LUNG CANCER

ODUNTAN DANIEL TOLUWANI

CLI/2017/082
Outline

 Introduction
 Epidemiology
 Categories of Tumors
 Etiology and pathophysiology
 Histological Classification of Lung Tumors
 Types of Lung Tumors
 Conclusion
 References
 Introduction

 Lung cancers are tumors originating within the lung parenchyma, within the bronchi,
bronchioles, alveoli or as a result of metastasis from other sites.
 Bronchogenic cancer refers to a malignant tumor of the lung arising within the wall or
epithelial lining of the bronchus
 The lung is a common site of metastatic neoplasms(from Sarcomas and Carcinomas).
However, the bronchogenic cancer is the most common primary malignant tumor of the
lungs
 The lung is also a common site of metastasis by way of venous circulation or lymphatic
spread.
 Roughly 95% of primary lung tumors are carcinomas; the remaining 5% constitute a
miscellaneous group that includes carcinoid, mesenchymal malignancies (e.g.,
fibrosarcomas, leiomyomas), lymphomas, and a few benign lesions.
Categories

 The lung tumors can be categorized into;

 EPITHELIAL TUMORS
 BENIGN TUMORS e.g Papilloma, Adenoma
 Dysplasia and Carcinoma In Situ
 MALIGNANT (Brochogenic Carcinoma)
 Squamous cell Carcinoma
 Small Cell Carcinoma
 Adenocarcinoma
 Large Cell Carcinoma
 OTHER CARCINOMAS
 Carcinoid Tumor
 Bronchial gland Carcinomas
Classification

 PLEURAL TUMORS
 Benign Mesothelioma
 Malignant Mesothelioma

 SOFT TISSUE TUMORS

 Hemangioma
 Lymphangioma
 Fibroma
Epidemiology

 Lung cancer is currently the most frequently diagnosed major cancer in the world with an
estimated 1.6million new cases in 2008.
 Primary lung cancer is the most common fatal cancer in both men and women worldwide.
It accounts for >30% of cancer deaths in men and for >25% of cancer deaths in women
 Black men have the highest incidence rates.
 Peak incidence is at 55 to 65 years of age
 Epidemiology

 In approximately 70% of lung cancer patients, the disease has spread

to regional lymphatics and other sites by the time of diagnosis.
 More than 85% of lung cancers are caused by the inhalation of
carcinogenic chemicals, most commonly cigarette
smoke(Schottenfeld, 2000).
 At diagnosis, more than 50% of patients already have distant
metastatic disease, while a fourth have disease in the regional lymph
nodes.
 The prognosis with lung cancer is dismal: The 5-year survival rate
for all stages of lung cancer combined is about 16%.
Risk Factors and Etiology

 The risk factors for lung cancers can be classified into 2 major
groups
 NON-GENETIC FACTORS
 GENETIC FACTORS
 Risk Factors and Etiology
 NON-GENETIC FACTORS
 Cigarette smoking.
 Most common cause of lung cancer
 Tobacco smoking accounts for 80% to 90% of cases and secondhand smoke for 3% to 5% of cases
 Risk increases with quantity and duration of smoking.
 Men who smoke have a greater risk for lung cancer than women who smoke.
 Non–smoking-related lung cancer is more common in women than men

 Asbestos and coal dust

 Certain metals: Chromium, Cadmium, Beryllium, and Arsenic
 Ionizing radiation
 Uranium mining
 History of tuberculosis and COPD
 Age; over 50 years
 Risk factors and Etiology

 GENETIC FACTORS
Mutation of certain proto-oncogenes and Tumor suppressor genes predisposes to the
development of lung cancers
 Proto-Oncogenes; HER-2, N-MYC,L-MYC, EGFR, K-ras
 Tumor suppressor genes; p53, RB-1
 Mutation of the CYP450 system
 Deletions in the short arm of chromosome 3 (3p):
Such deletions are frequently found in all types of lung
cancers
 Risk factors and Etiology

 Women seem to have a higher susceptibility to carcinogens than men

 Although, cessation of smoking decreases the risk of lung cancer overtime, it may
never return to baseline levels
 Passive smoking increases the risk for lung cancer development to approximately
twice that of non-smokers
 The carcinogenic effects of tobacco smoke extend to those who live and work with
smokers.
 These second-hand ‘smokers’ are also exposed to numerous human carcinogens.
 It is estimated that about 3000 non-smoking adults die of lung cancer each year as a
result of breathing of second hand smoke.
Pathogenesis

 Like other cancers, Lung tumours arise as a result of the

stepwise accumulation of driver mutations.
 Mutations results in the transformation of benign progenitor
cells in the lungs possessing all of the hallmarks of cancer.
 Cigarette smoking and other environmental carcinogens have
been implicated as the cause of these mutations resulting into
cancer.
 Histological classification of Tumors

 Squamous cell carcinoma

Keratinizing, non-keratinizing, basaloid
 Adenocarcinoma
Minimally invasive adenocarcinoma (non-mucinous, mucinous), Invasive Mucinous
Adenocarcinoma, Lepidic, papillary etc.
 Neuroendocrine Carcinoma
Small cell carcinoma, large cell neuroendocrine carcinoma, Carcinoid Tumor
 Other Uncommon types
Adenosquamous carcinoma, Large cell carcinoma, Sarcomatoid carcinoma
Squamous cell (Epidermoid) Carcinoma

 Account for 20%–30% of primary lung cancers and It is more common in men
than women
 Strong association with cigarette smoking
 High frequency of p53 mutations
 Tumor usually arise CENTRALLY from the large bronchus and there are
usually evidences of necrosis and massive cavitations.
 The neoplastic tissue is grey-white and firm to hard
 May ectopically secrete PTH-related protein (peptide)
 Squamous cell (Epidermoid) Carcinoma

 Most tumors have mutations in TP53, and p53 protein overexpression(as seen by
immunohistochemical staining)
 A marker of TP53 mutations, is an early event, reported in 10% to 50% of squamous
dysplasias and 60% to 90% of squamous cell carcinoma in situ.
 Histologically, squamous cell carcinoma is characterised by
the presence of keratinization and/or intercellular bridges.
 Keratinization may take the form of squamous pearls or individual
cells with markedly eosinophilic cytoplasm
 Well-differentiated squamous cell carcinomas
display keratin “pearls,” which are eosinophilic aggregates
of keratin surrounded by concentric (“onion skin”) layers of
squamous cells
 By contrast, some squamous tumours are so poorly differentiated that they show no foci of
keratinization and are difficult to distinguish from large-cell, small-cell or other lung cancers.
Squamous cell Carcinoma
Squamous cell (Epidermoid) Carcinoma
Squamous cell (Epidermoid) Carcinoma
 Small cell Carcinoma

 Accounts for 15%–20% of primary cancers

 Slightly more common in men than women
 Strong association with cigarette smoking
 The Tumors are usually HILAR or CENTRAL in location
 Widely regarded as the most aggressive form of lung cancer and metastasizes
early and widely
 Arise from neuroendocrine cells (Kulchitsky cells); neurosecretory granules are
noted on EM
 Small cell carcinoma

 High frequency of p53, RB1 mutations

 High expression of the BCL-2 gene
 Rapidly growing cancer that metastasizes early
 May ectopically secrete ADH or ACTH
 By Immunochemistry, these tumors are positive for neuroendocrine markers
like chromogranin, neuron-specific enolase(NSE), Synaptophysin and NCAM-1
Small cell carcinoma; Morphology

 Small cell carcinoma usually appears as a perihilar mass, frequently with

extensive lymph node metastases.
 On cut section, it is soft and white but often shows extensive haemorrhage
 Small cell carcinoma; Histology

 They usually grow as small cells with scant cytoplasm, small nucleoli, ill-
defined cell borders with a finely granular chromatin pattern
 The cells grow in clusters that usually do not show glandular or squamous
pattern
 There are usually areas of necrosis
Histology
 Small cell carcinoma Subtypes

 Oat cell Carcinoma; Composed of uniform, small cells, larger than lymphocytes,
round or oval nucleus with diffuse chromatin, inconspicuous nucleoli and sparse
cytoplasm (Oat like grains)

 Small cell Carcinoma (Intermediate cell type); Composed of cells slightly

larger than those of oat cell carcinoma, with similar nuclear characteristics but
more abundant cytoplasm

 Combined Oat cell carcinoma: A mixed tumor in which there is a definite

component of oat cell carcinoma with squamous cell and/or adenocarcinoma
 Adenocarcinoma

 Adenocarcinoma is an invasive malignant epithelial tumor with glandular

differentiation or mucin production by the tumor cells
 Most common primary cancer (35%–40%)
 Most common cancer in nonsmokers showing the weakest smoking relationship
 More common in women than men
 Grow slowly but metastasize early
 Usually located in the periphery of the lungs
 High frequency of KRAS and EGFR mutations
 Scar carcinomas: develop in scars (e.g., old tuberculous granuloma)
 Adenocarcinoma

 Atypical adenomatous hyperplasia (AAH) is recognized as a precursor lesion

for adenocarcinomas.
 AAH is a well-demarcated lesion, usually smaller than 5 mm, with atypical
proliferation(dysplatic) of epithelial cells along alveolar septa.
 Lung adenocarcinomas are thought potentially to originate as AAH and progress
to bronchioloalveolar carcinoma and then to more aggressive mixed-type
adenocarcinomas.
 There is a glandular pattern of tumor growth
 Cells are positive for mucin, TTF-1(Thyroid transcription factor) and Napsin-A.
 adenocarcinomas of the lung most often appear as irregular
masses 2 to 5 cm in diameter, although they may be so large as
to replace an entire lobe.
 On cut section, the tumor is greyish-white and often
glistening, depending on the amount of mucus production.
Adenocarcinoma; Subtypes

 There are four major subtypes of adenocarcinoma, as defined by the World

Health Organization.

(1) acinar,
(2) papillary,
(3) solid with mucus formation and
(4) bronchioloalveolar
Bronchioalveolar Carcinoma

 Bronchioloalveolar carcinoma is a distinctive subtype of adenocarcinoma that grows

along pre-existing alveolar walls (lepidic growth)
 Accounts for 1% to 5% of all invasive lung tumors
 Copious mucin in the sputum (bronchorrhea) is a distinctive sign of bronchioloalveolar
carcinoma
 On gross examination, bronchioloalveolar carcinoma
may appear as a single peripheral nodule or coin lesion, multiple nodules or a diffuse
infiltrate indistinguishable from a pneumonia
 Tumors can be non-mucinous, consisting of Clara cells and
type II pneumocytes, in which cuboidal cells grow along
the alveolar walls,
 Tumor can also be mucinous featuring columnar goblet cells filled with
mucus.
Bronchioalveolar Carcinoma
Bronchioalveolar Carcinoma
 Large cell carcinoma

 Large cell carcinoma is a diagnosis of exclusion in a poorly differentiated tumor

that does not show features of squamous or glandular differentiation and has
been shown not to be a small cell carcinoma
 Can appear centrally or peripherally in the lungs
 Accounts for 10%–15% of primary cancers
 More common in men than women
 Strong relationship with smoking
Large cell carcinoma

 The cells are large and exhibit ample cytoplasm

 The nuclei frequently show prominent nucleoli and vesicular
chromatin
 It expresses none of the markers associated with
adenocarcinoma (TTF-1, Napsin A) or squamous cell
carcinoma (p53)
 Carcinoid Tumors

 Carcinoid tumors are thought to arise from the resident neuroendocrine cells that are normally
found in the bronchial epithelium.
 Most common primary lung tumor in children
 No sex predilection or association with smoking

 Intraluminal mass that penetrates the bronchial wall and fans out (sometimes called
“iceberg” tumor)
 Approximately 20% locally metastasize
 Present with hemoptysis (most common), cough
 Some cases are associated with an endocrinopathy, such as Cushing syndrome with ectopic ACTH
production by tumor cell.
Carcinoid Tumors

 Most cases are slow-growing, indolent tumors which do not metastasize

and have
excellent prognosis with appropriate surgery (5-year survival: 90%). These
are known as
typical carcinoids.

 More aggressive behaviour has been observed in a subset of cases with

increased mitoses, tumour necrosis, and atypical cell types. These have
historically been deemed atypical
carcinoids
Carcinoid Tumors
Carcinoid Tumors
 Metastatic Tumors

 These are secondary tumors of the lungs

 Metastases from carcinomas as well as sarcomas arising from anywhere in the body may spread to the
lungs by hematogenous or lymphatic routes or by direct extension.
 Usually arising from the Breast (most common site), colon, stomach, pancreas and the kidneys
 Sites of lung metastasis include:
a. lung Parenchyma
b. Pleura and pleural space (malignant effusions).
c. Lymphatics
 In lymphangitic carcinoma a metastatic tumor spreads widely through
pulmonary lymphatic channels to form a sheath of tumor
around the bronchovascular tree and veins.
 Clinically, patients suffer from cough and shortness of breath.
 Bronchial hamartoma

 Non-neoplastic proliferation of cartilage and adipose tissue

 Appears as solitary “coin” lesion on chest radiography

 Can be;
 Chondromatous hamartoma; Solitary, spherical mass, 2-5cm in diameter, usually at
the periphery of the lungs. It shows nodules of cartilage associated with fibrous and
adipose tissue mixed with bronchial epithelium
 Leiomyomatous hamartoma; Prominent smooth muscle components mixed with
bronchial epithelium, more commonly related to the pleura.
References

 Robbins and Cotrans Pathological basis of Disease

 Essentials of Rubin Pathology
 Goljan Review of Pathology
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