Respiratory disorders Flashcards
Features of Adenocarcinoma
- These are tumours of glandular epithelium that normally arise in the peripheries of the lungs I.e. the terminal bronchioles and may have a pre-neoplastic stage (Atypical adenomatous hyperplasia).
- Commonest type of cancer in non-smokers
- They are slow growing but metastasis tends to occur early.
- Have several types on morphology such as lepidic predominant, acinar, papillary and mucinous
- Mutations are associated with EGFR, ALK, BRAF and KRAS genes
Features of squamous cell carcinoma
- This the most common type of cancer in smokers
- They are usually found in the centre of the lungs, especially in the hilar or large bronchus but may spread into the tracheal, bronchial and mediastinal nodes
- Arises from squamous metaplasia in the basal cells which leads to carcinoma in situ and eventually infiltrative carcinoma
- They are fast growing and large lesions may become necrotic causing cavitations
- These tumours may release parathyroid hormone related protein causing hypercalcaemia
- On histological section, well-differentiation tumours show keratinisation and intercellular bridges but poorly differentiated tumours loose these characteristic features
Features of small cell carcinoma
- This is an aggressive tumour that arises from neuroendocrine cells
- They tend to arise in the hilum or centrally
- They may produce hormones leading to paraneoplastic syndrome
- They are aggressive and fast growing
- On histology the cells form clusters. They have scant cytoplasm, ill-defined cell borders, absent or inconspicuous nucleoli. Nuclear moulding and necrosis is common
- They are chromogranin A positive when stained with immunohistochemistry
Features of large cell carcinoma
These are poorly differentiated and rapidly growing tumours without evidence of squamous, glandular or neuroendocrine differentiation.
• They arise peripherally or centrally
• On histology the cells are dyscohesive with loss of pattern
• Large pleomorphic cells with abundant cytoplasm, nuclei is dense and irregular with prominent nucleoli.
How is a wedge resection specimen treated in gross laboratory and what sections are taken?
- Check the patient identification on the container match the demographics on the request form. Look at the patient history to see what needs to be looked out for and the sections that need to be taken.
- Document the type of specimen, resection type and location from where it was taken
- Take measurements of the specimen (height, length and width) and give a description of the pleural surface. Note any areas of puckering, haemorrhage and necrosis.
- Remove staples from the parenchymal resection margins and ink this margin to see extent of tumour microscopically
- Palpate the section to identify the mass present
- Dissect the section perpendicular to the resection margin into thin section and describe the observations, including the lesions (e.g. well-circumcised white lesion observed).
- Describe the tumours relationship with the pleural surface, resection margin as well as vascular and bronchi margin if present. Measure each one from the tumour edge.
- Palpate each section and look for any small lesions and lymph nodes
- Submit sections of the tumour and normal lung for diagnosis, and the tumour relationship with pleural surface, resection margin, vascular and bronchi margin. Also submit sections from areas of puckering and any other abnormalities such as emphysema and any lymph nodes identified.
- Its important to give a description of each section placed in the cassette and the number of lymph nodes so that they can be checked they match the microscopic description.
- A 71-year-old non-smoker female went to her general practitioner in view of cough and shortness of breath. On further questioning the patient told the doctor that she had lost weight unintentionally and has loss of appetite. A plain chest radiograph was performed and revealed a lesion in the lower aspect of the right lung, associated with a right pleural effusion. In a computed tomographic (CT) scan of the chest the patient was found to have a tumour in the lower lobe of the right lung, located at the periphery and this was associated with a right pleural effusion. The patient underwent a transthoracic biopsy of the lesion and a sample of his pleural effusion was taken for analysis. The effusion was found to contain atypical cells and the biopsy showed an invasive tumour that consisted predominantly of well-formed neoplastic glands lined by atypical cells in a desmoplastic stroma. In view of this, a lung lobectomy was performed. The histopathology description confirmed the tumour that had been previously reported on the biopsy with lymphovascular invasion and one the lymph nodes contained tumour but the tumour was otherwise completely excised.
a) Mention the major different types of lung tumours. (2 marks) Which one is it most likely to be in this case and why? (2 marks)
b) What is a transthoracic lung biopsy and why was this the preferred method of sampling the lesion? (2 marks)
c) In which laboratory was the sample of fluid from the pleural effusion submitted? (1 mark) How does this differ from a core biopsy? (3 marks)
a) Adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell carcinoma
• In this case the patient most likely has Adenocarcinoma as it’s the most common lung cancer in non-smokers. In addition, the tumour is found in the periphery as this type of tumour typically arises hear from glandular cells of the terminal bronchi and histology showed neoplastic glands which is the cells from where adenocarcinoma originates.
b) A Transthoracic lung biopsy is a biopsy taken from the lung through the thoracic cavity which is the most preferred method for peripheral lesions as it has the highest sensitivity and specificity. Sputum cytology although non-invasive it is difficult to obtain sputum from peripheral lesions, but it is less invasive than an open lung biopsy. Moreover, it is generally preferred over FNA since the architecture is preserved with this method.
c) Cytology
What is a lung lobectomy specimen? (1 mark) In general how is this resection specimen treated in the gross laboratory and what important sections are taken? (7 marks)
A lobectomy is a resection a whole lobe of the lung.
- Check the patient identification on the container match the demographics on the request form. Look at the patient history to see what needs to be looked out for and see if findings correlates with clinical picture, including CT scan etc.
- Document the type of specimen, resection type and why this method was chosen, location from where it was taken
- Take measurements of the specimen (height, length and width) and give a description of the pleural surface. Note any areas of puckering, haemorrhage and necrosis
- Palpate the specimen to locate any lesions and document its location (central or peripheral).
- Dissect the airways and give a description of the mucosa and sample the regional lymph nodes, hilar lymph nodes and other peribronchial lymph nodes. It’s important to document the number of lymph nodes and site on the request form.
- Dissect the specimen according to the location of the tumour.
- The abnormalities or lesions observed are described e.g. well-circumcised white lesion observed. Any tumour-margin distances are also measured – from the pleural surface, parenchymal resection margin, vascular and bronchi margins.
- The tumours relationship with the pleural surface, resection margin as well as vascular and bronchi margin are measured and documented.
- Take sections of:
- tumour and normal lung for diagnosis and
- tumour relationship with pleural surface, resection margin, vascular and bronchi margin.
- Also submit sections from areas of puckering and any other abnormalities such as areas of inflammation.
- If the specimen is a pneumonectomy a section of the hilar node is taken.
e) One of the lymph nodes was found to have tumour. What does this imply? (1 mark) How does it relate to lymphovascular invasion? (2 marks)
This indicates that there is lymph node metastasis, which means that there was lymphovascular invasion by the tumour which lead to tumour cells taken to lymph node leading to this metastasis.
f) This tumour is well-differentiated. What part of the histopathology report implies this? (2 marks)
‘well-formed neoplastic glands’ indicates that the tumour is well-differentiated as glands are formed.
g) In a tumour that cannot be clearly diagnosed on microscopy, what other laboratory techniques can help differentiate between the different types? (2 marks)
Immunohistochemistry using immunostains to differentiate between the origin of the malignancy cells. . p63, CK5/6 and TTF-1 are useful ancillary tools that help differentiation squamous cell lung carcinoma from adenocarcinoma. SSC is positive with p63 and C5/6 while adenocarcinoma shows TTF1 expression.
Molecular studies - next generation sequencing of specific gene panels for lung cancer, however, this is more commonly used for determining therapy. E.g. Adenocarcinoma is associated with KRAS, EGFR and ALK mutations while Squamous cell carcinoma is associated with Del 3p
a. The use and rationale behind the use of immunohistochemistry on core biopsies from a lung lesion whose histology shows a well-differentiated adenocarcinoma. (7 marks)
The lung has an abundant vascular supply and receives blood from all areas of the body, therefore, the lung is a common site for metastasis especially through the haematogenous spread. Common malignancy that metastasis to the lung include gastrointestinal, breast, gynaecological, urologic and thyroid carcinomas. Most of these cancers that arise in these sites are also of glandular origin (Adenocarcinoma), therefore, immunohistochemistry is used to confirm that the cancer is of primary origin (from the lung) and not metastatic. Markers that confirm primary lung cancer include Cytokeratin (CK) 7, thyroid transcription factor-1 (TTF-1), Napsin A and CK20.
• CK-7 a marker for lung adenocarcinoma - however, this is not specific and is positive for other sites
• Thyroid transcription factor-1 (TTF-1) is positive in lung and thyroid adenocarcinoma
• Napsin A is more sensitive than TTF-1 but it is also positive in lung adenocarcinoma
• CK20 is a marker for colorectal carcinoma which is the common cancer than metastasises to the lungs, thus it is often used.
b. The need for clinical and radiological correlation in a lung lesion whose histology shows squamous cell carcinoma. (7 marks)
Squamous cell carcinoma is associated with smoking and often arises in the central region of the lung. These features are important for confirmation because a poorly-differentiated primary tumour can be an adenocarcinoma and if this is misdiagnosed it will lead to incorrect treatment given. Adenocarcinoma usually arise peripherally and is not associated with smoking. In addition metastasis of squamous cell carcinoma from other organs or tissue into the lungs can also be distinguished and warrant further investigations based on the clinical and radiological history of the patient. Metastasis to the lung can appear anywhere and is not associated with smoking.
c. The meaning of tumour grading using squamous cell carcinoma of the lung as an example. (6 marks)
Tumour grading is based on the morphology of the tumour, the degree of differentiation is an important observation when assessing the aggressiveness of the tumour. A grade 1 tumour is a well-differentiated tumour, in case of squamous cell carcinoma there is the presence of keratinocytes and intercellular bridge, grade 2 has less keratinisation and may lack intercellular bridge while grade 3 is poorly differentiate carcinoma, in case of squamous cell carcinoma there is no or very scant keratinisation and minimal squamous cell features.
d. What is a ‘precursor lesion of lung tumour’? Give one example. (5 marks)
A precursor lesion of the lung means that there pre-malignant cells present in the lung. These pre-malignant cells have genetic mutations giving them atypical or dysplastic appearance, thus they have features such as pleomorphism, increased nucleus to cytoplasm ration, loss of polarity but they are not malignant yet. These lesions are common in smokers and have an increased risk of developing into carcinoma but it cannot be predicted if they will or not. An example is squamous dysplasia and carcinoma in situ which can lead to squamous cell carcinoma.
- How is an FNA processed in the laboratory
a. A drop of the aspirate is placed on three slides – two of the slides are air dried and one is fixed with 95% ethanol.
b. The slide fixed in ethanol is stained with Papanicolaou stain
c. The slide that is air-dried is stained with may-grunwald giemsa stain, the other slide is left for additional staining if needed.
d. The needles is rinsed in saline to obtain the rest of the aspirate and a cellblock can be prepared and sent to histology for processing. This can be stained with Haematoxylin and Eosin (routine stain) or immunohistochemistry for better diagnosis.
Sample is centrifuged, and supernatant is removed
To the cell deposit, add a few drops of plasma and mix for a few seconds by a vortex mixer.
Add an equal number of Thrombin Reagent and mix for a few seconds by a vortex mixer.
Leave the mixture on a hot plate.
A coagulum will form at the bottom of the tube after 10-20 seconds.
By gentle tapping of the tube, the coagulum is detached and placed in a container with 10% formaldehyde solution.
The coagulum is left to fix for 24 hours and processed as a tissue section.
