lung carcinoma- pathology.

2.  The lungs are ingeniously constructed to carry out
their cardinal function, the exchange of gases between
inspired air and blood.
 Right lung
› Three lobes; superior, middle and inferior
› Oblique and horizontal fissure
 Left Lung
› Two lobes; superior and inferior also Lingula and
Cardiac notch, oblique fissure

3. THE LUNGS AND THE AIRWAY

5.  Numerous mucous secreting
goblet cells and submucosal
glands are dispersed through
the walls of trachea and
bronchi but not in the
bronchioles.
 Bronchioles lack of cartilages.
 Bronchioles have
neurosecretory granules that
secrets
serotonin,calcitonin,and
bombesin.
 Acinus- respiratory
bronchiole
alveolar duct
alveolar sac
alveoli.
3-5 terminal bronchiole is
referred to as the pulmonary
lobule.

6.  Except the vocal cord the entire respiratory
tree is lined by pseudo-stratified tall
columnar cilliated epthelium.
 The vocal cord is lined by stratified
squamous epithelial cell.

7.  Alveolar epithelium- type I pneumocytes
type II pneumocytes.
 Alveolar macrophages.
 Basement membrane.
 Anastomosing capillaries.
 Interstitial tissue-elastic tissue
collagen
fibroblast like interstitial cell
smooth muscle cell
mast cell
lymphocyte and monocyte(rare)
Pores of Kohn-passage of bacteria and exhudate
between adjacent alveoli.

9. A variety of benign and malignant tumors
are arising from lung.
1.carcinoma- 90%-95%.
2.Bronchilal carcinoid-5%.
3.Mesenchymal tumor and others-2-5%.

10.  Lung cancer is currently the most frequently
diagnosed major cancer in the world(estimated 1.6
million new cases in 2008) and the most common
cause of cancer mortality worldwide(1,380,000
deaths in 2008).
 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.
 Cancer of the lung occurs most often between ages 40
and 70 years, with a peak incidence in the 50s or 60s.

11.  About 80% of lung cancers occur in active smokers or those who
stopped recently.
 There is a nearly linear correlation between the frequency of lung
cancer and pack-years of cigarette smoking.
 The increased risk becomes 60 times greater among habitual heavy
smokers (two packs a day for 20 years) compared with nonsmokers.
 11% heavy smoker develop lung carcinoma.
 Women have a higher susceptibility to carcinogens in tobacco than men.
 Although cessation of smoking decreases the risk for lung cancer
over time, it may never return to baseline levels.
 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.

12. Procarcinogen
carcinogen
Activation of
polymorphic p-450
monoxygenase
enzyme system
Genetic variation
in genes
involved in DNA
repair
BASAL CELL
HYPERPLASI
A
METAPLASIA
DYSPLASIA
Carcinoma –in-
situ
Invasive
carcinoma

17. 1. Adenocarcinoma
Lepidic adenocarcinoma
Acinar adenocarcinoma
Papillary adenocarcinoma
Micropapillary adenocarcinoma
Solid adenocarcinoma
Invasive mucinous adenocarcinoma
Mixed invasive mucinous and
nonmucinous adenocarcinoma
Colloid adenocarcinoma
Fetal adenocarcinoma
Enteric adenocarcinomae
Minimally invasive adenocarcinoma
Nonmucinous
Mucinous
Preinvasive lesions
Atypical adenomatous hyperplasia
Adenocarcinoma in situ.
Nonmucinous
Mucinous Cont…

18. 2. Squamous cell carcinoma
Keratinizing squamous cell carcinoma
Nonkeratinizing squamous cell carcinoma
Basaloid squamous cell carcinoma
Preinvasive lesion
Squamous cell carcinoma in situ
3. Neuroendocrine tumors
Small cell carcinoma
Combined small cell carcinoma
Large cell neuroendocrine carcinoma
Combined large cell neuroendocrine carcinoma
Carcinoid tumors
Typical carcinoid tumor
Atypical carcinoid tumor
Preinvasive lesion
Diffuse idiopathic pulmonary neuroendocrine
cell hyperplasia
Large cell carcinoma
Adenosquamous carcinoma
Sarcomatoid carcinomas
Pleomorphic carcinoma
Spindle cell carcinoma
Giant cell carcinoma
Carcinosarcoma
Pulmonary blastoma Cont….

19. Other and Unclassified carcinomas
Lymphoepithelioma-like carcinoma
NUT carcinoma
Salivary gland-type tumors
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Epithelial-myoepithelial carcinoma
Pleomorphic adenoma
Papillomas
Squamous cell papilloma
Exophytic
Inverted
Glandular papilloma
Mixed squamous and glandular papilloma
Adenomas
Sclerosing pneumocytoma
Alveolar adenoma
Papillary adenoma
Mucinous cystadenoma
Mucous gland adenoma .

20.  ADENOCARCINOMA- 38%
 SQUAMOUS CELL CARCINOMA- 20%
 SMALL CELL CARCINOMA- 14%
 LARGE CELL CARCINOMA- 3%
 OTHERS- 25%.

25.  Highly associated with tobacco smoke.
 Deletion of tumor suppressor gene.
 Highest frequency of TP-53 mutation.
 P-16 loss is seen in 65% of tumors.
 EGFR-1 gene amplification.
 Grading of squamous cell carcinoma into well, moderately, and poorly
differentiated types will depend on the degree of squamous differentiation
within the tumor, such as the presence of intercellular bridges and
keratinization.
 Well-differentiated tumors are characterized by sheets of cells that adopt a
pavement-like architecture and contain ample eosinophilic
cytoplasm, round to oval nuclei, and prominent nucleoli.
 A central, comedo-type pattern of necrosis is typically seen in the higher
grade lesions .

26.  Most common carcioma in smoker.
 Most common type in India .
 Produces PTH,PTH-rp causes hypercalcemia.
 Centrally distributed.
 Prone to develop central necrosis and cavitation.
 It is associated with best prognosis.
 PANCOAST TUMOR is a type of squamous cell carcinoma.
TYPES - Keratinizing squamous cell carcinoma
Nonkeratinizing squamous cell carcinoma
Basaloid squamous cell carcinoma
Preinvasive lesion
Squamous cell carcinoma in situ

28. keratinization
LOWER MAGNIFICATION
HIGHER MAGNIFICATION
KERATIN PEARL

29. Well- to moderately
well-differentiated
squamous carcinoma
Poorly differentiated
squamous carcinoma with
central comedo-like areas of
necrosis.

31. Basaloid carcinoma is a variant of bronchogenic carcinoma
characterized by a proliferation of islands of relatively large,
hyperchromatic tumor cells showing prominent peripheral palisading
of nuclei .
• more aggressive clinical behavior than conventional squamous cell
carcinoma.
• Cellular atypia and mitotic figures are common.
Basaloid carcinoma showing
solid islands of tumor cells
with peripheral palisading of
nuclei.

32.  Results from the local extension of the tumor growing in
the apex of the lung.
 Involvement of C8,T1,T2 nerve.
 Shoulder pain radiates to the ulnar distribution of the
arm.
 Radiologic destruction of 1st and 2nd rib.
 Often Horner’s syndrome and pancoast tumor co-
exist.
 Histologicaly it is a type of squamous cell carcinoma.
 Peripheral radiotherapy followed by En-bloc resection
followed by post-opeartive RT/intraoperative
brachytherapy is given.

33.  Poorly differentiated SCC should not be
confused with small cell carcinoma.
 SCC lacks –individual cell necrosis
crush artifact
nuclear molding.
SCC positive for p63 by IHC,small cells are
not.

34.  PREINVASIVE LESION
Atypical Alveolar Hyperplasia(AAH)
Adenocarcinoma –in-situ/Bronchioloalveolar carcinoma(BAC)
typeI/ Mucinous
typeII/ Non Mucinous
Atypical Alveolar Hyperplasia(AAH) Bronchioloalveolar
carcinoma(BAC)
Small, <5 mm >5 mm
polymorphous monomorphous
Mildly atypical mildly atypical
often unsuspected, may be found in
grossly normal lung.
Radiographic and gross lesion is
presnt.

35. • Present as ground glass opacities on chest
x-ray.
• Dysplastic cell growing along the pre-existing
alveolar septae-LEPIDIC GROWTH pattern.
• More often in woman and non-smokers.
• Types-mucinous –intra alveolar mucin.
• non mucinous-peg shaped columnar
cell, HOBNAIL configuration.
• Lepidic-an allusion to the neoplastic cells
resembling butterflies sitting on a fence.

36. MUCINOUS VARIANT OF BAC.

37. NON MUCINOUS VARIANT OF BAC.

38.  Most common histological type worldwide.
 Most common in non smokers ,young adults
,and females.
 Located peripherally, slow growing.
 Propensity to metastasize in opposite lung.
 Metastasize more frequently in CNS.
 Most of the cells contain mucin.
 Noguchi classification is used for adeno
carcinoma.

39.  Majority expresses TTF-1.
 15% Case are EGFR mutation.
 EMA(Epithelial membrane
antigen),cytokeratin-7 positive.
 Napsin positve.
 CEA , CD 15, MOC 31 –genetic markers are
also positive.
 ERLOTINIB-(Anti EGFR)-effective in stage III/IV
Adenocarcinoma.
 CRIZOTINIB-(EML4-ALK translocation)
effective in mucinous and clear cell variant.

40. . Well differentiated
adenocarcinoma with TTF -1
POSITIVITY
Moderately differentiated
adenocarcinoma.

41.  Mucinous carcinoma represents a more recently described variant of
adenocarcinoma.
 The accumulation of abundant pools of mucin destroying the normal lung
parenchyma.
 Another distinctive and diagnostic feature of these tumors is the presence of
small clusters of, or singly scattered, mucinous tumor cells lying
within the pools of mucin.
 Capacity for distant metastasis is very much high .
 Aggressive behavior.
Mucinous (“colloid”)
carcinoma.

42.  Conventional adenocarcinoma, with or without a
prominent lepidic pattern.
 The tumors are characterized by numerous papillary
infoldings with thin fibro-connective tissue stalks
that completely fill and distort the air spaces.
 Psammoma bodies may also be present.
 A “micropapillary” variant of pulmonary
adenocarcinoma has also been described
characterized by small, abortive micropapillary
structures.
 Such tumors are associated with a highly aggressive
behavior and increased incidence of metastasis.

43. Papillary carcinoma of the lung.

44.  Highly malignant tumor.
 Strong relationship to cigaratte smoking.
 Only 1 % occur in non smoker.
 Major bronchi and periphery of the lung are involved.
 Most aggressive tumor.
 Metastasizing widely and virtually always to be fatal.
 Microscopy-relatively small cells with scant cytoplasm.
ill defined cell border.
finely granular nuclear chromatin.
(salt and pepper chromatin)
the cells are round oval spindle shaped.
 Azzopardi effect-basophilic staining of the vascular wall due to
encrustation by DNA from the necrotic tumor.
 Dense core neurosecretory granules seen in electron microscopy.
 Anti-apoptotic BCL-2 in 90% of the tumor.
 Chromogranin,synaptophysin,CD57 POSITIVE.
 5 year survival rate- 5%.

45. Poorly differentiated
neuroendocrine carcinoma
of the lung, small cell type
Small cell carcinoma with
spindle cell features
Poorly differentiated
neuroendocrine carcinoma
of lung, mixed small cell–large
cell type.

46.  The cellular proliferation may be
focally arranged in ribbons or cords
admixed with rosette like structures, giving
the lesion a neuroendocrine appearance.
 “Basaloid” appearance due to
peripheral palisading of nuclei.
 A high degree of overlap can be
observed between these tumors and
moderately differentiated neuroendocrine
carcinoma (atypical carcinoid).
 Diagnosis of exclusion.
 5 year survival rate- 30%.

47. Large cell neuroendocrine carcinoma.

48.  1%-5% of all lung tumor. Low grade tumor.
 Younger than 40 years of age.
 No gender preferrence.
 20%-40% non smokers are involved.
 Types- typical- <2 mitotic figure/10 HPF.
 atypical- 2-10 mitotic figure/10 HPF.
 Gross-fingerlike/spherical polypoidal masses project into the lumen of
bronchus, covered by mucous membrane.
 Rarely exceeds 3-4 cm in diameter.
 Collar button lesion- when penetrated the peri-bronchial tissue.
 Peripherally located tumor are solid and nodular.
 Cells are separated by delicate fibro-vascular stroma .
 Cells have regular uniform round nuclei and moderate amount of
cytoplasm.
 IHC-Serotonin,NSE(Neuron Specific Enolase),bombesin,calcitonin.
 Classic carcinoid syndrome- diarrhea ,flushing, cyanosis.
 5 year survival rate for typical and atypical carcinoid -95% and 75%.

49. Carcinoid growing as a
spherical mass (arrow)
protruding into the lumen
of the bronchus
The tumor cells have small,
rounded, uniform nuclei and moderate
amounts of cytoplasm.

50.  Unusual family of primary neoplasm of the lung.
 The tumor are most likely originate from the
sub-mucosal glands of the bronchi.
 May be arise from the pulmonary parenchyma.
Types- Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Epithelial-myoepithelial carcinoma
Pleomorphic adenoma.

51.  Most common salivary gland type neoplasm of the lung.
 Epidermoid differentiation with intracelluar and extracelluar
mucin.
 Low grade lacks of hemorrhage,necrosis,nuclear atypia,and
mitotic figure.
 PAS and mucicarmine positive.
Mucoepidermoid
carcinoma

52.  There are three types- cribriform ,solid and tubular.
 Peri-neural invasion present.
 Luminal spaces often filled with mucous material.
 Fibrous band.
 Scant eosinophilic cytoplasm.
Cribriform type of adenoid cystic
carcinoma

53.  Cells have abundant clear cytoplasm.
 Displacement of nuclei towards the periphery.
 Pleomorphism, nuclear atypia, mitotic figure are absent.
 Co-expression of actin and keratin.
 Focal positivity for vimentin and S-100.
clear
Myo-epithelial outer cell
layer in the glands.

55.  Small cell carcinoma-
ADH Hyponatremia
ACTH Cushing syndrome
Calcitonin Hypocalcemia
ANF,Gastrin releasing peptide,vasopressin
Squamous cell carcinoma-
PTH,PTH-rp Hypercalcemia.
Prostaglandin-E,cytokines.

56.  Peripheral neuropathy(purely sensory)-due to
auto-antibodies against neuronal calcium
channel.
 Acanthosis nigricanus.
 Leukemoid reaction.
 Trousseau syndrome
(DVT+THROMBOEMBOLISM)
 Hypertrophic pulmonary osteoarthropathy.

57.  Pleural surface cavity pericardium.
 Bronchial, tracheal, mediastinal lymph nodes.
 Nodal involvement>50%.
 Lymphatic and hematogenous spread occurs.
 Squamous cell carcinoma metastasize the thoracic
cavity lately.
 Adrenals are involved more than 50% cases.
 Liver is involved 30%-50% case.
 Brain is involved 20% cases.
 Bone is involved in 20% cases.

62.  Varying degree of
keratinization.
 Polygonal cell.
 Amphophilic
cytoplasm.
 Dark pyknotic
nuclei.
 Dirty background of
necrosis.

63.  Fine foamy vacuolated cytoplasm.
 Vesicular nuclei.
 Prominent nucleoli.
 Acinar pattern.

64.  Polygonal cells
with rounded
nuclei and
spindle cells with
elongated nuclei.
 Nucleoli are not
prominent.
 Nuclear
molding.
 Crush artifact.

65.  Cohesive group of cells with round to polygonal nuclei.
 Cells have prominent nucleoli.
 Vesicular nuclear chromatin.

66. Cells with small
amount of cytoplasm.
Nuclear molding.
Fine granular
chromatin.
Apoptotic debris.
Cellular necrosis.

69.  Stage IA,IB,IIA,IIB SURGICAL RESECTION.
 Adjuvant chemotherapy is gien to stage II.
 Stage IIIA with minimal N2 involvement-
neoadjuvant CT followed by surgical resection
with complete medistinal lymph node
dissection.
 Post-operative radiotherapy for patients found
to have N2 disease.
 SCLC-CISPLATIN+ ETOPOSIDE.
 NSCLC-CISPLATIN+VINORELBINE(+/-
)BEVACIZUMAB.
 CARCINOID-STREPTOZOCIN+ 5-FU.