Recurrent diffuse large B-cell lymphoma presenting initially as hemophagocytic syndrome

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Case report/Kazuistyka

Recurrent diffuse large B-cell lymphoma presenting initially as hemophagocytic syndrome

Zhenyu Lin, Yinchao Zhao, Gang Wu, Xiaorong Dong *

CancerCenter,Union Hospital,Tongji MedicalCollege,HuazhongUniversityofScienceandTechnology, Wuhan, Hubei,China

Introduction

Hemophagocyticsyndrome(HPS)isararedisordercharacter- izedbypersistentfeverwithoutclearcause,hepatosplenome- galy,cytopenia,derangedliverfunction,hypertriglyceridemia, hyperferritinemiaandhemophagocytosisinbonemarrow[1].

Acquired HPS in adults is associated with various causes including infections, connectivetissue diseases, and malignancies,especiallynon-Hodgkin'slymphoma[2].Incontrast to T or NK/T cell lymphoma, B-cell lymphoma associated with HPS is extremely rare [3, 4]. And hemophagocytic syndrome secondary to the relapsed B-cell lymphoma has never been reported before. We herein reported an unusualandlife-threateningpresentationofhemophagocytic syndrome in a patient with relapsed diffuse large B-cell lymphoma.

Case presentation

An81-year-oldmanwasadmittedtoourhospitalpresenting with a 4-week history of fever of exceeding 388C and weaknessofthelower limbs.Twoyearsbeforethisepisode, he had developed diffuse large B-cell lymphoma of the tongue, and had been successfully treated with wide excisionof thelesionfollowedbychemotherapyand radio- therapy.Onexamination, theabdomen showedhepatosple- nomegaly and there was no superﬁcial lymphadenopathy.

Laboratory examination showed normal white blood cell, thrombocytopenia with a platelet count of 7710⁹/L and hemoglobin level of 77g/L. Negative results of coagulation testingincludingactivatedpartialthromboplastintime(aPTT), prothrombintime(PT),antithrombinIII(AT)activity,fibrinogen concentration, fibrin–fibrinogen degradation product acta haematologica polonica 45 (2014)83–85

article info

Articlehistory:

Received:28.06.2013 Accepted:03.01.2014 Availableonline:15.01.2014

Keywords:

Hemophagocyticsyndrome

DiffuselargeB-celllymphoma

Thrombocytopenia

abstract

Hemophagocyticsyndrome(HPS)isanextremelyrareandlife-threateningabnormality, and the cases secondary to B cell lymphoma are rare. We report a case of relapsed diffuselargeB-celllymphomainitially presentingwithhemophagocyticsyndrome. The patient developed multiple erythematous macules and progressive thrombocytopenia during the treatment, anddied two weeks afteradmission. The HPS presentedas an initial manifestation of the relapsed diffuse B-cell lymphoma and the maculea that appearedduringthetreatmentmightbeastrongpredictorofunfavorableoutcome.

*Correspondingauthor at:CancerCenter,Union Hospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology, No.1277JiefangRoad,Wuhan,Hubei,China.Tel.:+862785726196;fax:+862785755457.

E-mailaddress:tojilzy@gmail.com(X.Dong).

ContentslistsavailableatScienceDirect

Acta Haematologica Polonica

journalhomepage:www.elsevier.com/locate/achaem

http://dx.doi.org/10.1016/j.achaem.2014.01.001

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(FDP) concentration,andD-dimerassays excludedthediag- nosisofdisseminatedintravascularcoagulation(DIC).Hewas alsonotedtohaveelevatedlevelsofaspartateaminotransfer- ase (105U/L), alanine aminotransferase (112U/L), lactate dehydrogenase(1257U/L)andferritin(10414.56pmol/L).Ser- ologicaltestsforvirusinfectionincludingEpstein–Barrvirus, cytomegalovirus, human immunodeficiency virus, hepatitis BandCviruswereallnegative.Thebonemarrowaspiration revealedmacrophagesdistributedthroughoutthebonemar- row. Computed tomographic (CT) scan revealed lesions of lungs suggesting localization of lymphoma and magnetic resonance imaging (MRI) showed multiple epidural mass lesionsatT4,L2andL4withcompressionofthespinalcord (Fig. 1). The result of CT-guided percutaneous lung biopsy was consistent with diffuse large B cell lymphoma. These findingstogetherfulfilledtheHLH-2004criteria(fever,splenomegaly,cytopenias,hyperferritinaemiaandhemophagocyto- sis in the bone marrow). Thus, a diagnosis of hemophagocyticsyndromesecondarytotherelapseddiffuse large B-cell lymphoma wasfinally made. Immediately after initiation of treatment with a 1000-mg methylprednisolone pulsefor 3days andintravenous immunoglobulin(0.4g/kg/

day for 5 days), the fever stopped and the platelet count returned to 10110⁹/L. However, on the 3rd day of the treatment, the patient suddenly developed various-sized, tenderandslightlyinﬁltratederythematousmaculeson the face and trunk (Fig. 2). A careful review of the patient's medication lists ruled out the possibility of drug-induced rash. Meanwhile, the platelet count decreased rapidly to 5910⁹/Lonthe5thdayoftreatmentandevento710⁹/L onthe9thdayoftreatment.Inaddition,thehemoglobinlevel alsodecreasedto57g/Lonthe5thdayoftreatment.During this period, the patient had been dependent on platelet transfusions,whichbecamegraduallymorefrequent.Hegot worse around the 12th day after admission. The family decidedtodiscontinuefurthertherapies,andthepatientdied

ofcirculatoryandrespiratorydistressesduetoHPSabouttwo weeksafteradmission.

Discussion

The clinical course of HPS may be fulminant with rapid progression of symptoms, and the disease is usually fatal without treatment. Theclinical features, propertreatment, and prognosticfactorsof HPSremainill-defined becauseof its rarity, difficulty in diagnosis, and the poor general condition ofthe patientat the timeof diagnosis[5–7]. The Histiocyte Society has established the clinicopathologic criteria for the diagnosis of HPS, which is defined by the presence of at least5 of the following8 criteria,including fever, splenomegaly, cytopenia (affecting 2 cell lines), hypertriglyceridemia, hemophagocytosis in the bone marrow, low or absent NK cell cytotoxicity, hyperferritinemia, and elevated soluble CD25 [8]. However, initial clinical diagnosis isdifficultsince notall patientsmeetallofthese diagnosticcriteriaandmanypatientsdosoonlyinthelate course oftheirdisease.Earlydiagnosisandtreatmentoften are essential for survival. In this case,the patientinitially presented with only fever and weakness of lower limbs which was quite inconspicuous and easily misdiagnosed.

There mayalsobealong prodromalperiod of non-speciﬁc illnessbeforedevelopmentofthecompletesyndrome.Since acquiredHPSisusuallyassociatedwithlymphoma,inthose patientswho presentwithmanifestation ofHPS,thesuspi- cionoftumorregressionisoftencrucial.

Cutaneous manifestations in HPS are relatively uncom- mon and detailed descriptions of skin lesions and their histopathologic ﬁndings have rarely been reported. It can accompany underlying hemophagocytic syndrome in the form of purpuric, macular, papular,erythrodermic, ormor- billiform eruptions [9–11]. Right now it is considered that the pathophysiology of its cutaneous manifestations is Fig.1–(A–C)CTandMRIimagesofthepatientatthe

diagnosisofHPS.CTimage(A)showedametastaticlesion (arrow)intherightlungonmediastinalwindow.

T2-weightedimages(B–C)showedepiduralmasslesion (arrow)atT4levelwithcompressionofthespinalcord (asterisk)

Fig.2–Widespreaderythematousmaculesonthetrunk acta haematologica polonica45(2014)83–85

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consistent with that of the current understanding of HPS.

Thelatter isassociatedwitha generalizedimmune activa- tion withrelease of proinflammatorycytokines, which can causetheviciouscircleofinflammatory‘‘cytokinestorm’’of infiltrated organ systems, including skin [12–14]. Thus,the clinicalcutaneouspresentationinHPSmaybeanimportant sign of the judgment of severity, effect of treatment, and prognosis of the disease. The reappearance of cutaneous manifestationsinapatientmayheraldarecurrenceofHPS [15].Inourcase,thefeverstoppedduringthefirstfewdays and the plateletcount evenreturned tothe normalrange.

However, the patient immediately developed widespread maculesaccompaniedwiththefollowingprogressivethrom- bocytopeniaand paralysisof the lowerlimbs,and failedto receive further chemotherapy. The macules that appeared during the therapy was quite rare and might serve as astrongpredictorofunfavorableoutcome.

In summary, hemophagocytic syndrome secondary to the relapse diffuse B cell lymphoma is rare and has a dismal prognosis with a quick disease progression. The cutaneous presentation in the clinical course might be astrongpredictorofunfavorableoutcome.

Authors' contributions/Wkład autorów

Accordingtoorder.

Conﬂict of interest/Konﬂikt interesu

Nonedeclared.

Financial support/Finansowanie

Nonedeclared.

Ethics/Etyka

Thework describedin this article has been carriedout in accordance with TheCode of Ethics of the World Medical Association(Declaration of Helsinki)for experimentsinvol- ving humans; EU Directive 2010/63/EU for animal experi- ments;UniformRequirementsformanuscriptssubmittedto Biomedicaljournals.

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