Lung cancer_Types_pa

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					                                          Tumours of the Respiratory Tract
Bronchial carcinoma is the most common, accounting for 95% of primary tumours of the lung. Alveolar cell carcinoma
accounts for 2% and other less malignant or benign tumours account for the remaining 3%.



Bronchial carcinomas are broken into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).

Small cell lung carcinoma
Type              Freq.    Macroscopic                Microscopic                       Metastases/Spread           Features
SMALL CELL        20-      Seldom in periphery        Homogenous population             Metastasise widely          Only 1% occur in non-
CARCINOMA         25%      (hilar or central)         of (small) oat-like cells         and early (most             smokers
(oat-cell                                             - Little cytoplasm                aggressive)
carcinoma)                 Usually don’t cavitate     - Round/oval shapes                                           Poor prognosis
                                                                                        Metastasis is via
                                                      Dense-core                        lymphatics/blood and is     Ectopic hormone
                                                      neurosecretory                    usually present at          production is common
                                                      granules as they arise            diagnosis
                                                      from neuroendocrine                                           Therapy: CT &/or RT
                                                      cells.                                                        Virtually incurable
                                                                                                                    with surgery

Non-small cell carcinomas
Three main types:
 Squamous cell carcinoma (SCC)
 Adenocarcinoma (AdenoCa)
 (Undifferentiated) Large cell carcinoma

Type             Freq.    Macroscopic               Microscopic                   Metastases/Spread             Features
Squamous cell    25-      Come from larger,            Intercellular bridges     Tends to spread               Most present as
carcinoma –      40%      more central                  visible                   locally & metastasise         obstructive lesions of the
most common               bronchi                      Keratin present           later in its course, but      bronchus leading to
type                                                   Cells form                does tend to grow more        infection
                          Cavitation sometimes          whorl/nest pattern        rapidly in their original
                          and necrosis                                            location  bronchial          Common in men
                                                    May be squamous               obstruction & sequelae        Hx of smoking
                                                    metaplasia/dysplasia &
                                                    foci of carcinoma in-situ     Lymphatic spread is           May secrete PTH-like
                                                    in the epithelium next to     more common than              peptide   Ca
                                                    the mass                      haematogenous
                                                                                                                Often an initial response to
                                                                                                                RT (not CT)

                                                                                                                About 60% are surgically
                                                                                                                resectable but recurrence
                                                                                                                is common

Type              Freq.    Macroscopic                     Microscopic                    Metastases/Spread         Features
Adenocarcinoma    10%      Typically peripherally          From mucous cells in                                     Grows more slowly
                                                           the bronchial                  Invasion of the           than SCC
                           Bronchial-derived               epithelium                     pleural and
                           Adenocarcinoma                                                 mediastinal lymph         M=F
                           (common)                        Small and vary from            nodes is common.
                                                           well-differentiated with                                 Not as closely
                           SUBTYPE:                        glandular elements to          Metastases to the         associated with
                           Bronchioloalveolar              papillary lesions to solid     brain and bones are       smoking
                           carcinoma (1-2% of lung         masses                         common.
                           Ca) (better 20-50% 5 year       80% contain mucin                                        Incidence increasing
                           Single nodule or more           In pulmonary                                             Most common
                           commonly, multiple diffuse      parenchyma in terminal                                   bronchial carcinoma
                           nodules that may coalesce       regions.                                                 associated with
                           into consolidation (like                                                                 asbestos
Type                 Freq.   Macroscopic       Microscopic                      Metastases/Spread   Features
Large cell           10-     Tend to be in     Anaplastic carcinoma with        Metastasise early   Very poor prognosis
(undifferentiated)   25%     periphery         large, more polygonal cells
tumour                                         & vesicular nuclei.
                                               More likely to be SCC &
                                               adenoCa so undiff. that it
                                               can’t be recognised.
                                               (Cells same size as SCC,
                                               but no characteristic whorls)
                                               Some have:
                                                   Intracellular mucin
                                                   Mutlinucleate cells
                                                    (giant cell Ca.)
                                                   Cleared cells (clear cell
                                                   Spindly appearance
                                                    (spindle cell Ca)

PRE-CURSOR LESIONS (may not actually progress to lung cancer)
 Squamous dysplasia/carcinoma in-situ
 Atypical adenomatous hyperplasia
 Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia


Pulmonary hamartoma (most common benign lesion)
 Usually seen on the X-ray as a well-defined round lesion 1-2cm in diameter in the periphery of the lung
 Growth is very slow (but the tumour can reach several cm in diameter)

Bronchial carcinoid (not actually benign, but it is a low grade tumour)
 Rare tumour ressembling intestinal carcinoid tumour
 It is locally invasive, eventually spreading to mediastinal lymph nodes and distant organs
 Highly vascular tumour that projects into the lumen of a major bronchus  recurrent haemoptysis
 Grows slowly, but eventually blocks the bronchus  lobar collapse
 May produce ACTH (are foregut derivatives)

Cylindroma, Chrondroma, Lipoma
 Extremely rare. They tend to grow and cause obstruction

Tracheal tumours – squamous papilloma, leiomyoma, haemangioma


Malignant Mesothelioma
 Due to asbestos exposure (latent period of 20-50 years)
 Presents with chest pain, dyspnoea, pleural effusion
 Histology: Often biphasic (epithelioid/sarcomatous)
 Treatment: Nil effective (only palliative)
 Prognosis: Poor – death within 10 months on average

Secondary mesothelioma (lung, breast)

Metastases to the lung are common and usually present as round shadows (1.5-3cm diameter).
 Typical sites for the primary tumour are: kidney, prostate, breast, bone, GIT, cervix, ovary

Metastases nearly always develop in the parenchyma and are often fairly asymptomatic even when the CXR shows
extensive pulmonary metastases. (Rarely, they can develop in the bronchi and the patient can present with haemoptysis).

Carcinoma, especially of the stomach, pancreas and breast can involve mediastinal glands and spread along the
lymphatics of both lungs (lymphangitis carcinomatosa)  progressive and severe breathlessness. See streaky basal
shadowing fanning out over both lung fields on the CXR as well as bilateral lymphadenopathy.

Occasionally, metastases may be only a solitary, round shadow on an X-ray of an asymptomatic patient. This is most
commonly due to renal cell carcinoma, but DDx. Includes:
 Primary bronchial carcinoma, tuberculoma, benign tumour of the lung, hydatid cyst
Part of the reason that lung cancers have such poor survival is that they are generally diagnosed at a late stage.
 Those arising centrally (bronchial tree) typically present with chest symptoms (e.g. haemoptysis)
 Peripheral tumours may grow silently without causing local symptoms until quite advanced

Thus, many tumours are found coincidentally on a CXR or present with non-specific general symptoms (e.g. weight loss),
with effects of metastases (e.g. to brain, bone (pain)) or with non-metastatic “paraneoplastic” syndromes (as a result of
hormones, peptides, antibodies, prostaglandins or cytokines produced by the tumour)

Symptoms                                      Signs
Cough (46%)                                   Clubbing (14%)
Dyspnoea (40%)                                Atelectasis (10%)
Haemoptysis (32%)                             Effusion (9%)
Chest pain (30%)                              Hepatomegaly (8%)
Anorexia (25%)                                SVC obstruction (5%)
Fatigue (24%)                                 Hypertrophic pulmonary osteoarthropathy (2%)
Weight loss >10% (17%)                        Paralysed diaphragm (2%)
Wheeze (12%)                                  Supraclavicular nodes (2%)
Bone pain (10%)                               Pancoast’s syndrome (2%)
Hoarseness (9%)                               Horner’s syndrome (1%)
Dysphagia (4%)                                NO clinical signs (53%)
Asymptomatic (13%)

Metastases may cause bone tenderness, hepatomegaly, confusion, fits, local CNS deficit, cerebellar syndrome, proximal myopathy or
peripheral neuropathy.

Paraneoplastic syndromes:
   Endocrine changes:
        o Hypercalcaemia due to PTH-like substance secretion from SCC
        o Hyponatremia due to ADH secretion by small cell carcinomas
        o Cushing’s (ACTH) – ectopic secretion by small cell carcinoma
        o Gynaecomastia – due to excessive gonadotrophin secretion
        o Hypoglycaemia – release of insulin-like peptide from SCC
   Neurological signs:
        o Eaton-Lambert syndrome (progressive muscle weakness) and retinal blindness due to small cell carcinoma
        o Peripheral neuropathy
        o Subacute cerebellar degeneration
        o Polymyositis
        o Cortical degeneration
        o Horner’s syndrome (partial ptosis of the eyelid, miosis of pupils, lack of sweating) – due to interruption of the sympathetic
            innervation of the eye by apical tumours (usually associated with pain in an ulnar nerve pattern)
   Haematological features:
        o Migrating venous thrombophlebitis
        o Disseminated intravascular coagulation
        o Anaemia
   Skin changes:
        o Acanthosis nigricans (brown to black velvety elevations of the epidermis due to confluent papillomas, usually in the axillae
            & nape of the neck)
        o Dermatomyositis (papules over the knuckles)


   There is overwhelming evidence that cigarette smoking is a major cause of lung cancer (including passive smoking)
   The specific causative agents in cigarette smoke are uncertain but potential carcinogenic substances such as poly-
    aromatic hydrocarbons, phenols & radioisotopes are implicated
   Many smoke particles are so small that they penetrate far into the lung (although most bronchogenic carcinomas
    originate in the large bronchi  this may be because the large bronchi are exposed to a higher [ ] of tobacco smoke
    products as the material is transported from the peripheral regions by the mucociliary system)
   Other factors include: radiation, asbestos, air pollution, nickel, chromates, arsenic
   These exposures are thought to act by causing genetic alterations in the lung cells, which accumulate and
    eventually  neoplasia (multi-hit theory of cancer)
   In lung cancers, it is estimated that 10-20 mutations have occurred by the time the cancer is clinically apparent. As in
    most cancers, there is a role for dominant oncogenes and the frequent loss & inactivation of recessive tumour
    suppressor genes.
         o Oncogenes: c-myc (growth responsive gene) in small cell carcinomas & K-ras (cellular transduction of
             GPCR) in adenocarcinomas
         o TSG: p53, Rb – both important in stopping the progression of the cell cycle
   There is a familial clustering of lung cancer – suggesting a genetic basis for susceptibility that may involve
    these genes or the cytochrome P450-A1 gene
                      NOTE – these genetic changes are not currently used for diagnosis or prognosis.

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