Lung Tumors

Objectives

• To known types of lung tumors.

• To known causes and pattern of lung
tumors.
• about 95% of primary lung tumors are carcinomas; the
remaining 5% span a miscellaneous group that
includes carcinoids, mesenchymal malignancies.
• the most common benign tumor is a spherical, small (1
to 4 cm), discrete “hamartoma” that often shows up as
a so-called “Coin lesion” on chest imaging.
 Carcinomas

• the four major histologic types of carcinomas of the

lung are adenocarcinoma, squamous cell
carcinoma, small cell carcinoma (a subtype of
neuroendocrine carcinoma), and large cell
carcinoma.
Cont. ….

• Squamous cell and small cell carcinomas have the

strongest association with smoking.

• Adenocarcinomas also are by far the most common

primary tumors arising in women, in never-smokers,
and in individuals younger than 45 years of age.
Etiology and Pathogenesis

• like other cancers, smoking-related carcinomas of

the lung arise by a stepwise accumulation of driver
mutations that result in transformation of benign
progenitor cells in the lung into neoplastic cells
possessing all of the hallmarks of cancer.
Cont. ….

• thus, inactivation of the putative tumor suppressor

genes is a very common early event, whereas
mutations in the TP53 tumor suppressor gene and the KRAS
oncogene occur relatively late.

• for unclear reasons, women are more susceptible to

carcinogens in tobacco smoke than men
Cont. ….

• passive smoking (proximity to cigarette smokers)

also increases the risk for developing lung cancer, as
does smoking of pipes and cigars, albeit only modestly.
Morphology

• Carcinomas of the lung begin as small lesions that

typically are arise as intraluminal masses, invade the
bronchial mucosa or form large bulky masses pushing
into adjacent lung parenchyma.
Adenocarcinomas

• usually peripherally located, but also may occur closer

to the hilum.
• it grow slowly and form smaller masses than do the
other subtypes, but they tend to metastasize
widely at an early stage.
Cont. ….

• they may assume a variety of growth patterns,

including acinar (gland-forming), papillary, mucinous
which is often multifocal and may manifest as
pneumonia-like consolidation, and solid types.
• the solid variant often requires demonstration of
intracellular mucin by special stains to establish its
adenocarcinomatous differentiation.
Cont. ….

• the putative precursor of adenocarcinoma is atypical

adenomatous hyperplasia (AAH), which is thought
to progress in a stepwise fashion to adenocarcinoma
in situ.
• Genetic analyses have shown that AAH is monoclonal
and shares many molecular aberrations with
adenocarcinomas (e.g KRAS mutations).
Cont. ….

• Adenocarcinoma in situ (AIS) (formerly

bronchioloalveolar carcinoma), often involves
peripheral parts of the lung as a single nodule.
• the key features of AIS are diameter of 3 cm or less,
growth along preexisting structures, and preservation
of alveolar architecture.
(A) (C)

• Adenocarcinoma and associated lesions.

(A) Atypical adenomatous hyperplasia with cuboidal
epithelium and mild interstitial fibrosis.
(B) Adenocarcinoma in situ, mucinous subtype, with
characteristic growth along preexisting alveolar septa,
without invasion.
(C) Gland-forming adenocarcinoma; inset shows thyroid
(B) transcription factor 1 (TTF-1) positivity, which is seen in a
majority of pulmonary adenocarcinomas.
Squamous cell carcinomas

• more common in men and are closely correlated with

a smoking history
• they tend to arise centrally in major bronchi and
eventually spread to local hilar nodes, but they
disseminate outside the thorax later than do
other histologic types.
• large lesions may undergo central necrosis, giving rise
to cavitation.
Cont. ….

• squamous cell carcinomas often are preceded by

the development, over years.
• squamous metaplasia or dysplasia in the bronchial
epithelium, which then transforms to carcinoma in
situ, a phase that may last for several years.
Cont. ….

• by this time, atypical cells may be identified in

cytologic smears of sputum or in bronchial
lavage fluids or brushings, although the lesion is
asymptomatic and undetectable on radiographs.
Cont. ….

• Histologic examination.

the tumors range from well differentiated squamous

cell neoplasms showing keratin pearls and
intercellular bridges to poorly differentiated
neoplasms exhibiting only minimal squamous cell
features
Precursor lesions of squamous cell carcinomas
 Squamous cell carcinoma. (A) Squamous cell carcinoma appearing as a central (hilar) mass
that is invading contiguous parenchyma. (B) Welldifferentiated
squamous cell carcinoma, showing keratinization and pearls.

(B)

(A)
Large cell carcinomas

• Large cell carcinomas are undifferentiated

malignant epithelial tumors that lack the cytologic
features of neuroendocrine carcinoma and show no
evidence of glandular or squamous
differentiation.
• the cells typically have large nuclei, prominent
nucleoli and moderate amounts of cytoplasm.
Small cell lung carcinomas (SCLCs)

• generally appear as pale gray, centrally located

masses that extend into the lung parenchyma.
• these cancers are composed of relatively small tumor
cells with a round to fusiform shape, scant
cytoplasm and finely granular chromatin with a
salt and pepper appearance.
• numerous mitotic figures are present.
Cont. ….

• necrosis is invariably present and may be extensive.

• the tumor cells are fragile and often show
fragmentation and “crush artifact” in small biopsy
specimens.
Cont. ….

• Cytologic specimens

nuclear molding resulting from close apposition of

tumor cells that have scant cytoplasm.

• by the time of diagnosis, most will have

metastasized to hilar and mediastinal lymph
nodes.
Cont. ….

• mixed patterns (e.g., adenosquamous carcinoma,

mixed adenocarcinoma, small cell carcinoma) are seen
in 10% or less of lung carcinomas
Small cell carcinoma with small deeply basophilic cells and areas of necrosis (top left). Note
basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells
Cont. ….

• each of these lung cancer subtypes tends to spread to

lymph nodes in the carina, the mediastinum, and the
neck (scalene nodes) and clavicular regions.
• involvement of the left supraclavicular node
(Virchow node) is particularly characteristic and
sometimes calls attention to an occult primary
tumor.
Thanks For Attention