TUMORS OF LUNG

PRESENTED BY DR. SWARUPA CHAKMA

PATHOLOGY DEPT

GMC PATIALA

Someone somewhere dies of lung cancer every

30 seconds.

1.59 million die of lung cancer each year more than

breast, prostate and colon cancer combined.

Not restricted to smokers anymore.

Never smoker cancer is the 7th most common cause of

cancer worldwide.

Survival depends on early diagnosis, sadly only 15% of pts

have their cancer diagnosed while still localised in lung.

WHO 2015 CLASSIFICATION OF LUNG

TUMOURS

Epithelial tumours

Mesenchymal tumours

Lymphohistiocytic tumours

Tumours of ectopic origin

Metastatic tumours

EPITHELIAL TUMOURS-

Adenocarcinoma-

lepidic, acinar, papillary,

micropapillary, solid,

mucinous (invasive, mixed

invasive)

non mucinous

colloid, fetal, enteric,

minimally invasive (mucinous,

non-mucinous),

preinvasive lesions- atypical

adenomatous hyperplasia,

adenocarcinoma in situ

(mucinous,non-mucinous)

SCC-

Keratinizing, non-

keratinizing, basaloid,

preinvasive-SCC in situ

Neuroendocrine-

Small cell, large cell

neuroendocrine, combined,

carcinoid-typical, atypical,

preinvasive lesion- diffuse

idiopathic pulmonary

neuroendocrine cell

hyperplasia

Large cell carcinoma

Adenosquamous

Sarcomatoid

Pleomorphic

Spindle cell

Giant cell

Carcinosarcoma

Pulmonary blastoma

Other and unclassified carcinomaLymphoepithelioma like

carcinoma

NUT carcinoma

Salivary gland tumour-

mucoepidermoid, adenoid cystic, epithelial-myoepithelial carcinoma and pleomorphicadenoma

Papillomas-

Squamous, exophytic , inverted, glandular, mixed

Adenomas-

Sclerosing, alveolar, papillary, mucinouscystadenoma, mucous gland adenoma

MESENCHYMAL

Pulmonary hamartoma

Chondroma

PEComatous tumours-

lymphangio-

leiomyomatosis, PEComa-

benign and malignant

Congenital peribronchial

myofibroblastic tumor

Diffuse pulmonary

lymphangiomatosis

Inflammatory

myofibroblastic tumor

Epithelioidhemangioendothelioma

Pleuropulmonary blastoma

Synovial sarcoma

Pulmonary artery intimalsarcoma

Pulmonary myxoid sarcoma with EWSR1–CREB1 translocation

Myoepithelial tumors

Myoepithelioma

Myoepithelial carcinoma

LYMPHOHISTIOCYTIC

Extranodal marginal zone lymphomas (MALT

lymphoma)

Diffuse large cell lymphoma

Lymphomatoid granulomatosis

Intravascular large B cell lymphoma

Pulmonary Langerhans cell histiocytosis

Erdheim–Chester disease

TUMOURS OF ECTOPIC ORIGIN

Germ cell tumors-

teratoma, mature and immature

Intrapulmonary thymoma

Melanoma

Meningioma, NOS

METASTATIC TUMOURS

NEW CHANGES IN 2015 CLASSIFICATION

Use of IHC throughout the classification

A new emphasis on genetic studies to help personalize treatment strategies for advanced lung cancer patients

A new classification for small biopsies and cytology similar to that proposed in 2011

A completely different approach to lung adenocarcinoma

restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories

Reclassifying SqCC into keratinizing, nonkeratinizingand basaloid subtypes with the nonkeratinizing tumors requiring IHC proof.

Grouping of neuroendocrine tumors together in one category

addingNUT carcinoma

changing the term sclerosing hemangioma to sclerosingpneumocytoma

changing the name hamartoma to “pulmonary hamartoma,”

creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and (c) PEComa, malignant,

Introducing the entity pulmonary myxoid sarcoma with an EWSR1–CREB1 translocation

Adding the entities myoepithelioma and myoepithelial carcinomas, which can show EWSR1 gene rearrangements

Recognition of usefulness of WWTR1–CAMTA1 fusions in diagnosis of epithelioid hemangioendotheliomas

Adding Erdheim–Chester disease to the lymphoproliferative tumor,

A group of tumors of ectopic origin to include germ cell tumors, intrapulmonary thymoma, melanoma and meningioma

New small bx/ cytology terminology 2015 WHO classification in resection

specimen

Adeno CA (describe the identifiable

patterns)

Adenocarcinoma of predominant

pattern

With lepidic pattern (if pure, add- an

invasive cant be excluded)

MIA, AIS or invasive adeno with a

lepidic component

Invasive mucinous adenoCA Invasive mucinous adenoCA

AdenoCA with colloid features Colloid adenocarcinoma

AdenoCA with fetal features Fetal adenocarcinoma

AdenoCA with enteric features Enteric adenocarcinoma

NSCC, favour adenocarcinoma (TTF-1

+ve)

Adenocarcinoma

Squamous cell carcinoma Squamous cell carcinoma

NSCC, favour SqCC (p-40+ve) SqCC (non keratinizing may be a

component

NSCC, NOS Large cell carcinoma

New small bx/ cytology terminology 2015 WHO classification in resection

specimen

Small cell carcinoma Small cell carcinoma

NSCC with NE morpho and NE markers,

possibly LCNEC

LCNEC

NSCC wth NE morpho and NE markers

negative

LCC with NE morpho

NSCC-NOS morpho adeno and SqCC

patterns present

Adenosquamous carcinoma (if both

components >=10%)

NSCC-NOS,morpho not present but

immunstains favour both types

adenoCA, SqCC, adenosquamous or

large cell carcinoma with unclear

immunohistochemical features

NSCC with spindle and or giant cell

carcinoma

Pleomorphic, spindle cell and or giant cell

carcinoma

BENIGN TUMORS

o Hamartoma

o Adenoma

o Papilloma

o Leiomyoma

o Atypical adenomatoid hyperplasia

o Diffuse idiopathic neuroendocrine hyperplasia

Relatively common benign lesion

More in males

Site -lung parenchyma( beneath pleura)

CXR -solitary, round (coin lesion), opaque, well circumscribed and 3-4

diameter. Popcorn calcification seen in 1/3rd cases.

M/E - islands of cartilage ,fat , smooth muscle and clefts lined by ciliated

/ non- ciliated respiratory epithelium

IHC- +ve for myoepithelial cells- actin,s-100, ER,PR, androgen receptor(

males)

Chromosomal aberration of 6p21 and 12q14-15

PULMONARY

HAMARTOMA

CYTOLOGY

Biphasic morphology

with a fragment of

benign appearing

epithelium and

fibromyxoid stroma

ADENOMA

Several types of adenomas occur in tne lung

Although very rare

Pulmonary adenoma includes bronchial adenoma,

alveolar adenoma, papillary adenoma

Pleomorphic adenoma subtype of bronchial

adenoma

Gross- polypoid peripheral lesions, attached to

bronchi, well circumscribed, no capsule, upto 10

cms, gray - white, soft, rubbery with chondroid cut

surface, may have tumor tongues outside

circumscribed margin.

M/E- Generally less cartilaginous stroma than salivary gland counterpart, with small branching ductules rather than ducts

Nests, tubules, trabeculae

Mixture of round or oval epithelial cells and myoepithelial cells in chondromyxoid or fibromyxoid stroma with focal hyalinization

Generally nuclear atypia / necrosis / hemorrhage / mitoses, occasional multinucleated giant cells

May show myoepitheliomatous, plasmacytoid, squamous features

Lumina may contain PAS+ eosinophilic secretions

PAPILLOMA

Grows outwards from the surface of the tissues.

Most common type is made up of squamous cells

Tend to grow in large bronchi

Morphologically same as laryngeal lesions

So has HPV connection too

1/3rd cases show malignant change later on

Gross-Tan-white, friable, pedunculated / polypoid, smooth to verrucoid, glistening with a few centimeters in size

May contain mixed squamous and glandular papilloma

May exhibit viral cytopathic effect: enlarged hyperchromatic nuclei, nuclear wrinkling, polychromasia, binucleate forms, perinuclear halos

SQUAMOUS PAPILLOMA M/E-

papillary lesion with arborizing fibrovascular cores lined by

mature squamous epithelium.may grow into adjacent

alveolar spaces,

mild to moderate stromal inflammation,

no mitoses, no necrosis.

CYTOLOGY

a) Atypical squamous cells

present in a background of

neutrophils (Pap smear)

b) Squamous cell resembling a

koilocyte identified in a bronchial

brushing specimen (ThinPrep)

c) Ball of squamous cells seen

on ThinPrep

d) Sheet of squamous cells (H

and E stain, cell block)

CK7, p40, CK5/6 (squamous markers)

Mucicarmine (glandular cells)

LEIOMYOMA

Endobronchial or intraparenchymal lesions

Multiple sited leimyomas (lung, esophagus and

uterus)– MEN 1

Middle aged asymptomatic females

Gross- Endobronchial lesion may be attached by a

broad stalk, firm, white, well circumscribed nodule.

M/E- Bland proliferation of intersecting and

whorled smooth muscle fascicles

Fusiform spindle cells with no atypia, no

hypercellularity, no necrosis, no mitoses

May show fibrosis and hyalinization

+ve for SMA, vimentin

-ve for desmin, S100,ER,PR,etc

ATYPICAL ADENOMATOID HYPERPLASIA

<=5mm area of atypical pneumocyte

proliferation lining centriacinar

alveoli

Minimal septal widening

Hobnail appearance with high N/C

ratio

Multifocal, incidental finding in

background of NSCLC

DD: type 2 pneumocyte hyperplasia

which is ill-defined and patchy in

contrast to AAH which is discrete

DIFFUSE IDIOPATHIC NEUROENDOCRINE

HYPERPLASIA

A generalized

proliferation of

scattered single

cells, small nodules

(neuroendocrine

bodies), or linear

proliferations of

pulmonary

neuroendocrine

cells (PNCs) that

may be confined to

the bronchial and

bronchiolar

epithelium.

ETIOPATHOGENESIS OF LUNG CANCER

1. Tobacco smoking:

Increased risk becomes 60 times greater among habitual heavy smokers (2 packs/day for 20 yrs)

Cessation of cigarette smoking brings the risk down but never to baseline.

Women are more vulnerable than men.

Passive smoking increases the risk to approximately twice than non-smokers.

Progressive alterations in the lining epithelium.

Second hand smoke contributes to cancer

Nicotine addiction

PAH, NNK and other

carcinogens

DNA adducts

Persistantmiscoding

Mutation RAS, MYC,

P53,P16,RB and FHIT

LUNG

CANCER

Metabolic

detox

repair

apoptosis

Nutritional

deficiency

2. Industrial hazards:

Certain industrial exposures increase the

risk of developing lung cancer.

Asbestos

Silica

Nickel

Arsenic

Chromium

Mustard gas

Uranium

3. Air pollution:

May play some role in increased incidence.

Indoor air pollution especially by radon.

4. Scarring:

Due to old infarcts, wounds, scar, granulomatous

infections are associated with adenocarcinoma

5. Pre existing lung disease:

COPD

1. Pulmonary lesion

2. Intrathoracic lesion

3. Extrathoracic lesion

4.Paraneoplastic syndromes

LUNG CANCER symptoms

ADENOCARCINOMA

Most common type of Ca among non-smokers

More in Asians, more in females, peripheral

38% out of 85% of NSCLC

Now emerging as most common form

Gross-

Single or multiple, no cavity seen like SCC

Poorly circumscribed grey yellow lesion

5 patterns-

1 2

4

53

peripheral central

diffuse pneumonia-like consolidation background of underlying fibrosis

diffuse pleural

thickening

DIAGNOSTIC CRITERIA OF ADENOCARCINOMA

IN SITU

A small tumor ≤3 cm

A solitary adenocarcinoma

Pure lepidic growth

No stromal, vascular or pleural invasion

No pattern of invasive adenocarcinoma

No spread through air spaces

Cell type mostly non mucinous, rarely may be

mucinous

Nuclear atypia is absent or inconspicuous

Septal widening with sclerosis/elastosis is common,

particularly in non mucinous AIS

NON MUCINOUS AIS MUCINOUS AIS

has hobnail morphology and discrete

borders.

DD: type 2 pneumocyte hyperplasia

or bronchiolar metaplasia

(monotonous morphology and strong

p53 expression helps in

differentiation)

It is composed of columnar mucinous

epithelium with foveolar/goblet cell

morphology.

DD: upper GI metastasis

MINIMALLY INVASIVE ADENOCARCINOMA

A small tumor ≤3 cm

A solitary adenocarcinoma

Predominantly lepidic growth

≤0.5 cm invasive component in greatest dimension in any one focus

Invasive component to be measured includes

° Any histologic subtype other than a lepidic pattern

° Tumor cells infiltrating myofibroblastic stroma

Minimally invasive adenocarcinoma diagnosis is excluded if the tumor

° Invades lymphatics. blood vessels, air spaces or pleura,

° Contains tumor necrosis,

° Spreads through air spaces

The cell type mostly non mucinous but rarely may be mucinous

LEPIDIC PATTERN

Larger (>3cm) adenocarcinomas that comprise mainly lepidic growth

but also display invasion.

Also included are <=3cm INAs that show necrosis, LVI and PNI

Stage1 LPAs show 90% 5 yr survival rate, good prognosis

DD: MIA

Acinar Papillary

Solid Micropapillary

Acinar cell Ca Papillary Solid Micropapillary

Glandular contain

secretory cells

True fibrovascular

core with papillary

structures

Sheets and nests

of tumor cells

Ill defined tufts

with no

fibrovascular core

Resemble salivary

gland tumor but

no perineural

invasion or

mitosis or

pleomorphism

Intermediate

grade tumour

Papillae replacing

normal alveolar

lining with

cuboidal/

columnar

neoplastic cells

Intermediate

grade tumour

Aggressive

tumour

Poor prognosis

High grade

tumour

Perineural, nodal,

intra and extra

pulmonary

invasion.

Aggressive and

poor prognosis

High grade

tumour

Cytokeratin+,

EMA +, Amylase-

D/D- LCC and

non-keratinizing

SCC

CK7+, CK20-,

TTF1+, Napsin A+

MUCINOUS ADENO CA

1. Colloid adenocarcinoma

2. Enteric adenocarcinoma

3. Fetal adenocarcinoma

This term replaces the former mucinous BAC

Genetic abnormality: KRAS mutations and EMLA4-ALK translocation

Smoking

Aerogenous spread.

Multifocal and presents at a higher stage so mistaken for metastatic disease or multifocal consolidation on imaging

Do not express TTF-1

Mucinous columnar or goblet cell epithelium with intracytoplasmic mucin production. Cells show minimal cytological atypia and maintain nuclear polarity

COLLOID ADENOCA- extracellular mucin lakes that expand and destroy

existing alveolar spaces and contain groups of malignant mucinous

epithelium (goblet or columnar cell type)

ENTERIC ADENOCARCINOMA

A. Tall-columnar tumor cells with eosinophilic cytoplasm and round or ovoid nuclei.

Nuclei arrange in a palisading pattern, with some cells possessing prominent nucleoli

and mitotic figure. B. Irregular glandular cavity with significant necrosis like MCC, the

mesenchyma was composed of loose fibrous tissue and inflammatory cells. C. Tumor

cells with a strong diffuse +ve for CK7. D. Carcinoma, strongly +ve for villin in the brush

border.

The presence of

enteric

differentiation

(acinar/cribriform

architecture and

intra-acinar

necrosis) in at least

50% of the tumor.

FETAL ADENOCA

•Cribriform and

tubular structures

composed of

columnar cells with

clear cytoplasm

(resembling fetal lung

tubules or secretory

endometrium).

•Morular metaplasia,

as in endometroid

adenocarcinoma is

also present.

•Cells show sub

nuclear vacuolization.

•Younger age groups

CYTOLOGY OF ADENOCARCINOMA

Discrete, in 3D clusters, pseudopapillae, true

papillae with fibrovascular core,and glandular

pattern

Sheets of cells with honey comb pattern

Round cells with moderate vacuolated cytoplasm

(signet ring), cyanophilic and more translucent than

SCC

central to eccentric nucleus

Fine chromatin

Prominent nucleoli

PAPILLARY ADENOCARCINOMA

Glandular pattern

Non mucinous

adenocarcinomaMucinous adenocarcinoma

DIFFERENTIAL DIAGNOSIS OF

ADENOCARCINOMA

Poorly differentiated SqCC

Metastatic adenocarcinoma

Reactive bronchial cell hyperplasia

Goblet cell hyperplasia

Reactive mesothelial cells

Hamartomas

Viral inclusions

IHC PROFILE

CK7+,CK20-, CK5-,CK6-

TTF1( nuclear positivity)-77%

Napsin A (cytoplasmic positivity)-80%

CD56+ in 3%

34βE12+ in 46%

CDX2 -

SQUAMOUS CELL CARCINOMA

More common in males

Usually smokers

More centrally located, tend to be larger

Undergo central necrosis with cavitation

Second most common after adeno

Seen in 20%

Epithelium damaged

(goblet cell

hyperplasia)

Basal cell hyperplasia Squamous metaplasia

Squamous dysplasia Carcinoma in situSquamous cell

carcinoma

WELL DIFFERENTIATED SCC

MODERATELY DIFFERENTIATED SCC

POORLY DIFFERENTIATED SCC

Some adenocarcinomas have a very squamous-like

morphology.

So in the absence of unequivocal keratinization,

immunohistochemistry with positive squamous

markers such as p40 or p63 is required to diagnose

surgically resected non keratinizing squamous cell

carcinoma.

There does not seem to be prognostic significance

to keratinizing versus nonkeratinizing squamous

carcinomas

BASALOID SCC

If basaloid component

is greater than 50%

of the tumor,

regardless of the

presence of any

keratinization.

In tumors with 50% or

less of a basaloid

component, this can

be acknowledged in

the diagnosis “with

basaloid features

Squamous metaplasia Atypical squamous metaplasia

CYTOLOGY OF SCC

Polyhedral cells, eosinophilic cytoplasm

Intracellular keratin

Round nucleus with moderate pleomorphism

Hyperchromatic nucleus, inconspicious nucleoli

Fiber cells and tadpole cells

B/g necrosis and granular debris

Keratin pearls seen

COMPARATIVE CYTOLOGY

Cytology features Keratinizing scc Non keratinizing scc

Cell clusters Less, usually discrete More clusters

Cytoplasm orangeophilic basophilic

N/C ratio low high

Nucleoli absent prominent

Chromatin coarse fine

Pyknotic nuclei frequent absent

Tadpole cells and fiber More frequent Less frequent

1.CYTO OF SCC 2.TADPOLE CELL

DIFFERENTIAL DIAGNOSIS OF SCC

Repair

Squamous metaplasia

Degeneration

Mesothelial cells

Radiation/chemotherap

y effect

Upper airway cancer

contamination

IHC-

CK 5/6+ in 100%

TTF1+ in 7%

CD 56+ in 6%

CD 117+ in 18%

34βE12+ in 97%

SMALL CELL CARCINOMA

Sheets,clusters,

rosettes or peripheral

pallisading of small to

medium sized round

cells with minimal

cytoplasm, salt and

pepper chromatin

without prominent

clumps, hyperchromatic,

indistinct nucleoli,

nuclear molding,

smudging, frequent MF

Stroma is scanty,

vascular, delicate

Necrosis and apoptotic

debris are common

More cytoplasm is

present in cells in

metastases or

resections than in small

biopsies

1.AZZOPARDI EFFECT 2.NUCLEAR MOLDING

basophilic nuclear chromatin spreading to

wall of blood vessels

CYTOLOGY

1. SPUTUM 2.FNA AND BRUSHINGS

Enlongated grouping of small dissociating tumourcells (twice the size of lymphocytes; occasionally larger)

Scanty cytoplasm, irregular carrot-shaped, hyperchromatic nuclei, showing molding

Coarse chromatin, incospicuous nucleoli

Mitosis

Degenerative changes

Local tumour diathesis

Better preserved larger cells than in sputum (oval or spindly)

Nuclear molding and clustering

Large coarsely granular or pyknotic nuclei

Open chromatin pattern

Artefactually crushed cells and nuclei

DIFFERENTIAL DIAGNOSIS

Reserve cell hyperplasia- show molding, but they are smaller and more cohesive

Lymphocytes- they usually do not form clusters and tend to be spaced

Pulmonary blastoma

Carcinoid- nuclear molding, necrosis and mitotic activity are not observed, and the chromatin texture is more coarse

Non-small cell carcinoma- powdery chromatin texture, incospicuous nucleoli and prominent nuclear molding are not seen

Ewing`s sarcoma

Neuroblastoma

IHC PROFILE OF SMALL CELL CA

Pan-keratin (100%) +ve

TTF1 (89%) +ve

Neuron specific enolase (77%) +ve

CD117 (75%) +ve

Chromogranin A (58%) +ve

synaptophysin (57%) +ve

CD3, CD20, CD45 –ve

P63 –ve

LARGE CELL CARCINOMA

LCCs are undifferentiated tumours lacking

squamous or glandular differentiation

Represent 10% of NSCLC

Strong association with cigarette smoking

Present as large peripheral tumours

Diagnosis of exclusion

Macroscopically shows a fleshy, necrotic cut

surface without cavitation

LCC SUBTYPES

Large cell neuroendocrine carcinoma

Express neuroendocrine markers including synaptophysin,

chromogranin and CD56

Expression of only one is required for diagnosis

Grouped with other neuroendocrine tumours.

Large cell undifferentiated carcinoma

At least 10% of tumor must show rhabdoid differentiation

Basaloid carcinoma

Rare as in its cutaneous counterpart

Has shifted to squamous cell carcinoma

Lymphoepithelial like carcinoma

Shows syncytial growth pattern

Prominent lymphocytic infiltrate

Associated with Epstein –Barr virus

This has shifted to otherwise and unclassified carcinomas

Clear cell carcinoma

Shows prominent glycogen containing clear cytoplasm

DD: metastatic RCC

LCC with rhabdoid differentiation

Usually express cytokeratins

Approximately half express TTF-1

Neuroendocrine markers are negative

These both clear cell and with rhabdoid phenotype are

cytologic features and not any histological subtype.

LARGE CELL NEUROENDOCRINE

UNDIFFERENTIATED LCC

CYTOLOGY OF LCNEC

Disorganized groups of large clearly malignant cells

Pleomorphic single cells population

Variable, often ill-defined and feathery cytoplasm

High N/C ratio

Irregular nuclei, striking chromatin clearing, multiple nucleoli

Intracytoplasmic neutrophils and necrotic background

Rare variants:

giant cell carcinoma

basaloid carcinoma

lymphoepithelioma-like carcinoma

clear cell carcinoma

large cell carcinoma with rhabdoid phenotype

large cell neuroendocrine carcinoma

Differential diagnosis-

Radiation reaction

Degenerating macrophages

Large cell non-Hodgkin lymphoma

Melanoma

Metastatic carcinoma

Sarcoma

TYPICAL CARCINOID

● Nests or trabeculae of medium sized polygonal cells with lightly eosinophilic

cytoplasm, low nuclear grade, round to oval finely granular nuclei; may have

rosettes or small acinar structures with variable mucin

● Scanty vascular stroma, occasionally amyloid stroma with bone

● No / minimal mitotic activity (<2/10HPF), no necrosis

FNA TYPICAL CARCINOID

Loosely cohesive groups and single cells

Acinar or rosette-like structures

Round, columnar or plasmacytoid cells

Uniform, moderately granular nuclei, 'salt and pepper' chromatin pattern

Ample eosinophilic cytoplasm

Branching capillaries

Mitoses uncommon

DIFFERENTIAL DIAGNOSIS OF CARCINOID

1. Benign bronchial epithelial cells- cohesive, less

coarse chromatin, cilia present

2. Adenocarcinoma- have rossettes but more

pleomorhic

3. Small cell carcinoma- have necrosis and mitosis

4. Atypical carcinoid- ”

5. Lymphoma- less cytoplasm, no clusters

6. Mesenchymal tumor (spindle cell carcinoid)

ATYPICAL CARCINOID

Carcinoid tumors with increased mitotic

activity (2-10 per 10 HPF), nuclear

pleomorphism or foci of necrosis

CYTOLOGY

Cells similar to typical carcinoid

Disorganized growth pattern

Necrosis

Pleomorphism

Mitosis

Prominent nucleoli

ADENOSQUAMOUS

• Shows both

squamous and

glandular

differentiation, with

each component

comprising at least

10%

•Associated with

cigarette smoking

•Present as a

peripheral mass and

can show central scar

formation

•IHC- adeno

component should

express TTF-1 and

CK7, while the

squamous component

expresses p63 and

CK5/6

SARCOMATOID CARCINOMA

Group of poorly differentiated NSCLC (1% of NSCLC)

Strongly associated with tobacco smoking

Commonly central except pleomorphic variant which tends to be peripheral showing predominantly chest wall involvement

Subtypes:

Pleomorphic carcinoma

Spindle cell carcinoma

Giant cell carcinoma

Carcinosarcoma

Pulmonary blastoma

SARCOMATIOD CHANGE WITH ADENOSQ

SPINDLE CELL CARCINOMA

Carcinoma composed exclusively of spindle-shaped

tumor cells.

Tumor cells often obliterate vessels

GIANT CELL CARCINOMA

Neoplastic, highly pleomorphic giant cells, often in inflammatory stroma

● Giant cells are multinucleated, may resemble syncytiotrophoblasts and

produce human chorionic gonadotropin

CARCINOSARCOMA

It is a biphasic tumour composed both of epithelial

and sarcomatoid elements: the carcinoma

component is generally SQCC. The sarcomatoid

component may display

Chondroid

Rhabdoid

Osteoid differentiation

TP53 mutations usually seen

PULMONARY BLASTOMA

Biphasic tumor in which epithelial and

mesenchymal components have a

primitive, “fetal-type” appearance

● Well formed tubular glands

surrounded by cellular stroma of

“embryonal” appearance

● Resembles Wilms' tumor and fetal

lung at 10-16 weeks

● Glandular cells are tall, columnar,

often with clear cytoplasm and

subnuclear and supranuclear

cytoplasmic vacuoles

● Morules with ground-glass nuclei are

common

● Stroma may differentiate towards

striated muscle, smooth muscle,

cartilage

● In infants/children, epithelial

component is benign appearing or

minimal pas +ve

NUT MIDLINE CARCINOMA

Associated with NUT gene chromosomal rearrangement

Affect any age and M=F

Sheets and nests of small sized to intermediate sized cells with

monomorphic appearance.

Abrupt keratinization may be seen.

EWSR1 gene rearrangement seen

Tumor cells are epithelioid or spindled with high mitotic rate, nuclear aypia and

necrosis seen

Keratin, S100, calponin and glial fibrillary acidic protein +ve

Desmin, CD34 -ve.

A. LOW GRADE B CELL LYMPHOMA

B. HIGH GRADE B CELL LYMPHOMA

C. LYMPHOMATOID GRANULOMATOSIS

RECENT ADVANCES

The IASLC in conjunction with the College of

American Pathologists (CAP) and Association for

Molecular Pathology (AMP) have published

guidelines that all lung adenocarcinomas should

undergo validation molecular testing

for EGFR mutation and ALK translocation.

Specific subtypes of NSCLC display varying

responses to different chemotherapeutic agents.

Key oncogenic ‘drivers’ are

EGFR mutations are associated with non

smokers, adenocarcinoma histology, female

gender, Asian ethnicity

EGFR mutation positive – Geftinib/ erlotinib

EGFR mutation negative – carboplatin/ paclitaxel

Smoking status is the the strongest clinical predictor

of response to EGFR-TKIs

Levels of thymidylate synthase (TS), the principal

enzymatic target of pemetrexed, are useful

predictor of response to it’s therapy.

TS levels are

high in SCLC and SQCC

low in adenocarcinoma.

Reduced efficacy of pemetrexed in SCLC and lung

SQCC compared to adenocarcinoma leading to its

exclusion in treatment in both SCLC and SQCC

TREATMENT OF NSCLC

NSCLC for systemic therapy

ALK + crizotinibNon-squamous

histology Platinum/ pemetrexed

Squamous histology Platinum/

gemcitabine or vinorelbine

EGFR mutation+ geftinib/ erlotinib

Regular exercise

Proper nutrition

Sufficient sleep

Meditation