhibited by miRNAs upregulated while the dysregulation of the intrinsic apoptotic pathway may be due to lower miRNAs expression level. [Extracted from the article]

Aims Mantle cell lymphoma ( MCL) is characterized by distinctive histological and molecular features. Aberrant expression of BCL6 and CD10 has been reported occasionally, but the biological features of such cases are largely unknown. This study aimed to define the epidemiological, histological and cytogenetic characteristics of BCL6 and CD10-positive MCLs, also investigating possible biological features. Methods and results A total of 165 cases of cyclin D1 and t(11;14)(q13;q34)-positive MCLs were studied for CD10 and BCL6 immunohistochemical expression, which was documented in 26 of 165 (15.8%) cases ( BCL6 17 of 165; CD10 11 of 165; BCL6 and CD10 co-expression two of 165). CD10-positivity was significantly more frequent in females (63.3%; P < 0.01). Either expression correlated significantly with higher mean proliferation index and higher prevalence of MUM1 positivity ( P < 0.05). Fluorescence in-situ hybridization ( FISH) for BCL6 (3q27) gene derangements was performed on the BCL6- and CD10-positive cases and 98 matched controls: amplifications were documented more frequently in BCL6-positive than -negative cases (50.0% versus 19.4% of cases) ( P < 0.05). The mutational status of the variable immunoglobulin heavy chain genes ( IGVH) was investigated by Sanger sequencing: five of the six successfully tested cases (83.3%) showed no somatic hypermutations. Conclusions Aberrant CD10 and BCL6 expression defines a subset of MCLs with higher mean Ki-67 index and higher prevalence of MUM1 expression. BCL6 protein positivity correlates with cytogenetic aberrations involving the BCL6 gene. Although examined successfully in few cases, the high prevalence of unmutated IGVH genes also points at a pregerminal cell origin for these phenotypically aberrant cases. [ABSTRACT FROM AUTHOR]

Aims Glycogen synthase kinase-3 beta ( GSK-3β) is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, metabolism, survival and cellular senescence. Its main biological function is to inhibit β-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway; however, GSK-3β interacts with multiple signalling pathways, and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3β in classical Hodgkin lymphomas (cHL). Methods and results We analysed the functional status of GSK-3β enzyme in cHL by using antibodies raised against fixation-resistant epitopes of phospho Y216 GSK-3β (active form), phospho S9 GSK-3β (inactive form) and β-catenin protein. We first detected the pY216 GSK-3β active form of the enzyme in 100 of 100 (100%) of the cases, and in line with the latter expression profile, the β-catenin protein was found in only 12 of 100 (12%) of the samples. As reported previously in bladder cancer, pancreatic adenocarcinoma and chronic lymphocytic leukaemia, we showed an aberrant nuclear localization in the neoplastic clone of active pY216 GSK-3β in 78 of 100 (78%) of cHL cases. Conclusions We demonstrated the activation of GSK-3β in cHL resulting in inhibition of the Wnt/β-catenin signal cascade and the aberrant accumulation of its activated form in nuclei of Hodgkin Reed-Sternberg and Hodgkin cells. These findings may be relevant for future clinical studies, identifying GSK-3β as a potential therapeutic target for cHL. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia ( CLL) is the most common leukemia in adults. Its clinical course is typically indolent; however, based on a series of pathobiological, clinical, genetic, and phenotypic parameters, patient survival varies from less than 5 to more than 20 years. In this paper, we show for the first time that the expression of the interferon-inducible DNA sensor IFI16, a member of the PYHIN protein family involved in proliferation inhibition and apoptosis regulation, is associated with the clinical outcome in CLL. We studied 99 CLLs cases by immunohistochemistry and 10 CLLs cases by gene expression profiling. We found quite variable degrees of IFI16 expression among CLLs cases. Noteworthy, we observed that a reduced IFI16 expression was associated with a very poor survival, but only in cases with ZAP70/ CD38 expression. Furthermore, we found that IFI16 expression was associated with a specific gene expression signature. As IFI16 can be easily detected by immunohistochemistry or flow cytometry, it may become a part of phenotypic screening in CLL patients if its prognostic role is confirmed in independent series. [ABSTRACT FROM AUTHOR]

Partial least squares regression is a very powerful multivariate regression technique to model multicollinear data or situation where the number of explanatory variables is larger than the sample size. Two algorithms, namely, Non-linear Iterative Partial Least Squares (NIPALS) and Straightforward implementation of a statistically inspired modification of the partial least squares (SIMPLS) are very popular to solve a partial least squares regression problem. Both procedures, however, are very sensitive to the presence of outliers, and this might lead to very poor fit for the bulk of the data. A robust procedure, which is a modification of the SIMPLS algorithm, is introduced and its performance is illustrated by an extensive Monte Carlo simulation and 2 applications to real data sets. The new procedure is compared with the most recent proposals in literature demonstrating a better robust performance. [ABSTRACT FROM AUTHOR]

Aims A new subtype of granzyme B (GrB)-producing regulatory B cells (Bregs) has been described recently; these peculiar cytotoxic B cells are increased significantly in interleukin ( IL)-21-rich settings, and in particular during HIV and Epstein-Barr virus ( EBV) infection. Our aim is to report a unique case of an EBV-positive diffuse large B cell lymphoma ( DLBCL) with cytotoxic features arisen in an HIV+ patient, and to understand if this lesion may represent a proliferation of neoplastic cytotoxic Bregs. Methods and results We describe a 66-year-old male patient who presented with cervical lymph node enlargement and B symptoms; subsequently, HIV infection was diagnosed. Histopathological, immunohistochemical and molecular studies were performed, and revealed an EBV-positive DLBCL with cytotoxic features. Considering the immunological setting and unconventional phenotype observed, we tried to evaluate further the expression of GrB and IL-21 in another 150 aggressive B cell lymphomas (17 of 150 EBV+, two of 150 EBV+/ HIV+). Minimal dot-like expression of GrB was found in seven lymphomas (in fewer than 1% of tumour cells), three of which were EBV-positive. Conclusions Breg origin has never been reported in B cell lymphomas. We describe an exceptional case of EBV-positive DLBCL with aberrant expression of cytotoxic markers in a patient with a previously unknown HIV infection. We propose cytotoxic Bregs as a possible normal counterpart for this unusual tumour. [ABSTRACT FROM AUTHOR]

Fine-needle aspiration cytology and core-needle biopsy in the diagnosis of lymphadenopathies: words of endorsement. For these reasons, they should be preferred to lymph node core biopsies and/or fine needle aspiration cytology in all suitable cases. Lymph node core needle biopsy in lymphoproliferative disorders - Authors' reply to Al-Abbadi and colleagues. [Extracted from the article]

The article offers information on the BRAF gene mutations, which is found in Richter syndrome. Topics discussed increase survival of patients with melanoma, identifying recurrent genetic abnormalities associated with transformation, sequences of allele-specific oligonucleotides, and frequency of BRAF mutations in Richter syndrome compared to untransformed chronic lymphocytic leukaemia.

Aims High levels of vascular endothelial growth factor A ( VEGFA) seem to herald a worse prognosis in mycosis fungoides ( MF). In this study, we aimed to characterize more clearly VEGFA gene and protein expression in MF. Methods and results First, we compared VEGFA mRNA levels in MF and in normal T lymphocyte samples; significantly higher VEGFA levels were found in MF. We then studied VEGFA expression in different normal T cell subsets, focusing on CD4+, CD8+, resting and activated T lymphocytes. We applied the gene signatures of the normal T cell subsets to MF samples and found that activated T lymphocytes represented the closest normal counterpart of the tumour. However, VEGFA mRNA levels were significantly higher in MF than in activated normal T cells, suggesting that VEGFA overexpression in MF represents an attribute acquired during neoplastic transformation: no significant VEGFA expression differences were recorded between early and advanced stages. Gene expression profile results were supported by immunohistochemistry in routine sections from 27 MF cases. Conclusions For the first time, we demonstrate VEGFA expression in MF cells, suggesting that the VEGF pathway may be implicated in MF pathogenesis and can represent a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue ( MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans ( P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl-2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype. Methods and results Two hundred and five follicular lymphomas were investigated with immunohistochemistry and fluorescence in-situ hybridization ( FISH). The use of three distinct anti-bcl-2 antibodies together with CD10 expression data and FISH analysis for bcl-2 and bcl-6 rearrangements allowed subclassification of follicular lymphoma into four distinct subgroups: (i) CD10-positive/bcl-2-positive, (ii) CD10-positive/bcl-2-negative, (iii) CD10-negative/bcl-2-positive, and (iv) CD10-negative/bcl-2-negative. All cases were bcl-6-positive. STMN1 (stathmin) was shown to be helpful in diagnosing bcl-2-negative and/or CD10-negative follicular lymphomas, and in their distinction from marginal zone B-cell lymphoma. Conclusions Combined immunohistological and molecular analyses reveal that follicular lymphomas showing an atypical immunophenotypic and molecular profile exist, and we demonstrate that STMN1 represents a novel useful diagnostic marker for these. [ABSTRACT FROM AUTHOR]

Falini B, Agostinelli C, Bigerna B, Pucciarini A, Pacini R, Tabarrini A, Falcinelli F, Piccioli M, Paulli M, Gambacorta M, Ponzoni M, Tiacci E, Ascani S, Martelli M P, Dalla Favera R, Stein H & Pileri S A (2012) Histopathology 61, 930-941 IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas Aims: The aim of this study was to search for a molecule selectively expressed by marginal zone (MZ) lymphomas (MZLs), whose diagnosis is currently based on morphological criteria and negativity for markers detectable in other B-cell lymphomas. Methods and results: Two thousand one hundred and four peripheral lymphomas of various types were immunostained with a monoclonal antibody against immunoglobulin superfamily receptor translocation-associated 1 (IRTA1), which recognizes the equivalents of MZ in human lymphoid tissues other than spleen. IRTA1 expression was restricted to extranodal (93%) and nodal MZLs (73%) and to lymphomas with MZ differentiation. Extranodal MZL cells with the strongest IRTA1 expression were usually located adjacent to epithelia, mimicking the IRTA1 expression pattern of normal and acquired mucosa-associated lymphoid tissue (MALT). The cytological features, growth pattern and IRTA1 positivity in nodal MZLs suggest they may derive from IRTA1+ perifollicular B cells or monocytoid B cells detectable in reactive lymph nodes. Double immunostaining for IRTA1/bcl-6 tracked the colonization of B-cell follicles by MZL cells, and showed modulation of their phenotype (e.g. acquisition of bcl-6) during recirculation through germinal centres. MZL cells differentiating into plasma cells usually lost IRTA1. Conclusions: These results further expand our knowledge of the biology of MZLs, and highlight IRTA1 as the first positive marker for MZLs, enabling more accurate diagnosis of these neoplasms. [ABSTRACT FROM AUTHOR]

Agostinelli C, Paterson J C, Gupta R, Righi S, Sandri F, Piccaluga P P, Bacci F, Sabattini E, Pileri S A & Marafioti T (2012) Histopathology 61, 33-46 Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non-haematopoietic tumours using a newly developed rabbit monoclonal antibody Aims: We describe a new rabbit monoclonal antibody, raised against a fixation-resistant epitope of the transcription regulator LIM domain only 2 (LMO2). Methods and results: Lymphoma cell lines and a large series of normal and neoplastic samples were investigated by Western blot and immunohistochemistry. The antibody detected nuclear positivity for the protein, with the exception of a proportion of classical Hodgkin lymphomas (HLs), peripheral T cell lymphomas (PTCLs) and solid tumours that showed granular cytoplasmic staining. In normal lympho-haematopoietic tissues, LMO2 was expressed at different intensities by CD34+ blasts, haematopoietic precursors, germinal centre (GC), mantle and splenic marginal zone B cells. While reactive with only scattered elements in the thymus and nine of 237 PTCLs, the antibody stained 31 of 39 T-acute lymphoblastic lymphoma/leukaemias (T-ALLs) and the T-ALL-derived human leukaemic cell line, CCRF-CEM. LMO2 was found in 88% of B-acute lymphoblastic lymphoma/leukaemias (B-ALLs), 5% chronic lymphocytic leukaemias (CLLs) and 14%, 57% and 41% of mantle, follicular and Burkitt lymphomas, respectively. In the setting of diffuse large B cell lymphomas (DLBCLs), LMO2-positivity was related strongly to a GC phenotype. LMO2 was found in 83% primary mediastinal large B cell lymphomas (PMBLs) and 100% nodular lymphocyte predominant Hodgkin lymphomas (NLPHLs), whereas only 10% of classical HLs were stained. Acute and chronic myeloid leukaemias were usually positive. Conclusions: The new anti-LMO2 antibody can be applied confidently to routine sections, contributing to the differential diagnosis of several lymphoma subtypes, subtyping of DLBCLs and potential development of innovative therapies. [ABSTRACT FROM AUTHOR]

Hartmann S, Agostinelli C, Klapper W, Korkolopoulou P, Koch K, Marafioti T, Piccaluga P P, Patsouris E, Pileri S & Hansmann M-L (2011) Histopathology 59, 1173-1182 Revising the historical collection of epithelioid cell-rich lymphomas of the Kiel Lymph Node Registry: what is Lennert's lymphoma nowadays? Aims: Lennert's lymphoma is a rare variant of peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS). The aim of this study was to further characterize this tumour. Methods and results: Historical material of 97 lymphomas with a high content of epithelioid cells, collected at the Kiel Lymph Node Registry were reviewed, by applying immunohistochemistry and current diagnostic criteria. Among all cases revised, various B-cell lymphoma entities (25 cases), Hodgkin lymphomas (21 cases) and PTCL subtypes (48 cases) could be identified. A distinctive subgroup of eight PTCLs was found that were regarded as genuine Lennert's lymphomas. These cases were characterized by mild atypia, a non-activated cytotoxic phenotype [TIA1 cytotoxic granule-associated RNA binding protein (TIA1)-positive+ and granzyme B-negative], and a substantial lack of follicular T-helper (TFH) cell markers. Among the other PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL NOS, many cases with positivity for more than three TFH cell-associated molecules were recorded. Conclusions: Our study shows that, according to current criteria, Lennert's lymphoma is a rare but distinctive entity among epithelioid cell-rich lymphomas, differing on grounds of morphology and immunophenotype from other PTCL subtypes. An additional finding is the broad morphological spectrum of epithelioid-cell rich PTCLs showing a TFH cell phenotype. [ABSTRACT FROM AUTHOR]

Agostinelli C, Hartmann S, Klapper W, Korkolopoulou P, Righi S, Marafioti T, Piccaluga P P, Patsouris E, Hansmann M-L, Lennert K & Pileri S A (2011) Histopathology 59, 679-691 Peripheral T cell lymphomas with follicular T helper phenotype: a new basket or a distinct entity? Revising Karl Lennert's personal archive Aims: To revise 25 cases selected from Karl Lennert's personal archive (21) and Bologna and Frankfurt Registries (four) because of cytological similarities. Methods and results: All cases were provided with paraffin blocks and studied by immunohistochemistry and molecular techniques. While phenotyping was very informative, among molecular studies only EBER in situ-hybridization (ISH) was successful. Twenty-two cases were concluded as peripheral T cell lymphomas (PTCL). Of these, six were reclassified as angioimmunoblastic T cell lymphoma (AITL), 13 as PTCL, not otherwise specified (NOS), including four follicular variants and one tumour with T-zone pattern, and three as borderline tumours between AITL and PTCL/NOS. All these cases consisted homogeneously of small/medium-sized elements with mild nuclear atypia and an evident rim of clear/pale cytoplasm. On immunohistochemistry, they regularly expressed three to six follicular helper T cell (FTH)-associated markers. EBER-ISH revealed scattered EBV-infected B cells in all tumours except those with 'follicular' growth pattern. The content of follicular dendritic cells and high-endothelial venules varied significantly depending on the histotype. Conclusions: This study shows that: (i) historical material can be still employed usefully, and (ii) the FTH-phenotype corresponds to a broad spectrum of PTCLs that might form a new category to be validated in future molecular and clinicopathological analyses. [ABSTRACT FROM AUTHOR]

Outliers and gross errors in the data, as well as deviations from the normality assumption of the error distribution, impact adversely statistical analyses that are based on classical procedures such as least squares and maximum likelihood methods. We briefly review the cross‐validation (CV) method to model selection and discuss its robust extension based on weighted likelihood methodology. The main advantage of weighted CV is that it is computationally fast, much faster than many of the robust model selection procedures proposed in the literature. We present the weighted CV algorithm, its operating characteristics, and illustrate its performance under symmetric and asymmetric contamination. The procedure, in the absence of contamination and under mild conditions, is asymptotically equivalent to the CV method for model selection. Additionally, it is asymptotically loss efficient and differs from the robust CV procedure introduced in the literature in that it downweights only those observations that do not fit well the full model. This article is categorized under: Statistical and Graphical Methods of Data Analysis > Modeling Methods and AlgorithmsStatistical and Graphical Methods of Data Analysis > Robust MethodsStatistical Models > Linear ModelsStatistical Models > Model Selection Classical cross‐validation method for model selection and its robustification via weighted likelihood estimating equations method. [ABSTRACT FROM AUTHOR]

The article presents the case of a 58-year-old immunocompetent man who was hospitalized for cough and dyspnea. Chest radiography showed an enlarged cardiac profile and computerized tomography indicated a large intra-pericardial mass in the sternum and ribs. The patient was then diagnosed with diffuse large B-cell Lymphoma, immunoblastic, with activated B-cell phenotype. The patient's condition showed improvement after chemotherapy under the CHOP-Rituximab scheme and pegylated filgrastim.

The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3 high patients displayed longer survival compared with NR1H3 low cases and a high-resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo-related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Ibrutinib is a Burton tyrosine kinase inhibitor (BTKi) approved for the treatment of several hematologic malignancies. Analyze skin adverse events (SAE). All the patients treated with Ibrutinib featuring cutaneous adverse events were selected. Twenty five patients were retrieved with a median interval between Ibrutinib start and SAE time of onset of 120 days. Most common SAE observed involved hairs and nails. Eczematous reaction and leucocytoclastic vasculitis were also detected. One patient had a long-history Ibrutinib treatment and experienced numerous cutaneous adverse events. Infective disease such as superficial mycosis and impetigo were rarely present in our series. Despite the development of cutaneous SAE, all the patients continued their concomitant drugs without the onset of any further SAE. Our data suggest Ibrutinib-associated rash should be distinguished in early and late events and a careful dermatologic management of patients should be scheduled., (© 2020 Wiley Periodicals LLC.)