THE LUNG II:

TUMOURS
 INTRODUCTION

▪ A variety of benign and malignant tumors may arise in the lung,

but 90% to 95% are carcinomas, about 5% are bronchial
carcinoids, and 2% to 5% are mesenchymal and other
miscellaneous neoplasms.
▪ 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.
▪ Since the early 1990s, lung cancer incidence and mortality rates
have been decreasing in men, due to the decreased smoking
rates over the past 35 years. However, decreases in smoking
patterns among women lag behind those of men. Since 1987
more women have died each year of lung cancer than of breast
cancer, which for more than 40 years had been the major cause
of cancer death in women.
▪ For reasons not entirely clear, women have a higher
susceptibility to carcinogens in tobacco than men.
▪ Passive smoking (proximity to cigarette smokers) increases the
risk for lung cancer development to approximately twice that of
nonsmokers. The smoking of pipes and cigars also increases the
risk, but only modestly.
Adenocarcinoma
▪ Adenocarcinoma is an invasive malignant
epithelial tumor with glandular differentiation
or mucin production by the tumor cells.
▪ Adenocarcinomas grow in various patterns,
including acinar, lepidic, papillary,
micropapillary, and solid with mucin formation.
▪ Lepidic adenocarcinoma formerly called
bronchioloalveolar carcinoma.
▪ Compared with squamous cell cancers, the
lesions are usually more peripherally located
and tend to be smaller.
▪ They vary histologically from well-differentiated
tumors with obvious glandular elements to
papillary lesions resembling other papillary
carcinomas to solid masses with only occasional
mucin-producing glands and cells.
▪ The majority express thyroid transcription
factor-1; first identified in the thyroid (TTF-1)
 Squamous cell carcinoma
▪ Squamous cell carcinoma is most commonly found in men
and is strongly associated with smoking.
▪ Squamous cell carcinomas are often antedated by
squamous metaplasia or dysplasia in the bronchial
epithelium, which then transforms to carcinoma in situ, a
phase that may last for several years .
▪ The tumor may then follow a variety of paths. It may grow
exophytically into the bronchial lumen, producing an
intraluminal mass. With further enlargement the bronchus
becomes obstructed, leading to distal atelectasis and
infection. The tumor may also penetrate the wall of the
bronchus and infiltrate along the peribronchial tissue into
the adjacent carina or mediastinum.
▪ Histologically, squamous cell carcinoma 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 . These features are prominent in well-
differentiated tumors, are easily seen but not extensive in
moderately differentiated tumors, and are focally seen in
poorly differentiated tumors.
 Cytologic diagnosis of lung cancer. A sputum specimen shows an
orange-staining, keratinized squamous carcinoma cell with a
prominent hyperchromatic nucleus

Squamous cell carcinoma well differenciated

 Small cell carcinoma
▪ Small cell carcinoma is a highly malignant tumor with a
strong relationship to cigarette smoking.
▪ They may arise in major bronchi or in the periphery of
the lung.
▪ They are the most aggressive of lung tumors,
In pathology, salt-and-pepper
metastasizing widely and virtually always proving to be chromatin, also salt-and-pepper
fatal. nuclei and stippled chromatin, refers
▪ Small cell carcinoma is comprised of relatively small cells to cell nuclei that demonstrate
granular chromatin (on light
with scant cytoplasm, ill-defined cell borders, finely microscopy)
granular nuclear chromatin (salt and pepper pattern),
and absent or inconspicuous nucleoli .
▪ The cells are round, oval, or spindle-shaped, and nuclear
molding is prominent.
▪ The mitotic count is high.
▪ Necrosis is common and often extensive.
▪ Expression of neuroendocrine markers such as
chromogranin, synaptophysin.
▪ Small cell carcinoma is the one that is most commonly
associated with ectopic hormone production.

Basophilic staining of vascular walls due to encrustation by DNA

from necrotic tumor cells (Azzopardi effect) is frequently present.
Paraneoplastic Syndromes.
• The hormones or hormone-like factors elaborated include:
• • Antidiuretic hormone (ADH), inducing hyponatremia due to
inappropriate ADH secretion
• • Adrenocorticotropic hormone (ACTH), producing Cushing
syndrome
• • Parathormone, parathyroid hormone-related peptide,
prostaglandin E, and some cytokines, all implicated in the
hypercalcemia often seen with lung cancer
• • Calcitonin, causing hypocalcemia
• • Gonadotropins, causing gynecomastia
• • Serotonin and bradykinin, associated with the carcinoid
síndrome
• Tumors that produce ACTH and ADH are predominantly small
cell carcinomas, whereas those that produce hypercalcemia
are mostly squamous cell carcinomas.
❑ Lambert-Eaton myasthenic syndrome : muscle weakness
caused by auto-antibodies directed to the neuronal calcium
channel
❑ Peripheral neuropathy, usually purely sensory
❑ Acanthosis nigricans
❑ Trousseau syndrome : hypercoagulable states s (deep vein
thrombosis and thromboembolism)
❑ Hypertrophic pulmonary osteoarthropathy (clubbing of the
fingers)
❑ Horner síndrome: enophthalmos, ptosis, miosis, and
anhidrosis on the same side as the lesion. Such tumors are
also referred to as Pancoast tumors.
Hypertrophic pulmonary
osteoarthropathy
Large cell carcinoma
▪ Large cell carcinoma is an Gross description:
undifferentiated malignant epithelial • Usually peripheral lung and unifocal; spherical
tumor that lacks the cytologic features of tumor with well defined borders and bulging,
other forms of lung cancer. lobulated, homogeneous gray white "fish
▪ The cells typically have large nuclei, flesh" cut surface
prominent nucleoli, and a moderate • Internal necrosis and hemorrhage common
amount of cytoplasm. • Frequently involves thoracic wall
▪ Large cell carcinoma is a diagnosis of
exclusion since is expresses none of the
markers associated with
adenocarcinoma (TTF-1, napsin A) and
squamous cell carcinoma (p63, p40).
Carcinoid Tumors
▪ Carcinoid tumors are low-grade malignant epithelial
neoplasms that are subclassified into typical and atypical
carcinoids.
▪ Carcinoid tumors represent 1% to 5% of all lung tumors.
▪ Most patients with these tumors are younger than 40 years
of age, and the incidence is equal for both sexes.
▪ Approximately 20% to 40% of patients are nonsmokers.
Morphology:
• Carcinoids may arise centrally or may be peripheral.
• The central tumors grow as fingerlike or spherical polypoid
masses that commonly project into the lumen of the bronchus
and are usually covered by an intact mucosa
• Histologically, the tumor is composed of organoid, trabecular,
palisading, ribbon, or rosette-like arrangements of cells
separated by a delicate fibrovascular stroma.
• Typical carcinoids have fewer than two mitoses per 10 high-
power fields and lack necrosis, while atypical carcinoids have
between two and 10 mitoses per 10 high-power fields and/or
foci of necrosis.
• By immunohistochemistry, are found to contain
neuroendocrine markers as: chromogranin A, synaptophisin
and CD56.
Carcinoid
syndrome
Granular cell tumor
▪ Sessile polypoid endobronchial neoplasm
Gross description:
▪ Similar to granular cell tumors at other sites
• White-tan, ill-defined mass with gritty cut surface
▪ Also known as Abrikossoff tumor
• Necrosis and hemorrhage are uncommon
▪ All ages, with peak in middle age (4th-6th
• Typically small (< 5 cm)
decades)
▪ Slight female predominance (3:2)
▪ Controversial histogenesis, but appears neural /
Microscopic (histologic) description:
schwannian
• Polygonal cells with abundant, eosinophilic, coarsely
granular cytoplasm and small, hyperchromatic, oval to
slightly irregular nuclei with indistinct nucleoli
• No / rare mitoses, no necrosis, no vascular invasion
Clear cell (sugar) tumor

• Benign/borderline peripheral lung neoplasm

derived from perivascular epithelioid cells
• Member of perivascular epithelioid cell tumor
(PEComa) or "myomelanocytoma" family
• Clear to eosinophilic, finely granular
cytoplasm containing abundant PAS+ glycogen
(sugar tumour)
• Stains with melanocytic and smooth muscle
markers by immunohistochemistry
• Generally incidental finding on imaging
 • Most common benign tumor of lung
• Benign, generally solitary lesion composed of mature but disordered hyaline cartilage,
fat and smooth muscle, with entrapped clefts of respiratory epithelium
Hamartoma • Sometimes with calcification / ossification
• RX: Incidental coin lesion; well circumscribed, small, smooth to lobulated nodule, with
irregular nodular “popcorn” calcifications
 • 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

Metastatic Tumors •
lymphatics or by direct continuity.
In the usual case, multiple discrete nodules (cannonball lesions) are scattered throughout all lobes, more being
at the periphery.
• Other patterns include solitary nodule, endobronchial, pleural, pneumonic consolidation, and combinations of
these.
 Pleural Tumors

▪ The pleura may be involved by primary or

secondary tumors.
▪ Secondary metastatic involvement is far
more common than are primary tumors.
▪ The most frequent metastatic
malignancies arise from primary
neoplasms of the lung and breast.
▪ In most metastatic involvements, a
serous or serosanguineous effusion
follows that often contains neoplastic
cells
Solitary Fibrous Tumor
• Solitary fibrous tumor is a soft-tissue tumor with a propensity to occur in the pleura
• The tumor is often attached to the pleural surface by a pedicle.
• It may be small (1 to 2 cm in diameter) or may reach an enormous size, but it tends to remain
confined to the surface of the lung .

• Morphology:

• Grossly, solitary fibrous tumor consists of dense fibrous tissue.

• Microscopically, the tumor shows whorls of reticulin and collagen fibers among which are
interspersed spindle cells resembling fibroblasts.
• The tumor cells are CD34+ and keratin-negative by immunostaining, features that are helpful in
distinguishing these lesions from malignant mesotheliomas (which show the opposite phenotype)
• The solitary fibrous tumor has no relationship to asbestos exposure.
Malignant Mesothelioma
▪ Malignant mesotheliomas, although rare, have assumed great
importance in the past few decades because of their increased
incidence among people with heavy exposure to asbestos.
▪ There is a long latent period of 25 to 45 years for the
development of asbestos-related mesothelioma, and there
seems to be no increased risk of mesothelioma in asbestos
workers who smoke. This is in contrast to the risk of asbestos-
related lung carcinoma, already high, which is markedly
magnified by smoking.
▪ Asbestos bodies are found in increased numbers in the lungs
of patients with mesothelioma.
Morphology
• Malignant mesothelioma is a diffuse lesion arising either from the
visceral or parietal pleura, that spreads widely in the pleural space
and is usually associated with extensive pleural effusion and
direct invasion of thoracic structures. The affected lung becomes
ensheathed by a thick layer of soft, gelatinous, grayish pink tumor
tissue .
• Microscopically, malignant mesotheliomas may be epithelioid
(60%), sarcomatoid (20%), or mixed (20%). This is in keeping with
the fact that mesothelial cells have the potential to develop as
epithelium-like cells or mesenchymal stromal cells.
HISTOLOGY

▪ The epithelioid type of mesothelioma consists of

cuboidal, columnar, or flattened cells forming tubular or
papillary structures resembling adenocarcinoma
▪ Immunohistochemical stains are very helpful in
differentiating it from pulmonary adenocarcinoma. Most
mesotheliomas show strong positivity for keratin
proteins, calretinin, Wilms tumor 1 (WT-1) and D240.
▪ The mesenchymal type of mesothelioma (sarcomatoid
type) appears as a spindle cell sarcoma.
▪ Sarcomatoid mesotheliomas tend to have lower
expression of many of the markers described previously
and some may be positive only for keratin.
▪ The mixed (biphasic) type of mesothelioma contains
both epithelioid and sarcomatoid patterns .