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Pulmonary Pathology Online

Cytological Pitfalls in the Diagnosis of Lung Cancer

Dr Sampurna Roy MD




The sensitivity for malignancy diagnosis by exfoliative cytology methods ranges from 50-85% for sputum examination, depending on whether the lesion is peripheral or central, and is 70% and 90% for peripheral and central lesions respectively using bronchial brushings and washings.

FNA sensitivity is usually higher [80-95%] depending on the experience of the radiologist and pathologist and on the size and location of the tumor.

Ample sampling of material, which is well fixed and stained , should minimize false positive diagnoses.

A full clinical history is always essential.

Pitfalls in the cytological diagnosis of lung cancer: 

                                                         Diagnosis             Pitfall           Pitfall findings
Sputum Squamous cell carcinoma   
Squamous metaplasia 




Carcinoma in situ
Cohesive groups ; Less keratinization; Less nuclear abnormality ; No necrosis;


Difficult/impossible; Less dissociation; Fewer abnormal cells ; Absence of necrosis.


Bronchioloalveolar Cell Carcinoma                            


Reactive bronchial epithelium.

Eg:  Asthma  with Creola bodies, post bronchoscopy etc      

Fewer cell groups, transient finding ciliated borders in some groups. Clinical details.


Sputum Non small cell carcinoma Drug and chemotherapy effects   Lesser nuclear changes, fewer cells Clinical details


Sputum Small cell carcinoma     Lymphocytes/lymphoma    Cell dissociation, Monotonous population; Nucleoli visible; No moulding ; “lymphoid” chromatin



     Diagnosis    Pitfall  Pitfall findings
Brushing/ Washings Squamous cell carcinoma Metaplasia/in situ squamous carcinoma         


Cohesive cell groups ; Layered microbiopsies with an anatomical border.


Brushing/ Washings Adenocarcinoma

Non small cell carcinoma

Reactive bronchial epithelium/ repair changes Fewer cell  groups Nuclei pleomorphic, Not malignant ; Inflammation but no true necrosis.


Brushing/ Washings Non-small cell carcinoma Small cell carcinoma Reduced cytoplasm; Nuclear moulding ; Nuclear spreading artifact, Coarse granular chromatin.


Brushing/ Washings  Small cell carcinoma Carcinoid tumor Regular round or elliptical nuclei ; No moulding ; Visible nucleoli  ; Scanty delicate cytoplasm.




     Diagnosis    Pitfall  Pitfall findings
FNA Squamous cell carcinoma Necrosis simulating keratinization.

Eg. rheumatoid granuloma, infection.

Absence of preserved malignant cells. Gram, ZN, Grocott stains.


FNA Adenocarcinoma 

[primary or metastatic]

Bronchioloalveolar cell carcinoma Smaller more regular cells, Intranuclear cytoplasmic inclusions ; Clinical details.


FNA Bronchioloalveolar cell carcinoma Carcinoid tumor

Pink granules in delicate cytoplasm; Palisades, rosettes; Many bare nuclei; Capillary vessels; Immunostaining.


FNA Non-small cell carcinoma Small cell carcinoma Coarsely granular, Chromatin, Nuclear crush artifact, Minimal cytoplasm.


FNA Small cell carcinoma
Squamous carcinoma: small cell variant
Atypical carcinoid tumor
More cytoplasm, denser, More cohesion, No moulding.

Non-smoker "Neuro endocrine" nucleus, Architectural features, vessels.

FNA Spindle cell carcinoid Other spindle cell tumours  

Marked pleomorphism ; Dense cytoplasm   Immunostaining.


Further reading:

Diagnostic dilemmas in pulmonary cytology.

Small cell carcinoma versus other lung malignancies: diagnosis by fine-needle aspiration cytology.

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients.



Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)







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