Pathology of Lung Cancer (Pulmonary Neoplasia) Flashcards
Types of lung neoplasms?
- Primary:
Benign - rare in lung cancer; assume all neoplasms in lungs are malignant
Malignant - very common - Metastatic - very common
Risk factors of lung cancer?
Tobacco smoke Asbestos Nickel Chromates Radiation Atmospheric pollution (genetics)
Local effects of lung cancer?
Obstruction of airway (pneumonia)
Invasion of chest wall (pain)
Ulceration (haemoptysis)
Cavitating tumours (all do this but SCC in part.)
Where does lung cancer commonly metastasise to?
Lymph nodes (neck and mediastinal lymph nodes are commonly affected)
Bones
Liver
Brain
Systemic effects of lung cancer?
Weight loss
“Ectopic” hormone production:
Parathyroid hormone (PTH) in squamous cancer (presents as hypercalcaemia)
ACTH in small cell cancer
Classification of lung tumours?
Very heterogeneous
4 common smoking-associated types: Adenocarcinoma (most common - 35%) Squamous carcinoma (30%) Small cell carcinoma (most aggressive - 25%) Large cell carcinoma (10%)
Neuroendocrine tumours
Bronchial gland tumours
Describe squamous carcinoma
Disordered, malignant growth of squamous, epithelial cells; these tumours tend to be central and are the ones that most commonly cavitate
Due to to secretion of PTH, hypercalcaemia can occur
Describe adenocarcinoma
Gland forming
Can be with mucin (blue stained)
Describe appearance of small cell carcinoma
Large nuclei, little cytoplasm
Describe appearance of large cell carcinoma
Different
Why is classification of cancer important?
For: Prognosis Treatment Pathogenesis/biology Epidemiology
Prognosis of different lung cancers?
Small cell is worst (almost all dead in one year after diagnosis)
Large cell worse than squamous or adenocarcinoma
Most simple classification of lung cancer?
Small cell lung cancer (SCLC)
VS
Non-small lung lung cancer (NSCLC)
Treatment of different types of lung cancer?
Small cell known to be most chemosensitive but with rapidly emerging resistance
SURGERY IS THE TREATMENT OF CHOICE IN OTHER TYPES
Non-small cell regimens have also been developed in chemotherapy/radiotherapy
New developments in chemotherapy include differing NSCLC regimens for squamous cells and adenocarcinoma (e.g: pemetrexed contraindicated in squamous carcinoma); but often difficult in sub-typing tumours in small biopsies (immunochemistry can help)
Describe immunohistochemistry in NSCLC
Adenocarcinoma expresses Thyroid Transcription Factor (TTF)
Squamous cell cancer expresses nuclear antigen p63 and high molecular wt. cytokeratins
Molecular genetic abnormalities in different types of lung cancer and their importance?
Are POTENTIAL THERAPEUTIC AGENTS:
Oncogenes:
SCLC - myc
NSCLC - myc, K-ras, her2(neu)
Tumour suppressor genes:
SCLC - p53, Rb, 3p
NSCLC - p53, 1q, 3p, 9p, 11p, Rb
Epithelial growth signalling in normal lung epithelium?
Epidermal Growth Factor (EGF) binds to EGF receptor (EGFR)
Causes activation of the RAS pathway and transcription of myc occurs
Epithelial growth signalling in cancer?
MAPK/ERK pathway (cancer associated lesions in the ERK signalling pathway)
In most carcinomas, the EGFR is OVER-EXPRESSED (specific point mutations render EGFR gene active even in the absence of EGF binding) :
There is a RAS mutation and BRAF mutation so mys is not transcribed properly
Targeted treatment of cancer?
Mutations in EGFR can be identified in DNA extracted via a biopsy/cytology samples
This mutation is seen almost exclusively in ADENOCARCINOMA (esp. in non-smokers and Asian population)
These tumours respond to TYROSINE KINASE INHIBITORS (e.g: Erlotinib); these are relatively non-toxic
EML4-ALK oncogene also identifies a target for specific drug treatment (Crizotinib)
Pathogenesis types of pulmonary epithelium?
Bronchial:
Ciliated, mucous, neuroendocrine, reserve
Bronchioles/alveoli:
Malignant clara cells (normally protect the broncheolar epithelium)
Malignant types 1 and 2 alveolar lining cells
Pre-invasive metaplastic changes in bronchial (large airway) tumours?
Squamous metaplasia
Dysplasia (not yet invaded)
Carcinoma in-situ
Invasive malignancy
What occur in basal cell hyperplasia?
Basal membrane thickens
Describe peripheral adenocarcinomas
Atypical adenomatous hyperplasia
Spread of neoplastic cells along alveolar walls (bronchoalveolar carcinoma)
True invasive adenocarcinome
Pattern is become more common
Prognostic indicators in lung cancer?
Tumour stage (TNM staging - Tumous Nodes Metastasis) Tumour histological sub-type
Other lung carcinomas?
Carcinoid - neuroendocrine neoplasms of low grade malignancy (can occur in all ages/non-smokers); more homogeneous cells with lower mitotic index
Bronchial gland neoplasms - tumours more often seen in salivary glands:
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Describe pleural neoplasia
Benign tumours are rare
Primary malignant neoplasm - mesothelioma
Also, a common site of invasion by lung carcinomas and metastatic cancers
