PULMONARY TUMORSKathryna Lesley T. Ayro

INTRODUCTION

Majority are malignant Currently:

o Most frequently diagnosed major cancer

o Most common cause of cancer mortality

Carcinogenic effects of cigarette smokeo Lung cancer incidence and

mortalityo Prevalence of various histologic

types

ETIOLOGY

Cigarette smokeo Frequency:

Amount of daily smoking tendency to inhale

Duration of smoking habito 10-60 fold greater risko Women are more susceptibleo P53 mutations

Industrial hazardso High dose ionizing radiationo Uraniumo Asbestos

Air pollutiono Radon- indoor air pollution

Molecular genetics

o Dominant genetics C-MYC, KRAS, EGFR, C-

MET and c-KITo Deletion of inactivated tumor

suppressor genes P53, RB1, p16 (INK4a) Chromosome 3p

FHIT, RASSF1A Telomerase activity is

increasedo Small cell carcinoma

C-KIT- over expressed, rarely mutated

MYCN MYCL P53 RB BCL2 3p

o Non small cell carcinoma EFGR KRAS P53 P16INIK4a LKB1, PTEN, TSC (m-TOR

pathway)o Activation of signal transduction

molecules AKT Phosphatidylinositol-3-

kinase ERK1/2 STAT5

Paxillino Precursor lesions

Squamous dysplasia CIS Atypical adenomatous

hyperplasia Diffuse idiopathic

neuroendocrine cell hyperplasia

Histologic Classification of Malignant Epithelial Lung Tumors

Squamous cell carcinomaSmall-cell carcinoma

Combined small-cell carcinomaAdenocarcinoma

Acinar; papillary, bronchioloalveolar, solid, mixed subtypes

Large-cell carcinomaLarge-cell neuroendocrine carcinoma

Adenosquamous carcinomaCarcinomas with pleomorphic, sarcomatoid, or sarcomatous elementsCarcinoid tumor

Typical, atypicalCarcinomas of salivary gland typeUnclassified carcinoma

MORPHOLOGY

Central/hilus of the lungo Small cell carcinomao Squamous cell carcinoma

Peripheralo Adenocarcinomas

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SQUAMOUS CELL CARCINOMA

Males Smoking history p53 mutations

ADENOCARCINOMA

females non smokers peripherally located small than SCCA grow slowly but with early and wider

metastasis may be associated with scarring KRAS mutations Pure or mixed Patterns:

o Acinaro Papillaryo Bronchioalveolaro Solid with mucin production

Bronchioalveolar carcinoma

Terminal bronchioalveolar region Single to multipla small nodules

o Pneumonia-like consolidation Does not involve major bronchi Emphysema and atelectasis are not

common Subtypes:

o Mucinous Mucin secreting clara cells

and type 2 pneumocytes

Aerogenous spreado Non mucinous

LARGE CELL CARCINOMA

Undifferentiated Lacks cytologic differentiation

SMALL CELL CARCINOMA

Highly malignant Cigarette smoking Major bronchi and peripheral lung No known pre invasive phase Most aggressive Widely metastasizing Associated with ectopic hormone

production P53 and RB gene Sheets of cells Cells with scant cytoplasm Molded nuclei Uniform fine chromatin “absent” nucleoli >10mitoses/10 HPF Necrosis (not shown) Few dense- cored granules by EM

CARCINOID TUMOR

Younger patients Equal sex incidence Low grade Typical or atypical Features:

o Intraluminal growtho Metastasizeo Elaborate vasoactive amines

Ribbon or sheet architecture Polygonal cells Moderate cytoplasm Regular nuclei Finely stippled chromatin Small nucleoli Delicate capillary stroma <2mitoses/ 10 HPF Chromogranin + By EM, many dense-colored, membrane-

bound granules are found in the cytoplasm (arrows).

ATYPICAL CARCINOID

Ribbon or sheet architecture Nuclei resemble carcinoid tumors but

show hyperchromatism, some irregularity in shape

Moderate cytoplasm Focal necrosis (left) 2-10 mitoses/HPF

HAMARTOMA

Benign neoplasm Well circumscribed Composed of mixture of cartilage, fat, and

fibromyxoid tissue Sharply circumscribed and surrounded by

normal lung (bottom) Cartilage lies to the right

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Lobules of fibromyxoid tissue to the left are covered by non-neoplastic respiratory epithelium (arrow).

PARANEOPLASTIC SYNDROMES

The hormones or hormone-like factors elaborated include:

ADH ACTH PTH Calcitonin Gonadotropins Serotonin

Pancoast tumorso Apical lung cancers

Superior pulmonary sulcus

Invade neural structures Severe pain in

ulnar nerve distribution

Horner’s syndrome Enophthalmus Ptosis Miosis Anhidrosis

Local Effects of Lung Tumor SpreadClinical Feature Pathologic BasisPneumonia, abscess, lobar collapse

Tumor obstruction of airway

Lipoid pneumonia Tumor obstruction;

accumulation of cellular lipid in foamy macrophages

Pleural effusion Tumor spread into pleuraHoarseness Recurrent laryngeal nerve

invasionDysphagia Esophageal invasionDiaphragm paralysis

Phrenic nerve invasion

Rib destruction Chest wall invasionSVC syndrome SVC compression by tumorHorner syndrome Sympathetic ganglia invasionPericarditis, tamponade

Pericardial involvement

International Staging System for Lung CancerT1 Tumor <3 cm without pleural or main stem

bronchus involvement (T1a, <2 cm; T1b, 2–3 cm)

T2 Tumor 3–7 cm or involvement of main stem bronchus 2 cm from carina, visceral pleural involvement, or lobar atelectasis (T2a, 3–5 cm; T2b, 5–7 cm)

T3 Tumor >7 cm or one with involvement of chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire lung atelectasis, or separate tumor nodule(s) in the same lobe

T4 Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina or separate tumor nodules in a different ipsilateral lobe

N0 No demonstrable metastasis to regional lymph nodes

N1 Ipsilateral hilar or peribronchial nodal involvement

N2 Metastasis to ipsilateral mediastinal or subcarinal lymph nodes

N3 Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes

M0 No distant metastasisM1 Distant metastasis (M1a, separate tumor

nodule in contralateral lobe or pleural nodules or malignant pleural effusion; M1b, distant metastasis)

STAGE GROUPINGStage Ia T1 N0 M0Stage Ib T2 N0 M0Stage IIa T1 N1 M0Stage IIb T2 N1 M0

T3 N0 M0Stage IIIa T1–3 N2 M0

T3 N1 M0Stage IIIb Any T N3 M0

T3 N2 M0T4 Any N M0

Stage IV Any T Any N M1

PLEURAL EFFUSION

Occurs in:

Increased hydrostatic pressure, as in congestive heart failure

Increased vascular permeability, as in pneumonia

Decreased osmotic pressure, as in nephrotic syndrome

Increased intrapleural negative pressure, as in atelectasis

Decreased lymphatic drainage, as in mediastinal carcinomatosis

Condition Type of fluid Common associationsInflammatorySerofibrinous pleuritis

Serofibrinous exudate

Inflammation in adjacent lungCollagen vascular dse

Suppurative Pus Suppurative infection

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pleuritis (empyema)

in adjacent lung

Hemorrhagic pleuritis

Bloody exudate

Tumor

Non inflammatoryHydrothorax Transudate CHFHemothorax Blood Ruptured aortic

aneurysm, traumaChylothorax Chyle

(lymoh)Tumor obstruction of normal lymphatics

PNEUMOTHORAX

Air/ gas in pleural cavities Spontaneous, traumatic, therapeutic

PLEURAL TUMORS

Primary VS secondary Secondary- more common

o Metastatic tumors

SOLITARY FIBROUS TUMOR

BENIGN Localized Not related to asbestos exposure Gross:

o Solid tumor with occasional cysts filled with viscid fluid

Microscopic:o Whorls of reticulin and collagen fiberso CD34+, cytkeratin-

MALIGNANT MESOTHELIOMA

Arise from visceral or parietal pleura Asbestos exposure

o Require 25-45 years of exposure

o Poorer prognosis for patients who also smoke

Markers of asbestos exposureo Asbestos bodieso Asbestos plaque

Morphologyo Widespread pleural involvemento Extensive pleural effusion

Microscopic Types:

o Sarcomatoido Epithelialo mixed

e.valerio

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