A targeted gene signature stratifying mediastinal gray zone lymphoma into classical HL-like or PMBL-like subtypes.

Not available.

Rapidly progressive dementia due to intravascular lymphoma: A prion disease reference center experience.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal lymphoma that is characterized by the selective growth of neoplastic cells in blood vessels, representing a potentially treatable cause of rapidly progressive dementia (RPD). Given its diverse clinical and instrumental presentation, it is often misdiagnosed with more common RPD causes, for example, Creutzfeldt-Jakob disease (CJD) or vascular dementia. METHODS: This study presents the clinical and histopathological characteristics of four IVLBCL cases that we diagnosed post-mortem over 20 years among over 600 brain samples received as suspected CJD cases at our prion disease reference center. RESULTS: Our patients exhibited various presenting symptoms, including behavioral disturbances, disorientation, and alertness fluctuations. The diagnostic tests performed at the time, including blood work, cerebrospinal fluid (CSF) analyses, electroencephalography, and neuroimaging, yielded nonspecific and occasionally misleading results. Consequently, the patients were repeatedly diagnosed as variably having CJD, epilepsy, vascular dementia, and encephalitis. The stored CSF samples of two patients tested negative at prion real-time quaking-induced conversion (RT-QuIC), which we performed afterwards for research purposes. Neuropathological analysis revealed a differential involvement of various brain areas, with frontotemporal neocortices being the most affected. CONCLUSIONS: Our results confirm the significant clinical and instrumental heterogeneity of IVLBCL. Neuropathological evidence of the preferential involvement of frontotemporal neocortices, potentially conditioning the clinical phenotype, could be relevant to reach an early diagnosis. Finally, given the therapeutic implications of its misdiagnosis with CJD, we emphasize the utility of prion RT-QuIC as a test for ruling out CJD in these patients.

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders (SMPLPD), demographical, clinical, therapeutic and prognostic aspects: a retrospective monocentric analysis.

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders (SMPLPD), also known as PCS-TCLPD, represent a rare group of hematologic diseases primarily affecting the skin. In this retrospective single-centre case series study, we aimed to investigate the demographic, clinical, therapeutic, and prognostic aspects of SMPLPD. We collected data from cases diagnosed between 2010 and the present, employing histopathological and immunohistochemical methods following WHO criteria. We included 22 patients with a median age of 61.50 years and median time between clinical onset and diagnosis of 3.00 months. Surgical excision with conservative margins was the primary choice, showing clinical remission in 17 cases, while non-surgical treatments, including radiotherapy, high-potency steroid treatment and ablative laser, achieved clinical remission in four cases. Clinical presentations varied, but the most common one was a single violaceous nodule/papule on upper body parts. In conclusion, our single-centre case series provides valuable insights into SMPLPD, highlighting the effectiveness of surgical treatments and the potential of non-surgical ones. Even if controversial, the benign nature of SMPLPD emphasizes the importance of achieving tumour clearance with acceptable aesthetic outcomes.

Genomic Profiling of Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System Suggests Novel Potential Therapeutic Targets.

Primary diffuse large B-cell lymphoma of the primary central nervous system (CNS-DLBCL) is an aggressive disease, with dismal prognosis despite the use of high-dose methotrexate-based polychemotherapy. Our study aimed to expand the biologic profiles of CNS-DLBCL and to correlate them with clinical/imaging findings to gain diagnostic insight and possibly identify new therapeutic targets. We selected 61 CNS-DLBCL whose formalin-fixed paraffin-embedded samples were available at first diagnosis. These were investigated by immunohistochemistry, cMYC rearrangements were explored by fluorescence in situ hybridization, and CNS-DLBCL mutated genes were evaluated by next-generation sequencing. CD10, BCL6, and IRF4 were observed in 16%, 83.6%, and 93% of cases, respectively. As typical of CNS lymphoma, 10 (16.4%) of 61 cases were classified as germinal center (GCB) type and 51 (83.6%) of 61 as non-germinal center (non-GCB) type according to the Hans algorithm. Double-expression status for BCL2 and cMYC was detected in 36 (59%) of 61 cases whereas 25 (41%) of 61 were non-DE. Rearrangement of the cMYC gene was detected in 2 cases, associated with BCL6 translocation only in 1 case MYD88, PIM1, CD79B, and TP53 were mutated in 54.5%, 53.5%, 30.2%, and 18.4% cases, respectively. Novel mutations not previously reported in CNS-DLBCL were found: AIP in 23.1%, PI3KCA in 15%, NOTCH1 in 11.4%, GNAS in 8.1%, CASP8 in 7.9%, EGFR in 6.4%, PTEN in 5.1, and KRAS in 2.6% of cases. Survival was significantly longer for patients with mutated MYD88 (8.7 months vs 1.7 months; log-rank test = 5.43; P = .020) and for patients with mutated CD79B (10.8 months vs 2.5 months; log-rank test = 4.64; P = .031). MYD88 and CD79B predicted a longer survival in patients affected by CNS-DLBCL. Notably, we identified novel mutations that enrich the mutational landscape of CNS-DLBCL, suggest a role of PTEN-PI3K-AKT and receptor tyrosine kinase-RAS-mitogen-activated protein kinase signaling in a subset of CNS-DLBCL, and provide new potential therapeutic targets.

Multicentric Castleman Disease and Concurrent Hematological Disorders: The Occurrence of Plasmacytoma and the Hypotheses Arising from Literature Review.

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms.

Follicular Lymphoma Microenvironment Traits Associated with Event-Free Survival.

The majority of patients with Follicular Lymphoma (FL) experience subsequent phases of remission and relapse, making the disease "virtually" incurable. To predict the outcome of FL patients at diagnosis, various clinical-based prognostic scores have been proposed; nonetheless, they continue to fail for a subset of patients. Gene expression profiling has highlighted the pivotal role of the tumor microenvironment (TME) in the FL prognosis; nevertheless, there is still a need to standardize the assessment of immune-infiltrating cells for the prognostic classification of patients with early or late progressing disease. We studied a retrospective cohort of 49 FL lymph node biopsies at the time of the initial diagnosis using pathologist-guided analysis on whole slide images, and we characterized the immune repertoire for both quantity and distribution (intrafollicular, IF and extrafollicular, EF) of cell subsets in relation to clinical outcome. We looked for the natural killer (CD56), T lymphocyte (CD8, CD4, PD1) and macrophage (CD68, CD163, MA4A4A)-associated markers. High CD163/CD8 EF ratios and high CD56/MS4A4A EF ratios, according to Kaplan-Meier estimates were linked with shorter EFS (event-free survival), with the former being the only one associated with POD24. In contrast to IF CD68+ cells, which represent a more homogeneous population, higher in non-progressing patients, EF CD68+ macrophages did not stratify according to survival. We also identify distinctive MS4A4A+CD163-macrophage populations with different prognostic weights. Enlarging the macrophage characterization and combining it with a lymphoid marker in the rituximab era, in our opinion, may enable prognostic stratification for low-/high-grade FL patients beyond POD24. These findings warrant validation across larger FL cohorts.

ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment.

ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3' region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment.

Thrombopoietin receptor agonists increase splenic regulatory T-cell numbers in immune thrombocytopenia.

Thrombopoietin receptor agonists (TPO-RA) are a valid therapy for immune thrombocytopenia (ITP), due to megakaryocyte stimulation and (poorly characterised) immune-modulatory effects. The spleen is pivotal in the pathogenesis of ITP, yet little is known on its immune microenvironment and on effects of TPO-RA on this organ. To address these topics, we analysed 35 spleens removed for primary refractory ITP. Pre-splenectomy TPO-RA administration correlated with increased splenic regulatory T cells (Tregs), type 2 T-helper cells and histiocyte density and with reduced red pulp sinusoids. Surgical outcome was not associated with TPO-RA administration, other pre-splenectomy therapies and/or Treg density. In conclusion, TPO-RA affect the splenic microenvironment, but this has no impact on splenectomy outcome.

Burkitt lymphoma with a granulomatous reaction: an M1/Th1-polarised microenvironment is associated with controlled growth and spontaneous regression.

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.

Droplet digital polymerase chain reaction for the assessment of disease burden in hairy cell leukemia.

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.

A three-gene signature based on MYC, BCL-2 and NFKBIA improves risk stratification in diffuse large B-cell lymphoma.

Recent randomized trials focused on gene expression-based determination of the cell of origin in diffuse large B-cell lymphoma could not show significant improvements by adding novel agents to standard chemoimmunotherapy. The aim of this study was the identification of a gene signature able to refine current prognostication algorithms and applicable to clinical practice. Here we used a targeted gene expression profiling panel combining the Lymph2Cx signature for cell of origin classification with additional targets including MYC, BCL-2 and NFKBIA, in 186 patients from 2 randomized trials (discovery cohort) (NCT00355199 and NCT00499018). Data were validated in 3 independent series (2 large public datasets and a real-life cohort). By integrating the cell of origin, MYC/BCL-2 double expressor status and NFKBIA expression, we defined a 3-gene signature combining MYC, BCL-2 and NFKBIA (MBN-signature), which outperformed the MYC/BCL-2 double expressor status in multivariate analysis, and allowed further risk stratification within the germinal center B-cell/unclassified subset. The high-risk (MBN Sig-high) subgroup identified the vast majority of double hit cases and a significant fraction of Activated B-Cell-derived diffuse large B-cell lymphomas. These results were validated in 3 independent series including a cohort from the REMoDL-B trial, where, in an exploratory ad hoc analysis, the addition of bortezomib in the MBN Sig-high subgroup provided a progression free survival advantage compared with standard chemoimmunotherapy. These data indicate that a simple 3-gene signature based on MYC, BCL-2 and NFKBIA could refine the prognostic stratification in diffuse large B-cell lymphoma, and might be the basis for future precision-therapy approaches.

Cytogenetic study in primary myelofibrosis at diagnosis: Clinical and histological association and impact on survival according to WHO 2017 classification in an Italian multicenter series.

We analyzed cytogenetic data at diagnosis in 395 primary myelofibrosis (PMF) patients to evaluate any possible association between karyotype and WHO 2017 classification and its impact on prognosis. All the cases were diagnosed and followed at five Italian Hematological Centers between November 1983 and December 2016. An abnormal karyotype (AK) was found in 69 patients and clustered differently according to bone marrow fibrosis grade as it was found in 31 (27.0%) cases with overt fibrotic and 38 (13.6%) with pre-fibrotic PMF (p = 0.001). Sex, anemia, thrombocytopenia, circulating blasts ≥1%, higher lactate dehydrogenase, and International Prognostic Scoring System risk classes were all significantly associated with karyotype. At a median follow-up of >6 years, 101 deaths were recorded. Survival was different between AK and normal karyotype (NK) patients with an estimated median overall survival (OS) of 11.6 and 25.7 years, respectively (p = 0.0148). In conclusion, in our cohort around 20% of patients had an AK, more frequently in subjects with an advanced bone marrow fibrosis grade and clinical-laboratory features indicative of a more aggressive disease. This study shows that an AK confers a more severe clinical phenotype and impacts adversely on OS, thus representing an additional parameter to be considered in the evaluation of PMF prognosis.

Histology of the spleen in immune thrombocytopenia: clinical-pathological characterization and prognostic implications.

OBJECTIVE: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. METHODS: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. RESULTS: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. CONCLUSION: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.

The treatment of hairy cell leukemia with a focus on long lasting responses to cladribine: A 30-year experience.

The treatment of hairy cell leukemia (HCL) has considerably changed over years. Purine analogues, namely cladribine, now represent the treatment of choice. One hundred and eighty-four patients were followed between 1986 and 2018 and treated according to era-specific guidelines. Responses were classified by combining Consensus Resolution criteria and marrow immunohistochemistry. Patients were grouped according to the number of treatment lines they received. Patients treated first line responded in 86% of cases, with complete response (CR) in 44% of cases. Response rates remained high throughout the first four lines (84%, 81%, 79% for the second line onward, with CR in 38%, 37%, 15% of cases respectively). One hundred and twenty-two patients received cladribine as first line treatment, with a response rate of 86% and a CR rate of 54%. Among the 66 CR patients, 45 (68%) have never received further therapy: 11 patients are in continuous CR between 5 and 10 years after treatment, 14 between 10 and 20 years and three patients at more than 20 years. Median time-to-next treatment (TTNT) for frontline cladribine-treated patients was 8.2 years: partial responders had a significantly shorter median TTNT than CR patients (5.3 years vs median not reached at 25.8 years, p < 0.001). Patients with HCL require subsequent lines of therapy in more than 50% of cases. Purine analogues allow significant response rates when applied first line and upon retreatment. Some patients may enjoy long lasting treatment-free intervals after one course of cladribine.

Correction: Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified.

Peripheral T-cell lymphoma not otherwise specified represents a diagnostic category comprising clinically, histologically, and molecularly heterogeneous neoplasms that are poorly understood. The genetic landscape of peripheral T-cell lymphoma not otherwise specified remains largely undefined, only a few sequencing studies having been conducted so far. In order to improve our understanding of the genetics of this neoplasm, we performed whole exome sequencing along with RNA-sequencing in a discovery set of 21 cases. According to whole exome sequencing results and mutations previously reported in other peripheral T-cell lymphomas, 137 genes were sequenced by a targeted deep approach in 71 tumor samples. In addition to epigenetic modifiers implicated in all subtypes of T-cell neoplasm (TET2, DNMT3A, KMT2D, KMT2C, SETD2), recurrent mutations of the FAT1 tumor suppressor gene were for the first time recorded in 39% of cases. Mutations of the tumor suppressor genes LATS1, STK3, ATM, TP53, and TP63 were also observed, although at a lower frequency. Patients with FAT1 mutations showed inferior overall survival compared to those with wild-type FAT1. Although peripheral T-cell lymphoma not otherwise specified remains a broad category also on molecular grounds, the present study highlights that FAT1 mutations occur in a significant proportion of cases, being provided with both pathogenetic and prognostic impact.

Diagnostic accuracy of positron emission tomography/computed tomography-driven biopsy for the diagnosis of lymphoma.

INTRODUCTION: Biopsy of affected tissue is required for lymphoma diagnosis and to plan treatment. Open incisional biopsy is traditionally the method of choice. Nevertheless, it requires hospitalization, availability of an operating room, and sometimes general anesthesia, and it is associated with several drawbacks. Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) can be potentially used to drive biopsy to the most metabolically active area within a lymph node or extranodal masses. METHODS: A study of diagnostic accuracy was conducted to assess the performance of a PET-driven needle biopsy in patients with suspect active lymphoma. RESULTS: Overall, 99 procedures have been performed: three (3.0%) were interrupted because of pain but were successfully repeated in two cases. Median SUVmax of target lesions was 10.7. In 84/96 cases, the tissue was considered adequate to formulate a diagnosis (diagnostic yield of 87.5%) and to guide the following clinical decision. The target specimen was a lymph node in 60 cases and an extranodal site in 36. No serious adverse events occurred. The sensitivity of this procedure was 96%, with a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 75%. CONCLUSION: Patients can benefit from a minimally invasive procedure which allows a timely and accurate diagnosis of lymphoma at onset or relapse.

Bendamustine-rituximab regimen in untreated indolent marginal zone lymphoma: experience on 65 patients.

First line therapy of patients with marginal zone lymphomas (MZL) is not well established and various regimens with chemo-immunotherapy can be used. Rituximab plus bendamustine (BR) is an effective and manageable treatment option for patients affected by indolent non-Hodgkin lymphoma. The aim of this monocentric retrospective study was to analyze the effectiveness and safety of the use of BR regimen in MZL patients in first line in daily clinical practice. The treatment schedule was rituximab at the dose of 375 mg/m2 on day 1 of each cycle and bendamustine at the dose of 90 mg/m2 on day 2 and 3, every 28 days for a maximum of 6 cycles. We analyzed 65 MZL patients (28 extranodal [EMZL], 23 splenic [SMZL], and 14 nodal [NMZL]) who underwent BR regimen as first line treatment. The median time from diagnosis to therapy was 2.5 months. Final responses were: 38 complete response (CR, 58.5%), 20 partial response and 7 progressive disease, leading to an overall response rate (ORR) of 89.2%. With respect to the histology, the ORR was 89.3% for EMZL, 82.6% for SMZL and 100% for NMZL, respectively (difference not statistically significant). With a median follow-up time of 44.6 months (range, 3.3-175.0 months), 2 (one EMZL after 42 months and one SMZL after 10 months) of 38 (5.2%) CR patients had disease relapse, yielding an estimated disease free survival of 89.2% at 61.1 months. The estimated 6-year progression free survival was 71.8% with 15 relapsed/progressed patients showing lymphoma recurrence within 48 months from end of treatment. The most frequently reported adverse events (any grade) were neutropenia (N = 35, 53.8%), fatigue (N = 15, 23.0%), and nausea (N = 12, 18.4%). All toxicities quickly resolved and no treatment-related death occurred. The BR regimen is effective and feasible in MZL patients inducing prolonged disease control with manageable toxicities.

Intrahepatocellular crystal storing mimicking a clinical liver disease during monoclonal gammopathy: report of a case and review of the literature.

We present an unusual case of liver involvement in monoclonal gammopathy with generalized crystal-storing histiocytosis (G-CSH).A bone marrow storage disease was diagnosed in a 79-year-old man with monoclonal gammopathy of uncertain significance (MGUS). The patient presented with pleural effusion, an osteolytic lesion of the humerus, and an increase of aspartate transaminase and cholestatic markers that raised the clinical suspect of liver disease. A second bone marrow biopsy confirmed the diagnosis of MGUS with a histiocytic component suggestive for G-CSH.Liver biopsy showed an unremarkable histology, no significant inflammatory infiltrates, and intrasinusoidal foamy histiocytes. PAS and Masson's trichrome stains, showed, in the cytoplasm of both histiocytes and hepatocytes, rod-shaped eosinophilic crystals, which were immunoreactive for kappa light chains. Transmission electron microscopy performed on reprocessed histological sections confirmed the presence of crystals in the hepatocyte cytoplasms. Immunogold labeling intensely stained crystals for kappa light chains.To the best of our knowledge, this is the second case in which an intrahepatocellular crystal storage is described during liver involvement in G-CSH. The present case also suggests that an increase in liver serum enzymes may support the clinical diagnosis of liver CSH in a patient with MGUS.

Gastrointestinal lymphoproliferative lesions: a practical diagnostic approach.

The gastrointestinal tract (GI) is the primary site of lymphoproliferative lesions, spanning from reactive lymphoid hyperplasia to overt lymphoma. The diagnosis of these diseases is challenging and an integrated approach based on clinical, morphological, immunohistochemical and molecular data is needed. To reach to confident conclusions, a stepwise approach is highly recommended. Histological evaluation should first assess the benign versus neoplastic nature of a given lymphoid infiltrate. Morphological and phenotypic analyses should then be applied to get to a definite diagnosis.This review addresses the key histological features and diagnostic workup of the most common GI non-Hodgkin lymphomas (NHLs). Differential diagnoses and possible pitfalls are discussed by considering distinct groups of lesions (i.e. small to medium B-cell NHLs; medium to large B-cell NHLs; T-cell NHLs; and mimickers of Hodgkin lymphoma). The key clinical and epidemiological features of each entity are also described.