04 Diagnostic Value of Cytohistopathologic Specimens Obtaine
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8/12/2019 04 Diagnostic Value of Cytohistopathologic Specimens Obtaine
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Diagnostic Value of CytohistopathologicSpecimens obtained by Bronchoscopy
4th Annual CME, MAMC, Delhi13th October, 2012
Harsh Mohan, MD, FAMS, FICPath, FUICC
GMCH-32, [email protected]
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Lay out
Introduction
Bronchoscopy
Pathologic specimens
Cytologic features
Histopathologic features
Cytohistopathologic correlation: our experience Representative cases: neoplasms, nonneoplastic
(infections, others)
Take home message
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Introduction
Lung cancer one of 3 most common cancers
Lacks effective screening program (unlike cacervix and ca breast)
Abnormal nodule in chest radiograph
Worked up by bronchoscopy and imagingguidance for cytologic material and by
biopsy
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Bronchoscopy: history
Killian (1885): translaryngeal approach for removalof foreign body
Jackson (1917): use of light at an end; peroral route;use for diagnosis and therapeutic purposes
Until 1960s: rigid bronchoscopes; limited access todistal airways
Machida (1968): first flexible/fibreopticbronchoscope (FOB)
Newer applications: Video bronchoscopy,bronchoscopic USG, fluorescence bronchoscopy,virtual bronchoscopy
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Pathologic specimens in
diagnosis of lung diseases Cytologic specimens (exfoliative, FNA):
Sputum (pre- and post-FOB)
BW
BAL
BB
FNA: TBNA, EBUS FNA, TTNA Biopsy specimens:
Forceps biopsy ((endobronchial, transbronchial)
Added techniques: imprint smears, rinse fluid
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Cytologic features: Sputum
Direct smears; stained with H&E and/or Pap
Mucus
Pulmonary alveolar macrophages
Pigmented macrophages
Bronchial epithelial cells
Upper respiratory tract squames Candida hyphae, spores
Charcot-Leyden crystals
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Cytologic features: BB
BB obtained by gently rolling over on the slidehaving 95% alcohol
BB better if taken before other procedures (BW,BAL, Bx)
Bronchial epithelial cells as sheets and plenty ofseparated cells
Goblet cell metaplasia may be seen
Upper respiratory squames seen
Metaplastic sq cells present
Pulmonary alveolar macrophages+ but < BAL, BW
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Cytologic features: BW
Direct smears at FOB (except in LBC)
Similar to sputum specimens except thatepithelial cells are more numerous
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Cytologic features: BAL
Thinner, less mucoid
Cytocentrifugation Pulmonary macrophages comprise 80% of
cells; others are inflammatory cells (PMNs,
L) and bronchial epithelial cells
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Needle aspiration
FOB: TBNA
Under imaging guidance
EUS-FNA
Direct smears; air-dried for MGG and Diff-Quik, alcohol fixed for Pap and H&E
Needle washings in formalin as cell block forICC
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Bronchial Bx
Paraffin-embedding technique
Gold standard versus longer TAT Additional uses: imprint, rinse fluid
Lower sensitivity, higher diagnostic yield
Cytologic-negative and histologic-positivecases
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Imprint (Touch) smears
Biopsied tissue imprinted on slides
Cell distribution and tissue architecture better Quality determining factors: fixation, speed
of imprinting, thickness of smears, bloody
smears, inflammatory cells, necrosis
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Rinse fluid
As exfoliative cytology: suspended in BSS
Described in many organs as biopsy-cytologytechnique
Advantages in pulmonary cytology:
distinctive cellular features in isolated cells,ICC
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Applications of cytohistologic
specimens in lung lesions
Neoplastic: Sq cell ca, adenoca, small cell ca,
large cell ca, carcinoid, metastasis
Nonneoplastic infectious: Abscess, TB,
fungi, aspergillosis, candida, mucor, hydatid
Nonneoplastic noninfectious: ILDs,Wegeners granulomatosis
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Combining cytohistologic techniques in
lung tumours: our experience
Increased diagnostic yield
Specificity=100%
Methods Sensitivity
BAL+BB = 72.9%
BB+FBx = 84.5%
BB+FBx+TBNA = 87.5% TTNA = 77.8%
Alone: sputum=27.6%; BAL=37.5%; BB=70%;TBNA=83.3%
Garg et al.Diagn. Cytopathol. 2007;35:26-31
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Combining cytohistologic techniques in TBlung: our experience
Specimen Sensitivity
BAL 80%
BB 60%
Post-FOB 45%
Bx 87%
Specificity =100% in all
Garg et al.Diagn. Cytopathol. 2007;35:26-31
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Statistical analysis of rinse fluid and imprintsmear examination: our experience
Sensiti-
vity %
Specifi
-city %
PPV
%
NPV % Diagn
acc %
K test
Rinse fluid 75 100 100 61.1 78.84 0.454
Imprintsmears
97.8 100 100 87.5 98.08 0.922
Goyal et al.Diagn. Cytopathol. 2012; 3:165-7
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What is new in pathology of
lung tumours ? Terms BAC and mixed type not used
NSCC categories: adenoca, sq cell ca, large cell ca.
SCC categories: pure, combined
Adenoca in situ: with lepidic growth pattern insmall solitary ca (
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Newer categories ofadenoca. classification
(formerly BAC)1. Adenoca in situ, non-mucinous and rarely
mucinous
2. Minimally invasive adenocarcinoma, non-mucinous and rarely mucinous
3. Lepidic predominant adenocarcinoma, non-mucinous
4. Adenocarcinoma, predominantly invasive withsome non-mucinous lepidic component(formerly mixed subtype and non-mucinousBAC)
5. Invasive mucinous adenocarcinoma (formerly
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Newer categories of
other NSCC lung Sq cell ca: subtypes
Papillary
Clear cell Small cell
Basaloid
Large cell ca: subtypes
Large cell NE ca
Large cell ca with NE morphology
Others:
Adenosquamous ca
Sarcomatoid
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New in small cell ca lung
Older classification:
Oat cell
Intermediate
Combined
Current:
Pure
Combined (containing any other NSCC component)
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A quick round of morphology
Neoplasms
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Bronchial carcinoid
Typical and atypical carcinoids low grade NEtumour (low mitotic and proliferation rates, less and
focal necrosis) Organoid pattern, uniform tumour cells; other
patterns: spindle cells, trabecular, palisading,rosette-like, papillary, follicular
Finely granular nuclear chromatin, moderatecytoplasm
IHC: Ki-67, NE markers (chromogranin,synaptophysin,CD56)
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Bronchial carcinoid:
cytologic features Cells smaller, round to oval
Nucleus: granular chromatin, 1-2 nucleoli;little evidence of moulding, pleomorphism or
necrosis
Cytoplasm: scanty, delicate, red granular
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Small cell ca lung
Patterns: diffuse sheets; others rosettes,palisading, organoid, streams, ribbons
Nuclear moulding, crushing artifacts
Small cells, round to fusiform nucleus,inconspicuous or absent nucleoli
Necrosis frequent and extensive
Cytology versusbiopsy
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Small cell ca: cytologic features
Isolated and small groups of cells, small and
intermediate in size
Cellular features: Scanty cytoplasm, nuclear
crushing artefacts, salt and pepper chromatin,
nuclear moulding, inconspicuous or absent nucleoli,
high mitoses Fragmented cells and necrosis in background
Paranuclear blue (inclusion) bodies
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Adenocarcinoma
Currently most common lung cancer
Adenoca in situ, minimally invasive,invasive
Mucinous, non-mucinous
Primary, metastatic Patterns of adenoca.
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Adenocarcinoma:
cytologic features Cohesive groups of cells
Patterns: acinar, papillary, micropapillary
Cytoplasmic vacuoles in some cells
Occasionally mucinous background
Subclassification based on above features
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Adenoca with
lepidic growth pattern Formerly bronchioloalveolar ca.
Monotonous population of atypical bronchiolo-
alveolar cells in monolayered sheets and papillae
Nuclear features: bland nuclei, nuclear clearing,
chromatin margination, intranuclear cytoplasmic
pseudoinclusions, nuclear grooves Psammoma bodies sometimes
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Sq cell ca lung
May be a classic NSCC: keratinising, non-
keratinising; varying grades of differentiation
May require distinction from small cell ca
and basaloid variant of large cell ca
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Sq cell ca: cytologic features
Cohesive groups and isolated pleomorphic
cells
Cellular features: hyperchromatic nuclei,
uniformly dense and focally eosinophilic
cytoplasm
Necrotic debris in background common
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Large cell ca: cytologic features
Poorly-differentiated non-small cell unclassifiable ca
Absence of squamous/glandular differentiation
Isolated cells and small cell clusters
Cellular features: large, pleomorphic nuclei,
parachrmatin clearing, presence of macronucleoli,
binucleation/ multinucleation common, N:C ratiolow
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IHC in various types of ca lung
Cancer type CK7 HMW-
CK5/6
TTF-1 p63
Adeno ca. + _ + _
Sq cell ca. _ + _ +
Small cell ca.* + _ + _
*NE markers + (chromogranin, NSE, synaptophysin)
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A quick round of morphology
Non-neoplastic lesions:infectious and noninfectious
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Tuberculosis: cytologic features
Epithelioid cell granulomas
Mixed inflammation; sometimes pus
Langhans giant cells
Caseation necrosis
AFB in ZN stain
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Others
Fungal infections: aspergillosis, mucor
Hydatid cyst
Wegeners granulomatosis
ILDs
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Diagnostic pitfalls in
pulmonary cytology Problems of false positive more serious than
false negative
Mimics mistaken for bronchogenic ca:
Reactive atypia secondary to inflammation
Reactive type II pneumocytes
Basal cell hyperplasia
Reactive squamous metaplasia
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Molecular diagnostics in
respiratory pathologyNeed to categorise lung cancer into not only
small cell and non-small cell type but also
further subtypes of the latter.
For targeted therapy and predicting
prognosis: molecular testing forEGFR and
KRASmutation,ALKrearrangement.
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