ACP L20 Pathology of lung and pleural tumors Flashcards
Give examples of local clinical features of lung cancer. (5)
- Cough
- Hemoptysis
- Obstructive pneumonia
- Compression effect: SVCO, Pancoast tumor
- Pleural effusion
Patient with severe shoulder pain radiating to axilla and scapula, atrophy of hand and arm muscles.
Ptosis, miosis, and enophthalmos spotted.
CXR showed edema.
DDx?
Pancoast tumor
- affects brachial plexus, cervical sympathetic nerves, Horner’s syndrome
- Compression of blood vessels with edema
Lung cancers cause systemic presentations such as constitutional symptoms (weight loss, LOA, cachexia, LG fever).
List paraneoplastic syndromes that are more common in SQCC, SCLC. (3)
- Neurological
- common in SCLC, e.g. Lambert-Eaton myasthenic syndrome (proximal muscle weakness) - Endocrine
- Cushing’s syndrome, SIADH, hypercalcemia of malignancy
- in SQCC but not in SCLC
- oncogenic osteomalacia - Rheumatological
- hypertrophic osteoarthropathy
- dermatomyositis
Most common metastases of lung cancer? (2)
- To bone - pathological fracture
2. To brain - seizures, neurological manifestations
How do we classify lung cancers?
- Primary
a) Small cell lung carcinoma (SCLC)
b) Non-small cell carcinoma (NSCLC)
- squamous cell carcinoma
- adenocarcinoma
- large cell carcinoma
- adenosquamous carcinoma
- Secondary
- Metastasis
Which lung cancer has the weakest association with smoking and happens most frequently in young female non-smokers?
- It is also the MC primary lung Ca
Adenocarcinoma
Comment on the glandular differentiation (gross + microscopic) of adenocarcinoma of the lung. (2)
Also state histochemical findings and immunohistochemical findings. (2)
Glandular differentiation
- gross: acinar (forming gland), with multiple patterns in a single tumor
- microscopic: mucin content
Histochemical: mucin stain
IHC: lung markers
A 75 years-old smoker, complained of productive cough, on-and-off fever and weight loss for 4 months.
PE revealed diminished inspiration and crepitation of his right chest. CXR suggested collapsed right middle lobe and haziness at the right central region.
What is the most likely histologic type of lung CA and why? (2)
(Primary) Squamous cell carcinoma.
- Elderly male smoker
- Malignancy match with cachexia and weight loss
- Location matches with the clinical picture
- central/peri-hilar lesion
- obstruction to distal bronchi
- collapse/obstructive pneumonia
What is the usual location for adenocarcinoma of the lungs?
From peripheral to central
For squamous cell carcinoma of the lungs, comment on the squamous differentiation (gross + microscopic) (2).
Also comment on the IHC findings of the course of developement. (3)
Squamous differentiation:
- Gross: keratinization
- Microscopic: intracellular bridges
IHC
- Squamous metaplasia > dysplasia > carcinoma
Small cell lung carcinoma of the lungs is strongly associated with smoking and is usually _________located.
What are the histological features of SCLC?
Centrally;
- “Small cell = oat cell”: moulding of nuclei + scanty cytoplasm
- Hyperchromatic nuclei
- Fine chromatin
- Inconspicuous (not prominent) nucleoli
- Frequent mitotic figures and apoptotic bodies
- Azzopardi effect: hematoxyphilic vascular walls
Chromogranin and synaptophysin are NE (neuroendocrine) markers that would be IHC +ve in __________ tumors? What prognosis?
Small cell lung carcinoma
- Poor prognosis
For Adenocarcinoma in situ, there can be single/multiple lesions <3cm, without any invasion.
What can be seen on CXR and what is its prognosis?
CXR:
- Ground glass appearance: spread along the wall without invading airway
Excellent prognosis
Minimally invasive adenocarcinoma is a single lesion <3cm with <5 mm of stromal invasion (lepidic pattern) without lymphatic vessels, blood vessels or __________ invasion.
What can be seen on CXR? Prognosis?
pleural invasion
- Ground glass appearance with central opacity
Excellent prognosis
How is large cell lung carcinoma diagnosed?
Diagnosed by exclusion: NSCLC lacking morphologic differentiation of adenocarcinoma/ SQCC
Carcinoid tumor of the lung accounts for 10% of all carcinoid tumor and is only 1% of all lung tumors.
It can be classified into typical (benign) and atypical (may be malignant).
What histological features? (2)
- Organoid pattern
2. Neuroendocrine features (+ve for NE markers, neuro-secretory granules)
The lung is a common site for metastasis.
List possible primary sites in order. (3)
Breast > Colon > RCC
For metastasis to the lungs, which 2 types of spread is possible and how do they differ in the presentation? (4)
- Hematogenous spread
- multiple cannon ball lesions
- distributed diffusely in the lung parenchyma - Lymphatic spread (lymphangitis carcinomatosis)
- peripheral (interlobular septum, pleural surface)
- central (bronchoalveolar interstitium)
What is a synchronous tumor and a metachronous tumor? (2)
How to differentiate them from others. (2)
Synchronous tumor: multiple primary tumors
Metachronous tumor: new primary tumor after surgery
Synchronous VS intra-pulmonary metastasis
Metachronous tumor VS metastasis after surgery
- differentiated by both pathological + radiological evidence
Pleural mesothelioma risk factor?
- Extensive pleural fibrosis
- Plaque
- Mesothelioma
Exposure to asbestos, with delayed presentation (25-40 latent years)
Clinical presentations in patients with pleural mesothelioma? (3)
- Pleural effusion
- Symptoms due to compression, i.e. SVCO, Pancoast tumor
- Relentless local spread, but metastasis rare
A 75 years-old smoker, complained of productive cough, on-and-off fever and weight loss for 4 months.
PE revealed diminished inspiration and crepitation of his right chest. CXR suggested collapsed right middle lobe and haziness at the right central region.
(b) How would you investigate and what are your reasons? (2)
- Blood tests: Neutrophilia and leucocytosis
- Sputum for cytology: malignancy
- Sputum for culture and sensitivity: infection and Abx needed
- Bronchoscopy with biopsy: central/perihilar lesion
- CT thorax: SOL in right chest
A 75 years-old smoker, complained of productive cough, on-and-off fever and weight loss for 4 months.
PE revealed diminished inspiration and crepitation of his right chest. CXR suggested collapsed right middle lobe and haziness at the right central region.
(a)DDx?
- Lung tumor
- Bronchiectasis
- Atelectasis
- COPD
- Chest infection
What are the molecular classifications of adenocarcinoma? (3)
EGFR > KRAS > ALK as driver mutations
KRAS > EGFR in western countries
EGFR mutation?
Constitutive activation of EGFR downstream signaling pathway independent of EGF, causing cell proliferation, migration, invasion and inhibition of apoptosis.
What is the significance of knowing whether the patient has EGFR mutation?
EGFR mutation enables the use of EGFR TKI (tyrosine kinase inhibitors) such as gefitinib, erlotinib
- responsive! in lung ADC
Other than lung ADC, EGFR overexpression is seen in 80% of Colorectal ADC.
What targeted therapy to be given (1) and what molecular tests have to be done before that? (1) Why? (1)
Anti-EGFR monoclonal Antibody
e.g. cetuximab, panitumumab
Molecular test
- if KRAS/NRAS mutation +ve > no response to the above treatment
Treatment for KRAS mutation and ALK mutation?
KRAS mutation - no drug
ALK inhibitors: crizotinib
Treatment for EGFR mutation in lung ADC? (name the drugs)
EGFR TKI: Gefitinib, erlotinib
What is PD-1? How is it related to treatment of lung tumor?
- Tumor cells express PD-L1 (programme death ligand_ in attempt to suppress T cell response
- Check PD-L1 expression on tumor cells
- Immunotherapy: PD-1 receptor agonist: pembrolizumab
How is ALK mutation be tested?
FISH - testing ALK translocation
(e) What are the treatments of choice for early-stage and advance-stage primary lung CA? (2)
Early-stage: surgical intervention +/- chemotherapy/radiotherapy
Advanced stage: Targeted therapy
