Acute Care and Long-Term Results in Treatment of Tracheal ...€¦ · Case n. Tumor histology Year Age Sex Tumor size Symptoms Treatment Techniques Follow-up 1 Subglottic hemangioma

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Journal of Rare Disorders: Diagnosis & TherapyISSN 2380-7245

2016Vol. 2 No. 1: 4

1

Review Article

© Under License of Creative Commons Attribution 3.0 License | This article is available from: //www.raredisorders.imedpub.com/

DOI: 10.21767/2380-7245.100033

Angela De Palma1, Francesco Sollitto2, Domenico Loizzi2, Mariagrazia Lorusso1, Francesco Di Gennaro1, Giovanni Mercadante1 and Michele Loizzi1

1 SectionofThoracicSurgery,DepartmentofEmergencyandOrganTransplantation,UniversityofBari"AldoMoro",Bari,Italy

2 SectionofThoracicSurgery,DepartmentofMedicalandSurgicalSciences,UniversityofFoggia,Foggia,Italy

Corresponding author: AngelaDePalma

SectionofThoracicSurgery,DepartmentofEmergencyandOrganTransplantation,UniversityofBari"AldoMoro",PiazzaGiulioCesare11,70124Bari,Italy.

[email protected]@uniba.it

Tel: +390805595101Fax:+390805593331

Citation: DePalmaA,SollittoF,LoizziD,etal.AcuteCareandLong-TermResultsinTreatmentofTrachealTumors:MonocentricExperienceoftheLastSevenYears. JRareDisDiagnTher.2016,2:1.

AbstractTracheal tumors are rareneoplasmswith extremelyheterogeneoushistologicalaspects and can be potentially life-threatening, due to airway obstruction.Wereportourresultsinmedical,endoscopicandsurgicaltreatmentofprimaryandsecondary tracheal tumors. From January 2008 to June 2015, on 35 patientstreatedforvarioustrachealdiseases,weobserved6patients(2males,4females;medianage:50,5years,range:2months-72years)withtrachealtumors:5primary(subglottichemangioma,inflammatorypseudotumor,condromatoushamartoma,squamous cell carcinoma, acinic cell carcinoma), 1 secondary (pulmonaryadenocarcinoma).Treatmentswere:medicalin1case(subglottichemangioma),endoscopicin2(squamouscarcinoma;metastaticadenocarcinoma),surgicalin3(inflammatorypseudotumor; condromatoushamartoma;acinic cell carcinoma).Post-treatmentcoursewasuneventfulandwithradicalresultsinallpatients.Atamedianfollow-upof42months(range:11-89months)fiveofsixpatientsarealive,ingoodconditionsandwithoutlocalordistantrecurrence.Treatmentoftrachealtumorsmayvaryinrelationshiptoclinicalconditionofpatients,gradeoftrachealobstruction,tumorextension,stage,histologyandbiologicalbehavior,whicharefactors affecting prognosis and long-term survival. Endoscopic evaluation andhistological diagnosis are mandatory to select the most adequate treatment;wheneverpossible,radicalsurgicalresectionshouldbeperformed.

Keywords:Trachealtumors;Airwayobstruction;Bronchoscopy;Surgicalresection

Acute Care and Long-Term Results in Treatment of Tracheal Tumors: Monocentric

Experience of the Last Seven Years

Received: January06,2016; Accepted: January09,2016;Published: January15,2016

IntroductionTrachealtumorsareextremelyrare,representinglessthan0.2%of all neoplasms of the respiratory system [1]. These tumorshave a heterogeneous histology and are not easily classifiable,thusare reported in theLiteratureaspartof large long-lastingstudiesormorefrequentlyascasereports,focusingonpeculiarandcharacteristicaspects[2].

Even if rare, tracheal neoplasms can be potentially life-threatening, due to the involvement of the airwaywhichmaycauseacuteasphycticsyndromes, requiringapromptdiagnosisand correct treatment (endoscopic and/or surgical) in order torestoreanormalairflow.

However, patients with tracheal tumors may present a longstoryofpersistentcoughandprogressiverespiratorysymptomssuch as dyspnea, stridor and wheezing, resembling asthmaticsyndromes,whicharemisinterpretedandwronglytreatedwith

corticosteroids,causingasignificantdelayindiagnosis.Thismayleadtoacuterespiratoryfailurerequiringemergencytreatment.

Tracheal tumors can be distinguished in epithelial andnonepithelial,benignandmalignant,primaryandsecondary.Themajorityofcases(90%)ofprimarytrachealneoplasmsinadultsaremalignantandamongthese75%arerepresentedbyepithelialhistotypes(mainlysquamouscellcarcinomaandadenoidcysticcarcinoma)[3,4].Asconcernsnonepithelialtrachealneoplasms,thedistinctionbetweenbenignandmalignantformsisgenerallyless evident than epithelial tumors [5], due to difficulties inhistological classification of these rare tumors, thus hiding apotentialmalignantbehavior.


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The distinction between benign and malignant neoplasms isusuallybasedonmorphologicalaspects,biologicalbehavior,localinvasivenessandmetastaticspread.

InagreementwithotherAuthors,webelievethatsometrachealtumors, even if benign, for their characteristicsof invasivenessand recurrency, should always be considered as potentiallymalignantandthusrequireamoreaggressivetreatment[2,4].Inourexperience,forthedefinitionofbenignormalignanttumor,theclinicalbehaviorandthenaturalhistoryofthetracheallesionwasdeterminant.Therefore,alltrachealtumors,alsoconsideringthe involvment of the main airway and the severe associatedsymptoms, could be better classified in low, intermediate andhighgrademalignantneoplasms,asdescribedbyGrilloandColl(Table 1)[1,4,6].

We report our experience about tracheal neoplasms, in orderto assess the epidemiology, clinical presentation, diagnosticevaluation,treatmentmodalities,prognosisandshort-andlong-term results obtained with surgical, endoscopic and medicaltreatmentofthisraredisease.

However,itshouldbetakenintoaccountthattheextremerarityofthesetumorsmakesdifficulttoobtainstatisticallysignificantdatafromtheanalysisofasingle-centerseriesandtothebetterofourknowledgethelargestpublishedseriesisthatofMassachusettsGeneralHospitaloftheHarvardUniversityinBoston(360casesinafortyyears’experience)[1,6].Thus,internationalguidelinesto standardize the approach to this rare disease could only beachievedjoiningdataofreferralcentres(multicenterstudies).

Materials and MethodFromJanuary2008toJune2015thirty-fivepatientswithtrachealdiseases (congenital, traumatic, inflammatory, idiopathic, post-intubationstenosisandtumors)weretreatedatourInstitution.Weexcludefromthepresentretrospectiveanalysis29patientswith non-oncologic tracheal diseases and focus our attentiononlyon6patientswithoncologictrachealobstruction,requiringacute care treament. On 35 patients, 6 were suffering fromtracheal neoplasms, 5 primary and one secondary (Table 2).Therewere2malesand4 females,withamedianageof50,5yearsandawideagerange(2months-72years).Twocaseswerediagnosedinpediatricageandfourinadultage,withnogenderprevalence. In all cases symptomswere related to progressiveobstruction of the airway: wheezing, stridor, cough, dyspneaand,intwopatients,respiratoryfailurewithoxigendesaturation.However,beforebeingreferredtoourInstitution,theseaspecificrespiratory symptoms had often been wrongly attributed toallergicdisorders(bronchialasthmaandasthma-likesyndromes),exceptforpatientswithaknownhistoryofcancer.However,uponarrivaltoourattention,allpatientshadmoreorlesssevereacuteasphycticsymptoms,requiringpromptandadequatetreatment.

Ineachpatientthediagnosisoftrachealtumorwasobtainedbothwith neck-chest computed tomography (CT) scan, with three-dimensional(3D)reconstructionoftheairwayandbronchoscopy(flexibleand/orrigid),allowingtopreciselyestablishthesiteandcharacteristics of the neoplasm (size, shape, grade of stenosis

of the tracheal lumen, possible presence of ulceration of themucosa,etc.)andtoobtainbiopsiesforhistologicexamination.In2casesrigidbronchoscopyrepresentedboththediagnosticandtherapeuticalapproach.

Malignant tumors N° of casesAdenoidcysticcarcinoma 135Squamouscellcarcinoma 135Nonsquamousbronchogeniccarcinoma 15 Small cell carcinoma 5 Adenocarcinoma 4 Large cell carcinoma 4 Adenosquamous carcinoma 2Mucoepidermoidcarcinoma 14Carcinoidtumors 11 Typical 10 Atypical 1Lymphoma 2Melanoma 1Sarcoma 13 Spindle cell sarcoma 6 Chondrosarcoma 3 Leiomyosarcoma 1 Carcinosarcoma (pseudosarcoma) 1 Invasive fibrous tumor 1 Malignant fibrous histiocytoma 1

Total of malignant tumors 326Benign tumors

Pleomorphicadenoma 3Squamouspapilloma 9 Mulltiple 5 Solitary 4Pyogenicgranuloma 1Capillaryhemangioma 1Chondroblastoma 1Chondroma 2Fibroushistiocytoma 1Glomustumor 1Granularcelltumor 2Hamartoma 2Hemangiomatousmalformationofmediastinum 1Leiomyoma 3Paraganglioma 1Neurogenictumor 3 Schwannoma 1 Peripheral nerve sheath tumor 1 Atypical schwannoma 1

Total of benign tumors 31Intermediate malignancy tumors

Vascolartumorofborderlinemalignancy 1Inflammatorypseudotumor(plasmacellgranuloma) 1Plexiformneurofibroma 1

Total of intermediate malignancy tumors 3Total 360

Table 1: Tracheal tumors classification. Forty years experience atMassachusetts General Hospital, Boston, USA (modified and adaptedfrom[1,6]).


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As concerns histology, three cases were classified as non-epithelial (subglottichemangioma, inflammatory pseudotumor,chondromatous hamartoma) and the other three as epithelialtumors (squamous cell carcinoma, acinic cell carcinoma inpreviouspleomorphicadenoma,highgradeadenocarcinoma inprevious squamous cell carcinoma and adenocarcinomaof thelung).

The typeof treatmentwasdecided considering theunderlyingclinical condition of patients, grade of tracheal obstruction,neoplastic extension and infiltration and histotype, usingfrom simple medical therapy to invasive technique, such asendoscopic treatment (laser, coring with rigid bronchoscope,biopsy forceps)or tracheal surgical resection (limited resectionand reconstruction with simple suture and/or tracheoplasty,completecircumferentialresectionfollowedbytermino-terminalanastomosis).

Due to the extreme histological variety and the differenttreatment options which were adopted, each case with itsspecific and peculiar clinical history and diagnostic-therapeuticapproachisdescribedbelow.

Case N. 1In2011weobservedasubglottichemangioma(SGH),arareandbenign vascular tumor of the head and neck in children, in a2-montholdinfantgirl.ShewasadmittedtoourInstitutionwith

stridor,severedyspneaandoxygendesaturation.Neck-chestCTscan and fiberbronchoscopy revealed a contrast-enhancing, 10mm,subglotticbluishellipticlesion,referabletoasub-occlusiveSGH,closingmorethan75%ofthelaryngotrachealairway.

After multidisciplinary discussion, in agreement with ourneonatologists and ear, nose and throat (ENT) specialists, wedecided to begin oral propranolol therapy (0,4 mg/kg/die for14 days), which rapidly and dramatically improved respiratorysymptoms,avoidingtheneedforatracheostomy.

Fiberbronchoscopysixdaysaftertreatmentconfirmedareductionof the size of the tumor and of the subglottic narrowing. Thepatient is doingwell,without respiratory symptoms four yearsaftertreatmentwithpropranolol.

This is the first reported case of successful treatment withpropranolol of an SGH obstructing more than 75% of theairway [7]. The case underscores the effectiveness of oralpropranolol as first-line treatment in the management ofseverely-obstructive paediatric SGH and the importance of CTand fiberbronchoscopy in the diagnosis; it also highlights theimportance of multidisciplinary cooperation between thoracicsurgeons,anaesthesiologists,neonatologistsandENTspecialistsinthetreatmentofthesepatients.

Case N. 2Ararecaseoftrachealinflammatorypseudotumor(IPT),usuallyaffecting pediatric and young patients and with a still unclearpathogenesis,wasdiagnosedin2008ina12-year-oldboy,who

Case n. Tumor histology Year Age Sex Tumor size Symptoms Treatment Techniques Follow-up

1 Subglottichemangioma 2011 2months F 10×10

mm

Stridor,dyspnea

andoxigendesaturation

Medical OralpropranololAliveat4years,norecurrence

2 Inflammatorypseudotumor 2008 12years M 15,2×13,8

mmDyspneaandwheezing

Endoscopicandsurgical

Rigidbronchoscopy+Nd-YAGlaser+trachealresectionandtermino-terminalanastomosis

Aliveat7years,norecurrence

3 Chondromatoushamartoma 2012 39years F

90%stenosisoftracheallumen

Dyspneaandstridor Surgical

Trachealresectionandtermino-terminalanastomosis


4 Squamouscellcarcinoma 2012 62years F 9×5mm Stridorand

dyspnea Endoscopic Rigidbronchoscopy+Nd-YAGlaser


5

Aciniccellcarcinomainprevious(2004)trachealpleomorphicadenoma

2011 69years F

30%stenosisoftracheallumen

Dyspnea SurgicalResectionthroughtranscervical-transtrachealapproach


6

Secondaryadenocarcinomainpreviouslungsquamouscellcarcinoma(2010-2012)andadenocarcinoma(2013)

2014 72years M 1cmDyspneaandrespiratoryfailure

Endoscopic

Rigidbronchoscopy+coring,biopsyforcepsandNd-YAGlaser

Deadat1yearforictus

cerebri

Table 2: Trachealtumors.Ourexperienceofthelastsevenyears.


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hadreceivedcorticosteroidtherapyfortwoyears.Hepresentedtoourinstitutionwithsuddendyspneaaftermonthsofwheezingandcough,wronglyconsideredandtreatedasasthma.

NeckandchestCTscan revealedan intraluminalpedunculatedtrachealmass(diameter15.2×13.8mm),originatingfromtheleftantero-lateraltrachealwall,at5,2cmfromthemaincarenaand4,6cmfromtheglottis(Figure 1A).Fiberbronchoscopyconfirmedthe lesion at the level of the fifth cartilagineous tracheal ring,involvingthreerings.

Atfirst,consideringtheyoungageofthepatientandthetypicalbenignbehaviorofthiskindof lesions,afterendoscopicbiopsyandpathological diagnosis, themasswas removedwith coring(totransectthepedicle),endoscopicforceps(totaketheresectedmassaway)andNd-Yaglaser(totreatthebaseofimplant)inrigidbronchoscopy.

However, due to a rapid tendency to recurrence of the lesion,

twomoreendoscopicrecanalizations,atoneandthreemonthsfrom the first one, were performed. Nevertheless, as a newrecurrenceappearedatbronchoscopyandCTshowedtransmuralinvolvementofthetrachealwall(Figure 1B)ataboutfourmonthsfrom the first observation, we decided to perform a trachealsurgicalresection.

Through cervicotomy and sternal split the three involvedtracheal rings (V–VII) were circumferentially resected and atermino-terminaltrachealanastomosiswasaccomplishedwithacontinuousrunningsuture(PDS4-0)posteriorlyandinterruptedsutures (Vicryl 3-0) anteriorly (Figures 1C-1E). Follow-up withCT scan and fiberbronchoscopy shows a stable tracheal lumenwithoutsignsofrecurrence,sevenyearsaftersurgery[8].

Case N. 3A39-year-oldwomancametoourattentionin2012foratrachealchondromatoushamartoma.Thepatientpresentedwitha2-year

Figure 1 (A)NeckandchestCTscanofa12-year-oldboy,showingasolidintraluminalpedunculatedtrachealmass(diameter15.2×13.8

mm),originatingfromtheleftantero-lateraltrachealwallandobstructingtheupperthirdofthetrachea;(B)afterbronchoscopicdiagnosisof inflammatorypseudotumorand threeendoscopic recanalizations, anew recurrenceappeared,withCTevidence(arrow)oftransmuralinvolvementofthetrachealwall,requiringsurgery;(C)operativefieldshowingtheinfiltration(arrow)oftheleftantero-lateraltrachealwallbytheinflammatorypseudotumor;(D)throughcervicotomyandsternalsplit,acircumferentialtrachealresectionofthethreeinvolvedtrachealringsandtermino-terminalanastomosiswasperformed:intraoperativeventilationwasguaranteedbyaMagillendotrachealtubebelowthesiteofresection;(E)postoperativebronchoscopiccontrolofthetrachealanastomosis.


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historyofdyspneaandstridor,atfirstattributedtoanasthma-likesyndrome,becauseofamedicalhistoryofallergicdiathesis.

NeckandchestCTscanshowedasubglotticintraluminaltrachealmasscausinga90%stenosisoftheairwaylumen,at2cmfromthecricoidcartilage.Fiberbronchoscopyconfirmedthepresenceofthetumor,originatingwithabroadbaseofattachmentfromtherightlateraltrachealwall.

Duetotheextentofthelesion(90%stenosis)wedecidedtoperformsurgical resection: through cervicotomy the patient underwenttrachealresectionandend-to-endanastomosis. Inparticular, inthispatienttheoperationwasperformedundermonitoredlocalanesthesia(stepwiselocalinfiltrationof2%lidocaineand7,5mg/mLropivacaine)andconscioussedation,whichwasachievedbybolusesofketamineandmidazolam.Thepatientremainedawakeduring theentireprocedure, thuspermitting themovementofthevocalcordstobemonitored.Mechanicalventilationwasnotrequired.Thepostoperativeperiodwasuneventfulandatthreeyearsfromsurgerybronchoscopyshowsastabletracheallumenwithoutsignsofrecurrence[9].

Case N. 4In2012a62-year-oldwomancametoourattentionforstridorand dyspnea. Neck and chest CT scan and fiberbronchoscopyrevealed a subglottic intraluminal squamous cell carcinomaoriginatingfromtheright lateraltrachealwall,causing laryngo-trachealstenosis.

Consideringthecomorbiditiesofthepatient(fattyliverdisease,diabetesmellitus, hypertension, depressive syndrome) and theresulting contraindications to surgery, rigid bronchoscopy withNd-Yag laser treatment of the subglottic tracheal lesion wasperformed.

Postoperative bronchoscopy some days later showed animprovementofthesubglottictracheallumen,butthepresenceof a little flap of mucosa moving with breaths. Thus a fiber-bronchoscopywasperformedandtheflapsimplyremovedwithbiopsyforceps.

Endoscopic treatment in this patient allowed to obtain theresolutionofrespiratorysymptoms.AtthreeyearsfromtreatmentthepatientisdoingwellandbronchoscopicandCTscanfollow-upshowsnorecurrencesofthetrachealtumor.

Case N. 5A 69-year-old woman was treated at our Institution in 2011for an acinic cell carcinoma (histological subtype of trachealadenocarcinoma).Shehadalreadyundergonesurgicalresectionthroughcervicotomyofatrachealpleomorphicadenomain2004andcametoourattentionforinspiratoryandexpiratorydyspnea7yearsaftersurgery.

Neck and chest CT scan and fiberbronchoscopy showed anintraluminal tracheal tumororiginating from theposteriorwallof theupper thirdof the trachea,causingastenosisof30%ofthetracheallumen(Figure 2).Atfirstthetumorwasinterpretedas a recurrence of the previous pleomorphic adenoma,however histological examination of biopsies collected duringfiberbronchoscopy revealed a different histotype from the

previousone:aciniccellcarcinomaofminorsalivaryglands.

Surgical resection of the tumor was performed through a re-cervicotomy and longitudinal incision of the anterior trachealwall(transcervical-transtrachealapproach)atthelevelofthefirstfive cartilagineous tracheal rings. Four years after surgery thepatientisdoingwell,withoutrespiratorysymptoms,andCTandbronchoscopicfollow-updonotshowanyotherrecurrence.

Case N. 6A 72-year-oldman, in follow-up at our Institution after a rightlung lobectomyforasquamouscellcarcinomaandsubsequentresection of an ipsilateral lung adenocarcinoma, came to ourattentionagain in 2014due to severedyspneaand respiratoryfailure.

In particular, the patient had been submitted to right lowerlobectomyin2010andtomediumlobectomywithresectionofthemaincarinain2012forasquamouscellcarcinoma;in2013a wedge pulmonary resection of the right upper lobe for anadenocarcinomahadbeenperformed.

Neck and chest CT scan allowed diagnosing an intraluminaltrachealmassofabout1cmlocatedatthemediumthirdofthetracheaand rightparatracheal lymphnodes, inaddition to leftmultiplepulmonarynodulesandarightlungnodule.PET-CTscanwaspositivebothatthelevelofthetrachealmassandofthelungnodules.

Fiberbronchoscopy confirmed the pedunculated intraluminaltracheal tumor, almost totally obstructing the airway lumen,withbaseofattachmentontheleftposteriorwalloftheupperthirdofthetrachea(Figure 3A).Consideringtheclinicalsituation(multipleandrecurrentlungcancers)andthecomorbiditiesofthepatient (hypertension, ischemic heart disease, bilateral carotidstenosis,chronicrespiratoryfailureinCOPDanddysthyroidism),wedecidedtoperformalessinvasive,endoscopictreatment.

Tracheal obstruction was removed in rigid bronchoscopy withmechanical coring and biopsy forceps and the base of implant

Figure 2 Neck and chest CT scan of a 69-year-old woman,showing an intraluminal tracheal tumor (arrow)originating from theposteriorwall of theupper thirdofthetrachea,causingastenosisof30%ofthetracheallumen(aciniccellcarcinomaofminorsalivaryglands).


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of the tumor was treated with Nd-Yag laser (Figures 3B-3D).Definitive histological diagnosis revealed a secondary trachealtumorfromlungadenocarcinoma.Thepatientdiedatoneyearfromsurgeryduetoastroke(ictuscerebri).

Results and DiscussionWhateverwastheapproach(medical,endoscopicandsurgical),inallpatientspost-treatmentcoursewasuneventful.Atamedianfollow-up of 42 months (range: 11-89 months) five of the sixpatients are alive, in good health condition and without localor distant recurrence. Only one patient died, one year afterbronchoscopictreatment,forcausesunrelatedtothehistoryofcancer(ictuscerebri).

Due to the rarity of tracheal tumors, few studies have beenpublished in theLiteratureconcerninghistologicalclassification[10],staging,strategiesoftreatment,shortandlong-termresultsandsurvivalrates[11].Thelowerincidenceofprimarytrachealtumorscomparedtoprimary lungandbronchialonescouldbe

explained by the reduced surface of the tracheal epithelium(ciliated pseudostratified), the presence ofmucinous secretingcells (ensuring a continuousmuco-ciliary clearance and thus abetterdefenseactionagainstexternal insults)and the tracheallaminarairflows(unlikethoseturbulentofthebronchialtree).

Among malignant tracheal neoplasms, the epithelial onesprevailintermofincidence,mainlythesquamoushistotypeandsecondarilythemucinousorglandular(adenoidcysticcarcinoma)one.Thisparticularaspecthasbeenattributedtothemetaplastictransformation of the respiratory epithelium in a squamousone,asa consequenceof theactionofdamagingagents (suchas cigarette smoke) on themucosa, although to date etiologicfactors relatedto theoriginof tracheal tumorsarestillunclear[12].

As concernsbenign tracheal tumors, etiology is unknownbothforepithelialandnonepithelialhistotypes,exceptforsquamouspapilloma,whichisassociatedtoinfectionbyhumanpapilllomavirus6and11[13].Squamouspapilloma(multipleorsolitary)and

(A) (B)

(C) (D)

Figure 3 (A)Fiberbronchoscopyof72-year-oldman,infollow-upforsquamouscellcarcinomaandadenocarcinomaofthelung,showingapedunculated intraluminal tracheal tumor,almost totallyobstructingtheairway lumen,withbaseofattachmentonthe leftposteriorwalloftheupperthirdofthetrachea;(B,C)consideringtheclinicalsituation(multipleandrecurrentlungcancers)andthecomorbiditiesofthepatient,endoscopictreatmentwasperformedandtrachealobstructionremovedinrigidbronchoscopywithmechanicalcoringandbiopsyforcepsandthebaseofimplantofthetumorwastreatedwithNd-Yaglaser;definitivehistologicaldiagnosisrevealedametastasisfromlungadenocarcinoma;(D)bronchoscopiccontrolafterendoscopictreatment.


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pleomorphicadenomaare themost commonbenignepithelialneoplasms.Mostofnonepithelialtrachealneoplasmsarebenign,arising from soft tissue cells (fibroblasts, smoothmuscle cells,chondrocytes, nerve sheaths cells, adipocytes), thus there isa considerable variety of extremely heterogeneous histotypes(fibromas,fibromatosis,fibromatoushistiocytomas,leiomyomas,lipomas, chondromas, chondroblastomas, hemangiomas,hamartomas,neurofibromas,etc.)[12],witharare,butpossible,potentialformalignanttransformation.

Prognosisandsurvivalofprimarytrachealneoplasmsarerelatedtoseveralelements,mainlythehistotype:lowsurvivalratesforsquamous cell carcinoma have been reported, while a bettersurvivalforadenoidcysticcarcinomahasbeendescribed,withapoorerprognosisincaseoflymphnodeinvolvement.Incaseofpositivelymphnodes,survivalinepithelialtumorsisreducedby50%[11].

Secondary tracheal neoplasms are extremely rare, oftenpresentingasdirectinvasionofthetracheabytumorsofadjacentorgans,suchasthelarynx,thiroid,esophagus,lungormediastinalstructures[14].Strictlyspeaking,trachealmetastasesarereallysporadic, in comparison to the bronchial tree, which is morefrequently site of metastases from primary tumors in distantorgans; breast, kidney and colon cancers and melanomas arethosemostcommonlymetastatizingtothetrachea[15].

Clinicalpresentationoftrachealtumorsistypicallycharacterizedby obstruction symptoms (asthma-like syndromes, dyspnea,wheezing, cough and hemoptysis) which may vary based onthe location and extent of the mass. Hemoptysis is generallyassociated toepithelial tumors in an advanced stage.A severeobstructionmayoccurwhen thepercentageof stenosis is onethird or a half of the total lumen [16]. The diagnosis is oftendelayedbecauseatthebeginningsymptomsareunderestimatedor wrongly attributed to COPD or asthma. Thus, a trachealneoplasm should always be suspected in any patients withasthmaticsymptomsunresponsivetodrugtreatment[1,9].

In our patients, symptoms were related to obstruction of theairway: wheezing, stridor, cough, dyspnea and, in two cases,respiratory failurewith oxygen desaturation.However, inmostpatientstheseaspecificrespiratorysymptomshadbeenwronglyattributedtoallergicdisorders(exceptforpatientswithaknownhistoryofcancer),thuscausingsomedelayindiagnosis.

The site and characteristics of tracheal tumors should bestudiedby imaging (CT) atfirst,but thegold standard remainsbronchoscopy, which can be used both for diagnostic andthrapeuticalaims.Infact,tracheo-bronchoscopy,withrigidand/or flexible instrument, under local anesthesia (with orwithoutsedation) or general anesthesia, is fundamental not only todirectlyvisualizetheintraluminaltrachealneoplasmandevaluateits morphology and development, grade of obstruction of theairwayandsurgicalresectability,butalsotodefinethehistotypebybiopsies[4,13].

At endoscopic examination these tumors usually present apolypoid growth within the tracheal lumen, often showing asubepithelial growth pattern and sometimes infiltrating thetrachealwallandtheadjacentsofttissues.Theliningepithelium

mayappearhyperplasticandulcerated.

Inourexperience,thediagnosisoftrachealtumorwasobtainedinallpatientsbothwithneck-chestCTscanwith3Dreconstructionoftheairwayandbronchoscopy(flexibleand/orrigid),allowingtopreciselyestablishthesiteandcharacteristicsoftheneoplasm(size, shape, gradeof stenosisof the tracheal lumen,presenceof ulceration of the mucosa, etc.) and to obtain biopsies forhistologicexamination.

Treatmentandprognosisdependonvariousfactors,suchasthesiteandhistotypeofthetumor,thestaging,theclinicalconditionandthedegreeofimpairmentoftherespiratoryfunctionandtheentityofstenosisofthetracheallumen[12].Treatmentincludesconservative(medical,endoscopic)andsurgicalprocedures.

In selected cases, treatment of tracheal neoplasms can beperformed with conservative modalities, mainly endoscopicprocedures. As concerns tracheal operative endoscopy, flexibleand/or rigidbronchoscopymaybeusedand the latter is tobepreferred to treat neoplastic obstruction, as it allows a bettercontrol of the airway and ventilation of the patient. Flexiblebronchoscopy,aloneorinassociationtorigidbronchoscopy,canbeusefulforlasertreatmentorothertechniques(brachytherapy,electrocoagulation, cryotherapy) to rapidly remove acute localobstruction,withtheaimofrestoringanadequateairwaylumen,improvingrespiratorysymptoms[13].

In malignant tumors which are not completely resectable byendoscopicprocedures, stabilizationof the tracheal lumenandpermanent palliative treatment can sometimes be achievedwiththe implantofstents (self-expandableornon-expandable,metallicorsilicone)[13].

However, surgery still represents the treatment of choicefor primary tracheal tumors and should always be preferred,whenever possible, as it allows to obtain radical oncologicalresection [1, 4]. The main aims are to completely resect thetumor, eliminate obstruction and permanently restore airwaypatency,improvinglong-termsurvival[16].

Surgical techniques may include: limited resection andreconstructionwith simple sutureand/or tracheoplasty,wedgeresection, complete circumferential resection followed bytermino-terminal (end-to-end) anastomosis. Surgical resectiondefinitely represents the best therapeutical option for primarytrachealtumors,beingcurativeforbenignandlow/intermediategrademalignantneoplasmsandimprovingsurvivalofhighgrademalignantones[16].

Asregardssurgicalapproach,tumorsofthesubglotticregionandoftheupperthirdandmiddlethirdofthetracheacanbetreatedby a cervicotomy (sometimeswith a sternal split),while thoseofthelowerthirdofthetracheaand/orofthemaincarinabyasternotomyorrightthoracotomy[13].

Themostfrequenttypeoftrachealresectionisacircumferentialresectionfollowedbya reconstructionwitha termino-terminalanastomosis[13].Thesuccessofthissurgicaltechniqueisrelatedtotherespectofthevascularizationofthetrachealstumpsandthe realizationofa tension-freeanastomosis, inorder toavoidnecrosisanddiastases/dehiscenceofthesutures.About3-5cm


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of the total lenght of the trachea can be resected, then usinga postoperative forced flextion of the neck according to thetechniqueofGrillo(chin-pectoralsutures)[4].

During surgery, the trachea is opened immediately below thetumorallesion(beingcarefultoleavenegativehistologicmargins)and the tracheo-bronchial tree usually ventilated through astandardMagillendotrachealtube[17]or,inselectedcases,jet-ventilation[13].

The anastomosis is generally accomplished with a continuousrunningsuture(PDS4-0or3-0)oftheposteriortrachealwallandinterruptedsutures(Vicryl3-0)oftheanteriorone[13,17].

In our experience conservative treatment was performed in3 patients: medical treatment with propranolol in one case(subglottichemangioma)andendoscopictreatmentintwocases(primary squamous cell carcinoma, removed by Nd-YAG laser,and secondary adenocarcinoma, resected by coring, biopsyforceps and Nd-YAG laser). The other 3 patients underwentsurgical resection (inflammatory pseudotumor, chondromatoushamartomaandaciniccellcarcinomaofminorsalivaryglands).

Dataofourseriesareinagreementwiththosereportedinbiggerseries. In fact, in the two youngest patients (a 2-month-oldinfantgirl,a12-year-oldboyanda39-year-oldwoman)benignor low grade malignant neoplasms (subglottic hemangioma,inflammatory pseudotumor and chondromatous hamartoma,respectively) were diagnosed, while adult patients (>60 yearsof age)mainly presentedmalignant epithelial tumors (primarysquamouscellcarcinoma,aciniccellcarcinomaofminorsalivaryglandsandmetastaticadenocarcinoma).

The acinic cell carcinoma was diagnosed in a patient with apreviously resected pleomorphic adenoma of the trachea,confirmingthattrachealtumorsmayrecurandhaveamalignanttransformation,evenafteralongtimefromfirsttreatment,thusrequiringalong-termfollow-up.

Inourexperience,abetterprognosiswasfoundinyoungpatients,in neoplasms limited to the trachea at diagnosis (early stagetumors)andinabsenceofcomorbidities.Inordertoprovidethepatientwithahigherprobabilityofcure,astrictmultidisciplinarycooperation of various specialists (surgeon, anesthesiologist,oncologist, radiotherapist, ENT specialist, pediatrician andneonatologist) is essential.Moreover, some specific aspects ofourseriesofpatientsshouldbeconsideredandanalyzed.

Our case of subglottic hemangioma was the first, reported intheLiterature,withseveretrachealstenosis(>75%),successfullytreated with medical therapy (propranolol). Subglottichemangioma is a benign tumor of childhood; however, asobserved in our patient, it can be potentially life-threateningincaseof severeairwayobstruction [7].Approximately50%ofaffectedchildrenalsohavecutaneoushemangiomas.Itisusuallynotevidentatbirth,butgrowsrapidlyduringthefirstyearoflifeand the proliferation phase begins around 1-2months of age,causingintermittentairwayobstructionwithstridor,dyspneaandrespiratory distress [7]. Themanagementmay vary dependingonthedimensionsandsiteof thetumorandthesymptomsofthepatient, thusa standardmethodhasnotbeenestablished.

Alternatives are conservative treatment (“wait and see”, withor without tracheotomy; systemic and intralesional steroid;interferon; propranolol; CO2 laser) or open surgical approach(laryngotracheoplasty, submucous resection, tracheostomy).In our patient medical therapy alone with oral propranololallowedtoobtainarapidimprovementofrespiratorysymptomsandpermanent successful results at four years fromdiagnosis.Therefore, an extensive knowledge ofmedical drugs and theiralternative indications may be useful even for treatment ofdiseases in surgical/endoscopic field and a multidisciplinaryapproach is mandatory. Moreover, an early diagnosis bybronchoscopy is fundamental to precociously start treatmentwithpropranolol,avoidingmoreinvasivesurgicalapproach,suchastracheotomy,inpediatricpatients[7].

Asconcernstrachealinflammatorypseudotumor,thisisgenerallya benign, polypoid or sessile, reactive lesion, characterized byproliferationofmyo-fibroblasticcellsassociatedwithavariablenumberandtypeofinflammatorycells;however,someAuthorsbelieve that it is a low grade fibrosarcoma with inflammatory(lymphomatous) cells, thus it is still not clear if it should beconsideredasarealtumororanentityof inflammatorynature[8]. It usually affects pediatric and young patients, as in ourexperience,andhasanunpredictablebiologicalcourse.Modalityoftreatmentcanvaryfromaconservativeapproach(endoscopicresectionwithcoringandlaser;corticosteroids;radiationtherapy)tosurgicalresectionandtermino-terminaltrachealanastomosis,which may sometimes be necessary, even in pediatric age,in case of transmural extent or tendency to recurrence afterendoscopicremoval,asoccurredinourpatient.Whenhecametoourattention,duetotheyoungage,wedecidedtoperforma conservative treatment; however, after three endoscopicresections a new recurrence appeared with infiltration ofthe tracheal wall. Surgical treatment became mandatory andallowed to obtain a radical oncological resection. CT scan andbronchoscopyfollow-upshowsastabletracheal lumenwithoutsigns of recurrence at seven years from surgery. Therefore,radical resection of inflammatory pseudotumor represents thegoldstandardoftreatment,topreventnotonlyrecurrences,butalsoanysarcomatoustransformation[8].

Inourseriesacaseofchondromatoushamartomawasdescribed,causingatrachealstenosisof90%inayoungwoman.Thisisararebenigntumorwhichistypicallylocalizedinthelungparenchyma;less than 2% of cases have an endobronchial localizationand extremely rare are the tracheal ones. Differently frompulmonaryhamartoma,predominantly containing cartilaginouselements, tracheal hamartoma mainly consists of lipomatoustissue, with a minimal part of cartilagineous tissue, smoothmusclecells,mucinousandinflammatorycells[18].Evenifthisis a benign, slow-growing tumor, without potential malignanttransformation, considering the extent of tracheal stenosis(>90%) and the transmural involvment at the base of implant,thetreatmentofchoiceinourpatientwassurgicalresectionwithtermino-terminalanastomosis,asithadalreadybeendescribedintheexperienceofMassachusettsGeneralHospital[1,6].Thepeculiarityofourcaseisrepresentedalsobythetypeofsurgicalapproach:infact,duetotheintraluminalinvolmentandthegradeoftrachealobstruction,surgicalresectionunderlocalanesthesia


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and conscious sedation was performed, this case being thefirst reported in the Literature [9]. Tracheal surgery is usuallyperformedundergeneral anesthesia:however, thereare somedisadvantages, that is the impossibility tocontrol theconditionand movements of the vocal cords (which may be checkedonly at the end of surgical operation and tracheal intubation)and thedifficulty tohavea satisfactory visionof theoperatingfielddue to thepresenceof theendotracheal tube. In2010,aseriesof21trachealresectionsperformedwithcervicalepiduralanesthesiaandconscioussedationwasdescibedbyMacchiariniandcolleagues [9,19]. Inourpatientweused localanesthesiaandconscioussedation[9].Advantagesofthesetechniquesaretheoptimalvisionoftheoperatingfield(asnotrachealtube ispresent)andthepossibilityofmonitoringthevoiceofthepatientandthemovementsofthevocalcordsatanytimeduringsurgery(without having towait for extubation) [9].Unfortunately, thistherapeuticoptionandapproach isapplicableonly inselected,cooperative patients. Moreover, local anesthesia infiltration ofthetrachealwallmaycauseatemporarypostoperativeparalysisof the vocal cords, while cervical epidural anesthesia may becomplicatedbyaccidentalintrathecaladministrationofthelocalanesthetic with consequent spinal block, epidural hematoma,spinalcordinjuryandphrenicnerveblock[9].

In our experience we observed one case of primary trachealsquamous cell carcinoma, epithelial tumor mainly affectingmale smokers, in an age range comprised between the fifthand sixth decades of life. As the patient suffered from variouscomorbiditiescontraindicatingsurgery,aconservativeapproachwaschosenandrigidbronchoscopywithNd-Yaglasertreatmentofthesubglottictracheallesionwasperformed.Thisisimportanttoemphasizetheprincipleofpersonalizationoftherapyinthesepatients(surgicalresectionwouldhaveprobablybeenperformedastreatmentofchoiceinanotherpatientwiththesametumor,butwithoutcomorbidities).

Acinic cell carcinoma, commonly considered a low grademalignant tumor, originates from the minor salivary glands[20]. Serousandmucinous submucosalepithelial glandsof thetracheobronchialtreearesimilartosalivaryglands.Therefore,thenaturalhistory,morphologicalaspectsandbiologicalbehaviorofneoplasmsoriginating fromtracheobronchialglandsaresimilarto thoseofsalivaryglandtumors, thusexplainingwhyadenoidcistic carcinoma, mucoepidermoid carcinoma and acinic cellcarcinomaofthetracheaareusuallycalled“salivarygland-typetumors”. These tumors generally involve theupper part of thetrachea,differently fromthesquamouscelloneswhichusuallyoriginatefromthelowerpartofthetrachea.Concerningourcaseofaciniccellcarcinoma,diagnosedina69-year-oldpatientwhohadalreadyundergonesurgerytoresectapleomorphicadenoma7 years earlier, we had the confirmation that some trachealneoplasms,even ifbenign,may recurand/orhaveamalignanttransformationyearsafter treatment [21].Thisemphasizes theimportance of regular and long-term follow-up with CT scanand bronchoscopy in patients treated for tracheal tumors, for

early detection of possible local or distant recurrences. In ourpatient,surgicalresectionoftheaciniccellcarcinomathroughatranscervical-transtrachealapproachwassuccessfullyperformed,without any recurrence four years later, thuspointingout thateven repeat tracheal resection may be indicated, in selectedpatients,toobtainpositivelong-termresults.

In our experience we only found one patient with secondarytracheal neoplasm, confirming the extreme rarity of trachealmetastases fromprimary tumors inadjacentordistantorgans,asreportedintheLiterature.Lessthan1%oflungtumorsduringtheir natural historymay cause a secondary localization to thetrachea. Due to the rarity of these conditions, it is difficult tostandardizetreatment.Moreover,consideringtheadvancedageandtheseverecomorbiditiesofourpatient,(includingpreviousmajor lung resections for two different tumors, squamous cellcarcinoma and adenocarcinoma), contraindicating surgery, wedecided to choose conservative treatment.Rigidbronchoscopywith coring,biopsy forcepsandNd-Yag laserallowedobtainingsuccessful complete resection of the tracheal metastasis fromlung adenocarcinoma. The patient died one year later for astroke,thusforcausesunrelatedtotheunderlyingdisease.Thisfactunderscoresthatanexperiencedsurgicalstaff,providingthecorrecttreatment,canachievegoodresultsintermsofsurvivaleveninselectedcasesofsolitarytrachealmetastasis.

ConclusionIn conclusion, treatment of tracheal tumors may vary inrelationship to the clinical conditions of the patient, the gradeoftrachealobstruction,theextensionandstageofthetumor,itshistologyandbiologicalbehavior,whicharefactorsaffectingtheprognosisandlong-termsurvival.

Bronchoscopic evaluation and histological diagnosis arefundamental to choose the most appropriate treatment;whenever possible, surgical resection should be performedto obtain the oncological radicality. Conservative treatment ispreferred in very young patients and in those with significantcomorbidities. In our experience, whatever was the approach(medical,endoscopicandsurgical),inallpatientspost-treatmentcoursewasuneventful.

Asnowadaysnointernationalguidelinesareavailable,furtherandmulticentricstudiesbyexpertsinthisrarediseaseareneeded,tostandardizetreatmentandimproveprognosis.

Moreover,inordertoincreasethenumberofpatientscandidatesto surgical resection, it is recommended to centralize trachealtumorcareinasmallnumberofhighlyspecializedreferralcenters,eachofwhich,accordingtoexpertestimates,shouldbeworkingforapopulationofaboutten/twentymillionunits[22,23].Inthisway itwouldbepossibletogreatly improvethequalityofcareandtheexperienceoftheoperatingteam,whichshouldbeabletodealwiththepresentingcaseswithgreatercompetenceandprofessionalism,thusachievinglevelsofexcellence.


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Acute Care and Long-Term Results in Treatment of Tracheal ...€¦ · Case n. Tumor histology Year Age Sex Tumor size Symptoms Treatment Techniques Follow-up 1 Subglottic hemangioma