Hyaline vascular Castleman's disease (HVCD) mimicking lung metastasis of renal carcinoma: A case report and literature review

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Case report/Kazuistyka

Hyaline vascular Castleman's disease (HVCD) mimicking lung metastasis of renal carcinoma:

A case report and literature review

Ai-Ying Qin

^1,3,4

, Xiu-Bao Ren

^2,3,4

, Shui Cao

^2,3,4,

*

1DepartmentofImmunology,TianjinMedicalUniversityCancerInstituteandHospital,Tianjin,China

2DepartmentofBiotherapy,TianjinMedicalUniversityCancerInstituteandHospital,Tianjin,China

3NationalClinicalResearchCenterofCancer,Tianjin,China

4KeyLaboratoryofCancerImmunologyandBiotherapy,Tianjin,China

Background

Castleman's disease is a rare atypical lymphoproliferative disorder, consistingof twomain entities– UCD(Unicentric Castleman's Disease) and MCD (Multicentric Castleman's Disease) withdifferentcharacteristics [1,2]. Coexistenceor subsequentialoccurrenceofCDandothermalignancieshas been rarely reported, and explanations other than coinci- dencearecontentious[3–8].

Case presentation

An asymptomatic 70-year-old man was found to have an enhancing right renal mass during a routine workup in acomputed tomographyinspection(CT)(Fig.1).AchestX- rayandallpreoperativelaboratoryﬁndingswerenormal.He underwent a radical right laparoscopic nephrectomy for suspected renal cell carcinoma. Gross pathology examina- tion demonstrated aductile, red andpale mass,limitedto

*Corresponding authorat: Tianjin MedicalUniversityCancer InstituteandHospital,Tianjin Hexi District,Huanhuxi Road, Tianjin, China.Tel.:+8603708772869;fax:+862223558988.

E-mailaddress:caoshui@yahoo.com(S.Cao).

article info

Articlehistory:

Received:24.07.2013 Accepted:10.03.2014 Availableonline:19.03.2014

Keywords:

Castleman'sdisease

Renalcancer

Completeresection

Histopathology

Occurrence

abstract

Castleman'sdisease(CD)isararelymphoproliferativedisordercharacterizedbyatypical lymphnodefollicularhyperplasia.SubsequentialoccurrenceofCDandcancershasbeen rarelyreportedandinterpretationsoftherelationshiparecontentious.Anasymptomatic 70-year-oldmanwasfoundtohavealeft-sidedhilarmassduringroutinefollow-upafter aradicalrightnephrectomyforclearcellcarcinoma,raisingsuspicionsoflungmetasta- sis.Because therewasnosignofrecurrenceintheoriginaloperativeregion,heunder- wentwedge resection ofthe left lung and lymph nodesdissection. Histologyshowed typical features of HVCD. Herein, we emphasize careful histopathology and complete resectionofCD.WespeculatethatsubsequentialoccurrenceofCDandcancersmaynot becoincidentalandwarrantsfurtherexploration.

ContentslistsavailableatScienceDirect

Acta Haematologica Polonica

journal homepage:www.elsevier.com/locate/achaem

http://dx.doi.org/10.1016/j.achaem.2014.03.001

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the rightrenal, measuring 3.2cm2.8cm3.0cm. Aclear cellcarcinomawasconﬁrmedonhistology(Fig.1).Observa- tion was suggestedas per National ComprehensiveCancer Center guidelines (Version 2. 2014). Follow-up CT and US (ultrasound) were normal until a CT (Figures not shown) demonstrated a distinct left-sided hilar mass two years postoperatively. A subsequent PET-CT (positron emission tomography/computed tomography) scan conﬁrmed an

abnormal soft tissue mass with increased 18F-FDG (18F- ﬂuorodeoxyglucose) uptake inthe inferior lobe of left lung near the diaphragm, raising suspicions of malignancy, but nosignofrecurrenceintheoriginaloperativeregion(Fig.2).

All preoperative laboratory ﬁndings including CRP (C reac- tive protein), ESR (Erythrocyte sedimentation rate) were normal.EtiologictestingincludingHIV(humanimmunodeﬁ- ciency virus) antibody and HHV8 (human herpes virus 8) Fig.1–Contrast-enhancedCTimageoftheabdomenshowinganenhancingmass,highlysuspiciousformalignancy(asthe arrowshowed).Hematoxylin-eosinstainedphoto-micrographshowstypicalpathologyofclearcellrenalcancer

Fig.2–Anabnormalsofttissuemasswithincreased18F-fluorodeoxyglucoseaccumulationsuspiciousformalignancy,with noevidencerecurrenceintheoriginaloperativeregion(asthearrowsshowed)

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Fig.3–(A)TypicalhistologicfeaturesofCastleman'sdiseasewithhyalinevascularvariant.Hematoxylin–eosinstainedphoto- micrographshowstheclassic'onionskin'appearanceinimmunohistochemistry.(B)Bcl-2negative.(C)CD3partiallypositive.

(D)CD5partiallypositive.(E)CD20prominentlypositive.(F)CD21follicularnegative.(G)Ki-6720%positive.(H)cyclinD1 negative(allofthephotomicrographsarepresentedwithmagnificationof4Tand20T)

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werenormal.Toestablishadeﬁnitivediagnosisandexclude lung metastasis,he underwentawedgeresectionof theleft lungandthe7,9,11groupslymphnodesdissection.Histolo- gicalsectionsofthemassrevealedtypicalfeaturesofHVCD:

manylymphoidfollicleswithhyalinizedgerminalcentersand broadmantlezones, showingthe classic'onionskin' appear- ance, with vascular proliferationprominent in the germinal centersand theinterfollicular areas inHEstaining (Fig. 3A).

The IHC (immunohistochemistry) showed blow (Fig. 3B–H), conﬁrmedtheHVCDhistology.Observationandregularcheck- upweresuggested.Untilnow,thereisnosignofreoccurrence.

Discussion

BenjaminCastlemanﬁrstreportedtherarelymphoprolifera- tive disorder that bears his name in 1954 [1]. CD is aheterogenousdiseaseseparatedintotwoentitiesclinically– UCD(unicentricCastleman'sdisease)andMCD(multicentric Castleman'sdisease),withdistincttreatmentalgorithmsand prognosis. CD is further divided into three variants histo- pathologically. The plasma cell and mixed type usually presentasMCD,often associatedwith constitutional symp- toms and require systematic therapy [5]. The hyalinized vasculartypeaccountsfor90%ofUCD,isoftenasymptomatic at presentation, and has a high cure rate with surgical excision [9]. Complete resection is required as recurrence followingsurgerydoesoccurinaminorityofUCDcases[10].

Relation with cancers

WhileCDisagroupof benignlymphoproliferativedisorder, thereare complexrelationshipsbetweenCDandmalignan- cies.Althoughrapidlyimprovingimagingtechniquesexists, especiallyPET-CT, may failedto differentiate CD and cancers. [11, 12]. Recent reports show that CD can mimic neoplasmcausingdiagnosticdilemmasrequiringpathology toresolve[12,13].Asinthiscase,diagnosismaybedifﬁcult toascertainandshouldrelyonhistology.

Concomitant or subsequential occurrences of CD and malignanciesincludinglymphoma,melanoma,Kaposi'ssarcoma, melanoma,hepatocellular carcinoma and renal can- cerhavebeenreported[3–8].Itdeservesconsiderationwhen a suspicious mass is present. In this case, CD in the mediastinum mimicked lung metastasis of renal cancer.

Complete resection and careful pathology were needed to guaranteeaccuratediagnosisandtherapy.

Potential theories

Concomitantor subsequentialoccurrencesof CD withcan- cers may be more than coincidental. A number of causal mechanismshavebeenproposed.

IL-6isinvolvedinawiderangeofbiologicactivities,such asauto-immunedisease,chronic inﬂammatoryproliferative diseaseandapoptosisresistance[14].StimulatingBlymphoid cellproliferationandplasmacelldifferentiation,highexpres- sion of IL-6 was discovered both in the lymph nodes and

serum of CD patients, and ﬂuctuation of IL-6 is correlated with symptom variation [15]. In recent case reports, Tissier and Deshmukh attributed CD synchronous with cancers to dysimmunity causedby IL-6elevation [3,4].Often reported coexistent with MCD,Kaposi'ssarcoma iscommonlyattrib- utedtoHHV-8infection[16].HHV-8canencodeviralIL-6(vIL- 6)inlatentlyinfectedcells,whichcaninitiateMCDbybinding toubiquitouslyexpressedgp130 receptorsubmitandsubse- quently JAK-STAT pathway [17]. Research onhepatocellular malignancy showed that elevation of IL-6 is insufﬁcient.

Experimentinvivo suggeststhatacertain thresholdofIL-6 stimulationisrequiredtoinitiatehepatocellularhyperplasia [18], whereas a second hit of CTNNB1 (c.121A >G; p.T41A) mutationisnecessaryforthedevelopmentofconcurrenceof hepatocellularcarcinomaandCD[6]. Siltuximab(achimeric human-murine anti-IL-6antibody)hasproduced afavorable responseinacaseofcutaneousCD[19].

In additiontoIL-6,evidence isaccumulatingthatabnor- mal expression ofVEGF (vascularendothelial growthfactor) may be another factor [4, 8]. Asan important hallmark of cancer,angiogenesislinksthemalignancyanddistantmetas- tasis, and frequently appears in the interfollicularspace of CD.Closelycorrelatedwithvesseldensity,VEGFseemstobe the most relevant cytokine in this respect. As for renal carcinoma,aVHLgenemutationoftenoccurs,activatingthe hypoxia-response pathway and inducing transcription of several genes, including VEGF, and subsequent tumor pro- gression [20]. Completeresectionof CDmay beessentialto avert susceptibility tomicroangiopathyrelated toVEGF [21].

A single case report discusses the successful embolization withpolyvinylalcoholmicroparticles[22].

There are several reports of concurrence of follicular dendritic cell sarcoma (FDCS) with HVCD [23]. Follicular dendriticcellsareakindofstromalcells,dysplasiaofwhich may provide a newpathogenetic hypothesis of HVCD[24].

Discoveriesonthechromosomallevelhaveprovidedgenetic interpretations and give clues that complication of HVCD andFDCSmaynotbecoincidental[25].

An intriguing question emerges: does CD contribute to the development of cancersor vice versa?CD was consid- ered a paraneoplastic phenomenon of spindle cell carcinoma[5]. Whenit coexistedwithHodgkin'sdisease,it was regarded as a reaction to malignancy [7]. In a case of occurrence with melanoma, CD was proposed to be aconsequenceofVEGFsecretionbysolidtumors[8].

Conclusion

ThiscaseofHVCDmimickinglungmetastasisofrenalclear cellcarcinomarequiredcarefulhistopathologyandcomplete resectionofCD.ThiscoexistenceofCDandcancermaynot bea coincidence.Further researchiswarranted to unmark therelevantoccultmechanism.

Consent

Written informedconsentwasobtainedfromthepatientfor publicationofthisCasereportandanyaccompanyingimages.

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Authors' contributions/Wkład autorów

ThestudywasdesignedanddatawerecollectedbySCand XBR. Statistical analysis and manuscript preparation were donebyAYQ.Datainterpretationandliteraturesearchwere performedbyAYQ.

Conﬂict of interest/Konﬂikt interesu

Nonedeclared.

Financial support/Finansowanie

NationalBasicResearchProgramofChina(973program)No.

2012CB9333004.

Ethics/Etyka

The work described in this article has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments invol- ving humans; EU Directive 2010/63/EU for animal experiments;UniformRequirementsfor manuscriptssubmittedto BiomedicalJournals.

Acknowledgement/Podziękowania

Authors thankJohn E.Anderson, M.D. from JohnsHopkins Universityfor hispersonalassistanceinthepreparation of thework.

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