LUNG TUMOURS

Alveoli contain type I and II pneumocytes Type I pneumocytes: 95%, flattened Type II pneumocytes: 5%, produce surfactant (lamellar bodies on EM), involved in repair if type I destroyed Bronchial-bronchioalvear epithelium contains goblet cells, neuroendocrine (Kultschitskys) cells, serous cells, basal cells, Clara cells and ciliated cells

ORIGIN
Carcinomas/adenomas Epithelial tumours Bronchial surface cell Goblet cell Bronchial gland cell Clara cell Type II alveolar epithelial cell Neuroendocrine tumours - Kultschitskys cells Sarcomas/benign soft tissue tumours -Mesenchymal tissue (Connective tissue Blood vessels, lymphatics, cartilage) Hematological lymphomas others
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BENIGN LESIONS TUMOURS AND TUMOUR-LIKE LESIONS

CONGENITAL CYSTS BRONCHOGENIC CYSTS BRONCHOPULMONARY SEQUESTRATION ADENOCHONDROMA SOFT TISSUE TUMOURS HAMARTOMAS
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HAMARTOMA
Incidental finding at autopsy in a 64-yearold male with liver cirrhosis.1.2 cm nodule.parenchyma of the RUL coin lesion on xray

HISTOLOGY
abnormal admixture of pulmonary tissue components Fat cartilage Fibrous tissue Smooth muscle

CARCINOID TUMOURS
also called well-differentiated neuroendocrine carcinoma <5% of primary lung tumors Locally invasive, rarely metastasizes low grade tumours younger and 20-40% nonsmokers m:f ratio 1:1 Rarely produces carcinoid syndrome (flushing, diarrhea, cyanosis) 10 year survival is 50% In children, involve lung or liver, may metastasize regardless of histology or classification as carcinoid vs. neuroendocrine carcinoma asymptomatic-peripheral obstruction, inflammation- central extremely vascular polypoid yellow tan or grey, well demarcated usually<2cm
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CARCINOID
May be associated with MEN syndrome micro: Rosettes, trabecular, solid

CARCINOID
Typical carcinoid:<2 mitosis/10 HPF Atypical :2-10 mitosis/10 HPF Malignant carcinoid: Mets LN, liver kidney, bone, adrenals Malignant carcinoid

MALIGNANT TUMOURS OF THE LUNGS

Risk factors Smoking- 80% in active smokers ,direct statistical correlation between death rate from lung cancer and total amount of cigerettes smoked
95% of lung tumors are bronchogenic ca bronchial carcinoids mesenchymal miscellaneous neoplasms
Peaks at ages 50-69 years; 2% occur before age 40 10

Classification: broad classification is non-small cell carcinoma (80%) versus small cell carcinoma (20%) 50% of non-small cell carcinomas are metastatic at diagnosis vs. 80% of small cell carcinomas Many have mixed histologic subtypes

CLASSIFICATION

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Gross/anatomic
HILAR TYPE ARISES IN THE MAIN BRONCHUS OR ONE OF ITS SEGMENTAL BRANCHES IN THE HILAR PARTS OF THE LUNGS PERIPHERAL TYPE

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Sputum cytology

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Clinical features due to local effects

pneumonia,abscess,lung collapse= obstruction lipid pneumonia= obstruction, accumulation of cellular lipid in macrophages pleural effusion =pleural spread hoarseness= recurrent laryngeal nerve invasion dysphagia :oes invasion diaphragm paralysis :phrenic nerve rib destruction :chest wall invasion pericarditis,tamponade:
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Systemic symptoms:
Cancer cachexia =TNF,IL-I,INF-gamma,proteolysis inducing factor,

Lambert-Eaton myasthenic syndrome (muscle weakness due to antibodies to neuronal calcium channel), sensory peripheral neuropathy, acanthosis nigricans, leukemoid reaction, hypertrophic pulmonary osteoarthropathy (clubbing), superior vena cava syndrome (compression/invasion of SVC causes venous congestion, circulatory compromise, dusky head, arm edema), pain in distribution of ulnar nerve Horners syndrome (enophthalmos, ptosis, miosis, anhidrosis) due to apical lung tumors called Pancoast 16 tumors

PARANEOPLASTIC SYNDROMES
ADH ACTH PARATHORMONE,PT RELATED PEPTIDE ,PGE,SOME CYTOKINES CALCITONIN,GONANDOTROPHINS SEROTONIN,BRADYKININ

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relative risk of smokers vs. nonsmokers is 10:1; increases to 20:1 for >40 cigarettes/day; risk is strongly related to number of cigarettes smoked, described in pack years (number of packs per day x number of years smoking)

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NON LETHAL GENETIC CHANGE= Acquired chemical, viruses, radiation Inherited in the germ line 20 A multi-step process at BOTH phenotypic and Genetic Level

RISK FACTORS
Petroleum products Tobacco use
Chronic scarring (SCAR CANCERS

Vitamin A deficiency

Atmospheric pollution asbestos Radon

Genetic

Radiation URANIUM MINERS

radiation exposure, uranium (RR with uranium exposure is 4:1 for nonsmokers, 10:1 for smokers vs. general population); asbestos (RR with asbestos exposure is 5:1 for nonsmokers, 50-90:1 for smokers vs. general population), exposure to nickel, chromate, coal, mustard gas, arsenic, beryllium, iron, vinyl chloride, radon radiation, gold miners Causes of death for asbestos workers are: 20% lung cancer, 10% mesothelioma, 10% GI carcinomas

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PRECURSOR LESIONS
Squamous dysplasia Carcinoma-in-situ Atypical adenomatous hyperplasia Diffuse idiopathic neuroendocrine cell hyperplasia

NOTE :not all cases progress to invasive cancer impossible to distinguish between preinvasive lesions that are likely to progress and those that will remain localized
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SQUAMOUS METAPLASIA

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CARCINOMA-IN-SITU

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Proto- oncogenes

Cancer suppressor genes apoptosis

DNA repair genes(MMR)

Cell cycle check

Genetic changes

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MOLECULAR GENETICS
10-20 GENETIC MUTATIONS HAVE OCCURRED BY THE TIME TUMOUR IS APPARENT FIELD EFFECT : GENETIC CHANGES IE LOSS OF CHR 3p MATERIAL CAN BE FOUND IN BENIGN BRONCHIAL EPITHELIUM IN PTS WITH LC AND IN SMOKERS SMALL CELL CA: P53,C-MYC,RB NON SMALL CELL CA: P53,RAS,P16INK4a
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limitless replicative potential (immortality);

P53,RAS,P16INK4a NON SMALL CELL CA

P53,C-MYC,RB SMALL CELL CA

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I am migrating to the brain , very overcrowded here

Many more mutations leading to mets

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MOLECULAR TARGETS FOR TREATMENT

Indications Non-Small Cell Lung Cancer Principal Targets Cell growth (EGFR and a variety of mutant forms of EGFR [e.g., T790M], HER2) Angiogenesis (VEGFR) EGFR and HER2 are targets for approved cancer therapies. Signaling through VEGF/VEGFR is the target of an approved cancer therapy. EGFR is mutationally activated in a subset of non-small cell lung cancer patients, and some EGFR mutations are associated with resistance to erlotinib and gefitinib.
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GROSS APPEARANCE
LUNG CANCER ARISING IN MAIN BRONCHUS NARROWING AND OCCLUDING THE LUMEN YELLOWISH -WHITE

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GROSS
NECROSIS HAEMORRHAGE CAVITATORY LESION

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SQUAMOUS CELL CARCINOMA HISTOLOGY

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SPREAD
DIRECT :lung,mediastinum,pericardium,heart, pleura ,vertibrae ,cervical sympathetic chain LYMPHATIC :hilar nodes, tracheobronchial mediastinum,cervical,supraclavicular, axillary BLOOD: adrenal,brain, TRANSCOELOMIC

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SMALL CELL CARCINOMA

cytology

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SMALL CELL CARCINOMA

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SMALL CELL CARCINOMA

accounts for about 20-30% of all lung cancers - older, male:female ratio 4:1, related to cigarette smokers - high-grade and rapid growth - secrete a large amount of polypeptide hormones, APUD SYSTEM This produces extra-pulmonary manifestations ie ectopic adrenocorticotrophin syndrome.
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SMALL CELL CARCINOMA

Site :major bronchi and periphery ,subepithelial along
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the bronchus, peribronchial growth in supporting tissue and lymphatics Gross white, fleshy, soft Spread: along bronchus distally and proximally, into lung parenchyma to mediastinum or pleura, causing pleural seeding, pleural effusion, involvement of diaphragm and chest wall mediastinal LN involvement occurs early Treatment complete excision for non-small cell lung carcinoma; radiation therapy (usually not-curative), chemotherapy (rarely curative, even for small cell carcinoma)
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BAL CYTOLOGY

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accounts for about 50% of all lung cancers, most common type in women and non smokers male:female ratio is about 2:1 less strongly associated with cigarette smoking they bear similarity to secondary tumours and must be distinguished CT scans and other investigations to check for presence of a primary- commonly arises around scar tissue associated with asbestos exposure k-ras mutation
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ADENOCARCINOMA

ADENOCARCINOMA Gross :
grey to tan, firm or soft depending on desmoplasia necrosis may be present commonly invade pleura and mediastinal lymph nodes often metastasize to the brain and bones. direct invasion into the thoracic wall
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Subtypes: /origin
Bronchial surface cell type with little/no mucin Goblet cell type Bronchial gland cell type Clara cell type Type II alveolar epithelial cell type Hepatoid Adenocarcinoma of fetal lung type
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micro

glandular diff shape and size differentiation mucin production intracytoplasmic/ glandular mucin desmoplastic stroma
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PERIPHERAL ADENOCARCINOMA
ORIGINATE FROM SMALL PERIPHERAL BRONCHIOLE SINGLE OR MULTIPLE PNEUMONIA-LIKE CONSOLIDATION OF LARGE PART OF LUNG GREYISH AND MUCOID

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BRONCHIOLOALVEOLAR CA
o arises from terminal bronchioles or alveolar walls o wide age distribution, associated with cigarette smoking o periphery, subpleural, no evidence of stromal, vascular or pleural invasion Stage I o are curable if < 2 cm
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SPECIAL STAINS
Positive stains: mucin, low molecular weight keratin (CK7), EMA, CEA, TTF1 (72%), surfactant apoprotein (50%), mesothelin (50%), vimentin (9%), S100 (Langerhans cells), p53, CD57/Leu7 (50% of well/moderately differentiated tumors), calretinin (11%) Negative stains: CK20, vimentin (usually), keratin 5 (usually), P504S EM: goblet cells, mucus cells, nonciliated bronchiolar cells, Clara cells DD: melanoma (may be mucin positive)
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Large cell carcinoma

o o o o o o o periphery > central males > females smoking spherical, well-defined, homogeneous fleshy necrosis: ++ metastasizes early thoracic wall is frequently involved

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Large cell carcinoma

large cells: > diameter of 3 lymphocytes o solid nests, polygonal cells, well defined cell borders

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PLEURAL TUMOURS
Benign mesothelioma mesothelial cells Resection curative Malignant asbestos SV 40 association. Chest pains ,recurrent effusions dyspnoea
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MICROSCOPY MALIGNANT MESOTHELIOMA SARCOMATOID

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MESOTHELIOMA EPITHELIAL TYPE

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METASTATIC TUMOURS
Cannon-ball secondaries Osteogenic sar, neuroblastomas ,wilm mm,lymphomas,leuk

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METS
CANNON-BALL SECONDARIES

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 THANK YOU

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