Sarcoma(2000) 4, 17± 26

ORIGINAL ARTICLE

Soft tissue tumours of theretroperitoneum

J.FRANS GRAADTVANROGGEN&PANCRASC.W.HOGENDOORN

Departmentof Pathology,Leiden University Medical Centre,TheNetherlands

Abstract Purpose. This reviewsummarizes themore prevalent soft tissuetumours arising inthe retroperitoneum and highlights somerecent fundamental and diagnostic developments relevant to mesenchymal tumours. Discussion. Theretroperitoneum is an underestimatedsite for benignand malignant neoplastic disease, andrepresents the secondmost common site of originof primary malignantsoft tissuetumours (sarcomas) after thedeep tissues ofthelower extremity.Incontrast to thepredominance of benignsoft tissuelesions over malignantsarcomas elsewhere,retroperitoneal mesenchymallesions are far morelikely to be malignant. The differential diagnosis is primarily withthe more common lymphoproliferative andparenchymatous epitheliallesions arising inthis area, andwith metastatic disease from knownor unknownprimary sites elsewhere.The most prevalent mesenchymal tumours at this siteare of alipomatous, myogenicor neuralnature. Theirgenerally late clinical presentation and poorly accessiblelocation provides numerousclinical challenges; optimal radiologicalimaging and a properly performed biopsy are essentialcogs in the management route. Histopathological diagnosismay becomplicated, but has beenaided by developmentsin the ® eldsof immunohistochemistryand tumour (cyto)genetics.Despite signi® cant advances inoncological management protocols, theprognosis remains generallyless favourable than for similar tumoursat more accessible sites.

Key words: softtissue tumour, sarcoma, review,retroperitoneum

Introduction Inadultsthe majority ofretroperitonealneoplasms arepr imarylymphoproliferative (Hodgkin’sand Theretroper itoneumreprese ntsthe lumbo-iliac non-Hodgkin’slymphoma)andparenchym atous anatomicalreg ionbou ndedan teriorlyby the epithelialtumour s(renal,adrenal, pancreas), or peritoneum,posteriorly by the posteriorabdominal representmetastatic diseasefrom known or unknown wall, superiorlyby the 12th riband vertebra, inferi- primarysiteselsewhere. 2 Ininfancy and early child- orlyby the sacrumand iliac crest and laterally by the hood,nephroblastoma (Wilms’ tumour), neuroblas- peripheralmarg inof the quadratuslu mborum toma andgerm cell tumours are the morecommon muscles.Present within the retroperitoneumare the retroperitonealneoplasms. 3 pancreasand duodenum, kidneys and ureters, adrenal Soft tissue(mesenchymal) tumours of the retroperi- glands,aorta andits branches,inferior vena cava and toneumare less common; nevertheless 15% of all its tributaries,lymph nodes and nerve branches, all primarysarcomasarise within the retroperitoneum, embeddedin alooseframework of connectivetissue. andconsequently this representsthe secondmost Therelative paucity of vital structures,and the commonsite for the originof malignantmesen- abundanceof looseconnective tissue in this area, results chymaltumours, after the deeptissues of the lower ina generallylate clinicalpresentation of space- extremity(thigh). 1 It isthe generalexperience that, occupyinglesions. Symptoms tend to berelated to althoughbenignsoft tissuelesionsat all sites gastrointestinal,urinary or vascular compromise, when outnumbertheir malignant counterparts by aratio of largelesional size and compression/ invasionof adjacent at least 100:1, inthe retroperitoneumsarcomas are structuresseverely limits the curativetreatment options. moreprevalent than theirbenign counterparts. In Collectively,malignant tumours of the retroperito- comparisonwith soft tissuelesio nselsewh ere, neumare roughly four times more frequent than however,the rangeof commonlyencountered retro- benignlesions, in sharp contrast to neoplasticdisease peritonealmesenchymal neoplasms is more limited, occurringelsewhere in the body,where benign disease with the mostcommon lesions being of alipomatous, predominates. 1,2 smoothmuscle or neural nature (T able 1). 1,2

Correspondenceto: P.C.W.Hogendoorn,MD, PhD, Department ofPathology, LeidenUniversity Medical Centre, Building I,L1-Q, PO Box9600, 2300RC, Leiden,The Netherlands. Tel:+31 71 526 6639; Fax: +3171 5248158; E-mail: p.c.w.hogendoorn@ pathology.medfac.leidenuniv.nl 1357-714Xprint/1369-1643online/00/010017-10 ½ 2000T aylor &FrancisLtd 18 J.FransGraadt VanRoggen& PancrasC.W .Hogendoorn

Table 1. Softtissue neoplasmsof theretroper itoneum

Malignant Benign

Lipomatous: Well-differentiatedliposarcoma Myolipoma Dedifferentiatedliposarcoma Myogenic: Leiomyosarcoma Neurogenic: Malignantperipheral nervesheath tumour (Anciant)schwannoma Miscellaneous: Neuro®broma Desmoplasticsmall roundcell tumour Pleomorphicsarcoma, undifferentiated Kaposiform haemangioendothelioma In¯ammatory myo® broblastic tumour

Whilemost of the betterdifferentiated retroperito- It isthe aimof this shortsynopsis to discussthe neallesion sgenerally donot posesign i®can t mostprevalent retroperitoneal soft tissuetumours diagnosticproble ms,high -gradesarcom as may andassociated differential diagnoses, and to highlight presentmor phologically as poorlydifferent iated someimportant recent developments in fundamental tumourslackingdistinct ive phenotypicfeatures. anddiagnostic aspects of mesenchymaltumours. Consequently,histomorpholo gicaland ultrastruc- turalanalysis may beinsufficient for reaching an Thehistopathology of retroperitonealsoft tissue accurate(differentia l) diagnosisin cer tain cases, tumours essentialfor directing patient managementstrategies. Fortunately,it has becomeapparent overthe last Thesoft tissuesare de® ned as consistingprimarily of decadethat certainsoft tissuetumours appear to be extraparenchymatousvoluntary muscle, fat, ®brous associatedwith tumour-speci®c geneticalterations (connective)tissue, and the neurovascularsupply of (Table 2), and(cyto)genetic analysis aimed at the thesetissues. 1 Nevertheless,mesenchymal tumours detectionof thesealterations is a helpfuladjunct in alsoregularly arise from the supportingconnective resolvingsome of thesediagnostic dilemmas. 4 tissuesof the variousorgans and are included in this Computerizedtomography(CT) scanningand review. (dynamic)magnetic resonance imaging (MRI) are the radiologicalprocedures of choicein determining Reactive non-neoplastic processes the extentof local,regional and distant tumour spread.These procedures are essential for clinical Retroperitonealmasses may beof anon-neoplastic staging,planning an appropriate and optimal biopsy orneoplastic nature. Non-neoplastic masses arising procedureprior to de®nitive treatment, as wellas at this siteare pred ominantly of areactive/ playingan important role in follow-up imaging to in¯ammatory orinfectious nature, involving either assessefficacy of treatmentregimens. 5± 7 Addition- the organsat this siteor the retroperitonealsoft tissues. ally, positronemission tomography (PET) scanning Thesegenerally do not pose a clinicalproblem, may, incertainsettings, be of clinicaluse, particularly althoughperiodically the differentialdiagnosis with inthe detectionof high-gradesarcomas and the neoplasticdisease may bemore complicated; for assessmentof localrecurrence. 8,9 examplethe differentialdiagnosis of reactive® brosis

Table 2. Genetic alterationsof diagnostic signi® cancein thesarcoma group

Tumour Geneticalteration Gene(s)

Alveolar rhabdomyosarcoma t(2;13)(q35; q14) FKHR/PAX3 t(1;13)(q36; q14) FKHR/PAX7 Atypical lipoma/well-differentiatedliposarcoma ring(chr. 12)/ marker chromosome ? Desmoplasticsmall roundcell tumour t(11;22)(p13; q12) EWS/WT1 Ewing’ssarcoma/ PNET t(11;22)(q24; q12) EWS/FLI1 t(21;22)(q22; q12) EWS/ERG t(7;22)(p22; q12) EWS/ETV1 Gastrointestinalstromal tumour mutationchromosome 4q11-21 c-kit losses chromosome14q Myxoidliposarcoma t(12;16)(q13; p11) CHOP/FUS t(12;22)(q13; q11) CHOP/EWS Synovial sarcoma t(X;18)(p11.2; q11.2) SYT/SSX1 SYT/SSX2 Soft tissue tumours ofthe retroperitoneum 19

(sometimesseen with non-Hodgkin’slymphoma) 10/ Liposarcoma ÐLiposarcomasare the mostcommon idiopathicretroperitoneal ® brosis(an in¯ammator y/ soft tissuetumours occurring within the retroperito- reactiveprocess often presenting as amass) 11,12/ neum,and probably accountfor 25± 35% of all mesen- retroperitoneal® bromatosis, 12 at this siteregularly chymal lesionsat this site. 21± 23 Althoughthe seenin the context of Gardner’ssyndrome 13/ liposarcomag roupis subdiv idedinto well - ®brosarcoma(rare), 12 andthe differentialdiagnosis differentiatedliposarcoma, dedifferentiated liposar- of xanthogranulomatouspyelonephritis coma,myxo id/roundcell liposa rcoma,an d (in¯am matory) 14/(sarcomatoid)renalc ell pleomorphicliposarcoma, the majority of retroperi- carcinoma15/soft tissuesarcoma with axanthogranu- tonealliposarcomas are of the well-differentiatedand lomatousmorphology . 12 dedifferentiatedtype. 22 Myxoid/roundcell liposar- comaoccur far lessfrequently in the retroperito- Neoplastic disease neum,while pleomorphic liposarcoma at this siteis very rare.22 Well-differentiatedand dedifferentiated Asalluded to earlier,the majority of retroperitoneal liposarcomashould probably beregarded as related tumoursare primary lymphoproliferative and paren- entitiessince the latter oftenarises from/ withinthe chymatousepithelial tumours. former,23± 25 andcommon genetic alterations are Themajority of lymphomasare non-Hodgkin’ s presentin these tumours (ring chromosomes derived B-celltype, butthese may beassociated with avari- fromchromosome 12 andlarge marker chromosomes; able degreeof contiguous® brosis/sclerosissometimes Table 2).26,27 Similarly(cyto)genetic analysis has complicatingthe clinicaldifferential diagnosis as establishedthat the vast majority (75%) of myxoid mentionedabove. 2,10 andround cell liposarcomas share a commont(12; Epithelial tumoursarising in the kidneys,ureters, 16)(q13; p11) translocation(T able 2), indicatingthat adrenalsand pancreas may invadethe retroperito- nealsoft tissues.Althou ghthe varioustumour thesetumours probably representthe low-gradeand high-gradecom ponentsrespect ively of asingle subtypesm ay posed iagnosticproble ms,these 4,22,27 tumoursare histopathologically rarely difficult to tumourentity . Furthermore,myxoid liposar- comahas alsobeen reported to undergodedifferen- distinguishfrom non-epithelial lesions, particularly with the useof immunohistochemistry. tiation, suggestinga closerrelationsh ipbetween myxoidand well-differe ntiatedliposarcom athan Primaryretroperitoneal seminomatousand 28 non-seminomatousextra-gonadal germ cell tumours previouslythought. areless frequent, although teratomas occurin a Clinically,distinctionbetween the variouscategories 16,17 withinthe liposarcomagroup remains important due relatively greaterperce ntageo fchildren. 22,29 Additionallyembryological remnants such as tailgut to theirdifferent modes of biologicalbehaviour. cysts andother an omaliesmay occurin the Liposarcomasmay beof variable size(reaching retroperitoneal/sacralarea, rarelyu ndergoing sizesof morethan 20 cm),are often well - 18 circumscribed/encapsulated,and frequently show a malignantchange. Metastatic diseaseto the retroperitoneum,from a distinctlobulation. The cut surface has avariable gamutof intra-and extraperitoneal sites, represents morphologydependent on tumourtype. anothersigni® cant proportionof masslesions at this (A)Well-differentiatedand dedifferentiated liposar- siteand needs to beconsidered in any differential coma.W ell-differentiatedliposarcoma is composed diagnosis.M etastasesfr oman und ifferentiated of abackgroundof mature-lookingadipocytes carcinomamay createdifficulties in the differential (althoughnuclei tend to beslightly larger and more diagnosiswith primaryspindle cell tumours of the pleomorphic),with avariable scatteringof lipoblasts retroperitoneum,although this dilemmais usually eachcontaining a singleatypical, hyperchromatic,scal- resolvedwith anappropriate immunohistochemical loped(indented), and eccentrically located nucleus panelincluding cytokeratins. with oneor more scattered cytoplasmic lipid droplets/ Themajority of soft tissuetumours arising in the vacuoles.The tumour may betraversed by dense retroperitoneum(T able 1) areof alipomatous, bandsof variably cellularcollagen and demonstrate a myogenicor neurogenic nature and are discussed variable in¯ammatory cellin® ltrate composedof below. lymphocytesand plasma cells; histopathologically the 1.Lipomatoustumours. LipomaÐMyolipoma(lipo- diagnosisis rarelytroublesome. leiomyoma),a benignencapsulated lesion of variable Althoughwell-differen tiated liposarcomashave sizeand compose dof anadmixtu reof mature beensubtyped (lipoma-like, in¯ ammatory, sclerosing adipocytesand bundles of smoothmuscle may be variants) dependenton the degreeof ®brosisand encounteredin the retroperitoneum. 19 Nevertheless, in¯am matoryin®ltrate, the clinicopathological pureretroperitoneal lipomas are a poorlydocumented relevanceof this isdebatable sincecombinations of andcon tentiousentity 20± 22 and,althoug hthey the variousmorphologies may beseen in individual theoreticallymust occur, all lipomatoustumours at tumours.22,30 this siteshould probably beregarded with ahigh Dedifferentiatedliposarcoma generally consists of levelof suspicionfor malignancy . well-differentiatedareas with asharptransition to 20 J.FransGraadt VanRoggen& PancrasC.W .Hogendoorn adjacentno n-lipogenicsarcom atousareas variably diffusein liposarcoma), as wellas cytomor- demonstratingeither a low-grade® bromatosisor well- phology.Thepresence of the characteristict(12; 16), differentiated® brosarcomamorphology ,ora high- andlack of the t(11; 22)(p13; q12) translocation grade® brosarcomaor undifferentiated sarcomatous foundin DSRCT (T able 2), 4 isa powerfuladjunct. morphology;occasionally the dedifferentiatedareas Puremyxoid liposarcoma is regarded as alow-grade may resemblecarcinoma or melanoma. 31 Dedifferen- sarcoma.A metastatic potentialexists, however, in tiation to morethan onehistogenetic tissue type (for about 10± 20% of cases,although this correlation exampleosteo- or chondrosarcoma) may occurin a probably dependsonthe adequacyof tumour minorityof cases. 31Thedifferential diagnosis of dedif- sampling(inadequate sampling will fail to identifya ferentiatedliposarcoma with otherlow- or high- roundcell component). 33,36 Furthermore,while a graderetroperitoneal spindle cell lesions is often myxoidliposarcoma with aroundcell component of difficultand may requireextensive sampling of the morethan 5± 10% isregarded as havinga signi®cant de®nitive surgical specimen to identifythe lipoma- metastatic risk,caution is necessar ysinceno clear touscomponent. criteriaare present for tumour grading, and there are Well-differentiatedliposarcoma is regarded as a oftenproblems with tumoursampling. 35,36 low-gradesarcoma that doesnot metastasize. 23,24,32,33 However,recurrence rates are high (approaching 2.Myogenic tumours. LeiomyomaÐPrimaryleio- 100% inthe retroperitoneumdue to the generally myomaof the retroperitoneumis an extremely rare late presentationÐand consequently large sizeÐ and occurrenceand should be diagnosed with extreme 2 problematicsurger y) anda signi®cant proportion caution(see below). (10± 20%) willdedifferentiate over a meanperiod of LeiomyosarcomaÐ Leiomyosarcomasof the retro- 7± 8yearswith anacquisition of the capacity to metas- peritoneumare the secondmost common primary tasize, irrespectiveof the extentof dedifferentia- malignantsarcoma at this site,after liposarcomas. 1 tion.32 Followingtreatmen tfordediffer entiated Thistumour should not be grouped with the gastroin- liposarcoma,the reportedrates of localrecurrence testinalstromal tumours (GIST) of the smalland andmetastatic diseaseare variable; localrecurrence largeintestine (occasionally seen in the retroperito- occurringin 40± 100% of casesand distant metas- neumas aresultof localspread), a complexgroup of tases inroughly 20% of cases. 31,34 However,the tumourspostulated to arisefrom pacemaker cells generalimpression remains that thesetumours prob- (interstitialcells of Cajal) locatedin the wall of the ably exhibita lessaggressive behaviour than dediffer- bowel,and demonstrating a variety of differentiation entiatedsarcomas in general. 31 patterns(see below). 38,39 (B) Myxoid/roundcell liposarcoma. Myxoid liposar- Roughlytwo-thirds of leiomyosarcomasoccur in coma,far lesscommon in the retroperitoneum, womenwith anaverage age at presentationof 60 consistsof anabundan thyaluronidase-sensitive years.The tumours are of variable size(average size myxoidmatrix with smallbland spindle-shaped or 10± 20 cm),and at surgeryofteninvolve adjacent morerounded cells, univacuolated (signet ring-like) structuresby directspread. Tumoursoften show foci 40 lipoblasts,and sporadic multivacuolated lipoblast- ofhaemorrhage,necrosis and cystic change. Histo- s.Thevasculature is composed of adelicateplexi- logically,the generalarchitecture is that ofafasicular formarrangement of thin-walledcapillaries described tumour.Cell morphology can be highly variable, as havinga chickenwire or crow’ sfeet distribution. rangingfrom well-differentiated to anaplastic, but Thepr esenceof amorecellu lar(round cell) the typical cellis elongated and tapering, contains a componentis associated with amoreaggressive cigar-shapednucleus with obviouspleomorphism, biologicalbehaviour. 33,35,36 Sinceno histopatho - bipolarperinuclear glycogen-containing vacuoles and logicalconsensus has beenreached on the percentage eosinophiliccytoplasm.The detectable mitotic activity of the roundcellcompon entrequ iredfor an may behighly variable and,since it isthe general unambiguousdiagnosisof high-graderound cell experiencethat eventumours with 1± 4mitoses/2mm 2 liposarcoma,we tend to reportthese neoplasms as canmetastasize, all tumourswith obviousnuclear mixedmyxoid and round cell liposarcoma and give atypia (irrespectiveof the mitoticactivity) shouldbe anapproxim ationof the percentageround cell regardedas potentially malignantwhen occurring in componentpresent. the retroperitoneum. 1 Immunohistochemicallythere Dependingonthe extentof aroundcell isvariable expressionof muscle-speci®c actin(MSA), component,the differentialdiagnosis is primarily with smoothmuscle actin (SMA) anddesmin; S100 malignantperipheral nerve sheath tumour(MPNST) proteinand CD34 expressionare absent. Although a andd esmoplastic small roundcell tum our partial deletionof chromosome1p ispresent in about (DSRCT).37 Thisdistinction is generally based on 50% of cases,no tumour-speci® c geneticalterations the relationshipof the tumourto alargener ve trunk areconsistently present, since this deletionalso occurs onimaging (MPNST), lack ofcoexpressionof neural inother soft tissuetumours. 41 epithelialand mesenchymal markers (DSRCT), the Thedifferential diagnosis is primarilywith spindle degreeof S100 proteinpositivity (spotty inMPNST, cellMPNST and® brosarcoma,generally resolvable Soft tissue tumours ofthe retroperitoneum 21 usingimmunohistochemistry (desmin positive, S100- Malignant peripheral nervesheath tumour Ð proteinnegative). MPNSTsare de® ned as malignantmesenchymal Thesetumours are highly aggressive with a5-year tumoursarising from, or differentiatingtowards, cells survivalbetween 0 and20%. 40 of the peripheralnerve sheath, butexcluding epineu- rialtumours and tumours arising from the neural Rhabdomyosarcoma ÐRhabdomyosarcoma, 51 althoughinfrequently seen in the retroperitoneum, vasculature. Roughlytwo-thirds of casesare associ- needsto beconsidered. 42,43Thisis primarily a tumour ated with apreexistingn euro®broma, while of childrenand young adults and, of the three approximatelyhalf ofMPNSTsarise in patients with neuro®bromatosis I (NF I)(presumablyhaving arisen describedsubtypes (embryonal, alveolar andpleomor- 52 phicrhabdomyosarcoma), embryonal rhabdomyosa- withina neuro®broma). MPNSTsare tumours of adults,although the ageat presentationin patients rcomais the mostcommon retroperitoneal tumour, 52 whilethe alveolar andpleomorphic subtypes are with NFIisyounger than inunaffected patients. extremelyunusual at this site.The presence of the Macroscopically,tumours are nodular and ® rmand characteristict(2;13)(q 35;q14)/t(1;13)(p36;q14) may showextensive necrosis. Microscopically, these translocationspresent in the vast majority of alveolar tumourhave ahighlyvaried mor phology(well- rhabdomyosarcomamay beof diagnosticuse 44± 46 differentiatedto anaplastic), althoughthe prototypical (Table 2). lesionis cellular with afasciculararchitecture; cells areelongated and tapering with wavy, pleomorphic 3.Neurogenictumours. SchwannomaÐSchwannoma, andhyperchromatic spindled nuclei. Mitoses are includingthe cellularvariant (cellularschwannoma), frequent ( 4/2 mm2).Classically S100-protein isthe mostcommon neurogenic soft tissuetumour 47 stainingis focal andweak to variably prominant.The occurringin the retroperitoneum. presenceof arhabdomyoblasticcom ponent Clinically,theselesions have abroadage range of (malignantT ritontumour), con® rmed by positive presentation,and often occur paraver tebrally. myogenicimmunohistochemistry, is an extremely rare Macroscopically,both schwannomaand cellular ®ndingand may occurboth withinand outside the schwannomaareencapsulate dnodulartumours, settingof NFI. 53 regularlyseen in association with anervetrunk, which MPNSTis a high-gradetumour with anextremely may beextremely large at presentation.On sectioning, poorprognosis ( 20± 30% 5-year survival). 52 the classicalschwannoma has avariably tan, haemor- rhagicand cystic appearance, while the cellularvariant 4.Pleomor phicsarcomas. So-called`malignant ® brous is® rmerand more homogeneously tan incolour. histiocytoma’(MFH) isfrequently regarded, prob- Microscopically,the schwannomais characterized ably incorrectly,as aspeci®c diagnosticentity and by the classicalAntoni A areascomposed of fasicles usedto denotea groupof tumourswith ananaplastic of spindle-shapedcells with focal nuclearpalisading, morphologyand without detectableevidence of soft hypocellularand mucoid Antoni B areas,V erocay tissuedifferentiation using current immunohisto - bodies,and vascular hyaliniza tion.The cellula r chemical methods.Althou ghthis remainsa schwannoma,however, as its namesuggests, is more controversialarea, it isnow likely that thesetumours cellular,composed primarily of AntoniA areasand representa heterogeneousgroup of extremelypoorly frequentlyhas capsularand perivascular lymphocytic differentiatedtumours which are as yet nothistoge- aggregates.Whileobvious nuclear pleomorphism and neticallyclassi® able with currenttechniques. 54 It is mitoticactivity isgenerally absent in the classical ourpreference to reportthese tumours as high-grade schwannoma,mild nuclear pleomorphism and a vari- pleomorphicsarcomas without detectabledifferentia- ably lowmitotic activity (notmore than fourmitoses/ 2 tion(NOS), andto avoidthe non-speci®c labelMFH. mm2)may beseen in the cellularschwannom a complicatingdiagnosis, particularly when the patholo- 5.Miscellaneous retroperitonealsoft tissue tumours. In gistreceives a minuteneedle-core biopsy . 48,49 An additionto the above-mentionedtumours, a variety accuratediagnosis is of signi®cant clinicalimportance of lesscomm onmesenc hymal tumoursare sincethe risksof complicatedsurgery at this sitefor encounteredin the retroperitoneum. what isa benignlesion should be properly considered. Desmoplasticsmall round celltumour Thedifferential diagnosis is with MPNSTand other (DSRCT)ÐDSRCT,a malignant tumourof spindlecell tumours, although the strongdiffuse posi- children,adolescents and young adults and belonging tivity forS100-protein, (peri)vascular hyalinization to the morphologicalcategory of smallblue round andAntoni A areasshould in most cases facilitate the celltumours (including Ewing’ ssarcoma,embryonal correctdiagnosis. rhabdomyosarcoma,lymphoma), periodically occurs Bothtumours are benign and although local recur- at this site. 55 Histologicallythe tumouris composed renceshave beennoted for cellular schwannoma, no 50 of solidnests of smallround to polygonalcells set metastaseshave beendocumented. withina densedesmopl astic stroma.Impor tant Neuro®broma ÐNeuro®bromas, identical to their diagnosticfeatures are the coexpressionof epithelial, counterparts elsewhere,are also per iodically neuraland mesenchymal markers, and the frequent encounteredin the retroperitoneum. presenceof atumour-speci®c t(11;22)(p13;q12) 22 J.FransGraadt VanRoggen& PancrasC.W .Hogendoorn translocationinvolving the EWSgeneon chromo- intermingledwith collagenbundles. The presence of some22, andthe WT1 (Wilms’tumour1) geneon signi®cant atypia, necrosisandmore than four chromosome1 (Table 2). 56 mitoses/2mm 2 arepoor prognostic factors although reliableprediction of theirbiological behaviour is Gastrointestinal stromaltumours (GIST) Ð The impossible.In the differentialdiagnosis with other GISTcategoryrepresentsa setof mesenchymal spindlecell tumours, the CD34 positivity isvery tumoursmost commonly present in the stomachand useful. smallintestine of adults,periodically involving the retroperitoneumeither by directextension from the HaemangiopericytomaÐ Haemangiopericytoma, intra-abdominalgastrointestinal tract, ororigin in as adistinctclinicopathological neoplasm, remains a 39 contentiousentity andvarious schools of thought the retroperitonealportion of the duodenum. This 62,63 complexgroup of tumoursare impor tant inthe existconcerning this subject Sincea numberof differentialdiagnosis since they areimmunohisto- differenttumours may exhibitthe presumedtypical chemicallyand genetically distinct from the classical `haemangiopericytoma-like’morphologyinthe leiomyoma/leiomyosarcoma,and are postulated to absenceof the expectedtypical myoidimmunohisto- arisefrom intramural `pacemaker cells’ (interstitial chemicalphenotype, it isprobable that this may not cellsof Cajal), demonstratingmyomatous and/ or representa singleentity butrather represent a variety neuraldifferentiation. 39,57 of differenttumours sharing a `haemangiopericytoma- Thesespindle and/ orepithelioid tumours gener- like’morphology .Nevertheless,not all tumourswith ally expressCD117, incontrast to smoothmuscle a`haemangiopericytoma-like’morphology can be readilycategorized as alludedto, leavinga smallsubset tumours.A spectrumof biologicalbehaviour is 62,63 present,as yet difficultto predicton histomorpho- oflesionswhose true nature remains contentious. Paraganglioma(including a pigmentedvariant), 64,65 logicalbasis (although a largesize and a mitotic 66 activity >5/2mm 2 arepointers of aggression). 38 A ®bromatosis, in¯am matorymyo®broblastic tumour,67 synovialsarcoma, 68 vascularintima l proposedassociation with cellularEpstein± Barr virus 69 70 infectionhas neverbeen convincingly supported. 57 sarcoma, malignantmesenchymoma, rhabdoid tumours,71 extraskeletal Ewing’ssarcoma 72 and Atthe geneticlevel a proportionof thesetumours are 73,74 characterizedby mutationsin c-kit proto-oncogene extraskeletalosteosarcoma, all describedat this (CD117) onchromosome 4q11-21, codingfor a cell site,are infrequently encountered but nevertheless surfacereceptor with atyrosinekinase function, and may enterthe differentialdiagnosis of retroperitoneal althoughthis isnot entirely tumour-speci® c it is soft tissuetumours. extremelyhelpful in the differentialdiagnosis with 39,58 otherretroperitoneal spindle cell lesions. Roleof ®ne needleaspiration/ needlecore biopsy Kaposiform hemangioendothelioma Ð This is an Dependingon the siteof the retroperitoneallesion, uncommonvascular tumour occurring primarily in ®neneedleaspiration/ needlecore biopsy may ormay youngchildren, with the retroperitoneumbeing one 59 notbe practically tenable.Fine needle aspiration of the preferentialsites of origin. Macroscopically (FNA), whenpossible, may bevery usefulas a®rst the tumouris poorlycircumscribed with agrey/white stepin resolving the differentialdiagnosis of primary appearance.Microscopically irregular cellular lobules ormetasta tic carcinoma,a lymphoproliferative with in®ltrative marginsare seen consisting of a disorder,or a mesenchymaltumour. Once carcinoma mixtureof capillariformvesselsoften containing andlymphoma have beenexcluded, its usefulnessis microthrombi,slit-like endotheli al-linedvascular limitedsince attempts at classi®cation of mesen- spacesand spindly endothelial cells. Haemosideren chymaltumours on FNA material,except in expert depositionis variably present.Nuclear pleomor- hands,75 isprobably unreliableand not advisable. phismis mild and mitoses scarce. The differential Therole of aneedlecore biopsy is probably diagnosisis with Kaposisarcoma, a tumourrarely controversial.While most retroperitoneal soft tissue foundin childhood, lacking a lobulararchitecture lesionsare probably malignant(exceptschwan - andcontaining a variable in¯ammator yin®ltrate. noma),and will need some form of de®nitive opera- Clinicallythe lesiondoes not appear to metastasize, tive procedure(including schwannomas as aresultof andit isthe locallyinvasive nature of the lesionwhich alocalmass effect), the riskof tumourspill following isresponsible for the highmortality rate. aneedlecore biopsy needs to beweighed up against Solitary ®brous tumour (SFT)Ð SFT,alesionof the possibility/needfor an optimal surgical interven- adultswhich can be either benign or malignant and tion. originallydescribed as apleurallesion, has nowbeen describedat numeroussites including the retroperi- Tumour grading, reporting and clinical staging toneumand pancreas. 60,61 Althoughthe morphology may behighly variable, the classicalexamples have a Tumourgrading, originally developed for soft tissue `hemangiopericytoma-like’vascularpatter nand tumourslocated within the extremeties,represents a fasciclesof CD34 positivespindle shaped cells histologicalassessment based primarily on the degree Soft tissue tumours ofthe retroperitoneum 23

Table 3. TheMusculoskeletal T umorSociety stagingsystem

Stage* Grade² Site³ Metastases

Benign 1 G0 T0 no 2 G0 T1 no 3 G0 T1/2 no/yes Malignant IA G1 T1 no IB G1 T2 no IIA G2 T1 no IIB G2 T2 no IIIA/B G1/2 T1/2 yes

Afrequentlyused staging system for benignand malignant musculoskeletal tumours of the extremeties.This system isnotparticularly applicable toretroperitoneal tumours where the conceptof compartmentalizationis amootpoint. *Stage:A=intracompartmental; B=extracompartmental. ²Grade: G0=benign;G1=low-grade malignant; G2=high-grade malignant. ³Site:T0=intracapsular;T1=extracapsular, intracompartmental;T2=extracapsular,extracom- partmental. of tumourdifferentiation, mitotic activity andthe spread,presenceo fmetastaticdiseas e) and extentof tumournecrosis. 76,77 Inthe absenceof histopathologicalexamination, serves to document sufficientdata concerningthe clinicalcourse of the natureand extent of the disease,ideally at the speci®c tumourtypes, dueto theirrelative rarity, the timeappropriate treatment is being initiated, and intentionwas to try andprovide an indication of the aimsto guidetherapy andprovide prognostic informa- potentialdegree of malignancyof alesionin orderto tion.While initiated by Enneking(Musculoskeletal beable to separate lesionswith agoodprognosis TumorSociety staging system; 79,80Table 3), asecond fromlesions with apoorprognosis and hence to (modi®ed) staging system, designed by the American facilitate decisionswith respectto the choiceof treat- Joint Committeeon Cancer(AJC) andbased on the mentmodalities available. 76,77 TNMsystem (tumour size; involvement of lymph Histologicaltype, however,increasingly appears to nodes;presence of metastases) andincorporating bethe mostimportant parameter in determining histologicaltumour grade, is also in use 81 (Table 4). clinicalbehaviour; for example synovial sarcoma is Whilethe Ennekingsystem (with its emphasison by de®nition a high-gradetumour irrespective of compartmentalization)is best suited for sarcomas mitoticactivity andextent of necrosiswhile in arisingin the extremeties,the AJCsystem can be extraskeletalmyxoid chondrosarcoma, patient ageand usedfor tumours at any sitebut is somewhat more tumoursize appear to bethe mostim portant complex. prognosticfactors. 78 Consequently,while grading Recently,the AmericanAssociation of Directorsof systemsmay broadlyspeaking be of clinicalvalue, it Anatomicand Surg icalPathology have provided isenvisaged that increasinglytumour-speci® c factors recommendationsfor reporting common malignant willbe identi® ed having an important bearing on tumoursincluding soft tissuesarcomas. 82 Their aim individualtumour behaviour. was to providea frameworkfor an informative and Clinicalstaging of musculoskeletaltumours, via clinicallyuseful report to facilitate the effortsat staging clinicalexaminati on,radiolog icalimaging (local andchoice of optimaltherapeutic regimens.

Table 4. AmericanJoint Committeeon Cancer staging system

Stage Grade* Tumour²Lymph nodes³Distant metastases§

Ia G1 T1 N0 M0 Ib G1 T2 N0 M0 IIa G2 T1 N0 M0 IIb G2 T2 N0 M0 IIIa G3/4 T1 N0 M0 IIIb G3/4 T2 N0 M0 IVa G1± 4 T1/2 N1 M0 IVb G1± 4 T1/2 N0± 1 M1

Awidelyused staging system for malignantmusculoskeletal tumours, and applicable tosoft tissuetumours in the retroperitoneum. *Histologicalgrade: G1=low (well-differentiated);G2=mode rate(moderat elywell- differentiated);G3=high (poorly differentiated);G4=undifferentiated. ²Tumoursize: T1=less than 5cmindiameter; T2=5cm ormorein diameter. ³Lymph nodestatus: N0=nolymph nodemetastases; N1=lymph nodemetastases. §Distantmetastases: M0=absent;M1=present. 24 J.FransGraadt VanRoggen& PancrasC.W .Hogendoorn

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