Copy of Lung Tumours - Copy

8/13/2019 Copy of Lung Tumours - Copy

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LUNG TUMOURS
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Alveoli contain type I and IIpneumocytes

Type I pneumocytes: 95%,flattenedType II pneumocytes: 5%,produce surfactant (lamellarbodies on EM), involved inrepair if type I destroyed

Bronchial-bronchioalvearepithelium contains gobletcells, neuroendocrine(Kultschitskys) cells, serouscells, basal cells, Clara cellsand ciliated cells


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ORIGIN

Carcinomas/adenomas Epithelial tumours B ron ch ial su rface cel l Gob let cel l Bro nch ial g land ce l l Clara cell Type II alveolar epith elial c el l 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

BRONCHOPULMONARYSEQUESTRATION

ADENOCHONDROMA

SOFT TISSUE TUMOURS HAMARTOMAS
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HAMARTOMA

Incidental finding atautopsy in a 64-year-old male with liver

cirrhosis.1.2 cmnodule.parenchymaof the RUL

coin lesion on xray


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HISTOLOGY

abnormaladmixture ofpulmonary tissuecomponents

Fat cartilage Fibrous tissue

Smooth muscle


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CARCINOID TUMOURS also called well-differentiated neuroendocrine carcinoma


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CARCINOID

May be associatedwith MEN syndrome

micro : Rosettes,

trabecular, solid


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CARCINOID

Typical carcinoid:


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MALIGNANT TUMOURS OF THELUNGS

Risk factors Smoking- 80% in active smokers ,direct

statistical correlation between death ratefrom lung cancer and total amount ofcigerettes smoked

95% of lung tumors are bronchogenic ca

bronchial carcinoids mesenchymal miscellaneous neoplasms Peaks at ages 50-69 years; 2% occur before age 40


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CLASSIFICATIONClassification : 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


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Gross/anatomic

HILAR TYPE ARISES IN THE MAINBRONCHUS OR ONE OF ITSSEGMENTAL BRANCHES IN THE HILARPARTS 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 calciumchannel),

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 Pancoasttumors


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PARANEOPLASTIC SYNDROMES

ADH ACTH

PARATHORMONE,PT RELATEDPEPTIDE ,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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Tobacco use

Petroleum products

Atmospheric pollutionasbestos

Genetic

RISK FACTORS

Radon

RadiationURANIUM MINERS

Vitamin A deficiency

Chronic scarring(SCAR CANCERS

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 minersCauses 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 likelyto progress and those that willremain localized


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SQUAMOUS METAPLASIA


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CARCINOMA-IN-SITU


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Proto- oncogenes Cancer suppressorgenes

apoptosis DNA repairgenes(MMR)

Cell cycle check

Genetic changes


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MOLECULAR GENETICS

10-20 GENETIC MUTATIONS HAVEOCCURRED BY THE TIME TUMOUR IS

APPARENT

FIELD EFFECT : GENETIC CHANGES IELOSS OF CHR 3p MATERIAL CAN BE FOUNDIN BENIGN BRONCHIAL EPITHELIUM IN PTSWITH 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,C-MYC,RBSMALL CELL CA

P53,RAS,P16INK4aNON SMALL CELL CA


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Many more mutations leading to mets

I am migrating to the brain ,very overcrowded here


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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 forapproved cancer therapies.

Signaling through VEGF/VEGFRis the target of an approvedcancer therapy.

EGFR is mutationally activated in a subset of non-small cell lungcancer patients, and some EGFRmutations are associated withresistance to erlotinib andgefitinib.

MOLECULAR TARGETS FOR TREATMENT


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GROSS APPEARANCE

LUNG CANCER ARISING IN MAINBRONCHUS

NARROWING ANDOCCLUDING THELUMEN

YELLOWISH -WHITE


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GROSS

NECROSIS HAEMORRHAGE CAVITATORY

LESION


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SQUAMOUS CELL CARCINOMAHISTOLOGY


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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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accounts for about 20-30% of all lungcancers- 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-pulmonarymanifestations ie ectopicadrenocorticotrophin syndrome.


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Site :major bronchi and periphery ,subepithelial alongthe bronchus, peribronchial growth in supporting tissueand lymphatics

- Gross white, fleshy, soft

- Spread: along bronchus distally and proximally, into lungparenchyma to mediastinum or pleura, causing pleuralseeding, pleural effusion, involvement of diaphragm andchest wall

- mediastinal LN involvement occurs early

- Treatment complete excision for non-small cell lungcarcinoma; radiation therapy (usually not-curative),chemotherapy (rarely curative, even for small cellcarcinoma)


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BAL CYTOLOGY


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ADENOCARCINOMAaccounts 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 Gross :

grey to tan, firm or soft depending ondesmoplasia

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

B ron ch ial su rface ce ll typ e w i th l i t t le/nom u c i n

Gob let cel l typ e

B ron ch ial g land ce ll type Clara c el l ty p e Typ e II alveolar epith el ial c el l typ e

Hepatoid A denoc arc inom a of fetal lung type


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glandular diff shape and size differentiation

mucin production intracytoplasmic/

glandular mucin

desmoplasticstroma

micro


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PERIPHERAL ADENOCARCINOMA

ORIGINATE FROMSMALL PERIPHERALBRONCHIOLE

SINGLE OR MULTIPLE PNEUMONIA-LIKE

CONSOLIDATION OFLARGE PART OF LUNG

GREYISH AND MUCOID


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BRONCHIOLOALVEOLAR CA

o arises from terminal bronchioles oralveolar walls

o wide age distribution, associated withcigarette smoking

o periphery, subpleural, no evidence ofstromal, vascular or pleural invasionStage I

o are curable if < 2 cm


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SPECIAL STAINS

Positive stains: mucin, low molecular weightkeratin (CK7), EMA, CEA, TTF1 (72%),surfactant apoprotein (50%), mesothelin (50%),vimentin (9%), S100 (Langerhans cells), p53,

CD57/Leu7 (50% of well/moderatelydifferentiated 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 periphery > centralo males > femaleso smokingo spherical, well-defined, homogeneous fleshyo necrosis: ++o metastasizes earlyo thoracic wall is frequently involved


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Large cell carcinoma

large cells: >diameter of 3lymphocytes

o solid nests, polygonalcells, well defined cellborders


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PLEURAL TUMOURS

Benignmesothelioma

mesothelial cells Resection curative Malignant asbestos SV 40 association. Chest pains ,recurrent

effusions dyspnoea

MICROSCOPY MALIGNANT


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MICROSCOPY MALIGNANTMESOTHELIOMA

SARCOMATOID


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MESOTHELIOMA EPITHELIALTYPE


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METASTATIC TUMOURS

Cannon-ballsecondaries

Osteogenic sar,

neuroblastomas ,wilmmm,lymphomas,leuk


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METS

CANNON-BALLSECONDARIES


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Copy of Lung Tumours - Copy