[Interpretation of T-cell and NK-cell lymphoid proliferations and lymphomas in the 5th edition of the WHO classification of haematolymphoid tumours].

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.

Genomic landscape and distinct molecular subtypes of primary testicular lymphoma.

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.

[New classifications of malignant lymphomas - What changes are relevant for practice?] / Neue Klassifikationen maligner Lymphome ­ Welche Änderungen sind für die Praxis relevant?

An internationally uniform lymphoma classification is of fundamental importance for the comparability of clinical studies. There are currently 2 parallel classifications: the "International Consensus Classification" and the WHO-classification. Follicular lymphoma 3B is classified separately as follicular large cell lymphoma in WHO-HAEM5. The diagnostic criteria of lymphoplasmocytic lymphoma (LPL) have been adjusted, both classifications recommend molecular testing for MYD88 and CXCR4 mutations. There are no significant diagnostic changes in aggressive B-cell lymphomas. The ICC classify NLPBL and THRLBCL into the group of large B-cell lymphomas (LBCL). NLPHL/NLPBL-specific therapy must be considered, which differs greatly from the therapy of DLBCL, especially in the early stages. Peripheral T-cell lymphomas are a group of nodal T-cell lymphomas with a TFH phenotype and frequent mutations; peripheral T-cell lymphoma (NOS) is therefore a diagnosis of exclusion. Indolent T-cell lymphomas/lymphoproliferations of the GI tract are rare but must be differentiated from aggressive T-cell lymphomas. The WHO-HAEM5 also includes reactive/non-neoplastic lymph node lesions classified according to B or T cell predominance.

Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento / Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years

Antecedentes y objetivos Los linfomas cutáneos primarios (LCP) son un conjunto de entidades poco frecuentes. En febrero del 2018 se describieron los resultados del primer año de funcionamiento del Registro de linfomas cutáneos primarios de la AEDV. En el presente trabajo actualizamos los resultados tras 5 años de funcionamiento. Pacientes y métodos Registro de enfermedad de pacientes con LCP. Se recogieron datos prospectivamente de los pacientes, incluyendo diagnóstico, tratamientos, pruebas realizadas y estado actual del paciente. Se realizó un análisis descriptivo. Resultados En diciembre del 2021 se había incluido a un total de 2020 pacientes en el Registro, pertenecientes a 33 hospitales españoles. El 59% fueron hombres, la edad media fue de 62,2 años. Se agruparon en 4grandes grupos diagnósticos: micosis fungoide/síndrome de Sézary (1.112, 55%), LCP de células B (547, 27,1%), trastornos linfoproliferativos de células T CD30+(222, 11%) y otros linfomas T (116, 5,8%). La mayoría presentó estadio T1, encontrándose actualmente casi el 75% en remisión completa (43,5%) o enfermedad estable (EE; 27%). Los tratamientos más usados fueron corticoides tópicos (1.369, 67,8%), fototerapia (890, 44,1%), cirugía (412, 20,4%) y radioterapia (384, 19%). Conclusión Las características del paciente con LCP en España no difieren de otras series. El mayor tamaño del registro permite precisar mejor los datos con respecto a los resultados del primer año. Este registro facilita al grupo de linfomas de la AEDV realizar investigación clínica, surgiendo ya trabajos publicados de dicho registro (AU)

Background and objective Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. Patients and methods RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. Results Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). Conclusion The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data (AU)

[Translated article] Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento

Background and objective Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. Patients and methods RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. Results Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). Conclusion The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data (AU)

Antecedentes y objetivos Los linfomas cutáneos primarios (LCP) son un conjunto de entidades poco frecuentes. En febrero del 2018 se describieron los resultados del primer año de funcionamiento del Registro de linfomas cutáneos primarios de la AEDV. En el presente trabajo actualizamos los resultados tras 5 años de funcionamiento. Pacientes y métodos Registro de enfermedad de pacientes con LCP. Se recogieron datos prospectivamente de los pacientes, incluyendo diagnóstico, tratamientos, pruebas realizadas y estado actual del paciente. Se realizó un análisis descriptivo. Resultados En diciembre del 2021 se había incluido a un total de 2020 pacientes en el Registro, pertenecientes a 33 hospitales españoles. El 59% fueron hombres, la edad media fue de 62,2 años. Se agruparon en 4grandes grupos diagnósticos: micosis fungoide/síndrome de Sézary (1.112, 55%), LCP de células B (547, 27,1%), trastornos linfoproliferativos de células T CD30+(222, 11%) y otros linfomas T (116, 5,8%). La mayoría presentó estadio T1, encontrándose actualmente casi el 75% en remisión completa (43,5%) o enfermedad estable (EE; 27%). Los tratamientos más usados fueron corticoides tópicos (1.369, 67,8%), fototerapia (890, 44,1%), cirugía (412, 20,4%) y radioterapia (384, 19%). Conclusión Las características del paciente con LCP en España no difieren de otras series. El mayor tamaño del registro permite precisar mejor los datos con respecto a los resultados del primer año. Este registro facilita al grupo de linfomas de la AEDV realizar investigación clínica, surgiendo ya trabajos publicados de dicho registro (AU)

Epstein-Barr virus prevalence among subtypes of malignant lymphoma in Rwanda, 2012 to 2018.

Few data exist on Epstein-Barr virus (EBV) prevalence across the full spectrum of lymphoma subtypes, particularly in sub-Saharan Africa. The objective of our study was to test the presence of EBV in a nationally representative sample of malignant lymphomas diagnosed in the Butaro Cancer Center of Excellence (BCCOE) in Rwanda. Of 102 Hodgkin (HL) and 378 non-Hodgkin lymphomas (NHL) diagnosed in BCCOE between 2012 and 2018, 52 HL and 207 NHL were successfully tested by EBV-encoding RNA in situ hybridization. EBV prevalence was 54% in HL, being detected in all classical HL subtypes: mixed-cellularity (n = 3/8), nodular-sclerosis (n = 7/17) and lymphocyte-rich (n = 2/3). EBV prevalence was 9% in NHL, being 10% among 158 B-cell NHL, 3% among 35 T-cell NHL and the single NK-cell NHL was EBV-positive. Among B-cell NHL, EBV was present in the majority of Burkitt (n = 8/13), and was also rarely detected in follicular (n = 1/4) and acute B-cell lymphoblastic (n = 1/45) lymphomas. Five of the 45 (11%) diffuse large B-cell lymphomas (DLBCLs) were EBV-positive, including three out of five plasmablastic lymphoma (PBL). Of 39 HL and 163 NHL of known human immunodeficiency virus (HIV) status, 2 (5%) and 14 (9%) were HIV-positive, respectively, of which only four were also EBV-positive (2 PBL, 2 HL). In summary, we report rare regional-level data on the association of EBV with classical HL, Burkitt and DLBCLs, and report sporadic detection in other subtypes possibly related to EBV. Such data inform the burden of disease caused by EBV and can help guide application of future advances in EBV-specific prevention and therapeutics.

Genetic predisposition to lymphomas: Overview of rare syndromes and inherited familial variants.

Approximately 10 % of malignancies occur in carriers of germline mutations predisposing to cancer. A high risk of developing lymphomas has been noted in many primary immunodeficiencies, including DNA repair disorders. Moreover, implementation of next-generation sequencing has recently enabled to uncover rare genetic variants predisposing patients to lymphoid neoplasms. Some patients harboring inherited predisposition to lymphomas require dedicated clinical management, which will contribute to effective cancer treatment and to the prevention of potential severe toxicities and secondary malignancies. In line with that, our review summarizes the natural history of lymphoid tumors developing on different germline genetic backgrounds and discusses the progress that has been made toward successfully treating these malignancies.

Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age.

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues.

Prognostic role of clinical presentation, cytological picture and response to treatment in canine centroblastic lymphoma.

Centroblastic lymphoma (CBL) is the most common type of lymphoma in dogs and it usually responds well to chemotherapy. The aim of the study was to provide useful prognostic factors for dogs with CBL. Data regarding sex, breed, age, signalment, treatment and clinical course of the disease from 52 dogs diagnosed with centroblastic lymphoma (CBL) with cytology and immunocytochemistry were provisionally collected and related to the treatment outcome and survival. More than 80% of dogs were treated with chemotherapy and achieved complete remission in 80% of cases. Among the prognostic factors positively related to the overall survival time of dogs with CBL were: the application of chemotherapy, achieving a complete remission, application of at least one additional chemotherapeutic agent to the basic protocol, especially the administration of mitoxantrone and asparaginase. Moreover, mitotic count 14 or higher measured in cytological slides in the area of 2,37 mm2 have been linked to shorter overall survival in dogs with CBL.

Bioluminescent Tumor Signal Is Mouse Strain and Pelt Color Dependent: Experience in a Disseminated Lymphoma Model.

BACKGROUND: Many preclinical cancer studies use mice with varied phenotypes to monitor tumor treatment. We compared survival and optical imaging characteristics of strains with varied coat colors harboring luciferase-expressing disseminated lymphoma. RESULTS: Luciferase-expressing lymphoma cells (Raji-luc) were injected via tail vein into severe combined immunodeficient (SCID) and Rag2-IL2rg (R2G2) mice, and survival was tracked. Tumor signals were obtained by imaging ventral and dorsal aspects of mice. Signal attenuation by isolated mouse pelts was measured in vitro. R2G2 mice had decreased survival compared to SCID mice (17 vs. 32 days, p<0.001) despite similar bioluminescence signal when mice were imaged dorsally (p=0.37). However, signal was 17.3-fold higher in R2G2 mice compared to SCID (p<0.001) when imaged ventrally. Isolated dark R2G2 dorsal pelts attenuated signal more than ventral pelts when placed over cells in vitro. CONCLUSIONS: Mouse pelt color and imaging aspect are critical considerations for quantifying bioluminescent tumor signal, and the R2G2 mouse strain may prove useful for preclinical targeted therapy studies.

Variation of apoptotic and proliferative activity among lymphoma subtypes in dogs: A flow cytometric study.

Tumor growth depends on both proliferative and apoptotic rate of neoplastic cells. High proliferation index is a well-known negative prognostic factor in canine lymphomas, whereas little is known about apoptotic activity. We describe proliferative and apoptotic rates in different canine lymphoma subtypes at diagnosis. Flow cytometry (FC) was used to assess the percentage of proliferating cells (Ki67%) and of apoptotic cells (AnnV%) in 128 lymph node (LN) aspirates from dogs with lymphoma. Proliferation/apoptosis ratio (PAR) and turnover index (TI; Ki67% + AnnV%) were then calculated for each case. High-grade B-cell lymphomas showed high values for both Ki67% and AnnV%, low-grade B-cell lymphomas showed low Ki67% and high AnnV%, high-grade T-cell lymphomas showed high Ki67% and low AnnV%, and low-grade T-cell lymphomas showed low levels of both parameters. Lymphoblastic lymphomas had the highest PAR values. High-grade B-cell lymphomas had the highest TI values while small clear cells lymphomas the lowest. The panorama of proliferative and apoptotic activity widely varies among lymphoma subtypes. Our results lay the ground for future clinical and pharmacological studies.

Impact of laboratory work-up of lymphoma guidelines on cytopathology practices.

A multi-society expert panel recently published evidence-based guidelines and recommendations for the primary diagnosis and classification of lymphoma, which included a public comment period. The guideline concludes: "primary diagnosis and classification of lymphoma can be achieved with a variety of specimens." The guideline recommends that fine-needle aspiration biopsy (FNAB) cytomorphology not be used without ancillary testing, and that either flow cytometry or immunohistochemical immunophenotyping be performed for any type of specimen. Either excisional or core biopsy should be obtained when there is a high suspicion of lymphoma, and excision is recommended when feasible for Hodgkin lymphoma primary diagnosis. The use of cerebrospinal fluid to diagnose central nervous system lymphoma is discussed. For any patient with initial negative biopsy or fluid specimens and a high suspicion of lymphoma, additional tissue samples should be obtained. Additional molecular testing and good practice statements are summarized in the guideline. Cytopathologists should continue to advocate for judicious use of lymph node FNAB as an excellent triage tool that may require additional tissue biopsy for definitive diagnosis.

Lymphoma subtypes in India: a tertiary care center review.

Lymphomas are a group of neoplasm arising from immune cells with varied clinical presentation, molecular profile, morphology and immunophenotype. The epidemiology and response to treatment varies among patients from different geographical locations. We analyze the demographic characteristics of lymphomas in a tertiary care center of India over a period of five years. This was a retrospective study including cases from 2015 to 2019 which were classified according to WHO classification 2017. A total of 4115 lymphoma cases were diagnosed. Hodgkin lymphomas (HL) comprised 30.35% (n = 1249), and non-Hodgkin lymphoma (NHL) was 69.65% (n = 2866). Site of presentation was nodal in 64.76% cases, and 35.23% were extranodal. There was an overall male predominance. Among the NHLs, B-cell type comprised of 84.08% and 15.38% was T- and NK cell lymphomas. Mature B cell lymphomas comprised 82.41% with predominant being diffuse large B cell lymphoma type (42.53%) followed by follicular lymphoma (10.81%) and small lymphocytic lymphoma (6.10%). Among the T-cell type, PTCL NOS (2.65%) was the predominant subtype followed by ALK positive anaplastic large cell lymphoma (ALCL-ALK+) (2.44%), extranodal NK-T cell lymphoma (2.02%) and others. Classical type was predominant type (97.91%) among HL, and 2.08% were nodular lymphocyte predominant type. Among the classical HL, nodular sclerosis (28.1%) and mixed cellularity (32.18%) co-dominated. Our study indicates that the Indian population differs in the prevalence, presentation and the subtyping among various lymphomas. Higher prevalence of Hodgkin lymphoma, DLBCL, ALK + ALCL and immature cell neoplasm was noted.

Differential diagnostic ability of 18F-FDG PET/CT radiomics features between renal cell carcinoma and renal lymphoma.

BACKGROUND: The aim of this study is to determine the differential diagnostic value of texture parameters of PET/CT on renal cell carcinoma and renal lymphoma. METHODS: Twenty renal lymphoma and 18 renal cell carcinoma (RCC) patients were analyzed in this study. The pathological information and basic characteristics were extracted from the electronic medical record system of our hospital. We used LIFEx package to extract data from the radiomics images. Receiver operating characteristic analysis and binary logistic regression analysis was applied in determining the diagnostic accuracy of texture parameters as well as the synthetic parameter, of which the sensitivity and specificity was improved. RESULTS: There were 14 (two in Histogram, two in Grey Level Co-occurrence Matrix, five in Grey-Level Run Length Matrix, five in Grey-Level Zone Length Matrix) out of the texture parameters showing an area under the curve (AUC) >0.7 and P<0.05. Synthesized parameters of each section showed even higher differentiation ability, with AUC varying from 0.725 to 1.000. CONCLUSIONS: Texture analysis of 18F-FDG PET/CT could effectively differentiate between RCCs and renal lymphomas.

Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification.

BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.

Laboratory Workup of Lymphoma in Adults: Guideline From the American Society for Clinical Pathology and the College of American Pathologists.

CONTEXT.­: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. OBJECTIVE.­: To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. DESIGN.­: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.­: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS.­: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

Myeloid/lymphoid neoplasms with eosinophilia and FLT3 rearrangement.

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement are a unique category in the WHO classification, and include cases with rearrangement of PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2. We report three patients presented with eosinophilia and FLT3 rearrangement: the first case with chronic eosinophilic leukemia, not otherwise specified and T-lymphoblastic leukemia/lymphoma; the second case with myeloid sarcoma; and the last case with high-grade myelodysplastic syndrome. The first case showed t(13;14)(q12;q32), which encoded FLT3-TRIP11. The patient was treated with intense chemotherapy and subsequently sorafenib with clinical improvement. Unfortunately, the patient showed persistent residual disease and passed away 9 months after the diagnosis from pneumonia. The other two cases both showed ETV6-FLT3. The second patient was treated with local radiation and systemic chemotherapy including sorafenib and was alive. The third patient was treated with chemotherapy but showed transformation to acute myeloid leukemia and died 15 months after diagnosis. These cases are among a growing number of cases with FLT3 rearrangement that all showed similar clinicopathologic features characterized by myeloproliferative neoplasm with eosinophilia and frequent T lymphoblastic leukemia/lymphoma. Therefore, we propose that the myeloid/lymphoid neoplasms with eosinophilia and FLT3 rearrangement be included in the WHO category of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement.

Comparison of 11 automated PET segmentation methods in lymphoma.

Segmentation of lymphoma lesions in FDG PET/CT images is critical in both assessing individual lesions and quantifying patient disease burden. Simple thresholding methods remain common despite the large heterogeneity in lymphoma lesion location, size, and contrast. Here, we assess 11 automated PET segmentation methods for their use in two scenarios: individual lesion segmentation and patient-level disease quantification in lymphoma. Lesions on 18F-FDG PET/CT scans of 90 lymphoma patients were contoured by a nuclear medicine physician. Thresholding, active contours, clustering, adaptive region-growing, and convolutional neural network (CNN) methods were implemented on all physician-identified lesions. Lesion-level segmentation was evaluated using multiple segmentation performance metrics (Dice, Hausdorff Distance). Patient-level quantification of total disease burden (SUVtotal) and metabolic tumor volume (MTV) was assessed using Spearman's correlation coefficients between the segmentation output and physician contours. Lesion segmentation and patient quantification performance was compared to inter-physician agreement in a subset of 20 patients segmented by a second nuclear medicine physician. In total, 1223 lesions with median tumor-to-background ratio of 4.0 and volume of 1.8 cm3, were evaluated. When assessed for lesion segmentation, a 3D CNN, DeepMedic, achieved the highest performance across all evaluation metrics. DeepMedic, clustering methods, and an iterative threshold method had lesion-level segmentation performance comparable to the degree of inter-physician agreement. For patient-level SUVtotal and MTV quantification, all methods except 40% and 50% SUVmax and adaptive region-growing achieved a performance that was similar the agreement of the two physicians. Multiple methods, including a 3D CNN, clustering, and an iterative threshold method, achieved both good lesion-level segmentation and patient-level quantification performance in a population of 90 lymphoma patients. These methods are thus recommended over thresholding methods such as 40% and 50% SUVmax, which were consistently found to be significantly outside the limits defined by inter-physician agreement.

Scientific Advances and the Evolution of Diagnosis, Subclassification and Treatment of Lymphoma.

The diagnosis of lymphoma has evolved tremendously over time. Initially, diagnosis of lymphoma was largely based on morphology alone. Over time, immunophenotyping using flow cytometry and immunohistochemistry, and then in situ hybridization, have contributed dramatically to the pathologist's ability to recognize, diagnose and subclassify lymphomas more precisely. In recent years, cytogenetic and molecular genetic techniques have developed that allow evaluation of abnormalities in lymphomas, leading to an understanding of their pathogenesis and opening the door to targeted therapies that will lead to better outcomes for lymphoma patients.