Lung Carcinoma

Brenda

Aqilah

Robin
 Case Presentation
• This cachexic patient has a productive cough and is breathless at
rest. The fingers are clubbed with presence of nicotine staining.
There is wasting of small muscles of the right hand and reduced
sensation in C8-T1 dermatomes. There are palpable lymph nodes in
the right axilla and supraclavicular fossa. The venous pressure is
not elevated. There is right partial ptosis, mitosis and anhidrosis,
constituting a right Horner’s Syndrome. No peripheral edema noted.

• On examination of the chest, there is a radiation burn on the right

upper chest wall. The trachea is deviated to the right and the
cricoid notch distance is not reduced. Chest expansion is reduced
over right upper chest with dull percussion note and increased
vocal fremitus. On auscultation there is a bronchial breathing at this
area.
How lung CA usually presents
in physical examination?

• pleural effusion

• collapse/consolidation

• pancoast tumour

• Sometimes there may be no respiratory sign, and the only

positive clinical findings may be cachexia, clubbing,
nicotine staining +/- lymphadenopathy.
 How about in history?
• change in nature of a chronic cough (>8 weeks)

• obstructive symptoms: wheezing, SOB

• haemoptysis

• hoarseness of voice

• unexplained weight loss & anorexia

• risk factor for lung CA

• chest pain if involves the pleura/chest wall

• history of recurrent pneumonia

Pathophysiology
 LOCOREGIONAL SPREAD
1. Hoarseness 

involvement of recurrent laryngeal nerve, resulting vocal cord
paralysis

2. Pleural effusion

(dyspnea, pleuritic chest pain)

direct invasion of pleural space cause pleural thickening,
mediastinal lymphatic obstruction

3. Dysphagia 

Esophageal compression

4. Diaphragm paralysis 

(SOB)

compression of phrenic nerve
4. Malignant Pericardial effusion 

(chest pain, dyspnea, palpitation, light headed)

involve the pericardium by direct local invasion or
through metastatic spread via the lymphatics or
bloodstream

5. Superior Vena Cava Syndrome


(facial & upper extremities edema, facial plethora, fixed
engorged neck veins, distended chest veins, cyanosis) 

compression/invasion of the SVC

6. Horner’s Syndrome
• A 68-year-old man noticed progressive enlargement of the
superficial veins on his anterior chest. One month later he
developed dyspnea, headache and swelling of the neck and face.
On examination, telangiectatic distension of the superficial veins of
the anterior chest wall was found to be prominent (Figure 1). A
clinical diagnosis of superior vena cava syndrome was made.

• Further investigation by computer tomography of the chest showed

extensive mediastinal lymph node enlargement with
obstruction of the superior cava vein. Histological work up
revealed small cell lung cancer.

• Tortuous dilatation of the subcutaneous veins of the chest wall

in the shape of a garland may be an early sign of impaired
venous return from the upper extremity and often precedes
other signs of the superior vena cava syndrome for weeks. Its’
appearance should lead to a thorough investigation of the etiology.
In most cases, it is caused by malignant disorders, but thrombosis
or inflammatory disease is also possible.
F: Computed tomogram shows compression of the superior
vena cava (arrow) due to a large mediastinal mass, causing
(F Ј ) tracheal compression and deviation, and stridor. 

B: Distended
A: Plethora of jugular veins
face and neck

C: Cyanosis
of the lips

E: Substantial collateral circulation D: Right arm and hand

massively swollen
Fig. 1. Typical clinical findings in a patient with superior vena cava syndrome due to small-cell lung cancer.
This patient presented with dyspnea and elevated PaCO2 .
 Pancoast’s tumor
• tumor of apical region of lung that
invade the pleura, brachial plexus
and cervical sympathetic chain

• Involvement of brachial plexus:

typically c8-t1 nerve roots, causing
wasting of small muscles of hands
and sensory loss accordingly.

• Involvement of cervical
sympathetic chain lead to
ipsilateral horner’s syndrome:
miosis, partial ptosis, anhidrosis.

• Pancoast’s syndrome is a
constellation of characteristics
signs and symptoms
 DISTANT SPREAD
1. Lymph nodes: lump at neck or armpit

2. Bony metastasis are common, giving rise to severe pain and

pathological #

3. Secondary deposits in the brain present as a change in mental

state, headache, epilepsy or as focal neurological lesion

4. Spinal cord compression may occur and requires urgent

treatment

5. Secondary deposits in the adrenal gland are frequently found

from imaging, often asymptomatic

6. Liver metastasis: Hepatomegaly, pain

 Paraneoplastic Syndrome
• Clinical syndromes involving non metastatic systemic effects that accompany
malignant disease. Commonly occur in SCLS

System Extrapulmonary manifestation

Endocrine • Cushing Sundrome (Ectopic ACTH)
• SIADH (Ectopic ADH)
• Hypercalcemia (ectopic PTH-related)
• Hyperthyroidism (ectopic TSH)
• Hypoglycemia (ectopic insulin-like growth factor)
• Gynaecomastia (ectopic HCG)
Neurological • Subacute cerebellar degeneration (anti-Yo/anti-purkinje cell ab)
• Sensory neuropathy (anti-Hu ab)
• Lambert Eaton Myasthenic Syndrome (presynaptic V-gated Ca channel ab)
• Limbic encephalopathy (anti-Hu & anti-Yo ab)
Musculoskeletal • Clubbing
• HPOA
• Polymyositis/Cermatomyositis
Cutaneous • Acanthosis nigricans
• Thrombophlebitis
• Thrombosis
• Hypertrichosis
• Herpes Zoster
 RISK FACTORS
1. Tobacco Smoke Exposure (90%)
• Includes both active and passive smoker


• Depend on

A. number of cigarettes smoked per day

B. duration of smoking habits

C. age of initiation of smoking

D. the depth of inhalation

E. the composition of the cigarette


• When a smoker quits smoking, the risk of lung cancer is

reduced. After quitting for 15 years, the risk of getting lung
cancer is the same as non-smokers.


• Smoking 20 cigarettes per day increases the risk to 20-25

times compared to non smokers.
 CONT…
• Potential carcinogens in cigarette smoke:

▪ Polycyclic aromatic hydrocarbons

▪ Nitrosamines

▪ Vinyl chloride

▪ Aldehydes

▪ Catechols

▪ Peroxides

▪ Nickel
 CONT…
2. Occupational Exposures
• Arsenic – Agricultures
(pesticides), Alloy
manufacturing

• Asbestos – in miners and

construction workers

• Chromium -  in the metal and

chemical manufacturing
industries

• Radon gas – In miners (uranium

decay)

• Ionizing radiation

• Nickel

• Hydrocarbons
 CONT…
3. Environmental Exposure
• atmospheric pollutants especially by radon
(indoor air pollution in homes in areas of
high radon in soil)

4. Other Factors
• Chronic obstructive pulmonary disease,
tuberculosis

• Genetic predisposition

• Dietary factors: Vitamin A , E deficiency

 Classification of Lungs Cancer
• Classified using 2015 WHO classification of
lung tumor
• Relies more on immunohistochemical stain
to guide treatment strategy and predict
clinical course
• Standardized criteria and terminology for
lung cancer diagnosis on small biopsies and
cytology
• Guidance for doing molecular testing
Classification of Lung Cancer
Classification of Lung Cancer
 Classification of Lung Cancer

Non small cell Lung Ca Small cell Lung Ca

• Adenocarcinoma Small cell lung

• Squamous cell carcinoma
carcinoma
• Large cell carcinoma
• Adenosquamous
carcinoma
• Sarcomatoid Carcinoma
 ADENOCARCINOMA
• Malignant epithelial tumor with glandular
differentiation or mucin production by
tumour cells.
• Most common cell type in Malaysia (Kan et al,
2016)
• Most common in women and non-smoker
• Originate from mucin secreting glandular
cells
• Often causes peripheral lesion on CXR and
CT scan
 ADENOCARCINOMA
• Grow slowly and smaller masses than other
subtypes, but tend to metastasize widely at
early stage
• Metastases common: pleura, lymph node,
brain, bone and adrenal gland
• K-RAS mutation: highly correlate with
worse outcome
• Thyroid transcription factor-1 (TTF-1):
Majority are positive
 ADENOCARCINOMA

• Usually are more

peripherally
located
 ADENOCARCINOMA
• Histologic diagnosis requires evidence of
either neoplastic gland formation,
pneumocyte marker expression (TTF-1 +/-
napsin), or intracytoplasmic mucin
 ADENOCARCINOMA

Preinvasive Adenocarcinoma Invasive adenocarcinoma

• Atypical adenomatous • Minimally invasive

hyperplasia • Lepidic
• Adenocarcinoma in situ • Acinar
• Paipillary
• Micropapillary
• Invasive mucinous
• Colloid
• Fetal
• Signet ring and clear cell feature
• enteric
 SQUAMOUS CELL CARCINOMA
• More common in men
• Closely related to smoking
• Usually arise centrally in major bronchi and
spread to local hilar lymph node
• Mostly arise in the proximal portions of the
tracheobronchial tree through squamous
metaplasia-dysplasia-carcinoma in situ
sequence (squamous carcinoma in situ)
• P/w persistent cough, recurrent hemoptysis, or
relapsing pulmonary infections due to airway
obstruction.
 SQUAMOUS CELL CARCINOMA

• Arise centrally in
major bronchi
 SQUAMOUS CELL CARCINOMA
• Presence of keratin production by tumor
cells and/or intercellular desmosomes
(referred to as "intercellular bridges")
• IHC (ie, expression of p40, p63, CK5, or
CK5/6, desmoglein)
• Classified into Keratinised, Non keratinized
and Basaloid
 LARGE CELL CARCINOMA
• a malignant epithelial neoplasm lacking both
glandular and squamous differentiation by
light microscopy and immunohistochemistry,
and lacking cytologic features of small cell
carcinoma.
• usually presents as a large peripheral mass with
prominent necrosis.
• Histologically, LCC is characterized by sheets of
round to polygonal cells with prominent
nucleoli and abundant pale staining cytoplasm
without differentiating features
LARGE CELL CARCINOMA
High-magnification
photomicrograph showing large
cell undifferentiated carcinoma
of the lung. The tumor cells have
vesicular nuclei, prominent
nucleoli, and abundant
eosinophilic cytoplasm. The cells
are arranged in sheets without
distinct architectural features.
Tumor cells did not express
TTF-1 (adenocarcinoma marker)
or p40 (squamous marker) by
IHC. This indicated the null
phenotype of large cell
carcinoma.
 SMALL CELL CARCINOMA

• One of the neuroendocrine tumour

• occurs almost exclusively in smokers and
appears to be most common in heavy smokers
• What makes it different with NSCLC?
Small Cell lung Ca has
• rapid doubling time,
• high growth fraction,
• early development of widespread
metastases.

Highly malignant tumour !!!!

 SMALL CELL CARCINOMA
• Generally central located mass with extension
into lung parenchyma and early involvement of
hilar and mediastinal node.
• Composed of cells with a size no larger than the
size of three resting lymphocyte nuclei.
• May be round, oval, angulated, and with usually
small amounts of cytoplasm.
• The nuclei are typically hyperchromatic and
either have a dispersed "salt and pepper"
chromatin.
• Nuclear molding is prominent.
SMALL CELL CARCINOMA
small cell carcinoma in
which small dark blue cells
with minimal cytoplasm are
packed together in sheets.

Oat seed

Nuclear
moulding
 SMALL CELL CARCINOMA

Small cell lung Ca elaborate peptide

hormone: Cushing syndrome
• Adrenocorticotrophic hormone
• Antidiuretic hormone SIADH
Some patient produce autoantibodies that
crossreact with both SCLC cells and the central
nervous system or the neuromuscular junction
Lambort Eaton Myasthenic
Syndrome
Comparison of SCLC and NSCLC

ALK: anaplastic lymphoma kinase

 CARCINOID TUMOUR
• Neuroendocrine epithelial malignancies
with a lower grade than large cell
neuroendocrine or small cell carcinoma.
• Can be further divided into typical or
atypical carcinoid tumors.
• Carcinoid syndrome: systemic release of
vasoactive substances such as serotonin and
other bioactive amines
 CARCINOID TUMOUR
• Acute symptoms : cutaneous flushing,
diarrhea, and bronchospasm
• long-term sequelae of prolonged elevated
hormone levels include venous
telangiectasias, right-side-predominant
valvular heart disease, and fibrosis in the
retroperitoneum and other sites.
CARCINOID TUMOUR
 CARCINOID TUMOUR
• Organoid, trabecular, palisade arrangements
of
uniform cells separated by a thin fibrovascular
stroma
• Individual cell: regular, uniform round nuclei,
moderate amount of cytoplasm containing
dense core neurosecretory granules
• IHC – positive for neuroendocrine markers
(serotonin, neuron-specific enolase, calcitonin,
bombesin and other peptides)
CARCINOID TUMOUR

palisade arrangements of
uniform cells separated by a thin
fibrovascular stroma
 SECONDARY LUNG TUMOUR
• Typical metastasis sites for primary tumour of
kidney, prostate, breast, bone, GIT, cervix or
ovary
• Mets always develop in the parenchyma
• Morphology: multiple discrete nodules (cannon
ball lesions) are scattered throughout all lobes
& occur in the periphery of the lung
• Ocassionally, a lung mets is detected as a
solitary round shadow on CXR in an
asymptomatic pt: Renal cell Ca
SECONDARY LUNG TUMOUR

Cannon balls lesion

are scattered
throughout all lobes
Investigations, staging and principle
of management of Lung cancer

Wong Siew Bing

 Investigation
➢Imaging
➢Laboratory
➢Cytology / tissue diagnosis
 Investigation
➢Imaging
✓ Chest x ray (nodules, mass, pleural effusion,
collapse, mediastinal fullness)
✓ CECT (lower neck, thorax, upper abdomen,
assess location, size, extension, hilar/
mediastinal LN, distant metz)
✓PET scan (useful for occult hypermetabolic
metastasis)
✓ CT/MRI brain for advanced adenocarcinoma
 Investigation
➢Laboratory
✓ FBC (Hb normal or low, baseline before invasive
procedure or starting chemo)
✓ BUSE (Hyponatremia in SIADH for small cell LC)
✓Creat (baseline RFT before treatment)
✓ Serum Ca (hypercalcemia in SCC, PTH-P)
✓ LFT (ALP-bone metz, AST, ALT, TB-liver metz)
 Investigation
➢Cytology / tissue diagnosis
✓ Sputum cytology to look for malignant cells (non-
invasive, but low sensitivity. Limited to central lesion)
✓ Flexible bronchoscopy + biopsy (endobronchial lesion.
Transbronchial for LN. 90% sensitivity for central
lesion, lower for peripheral but improved by
endobronchial ultrasound)
✓ CT guidance transthoracic needle aspiration biopsy
(lesions inaccessible by bronchoscopy)
✓ Thoracentesis to sample fluid for malignant cells
✓ Thoracoscopy for pleural biopsy
Staging
Prognosis by stage
 Principle of Treatment
• Non small cell lung cancer
• Small cell lung cancer

◆ Surgical resection
◆ Chemotherapy
◆ Immunotheraoy
◆ Radiotherapy
 Treatment
• Non small cell lung cancer
– Surgical resection* for stage I & II whenever possible +/-
adjuvant chemotherapy
– Non surgical radiofrequency ablation / cryoablation f or
stage I & II who are not suitable candidate for surgery
– Stage III require combined modality of chemoradiotherapy
with immunotherapy +/- surgery following
– Stage IV generally treated with symptom based palliative
approach (debulking, airway stenting, ext beam radiation,
brachytherapy), unless isolated metz to brain, adrenal
which local resection + aggressive primary tumour
treatment may benefit.
*Suitable if performance status is good and postresection pulmonary reserve is adequate
(FEV1>0.8L)
 Treatment
• Small cell lung cancer
– Chemosensitive
– Chemotherapy (integral) + radiotherapy (prolongs
survival)
– Surgery generally not indicated unless solitary mass
without LN involvement / distant metz
– Prophylactic cranial irradiation decrease incidence of
brain metz and prolongs survival in patient responded
initial treatment
– Extensive stage SCLC treated with chemotherapy +/-
immunotherapy. Radiotherapy (cranial irradiation and
thoracic RT) may be beneficial in patient responded their
initial treatment