Download bronchial carcinoma - UCT Digital Pathology Teaching Collection

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Hypertrophic osteoarthropathy (HOA) is a syndrome of clubbing of the digits,
periostitis of the long (tubular) bones (swelling of the forearms and lower thighs), and
arthritis. Although not entirely understood, it has become sign looked for in
diagnostic circumstances with regards to lung cancer.
Although no lesion could be seen, it is important to remember that that does not
mean there was no lesion there. The possibility of it being a very small lesion that
could have easily been lost or over looked – especially considering the year this
particular patient was seen in (1945) – was extremely likely.
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The damage smoking does on one’s lungs is subject to the amount smoked daily, the
tendency of the patient to inhale and the duration of their smoking habit.
There are 55 different carcinogens (including PAH (= polycyclic aromatic hydrocarbons
- Bap (benzo[a]pyrene) being the most extensively studied) and NNK = 4 –
(methylnitrosamino) – 1- (3 – pridyl) – 1 – butanone) in cigarette smoke for which
“there is sufficient evidence of carcinogenicity”.
During the metabolic processes of PAH and NNK, carcinogen metabolites are made
and bind covalently to DNA in cells creating DNA adducts. If these adducts escape
cellular repair mechanisms and persist, they can cause miscoding which can lead to
permanent mutations. If this mutation occurs on the loci of oncogenes or tumour
suppressor genes, it may cause activation or deactivation respectively. If this happens
often enough, it will create abnormal cells that lose their growth control and
consequently become cancer cells.
There is also the possibility of DNA damage as a result of free radicals and reactive
oxygen species. Reactive oxygen species and free radicals also inhibit the enzyme α1
antitrypsin, consequently allowing enzymes such as elastase released by neutrophils
to break down the elastic fibers in the parenchyma of the lungs.
Epithelial changes usually take the progressive course of squamous metaplasia,
squamous dysplasia, carcinoma in situ and finally invasive carcinoma.
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Bronchial carcinoma can be divided into primary or bronchogenic carcinoma (cancer that
begins in the lungs or the lungs being the site of the primary carcinogenic lesion) or secondary
carcinoma (cancer that started somewhere else in the body and metastasised to the lungs).
Primary or Bronchogenic carcinoma can be further divided into Small cell carcinoma (which is
can of the small round cells in the lungs) or non-small cell cancer (cancer of the all the rest of
the cells that make up the lungs). Non-small cell carcinoma can then be classified as either:
squamous cell carcinoma, adenocarcinoma or large cell carcinoma.
The most important reason classification of carcinomas is done, is to determine treatment,
different options for best prognosis in each subset; the faster the cancer can be identified,
the better and more specific care the patient can receive, the better the prognosis. Small cell
carcinoma is highly metastatic and has a high initial response to chemotherapy whereas Nonsmall cell is the less metastatic and less responsive.
Small cell carcinoma
Males (14%), Females (18%) and overall (20 – 25%)
It is a cancer of the round cells within the lung
Its strongest association is with cigarette smoking
It is a highly malignant cancer
Infiltrate widely; disseminate early; rarely resectable
It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus and
are often associated with the ectopic production of hormones like ADH
and ACTH that may result in paraneoplastic syndromes such as the syndrome of
inappropriate ADH secretion (SIADH) or Cushing’s syndrome.
Adenocarcinoma
Males (37%), females (47%) and overall (25 – 40%)
Most common type in North America; with women and non-smokers
Affects bronchiolar or alveolar tissue of lung
Peripherally located
Poorer stage-to-stage prognosis than squamous cell carcinoma
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Squamous cell carcinoma
Males (32%), females (25%) and overall (25 – 40%)
Most common in men with a smoking history
Cancer linked most commonly with tobacco smoking
Originates in central bronchi as an intraluminal growth
Therefore, early detection through sputum sampling possible.
Large Cell carcinoma
Males (18%), females (10%) and overall (10 – 15%)
Large Polygonal Cells – undifferentiated
Highly anaplasitc neoplasms
Peripherally located; invading segmental bronchi and larger airways
Poor prognosis because of tendency to spread
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Although seemingly uncomplicated, clarifying the stages of development of a cancer
is very difficult – especially in the lungs where palpation is impossible and biopsies are
difficult and dangerous.
Classification of most neoplasms falls under grading and stages which are essential for
management, determining prognosis and treatment and documenting results of
therapy.
Grading is assessed via:
The degree of histological differentiation
The amount of anaplasia
Mitotic activity
The TMN system of staging is used more widely:
T – Tumour – representing the size of the tumour
N – Nodal – whether or not it has spread the nearest nodes
M – Metastasis – whether or not the cancer has disseminated to
distant parts of the body
Table showing the staging of lung cancer as defined by the Radiological Society of
North America
http://radiographics.rsna.org/content/30/5/1163/F1.expansion.html
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The macroscopic appearance of bronchial carcinoma is generally the same across the
different types and subsets of carcinoma; there are, however, differences (as can be
expected) that account for the differences in treatment and prognosis. For this
student case, the slide focuses on the morphological appearance of the case at hand
rather than covering all possibilities.
Most lung cancers originate around the hilus of the lung although adenocarcinomas
as a primary carcinoma appear more frequently around the periphery.
Lesions are often described as cauliflower-like, grey-white, firm intraparenchymal
masses; some fungate into bronchial lumens to produce intraluminal masses.
Infiltration of surrounding areas is not uncommon: peribronchial spaces and tissues,
pleural spaces; if the tumour grows large enough, haemorrhage, necrosis and
cavitation may occur centrally. Extension to bronchial, tracheal and mediastinal lymph
nodes is fairly common (50%); distant metastasis varying (liver 30-50%, brain 20%,
bone 20%).
SCC spread to the adrenals is disproportionately common.
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The microscopic morphology of carcinomas is where most of the differentiation is seen. In
the slide, the characteristics of Large cell carcinoma are highlighted because they relate
directly to the case.
Adenocarcinoma
Malignant epithelial carcinoma with glandular differentiation (mucin production by
cancer cells)
Its subtype, bronchioalveolar adenocarcinoma is the most distinctive microscopically.
Key feature: ability to grow into pre-existing structures without destroying
the alveolar architecture. Growth pattern = lepidic, or like butterflies sitting
on a fence.
Squamous Cell Carcinoma
Characterised by presence of keratinization and/or the presence of intracellular
bridges.
Moderately to well differentiated
Small Cell Carcinoma
Highly malignant epithelial cell, round with limited cytoplasm, ill-defined borders and
“salt and pepper” or grainy chromatin network in absent or barely noticeable nuclei.
High mitotic count; cells grow in clusters.
Large Cell Carcinoma
Detail on slide.
Multinucleated, large, prominent nuclei
Moderate amounts of cytoplasm
Ill-defined borders
Undifferentiated on light microscopy
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Although common, in this case as well as others, lung cancer often presents and/or is
diagnosed toward the end stages. Its signs are common and are – occasionally and
unfortunately - misunderstood in clinical practice for symptoms of basic pulmonary disease;
each symptom however, can be explained and rationalised with cancer in mind.
Dyspnoea
In the case of an infiltrative, intraluminal mass, an obstruction to an airway would
result in difficulty breathing, manifesting as shortness of breath, gasping, inability to
take in or let out deep breaths with coughing or pain.
Chest Pain
There may be many explanations for the sensation of pain in the chest for something
such as bronchial carcinoma but one highlighted is one most applicable to the case –
pleuritic chest pain. The likelihood was that the increase growth of the tumour
pushed against the pleural causing a sharp or stabbing pain.
Loss of Weight
This is very briefly explained in the slide: because of the presence of the tumour,
there is secretion of tumour necrosis factor (defence mechanism), the presence of
TNF in the blood is sensed by the hypothalamus in the brain and this inhibits the
centre of the brain responsible for creating a sense of hunger, so decreasing food
intake.
There is also the possibility that this patient’s loss of weight was as a result of an
increased energy expenditure (↑basal metabolic rate) in attempts to combat the
tumour (as well as to supply the cells of the tumour with nutrients).
Clubbing
Clubbing under any circumstance is difficult to explain, leaving all ideas of
pathogenesis speculation. In this particular case, the idea of a paraneoplastic
syndrome causing an increase in substance to stimulate the cellular growth in the nail
bed.
Clubbing can also occur secondary to bronchiectasis (bronchiectatic infection).
Another important sign in lung cancer (not noted in our patient) is haemoptysis – the
coughing up of blood due to erosion of the cancer into a blood vessel.
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Paraneoplastic syndrome or ‘the great mimic’ is a condition that is borne from
neoplasms in the body replicating the role of endocrine glands, secreting their
substances (e.g. hormones) in excessive amounts or in places around the body where
it isn’t needed and could possibly cause harm. Lung cancers are associated with
several paraneoplastic syndromes (the syndromes sometimes leading to the discovery
of the primary neoplastic lesion). Some of the hormones or hormone-like factors
commonly produced include:
> Antidiuretic Hormone (ADH) causing hyponatraemia
as a result of inappropriate ADH secretion
> Adrenocorticotropic hormone (ACTH) creating
Cushing’s syndrome
> Parathyroid Hormone, parathyroid releasing hormone,
prostaglandin E and some cytokines –
all leading to hypercalcaemia
> Calcitonin causing hypocalcaemia
> Serotonin and bradykinin which are
associated with carcinoid syndrome
> Gonadotropins causing gynaecomastia
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