CONTENT:
6.3 Lung Cancer Cytology
6.3.1 Lung Samples for Cytology
i. Sputum
ii. Bronchial Brushings and Washings
iii. Broncho-alveolar Lavage (BAL)
iv. Fine Needle Aspiration (FNA) Cytology
6.3.2 Sensitivity of Lung Cytology
6.3.3 Diagnostic Categories for Reporting Lung Cancer Cytology
6.4 Histological Examination of Lung Tissue
Forward to 6D Diagnosis and Guidelines. Back to 6B Lung Sampling for Diagnosis
6.3 Lung Cancer Cytology
Cytology samples are usually obtained during bronchoscopy and are called ‘bronchial brushings’ and ‘bronchial washings.’ Cytology samples may also be obtained during endobronchial ultrasound (EUS) examination. These samples fixed in alcohol or acetone, spun down, smeared onto a glass slide and stained with histochemical dyes (PAP, H&E or modified Giemsa) to allow the cells to be analyzed using light microscopy.
Figure 6.3 Lung Cancer Cytology.
A. Photomicrograph of lavage fluid shows irregular, large cells,
some with foamy and vacuolated cytoplasm. This is a non small
cell carcinoma, with features of adenocarcinoma. B. Photomicrograph
of a sputum cytology sample shows malignant cells (blue) with keratin
formation (orange) consistent with squamous cell carcinoma.
C. Photomicrograph of the cytology of bronchial brushings shows
cohesive, small malignant cells with little cytoplasm, consistent with
small cell carcinoma. (PAP x 60)
6.3.1 Lung Samples for Cytology
i. Sputum
Sputum for cytology is obtained as ‘spontaneous’ or ‘induced’ samples. Sensitivity for diagnosis of lung cancer increases with the ‘adequacy‘ of the samples; usually between 3 to 5 samples are necessary. A minimum of 2 smears per sample are prepared.
ii. Bronchial Brushings and Washings
Sensitivity of the bronchoscopic samples for diagnosing bronchogenic lung cancer is dependent on the experience and skill of the endoscopist; it can be similar to the sensitivity of a bronchial biopsy.
Bronchial washings and brushings can either be prepared on-site and fixed with alcohol or the brush can be rinsed in cytology fixative.
iii. Bronchiolo-alveolar Lavage (BAL)
Bronchiolo-alveolar lavage (BAL) is used to assess the contents of the terminal airspaces.
iv. Fine Needle Aspiration (FNA) Cytology
Fine needle aspiration (FNA) cytology is performed for the evaluation of localized pulmonary lesions and mediastinal sampling in the context of lung cancer.
The techniques used include transthoracic percutaneous FNA, transtracheal/transbronchial FNA, endobronchial ultrasound-assisted needle aspiration (EBUS-FNA) or endoscopic ultrasound-assisted FNA (EUS-FNA) (performed via the esophagus).
The cytology specimens are splint into 3 groups for microbiology, flow cytometry, cell blocks or smears.
Air-dried slides with ‘Diff-Quik’ cell staining are used for rapid on-site evaluation. Some slides may also be fixed with an alcohol solution and stained with H&E or Papanicolaou (PAP) stain.
6.3.2 Sensitivity of Lung Cytology
Published studies by the College of American Pathologists (CAP) have shown that the sensitivity of FNA lung cytology for the diagnosis of lung cancer ranges from 50 % to more than 90 %. The specificity is close to 100%. The ‘false positive’ rate is less than 1%, and the ‘false negative’ rate (usually due to poor sampling) is approximately 10%.
Sensitivity
Sputum:
Central tumors 71%
Peripheral tumors 49%
Bronchial Brushings:
Endobronchial tumors 59%
Peripheral tumors 52%
Bronchial Washing/Lavage:
Endobronchial tumors 48%
Peripheral tumors 43%
Transthoracic FNA 90%
6.3.3 Diagnostic Categories for Reporting Lung Cancer Cytology
Cytology samples can be preserved and prepared for light microscopy quite quickly. For reporting of the cytology findings, the following diagnostic criteria is useful:-
i. Unsatisfactory/Non-Diagnostic
If the specimen if of low cellularity, contains a lot of blood, or the cells are not well preserved a differential diagnosis may not be possible.
ii. Benign/Non-Malignant
For a benign (non malignant) diagnosis, a cytology sample must be satisfactory (adequate) for evaluation.
iii. Atypical
This classification is for cells that are not clearly benign or malignant and show cells that carry likelihood of malignancy. Definitive diagnosis may not be possible in such cases due to lack of clear cellular morphological features, few cells, obscuring blood and poor cell preservation.
iv. Suspicious for Malignancy
The cellular appearances strongly favor cancer, but the morphological appearances or the low cellularity prevent a definitive diagnosis.
iv. Malignant
Because of its high specificity, a malignant cytological diagnosis is a definitive diagnosis. However, a malignant diagnosis only occurs when there are definitive morphological features in a satisfactory and optimal specimen. The diagnosis of malignancy should always be further qualified, if possible.
6.4 Histological Examination of Lung Tissue
Lung tissue from a biopsy procedure is sent to the Pathology Laboratory. The lung tissue is received and described by the Pathologist, who selects small pieces for further examination.
Firstly, in preparation, fixatives or preservatives, such as formalin, set the lung tissue samples. Secondly, paraffin wax is used to embed the lung tissue samples. Thirdly, the lung tissue samples are cut into thin slices and placed on glass slides. Finally, the thin tissue sections are stained with ‘histochemical’ cell dyes. The dye allows for assessment of cells and tissues under the microscope. The process of tissue fixation, processing, sectioning and histochemical staining takes at least 24 hours to complete.
Finally, at the end of the processing techniques, the lung tissue samples can be stored for years. Thus the samples are available for sectioning and examination again, as formalin-fixed, paraffin-embedded (FFPE) samples.
References:
Böcking A, Klose KC, Kyll HJ, Hauptmann S. (1995). Cytologic versus histologic evaluation of needle biopsy of the lung, hilum and mediastinum. Sensitivity, specificity and typing accuracy. Acta Cytol. 39(3), 463. (Retrieved 19th Feb 2015). http://www.ncbi.nlm.nih.gov/pubmed?term=7762333
Hammar SP. (2006). Macroscopic, histologic, histochemical, immunohistochemical, and ultrastructural features of mesothelioma. Ultrastruct Pathol. 30(1), 3. (Retrieved 10th Feb 2015): http://informahealthcare.com/doi/abs/10.1080/01913120500313143
Patient Information:
Cancer.Net Lung Cancer: Diagnosis (Retrieved 26th April 2015): http://www.cancer.net/cancer-types/lung-cancer/diagnosis
Patient UK Lung Cancer (Retrieved 26th April 2015): http://www.patient.co.uk/doctor/lung-cancer-pro
Forward to 6D Diagnosis and Guidelines. Back to 6B Lung Sampling for Diagnosis