Lung Cytopathology Irish Society of Surgical...
Transcript of Lung Cytopathology Irish Society of Surgical...
Dr Stephen CrowtherTallaght Hospital
Lung CytopathologyIrish Society of Surgical Pathology
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
ContentsSpecimens, preparation and adequacyProposed classification systemCommon malignancies Pitfalls
What is the role of cytologyLung cancer presents at advanced stageIncreased number of nodules sampled (screening)
DiagnosisStagingMolecular testing
SpecimensSputumBronchoscopic derived specimens
Bronchial brushingsBronchial washings Bronchoalveolar lavage (BAL)Endobronchial ultrasound guided aspiration (lung, lymph nodes)
Percutaneous trans-thoracic CT-guided FNAPleural Fluid
PreparationsDirect smears
Air dried (MGG)Alcohol fixed (Pap, H&E)
Touch imprints – core biopsyConcentration methods
Cytospin (Hanks)Liquid-based preparations (Cytolyte)
Cell block
Sputum
Non invasiveEarly morning, induced, post BronchoscopicPreparation
Pick and smearAdequacy
2 smears with easily identifiable pulmonary macrophages
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!
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
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!
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
Pleural FluidDiagnose & Stage (M stage)No adequacy criteriaCytospins (2 PAP, 2 MGG)
Peg for immunocytochemistryCell block for molecular
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
Risk of Malignancy
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
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)
PASF
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
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)
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
VI. MalignantNon small cell carcinoma – need to further classify
AdenocarcinomaSquamous cell carcinomaLarge cell carcinoma
Small cell carcinomaNeuroendocrine (TC, AC, LCNEC)Adenoid cystic carcinomaMucoepidermoidLymphomaMetastases
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
Washings
FNA
FNA
PitfallsUpper RTI with reactive changes (sputum, washings)Reactive changes in cavities (aspergillus), bronchiectasis, infection,radiationContamination – EBUS LNNecrosis can mimic keratinisationIn situ v invasive
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
Washings
FNA
FNA
PitfallsReactive bronchial epithelium (washings)Pseudoglandular squamous cellMetastasesLepidic
Adenocarcinoma with lepidic patternAdenocarcinoma-in-situMinimally invasive adenocarcinomaInvasive adenocarcinoma with lepidic pattern
Can you go any further on cytology??Adequate classification can require resection
ImmunocytochemistryTissue preservation importantCocktail of two markers
TTF1, ck5/6P63(p40)Nap
Special stainsMucin for adenocarcinoma
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
? 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
Non small cell carcinoma NOS
Small cell carcinomaSingle and loose clusters of cellsScant cytoplasmGranular/clumped chromatin Indistinct nucleoliNuclear mouldingNecrosis and Azzopardi affect
Washings
Washings
Washings
FNA
FNA
FNA
PitfallsDegenerate bronchial cells (washings)Lymphocytes (washings)Poorly differentiated squamous cell carcinoma Lymphoma – CD56
CD56
CD3AE1/3
CarcinoidUniform small cells, rounded nuclei, stippled chromatinPalisades, trabeculaeBare nucleiNecrosis rareBrushings and FNARarely exfoliates into washings
Atypical carcinoidNeuroendocrine cytologyIncreased pleomorphism, mitoses, necrosis (v TC)No moulding, smearing, no abundant mitoses & necrosis (v SCC)Cell block – MIB 1 helps v SCC
FNA
Adenoid cysticPrimary or metastaticLarge acellular basement membrane spheres (MGG)Background of small cells with uniform nuclei
NA
FNA
Metastatic urothelial carcinoma
FNA
Pleural fluid
Pleural fluid
CD56 BerEp4
Pleural fluid – cell block CD56
TTF1
Concluding remarksProposed new classificationTerminology
Non small cell NOS!!Consider cellblockThink molecular