Lung tumors Maram abdaljaleel - PowerPoint Presentation

Slide1

Lung tumors

Maram

abdaljaleel

, MD

Dermatopathologist

&

neuropathologist

Slide2

95

%

of primary lung tumors are

carcinomas

Slide3

hamartoma

The most common benign tumor

It’s clonal, so the name

hamartoma

is a misnomer

Gross: spherical

, small (

1 to

4 cm),

discrete

CXR: coin lesion.

Microscopic: mature cartilage, fat

, fibrous tissue,

and blood vessels.

Slide4

Carcinoma OF THE LUNG

Slide5

The

most important cause

of cancer-related

deaths in industrialized

countries

The

incidence

among males

is gradually

decreasing, but it continues to increase

among females

BECAUSE

the

incidence

of smoking

in women

increased markedly over the past half century.

Slide6

peak incidence at

50s & 60s

.

At

diagnosis

:

>50% of

pts

have distant metastases

¼ have disease in the regional

LNs.

The prognosis

is dismal

:

the 5-year survival rate for all stages of lung cancer combined is about

16

%

Prognosis has

not changed

over

the last 35

yrs

; even with disease localized to the

lung, the

5-year survival rate is only 45%.

Slide7

The four major histologic types of carcinomas of

the lung

adenocarcinoma

squamous

cell

carcinoma

small

cell carcinoma (a subtype

of neuroendocrine

carcinoma

)

large

cell

carcinoma

Slide8

Slide9

Squamous cell and small cell carcinomas

have the strongest association with

smoking

adenocarcinoma

has replaced squamous cell carcinoma as

the most common

primary lung

tumor

in recent

yrs

, because

of changes in smoking patterns in

US.

Adenocarcinomas is

the most common primary tumors arising in women, in never-smokers, and in individuals younger than 45 years of age.

Slide10

Old

designation to small cell lung cancer

(SCLC)

and non–small

cell lung cancer

(

NSCLC)

NSCLC

includes adenocarcinoma

, squamous and large cell carcinoma,

and large

cell neuroendocrine

carcinomas

Slide11

SCLCs:

virtually all cases have metastasized by the time of diagnosis

not curable by surgery.

best treated by chemotherapy, +/-radiation therapy

.

NSCLCS:

more

likely to be

Resectable

Respond poorly

to chemotherapy

targeted

therapy nowadays for

adenocarcinoma

and

SqCC

.

Slide12

Cigerrate

smoking (90% of cases)

Only 11% of heavy smokers develop lung cancer

Passive smoking

Other carcinogens: miners of radioactive ores; asbestos workers and workers exposed to arsenic, chromium, uranium, nickel, vinyl chloride, and mustard gas

SMOKING +ASBESTOS= 55x risk

Slide13

Accumulation of

genetic abnormalities

after exposure to

carcinogens

resulting in a stepwise accumulation of driver

mutations



transformation

of benign

progenitor cells

in the lung into neoplastic cells possessing all of

the hallmarks

of cancer

Pathogenesis:

Genetic abnormalities

carcinogens

Slide14

:

Inactivation of tumor

suppressor genes located on

chromosome

3

(3p)

as an early

event

mutations

in

TP53

tumor

suppressor gene

and

KRAS

oncogene

as a late event

mutations

that activate the epidermal growth factor receptor (EGFR)

Genetic abnormalities:

Slide15

Carcinogens:

cigarette smoking

environmental carcinogens

Slide16

cigarette

smoking

90

%

in active smokers

or those who stopped recently.

linear

correlation between the frequency of

lung cancer

and pack-years of cigarette smoking.

habitual

heavy

smokers

(two

packs a day for 20 years

) have

60X

more risk

than among nonsmokers

.

For unclear reasons,

women are more susceptible

to

carcinogens

in

tobacco smoke than men.

Slide17

Although smoking cessation

decreases

the risk over time, it

never

returns to baseline

levels

smoking of pipes, cigars and passive

smoking increases the risk

.

11% of heavy smokers develop lung

cancer

Not all individuals exposed to tobacco smoke develop

cancer

because

the mutagenic

effect of carcinogens is modified by hereditary (genetic) factors

Slide18

Environmental carcinogens:

Occupational exposures

to some environmental carcinogens may

sometimes be responsible for lung cancer

all by

themselves

,

e.g

:

uranium mines

work with

asbestos

inhalation

of dusts containing

arsenic, chromium

, nickel, or vinyl chloride.

Slide19

asbestos and tobacco smoking

SYNERGISTIC INTERACTION:

Exposure

to asbestos

in nonsmokers

increases the risk

for developing

lung

cancer 5-fold

heavy

smokers exposed to asbestos

the risk

is elevated approximately 55-fold

.

Slide20

Some

invasive

adenocarcinomas of

the lung arise through an

atypical

adenomatous hyperplasia–adenocarcinoma

in situ–invasive

adenocarcinoma

sequence

.

Slide21

The four major histologic types of carcinomas of

the lung

A

denocarcinoma

S

quamous Cell Carcinoma

S

mall

C

ell

C

arcinoma

(a subtype

of neuroendocrine

carcinoma

)

L

arge

C

ell

C

arcinoma

Slide22

usually

peripherally located,

but also may occur closer to the hilum.

grow

slowly

form

smaller masses

tend

to metastasize

widely at

an early

stage

Adenocarcinomas

Slide23

variety of growth

patterns

including

acinar

(gland-forming

)

;

papillary; mucinous and solid types

MORPHOLOGY, MICROSCOPIC:

Slide24

atypical

adenomatous

hyperplasia (AAH)

adenocarcinoma in situ (AIS)

Adenocarcinoma,

minimally invasive or invasive

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide25

Atypical adenomatous

hyperplasia:

well-demarcated

focus of epithelial proliferation

diameter

of

<

5

mm

composed

of cuboidal to low-columnar cells

demonstrating

nuclear

hyperchromasia

,

pleomorphism

, and prominent nucleoli.

monoclonal

and shares many molecular aberrations with adenocarcinomas (e.g.,

KRAS

mutations).

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide26

Adenocarcinoma in situ

(AIS

):

formerly

bronchioloalveolar

carcinoma

often

involves

peripheral parts

of the lung as a single nodule.

diameter

of

<

3

cm

growth

along preexisting structures, and preservation of alveolar architecture

.

Slide27

The tumor cells, which may be

nonmucinous

, mucinous, or

mixed

grow in a monolayer along the alveolar septa, which serve as a

scaffold.

Slide28

By

definition,

AIS

DOES NOT

demonstrate

destruction of alveolar

architecture or

stromal invasion

with

desmoplasia

, features that would

merit the

diagnosis of invasive adenocarcinoma.

Slide29

M

inimally

invasive

adenocarcinoma

:

<3

cm

in diameter with an invasive component of

<5

mm

I

nvasive

adenocarcinoma

a

tumor of any size with an area of invasion

>5

mm.

Slide30

Atypical adenomatous

hyperplasia

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide31

Adenocarcinoma in situ, no invasion

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide32

Gland-forming adenocarcinoma

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide33

The four major histologic types of carcinomas of

the lung

A

denocarcinoma

S

quamous Cell

Carcinoma

S

mall

C

ell

C

arcinoma

(a subtype

of neuroendocrine

carcinoma

)

L

arge

C

ell

C

arcinoma

Slide34

More common in

men

Closely correlated with

smoking history

Arise

Centrally in major bronchi

and

eventually

s

pread to local

hilar

nodes and outside the thorax

Large lesions

may undergo

central necrosis

, giving rise to

cavitation.

SQUAMOUS cell carcinomas

Slide35

Pre-neoplastic

lesions:

squamous metaplasia or dysplasia

in the bronchial

epithelium



carcinoma in

situ

 Squamous cell carcinoma

the

lesion is

asymptomatic until reaches

a symptomatic

stage when it begins

to obstruct the lumen of a major bronchus,

+/- atelectasis

and

infection.

Slide36

Ranges from

Well differentiated squamous cell neoplasms

showing keratin pearls and intercellular bridges to

Poorly differentiated neoplasms

with only minimal residual squamous cell features.

MORPHOLOGY:

Slide37

goblet cell hyperplasia

Basal cell

hyperplasia

Squamous metaplasia

Squamous dysplasia

Carcinoma in situ (CIS)

invasive

squamous

cell carcinoma

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide38

ROBBINS BASIC PATHOLOGY, 10

TH

EDITION

Slide39

Well-differentiated SQUAMOUS cell carcinoma showing keratinization and pearls.

Slide40

The four major histologic types of carcinomas of

the lung

A

denocarcinoma

S

quamous Cell

Carcinoma

S

mall

C

ell

C

arcinoma

(a subtype

of neuroendocrine

carcinoma

)

L

arge

C

ell

C

arcinoma

Slide41

Are undifferentiated malignant epithelial tumors.

Lack

cytologic

features of small cell carcinoma and have no glandular or squamous differentiation.

Large nuclei, prominent nucleoli, and a moderate amount of cytoplasm.

Large cell carcinomas

Slide42

https://www.verywellhealth.com/large-cell-carcinoma-of-the-lungs-2249356

Slide43

The four major histologic types of carcinomas of

the lung

A

denocarcinoma

S

quamous Cell

Carcinoma

S

mall

C

ell

C

arcinoma

(a subtype

of neuroendocrine

carcinoma

)

L

arge

C

ell

C

arcinoma

Slide44

Centrally located with extension into the

lung

paranchyma

Early involvement of the

hilar

and

mediastinal

nodes

.

By the time

of diagnosis

, most will have metastasized to

hilar

and

mediastinal

lymph

nodes.

In

the 2015 WHO Classification, SCLC is

grouped together

with large cell neuroendocrine

carcinoma

SMALL cell carcinomas (SCLC)

Slide45

Pale grey tumor

Small tumor cells:

Round

to

fusiform,

scant cytoplasm, finely granular

chromatin

a salt and

pepper appearance

Cells

are twice the size of resting lymphocytes.

Morphology:

Slide46

Frequent

mitotic

figures

Necrosis invariably present,

can be extensive.

Morphology:

Slide47

Slide48

Fragile

tumor cells with

“crush artifact

” in small biopsy

specimens

Nuclear molding

due to close

apposition of tumor cells that have scant

cytoplasm

Express

neuroendocrine

markers

Secreting

hormones



paraneoplastic

syndromes .

Morphology:

Slide49

Mixed patterns

(e.g.,

adenosquamous

carcinoma

, mixed adenocarcinoma, small cell

carcinoma)

are

seen in 10% or less of lung carcinomas.

Slide50

basophilic staining of vascular walls due to encrustation by and from necrotic tumor cells (

A

zzopardi

effect).

Slide51

Each of the Tumor types tends to spreads to nodes around the carina, mediastinum, and in the neck and

clavicular

regions

Left supraclavicular node (

Virchow node

) involvement is particularly characteristic.

When advanced, Extend into the pleural or pericardial space, leading to inflammation and effusion or may Compress or infiltrate the SVC to cause either venous congestion or the

vena

caval

syndrome.

Spread and metastasis

Slide52

Pancoast

tumors (

Pancoast

syndrome

): Apical neoplasms that may Invade the brachial or cervical sympathetic plexus to cause:

Severe pain in the distribution of the ulnar nerve.

Horner syndrome (

ipsilateral

enophthalmos

, ptosis,

miosis

, and

anhidrosis

).

Destruction of the first and second ribs and sometimes thoracic vertebrae.

tumor-node-metastasis(TNM

) categories are used to indicate the

size and spread

of the primary neoplasm.

Slide53

Mostly Silent, insidious lesions

Chronic cough and expectoration

Hoarseness, chest pain, superior vena cava syndrome, pericardial or pleural effusion, or persistent segmental atelectasis or pneumonitis

Symptoms from metastatic spread:

Brain (mental or neurologic changes)

Liver (

hepatomegaly

),

Bones (pain).

Clinical Course

Slide54

NSCLCs

carry a better prognosis than

SCLCs

.

If

NSCLCs

detected before metastasis or local spread,

cure is possible

by

lobectomy

or

pneumonectomy

.

Prognosis, NSCLCs:

Slide55

Prognosis, SCLCs:

SCLCs

, invariably spread by the time they are first detected even if the primary tumor appears to be small and

localized

Surgical

resection is not a viable treatment.

Very

sensitive to chemotherapy but invariably recur

.

Median survival even with treatment is 1 year.

Slide56

(

1)

Hypercalcemia

(secretion of a PTH related peptide)

(2)

Cushing syndrome

(production of ACTH)

(3)

Syndrome of inappropriate secretion of ADH

(4)

Neuromuscular syndromes,

including a

myasthenic

syndrome, peripheral neuropathy, and

polymyositis

(5)

Clubbing

of the fingers and hypertrophic pulmonary

osteoarthropathy

(6)

Coagulation abnormalities

, including migratory thrombophlebitis, nonbacterial endocarditis, and DIC.

paraneoplastic

syndromes

Slide57

Carcinoid Tumors

Slide58

Carcinoid

Tumors

5%

of all

pulmonary neoplasms.

malignan

t tumors,

low-grade

neuroendocrine carcinomas

composed

of

cells containing

dense-core

neurosecretory

granules in

their cytoplasm

and, rarely, may secrete hormonally

active polypeptides.

Slide59

subclassified

as

typical or atypical

; both are often

resectable

and curable

.

May

occur as part of the

multiple endocrine neoplasia

syndrome (MEN syndrome)

young adults

(mean

40 years

)

5% to15%

of carcinoids have metastasized to the

hilar

nodes at presentation

distant

metastases are

rare

Slide60

Morphology, macroscopically:

originate in

main

bronchi

mostly,

Peripheral carcinoids are less

common

well

demarcated

grow

in one

of two

patterns

:

an

obstructing

polypoid

, spherical,

intraluminal mass

a

mucosal plaque

penetrating the bronchial wall to fan out in the peribronchial

tissue—the so-called

collar-button lesion

Slide61

Slide62

Morphology, microscopically:

T

ypical carcinoids:

composed

of nests of uniform cells that have regular round

nuclei with

“salt-and-pepper” chromatin, a

bsent

or rare mitoses and little

pleomorphism

Atypical

carcinoid:

tumors display a higher mitotic rate and small foci of necrosis. These tumors have a higher incidence of lymph node and distant metastasis than typical

carcinoids

have

TP53

mutations in 20% to 40% of cases

Slide63

CLINICALLY:

Mostly manifest

with signs and

symptoms related

to their

intraluminal growth

, including

cough, hemoptysis

, and recurrent bronchial and pulmonary infections

.

Peripheral tumors

are often

asymptomatic

and

discovered incidentally.

Rarely induces

the

carcinoid

syndrome:

intermittent

attacks of diarrhea,

flushing, and cyanosis.

Slide64

Slide65

Prognosis:

5- and 10-year survival rates:

for typical carcinoids are above

85

%

For atypical carcinoid

56% and 35%,

respectively

Slide66

Malignant Mesothelioma

Slide67

Rare cancer of

mesothelial

cells

lining parietal or visceral pleura

Less commonly in the peritoneum and

pericardium

highly related to

exposure to airborne

asbestos

(

80% to 90%

of cases

):

Not only limit to people working with asbestos but also

only exposure was living in

proximity to

an asbestos factory or being a relative of an

asbestos worker.

Malignant

Mesothelioma

Slide68

Long

latent

period: 25

to 40 years

after initial asbestos

exposure

The combination of cigarette smoking and asbestos exposure

DOES NOT

increase

the risk of developing malignant

mesothelioma

BUT INCREASES

the risk for developing

lung carcinoma

Once inhaled,

asbestos fibers remain in the body for

life

.

the

lifetime risk after exposure

DOES NOT

diminish over

time (unlike with smoking, in which the risk

decreases after

cessation).

Slide69

Preceded

by extensive pleural fibrosis and plaque

begin in a localized area and spread widely, either by contiguous growth or by diffusely seeding the pleural surfaces.

Distant metastases are rare.

Morphology, macroscopic:

Slide70

At autopsy,

the affected

lung typically

is

ensheathed

by a layer of yellow-white,

firm, variably

gelatinous tumor that obliterates the pleural space

Slide71

thick, firm, white pleural tumor that

ensheathes

this bisected lung.

Slide72

Normal

mesothelial

cells are biphasic, giving rise to

pleural lining

cells as well as the underlying fibrous tissue.

Normal histology:

Diagnostic pathology, normal histology text book

Slide73

one

of

three

morphologic

appearances:

Epithelial:

cuboidal cells with small papillary buds line tubular and

microcystic

spaces (the

most common &

confused

with a pulmonary

adenocarcinoma)

(2

)

sarcomatous

:

spindled cells grow

in sheets

(3)

biphasic

: both sarcomatous and epithelial areas

Morphology, microscopic:

Slide74

Thank you!