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Recommendations for Initial Evaluation,Staging,and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma:The Lugano Classi?cation

Bruce D.Cheson,Richard I.Fisher,Sally F.Barrington,Franco Cavalli,Lawrence H.Schwartz,Emanuele Zucca,and T.Andrew Lister

See accompanying article on page 3048

Bruce D.Cheson,Georgetown Univer-sity Hospital,Lombardi Comprehensive Cancer Center,Washington,DC;Rich-ard I.Fisher,Fox Chase Cancer Center,Philadelphia,PA;Sally F.Barrington,St Thomas’Hospital;T.Andrew Lister,St Bartholomew’s Hospital,London,United Kingdom;Franco Cavalli and Emanuele Zucca,Oncology Institute of Southern Switzerland,Bellinzona,Swit-zerland;and Lawrence H.Schwartz,Columbia University,New York,NY.Published online ahead of print at https://www.wendangku.net/doc/3f8018073.html, on August 11,2014.Processed as a Rapid Communication manuscript.

Written on behalf of the following groups:Alliance,Australasian Leukae-mia and Lymphoma Group,Eastern Cooperative Oncology Group,European Mantle Cell Lymphoma Consortium,Italian Lymphoma Foundation,Euro-pean Organisation for Research and Treatment of Cancer/Dutch Hemato-Oncology Group,Grupo Espan ?ol de Linfomas y Trasplantes de Me ′dula O

′sea,German High-Grade Lymphoma Study Group,German Hodgkin’s Study Group,Japanese Lymphoma Study Group,Lymphoma Study Association,NCIC Clinical Trials Group,Nordic Lymphoma Study Group,Southwest Oncology Group,and United Kingdom National Cancer Research Institute.Presented in part at the 12th Interna-tional Conference on Malignant

Lymphoma,Lugano,Switzerland,June 19-22,2013.

Authors’disclosures of potential con-?icts of interest and author contribu-tions are found at the end of this article.

Corresponding author:Bruce D.

Cheson,MD,Georgetown University Hospital,Lombardi Comprehensive

Cancer Center,3800Reservoir Rd,NW,Washington,DC 20007;e-mail:bdc4@https://www.wendangku.net/doc/3f8018073.html,.

?2014by American Society of Clinical Oncology

0732-183X/14/3227w-3059w/$20.00DOI:10.1200/JCO.2013.54.8800

Abstract

The purpose of this work was to modernize recommendations for evaluation,staging,and response assessment of patients with Hodgkin lymphoma (HL)and non-Hodgkin lymphoma (NHL).A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano,Switzerland,in June 2011,that included leading hematologists,oncologists,radiation oncologists,pathologists,radiologists,and nuclear medicine physicians,representing major international lymphoma clinical trials groups and cancer centers.Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma,leading to revised criteria for staging and of the International Working Group Guidelines of 2007for response.As a result,?uorodeoxyglucose (FDG)positron emission tomography (PET)–computed tomogra-phy (CT)was formally incorporated into standard staging for FDG-avid lymphomas.A modi?cation of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent,but the suf?xes A or B for symptoms will only be included for HL.A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas.However,regardless of stage,general practice is to treat patients based on limited (stages I and II,nonbulky)or advanced (stage III or IV)disease,with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors.PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale.The product of the perpendicular diameters of a single node can be used to identify progressive disease.Routine surveillance scans are discouraged.These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.

J Clin Oncol 32:3059-3067.?2014by American Society of Clinical Oncology

INTRODUCTION

The availability of more effective therapies for lymphoma and the increasingly sensitive and spe-ci?c technologies for disease assessment provide rationale for updated patient evaluation,staging,and response criteria.These should be unambig-uous and universally applicable and facilitate the comparison of patients and results among studies and the evaluation of new therapies by regula-tory agencies.

Staging de?nes disease location and extent,suggests prognostic information,allows compari-sons among studies,and provides a baseline against which response or disease progression can be com-pared.Initial staging criteria were designed primar-ily for Hodgkin lymphoma (HL)1-3and were superseded by the Ann Arbor classi?cation,4which

subdivided HL patients into four stages and subclas-si?cation A and B based on the presence of fevers to greater than 101°F (38.3°C),weight loss,and night sweats and which has been the most widely used classi?cation since its introduction.The Cotswold classi?cation 5?rst formally incorporated computed tomography (CT)scans and introduced “X”for bulky disease and complete remission uncon?rmed (CRu)to describe patients with a residual mass after treatment that was most likely ?brous tissue.

The ?rst universally accepted response criteria for non-Hodgkin lymphoma (NHL),used also for HL,were published in 1999by the National Cancer Institute Working Group 6and revised in 2007by the International Working Group (IWG)7to incorpo-rate positron emission tomography (PET)and bone marrow immunohistochemistry and ?ow cytom-etry in response assessment,eliminating CRu.

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After extensive experience with these criteria,and recognizing the progress made after their publication,particularly in imaging tech-niques,a workshop was held at the11th International Conference on Malignant Lymphoma in Lugano,Switzerland,in June2011, which was attended by leading hematologists,oncologists,radia-tion oncologists,pathologists,radiologists,and nuclear medicine physicians,representing major lymphoma clinical trials groups and cancer centers in North America,Europe,Japan,and Austral-asia.The aim was to develop improved staging and response criteria for HL and NHL,relevant for community physicians, investigator-led trials,cooperative groups,and registration trials. Subcommittees focused on clinical and imaging issues,and a sub-sequent workshop at the12th International Conference on Malig-nant Lymphoma in2013led to the following revisions.

INITIAL EVALUATION

Diagnosis

Lymphoma diagnosis depends on morphology,immunohisto-chemistry,and?ow cytometry reviewed by an experienced lymphoma pathologist and,where appropriate,molecular studies to accurately categorize the lymphoma.8A?ne-needle aspirate is inadequate for initial diagnosis.An incisional or excisional biopsy is preferred to provide adequate tissue for these examinations,but a core-needle biopsy can be considered when excisional biopsy is not possible9,10 and to document relapse;however,a nondiagnostic sample must be followed by an incisional or excisional biopsy.With consent,addi-tional paraf?n-embedded,fresh-frozen tissue,or cell suspensions should be stored for future research.

Patient Evaluation

Clinical evaluation requires a comprehensive history including age;sex;absence/presence of fevers to more than101°F(38.3°C), chills,drenching night sweats,or unexplained weight loss more than 10%of body mass over6months;and history of malignancy.Fatigue, pruritus,and alcohol-induced pain in patients with HL should also be noted.Whereas these factors rarely direct treatment,their recurrence may herald disease relapse.

Physical examination includes measurement of accessible nodal groups and the size of the spleen and liver in centimeters below their respective costal margins in the midclavicular line.However,the sen-sitivity of physical examination is variable among observers.There-fore,organomegaly is formally de?ned by CT imaging(Table1).

Laboratory tests and other investigations necessary for the deter-mination of the prognostic indices for the different lymphoma sub-types and general patient management,including assessment of comorbidities,must be recorded.

Anatomic Staging

Historical series and prospective clinical trials have used the Ann Arbor staging system5to select patients and report outcomes. Now,stage is only one component of factors in prognostic indices increasingly used for pretreatment risk strati?cation and selection of therapy.11-15

PET-CT scanning has become the standard for assessment of response in most lymphomas.7For HL and?uorodeoxyglucose (FDG)-avid NHL subtypes,PET and PET-CT improve the accuracy of staging compared with CT scans for nodal and extranodal sites.16 PET-CT leads to change in stage in10%to30%of patients,more often upstaging,although alteration in management occurs in fewer pa-tients,with no demonstrated impact on overall outcome.However, improving staging accuracy ensures that fewer patients are under-treated or overtreated.16PET-CT is particularly important for staging before consideration of radiation therapy.17,18Although most lym-phomas are FDG avid,because of greater variability in FDG uptake, metabolic imaging is less reliable in other lymphomas.19-24Whereas mantle-cell lymphoma is routinely FDG avid,limited data suggest that the sensitivity and speci?city of identifying bowel involvement are low and should not replace other investigative measures.25,26 RECOMMENDATION FOR REVISIONS TO STAGING CRITERIA

PET-CT is already widely used for pretreatment assessment,often outside of clinical trials,to assign stage and has already been incorpo-rated into response assessment.7Although physical examination re-mains important,and despite concerns that more sensitive staging can

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result in stage migration,impairing the use of historically controlled data,PET-CT is critical as a baseline measurement before therapy to increase the accuracy of subsequent response assessment27,28(Table 1).Therefore,the consensus was that PET-CT should be recom-mended for routine staging of FDG-avid,nodal lymphomas(essen-tially all histologies except chronic lymphocytic leukemia/small lymphocytic lymphoma,lymphoplasmacytic lymphoma/Walden-stro¨m’s macroglobulinemia,mycosis fungoides,and marginal zone NHLs,unless there is a suspicion of aggressive transformation)as the gold standard.24

The following recommendations are intended for lymphomas with primarily nodal involvement,although they are also applicable to primary extranodal diffuse large B-cell lymphoma(DLBCL).Separate criteria have been proposed for primary extranodal29,30and cutane-ous lymphomas.31

Imaging

PET-CT is preferred for staging of FDG-avid lymphomas,and CT scan is preferred in the other lymphomas.A chest x-ray is no longer required in lymphoma staging because it less accurate than CT.32Moreover,CT identi?es more hilar nodes and may better discriminate between a single large nodal mass and an aggregate of individual nodes.Bulk is a negative prognostic factor,11,13-15but there is little agreement on its de?nition,which is disease,stage, and treatment speci?c.

These criteria strongly recommend PET-CT for staging of routinely FDG-avid histologies,especially in clinical trials.A contrast-enhanced CT scan should be included for a more accurate measure-ment of nodal size if required for trials;if necessary,to more accurately distinguish bowel from lymphadenopathy;and in the setting of com-pression/thrombosis of central/mediastinal vessels.Contrast-enhanced CT is also preferred for radiation planning.Variably FDG-avid histologies should be staged with a CT scan.

For patients staged with PET-CT,focal uptake in nodal and extranodal sites that is in keeping with lymphoma,according to the distribution and/or CT characteristics,is considered involvement with lymphoma,including spleen,liver,bone,thyroid,and so on.For patients staged with CT,up to six of the largest target nodes,nodal masses,or other lymphomatous lesions that are measurable in two diameters(longest diameter[LDi]and shortest diameter)should be identi?ed from different body regions representative of the patient’s overall disease burden and include mediastinal and retro-peritoneal disease,if involved.A measurable node must have an LDi greater than1.5cm.Measurable extranodal disease(eg,he-patic nodules)may be included in the six representative,measured lesions.A measurable extranodal lesion should have an LDi greater than1.0cm.All other lesions(including nodal,extranodal,and assessable disease)should be followed as nonmeasured disease(eg, cutaneous,GI,bone,spleen,liver,kidneys,pleural or pericardial effusions,ascites).In patients in whom a discordant histology or malignant transformation is suspected,a PET-CT may identify the optimal site to biopsy for con?rmation.20,21

Tumor Bulk

A single nodal mass,in contrast to multiple smaller nodes,of10 cm or greater than a third of the transthoracic diameter at any level of thoracic vertebrae as determined by CT is retained as the de?nition of bulky disease for HL.5A chest x-ray is not required to determine bulk because of its high concordance with CT.32However,a variety of sizes have been suggested for NHL,15,33with limited evidence suggesting6 cm as best for follicular lymphoma15and6to10cm in the rituximab era for DLBCL.34However,none of the proposed sizes have been validated in the current therapeutic era.Therefore,the recommenda-tion for HL and NHL is to record the longest measurement by CT scan,with the term X no longer necessary.

Spleen Involvement

A wide range of normal spleen sizes has been reported,35-37re-lated to race,body size,and height.38A spleen may be of normal size and still contain lymphoma or may be enlarged as a result of variations in blood volume,use of hematopoietic growth factors,or lymphoma-unrelated causes.Splenic involvement is best determined by PET-CT and may be characterized by homogeneous splenomegaly,diffuse in?ltration with miliary lesions,focal nodular lesions,or a large soli-tary mass.39There is no agreement on whether single,multiple,or volumetric measurements should be used to measure spleen size35or what cutoff to use for splenomegaly.For simplicity,a single measure-ment that correlates well with volume40,41is preferable to a volumetric measurement or estimation by equations,with special software,which are unlikely to be used routinely.

Most studies use10to12cm for vertical length.Our recommen-dation is to use a cutoff for splenomegaly of more than13cm.

Liver Involvement

Given variability in body habitus and the impact of numerous medical conditions,liver size by physical examination or CT scan is not a reliable measure of hepatic involvement by lymphoma.Similar to splenic involvement,diffusely increased or focal uptake,with or without focal or disseminated nodules,supports liver involvement. Bone Marrow Involvement

Bone marrow biopsy(BMB)has been standard in lymphoma staging,5although it is often performed even when the likelihood of involvement is low.The high sensitivity of PET-CT for bone mar-row involvement has recently called into question the continued use of BMB in several common histologies.42-46In one study in HL, 18%of patients had focal skeletal lesions on PET-CT,but only6% had positive BMB,46all with advanced disease on PET-CT.None of the patients would have been allocated to another treatment based on BMB results.Patients with early-stage disease rarely have in-volvement in the absence of a suggestive PET?nding,and those with advanced-stage disease rarely have involvement in the ab-sence of disease-related symptoms or other evidence of advanced-stage disease.Thus,if a PET-CT is performed,a bone marrow aspirate/biopsy is no longer required for the routine evaluation of patients with HL.

In DLBCL,PET-CT is also more sensitive than BMB but has been reported to miss low-volume diffuse involvement of10%to20%of the marrow.42,47-49Nevertheless,patients with clinical early-stage dis-ease rarely have involvement in the absence of a suggestive PET?nd-ing.In one study in DLBCL,27%of patients were found to have marrow involvement(94%by PET-CT and only40%by BMB).BMB was negative in21of28patients with focal disease on PET-CT and did not upstage any patients.Two cases(1.5%)of bone marrow involve-ment went undetected by PET-CT,with a10%in?ltrate of large cells. Thus,a PET-CT scan indicating bone or marrow involvement is

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usually suf?cient to designate advanced-stage disease,and a BMB is not required.Patients with a positive BMB generally have other fac-tors consistent with advanced stage or poor prognosis.49,50If the scan is negative,a BMB is indicated to identify involvement by discordant histology if relevant for a clinical trial or patient management.51 The data in all other lymphoma histologies are insuf?cient to change the standard practice,and a2.5-cm unilateral BMB is recom-mended,along with immunohistochemistry and?ow cytometry.

PROGNOSTIC GROUPS AND TREATMENT ALLOCATION

The increased use of systemic and multimodality approaches has made Ann Arbor stage less relevant in directing the choice of therapy. Nevertheless,we recommend a modi?cation of the Ann Arbor classi-?cation(Table2)for anatomic description of disease extent.However, regardless of stage,general practice is to treat patients based on limited (stages I and II,nonbulky)or advanced(stages III or IV)disease,with stage II bulky disease considered limited or advanced as determined by histology and a number of prognostic factors.The designation E for extranodal disease is relevant only for limited extranodal disease in the absence of nodal involvement(IE)or in patients with stage II disease and direct extension to a non-nodal site.E is not relevant to patients with advanced-stage disease.

The Ann Arbor classi?cation subdivides patients according to the absence(A)or presence(B)of disease-related symptoms.However, these features are frequently neither recorded nor accurate.Moreover, in the International Prognostic Index,12Follicular Lymphoma Inter-national Prognostic Index,13Follicular Lymphoma International Prognostic Index2,15Mantle Cell International Prognostic Index,14 and International Prognostic Score,11constitutional symptoms do not confer an unfavorable outcome.Thus,only patients with HL need be assigned the designations A or B because symptoms only direct treat-ment in that disease.Summary

Excisional biopsy is preferred for diagnosis,although core-needle biopsy may suf?ce when not feasible.

Clinical evaluation includes careful history,relevant laboratory tests,and recording of disease-related symptoms.

PET-CT is the standard for FDG-avid lymphomas,whereas CT is indicated for nonavid histologies.

A modi?ed Ann Arbor staging system is recommended;how-ever,patients are treated according to prognostic and risk factors.

Suf?xes A and B are only required for HL.

The designation X for bulky disease is no longer necessary;in-stead,a recording of the largest tumor diameter is required.

If a PET-CT is performed,a BMB is no longer indicated for HL;a BMB is only needed for DLBCL if the PET is negative and identifying a discordant histology is important for patient management.

ASSESSMENT OF RESPONSE AFTER TREATMENT

End-of-treatment assessment is more accurate with PET-CT,espe-cially for patients with radiologic(CT)CRu or partial response(PR)in HL,DLBCL,and follicular lymphoma.7,52-55PET-CT–based criteria eliminate CRu and improve the prognostic value of PR.In early-and advanced-stage patients with HL,a negative predictive value of95%to 100%and positive predictive value of more than90%have been reported.56,57In aggressive NHL,studies have reported a negative predictive value of80%to100%but a lower positive predictive value, ranging from50%to100%.58-61If further treatment based on residual metabolically active disease on PET-CT is being considered,either biopsy or follow-up scan is advised.In these lymphoma subtypes, response assessment with PET-CT may be preferred.

The IWG criteria for reviewing PET scans were based on visual interpretation and intended for end-of-treatment evaluation,62using mediastinal blood pool as the comparator.The current recommenda-tion is to use the5-point scale,both for clinical trials including interim analysis and for end-of-treatment assessment(Table3).24Interim

treatment response and,at end of

status.A score of1or2is considered

response at interim and end of treat-

therapy in chemotherapy-sensitive

higher than normal liver uptake is

who achieve complete metabolic

More recent data also suggest that

than mediastinum but less than or

3)have good prognosis at the end of

in HL,63DLBCL,61and follicular

trials exploring treat-

approach may be preferred,judg-

response to avoid undertreatment.

a score of3depends on the timing of

and the treatment.A score of4or5at

disease,provided uptake has

considered to represent partial meta-

treatment,residual metabolic disease

treatment failure even if uptake has

of4or5with intensity that does not

baseline and/or new foci compatible

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with lymphoma represents treatment failure at interim and at the end-of-treatment assessment.

In most cases,lack of signi?cant response can be interpreted visually.Although ideally a quantitative cutoff might improve consis-tency,there is insuf?cient evidence to quantify precisely the reduction in uptake that predicts adequate response using FDG-PET for lym-phoma,which is dependent on disease type,timing,and treatment given.Recent data suggest that the CT scan may play a complimentary role in patients with HL who have either a positive interim or post-treatment PET-CT,with a greater reduction in tumor mass correlat-ing with an improved outcome.64,65How best to use this information remains to be determined.

CT-based response is preferred for histologies with low or vari-able FDG avidity and in regions of the world where PET-CT is unavail-able.However,in the absence of a PET-CT scan,a mass that has decreased in size but persists is considered at best a PR in the absence of biopsy documenting absence of lymphoma,and the former term CRu is not to be considered.7In trials exploring new agents in multiply relapsed disease where data are lacking regarding PET-CT and where assessment of disease control is more important than likelihood of cure,CT-based response may also be more relevant(Table3).

At interim or end of therapy,tests that were abnormal before treatment should be repeated,including assessment of extranodal sites.Response assessment is detailed in Table3and in the follow-ing sections.

Nodes or Extranodal Lesions That Split When Disease Is Responding

If a con?uent nodal mass splits into several discrete nodes,the individual product of the perpendicular diameters(PPDs)of the nodes should be summed together to represent the PPD of the split lesion;this PPD is added to the sum of the PPDs of the remaining lesions to measure response.If subsequent growth of any or all of these discrete nodes occurs,the nadir of each individual node is used to determine progression(as if each individual node was selected as a target lesion at baseline).

Nodes or Extranodal Lesions That Become Con?uent When Disease Is Progressing

If a group of target lymph nodes becomes con?uent,the PPD of the current con?uent mass should be compared with the sum of the PPDs of the individual nodes,with more than50%increase in the PPD of the con?uent mass compared with the sum of individual nodes necessary to indicate progressive disease.The LDi and shortest diameter are no longer needed to determine progression. Additional Response Assessment Guidelines

The presence of residual symptoms in the absence of detectable disease by imaging does not preclude the designation CR.In the context of an agent associated with a?are reaction,caution must be exercised not to confuse the possible tumor?are with progressive disease.It is recommended that either a biopsy be performed or the lesion be reassessed in at least2weeks,and if there is continued evidence of tumor progression,the date of progressive disease is the previous evaluation.

FOLLOW-UP EVALUATIONS

Good clinical judgment,a careful history,and physical examination are the cornerstones of patient follow-up.The IWG,National Com-prehensive Cancer Network,and European Society for Medical On-cology published recommendations for follow-up that vary by histology(curable v incurable),whether a patient is on a clinical trial or managed with standard of care,or the clinical setting(eg,initial v relapsed/refractory disease;complete response v PR to treat-ment).7,66,67For example,for curable histologies such as HL and DLBCL,the likelihood of relapse decreases over time;thus,the fre-quency of follow-up should decrease,with visits being reduced from every3months during the?rst2years,to every6months for the next 3years,and then annually thereafter to monitor for late relapse and treatment-related adverse effects.In contrast,in follicular lymphoma, mantle-cell lymphoma,and other incurable histologies,the likelihood of recurrence continues or increases over time,and patients should be observed every3to6months,determined by pretreatment risk fac-tors,whether the patient is being managed conservatively,and whether treatment has achieved a complete or less than complete response.In addition,a CBC,metabolic panel,and serum lactate dehydrogenase are recommended.

Published studies fail to support routine surveillance scans,and they are discouraged.68-70The false-positive rate with PET scans is greater than20%,leading to unnecessary investigations,radiation exposure,biopsies,expense,and patient anxiety.Follow-up scans should be prompted by clinical indications.In clinical trials with time-dependent end points(eg,progression-free survival,event-free survival),a CT scan is determined by the study-designated interval.In the indolent lymphomas,asymptomatic intra-abdominal or retroper-itoneal disease progression may be a concern in patients with residual disease in those areas after therapy.In such patients,judicious use of scans can be considered.In clinical practice and in clinical trials, attempts should be made to limit the number of scans to which a patient is exposed.

Summary

PET-CT should be used for response assessment in FDG-avid histologies,using the5-point scale;CT is preferred for low or variable FDG avidity.

A complete metabolic response even with a persistent mass is considered a complete remission.

A PR requires a decrease by more than50%in the sum of the product of the perpendicular diameters of up to six representative nodes or extranodal lesions.

Progressive disease by CT criteria only requires an increase in the PPDs of a single node by?50%.

Surveillance scans after remission are discouraged,especially for DLBCL and HL,although a repeat study may be considered after an equivocal?nding after treatment.

Judicious use of follow-up scans may be considered in indolent lymphomas with residual intra-abdominal or retro-peritoneal disease.

MEASUREMENT OF OUTCOME

De?nitions are consistent with the IWG de?nitions.7

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CONCLUDING REMARKS

Accurate pretreatment evaluation and response assessment are critical to the optimal management of patients with lymphoma. With increasing knowledge of the disease,new prognostic factors, and a better understanding of tumor biology comes a need to update prior systems.Despite the importance of a physical exam-ination,imaging studies have become the standard.The present recommendations are directed primarily at initial staging and as-sessment,and their role in the multiply relapsed setting and early clinical trials remains to be con?rmed.A major departure from the Ann Arbor system and the IWG criteria is that PET-CT is included in staging for FDG-avid lymphomas,because it is more sensitive than CT and provides a baseline against which response is more accurately assessed.Patients should be treated based on prognostic factors.Subclassi?cation of A and B is now only indicated if prog-nostically important(ie,HL).Patients,including those with HL and most with DLBCL,can be spared a staging BMB,71and a routine chest x-ray is unnecessary for staging,although it may be useful for monitoring select patients with HL.Although the cur-rent de?nition of bulk is retained for HL,further correlations between maximum tumor diameter and outcome are needed to provide a clinically meaningful de?nition of bulk with current treatment approaches for NHL.Response assessment is preferred for FDG-avid lymphomas where possible,using the5-point scale, whereas CT-based response remains important in lymphomas with low or variable FDG avidity,and in multiply relapsed disease, CT criteria for progressive disease can be based on an increase of a single lesion.The better we are able to exploit the biology of lymphomas for therapeutic bene?t,the more our treatment strat-egies will be determined by relevant receptors and pathways,with even less reliance on Ann Arbor staging.Hopefully,the current recommendations will provide the necessary standardization of clinical trial conduct and interpretation that leads to improved therapies for patients with lymphoma.

AUTHORS’DISCLOSURES OF POTENTIAL CONFLICTS

OF INTEREST

Although all authors completed the disclosure declaration,the following author(s)and/or an author’s immediate family member(s)indicated a

?nancial or other interest that is relevant to the subject matter under consideration in this article.Certain relationships marked with a“U”are those for which no compensation was received;those relationships marked with a“C”were compensated.For a detailed description of the disclosure categories,or for more information about ASCO’s con?ict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Con?icts of Interest section in Information for Contributors. Employment or Leadership Position:None Consultant or Advisory Role:Bruce D.Cheson,Gilead(C),Celgene(C),Genentech(C), Pharmacyclics(C),AstraZeneca(C),Spectrum(C);Lawrence H. Schwartz,Novartis(C),BioImaging(C),Icon Medical(C);Emanuele Zucca,Roche(C),Mundipharma(C),Celgene(C),Janssen(C)Stock Ownership:None Honoraria:Emanuele Zucca,Roche, Mundipharma,Celgene,Janssen Research Funding:Bruce D. Cheson,Gilead,Celgene,Genentech,Pharmacyclics;Emanuele Zucca,Roche,Mundipharma,Novartis Expert Testimony:None Patents,Royalties,and Licenses:None Other Remuneration:Bruce D.Cheson,Gilead,Celgene,Genentech,Pharmacyclics;Emanuele Zucca,Roche,Mundipharma,Janssen;T.Andrew Lister,Millennium

AUTHOR CONTRIBUTIONS

Conception and design:All authors

Collection and assembly of data:All authors

Data analysis and interpretation:All authors

Manuscript writing:All authors

Final approval of manuscript:All authors

Table3.Revised Criteria for Response Assessment(continued)

Response and Site PET-CT–Based Response CT-Based Response

New lesions New FDG-avid foci consistent with lymphoma rather than

another etiology(eg,infection,in?ammation).If

uncertain regarding etiology of new lesions,biopsy or

interval scan may be considered Regrowth of previously resolved lesions

A new node?1.5cm in any axis

A new extranodal site?1.0cm in any axis;if?1.0cm in

any axis,its presence must be unequivocal and must be attributable to lymphoma

Assessable disease of any size unequivocally attributable to lymphoma

Bone marrow New or recurrent FDG-avid foci New or recurrent involvement

Abbreviations:5PS,5-point scale;CT,computed tomography;FDG,?uorodeoxyglucose;IHC,immunohistochemistry;LDi,longest transverse diameter of a lesion; MRI,magnetic resonance imaging;PET,positron emission tomography;PPD,cross product of the LDi and perpendicular diameter;SDi,shortest axis perpendicular to the LDi;SPD,sum of the product of the perpendicular diameters for multiple lesions.

?A score of3in many patients indicates a good prognosis with standard treatment,especially if at the time of an interim scan.However,in trials involving PET where de-escalation is investigated,it may be preferable to consider a score of3as inadequate response(to avoid undertreatment).Measured dominant lesions:Up to six of the largest dominant nodes,nodal masses,and extranodal lesions selected to be clearly measurable in two diameters.Nodes should preferably be from disparate regions of the body and should include,where applicable,mediastinal and retroperitoneal areas.Non-nodal lesions include those in solid organs(eg,liver,spleen,kidneys,lungs),GI involvement,cutaneous lesions,or those noted on palpation.Nonmeasured lesions:Any disease not selected as measured,dominant disease and truly assessable disease should be considered not measured.These sites include any nodes,nodal masses, and extranodal sites not selected as dominant or measurable or that do not meet the requirements for measurability but are still considered abnormal,as well as truly assessable disease,which is any site of suspected disease that would be dif?cult to follow quantitatively with measurement,including pleural effusions,ascites,bone lesions,leptomeningeal disease,abdominal masses,and other lesions that cannot be con?rmed and followed by imaging.In Waldeyer’s ring or in extranodal sites(eg,GI tract,liver,bone marrow),FDG uptake may be greater than in the mediastinum with complete metabolic response,but should be no higher than surrounding normal physiologic uptake(eg,with marrow activation as a result of chemotherapy or myeloid growth factors).

?PET5PS:1,no uptake above background;2,uptake?mediastinum;3,uptake?mediastinum but?liver;4,uptake moderately?liver;5,uptake markedly higher than liver and/or new lesions;X,new areas of uptake unlikely to be related to lymphoma.

Staging and Response Assessment in Lymphoma

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Staging and Response Assessment in Lymphoma

https://www.wendangku.net/doc/3f8018073.html,?2014by American Society of Clinical Oncology3067

Cheson et al

Acknowledgment

We thank the following contributors to the writing of this article:Ranjana Advani,Kirit Ardeshna,Jim Armitage,Matthew Barish,Alberto Biggi,George Canellos,Luca Ceriani,Bertrand Coif?er,Joe Connors,Michael Crump,Martin Dreyling,Andreas Engert,Massimo Federico, Andrea Gallamini,Randy Gascoyne,Christian Gisselbrecht,Mary Gospodarawicz,Armando Lopez Guillermo,Ton Hagenbeek,Michael Herold,Richard Hoppe,Martin Hutchings,Peter Johnson,Brad Kahl,Won Seog Kim,Eva Kimby,Lale Kostakoglu,John Leonard,Kelie Luby, Elly Lugtenburg,Michel Meignan,N.George Mikhaeel,Silvia Montoto,Craig Moskowitz,Stefan Mueller,Michinori Ogura,Michael Pfreund-schuh,Aaron Polliack,John Radford,Gilles Salles,Laurie Sehn,John Seymour,Ritsuro Suzuki,Kensei Tobinai,Judith Trotman,Wyndham Wilson,Umberto Vitolo,Julie Vose,Anas Younes,Andrew Zelenetz,Jose′Zijlstra,and Pier-Luigi Zinzani.We also thank Cristiana Brentan for her invaluable administrative support.

?2014by American Society of Clinical Oncology J OURNAL OF C LINICAL O NCOLOGY

恶性淋巴瘤诊疗规范(2015年版)

恶性淋巴瘤诊疗规范（2015年版）一、概述恶性淋巴瘤（也称为淋巴瘤）是我国最常见的十大肿瘤之一。根据《中国肿瘤登记年报》公布的数据，2003年至2013年，恶性淋巴瘤的发病率约为５/10万。由于淋巴瘤病理类型复杂，治疗原则各有不同，为进一步规范我国淋巴瘤诊疗行为，提高诊疗水平，改善患者预后，保障医疗质量和医疗安全，国家卫生和计划生育委员会医政医管局委托中国抗癌协会肿瘤临床化疗专业委员会，制订我国常见病理类型恶性淋巴瘤的诊疗规范。二、淋巴瘤的诊断应当结合患者的临床表现、体格检查、实验室检查、影像学检查和病理学检查结果等进行诊断。（一）临床表现淋巴瘤的症状包括全身症状和局部症状。全身症状包括不明原因的发热、盗汗、体重下降、皮肤瘙痒和乏力等。局部症状取决于不同的原发和受侵部位，最常见表现为无痛性的进行性淋巴结肿大。（二）体格检查应特别注意不同区域的淋巴结是否增大、肝脾的大小、伴随体征和一般状态等。（三）实验室检查应完成的实验室检查包括血常规、肝肾功能、乳酸脱氢酶（Lactate dehydrogenase，LDH）、β２微球蛋白、血沉、乙肝和丙肝病毒检测，以及骨髓穿刺细胞学和（或）活检等。对于存在中枢神经系统受侵危险的患者应进行腰穿，予以脑脊液生化、常规和细胞学等检查。对NK/Ｔ细胞淋巴瘤患者，应进行外周血EB病毒DNA滴度检测。

（四）影像学检查常用的影像学检查方法为CT、核磁共振成像（nuclear magnetic resonance imaging ,MRI）、正电子发射计算机断层显像（positron emission tomography-computed tomography，PET-CT）、超声和内窥镜等。１．CT：目前仍作为淋巴瘤分期、再分期、疗效评价和随诊的最常用影像学检查方法，对于无碘对比剂禁忌证的患者，应尽可能采用增强CT。２．MRI：对于中枢神经系统、骨髓和肌肉部位的病变应首选MRI 检查；对于肝、脾、肾脏、子宫等实质器官病变可以选择或者首选MRI 检查，尤其对于不宜行CT 增强者，或者作为CT 发现可疑病变后的进一步检查。３．PET-CT：除惰性淋巴瘤外，PET-CT 推荐用于有条件者的肿瘤分期与再分期、疗效监测、肿瘤残存及复发时的检查；PET-CT 对于疗效和预后预测好于其他方法，可以选择性使用。４．超声：一般不用于淋巴瘤的分期。对于浅表淋巴结和浅表器官（如睾丸、乳腺）病变的诊断和治疗后随诊具有优势，可以常规使用；对于腹部、盆腔淋巴结可以选择性使用；对于肝、脾、肾、子宫等腹盆腔实质性器官的评估，可以作为CT 和MRI 的补充，尤其是不能行增强CT 时。超声可用于引导穿刺活检、胸腹水抽液和引流。（五）病理诊断病理诊断是淋巴瘤诊断的主要手段。病理诊断的组织样本应首选切除病变或切取部分病变组织。如病变位于浅表淋巴结，应尽量选择颈部、锁骨上和腋窝淋巴结。粗针穿刺仅用于无法有效、安全地获得切除或切取病变组织的患者。初次诊断时，最好是切除或切取病变组织。对于复发患者，可以通过粗针或细针穿刺获取的病变组织来诊断。淋巴瘤的病理诊断需综合应用形态学、免疫组化、遗传学及分子生物学等技术，尚无一种技术可以单独定义为金标准。

外周T细胞淋巴瘤诊疗规范

外周T细胞淋巴瘤（非特指型）诊疗规范（征求意见稿）苏州大学附属第一医院血液科 1. 概述外周T细胞淋巴瘤（Peripheral T-cell lymphoma, PTCL）是一组起源于胸腺后成熟T 淋巴细胞的淋巴系统恶性肿瘤。NCCN2014版明确指出PTCL包括4类亚型：外周T细胞淋巴瘤-非特指型（Peripheral T-cell lymphoma, not otherwise specified, PTCL-NOS），血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T-cell lymphoma, AITL），间变大细胞淋巴瘤（anaplastic large cell lymphoma, ALCL）和肠病相关T 细胞淋巴瘤（Enteropathy associated T-cell lymphoma, EATL）。外周T细胞淋巴瘤，非特指型（PTCL-NOS）是PTCL中最常见的亚型。所谓“非特指型”，是强调这一亚型与已明确的各种独立的成熟T细胞淋巴瘤均不符合，即PTCL-NOS其实是一大组不属于已明确的任何一类独特亚型的成熟T细胞淋巴瘤。PTCL-NOS是一类异质性疾病，在细胞形态学、遗传学、分子生物学和临床表现等方面均无特异性。本病属于排除性诊断，即只有在排除其它独立分型的T细胞淋巴瘤后，方能做出PTCL-NOS的诊断。本病临床表现为侵袭性病程，对化疗不敏感，易复发，5年生存率仅为25～45%。 2. 流行病学 PTCL-NOS是最常见的T细胞淋巴瘤亚型。在西方国家，PTCL-NOS占所有NHL的7%～10%，占PTCL发病的30%。而亚洲国家发病率更明显高于欧美，占所有NHL的15%～22%，占PTCL发病的50%。发病常见于中老年人，中位年龄55岁，儿童少见。男性多见，男女比例约为2:1。 3. 病因及发病机制本病病因尚未明确，可能与EBV感染有一定关系，也可能与自身免疫功能降低或周围环境影响有关。发病机制有待进一步研究。 4. 临床表现

淋巴瘤病理规范化诊断专家共识

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中国淋巴瘤病理规范化诊断专家共识李小秋汝昆陈刚林素暇周小鸽高子芬刘卫平姜文奇朱雄增作者单位：200032 复旦大学附属肿瘤医院病理科复旦大学上海医学院肿瘤学系（李小秋、朱雄增）；300041中国医学科学院血液病医院(血液学研究所)病理中心（汝昆）；350014 福建省肿瘤医院（陈刚）；510060 中山大学肿瘤防治中心病理科（林素暇）；100050 首都医科大学附属北京友谊医院病理科（周小鸽）；100191 北京大学医学部病理学系（高子芬）；610041 四川大学华西医院病理科（刘卫平）；510060 中山大学肿瘤防治中心肿瘤内科（姜文奇）执笔人单位：200032 复旦大学附属肿瘤医院病理科复旦大学上海医学院肿瘤学系[李小秋（E-mail：leexiaoqiu@https://www.wendangku.net/doc/3f8018073.html,）、朱雄增（E-mail：xiongzengzhu@https://www.wendangku.net/doc/3f8018073.html,）]；300041中国医学科学院血液病医院(血液学研究所)病理中心（汝昆，E-mail：kunru@https://www.wendangku.net/doc/3f8018073.html,）；350014 福建省肿瘤医院（陈刚，E-mail：naichengang@https://www.wendangku.net/doc/3f8018073.html,）恶性淋巴瘤（以下称“淋巴瘤”）是一组B、T或NK细胞起源、类型复杂的肿瘤总称，广义的淋巴组织肿瘤还包括组织细胞和树突细胞来源的肿瘤。近年来，淋巴瘤临床诊治与基础研究均取得了长足的进步，推动着淋巴瘤病理分类不断向前演进，也对淋巴瘤的病理诊断提出了更高的要求。为了更好适应淋巴瘤现代诊疗模式的需求，促进国内不同层次的病理科对淋巴瘤诊断水平的提高，本文作者于2013年11月9日和2014年2月22日先后两次召开会议，探讨适合我国国情的淋巴病理诊断相关流程与规范，现将与会专家达成的共识总结如下。一、淋巴瘤病理诊断总则目前，淋巴瘤的类型区分和诊断标准主要是依据世界卫生组织（WHO）制定的造血和淋巴组织肿瘤分类。WHO分类认为不同类型或亚型的淋巴瘤在其形态、免疫表型、遗传学以及临床表现等方面各自具备独特的特征。对这些疾病的识别，因此也应建立于对上述参数全面评估、综合判断的基础之上。淋巴瘤病理诊断整合了组织形态、免疫组织化学染色、流式细胞分析、细胞遗传学以及分子生物学等多种辅助检测技术。当前，

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https://www.wendangku.net/doc/3f8018073.html,/ 淋巴瘤的诊断标准专家说任何疾病及早的诊断都可以使疾病得到更好的治疗，淋巴癌也是一样的，淋巴瘤的诊断标准是什么?专家说一般以患者的体征、病史以及特殊的检查来做为诊断淋巴癌的依据，只有得到确诊患者才能及时的接受治疗，下面就请专家为您详细介绍淋巴癌的诊断标准。一、体征，全身浅表淋巴结是否肿大，皮肤及附件有否侵犯，应注意咽淋巴环、乳腺、睾丸等有否侵犯。其他静脉或淋巴回流受阻，气管受压，上腔静脉综合症等。这些淋巴癌的诊断比较常见。二、特殊检查，血常规检查，包括血红蛋白、白细胞计数与分类、血小板计数、血沉率等。淋巴癌的诊断标准是什么呢?血化学检查，包括尿素氮、非蛋白氮、肌酐、硷性磷酸酶、总蛋白与白蛋白、球蛋白、转氨酶及转肽酶等测定。这也是淋巴癌的诊断方法。三、详细询问病史，包括首发症状、淋巴结肿大出现的时间与以后的增大速度、有无全身症状，如发热、盗汗、皮肤搔痒、消瘦等，非何杰金淋巴癌应询问有无消化道症状等。这也属于淋巴癌的诊断依据。淋巴瘤临床表现多样，虽然可以有慢性、进行性、无痛性淋巴结肿大，但也可以表现为其他系统受累或全身症状。临床上怀疑淋巴瘤时，可以做淋巴结或其他受累组织或器官的病理切片检查(活检)以确诊。以上介绍的是淋巴癌的诊断标准，相信大家都已经了解了，专家说淋巴癌一旦得到确诊，那么就要及时治疗了，目前治疗淋巴癌的方法主要以手术治疗、化疗为主，在使用这些治疗方法同时再配合中医的调理，可以更好的缓解淋巴癌的症状。原文链接：https://www.wendangku.net/doc/3f8018073.html,/lbl/2015/0720/226223.html

淋巴瘤病理规范化诊断专家共识

淋巴瘤病理规范化诊断专家共识恶性淋巴瘤（以下称“淋巴瘤”）是一组B、T或NK细胞起源、类型复杂的肿瘤总称，广义的淋巴组织肿瘤还包括组织细胞和树突细胞来源的肿瘤。近年来，淋巴瘤临床诊治与基础研究均取得了长足的进步，推动着淋巴瘤病理分类不断向前演进，也对淋巴瘤的病理诊断提出了更高的要求。为了更好适应淋巴瘤现代诊疗模式的需求，促进国内不同层次的病理科对淋巴瘤诊断水平的提高，本文作者于2013年11月9日和2014年2月22日先后两次召开会议，探讨适合我国国情的淋巴病理诊断相关流程与规范，现将与会专家达成的共识总结如下。一、淋巴瘤病理诊断总则目前，淋巴瘤的类型区分和诊断标准主要是依据世界卫生组织（WHO）制定的造血和淋巴组织肿瘤分类。WHO分类认为不同类型或亚型的淋巴瘤在其形态、免疫表型、遗传学以及临床表现等方面各自具备独特的特征。对这些疾病的识别，因此也应建立于对上述参数全面评估、综合判断的基础之上。淋巴瘤病理诊断整合了组织形态、免疫组织化学染色、流式细胞分析、细胞遗传学以及分子生物学等多种辅助检测技术。当前，对于绝大部分病例而言，经典的组织病理学检查仍然是诊断淋巴瘤最主要的方法，而免疫组织化学染色则是判断肿瘤免疫表型以及检测部分遗传学异常的重要手段。所以，几乎所

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恶性淋巴瘤诊疗规（2015年版）一、概述恶性淋巴瘤（也称为淋巴瘤）是我国最常见的十大肿瘤之一。根据《中国肿瘤登记年报》公布的数据，2003年至2013年，恶性淋巴瘤的发病率约为５/10万。由于淋巴瘤病理类型复杂，治疗原则各有不同，为进一步规我国淋巴瘤诊疗行为，提高诊疗水平，改善患者预后，保障医疗质量和医疗安全，国家卫生和计划生育委员会医政医管局委托中国抗癌协会肿瘤临床化疗专业委员会，制订我国常见病理类型恶性淋巴瘤的诊疗规。二、淋巴瘤的诊断应当结合患者的临床表现、体格检查、实验室检查、影像学检查和病理学检查结果等进行诊断。（一）临床表现淋巴瘤的症状包括全身症状和局部症状。全身症状包括不明原因的发热、盗汗、体重下降、皮肤瘙痒和乏力等。局部症状取决于不同的原发和受侵部位，最常见表现为无痛性的进行性淋巴结肿大。（二）体格检查应特别注意不同区域的淋巴结是否增大、肝脾的大小、伴随体征和一般状态等。（三）实验室检查应完成的实验室检查包括血常规、肝肾功能、乳酸脱氢酶（Lactate dehydrogenase，LDH）、β２微球蛋白、血沉、乙肝和丙肝病毒检测，以及骨髓穿刺细胞学和（或）活检等。对于存在中枢神经系统受侵危险的患者应进行腰穿，予以脑脊液生化、常规和细胞学等检查。对NK/Ｔ细胞淋巴瘤患者，应进行外周血EB病毒DNA滴度检测。

（四）影像学检查常用的影像学检查方法为CT、核磁共振成像（nuclear magnetic resonance imaging ,MRI）、正电子发射计算机断层显像（positron emission tomography-computed tomography，PET-CT）、超声和窥镜等。１．CT：目前仍作为淋巴瘤分期、再分期、疗效评价和随诊的最常用影像学检查方法，对于无碘对比剂禁忌证的患者，应尽可能采用增强CT。２．MRI：对于中枢神经系统、骨髓和肌肉部位的病变应首选MRI 检查；对于肝、脾、肾脏、子宫等实质器官病变可以选择或者首选MRI 检查，尤其对于不宜行CT 增强者，或者作为CT 发现可疑病变后的进一步检查。３．PET-CT：除惰性淋巴瘤外，PET-CT 推荐用于有条件者的肿瘤分期与再分期、疗效监测、肿瘤残存及复发时的检查；PET-CT 对于疗效和预后预测好于其他方法，可以选择性使用。４．超声：一般不用于淋巴瘤的分期。对于浅表淋巴结和浅表器官（如睾丸、乳腺）病变的诊断和治疗后随诊具有优势，可以常规使用；对于腹部、盆腔淋巴结可以选择性使用；对于肝、脾、肾、子宫等腹盆腔实质性器官的评估，可以作为CT 和MRI 的补充，尤其是不能行增强CT 时。超声可用于引导穿刺活检、胸腹水抽液和引流。（五）病理诊断病理诊断是淋巴瘤诊断的主要手段。病理诊断的组织样本应首选切除病变或切取部分病变组织。如病变位于浅表淋巴结，应尽量选择颈部、锁骨上和腋窝淋巴结。粗针穿刺仅用于无法有效、安全地获得切除或切取病变组织的患者。初次诊断时，最好是切除或切取病变组织。对于复发患者，可以通过粗针或细针穿刺获取的病变组织来诊断。淋巴瘤的病理诊断需综合应用形态学、免疫组化、遗传学及分子生物学等技术，尚无一种技术可以单独定义为金标准。

2014外周T细胞淋巴瘤,非特指型诊疗规范修订版(沈建箴组)

外周T细胞淋巴瘤，非特指型【概述】外周T细胞淋巴瘤，非特指型（peripheral T-cell lymphoma, not otherwise specified, PTCL, NOS）是除有独特临床病理学表现的成熟T细胞淋巴瘤以外，剩下的一大组不属于任何一类亚型的结内和结外成熟T细胞淋巴瘤。约占NHL的10%。是西方国家最常见的外周T细胞肿瘤，占外周T细胞淋巴瘤的26%，占我国T-NHL的40%。多见于成年人，儿童罕见，平均发病年龄61岁，男女比例2：1。疾病具有侵袭性，相较于B细胞淋巴瘤，预后更差。PTCL-NOS病因不明，可能与EBV感染有关。90%的患者有TCRγ基因重排，以位点多见，因此对TCRγ位点的分析有助于本病的诊断。遗传学异常较常见，如+7q、+8q、+17q、+22q，5q-、10q-、12q-、13q-等。【临床表现】患者经常表现为全身淋巴结肿大为主（50%-75%），还可以累及全身其他部位，如骨髓、肝脾和结外组织，结外受累以皮肤和胃肠道多见，其次肺、唾液腺和中枢神经系统也容易受累。大部分患者有B症状（50%-60%），如发热、体重减轻、盗汗等，常伴有嗜酸性粒细胞增多、瘙痒、噬血细胞综合症。病程具有侵袭性，比同样恶性的B细胞淋巴瘤更容易复发。病理外周T细胞淋巴瘤免疫化学抗体谱：CD2、CD3、CD5、CD7、CD4、CD8、CD30、CD56、CD57、CD10、CD20、CD21、CD23、ALK、EBER-ISH、BCL6、ki-67 流式细胞术抗体谱：CD2、CD3、CD5、CD7、CD4、CD8、CD30、CD10、CD19、CD20、CD45、kappa/lambda、TCRαβ、TCRγ 符合异常的成熟T细胞表型，并能除外其他独立分型的T细胞淋巴瘤者诊断为PTCL-NOS。实验室检查 1. 全血细胞计数及分类。 2. 骨髓活检+骨髓涂片，骨髓染色体核型分析，淋巴瘤FISH检测，IgVH/TCR重排。必要时行骨髓流式免疫分型。 3. 生化全套（含肝肾功能、LDH、尿酸）。 4. β2-MG、血沉、CRP。

淋巴瘤分期及IPI评分审批稿

淋巴瘤分期及I P I评分 YKK standardization office【 YKK5AB- YKK08- YKK2C- YKK18】

IA <10%皮疹或斑疹（T1） IB≥10%皮疹或斑疹（T2） IIA T1-2，淋巴结肿大但活检阴性中期 IIB 皮肤肿瘤（T3） III 红皮病（T4） IVA T1-4，淋巴结肿大且活检阳性晚期 IVB T1-4，内脏侵犯。三．分期步骤临床上应完善下列检查： 1．详细的病史（盗汗，体重下降，发热，神经系统、肌肉骨骼或胃肠的症状）和体格检查（淋巴结；心包摩擦音，胸腔积液，颈部和/或末梢静脉扩张的上腔静脉压迫综合症；乳腺肿块；肝脾肿大，肠梗阻，肾脏肿块，和睾丸或卵巢肿块；神经系统局部定位体征，如神经丛病，脊髓压迫，神经根浸润和脑膜侵犯；皮肤损害）。 2．外周肿大淋巴结活检或肿块活检。 3．全血细胞常规检查；生化常规检查包括LDH，β2微球蛋白检查；HIV血清学检查；皮肤T细胞淋巴瘤的病人要检查HTLV-1血清学。 4．胸部X线检查和胸部CT扫描 5．腹部和盆腔的CT或B超扫描 6．骨髓穿刺。

淋巴瘤诊疗规范(完整版)

淋巴瘤诊疗规范（完整版）一、概述淋巴瘤（lyphoma）是我国最常见的恶性肿瘤之一。根据国家癌症中心公布的数据，2014年我国淋巴瘤的确诊发病率为5.94/10万，2015年预计发病率约为6.89/10万。由于淋巴瘤病理类型复杂，治疗原则各有不同，为进一步提高淋巴瘤诊疗能力和规范化水平，配合抗肿瘤药品供应保障有关政策调整，保障医疗质量与安全，现对《中国恶性淋巴瘤诊疗规范（2015年版）》进行修订和更新。二、淋巴瘤的诊断应当结合患者的临床表现、体格检查、实验室检查、影像学检查和病理学等进行诊断。（一）临床表现淋巴瘤的症状包括全身和局部症状。全身症状包括不明原因的发热、盗汗、体重下降、皮肤瘙痒和乏力等。局部症状取决于病变不同的原发和受侵部位，淋巴瘤可以原发于身体的任何器官和组织，通常分为原发于淋巴结和淋巴结外两大类。最常见表现为无痛性的进行性淋巴结肿大。如有以上述症状的患者在基层医院就诊时，应予以重视，并尽早转诊至上级医院或肿瘤专科医院。（二）体格检查应特别注意不同区域的淋巴结是否增大、肝脾的大小、伴随体征和一般状态等。

（三）实验室检查应完成的实验室检查包括血常规、肝肾功能、乳酸脱氢酶（lactate dehydrogenase，LDH）、β2微球蛋白、红细胞沉降率、乙型肝炎和丙型肝炎病毒检测以及骨髓穿刺细胞学和活检等，还应包括人类免疫缺陷病毒（human immunodeficiency virus，HIV）筛查在内的相关感染性筛查。对原发胃的黏膜相关边缘带B细胞淋巴瘤，应常规进行幽门螺杆菌（helicobacter pylori，Hp）染色检查；对NK/T细胞淋巴瘤患者，应进行外周血EB病毒DNA滴度检测。对于存在中枢神经系统受累风险的患者应进行腰穿，予以脑脊液生化、常规和细胞学等检查。（四）影像学检查常用的影像检查方法：计算机断层扫描（computed tomography，CT）、核磁共振（nuclear magnetic resonance，MRI）、正电子发射计算机断层显像（positron emission tomography，PET-CT）、超声和内镜等。 1. CT：目前仍作为淋巴瘤分期、再分期、疗效评价和随诊的最常用影像学检查方法，对于无碘对比剂禁忌证的患者，应尽可能采用增强CT扫描。 2. MRI：对于中枢神经系统、骨髓和肌肉部位的病变应首选MRI检查；对于肝、脾、肾脏、子宫等实质器官病变可以选择或者首选MRI检查，尤其对于不宜行增强CT扫描者，或者作为CT发现可疑病变后的进一步检查。 3. PET-CT：目前是除惰性淋巴瘤外，淋巴瘤分期与再分期、疗效评价和预后预测的最佳检查方法。对于下列情况，有条件者推荐使用PET-CT：①PET-CT可作为霍奇金淋巴瘤（Hodgkin lymphoma，HL）以及氟脱

淋巴瘤诊疗规范(2018年版)

淋巴瘤诊疗规（2018年版）一、概述淋巴瘤（lyphoma）是我国最常见的恶性肿瘤之一。根据国家癌症中心公布的数据，2014年我国淋巴瘤的确诊发病率为5.94/10万，2015年预计发病率约为6.89/10万。由于淋巴瘤病理类型复杂，治疗原则各有不同，为进一步提高淋巴瘤诊疗能力和规化水平，配合抗肿瘤药品供应保障有关政策调整，保障医疗质量与安全，现对《中国恶性淋巴瘤诊疗规（2015年版）》进行修订和更新。二、淋巴瘤的诊断应当结合患者的临床表现、体格检查、实验室检查、影像学检查和病理学等进行诊断。（一）临床表现淋巴瘤的症状包括全身和局部症状。全身症状包括不明原因的发热、盗汗、体重下降、皮肤瘙痒和乏力等。局部症状取决于病变不同的原发和受侵部位，淋巴瘤可以原发于身体的任何器官和组织，通常分为原发于淋巴结和淋巴结外两大类。最常见表现为无痛性的进行性淋巴结肿大。如有以上述症状的患者在基层医院就诊时，应予以重视，并尽早转诊至上级医院或肿瘤专科医院。（二）体格检查应特别注意不同区域的淋巴结是否增大、肝脾的大小、

伴随体征和一般状态等。（三）实验室检查应完成的实验室检查包括血常规、肝肾功能、乳酸脱氢酶（lactate dehydrogenase，LDH）、β2微球蛋白、红细胞沉降率、乙型肝炎和丙型肝炎病毒检测以及骨髓穿刺细胞学和活检等，还应包括人类免疫缺陷病毒（human immunodeficiency virus，HIV）筛查在的相关感染性筛查。对原发胃的黏膜相关边缘带B细胞淋巴瘤，应常规进行幽门螺杆菌（helicobacter pylori，Hp）染色检查；对NK/T细胞淋巴瘤患者，应进行外周血EB病毒DNA滴度检测。对于存在中枢神经系统受累风险的患者应进行腰穿，予以脑脊液生化、常规和细胞学等检查。（四）影像学检查常用的影像检查方法：计算机断层扫描（computed tomography，CT）、核磁共振（nuclear magnetic resonance，MRI）、正电子发射计算机断层显像（positron emission tomography，PET-CT）、超声和镜等。 1. CT：目前仍作为淋巴瘤分期、再分期、疗效评价和随诊的最常用影像学检查方法，对于无碘对比剂禁忌证的患者，应尽可能采用增强CT扫描。 2. MRI：对于中枢神经系统、骨髓和肌肉部位的病变应首选MRI检查；对于肝、脾、肾脏、子宫等实质器官病变可以选择或者首选MRI检查，尤其对于不宜行增强CT扫描者，

淋巴瘤诊疗规范

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淋巴瘤分期及IPI评分讲课稿

淋巴瘤分期及IPI评分淋巴瘤分期目前采用分期Ann Arbor系统一．Ann Arbor系统虽然最初为霍奇金淋巴瘤设计，但也常规应用于非霍奇金氏淋巴瘤的临床分期。但应了解对NHL来说，临床分期不象霍奇金淋巴瘤那样重要。特别是进展型或高度进展型NHL，即使临床分期比较局限，仍应视为全身性疾患，着重给予系统治疗。 Ann Arbor分期系统 I 侵犯单个淋巴结区域（I）或单个结外部位（IE） II 侵犯2个或2个以上淋巴结区域，但均在隔肌的同侧（II），可伴有同侧的局限性结外器官侵犯（IIE） III 隔肌上下淋巴结区域均有侵犯（III），可伴有局限性结外器官侵犯（IIIE）或脾侵犯（IIIS）或两者均侵犯（IIIES）。 IV 在淋巴结、脾脏和咽淋巴环之外，一个或多个结外器官或组织受广泛侵犯，伴有或不伴有淋巴结肿大等。各期患者按有无B症状分为A、B两类。B症状包括：6个月内不明原因的体重下降＞10％；原因不明的发热（38OC以上）；盗汗。二．而对于原发皮肤的非霍奇金氏淋巴瘤，皮肤T细胞淋巴瘤的TNM分期系统对指导治疗和预测预后更有价值。皮肤淋巴瘤的TNM分期系统早期 IA <10%皮疹或斑疹（T1） IB≥10%皮疹或斑疹（T2） IIA T1-2，淋巴结肿大但活检阴性中期 IIB 皮肤肿瘤（T3） III 红皮病（T4） IV A T1-4，淋巴结肿大且活检阳性晚期 IVB T1-4，内脏侵犯。三．分期步骤临床上应完善下列检查： 1．详细的病史（盗汗，体重下降，发热，神经系统、肌肉骨骼或胃肠的症状）和体格检查（淋巴结；心包摩擦音，胸腔积液，颈部和/或末梢静脉扩张的上腔静脉压迫综合症；乳腺肿块；肝脾肿大，肠梗阻，肾脏肿块，和睾丸或卵巢肿块；神经系统局部定位体征，如神经丛病，脊髓压迫，神经根浸润和脑膜侵犯；皮肤损害）。 2．外周肿大淋巴结活检或肿块活检。

淋巴瘤分期及IPI评分

淋巴瘤分期及IPI 评分淋巴瘤分期目前采用分期Ann Arbor 系统一.Ann Arbor系统虽然最初为霍奇金淋巴瘤设计，但也常规应用于非霍奇金氏淋巴瘤的临床分期。但应了解对NHL 来说，临床分期不象霍奇金淋巴瘤那样重要。特别是进展型或高度进展型NHL ，即使临床分期比较局限，仍应视为全身性疾患，着重给予系统治疗。 Ann Arbor 分期系统 I侵犯单个淋巴结区域（I）或单个结外部位（IE） II 侵犯2 个或2个以上淋巴结区域，但均在隔肌的同侧（II），可伴有同侧的局限性结外器官侵犯（IIE） III隔肌上下淋巴结区域均有侵犯（III），可伴有局限性结外器官侵犯（IIIE ）或脾侵犯（IIIS）或两者均侵犯（IIIES ）。 IV 在淋巴结、脾脏和咽淋巴环之外，一个或多个结外器官或组织受广泛侵犯，伴有或不伴有淋巴结肿大等。各期患者按有无B 症状分为A、B 两类。B 症状包括：6 个月内不明原因的体重下降〉10% ;原因不明的发热（38OC以上）；盗汗。二.而对于原发皮肤的非霍奇金氏淋巴瘤，皮肤T 细胞淋巴瘤的TNM 分期系统对指导治疗和预测预后更有价值。皮肤淋巴瘤的TNM 分期系统早期 IA <10%皮疹或斑疹（T1） IB > 108皮疹或斑疹（T2） IIA T1-2，淋巴结肿大但活检阴性中期 IIB 皮肤肿瘤（T3） III 红皮病（T4） IVA T1-4，淋巴结肿大且活检阳性晚期 IVB T1-4，内脏侵犯。三.分期步骤临床上应完善下列检查： 1. 详细的病史（盗汗，体重下降，发热，神经系统、肌肉骨骼或胃肠的症状）和体格检查（淋巴结；心包摩擦音，胸腔积液，颈部和/或末梢静脉扩张的上腔静脉压迫综合症；乳腺肿块；肝脾肿大，肠梗阻，肾脏肿块，和睾丸或卵巢肿块；神经系统局部定位体征，如神经丛病，脊髓压迫，神经根浸润和脑膜侵犯；皮肤损害）。 2. 外周肿大淋巴结活检或肿块活检。 3. 全血细胞常规检查；生化常规检查包括LDH , B2微球蛋白检查；HIV血清学

肿瘤疗效评价标准

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