Lung tumors can be carcinomas, bronchial carcinoids, or mesenchymal neoplasms. Lung cancer is the leading cause of cancer death worldwide, largely due to cigarette smoking. The risk increases based on amount smoked, inhalation, and duration of smoking. Occupational exposures like asbestos, radiation, and air pollution also increase risk. The major lung cancer types are squamous cell carcinoma, adenocarcinoma, small cell carcinoma, and large cell carcinoma. Squamous cell carcinoma is associated with smoking and keratinization. Adenocarcinoma occurs more in women and nonsmokers and shows glandular differentiation. Small cell carcinoma is very aggressive and metastatic.

1. LUNG TUMORS

2. LUNG TUMORS
• Variety of tumor can arise from lung
- Carcinomas ( 90 – 95%).
- Bronchial carcinoids (5%) and
- Mesenchymal neoplasms (2-5%).

3. Lung carcinoma
• Lung cancer is currently the most frequently
diagnosed major cancer in the world and the
most common cause of cancer mortality
worldwide.
• This is largely due to the carcinogenic effects of
cigarette smoke.
• It occurs most often between ages 40 and 70
years.

4. Etiopathogenesis:
1. Tobacco Smoking:
• 87% of lung carcinomas occur in active smokers
or those who stopped recently.
• There was a statistical association between
smoking and frequency of lung cancer
- (1) The amount of daily smoking,
- (2) The tendency to inhale, and
- (3) The duration of the smoking habit.

5. • Risk of developing cancer is 10-fold greater in smoker
and 60-fold greater risk in heavy smokers
• Cessation of smoking for 10 years reduces risk of
carcinoma of lung.
• There is also association between cigarette smoking
and carcinoma of the mouth, pharynx, larynx,
esophagus, pancreas, uterine cervix, kidney, and
urinary bladder.
• Secondhand smoke, or environmental tobacco
smoke, contains numerous human carcinogens for
which there is no safe level of exposure.

6. • These sequential changes have been best
documented for squamous cell carcinoma,
Respiratory coloumnar cells
Squamous metaplasia
Squamous dysplasia
Carcinoma in situ
INVASIVE SQUAMOUS CELL CARCINOMA

7. • More than 1200 potential carcinogens are present in
the cigarette smoke.
• They include both initiators (polycyclic aromatic
hydrocarbons such as benzo[a]pyrene) and promoters,
such as phenol derivatives.
• Radioactive elements may also be found (polonium-
210, carbon-14, potassium-40) as well as other
contaminants, such as arsenic, nickel, molds, and
additives.
• Bronchio-alveolar carcinomas, a type of tumor that is
not strongly associated with smoking in humans.

8. 2.Industrial Hazards
• High-dose ionizing radiation is carcinogenic.
• Studies shows that there was an increased incidence
of lung cancer among survivors of the Hiroshima and
Nagasaki atomic bomb blasts.
• Uranium is weakly radioactive, but lung cancer rates
among nonsmoking uranium miners are 4 times
higher.
• The risk of lung cancer is increased with asbestos.
Among asbestos workers, one death in five is due to
lung carcinoma, 1 in 10 to pleural or peritoneal
mesotheliomas and 1 in 10 to gastrointestinal
carcinomas

9. 3. Air Pollution:
• Radon is a ubiquitous radioactive gas that has
been linked epidemiologically to increased lung
cancer in miners exposed to relatively high
concentrations.
• Low-levels of indoor exposure (e.g., in homes in
areas of high radon in soil) could also lead to
increased incidence of lung tumors.

10. Molecular Genetics:
• Exposures act by causing genetic alterations in lung
cells, which accumulate and eventually lead to the
neoplastic phenotype.
• Dominant oncogenes- c-MYC, K-RAS, EGFR, and HER-
2/neu.
• Inactivated tumor suppressor genes- p53,RB,
p16INK4a.
• P53- Both small and non-small cell carcinomas.
• c-MYC and RB gene- Small cell tumor.
• RAS and p16INK4a - Non small cell tumor.

11. Precursor lesions
• Three types of precursor epithelial lesions are
recognized:
1. Squamous dysplasia and carcinoma in situ,
2. Atypical adenomatous hyperplasia, and
3.Diffuse idiopathic pulmonary neuroendocrine
cell hyperplasia.

12. Classification of lung carcinoma:
• Squamous cell carcinoma (25% to 40%)
• Adenocarcinoma (25% to 40%)
• Small cell carcinoma (20% to 25%)
• Large cell carcinoma (10% to 15%)

13. Histologic Classification of Malignant
Epithelial Lung Tumors
• Squamous cell carcinoma
• Small cell carcinoma
• Combined small cell carcinoma
• Adenocarcinoma:
- Acinar, papillary, bronchioloalveolar, solid,
mixed subtypes
• Large cell carcinoma
• Large cell neuroendocrine carcinoma

14. • Adenosquamous carcinoma.
• Carcinomas with pleomorphic, sarcomatoid,
or sarcomatous elements.
• Carcinoid tumor:
- Typical, atypical.
• Carcinomas of salivary gland type.
• Unclassified carcinoma.

15. 1.Squamous Cell Carcinoma:
• It is common in men and with a smoking history.
• Gross: Large grey white tumor near the hilum(central).
• Histologically, this tumor is characterized by the
presence of keratinization and/or intercellular bridges.
• Keratinization may take the form of squamous pearls
or individual cells with markedly eosinophilic dense
cytoplasm.
• Mitotic activity is higher in poorly differentiated
tumors.

16. • Squamous cell carcinomas show the highest
frequency of p53 mutations.
• Loss of protein expression of the tumor
suppressor gene RB is detected by
immunohistochemistry in 15% of squamous cell
carcinomas.
• The CDK-inhibitor p16INK4 is inactivated, and its
protein product is lost in 65% of tumour.
• HER-2/neu is highly expressed in 30% of these
cancers.

17. Gross – Squamous cell carcinoma

18. Squamous cell carcinoma

19. 2. Adenocarcinoma:
• It is common in women and nonsmokers.
• This tumor shows glandular differentiation or
mucin production by the tumor cells.
• Gross – tumor is solid with more peripheral
location.
• Adenocarcinomas show various growth patterns
like acinar, papillary, bronchioloalveolar, and solid
with mucin formation.

20. • Histologically shows well-differentiated tumors
with obvious glandular elements to papillary
lesions.
• K-RAS mutations are seen primarily in
adenocarcinoma, with a much lower frequency in
nonsmokers (5%) than in smokers (30%).
• p53, RB, and p16 mutations and inactivation have
the same frequency in adenocarcinoma as in
squamous cell carcinoma.

21. Gross – Adenocarcinoma

22. Adenocarcinoma

23. Nuclear feautres

24. Broncho- alveolar carcinoma:
• It occurs in the terminal bronchioloalveolar
regions.
• Gross- It almost always occurs in the peripheral
portions of the lung either as a single nodule or,
more often, as multiple diffuse nodules that
sometimes coalesce to produce a pneumonia-like
consolidation.
• The parenchymal nodules have a mucinous, gray
translucence when secretion is present but
otherwise appear as solid and gray-white

25. • Histologically, the key feature is their growth along
preexisting structures without destruction of alveolar
architecture.
• The growth pattern has been termed "lepidic," an
allusion to the neoplastic cells resembling butterflies
sitting on a fence.
It has two subtypes:
• 1. Nonmucinous- Columnar, peg-shaped, or cuboidal
cells.
• 2. Mucinous- Tall, columnar cells with cytoplasmic and
intra-alveolar mucin, growing along the alveolar septa.

26. Broncho-alveolar carcinoma

27. 3. SMALL CELL CARCINOMA:
• The epithelial cells are small, with scant
cytoplasm, ill-defined cell borders, finely granular
nuclear chromatin (salt and pepper pattern), and
absent or inconspicuous nucleoli.
• The cells are round, oval, and spindle-shaped,
and nuclear molding is prominent.
• The mitotic count is high.
• Necrosis is common and often extensive.

28. • Electron microscopy- Dense-core neurosecretory
granules 100 nm in diameter in the cytoplasm.
• IHC stain- Chromogranin, synaptophysin, and Leu-7
(in 75% of cases) and parathormone-like
substances.
• It is most aggressive tumors, metastasize widely,
and are virtually incurable by surgical means.
• p53 and RB tumor suppressor genes are frequently
mutated (50% to 80% and 80% to 100% of small
cell carcinomas, respectively).

29. Small cell carcinoma

30. 4. LARGE CELL CARCINOMA:
• This is an undifferentiated malignant epithelial tumor
that lacks the cytologic features of small cell carcinoma
and glandular or squamous differentiation.
• The cells typically have large nuclei, prominent nucleoli,
and a moderate amount of cytoplasm.
• Ultrastructurally, however, minimal glandular or
squamous differentiation is common.
• One histologic variant is large cell neuroendocrine
carcinoma. This is recognized by such features as
organoid nesting, trabecular, rosette-like and palisading
patterns - Neuroendocrine differentiation.

31. Large cell carcinoma

32. 5. CARCINOID TUMOR
• It represent 1% to 5% of all lung tumors.
• Most patients with these tumors are younger
than 40 years of age and affects both sexes.
• Carcinoid tumors are subclassified into typical and
atypical carcinoids.
• Typical carcinoids have no p53 mutations or
BCL2/BAX imbalance.

33. • Gross:
- Carcinoids may centrally or peripheral lesion.
- Central tumors grow as finger-like or
spherical polypoid masses that commonly project
into the lumen of the bronchus and measures 3 to
4 cm in diameter.( collarbutton lesion ).
- Peripheral tumors are solid and nodular.
- Spread to local lymph nodes is more likely
with atypical carcinoid.

34. • Microscopy:
-Tumor is composed of organoid, trabecular,
palisading, ribbon, or rosette-like arrangements of cells
separated by a delicate fibrovascular stroma.
-The individual cells are quite regular and
have uniform round nuclei and a moderate amount of
eosinophilic cytoplasm.
Typical carcinoids- 2 mitoses per 10 hpf and no necrosis.
Aypical carcinoids- 2 to 10 mitoses per 10 hpf and foci of
necrosis.

35. Carcinoid tumors

36. Secondary Pathology:
• Partial obstruction may cause marked focal
emphysema.
• Total obstruction may lead to atelectasis.
• severe suppurative or ulcerative bronchitis or
bronchiectasis.
• Pulmonary abscesses.
• Compression or invasion of the superior vena cava
can cause venous congestion, dusky head and arm
edema, and, ultimately, circulatory compromise—the
superior vena cava syndrome.

37. TNM STAGING:
• T1- Tumor <3 cm without pleural or main stem
bronchus involvement.
• T2- Tumor >3 cm or involvement of main stem
bronchus 2 cm from carina, visceral pleural
involvement, or lobar atelectasis.
• T3- Tumor with involvement of chest wall,
diaphragm, mediastinal pleura, pericardium, main
stem bronchus 2 cm from carina, or entire lung
atelectasis.
• T4- Tumor with invasion of mediastinum, heart, great
vessels, trachea, esophagus, vertebral body, or carina
or with a malignant pleural effusion.

38. • N0- No demonstrable metastasis to regional
lymph nodes.
• N1- Ipsilateral hilar or peribronchial nodal
involvement.
• N2- Metastasis to ipsilateral mediastinal or
subcarinal lymph nodes.
• N3- Metastasis to contralateral mediastinal or
hilar lymph nodes, ipsilateral or contralateral
scalene, or supraclavicular lymph nodes.
• M0- No (known) distant metastasis.
• M1- Distant metastasis present.

39. Clinical features:
• Major complaints are
- Cough (75%),
- Weight loss (40%),
- Chest pain (40%),
- Dyspnea (20%) and
- Haemoptysis.

40. PARA-NEOPLASTIC SYNDROME
• Antidiuretic hormone (ADH).
• Adrenocorticotropic hormone (ACTH), producing
Cushing syndrome.
• Parathormone, parathyroid hormone-related
peptide.
• Calcitonin, causing hypocalcemia.
• Gonadotropins, causing gynecomastia.
• Serotonin and bradykinin, associated with the
carcinoid

41. • Lambert-Eaton myasthenic syndrome.
• Acanthosis nigricans.
• Apical lung cancers in the superior pulmonary
sulcus tend to invade the neural structures around
the trachea, including the cervical sympathetic
plexus, and produce a group of clinical findings
that includes severe pain in the distribution of the
ulnar nerve and Horner syndrome (enophthalmos,
ptosis, miosis, and anhidrosis) on the same side as
the lesion. Such tumors are also referred to as
Pancoast tumors.

42. Metastases to lung:
• The lung is the most common site of metastatic
neoplasms.
• Both carcinomas and sarcomas arising anywhere
in the body may spread to the lungs via the blood
or lymphatics or by direct continuity.
• Growth of contiguous tumors into the lungs
occurs most often with esophageal carcinomas
and mediastinal lymphomas.

43. • GROSS- Multiple discrete nodules (cannonball
lesions) are scattered throughout all lobes.
• These discrete lesions tend to occur in the
periphery of the lung rather than in the central
locations of the primary lung carcinoma.
• Other patterns include solitary nodule,
endobronchial, pleural, pneumonic consolidation,
and mixtures of the above.

44. Metastases to lung

45. Metastases to lung

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