Mediastinal Pathology Compartmental Approach

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Mediastinal Pathology: Mediastinal Pathology: Compartmental ApproachCompartmental Approach

Teri J. Franks, MDTeri J. Franks, MD

ChairmanChairmanDepartment of Pulmonary and Mediastinal PathologyDepartment of Pulmonary and Mediastinal Pathology

Faculty Disclosure InformationAt the time of the VTC, At the time of the VTC, Teri J. Franks, MDTeri J. Franks, MD had no significant financial interests had no significant financial interests or relationships to disclose.or relationships to disclose.

As a provider accredited by the Accreditation Council for ContinAs a provider accredited by the Accreditation Council for Continuing uing Medical Education, the Department of Medical Education of The Medical Education, the Department of Medical Education of The Armed Forces Institute of Pathology must insure balance, Armed Forces Institute of Pathology must insure balance, independence, objectivity and scientific rigor in all its indiviindependence, objectivity and scientific rigor in all its individually dually sponsored or jointly sponsored educational activities. All faculsponsored or jointly sponsored educational activities. All faculty ty participating in a sponsored educational activity are expected tparticipating in a sponsored educational activity are expected to o disclose to the activity audience any significant financial intedisclose to the activity audience any significant financial interest or rest or other relationship (1) with the other relationship (1) with the manufacturer(smanufacturer(s) of any commercial ) of any commercial product(sproduct(s) and/or ) and/or provider(sprovider(s) of commercial services discussed in ) of commercial services discussed in an educational presentation and (2) with any commercial an educational presentation and (2) with any commercial supporters of the activity (significant financial interest or otsupporters of the activity (significant financial interest or other her relationship can include such things as grants or research supporelationship can include such things as grants or research support, rt, employee, consultant, major stock holder, member of speakers employee, consultant, major stock holder, member of speakers bureau, etc.). The intent of this disclosure is not to prevent abureau, etc.). The intent of this disclosure is not to prevent aspeaker with a significant financial or other relationship from speaker with a significant financial or other relationship from making a presentation, but rather to provide listeners with making a presentation, but rather to provide listeners with information on which they can make their own judgments. It information on which they can make their own judgments. It remains for the audience to determine whether the speakerremains for the audience to determine whether the speaker’’s s interests or relationships may influence the presentation with interests or relationships may influence the presentation with regard to exposition or conclusion.regard to exposition or conclusion.

Main TopicsMain Topics

•• Clinical featuresClinical features•• Organization of lesionsOrganization of lesions

–– Mediastinal anatomyMediastinal anatomy–– Compartment approachCompartment approach

•• Selected lesionsSelected lesions–– Thymoma and thymic carcinomaThymoma and thymic carcinoma

Mediastinal LesionsMediastinal LesionsClinical featuresClinical features

•• Uncommon, 1% of all tumorsUncommon, 1% of all tumors•• Infant to 83 years, mean 35.4 yearsInfant to 83 years, mean 35.4 years•• No gender biasNo gender bias•• 60% benign, 40% malignant60% benign, 40% malignant•• 60% symptomatic60% symptomatic

–– Chest pain, cough, dyspnea, dysphagia, superior vena cava syndroChest pain, cough, dyspnea, dysphagia, superior vena cava syndromeme

•• 97% can be detected on PA and lateral chest radiographs97% can be detected on PA and lateral chest radiographs•• Surgical resectionSurgical resection

–– Low operative morbidity and mortalityLow operative morbidity and mortality

MediastinumMediastinumGross anatomyGross anatomy

•• BoundariesBoundaries–– Anterior: sternumAnterior: sternum–– Posterior: vertebral columnPosterior: vertebral column–– Superior: thoracic inletSuperior: thoracic inlet–– Inferior: diaphragmInferior: diaphragm–– Lateral: parietal pleuraLateral: parietal pleura

MediastinumMediastinumCompartmentsCompartments

•• AnteriorAnterior•• MiddleMiddle•• PosteriorPosterior

•• AnteriorAnterior

•• AnteriorAnterior•• MiddleMiddle

•• AnteriorAnterior•• MiddleMiddle•• PosteriorPosterior

MediastinumMediastinumDistribution of lesionsDistribution of lesions

•• AnteriorAnterior 50%50%•• MiddleMiddle 25%25%•• PosteriorPosterior 25%25%

MediastinumMediastinumContentsContents

•• AnteriorAnterior–– ThymusThymus–– Lymph nodesLymph nodes–– Heart and pericardiumHeart and pericardium–– Ascending aortaAscending aorta–– BrachiocephalicBrachiocephalic vesselsvessels–– Superior and inferior vena cavaSuperior and inferior vena cava–– PhrenicPhrenic nervesnerves–– FatFat–– EctopicEctopic tissuetissue

•• MiddleMiddle–– TracheaTrachea–– MainstemMainstem bronchibronchi–– EsophagusEsophagus–– Lymph nodesLymph nodes–– Descending aortaDescending aorta–– Pulmonary arteries and veinsPulmonary arteries and veins–– AzygosAzygos and and hemiazygoshemiazygos veinsveins–– Thoracic ductThoracic duct–– VagusVagus and and phrenicphrenic nervesnerves

•• PosteriorPosterior–– Sympathetic gangliaSympathetic ganglia–– Peripheral nervesPeripheral nerves–– ParagangliaParaganglia–– Lymph nodesLymph nodes

Davis, Ann Thorac Surg, 1987Davis, Ann Thorac Surg, 1987

AnteriorAnterior MiddleMiddle PosteriorPosterior

ThymicThymic lesionslesions 30%30% 0%0% 0%0%

LymphomasLymphomas 20%20% 21%21% 20%20%

Germ cell tumorsGerm cell tumors 18%18% 0%0% 0%0%

CarcinomaCarcinoma 13%13% 7%7% 0%0%

CystsCysts 7%7% 60%60% 34%34%

MesenchymalMesenchymal tumorstumors 5%5% 9%9% 9%9%

Endocrine tumorsEndocrine tumors 5%5% 0%0% 2%2%

NeurogenicNeurogenic tumorstumors 0%0% 0%0% 53%53%

MiscellaneousMiscellaneous 2%2% 3%3% 2%2%

MediastinumMediastinumDistribution of lesions (n=400)Distribution of lesions (n=400)

CystsCysts 7%7% 60%60% 34%34%

MediastinumMediastinumLesions occurring in one compartmentLesions occurring in one compartment

CystsCysts 7%7% 60%60% 34%34%

MediastinumMediastinumLesions occurring in two compartmentsLesions occurring in two compartments

CystsCysts 7%7% 60%60% 34%34%

MediastinumMediastinumLesions common to all compartmentsLesions common to all compartments

Davis, Ann Thorac Surg, 1987Davis, Ann Thorac Surg, 1987

CystsCysts 7%7% 60%60% 34%34%

MediastinumMediastinumMost common lesion in each compartmentMost common lesion in each compartment

•• ThymicThymic lesionslesions–– AnteriorAnterior

•• Germ cell tumorsGerm cell tumors–– AnteriorAnterior

•• NeurogenicNeurogenic tumorstumors–– PosteriorPosterior

ThymusThymus

•• Thymic lesions dominant mediastinal pathologyThymic lesions dominant mediastinal pathology–– 50% of mediastinal lesions occur in the anterior compartment50% of mediastinal lesions occur in the anterior compartment–– Major organ of the anterior mediastinumMajor organ of the anterior mediastinum

ThymusThymusEmbryologyEmbryology

•• 66thth weekweek–– Primordia arise from 3Primordia arise from 3rdrd

pharyngeal pouches pharyngeal pouches

ThymusThymusEmbryologyEmbryology

•• 66thth weekweek–– Primordia arise from 3Primordia arise from 3rdrd

pharyngeal pouchespharyngeal pouches

•• 88thth weekweek–– Primordia elongatePrimordia elongate–– Fragment during migrationFragment during migration

•• 1414thth week to 16week to 16thth weekweek–– Cortex and medulla completeCortex and medulla complete–– Phenotypic characterizationPhenotypic characterization

ThymusThymusLocationLocation

•• Anterior mediastinumAnterior mediastinum–– Base rests on pericardium and Base rests on pericardium and

great vesselsgreat vessels

ThymusThymusLocation Location

•• Anterior mediastinumAnterior mediastinum–– Base rests on pericardium and Base rests on pericardium and

great vesselsgreat vessels–– Upper poles extend along Upper poles extend along

trachea, attach to trachea, attach to corresponding lobe of thyroid corresponding lobe of thyroid via thyrothymic ligamentvia thyrothymic ligament

•• XX-- or Hor H--shapedshaped•• Fibrous capsuleFibrous capsule•• Wide variation in weightWide variation in weight

–– Mainly related to ageMainly related to age–– Affected by state of Affected by state of

healthhealth–– AverageAverage

•• 15 grams at birth15 grams at birth•• 3030--40 grams at puberty40 grams at puberty•• 1010--15 grams at 60 years 15 grams at 60 years

ThymusThymusGrossGross

LobulesLobules

Starry skyStarry sky

Corticomedullary junctionCorticomedullary junction

Cortex MedullaCortex Medulla

ThymusThymusInvolutionInvolution

•• Decrease in weight and sizeDecrease in weight and size•• AtrophyAtrophy

–– Cortical lymphocytesCortical lymphocytes–– Epithelial elementsEpithelial elements

•• Cystic Hassall corpusclesCystic Hassall corpuscles

•• Cystic Hassall corpusclesCystic Hassall corpuscles•• Increasing adipose tissueIncreasing adipose tissue

•• Small lymphocytesSmall lymphocytes•• Islands of epithelial cells Islands of epithelial cells

•• Small lymphocytesSmall lymphocytes•• Islands of epithelial cellsIslands of epithelial cells

–– SpindleSpindle--shapedshaped–– RosettesRosettes–– Solid nestsSolid nests–– Elongated strandsElongated strands

•• Involution accelerated byInvolution accelerated by–– StressStress–– RadiotherapyRadiotherapy–– ChemotherapyChemotherapy

Tumors of the Thymus and Mediastinum Tumors of the Thymus and Mediastinum WHO ClassificationWHO Classification

•• Epithelial tumorsEpithelial tumors•• Germ cell tumorsGerm cell tumors•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms•• Mesenchymal tumorsMesenchymal tumors•• Rare tumorsRare tumors•• MetastasisMetastasis

•• Epithelial tumorsEpithelial tumors–– ThymomaThymoma–– Thymic carcinomaThymic carcinoma

•• Germ cell tumorsGerm cell tumors•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms•• Mesenchymal tumorsMesenchymal tumors•• Rare tumorsRare tumors•• MetastasisMetastasis

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaClinical featuresClinical features

•• UncommonUncommon–– Incidence of 1Incidence of 1--5/million population/year5/million population/year–– Incidence has not changed significantly over past three decadesIncidence has not changed significantly over past three decades

•• Wide age range, 7Wide age range, 7--89 years89 years–– Peak 55Peak 55--65 years65 years–– Rare in children and adolescentsRare in children and adolescents

•• No gender biasNo gender bias•• Increased incidence of second cancersIncreased incidence of second cancers

–– Irrespective of histologic type of thymic epithelial tumorIrrespective of histologic type of thymic epithelial tumor

•• Autoimmune diseaseAutoimmune disease–– MG: variable in thymoma (10MG: variable in thymoma (10--80%), rare in thymic carcinoma80%), rare in thymic carcinoma–– Other: common in thymoma, rare in thymic carcinoma Other: common in thymoma, rare in thymic carcinoma

Thymoma and Thymic CarcinomaThymoma and Thymic Carcinoma

•• ThymomasThymomas–– Arise from thymic epithelial cellsArise from thymic epithelial cells–– Exhibit organotypic (thymusExhibit organotypic (thymus--like) architectural featureslike) architectural features

•• Lobular pattern, perivascular spaces, immature TdT/CD1a/CD99+ TLobular pattern, perivascular spaces, immature TdT/CD1a/CD99+ T--cellscells

–– No, mild, or moderate atypia of epithelial cellsNo, mild, or moderate atypia of epithelial cells–– CD5, CD70, CD117 negative epithelial cellsCD5, CD70, CD117 negative epithelial cells–– Not observed in organs other than thymusNot observed in organs other than thymus

•• Arise from heterotopic tissue in head, neck, mediastinum, pleuraArise from heterotopic tissue in head, neck, mediastinum, pleura, lung, lung

–– Absent/low to moderate biologic potentialAbsent/low to moderate biologic potential•• Often curable by surgeryOften curable by surgery•• Variable invasion, metastases rareVariable invasion, metastases rare•• Typically long survival due to indolent clinical courseTypically long survival due to indolent clinical course

•• 33 year old male33 year old male•• Three month history Three month history

–– CoughCough–– Intermittent chest painIntermittent chest pain

ThymomaThymomaGrossGross

•• WellWell--circumscribed, firmcircumscribed, firm•• Up to 34 cmUp to 34 cm•• Fibrous capsuleFibrous capsule•• PinkPink--tan lobulated cut surfacetan lobulated cut surface

ThymomaThymomaGrossGross

•• WellWell--circumscribed, firmcircumscribed, firm•• Up to 34 cmUp to 34 cm•• Fibrous capsuleFibrous capsule•• PinkPink--tan lobulated cut surfacetan lobulated cut surface•• Cystic change commonCystic change common•• Adherence to adjacent Adherence to adjacent

structuresstructures

ThymomaThymoma

•• Biphasic cell populationBiphasic cell population

ThymomaThymoma

•• Biphasic cell populationBiphasic cell population–– Neoplastic epithelial cellsNeoplastic epithelial cells

•• Keratin positiveKeratin positive

ThymomaThymomaHistologyHistology

•• Biphasic cell populationBiphasic cell population–– Neoplastic epithelial cellsNeoplastic epithelial cells

•• Keratin positiveKeratin positive

–– Nonneoplastic lymphocytesNonneoplastic lymphocytes•• CD1a positive TCD1a positive T--cellscells

ThymomaThymoma

•• Biphasic populationBiphasic population•• Organotypic featuresOrganotypic features

–– Lobular patternLobular pattern

ThymomaThymoma

–– Lobular patternLobular pattern–– Perivascular spacesPerivascular spaces

ThymomaThymoma

•• Longitudinal spacesLongitudinal spaces

ThymomaThymoma

•• Longitudinal spacesLongitudinal spaces•• HyalinizedHyalinized

ThymomaThymoma

–– Lobular patternLobular pattern–– Perivascular spacesPerivascular spaces–– Immature TImmature T--cellscells

•• TdT+/CD1a+/CD99+TdT+/CD1a+/CD99+

Thymoma and Thymic CarcinomaThymoma and Thymic Carcinoma

•• Thymic carcinomaThymic carcinoma–– Arise from thymic epithelial cellsArise from thymic epithelial cells–– No or abortive organotypic architectural featuresNo or abortive organotypic architectural features–– ClearClear--cut cytologic atypiacut cytologic atypia–– Frequent CD5, CD70, CD117 expression in epithelial cells, ~ 60%Frequent CD5, CD70, CD117 expression in epithelial cells, ~ 60%–– Resemble carcinomas in other organsResemble carcinomas in other organs–– Malignant Malignant

•• Often unresectableOften unresectable•• Almost always invasive, metastases frequentAlmost always invasive, metastases frequent•• Short survival due to progressive diseaseShort survival due to progressive disease

•• 56 year old male56 year old male•• Two month historyTwo month history

–– Chest painChest pain–– CoughCough

Thymic CarcinomaThymic CarcinomaGrossGross

•• Firm, gritty, grayFirm, gritty, gray--white masswhite mass•• Usually lacks wellUsually lacks well--defined defined

capsule and fibrous bandscapsule and fibrous bands

Thymic CarcinomaThymic CarcinomaGrossGross

•• Firm, gritty, grayFirm, gritty, gray--white masswhite mass•• Usually lacks wellUsually lacks well--defined defined

capsule and fibrous bandscapsule and fibrous bands•• Foci of hemorrhage and Foci of hemorrhage and

necrosisnecrosis

Thymic CarcinomaThymic CarcinomaHistologyHistology

•• Loss of organotypic featuresLoss of organotypic features•• Cytologically malignantCytologically malignant

–– High N:C ratioHigh N:C ratio–– Cellular pleomorphismCellular pleomorphism–– NucleoliNucleoli–– MitosesMitoses–– NecrosisNecrosis

B3 CaB3 Ca

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaClassificationClassification

BernatzBernatz19611961

Suster & MoranSuster & Moran19991999

WHOWHO19991999

WHOWHO20042004

Spindle cellSpindle cell WellWell--diff thymomadiff thymoma Type AType A Type AType A

-- ““ ““ Type ABType AB Type ABType AB

Lymphocyte richLymphocyte rich ““ ““ Type B1Type B1 Type B1Type B1

MixedMixed ““ ““ Type B2Type B2 Type B2Type B2

Epithelial richEpithelial rich Atypical thymomaAtypical thymoma Type B3Type B3 Type B3Type B3

-- Thymic carcinomaThymic carcinoma Type CType C Thymic carcinomaThymic carcinoma

Tumors of the Thymus and Mediastinum Tumors of the Thymus and Mediastinum Epithelial tumorsEpithelial tumors

•• Epithelial tumorsEpithelial tumors–– ThymomaThymoma

•• Type A (spindle cell; medullary)Type A (spindle cell; medullary)•• Type AB (mixed)Type AB (mixed)•• Type B1 (lymphocyteType B1 (lymphocyte--rich; lymphocytic; predominantly cortical; organoidrich; lymphocytic; predominantly cortical; organoid•• Type B2 (cortical)Type B2 (cortical)•• Type B3 (epithelial; atypical; squamoid; wellType B3 (epithelial; atypical; squamoid; well--differentiated thymic ca)differentiated thymic ca)•• Rare thymomasRare thymomas

–– Micronodular thymoma with lymphoid stromaMicronodular thymoma with lymphoid stroma–– MetaplasticMetaplastic–– MicroscopicMicroscopic–– SclerosingSclerosing–– LipofibroadenomaLipofibroadenoma

Tumors of the Thymus and Mediastinum Tumors of the Thymus and Mediastinum Epithelial tumorsEpithelial tumors

•• Epithelial tumorsEpithelial tumors–– Thymic carcinomaThymic carcinoma

•• Squamous cell carcinomaSquamous cell carcinoma•• Basaloid carcinomaBasaloid carcinoma•• Mucoepidermoid carcinomaMucoepidermoid carcinoma•• LymphoepithelialLymphoepithelial--like carcinomalike carcinoma•• Sarcomatoid carcinoma (carcinosarcoma)Sarcomatoid carcinoma (carcinosarcoma)•• Clear cell carcinomaClear cell carcinoma•• AdenocarcinomaAdenocarcinoma•• Papillary adenocarcinomaPapillary adenocarcinoma•• Carcinoma with t(15;19) translocationCarcinoma with t(15;19) translocation•• Neuroendocrine carcinomaNeuroendocrine carcinoma

–– Typical and atypical carcinoidTypical and atypical carcinoid–– Large cell neuroendocrine and small cell carcinomaLarge cell neuroendocrine and small cell carcinoma

•• Undifferentiated carcinomaUndifferentiated carcinoma•• Combined thymic epithelial tumorsCombined thymic epithelial tumors

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaTermsTerms

•• EncapsulatedEncapsulated–– Completely surrounded by a fibrous capsuleCompletely surrounded by a fibrous capsule

•• Minimally or microscopically invasiveMinimally or microscopically invasive–– Invasive through the capsule to involve pericapsular tissueInvasive through the capsule to involve pericapsular tissue

•• Usually identified only after microscopic examinationUsually identified only after microscopic examination•• Generally appears encapsulated to surgeonGenerally appears encapsulated to surgeon

•• Widely invasiveWidely invasive–– Spread by direct extension into adjacent structuresSpread by direct extension into adjacent structures

•• ImplantsImplants–– Nodules separate from main mass on pericardium or pleuraNodules separate from main mass on pericardium or pleura

•• Lymph node metastasesLymph node metastases–– Nodes separate from main mass, excludes direct extension into noNodes separate from main mass, excludes direct extension into nodede

•• With distant metastasesWith distant metastases–– Most commonly to lung, liver, skeletal systemMost commonly to lung, liver, skeletal system

Capsular InvasionCapsular Invasion

•• Evaluation of capsule is Evaluation of capsule is essentialessential–– Ink marginsInk margins

•• Adherence to adjacent Adherence to adjacent structuresstructures–– CommonCommon–– DoesnDoesn’’t always indicate true t always indicate true

invasioninvasion

Tumor 400x InvolutionTumor 400x Involution

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaPrinciples of classificationPrinciples of classification

•• ThymomaThymoma–– Two major typesTwo major types

•• Uniformly bland spindle or oval epithelial cells Uniformly bland spindle or oval epithelial cells –– Type AType A•• Predominantly round or polygonal epithelial cells Predominantly round or polygonal epithelial cells –– Type BType B

–– Type B subdivided by extent of lymphoid infiltrates and cellularType B subdivided by extent of lymphoid infiltrates and cellularatypiaatypia•• B1 B1 –– lymphocyte richlymphocyte rich•• B2 and B3 B2 and B3 –– epithelial cell richepithelial cell rich

–– Type A plus B1Type A plus B1--like, and rarely B2like, and rarely B2--like, are designated ABlike, are designated AB

•• Thymic carcinomaThymic carcinoma–– Thymic carcinomas are termed according to differentiationThymic carcinomas are termed according to differentiation–– Combined thymomas are termed by WHO histology and %Combined thymomas are termed by WHO histology and %–– ““Malignant thymomaMalignant thymoma”” is discouragedis discouraged

ThymomaThymomaType AType A

•• Lymphocyte poorLymphocyte poor•• Solid sheetsSolid sheets

–– No patternNo pattern

–– No pattern or storiformNo pattern or storiform

–– No pattern or storiformNo pattern or storiform–– CystsCysts–– Lobules and bands less Lobules and bands less

conspicuous than other typesconspicuous than other types

•• Spindle or oval epithelial cellsSpindle or oval epithelial cells–– Reticulin fibers surround cellsReticulin fibers surround cells

•• Bland nucleiBland nuclei–– Dispersed chromatinDispersed chromatin–– Inconspicuous nucleoliInconspicuous nucleoli

ThymomaThymomaType ABType AB

•• Mixture of Type A and Type BMixture of Type A and Type B–– Discrete separate nodules orDiscrete separate nodules or

•• Mixture of Type A and Type BMixture of Type A and Type B–– Discrete separate nodules orDiscrete separate nodules or–– Intermixed A and BIntermixed A and B

•• Type B epithelial cells Type B epithelial cells –– Small polygonalSmall polygonal–– Dispersed chromatinDispersed chromatin–– Inconspicuous nucleoliInconspicuous nucleoli

•• B areasB areas–– Medullary differentiation rareMedullary differentiation rare–– Hassall corpuscles absentHassall corpuscles absent–– Reticulin around B nodulesReticulin around B nodules

•• Not around individual cellsNot around individual cells

ThymomaThymomaType B1Type B1

•• Resembles cortexResembles cortex

•• Resembles cortexResembles cortex•• Scant small epithelial cellsScant small epithelial cells

–– Pale nucleiPale nuclei–– Small nucleoliSmall nucleoli

•• Dispersed epithelial cellsDispersed epithelial cells–– Do not from groupingsDo not from groupings

•• Medullary differentiation always present

Medullary differentiation always present

•• Resembles cortexResembles cortex•• Dispersed epithelial cellsDispersed epithelial cells

–– Do not from groupingsDo not from groupings

•• Scant small epithelial cellsScant small epithelial cells–– Pale nucleiPale nuclei–– Small nucleoliSmall nucleoli

•• Medullary differentiation always present

Medullary differentiation

always present

•• Hassall corpuscles may be present Hassall corpuscles may be present

•• Large course lobulesLarge course lobules–– Separated by delicate septaSeparated by delicate septa

•• Large polygonal epithelial cellsLarge polygonal epithelial cells–– Open chromatinOpen chromatin–– Prominent nucleoliProminent nucleoli

•• Medullary differentiation absent or inconspicuous

Medullary differentiation absent or inconspicuous

•• Abortive Hassall in 25%Abortive Hassall in 25%–– Typical Hassall rareTypical Hassall rare

•• B3 occurs in B2B3 occurs in B2–– 1717--29% of cases29% of cases–– Designate B2/B3Designate B2/B3

•• Lobules with thick septaLobules with thick septa

•• Lobules with thick septaLobules with thick septa•• Paucity of lymphoctyesPaucity of lymphoctyes

–– Results in sheetResults in sheet--like growthlike growth

–– Results in sheetResults in sheet--like growthlike growth–– Solid or epidermoid patternSolid or epidermoid pattern

•• No intercellular bridgesNo intercellular bridges

•• MediumMedium--size epithelial cellssize epithelial cells–– Small nucleoliSmall nucleoli–– Often grooved nucleiOften grooved nuclei

•• Perivascular palisadingPerivascular palisading

•• Perivascular palisadingPerivascular palisading•• Foci of keratinizationFoci of keratinization

–– Mimicking Hassall corpusclesMimicking Hassall corpuscles

•• Medullary differentiation usually absent

Medullary differentiation usually absent

A B3 A B3

B1 B2B1 B2B3 CaB3 Ca

B1 B2B1 B2

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaPrevalence of subtypesPrevalence of subtypes

•• AB AB –– 2020--35%35%•• B2 B2 –– 2020--35%35%•• A A –– 55--10%10%•• B1 B1 –– 55--10%10%•• Thymic carcinoma 10Thymic carcinoma 10--25%25%

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaSpectrum of MalignancySpectrum of Malignancy

•• ThymomaThymoma–– Type AType A–– Type ABType AB–– Type B1Type B1–– Type B2Type B2–– Type B3Type B3

•• Thymic carcinoidsThymic carcinoids•• Thymic carcinomaThymic carcinoma

–– Squamous cell, basaloid, mucoepidermoidSquamous cell, basaloid, mucoepidermoid–– Other subtypesOther subtypes

•• Small cell and large cell neuroendocrineSmall cell and large cell neuroendocrine

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaPrognosisPrognosis

•• Most important prognostic factorsMost important prognostic factors–– Tumor stageTumor stage

•• MasaokaMasaoka stage is the most important and statistically most significant stage is the most important and statistically most significant independent prognostic indicator of survival in most studiesindependent prognostic indicator of survival in most studies

–– WHO histologic typeWHO histologic type–– Completeness of resectionCompleteness of resection

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaPrognosisPrognosis

HistologyHistology StageStage Biologic PotentialBiologic Potential

A, AB, B1A, AB, B1 l and lll and llllllll

None/very lowNone/very lowLowLow

B2, B3B2, B3 llll and lllll and lll

LowLowModerateModerate

Squam, basaloid, Squam, basaloid, mucoep, carcinoidmucoep, carcinoid

l and lll and llllllll

ModerateModerateHighHigh

Other histologyOther histology AnyAny HighHigh

StagingStagingTNM TNM

•• T1 T1 –– tumor completely encapsulatedtumor completely encapsulated•• T2 T2 –– tumor invades pericapsular connective tissuetumor invades pericapsular connective tissue•• T3 T3 –– tumor invades into neighboring structures, such as tumor invades into neighboring structures, such as

pericardium, mediastinal pleura, thoracic wall, great vessels pericardium, mediastinal pleura, thoracic wall, great vessels and lungand lung

•• T4 T4 –– tumor with pleural or pericardial disseminationtumor with pleural or pericardial dissemination

•• Currently no authorized TNM system for thymic epithelial or Currently no authorized TNM system for thymic epithelial or neuroendocrine tumorsneuroendocrine tumors

StagingStagingModified Masaoka Modified Masaoka

•• Stage 1:Stage 1: intact capsule or growth within capsuleintact capsule or growth within capsule•• Stage 2a:Stage 2a: microscopic invasion through capsulemicroscopic invasion through capsule

2b:2b: gross and microscopic invasiongross and microscopic invasion•• Stage 3:Stage 3: invasion into surrounding structuresinvasion into surrounding structures•• Stage 4a:Stage 4a: pleural or pericardial disseminationpleural or pericardial dissemination

4b:4b: lymphatic or hematogenous metastaseslymphatic or hematogenous metastases

Thymoma and Thymic CarcinomaThymoma and Thymic CarcinomaDiagnosisDiagnosis

•• ThymomaThymoma–– EncapsulatedEncapsulated–– Invasive (term malignant thymoma is discourage)Invasive (term malignant thymoma is discourage)

•• Surgical pathology reportSurgical pathology report–– Correct diagnosisCorrect diagnosis

•• Up to 20% in some studies incorrectly diagnosedUp to 20% in some studies incorrectly diagnosed

–– Assessment of surgical marginsAssessment of surgical margins•• Requires inkingRequires inking

–– Determination of invasivenessDetermination of invasiveness•• Multiple sections through capsuleMultiple sections through capsule

•• Thymic carcinomaThymic carcinoma–– Separation from metastatic carcinoma may be difficultSeparation from metastatic carcinoma may be difficult

•• Lung, thyroid, breast, prostate are most commonLung, thyroid, breast, prostate are most common

–– May only be able to suggest or favor diagnosis May only be able to suggest or favor diagnosis •• Clinical history and radiologic studies are essentialClinical history and radiologic studies are essential

TumorTumor Thymic primaryThymic primary Lung or head/neckLung or head/neck

Squamous, basaloid, Squamous, basaloid, lympholympho--epi caepi ca Lobular growth 70%Lobular growth 70% Lobular growth rareLobular growth rare

Perivascular spaces 50%Perivascular spaces 50% Perivascular spaces rarePerivascular spaces rare

CD5 50%CD5 50% CD5 not expressedCD5 not expressed

CD70 50%CD70 50% CD70 not expressedCD70 not expressed

CD117 40CD117 40--100%100% CD117 not expressedCD117 not expressed

NE carcinomaNE carcinoma TTFTTF--1 absent1 absent TTFTTF--1 frequent (lung)1 frequent (lung)

•• Epithelial tumorsEpithelial tumors•• Germ cell tumorsGerm cell tumors

–– 2003 WHO Classification of Germ Cell Tumors2003 WHO Classification of Germ Cell Tumors•• TeratomaTeratoma•• SeminomaSeminoma

•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms•• Mesenchymal tumorsMesenchymal tumors•• Rare tumorsRare tumors•• MetastasisMetastasis

•• Epithelial tumorsEpithelial tumors•• Germ cell tumorsGerm cell tumors•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms

–– 2001 WHO Classification of Hematopoietic and Lymphoid Tumors2001 WHO Classification of Hematopoietic and Lymphoid Tumors•• NS Classical HLNS Classical HL•• PMLBPMLB--CLCL•• TT--lymphoblastic leukemia/lymphomalymphoblastic leukemia/lymphoma•• MALT lymphomaMALT lymphoma

•• Mesenchymal tumorsMesenchymal tumors•• Rare tumorsRare tumors•• MetastasisMetastasis

•• Epithelial tumorsEpithelial tumors•• Germ cell tumorsGerm cell tumors•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms•• Mesenchymal tumorsMesenchymal tumors

–– 2000 WHO Classification of Nervous System2000 WHO Classification of Nervous System•• SchwannomaSchwannoma

–– 2002 WHO Classification of Soft Tissue and Bone2002 WHO Classification of Soft Tissue and Bone•• ThymolipomaThymolipoma

•• Rare tumorsRare tumors•• MetastasisMetastasis

•• Epithelial tumorsEpithelial tumors•• Germ cell tumorsGerm cell tumors•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms•• Mesenchymal tumorsMesenchymal tumors•• Rare tumorsRare tumors

–– Ectopic tumors of the thymusEctopic tumors of the thymus•• Ectopic thyroid tumorsEctopic thyroid tumors•• Ectopic parathyroid tumorsEctopic parathyroid tumors

•• MetastasisMetastasis

Rare TumorsRare TumorsEctopic tumorsEctopic tumors

•• Uncommon, benign or Uncommon, benign or malignantmalignant

•• Anterior or posterior Anterior or posterior compartmentcompartment

•• ThyroidThyroid–– Extension from neck or Extension from neck or

ectopic tissueectopic tissue

•• ParathyroidParathyroid–– Found adjacent to or within Found adjacent to or within

thymusthymus

•• Epithelial tumorsEpithelial tumors•• Germ cell tumorsGerm cell tumors•• Lymphomas and hematopoietic neoplasmsLymphomas and hematopoietic neoplasms•• Mesenchymal tumorsMesenchymal tumors•• Rare tumorsRare tumors•• MetastasisMetastasis

–– Thymus and anterior (middle) mediastinumThymus and anterior (middle) mediastinum•• Lung, thyroid, breast, prostate are most commonLung, thyroid, breast, prostate are most common

•• Three compartmentsThree compartments•• Mediastinal lesionsMediastinal lesions

–– 50% of lesions50% of lesions•• Anterior compartmentAnterior compartment

–– ThymicThymic lesions dominatelesions dominate–– Organization by compartmentOrganization by compartment

Mediastinal PathologyMediastinal PathologySummarySummary

CystsCysts 7%7% 60%60% 24%24%

MediastinumMediastinumLesions occurring in two compartmentsLesions occurring in two compartments

CystsCysts 7%7% 60%60% 24%24%

MediastinumMediastinumLesions occurring in all compartmentsLesions occurring in all compartments

CystsCysts 7%7% 60%60% 24%24%

MediastinumMediastinumMost common lesionMost common lesion

Mediastinal Pathology Compartmental Approach

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Transcript of Mediastinal Pathology Compartmental Approach

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