Lung Cytopathology Irish Society of Surgical...
Transcript of Lung Cytopathology Irish Society of Surgical...
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Dr Stephen CrowtherTallaght Hospital
Lung CytopathologyIrish Society of Surgical Pathology
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First Draft ISSP Saturday morningSATURDAY: Lung Neoplasms9.00 - 9.40: My Holidays Stephen Crowther (sponsored by British
Airways)9.40 - 10.20: Lung Tumours : Louise Burke (TBC)10.20 - 11.00: Mesenchymal Lung tumours: Leona Doyle
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ContentsSpecimens, preparation and adequacyProposed classification systemCommon malignancies Pitfalls
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What is the role of cytologyLung cancer presents at advanced stageIncreased number of nodules sampled (screening)
DiagnosisStagingMolecular testing
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SpecimensSputumBronchoscopic derived specimens
Bronchial brushingsBronchial washings Bronchoalveolar lavage (BAL)Endobronchial ultrasound guided aspiration (lung, lymph nodes)
Percutaneous trans-thoracic CT-guided FNAPleural Fluid
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PreparationsDirect smears
Air dried (MGG)Alcohol fixed (Pap, H&E)
Touch imprints – core biopsyConcentration methods
Cytospin (Hanks)Liquid-based preparations (Cytolyte)
Cell block
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Sputum
Non invasiveEarly morning, induced, post BronchoscopicPreparation
Pick and smearAdequacy
2 smears with easily identifiable pulmonary macrophages
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Bronchial Brush & WashingsCentral tumour exfoliating into the bronchiSquamous cell carcinoma and small cell most sensitiveWashings
5mls of salt solution instilled and then re-aspirated
BrushRolled on a glass slideBefore biopsy
AdequacyPulmonary macrophages, squamous cells, bronchial epithelial cellsAdequate if positive!
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Bronchoalveolar LavageUseful in benign disease
Cell differentialCD4:CD8 ratio
Assessment of terminal air spaces50-100 mls of warm salineFlood distal airspace and re-aspiratedAdequacy
Alveolar macrophages (>10 per 10 HPF)<5% BE or Squamous cells
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Lung FNAMost effective cytological technique to diagnose pulmonary carcinomaClose radiological correlation requiredOnsite rapid assessment - triage materialDirect smears (AD, IMS)Needle rinse
Hanks/PEG - ICC RPMI - flowCell block – IHC, molecular
Adequate if malignant!
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EBUS Lymph node FNADiagnose and Stage (N stage)Preparation
Rapid onsite assessment and smearsCytolyte, Thinprep and cell block
Adequacy Minimum number of lymphocytes (>40 at x40)Pigment laiden macrophagesGerminal centre fragments
Cellblock for molecular
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Pleural FluidDiagnose & Stage (M stage)No adequacy criteriaCytospins (2 PAP, 2 MGG)
Peg for immunocytochemistryCell block for molecular
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Standardized Terminology and Nomenclature for Respiratory Cytology
I Non diagnosticII Negative (for malignancy)III AtypicalIV Neoplasm, benign neoplasm, and low-grade malignancyV Suspicious for malignancyVI Malignant
The Papanicolaou Society of Cytopathology GuidelinesDiagnostic Cytopathology
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Risk of Malignancy
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I. Non diagnosticAdequacy
Defined for sputum and LN EBUS-FNANot for brush, washing and Lung FNA (adequate if malignant!)Doesn't mean lesion has been sampled
Poor SamplingMultidisciplinary approachOn-site evaluation
Technical issuesSmearing, fixation, staining
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II. Negative for malignancy
AdequateAbsence of cellular atypiaDiagnose a lesion defined radiologically
Infection (abscess, TB, fungi, parasite, viral)InfarctionSarcoidAspirationAmyloidLipoid
Normal tissue – radiology vague (no definite lesion)
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PASF
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III. Atypical
Limited use of this category – not a wastebasket!Two types
Abnormalities greater than inflam/repair but less than suspicious for malignancyHighly suspicious for a benign neoplasm
Eg bland spindled cells suggestive of SFT
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IV. Neoplasm, benign neoplasm and low-grade malignancy
Allows discretion in treatment of elderly/medically unfitAdequately cellular and diagnostic
Solitary fibrous tumourPulmonary hamartomaSquamous papillomaGranular cell tumourPEComa (clear cell sugar tumour)MeningiomaInflammatory myofibroblastic tumourLangerhan’s cell histiocytosis
Does not include neuroendocrine tumours (carcinoids)
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V. Suspicious for malignancyNot diagnostic of malignancy – inform your clinicans!Carcinomas (NSCLC, SCLC, NEC), Carcinoids, Lymphoma, MetastasesInter-observer variability & experience
Scant cellularityPeripheral samplingCavitationContamination of adjacent materialHigh level of differentiation in adca
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VI. MalignantNon small cell carcinoma – need to further classify
AdenocarcinomaSquamous cell carcinomaLarge cell carcinoma
Small cell carcinomaNeuroendocrine (TC, AC, LCNEC)Adenoid cystic carcinomaMucoepidermoidLymphomaMetastases
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Squamous cell carcinomaSingle cell and flat sheets with well defined cell membranesCytoplasm: polygonal, oval, spindled and irregular cell contourswith dense or keratinised cytoplasmNuclei: oval, rectangular, irregular contours, centrally situated, coarse to pyknotic like dark chromatinNucleoli often inconspicuous
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Washings
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FNA
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FNA
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PitfallsUpper RTI with reactive changes (sputum, washings)Reactive changes in cavities (aspergillus), bronchiectasis, infection,radiationContamination – EBUS LNNecrosis can mimic keratinisationIn situ v invasive
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AdenocarcinomaMostly flat to three-dimensional aggregates and variable number of individual tumour cellsAcinar and glandular structures in aggregatesCytoplasm: abundant, delicate, granular to vacuolated, mucinNuclei: eccentric round to oval structures with minor membrane irregularities and fine chromatinProminent nucleoli
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Washings
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FNA
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FNA
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PitfallsReactive bronchial epithelium (washings)Pseudoglandular squamous cellMetastasesLepidic
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Adenocarcinoma with lepidic patternAdenocarcinoma-in-situMinimally invasive adenocarcinomaInvasive adenocarcinoma with lepidic pattern
Can you go any further on cytology??Adequate classification can require resection
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ImmunocytochemistryTissue preservation importantCocktail of two markers
TTF1, ck5/6P63(p40)Nap
Special stainsMucin for adenocarcinoma
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International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma
Morphologic adenocarcinoma patterns clearly presentAdenocarcinoma
Morphologic adenocarcinoma patterns not present (supported by special stains)
Non-small cell carcinoma, favour adenocarcinomaMorphologic squamous cell patterns clearly present
Squamous cell carcinomaMorphologic squamous cell patterns not present (supported by stains)
Non-small cell carcinoma, favour squamous cell carcinoma
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? Large cell carcinomaGroups of large clearly malignant cellsPleomorphic single cell populationHigh N/C ratioNecrotic backgroundImmunos equivocal/negativeHistological (resection) diagnosisCyto dx – Non-small cell carcinoma, NOSLarge cell neuroendocrine carcinoma – NE markers
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Non small cell carcinoma NOS
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Small cell carcinomaSingle and loose clusters of cellsScant cytoplasmGranular/clumped chromatin Indistinct nucleoliNuclear mouldingNecrosis and Azzopardi affect
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Washings
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Washings
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Washings
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FNA
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FNA
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FNA
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PitfallsDegenerate bronchial cells (washings)Lymphocytes (washings)Poorly differentiated squamous cell carcinoma Lymphoma – CD56
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CD56
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CD3AE1/3
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CarcinoidUniform small cells, rounded nuclei, stippled chromatinPalisades, trabeculaeBare nucleiNecrosis rareBrushings and FNARarely exfoliates into washings
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Atypical carcinoidNeuroendocrine cytologyIncreased pleomorphism, mitoses, necrosis (v TC)No moulding, smearing, no abundant mitoses & necrosis (v SCC)Cell block – MIB 1 helps v SCC
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FNA
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Adenoid cysticPrimary or metastaticLarge acellular basement membrane spheres (MGG)Background of small cells with uniform nuclei
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NA
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FNA
Metastatic urothelial carcinoma
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FNA
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Pleural fluid
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Pleural fluid
CD56 BerEp4
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Pleural fluid – cell block CD56
TTF1
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Concluding remarksProposed new classificationTerminology
Non small cell NOS!!Consider cellblockThink molecular