atcwong 4May07 Respiratory Cytology
Respiratory Cytology for junior colleagues, ACP, PWH
4 May 2007
Respiratory tract (Airways)

Upper – Nasal cavity, paranasal sinuses, buccal cavity, pharynx

Intermediate – Larynx, epiglottis, trachea, left and right main bronchi

Lower – lobar bronchi, segmental bronchi, bronchioles, respiratory bronchioles, and alveoli
Cells of the respiratory tract

Non-keratinizing stratified squamous epithelium

Pseudostratified columnar respiratory epithelium – ciliated columnar cells, goblet cells, reserve cells, Clara cells,
Kulchitsky cells

Pneumocytes type I & II
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Pulmonary alveolar macrophages (dust cells, carbon-laden macrophages)
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Leukocytes – polymorphs, eosinophils, lymphocytes, plasma cells, mast cells, monocytes, etc
Noncellular endogenous materials

Inspissated mucus, Curschmann’s spirals
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Corpora amylacea
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Amyloid and pseudoamyloid
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Calcified concretions, psammoma bodies
Exogenous foreign materials
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Furruginous (Asbestos) bodies
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Vegetable and meat cells, food particles
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Pollen grains
Benign abnormal changes in bronchial epithelial cells
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Loss of cilia and terminal plate
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Multinucleation – the nuclei within a single cells look very similar to each other
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Cell and nuclear enlargement
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Nucleolar enlargement
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Ciliocytophthoria – distal ciliated portion pinched off – anucleated ciliated tufts and nucleated cytoplasmic remnants,
possibly due to adenoviral infection
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Lipochrome pigmentation
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Immobile cilia syndrome
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Increased number of goblet cells
Proliferative benign changes in respiratory epithelium
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Papillary hyperplasia (Creola bodies) – vs. bronchioloalveolar adenoCa
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atcwong 4May07 Respiratory Cytology

Basal (reserve) cell hyperplasia – vs. small cell Ca
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Squamous metaplasia
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Tracheitis Sicca – patients with prolonged tracheostomy – cells mimic keratinizing SCC
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Reactive pneumocyte type II – important source of false-positive diagnosis of adenoCa
Specific Inflammatory processes

Tuberculosis – caseation, epithelioid cells, Langhan’s giant cells, tubercles
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Sarcoidosis – like TB but no caseation, unknown cause

Actinomycosis and Norcardiosis
Specific viral infections

Herpes Simplex virus – multiple molded ground-glass nuclei with large intranuclear eosinophilic inclusions
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Cytomegalovirus – Enlarged cells with large basophilic intranuclear inclusions with clear halo
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Adenovirus – multiple eosinophilic intranuclear inclusions with halos
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Parainflurenza virus – ciliocytophthoria, multiple cytoplasmic eosinophilic inclusions
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Respiratory syncytial virus – large syncytial cell aggregates; eosinophilic cytoplasmic inclusions
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Measles (Rubella)
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Polyomavirus
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Human papillomavirus
Pulmonary Mycosis (Pathogenic)
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Cryptococcus neoformans
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Blastomyces dermatitidis
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Coccidioles immitis
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Paracoccidioides brasiliensis
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Histoplasma capsulatum
Pulmonary Mycosis (Opportunistic)
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Candida albicans
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Mucor species
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Aspergillus species
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Pneumocystis carinii
Parasites
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Amoebiasis
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Trichomoniasis
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Strongyloidiasis
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Hookworm
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Echincoccus (tapeworm)
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Lung flukes
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atcwong 4May07 Respiratory Cytology
Other benign conditions

Lipid pneumonia, exogenous and endogenous
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Alveolar Proteinosis
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Malakoplakia
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Rheumatoid granuloma
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Gaucher’s disease
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Follicular bronchitis
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Thermal injury
Treatment effects
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Radiation therapy
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Chemotherapy
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Tumors of the lung
Lung Cancers remain the most common cause of cancer deaths in men and women alike, as it has been for many years
Basic golden rules for cytologic diagnosis of lung cancers

All ciliated cells or cells with terminal bar should be regarded as benign

Benign reactive bronchial cells could vary in nuclear sizes and show nuclear hyperchromasia but they share the
same uniform granular chromatin pattern
Method of Diagnosis
1.
Sputum Cytology – most effective for dx of SCC
2.
Bronchial brushings (± biopsy) and washings
3.
Bronchoalveolar larvage (BAL) – can detect peripheral adenoCa
4.
Cell blocks – a supplement, not to replace cytology
5.
Roentgenograms (X-ray)
6.
Computed Tomography (CT)
7.
Guided percutaneous FNA – for peripheral lung and mediastinal lesions
8.
Transbronchial FNA biopsy – for lesions inside lung proper
9.
CT-guided core biopsy
Classification of primary lung cancers
1.
Squamous carcinoma (SCC) – keratinizing, and non-keratinizing (epidermoid Ca)
2.
Adenocarcinoma – central, and peripheral (bronchioloalveolar adenoCa)
3.
Large cell undifferentiated carcinoma
4.
Small cell undifferentiated carcinoma (oat cell type and intermediate cell type)
5.
Adenosquamous carcinoma
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6.
Mucoepidermoid carcinoma
7.
Neuroendocrine tumors – carcinoids
8.
Rare carcinomas
Keratinizing Squamous cell carcinomas, in sputum or bronchial secretions

Malignant cells tends to exfoliate and lie singly

Cells vary considerably in shape and size – spindle cell and tadpole cells

Brilliant orange or yellow color cytoplasm – keratinized cytoplasm
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Markedly inflammatory and necrotic smears are common
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Nucleus evenly hyperchromatic and pyknotic, vary in sizes and shapes

Malignant pearl formation
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Nucleolus, mitotic figures, and high N/C ratio are uncommon
Non-keratinizing squamous (epidermoid) carcinoma, (once predominant type)

Cytoplasm less abundant, more transparent and being cyanophilic or amphophilic

Nuclei hyperchromatic with coarsely textured chromatin, not pyknotic

Nucleolus may be seen

Occasional keratinizing cancer cells may even be helpful for the proper diagnosis
SCC in brushing and FNA specimens
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Tumor cells occur in sheets or loose clusters
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Cell outline ill-defined

Cytoplasm cyanophilic

Nuclei coarsely granular but rarely pyknotic

Nucleoli more common

Distinction between non-keratinizing SCC and adenoCa would be more difficult
Source of error in diagnosis of primary lung SCC

Vegetable cells, pollen

Irradiation and chemotherapy effect

Tracheitis sicca

Atypical squamous metaplastic cells, e.g. under mycetoma
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Mucoepidermoid Ca
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Metastatic and upper tract SCC
Large cell undifferentiated carcinoma

Cells lie singly or in loose flat sheets with variation in cell sizes

Cytoplasm range from scant to moderate amount, delicate and palely stained

Cell outline can be indistinctive
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Large nuclei with irregular contour, and sharply outlined
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atcwong 4May07 Respiratory Cytology
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Single or multiple prominent nucleoli are frequent
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Likely to have some features suggesting adenoCa
Small cell carcinoma (20% of all lung cancers)

Highly aggressive, hormone-secreting

Neuroendocrine cytoplasmic granules identifiable under EM

Unlike carcinoids, they are believed to arise from epithelial cells

Loosely arranged clusters of small cells of variable sizes, somewhat larger than lymphocytes

Nuclear molding is characteristic, pyknosis is frequent

Very scanty basophilic cytoplasm

Tumor necrosis is common, producing streaks of nuclear materials

More viable cells may exhibit tiny nucleoli

Sometimes specimen looks salivary
Source of diagnostic error for small cell carcinoma (SSC)

Reserve cell hyperplasia

Pools of lymphocytes
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Small cell adenocarcinoma

Lymphoma

Carcinoid

Other small cell tumors

Inspissated mucus
Adenocarcinoma (now more common than SCCs)

Clearly associated with cigarette smoking

Better response by surgical treatment, compared to small cell Ca

Large round, polygonal and occasionally columnar cells in clusters or singly

Cytoplasm usually basophilic, faintly staining and finely to coarsely vacuolated, may be scant or moderate amount

Nuclei are large, finely granular chromatin and slightly to moderately hyperchromatic

Often with single or multiple prominent nucleoli
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Multinucleation is common

Papillary clusters may be seen and can help securing the dx of adenoCa
Source of diagnostic error for primary lung adenocarcinoma

Creola bodies

Atypical bronchial cells, e.g., post-bronchoscopy, atypical pneumocyte II
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Goblet cells in clusters
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Viral cytopathic changes
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Pemphigus
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Reactive mesothelium
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atcwong 4May07 Respiratory Cytology
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Mucoepidermoid CA
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Metastatic adenoCa
Bronchioloalveolar Carcinoma (BAC)

Treatment effective by special molecular-based chemotherapy

Arise in bronchiolar or alveolar epithelium (type II pneumocyte) of peripheral lung tissue

Well-demarcated, round, or papillary clusters of tumor cells

Clusters composed of overlapping small, round, or roughly cuboidal cells with scant clear cytoplasm

Nuclei moderately hyperchromatic with one or two small nucleoli, with limited pleomorphism

Isolated cancer cells are few and difficult to identify
Source of diagnostic error for BAC

Hyperplastic benign bronchial cell clusters (Creola bodies) from bronchiectasis, asthma, etc

Busulfan-treated patients

Other metastatic adenoCa with similar cytological features as BAC
Adenosquamous carcinoma

Bronchogenic carcinomas with both epidermoid and glandular differentiations. Mucin and keratin are demonstrable
in major part of the tumor
Mucoepidermoid carcinoma (0.2% of lung cancers)

Squamous cancer cells in majority while there are interspersed mucinous glands or single mucin-secreting cells
Carcinoid tumor

Occur in adults, unrelated to cigarette smoking

Cells secrete serotonin and other polypeptide hormones, chromogranin-postive, reluctant to exfoliate, better yield
after bronchoscopy

Composed of nests, rosettes, or ribbons of tightly packed, quite regular, small, polyhedral cells

Variants: spindle cells, oncocytic cells

Cells, 15-20 microns, are typically dispersed or in small clusters, variably cuboidal and rectangular, with faint
basophilic cytoplasm, nuclei are uniform and eccentric, giving a plasmacytoid appearance

Monotony of nuclear size, uniform “salt & pepper” chromatin pattern, and absence of necrosis are characteristics

Atypical carcinoids are more malignant in behavior as well as in morphology.
Rare lung tumors

Adenoid Cystic Carcinoma

Blastomas

Sarcomas, fibrous histiocytoma

Lymphomas

Melanoma
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