Pathology of Lung Cancer (Pulmonary Neoplasia)

Question 1

Types of lung neoplasms?

Answer 1

1. Primary:
   Benign - rare in lung cancer; assume all neoplasms in lungs are malignant
   Malignant - very common
2. Metastatic - very common

Question 2

Risk factors of lung cancer?

Answer 2

Tobacco smoke
Asbestos
Nickel
Chromates
Radiation
Atmospheric pollution
(genetics)

Question 3

Local effects of lung cancer?

Answer 3

Obstruction of airway (pneumonia)
Invasion of chest wall (pain)
Ulceration (haemoptysis)
Cavitating tumours (all do this but SCC in part.)

Question 4

Where does lung cancer commonly metastasise to?

Answer 4

Lymph nodes (neck and mediastinal lymph nodes are commonly affected)
Bones
Liver
Brain

Question 5

Systemic effects of lung cancer?

Answer 5

Weight loss
“Ectopic” hormone production:
Parathyroid hormone (PTH) in squamous cancer (presents as hypercalcaemia)
ACTH in small cell cancer

Question 6

Classification of lung tumours?

Answer 6

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

Question 7

Describe squamous carcinoma

Answer 7

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

Question 8

Describe adenocarcinoma

Answer 8

Gland forming

Can be with mucin (blue stained)

Question 9

Describe appearance of small cell carcinoma

Answer 9

Large nuclei, little cytoplasm

Question 10

Describe appearance of large cell carcinoma

Answer 10

Different

Question 11

Why is classification of cancer important?

Answer 11

For:
Prognosis
Treatment 
Pathogenesis/biology
Epidemiology

Question 12

Prognosis of different lung cancers?

Answer 12

Small cell is worst (almost all dead in one year after diagnosis)
Large cell worse than squamous or adenocarcinoma

Question 13

Most simple classification of lung cancer?

Answer 13

Small cell lung cancer (SCLC)

VS

Non-small lung lung cancer (NSCLC)

Question 14

Treatment of different types of lung cancer?

Answer 14

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)

Question 15

Describe immunohistochemistry in NSCLC

Answer 15

Adenocarcinoma expresses Thyroid Transcription Factor (TTF)

Squamous cell cancer expresses nuclear antigen p63 and high molecular wt. cytokeratins

Question 16

Molecular genetic abnormalities in different types of lung cancer and their importance?

Answer 16

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

Question 17

Epithelial growth signalling in normal lung epithelium?

Answer 17

Epidermal Growth Factor (EGF) binds to EGF receptor (EGFR)

Causes activation of the RAS pathway and transcription of myc occurs

Question 18

Epithelial growth signalling in cancer?

Answer 18

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

Question 19

Targeted treatment of cancer?

Answer 19

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)

Question 20

Pathogenesis types of pulmonary epithelium?

Answer 20

Bronchial:
Ciliated, mucous, neuroendocrine, reserve

Bronchioles/alveoli:
Malignant clara cells (normally protect the broncheolar epithelium)
Malignant types 1 and 2 alveolar lining cells

Question 21

Pre-invasive metaplastic changes in bronchial (large airway) tumours?

Answer 21

Squamous metaplasia
Dysplasia (not yet invaded)
Carcinoma in-situ

Invasive malignancy

Question 22

What occur in basal cell hyperplasia?

Answer 22

Basal membrane thickens

Question 23

Describe peripheral adenocarcinomas

Answer 23

Atypical adenomatous hyperplasia
Spread of neoplastic cells along alveolar walls (bronchoalveolar carcinoma)
True invasive adenocarcinome

Pattern is become more common

Question 24

Prognostic indicators in lung cancer?

Answer 24

Tumour stage (TNM staging - Tumous Nodes Metastasis)
Tumour histological sub-type

Question 25

Other lung carcinomas?

Answer 25

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

Question 26

Describe pleural neoplasia

Answer 26

Benign tumours are rare

Primary malignant neoplasm - mesothelioma

Also, a common site of invasion by lung carcinomas and metastatic cancers