tumors of lung seminar dr. swarupa
TRANSCRIPT
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