Lung cancer

MANIFESTATION OF THE LUNG CANCER

The clinical picture of a LC is complex and diverse. It depends on type of a tumor growth, clinico-anatomical form of a LC, rates of growth and innidiation, accompanying secondary inflammatory changes (Fig. 6). There are three groups of LC signs: local, secondary and common signs.

Fig. 6. Intrathoracic spread of LC with associated symptoms.

LOCAL SIGNS

Cough is the most often and, as a rule, the first sign of a LC. Its occurrence is explained by reflex reaction to a boring of a bronchus mucous. In case of the central cancer frequency of this sign reaches 80-90%. Cough as a rule is dry, in the beginning transient, then constant. Cough may be hoarse, excruciating, sometimes it characterizes as "pertussislike". Especially strong cough happens at transition of a tumor to a trachea or carina.

Haemoptysis is the second on frequency sign of a LC. It is caused by disintegration of the tumor, which invades bronchus wall. The haemoptysis meets in 25,3 % of patients with LC. The impurity of a blood in sputum happens more often as small blood particles. Sometimes patients expectorate small blood clots. Oncologists consider that even the small haemoptysis should be as an indication for radiological and bronchoscopic examination of the patient and his direction to the thoracic surgeon.

Besides realization of haemostatic therapy is necessary because haemoptysis may transform at any moment to a profuse pulmonary bleeding and as a result to fatal outcome.

Chest pain is a frequent sign of a LC. The pain meets on the side of defeat, less often – on the opposite side. Pain meets in 60-77 % of patients with LC, however frequency of this sign depends on a stage of disease. The reasons of occurrence of chest pains are various and may be caused by involving parietal pleura, thoracic wall, diaphragm, pericardium, trachea, nervous trunks and plexuses, and also mediastinal organs. The persistent pain has adverse prognose. Occurrence of a pain outside of a chest (in the field of a neck, backbone, top and bottom extremities) frequently testifies to defeat of the specified departments of a skeleton by metastases of a cancer.

Dyspnea is observed in 30-40 % of patients with the central LC and expressed more strongly, than larger a diameter of the affected bronchus. However in some cases the dyspnea occurs long before an obturation of a bronchus and, probably, has a reflex or inflammatory genesis. In some cases the dyspnea may be caused by haemodynamic infringements in lung due to compression by the tumor of large pulmonary veins and arteries, and also vessels of a mediastinum (superior vena cava) or a pleural exudate.

The peripherial LC long time proceeds without clinical signs and determings clinically late. Chest pain occurs at invasion by tumor of a pleura or a thoracic wall. The haemoptysis and cough at a peripherial LC are not early signs. The dyspnea is also not characteristic for initial stages of a peripherial LC.

The peripherial cancer of a lung apex (Fig. 7), which clinical picture was described in 1924 by the american roentgenologist H. Pancoast has the brightest clinical picture. Tumor invades first rib, causing its destruction, nerves of plexus brahialis and a sympathetic nerve. It is accompanied by a pain in the top extremity on the side of defeat and development of Horner's syndrome (ptosis, miosis, enophtalmus).



Fig. 7. Coronal T1-weighted magnetic resonance imaging showing subtle Pancoast tumour (open arrow) with extension into the superior sulcus and erosion of the adjacent vertebral body (arrow).

Cavitary forms of a peripherial LC may have also more expressed clinical picture that is caused by disintegration of a tumor in its center. If tumor drained into a bronchus patients have a severe cough with a lot of purulent sputum.

SECONDARY SIGNS

High temperature concerns to the secondary signs developing as a result of complications of an inflammatory nature accompanying a bronchogenic cancer. Increase of a temperature, is especial in case of the central LC, is observed almost in all patients. At the beginning of disease tumor partially obturates the bronchus cavity. As a result its drainage function decreases that conducts to a relapsing endobronchitis and a cancer pneumonitis in the appropriate lung site. The temperature in this period has subfebrile character. After complete obturation of bronchus by a tumor and development of an atelectasis of obctricted part of the lung there begins inflammation. In this case high and long rise of temperature (hectic character) is observed.

Paresis of a recurrent laryngeal nerve in patients with LC develops as a result of metastatic defeat of lymph nodes in the field of an aortal window, less often as result of a invasion or compression of nerve by a tumor. For recurrent nerve paresis is typical occurrence of hoarseness. More infrequent sign is choking during eating of liquid foods. This sign is caused by absence of complete closing of vocal chords during swallowing that is accompanied by passing of nutrition in trachea.

The central cancer in some cases may be accompanied by a dysphagia caused by metastatic defeat of paraesophageal group of mediastinal lymph nodes. More often the stenosis develops at a level of a bifurcation of trachea. The direct tumor invasion into an esophagus is possible also, that also may be complicated by its stenosis.

The liquid in a pleural cavity is observed approximately in 1/3 of patients with LC. The mechanism of development of a pleural exudate at tumoral defeat is not always identical. The isolated infringement of lymphatic outflow conducts to occurrence in a pleural cavity of an exudate with properties of transsudate. In some cases the cause of an exudate is the perifocal pneumonia.

But more often it is exudate with a plenty of erythrocytes (hemorrhagic exudate). It is possible to count essential attributes of tumoral pleurites hemorrhagic character of an exudate and its fast accumulation after a puncture. The hemorrhagic exudate, as a rule, is observed at canceromatosis of pleura.

GENERAL SIGNS

General signs develop owing to influence on an organism of a lung tumor. The most often general signs: weakness, fatigability, weight loss. Sometimes patients mark disgust for meat nutrition. The specified sign develops in some cases long before clinical display of disease.

Under influence of malignant process not oncologic diseases called "paraneoplastic" may develop. They develop not owing to direct action of a tumor on tissues and organs, but due to its influence on a metabolism, immunity and functional activity of regulating systems of an organism. The paraneoplastic syndromes can be characterized as constitutional, hematologic, skeletal, neuromuscular, cutaneous, and endocrine.

Constitutional symptoms such as weight loss, anorexia, and fatigue are probably the most common. Their presence or magnitude cannot be explained by tumor size, and their cause is unknown. Cachexia is a significant prognostic factor in the course of lung cancer. Recent studies suggest that splenic cytokines such as tumor necrosis factor may influence cachexia, as well as tumor growth. Megestrol acetate, a synthetic progestin, has been found to improve well-being, as well as allow weight gain, in many types of lung cancer.

A normochromic, normocytic anemia occurs in less than 10% of patients with bronchogenic carcinoma and is unrelated to marrow infiltration or therapy. A number of coagulopathies are associated with lung cancer. They include migratory thrombophlebitis (Trousseau's syndrome), disseminated intravascular coagulation, chronic hemorrhagic diathesis, nonbacterial thrombotic endocarditis, and arterial embolization. Trousseau's syndrome often involves unusual sites such as the upper extremities or the vena cava and is frequently unresponsive to anticoagulant therapy.

Hypertrophic pulmonary osteoarthropathy occurs in 4-12% of patients with lung cancer, most commonly with epidermoid carcinoma and only rarely with small-cell carcinoma (5%). It consists of periosteal new bone formation in the long bones, with digital clubbing and symmetric arthritis. Vasomotor instability is often present with episodic blanching, swelling, and diaphoresis of the hands and feet. The ankles, wrists, and long bones can be very painful and tender. Although new bone growth is present, the syndrome does not seem to be caused by ectopic human growth hormone production, but it may be mediated by autonomic reflexes. It usually regresses after tumor removal, vagotomy, or thoracotomy without tumor resection.

An increasing number of neuromuscular syndromes have been reported in association with bronchogenic carcinoma, most commonly small-cell carcinoma. These syndromes may precede the clinical appearance of the tumor by months to years. The most potentially devastating are cerebral encephalopathy and cortical cerebellar degeneration, both of which may occur precipitously. Peripheral neuropathies, usually sensorimotor and often presenting as pain and paraesthesias of the lower extremities, occur in up to 15% of patients with lung cancer. A myasthenia (Eaton-Lambert) syndrome occurs in 6% of patients with small-cell carcinoma and differs from myasthenia gravis primarily by an increase in the muscle action potential on repetitive stimulation and the lack of improvement in muscle strength with anticholinesterases. A symmetric proximal muscle neuromyopathy is also common and is associated with muscle wasting.

Cutaneous manifestations include features of dermatomyositis, hyperpigmentation caused by ectopic production of melanocyte-stimulating hormone, and acanthosis nigricans. The last is a hyperkeratotic, hyperpigmented dermatosis with small papillomatous lesions giving the skin a velvety texture. It is symmetric and prominent in skin folds. When it occurs after age 40, it is almost always associated with cancer (90% intra-abdominal, 5% lung).

A large number of endocrine and metabolic syndromes are associated with bronchogenic carcinoma. Many are primarily, but not exclusively, associated with small-cell carcinoma. It is theorized that lung cells embryologically derived from neural crest cells with the ability for amine precursor uptake and decarboxylation (APUD) undergo malignant derepression and secrete one or more peptide hormones. Overt clinical syndromes appear in about 10% of patients with lung cancer, although subclinical hormone production is more common.

The hormones produced are peptides and include adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormone, parathyroid hormone, antidiuretic hormone (ADH), human chorionic gonadotropin, prolactin, serotonin, insulin, glucagon, corticotropin-releasing factor, and calcitonin. Most is known about ectopic ACTH, parathyroid hormone, and ADH.

ACTH is probably the most commonly produced ectopic hormone (50% of patients with small-cell carcinoma), although Cushing's syndrome is rare with bronchogenic carcinoma. Tumors appear to elaborate both active ACTH (in small amounts) and an immunoreactive, but biologically weak "big" ACTH, which may be a precursor molecule. Big ACTH was evaluated as a marker for lung cancer, since it is present in over 80% of all lung cancer patients. It is not, however, specific, since it also occurs in a significant number of patients with chronic obstructive pulmonary disease (COPD). When Cushing's syndrome does occur in association with tumor ACTH secretion, it is a virulent disease with poor prognosis.

Hypercalcemia occurs in at least 12% of patients with lung cancer, mainly with epidermoid carcinomas. Although small-cell carcinoma frequently metastasizes to bone, it rarely causes hypercalcemia. Ectopic parathyroid hormone production is one cause of hypercalcemia that usually responds to therapy. Some cases may be caused by tumor-secreted prostaglandin E. The hypercalcemia in these cases can be suppressed by aspirin or indomethacin. Other cases may be caused by tumor production of a peptide with significant structural homology to parathyroid hormone, but without immunologic cross-reactivity.

The syndrome of inappropriate ADH secretion (SIADH) results from ectopic ADH secretion. It occurs in 11% of patients with small-cell carcinoma, and although hyponatremia may be severe, symptoms occur in only about 25% of patients with tumor-induced SIADH. It usually resolves within 3 weeks of the initiation of chemotherapy. Occasionally, severe SIADH can occur in the first 5 days following the start of chemotherapy, so patients should be monitored carefully during this time. Preliminary studies have utilized iodine 131-labeled antibodies against vasopressin-associated neurophysin to localize tumors utilizing radioimaging.

Gonadotropin production occurs predominantly with large-cell carcinoma and can cause gynecomastia, which may be unilateral. Prolactin production by anaplastic tumors may cause lactation in women. Epidermoid carcinomas have rarely been associated with production of vasoactive intestinal peptides with a syndrome of watery diarrhea, hypokalemia, and achlorhydria. In addition, bronchogenic carcinomas have been found to produce small, biologically active amines or peptides including serotonin, histamine, and a substance resembling eosinophilic chemotactic factor of anaphylaxis.

At the present time, most of these hormones represent curiosities. In the future, some may become useful markers of disease or response to therapy, and the mechanisms of their production may provide insights into the behavior of carcinoma.

HISTORY AND PHYSICAL EXAMINATION

A detailed history and accurate physical examination remain the most important steps in assessing a patient with lung cancer. Smoking history, past exposure to environmental carcinogens, and family history may suggest a higher probability of lung cancer. New symptoms, including a change in cough, hemoptysis, or history of recurrent respiratory infection, are suggestive. Symptoms suggesting locoregional spread include chest pain, symptoms of recurrent nerve palsy, or superior vena cava obstruction. Symptoms suggestive of metastatic disease frequently include cerebral metastases, bone pain, or weight loss. Occasionally, patients suffering from NSCLC present with symptoms and signs of a paraneoplastic syndrome, but not as frequently as with small cell tumors.

Physical examination should look for signs of partial or complete obstruction of airways, atelectasis or pneumonia, and pleural effusions. Examination of the head and neck, including draining regional lymph node areas, may demonstrate lymphadenopathy, indicating regional lymphatic (N3) spread.
ADDITIONAL EXAMINATIONS IN CASE OF LUNG CANCER

Chest radiograph. The chest radiograph is probably the most valuable tool in the diagnosis of lung cancer. A perfectly normal chest radiograph rules out this diagnosis in most instances, except for the rare occult tumor. Plain chest radiography can reveal peripheral nodules and hilar and mediastinal changes suggestive of lymphadenopathy or pleural effusions, all suggestive of possible malignancy. Areas of subsegmental, segmental, lobar, or lung collapse suggest an endobronchial obstruction.

X-ray inspection of chest:

a) Chest x-ray in two projections (front and lateral);

b) Tomography in a front projection in a section of a bifurcation of a trachea;

c) Tomography of a lung hilar in a lateral projection.

The radiological semeiology of a LC is caused by infringement of bronchial permeability, complications сonnected with growth of tumors and metastases. At presence of the preliminary diagnosis of a LC inspection of the patient should be started with multiprojective roentgenoscopy, which allows to receive the general representation about presence of pathological process, its localization and about a degree of diffusion.

At a roentgenoscopy it is possible to determine localization of a LC (central or peripherial) and also to find out connection of a tumor with a thoracic wall, diaphragm, mediastinum. At a roentgenoscopy condition of hilar elements and regional lymph nodes are defined. Only with the help of a roentgenoscopy it is possible to estimate a functional condition of chest organs and diaphragm: at a sharp inspiration it is possible to notice jerky shift of mediastinum organs in the affected side (positive sign of Golkskneht-Yacobson). At invasion of a phrenic nerve as a result is a phrenasthenia and due to it high location of diaphragm and paradoxical its mobility is marked at respiration (during an inspiration the diaphragm on the side of defeat moves upwards, and at an exhalation falls downwards).

Then we need to performe a roentgenogram in frontal and lateral projections. On the tomograms which made through the hilar, it is possible to receive the image of peribronchial lymph nodes with circular or excentric narrowing of a bronchus. Contours of walls of the affected department of bronchus are rough. Frequently on tomograms the image of a pencil-point stump of a bronchus is received. At the tree-like form of a LC on tomograms it is marked uniform narrowing of the affected bronchi, a thickening of their walls and smoothness of intersegmental and interlobar carinas. Diagnostics at this form of tumor growth is the most difficult.

The peripherial cancer (Fig. 8) on intact pulmonary background at the sizes of node of 1-1,5 cm has a polygonal contour with the unequal on extent sides. Tumors which diameter exceeds 3-4 cm, have mainly ball-shaped form. Studying of contours of tumoral unit shows, that they always are indistinct, have short “rays”, or "spicules", invading environmental pulmonary tissue. Their length varies from 0,2 up to 1,5 cm and more. Presence of "spicules" testifies about invasive growth of a tumor in environmental tissues along walls of bronchi, lymphatic and blood vessels.



Fig. 8. A 50-yr-old female with irregular cavitating squamous cell carcinoma in the right upper lobe (arrows).
Tumoral infiltration of environmental pulmonary tissue results in formation around of tumoral node original "radiant crown", so-called “corona maligna”. Radiance is sometimes non-uniform and also may be found out only along one tumor edge.

At augmentation of bronchopulmonary lymph nodes on x-ray films expansion of hilar is determined. Its vascular frame is not differentiated. An external contour of a root is polycyclic.

The augmentation of upper tracheobronchial lymph nodes gives expansion of a shadow of a mediastinum to the right or to the left. Its contour is convex and polycyclic. The major sign of augmentation of this group of lymph nodes is loss of shadow of an azigous vein.

Computed tomography. With the introduction of CT scanning in the late 1970s, a giant step was taken in the ability to diagnose and stage lung cancer employing noninvasive imaging techniques. CT imaging can confirm abnormalities seen on plain chest radiographs (Fig. 9), can often detect lesions that cannot be resolved on chest radiographs, and has played an important role in staging of lung cancer, especially spread to areas of the mediastinum undetected on plain films. There is general agreement that normal mediastinal lymph nodes are less than 1 cm in transverse diameter. Any lymph node larger than this suggests lymphadenopathy and should be investigated further by more invasive techniques.



Fig. 9. Spiculated mass typical of a carcinoma.
CT scans also suggest possible areas of local invasion of the primary tumor to chest wall, vertebrae, or mediastinal structures. Small pleural effusions or pleural nodules, often undetected on plain films, may be evident on CT scans.

The computer tomography is capable to reveal atelectases of small volume (subsegmentary and segmentary level). Tumoral atelectases on computer tomograms have equal polygonal or slightly wavy contours, homogeneous structure and soft-tissue density, which depends on a phase or a limitation period of a sign. On a computer tomogram reorganization of an atelectasis frame with sites of disintegration, small air cavities are clearly determined. High parameters of density of a tumoral conglomerate clearly allow to define medial border of diffusion.

CT can also identify specific features in lung nodules that are diagnostic, e.g. arteriovenous fistulae, rounded atelectasis, fungus balls, mucoid impaction and infarcts. High-resolution scanning further refines this diagnostic process. The ability of CT scanning to evaluate the entire thorax at the time of nodule assessment is of further benefit.

An added advantage of CT scanning is the ability to detect abnormalities below the diaphragm, especially metastases to liver and adrenal glands. For the investigation of lung cancer, CT scanning should include upper abdominal scanning to the level of the kidneys to include imaging of the liver and adrenal gland.

Spiral or helical CT is advantageous as small nodules are not missed between slices as may happen on older, nonspiral machines. It also increases the detection rate of nodules < 5 mm in diameter, especially when viewed in cine-format on a workstation. The acquisition of continuous volume data sets permits three-dimensional image reconstruction and multiplanar (i.e. nonaxial) reformatting. These techniques have been shown to improve the detection of pleural invasion by tumour and clarify the origin of peridiaphragmatic tumours respectively.

Further manipulation of raw data sets enables the technique of virtual bronchoscopy. An interactive, simulated bronchoscopy can be performed with the added benefit of simultaneous information on adjacent mediastinal structures. This technique has far reaching potential both as a teaching tool and as a means of evaluating patients thoracic and bronchial anatomy prior to interventional procedures and stent placement.

The spiral CT, using a special staging technique, is the mainstay of staging in lung cancer. This involves an automated bolus injection of contrast 20–30 seconds before the scanning is initiated. This time interval allows optimal enhancement of the mediastinal blood vessels. A maximum slice thickness of 5 mm is used to prevent errors from partial volume effects. The new multislice CT systems allow the whole thorax to be scanned with 3-mm slices during a single breath hold.

The recent advent of multislice scanners has seen advances in image resolution with a substantial reduction in both tube loading and scanning time as up to four slices can be acquired simultaneously. Both spiral and multislice machines suffer less from respiratory motion artefact due to their shorter scanning times.

Despite advances in CT scanning technology, there remain important limitations for its use in staging, with preoperative predictions differing from operative staging in 35–45% of cases, with patients being both over- and understaged. CT staging remains unsatisfactory for detecting hilar (N1) and mediastinal (N2 and N3) lymph node metastases, and for chest wall involvement (T3) or mediastinal invasion (T4), in which sensitivity and specificity can be less than 65%. These are critical areas that may make the difference between surgical and nonsurgical management decisions.

Abnormalities seen on CT scan, unless associated with unequivocal signs of malignancy, should be confirmed by more invasive cytologic or histologic investigation.

Radiological characteristics by cell type.

Adenocarcinoma represents 31% of all lung cancers, including bronchoalveolar carcinoma. Adenocarcinomas are typically peripherally located and measure < 4 cm in diameter; only 4% show cavitation. Hila or hila and mediastinal involvement is seen in 51% of cases on chest radiography and a recent study describes two characteristic appearances on CT: either a localized ground glass opacity which grows slowly (doubling time > 1 yr) or a solid mass which grows more rapidly (doubling time < 1 yr).

Bronchoalveolar carcinoma is regarded as a subtype of adenocarcinoma and represents 2–10% of all primary lung cancers. There are three characteristic presentations: most common is a single pulmonary nodule or mass in 41%; in 36% there may be multicentric or diffuse disease; finally, in 22% there is a localized area of parenchymal consolidation. Bubble-like areas of low attenuation within the mass are a characteristic finding on CT. Hilar and mediastinal lymphadenopathy is uncommon. Persistent peripheral consolidation with associated nodules in the same lobe or in other lobes should raise the possibility of bronchoalveolar carcinoma.

Adenosquamous carcinoma represents 2% of all lung cancers. This cell type is typically identified as a solitary, peripheral nodule. Over one-half are 1–3 cm in size and cavitation is seen in 13%. Evidence of parenchymal scars or fibrosis in or next to the tumour is seen in 50%.

Squamous cell carcinoma represents 30% of all lung cancers. These tumours are more often centrally located within the lung and may grow much larger than 4 cm in diameter. Cavitation is seen in up to 82%. They commonly cause segmental or lobar lung collapse due to their central location and relative frequency.

Small cell lung cancer represents 18% of all lung cancers. SCLC often present with bulky hila and mediastinal lymph node masses. A noncontiguous parenchymal mass can be identified in up to 41% at CT that very rarely cavitates. They form the malignant end of a spectrum of neuroendocrine lung carcinomas with typical carcinoid tumours being at the more benign end. A mass in or adjacent to the hilum is characteristic of SCLC and the tumour may well show mediastinal invasion.

Large cell carcinoma represents 9% of all lung cancers. Large or giant cell carcinoma is a poorly differentiated nonsmall cell carcinoma and is diagnosed histologically after exclusion of adenocarcinomatous or squamous differentiation. It may grow extremely rapidly to a large size but metastasizes early to the mediastinum and brain. It should be noted that there seems to be a change occurring in the prevalence of the described histological subtypes.

Carcinoid tumour represents 1% of all lung cancers. Atypical carcinoid tumours tend to be larger (typically > 2.5 cm at CT) with typical carcinoid tumours being more often associated with endobronchial growth and obstructive pneumonia. Carcinoids tend to be centrally rather than peripherally located and calcification is seen in 26–33%. The 5-yr survival for typical carcinoids is 95% against 57–66% for atypical carcinoids.

Magnetic resonance imaging. Magnetic resonance imaging is becoming more available but pressure on MRI scanning time is so intense that it is usually used for problem solving and where administration of contrast media is contraindicated. MRI can be more accurate than CT in separating stage IIIa (resectable) from IIIb (generally unresectable) tumours in selected patients due to its ability to detect invasion of major mediastinal structures, i.e. T4 disease (fig. 10).

The advantages MRI has over CT include: better soft tissue contrast, multiplanar imaging capability, and therefore useful for superior sulcus tumours and evaluation of the aortopulmonary window, and cardiac gating which enables excellent delineation of the heart and great vessels and removes cardiac pulsation artefact.

MRI is also useful in the assessment of mediastinal and chest wall invasion by virtue of its ability to determine fat-stripe invasion and involvement of the diaphragm and spinal canal. In addition, it has been shown to aid in differentiating lymph nodes from hila vessels due to the "flow void" phenomenon.

MRI has disadvantages compared to CT, being slower and more expensive with poorer spatial resolution and providing limited lung parenchyma information. MRI can overestimate lymph node size because of respiratory movement, causing the blurring together of discrete nodes into a larger, conglomerate mass.

MRI is also poorly tolerated by claustrophobic patients and is contra-indicated in patients with indwelling electromagnetic devices and some prosthetic heart valves. T1-weighted sequences are used for the visualization of fat planes and improved spatial resolution. T2-weighted sequences are useful for detection of high-signal tumour infiltration. Gadolinium enhancement can further enhance the diagnostic yield.



Fig. 10. Coronal magnetic resonance imaging showing an adenocarcinoma in a young male infiltrating the aortopulmonary window. There is loss of the fat plane against the aorta (arrows) and invasion of the main pulmonary artery (arrowhead).
Radionuclide scanning. The ability of radionuclide scanning to diagnose and stage lung cancer is limited by its lack of specificity. Scanning with gallium citrate-67 is widespread for an estimation of intrathoracic lymph nodes defeat. It is applied also 99Tc and 131I. . The rate of incorporation of the radioisotope by the primary tumor and its metastatic foci is variable, however, and thus has limited its clinical use in both diagnosis and staging. Routine radionuclide bone scanning to rule out asymptomatic, unsuspecting bone metastases in early-stage disease has never been shown to be cost-effective but is still advocated by many practitioners. In clinical stage III disease, before considering curative therapy, bone scans may be more valuable.

Isotope-labeled monoclonal antibodies have been investigated as a technique for staging and diagnosing lung cancer. Specific monoclonal antibodies directed to lung cancer cells may prove valuable as diagnostic and staging modalities in the future.

Positron emission tomography. Positron emission tomography (PET) scanning is a new imaging modality whose role in the assessment of lung cancer is still being determined.

Its advantage over other modalities lies in its sensitivity in detecting malignancy and its ability to image the entire body in one examination.

PET is a physiological imaging technique that uses radiopharmaceuticals produced by labelling metabolic markers such as amino acids or glucose with positronemitting radio nuclides such as fluorine-18. The radiomarker is then imaged by coincidence detection of two 511 KeV photons that are produced by annihilation of the emitted positrons. The radiopharmaceutical, 18F-2-deoxy-D-glucose (FDG) is ideally suited for tumour imaging.

PET performed with this agent exploits the differences in glucose metabolism between normal and neoplastic cells, allowing accurate, noninvasive differentiation of benign versus malignant abnormalities.

Uptake of FDG is known to be proportional to tumour aggressiveness and growth rates. FDG uptake can be assessed visually on PET images by comparing the activity of the lesion with the background or by semiquantitative analysis using calculated standardized uptake ratios. An uptake ratio of < 2.5 is considered indicative of a benign lesion.

PET scanning detects malignancy in focal pulmonary opacities (fig. 11) with a sensitivity of 96%, specificity of 88% and an accuracy of 94% in lesions of more or equal 10 mm. However, compared to CT, PET has poorer spatial resolution, which precludes it from accurate anatomical assessment of primary tumour status.

False-positive PET findings in the lung are seen in tuberculous infection, histoplasmosis and rheumatoid lung disease. False negatives are seen with carcinoid tumours, bronchoalveolar carcinoma and lesions < 10 mm in size.



Fig. 11. Avid uptake of ¹⁸F-2-deoxy-d-glucose in left apical tumour (arrow).

PET is more accurate than CT in the detection or exclusion of mediastinal nodal metastases (fig. 12): sensitivity is 67–83% and specificity is 81–100%. PET has been shown to correctly increase or decrease nodal staging as initially determined by CT in 21% of presurgical patients.

PET has been shown to detect occult extrathoracic metastases in 11–14% of patients selected for curative resection and alter management in up to 40% of cases.

PET is more sensitive and specific than bone scintigraphy for the detection of bone metastases and has a 100% positive predictive value for the presence of adrenal deposits as against 43% for conventional imaging.

The technique faired poorly in the detection of brain metastases (60% sensitivity) prompting the authors to recommend the continued use of conventional imaging for routine staging of the brain.



Fig. 12. Middle-aged-female with a) right hilar mass (arrow) and b) equivocal precarinal lymph node (arrow). c) PET scan shows increased uptake in mediastinal nodes (arrows) and small peripheral nodule (open arrow). Biopsy of hilar mass confirmed nonsmall cell lung cancer.

The main disadvantage for PET is the lack of availability and relatively high cost of each examination. However, decision analysis models indicate that combined use of CT and PET imaging for evaluating focal pulmonary lesions is the most cost-effective and useful strategy in determining patient management with a pretest likelihood of having a malignant nodule of 0.12–0.69.

PET is more accurate than conventional studies in detecting recurrent lung cancer and appears to be superior in distinguishing persistent or recurrent tumour from fibrotic scars. However, false-positive studies do occur secondary to postirradiation inflammatory change and delaying the examination until 4 or 5 weeks postirradiation is recommended.

The clinical blood test allows to find out in the majority of patients with LC (75 %) rising ESS more than 30 mm/hour. Change of this parameter is observed in patients with the central and peripherial LC.

Sputum Cytology. Once the disease is suspected, a simple and effective method of obtaining a positive diagnosis of lung cancer is sputum cytology. It allows to reveal the x-ray-negative cancer and even carcinoma in situ. The yield from sputum cytology depends on many factors, including the ability of the patient to produce sufficient sputum, the size of the tumor, the proximity of the tumor to major airways, and to a lesser extent, the histologic type of the tumor. With three sputum samples, up to 80% of central tumors can be diagnosed. The yield is much smaller for peripheral tumors, dropping to less than 20% for peripheral tumors less than 3.0 cms. in diameter. A 3-day collection of early morning sputa, preserved in Saccamano's solution, appears to be the optimal method of assessment. Squamous cell tumors are more frequently diagnosed by cytology than adenocarcinoma or large cell tumors.

Another factor affecting the ability of sputum cytology to diagnose malignancy is the experience and training of the cytopathologist. Viral infections and other acute inflammations can produce cellular changes difficult to distinguish from malignancy, especially adenocarcinoma. Frequently, severe dysplasia is misinterpreted as a malignancy, and vice versa. Tockman and colleagues have described a monoclonal antibody staining technique that may more accurately diagnose the presence or absence of malignancy in severely dysplastic cells. This is being tested prospectively.

Transthoracic needle biopsy. Transthoracic needle biopsy of a primary lung tumour is controversial when considering a solitary nodule or mass. A negative biopsy needs repeating and the patient will invariably proceed to surgery unless a positive benign result is obtained. Biopsy is useful in determining cell type in inoperable disease to guide further therapy and is essential to confirm the presence of distant metastatic disease.

Needle biopsy is usually performed under either ultrasound or CT guidance. Ultrasound guided biopsy is quick and allows the operator to guide the needle under direct vision but can only be used with peripheral tumours that abut the pleura or invade the chest wall. It is then usually possible to obtain a tissue core using an 18-gauge cutting needle although FNA may be used.

CT guided biopsy (fig. 13) takes longer and systemic analgesia and sedation may be necessary to maintain patient compliance. CT affords good visualization of all thoracic structures and CT guided biopsy has an accuracy for diagnosing malignancy of 80–95%. It is the procedure of choice for sampling peripheral nodules (<2 cm in diameter) as the yield for transbronchial needle biopsy, in the absence of an endobronchial lesion, falls from 92–95% to 50–80%.

FNA is the preferred sampling method of parenchymal nodules in order to reduce the incidence of complications and is known to have a similar sensitivity in detecting malignancy as core biopsy. However, small tissue fragments for histological evaluation can generally be obtained with 19–22 gauge needles in 40–75% of patients. Such evaluation is valuable because it lends confidence to a cytological diagnosis of cancer, to cell-type determination and to the reliability of a negative result.

a b

Fig. 13. Versatility of transthoracic needle biopsy with needle tip in a) mediastinal mass (note safe approach) and b) peripheral solitary nodule.
When a cavitatory or necrotic lesion is encountered, sampling of the wall is recommended to obtain viable tumour material. A single negative biopsy does not exclude malignancy and should prompt a repeat biopsy. When performing biopsies of mediastinal lesions it is usually possible to use an 18-gauge cutting needle after selecting a safe route. This is especially important in the diagnosis of lymphomas.

Bronchoscopy. The bronchoscopy is one of main methods in diagnostics of a LC. It visually allows to examine a trachea, main, lobular, segmentary and subsegmental bronchi, to see directly a tumor and to estimate its sizes and, that it is especially important, localization. Localization of a tumor frequently allows to define volume of surgery (pneumonectomy, lobectomy, bilobectomy) or impossibility of its performance.

Although rigid bronchoscopy was used for many years to confirm the diagnosis of lung cancer, the introduction of flexible fiberoptic bronchoscopy more than 20 years ago has revolutionized this approach. The procedure, although invasive, can be performed under local anesthesia with or without sedation and with minimal morbidity and exceptional safety. Using flexible fiberoptic instruments, the proximal tracheobronchial tree can be examined up to the second or third subsegmental division, and cytology or histologic specimens can be obtained from abnormal lesions identified. Diagnostic yield of fiberoptic bronchoscopy with cytology brushing and biopsy for histology when a visible lesion is identified is higher than 90%. Even with no visible lesion seen, the bronchus draining the area of suspicion can be irrigated and lavaged, obtaining cytologic material. Using fiberoptic bronchoscopy and image intensification, peripheral lesions can be reached by cytology brushes, needles, or biopsy forceps, and specimens can be obtained. This is most effective in lesions larger than 2 cm in diameter.

The bronchoscope is also valuable for staging. The site of the primary tumor in a major airway may affect its stage (T3 versus T2 versus T1), and transbronchoscopic needle aspiration through the airway wall was popularized. Except for intrabronchial diffusion the bronchoscopy indirectly allows to define extrapulmonary diffusion of metastases of a tumor (subcarinal and paratracheal lymph nodes).

Fluorescence bronchoscopy is currently being developed as a method for detecting early lung cancers, carcinoma in situ, and dysplastic lesions of the tracheobronchial tree. If progress is to be made in the early detection and treatment of lung cancer then we need to detect lesions before they become invasive. The World Health Organization has published the third edition of International Histological Classification of Tumors and lists three main forms of preinvasive lesion in the lung: (1) squamous dysplasia/carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).

SD/CIS is graded into four stages (mild, moderate, severe and CIS). Little is known about the progression of these lesions, but it is generally thought that squamous cell carcinomas have their origin in SD/CIS, and there is reasonable morphologic evidence that AAH may progress through low to high grade and then to bronchoalveolar cell carcinoma (a noninvasive lesion) and finally peripheral adenocarcinoma. DIPNECH is rare and associated with the development of multiple carcinoid tumors. A knowledge of these preinvasive lesions and how they might evolve is essential in interpreting the results of studies that aim to detect and treat them early. Attention has focused on detection of early central squamous cell lesions (SD/CIS); it is less clear how peripheral lesions such as AAH might be detected.

The development of fluorescence bronchoscopy is considered to be one of the most important new initiatives in the detection of early squamous cell lung cancer. Although traditional white light bronchoscopy has a yield of greater than 90% for picking up macroscopic lesions, it is less good at picking up SD/CIS.

It has been recognized for some time that dysplastic and malignant cells exposed to light of a specific frequency will emit light of a wavelength different from that of normal tissue. Fluorescence bronchoscopy takes advantage of this difference and uses a blue light for illumination. Under this illumination premalignant and malignant tissues give off slightly weaker red fluorescence but much weaker green fluorescence than normal tissues, which can be recognized by an experienced operator.

SD/CIS and early invasive lesions detected by fluorescence bronchoscopy are thought to be the earliest manifestation of lung cancer and it is hoped that their detection and treatment will improve prognosis in a subsection of high-risk patients. False-positive abnormal fluorescence can occur in patients with suction trauma, bronchial asthma, severe mucous gland hyperplasia, or acute purulent bronchitis. Several systems are available for fluorescence bronchoscopy, of which the best known are the light-induced fluorescence endoscopy (LIFE) device and the SAFE-1000.

Endoscopic ultrasound with fine needle aspiration. Another technique that is becoming increasingly important in the sampling of mediastinal, but not hilar, lymph nodes is transesophageal lymph node sampling under endoscopic ultrasound guidance (EUS). This has the added advantage of avoided contamination of lymph node samples with malignant cells from the bronchial tree.

EUS is a technique that has been in use for more than 10 years. It makes use of a modified endoscope with an ultrasound transducer at the tip and gives excellent views of the structures that lie adjacent to the gut lumen. EUS from the esophagus gives access to the subcarinal, aortopulmonary, and posterior mediastinum and is able to resolve nodes as small as 3 mm.

However, the views of the paratracheal and anterior mediastinal areas are limited by distortion caused by tracheal air. By using curved echo-endoscopes it is possible to perform fine needle aspiration (EUS-FNA) of abnormal subcarinal and aortopulmonary window nodes with negligible risk of infection or bleeding. This had a sensitivity of 96% for malignancy in lymph nodes when bronchoscopy had been unhelpful.

Mediastinoscopy and mediastinotomy. Mediastinoscopy was developed by Carlens about 35 years ago to facilitate staging of superior mediastinal lymph nodes (N2 or N3) before consideration of therapy in patients with lung cancer. It remains the most accurate lymph node staging technique to assess superior mediastinal lymph nodes, which are frequently involved in this disease.

In the future, if early experience proves correct, PET scanning may replace this invasive procedure as a method of accurately identifying mediastinal involvement.

Thoracoscopy. Video-assisted thoracoscopy has been used in the diagnosis and staging of lung cancer. Peripheral nodules can be identified and excised using video-assisted minimally invasive techniques, and mediastinal lymph nodes can be sampled for histologic examination. This technique also can identify suspected pleural disease and has the ability to assess accurately the status of pleural effusions. The exact indications and use of this minimally invasive technique await further prospective studies, but it has been used for assessment of mediastinal nodes and T4 status, especially effusions.

Thoracotomy. Thoracotomy continues to be used in the diagnosis and staging of lung cancer. Using less invasive procedures, however, more than 95% of tumors can be accurately diagnosed and staged without thoracotomy. Despite this, there remains a small minority of patients in whom the diagnosis of lung cancer is made only at thoracotomy.

At the time of thoracotomy, the diagnosis can be confirmed by fine-needle aspiration, incisional or preferably excisional biopsy, and frozen-section analysis. All of these techniques can provide tissue that can be rapidly assessed by pathologists. At the time of thoracotomy, further staging is mandatory by the surgeon using hilar and mediastinal lymph node sampling or complete lymph node dissection. Not infrequently, unsuspected involvement of adjacent structures is recognized only at the time of surgery, identifying T3 or T4 tumor.

DIAGNOSTIC APPROACH

The solitary pulmonary nodule

Only 20% of carcinomas are resectable at diagnosis and 50% of "coin lesions" on chest radiography are malignant: 40% representing primary lung cancers whilst the other 10% are solitary metastases.

However, 20–30% of all cancers present as a solitary pulmonary nodule (SPN) of which 88% are resectable with a 5-yr survival rate around 50%. The early identification and correct assessment of such nodules is therefore of the utmost importance.

Benign nodules

Chest radiography.A number of findings enable a nodule to be classed as benign on the basis of chest radiographical findings.

1) age < 35 yrs, no history of cigarette smoking and no history of extrathoracic malignancy;

2) comparison with old films and establishment of no growth over at least a 2-yr period;

3) if the nodule contains fat density or a benign pattern of calcification such as central nidustype, popcorn, laminated or diffuse.

Note should be made that eccentric or stippled calcification is seen in approximately 10% of lung cancers. An appropriate history such as fever or chest pain may promote the likelihood of a benign process such as focal pneumonia or an infarct presenting as an SPN. A repeat radiograph should be performed at 2–6 weeks to assess resolution.

Computed tomography scanning, densitometry and enhancement.

CT scanning can further refine the detection of calcification and fat within nodules. A total 22–38% of noncalcified nodules on chest radiographs appear calcified on CT. Using CT densitometry, a "pixel map" of a nodule can be created with Hounsfield Unit (HU) values, > 200 being indicative of calcification.

Only characteristic patterns of calcification such as central, diffuse, laminar or popcorn are indicative of benignity. The presence of fat (-40 – -120 HU) or calcification or a combination of the two has been shown to correctly identify 64% with hamartomas on 2-mm section CT in one series. However, at least one-third of hamartomas in this series contained neither fat nor calcium leading to an indeterminate assessment.

Changes in attenuation after intravenous contrast administration at CT can also be used to distinguish benign from malignant parenchymal nodules. By retrospectively reducing the cut-off threshold to 10 HU it was possible to increase the techniques sensitivity in excluding malignancy from 98 to 100%.

Malignant nodules

A nodule size > 3 cm is associated with malignancy in 93–99% of cases. If the nodule is spiculated 88–94% will be malignant although 11% of malignant nodules do have distinct margins. The presence of calcification in larger (> 3 cm) and spiculated nodules should not be viewed as indicative of benignity.

Indeterminate nodules

Small size should not be used as a discriminator for exclusion of malignancy. One in seven nodules < 1 cm in size have been shown to be malignant and in a recent study of nodules resected at videoassisted thoracoscopic surgery, 31% of nodules < 1 cm in size in patients with no known malignancy were malignant. Cavitation and lobulation are not helpful discriminators in favour of malignancy as granulomas and hamartomas can both have these appearances.

Central tumours

Distinct from the solitary pulmonary nodule, central lung cancers often present radiographically as a hila mass or as collapse and consolidation of lung beyond the tumour with accompanying volume loss. Air bronchograms may be seen at CT.

Differentiating central tumours from distal collapse can be difficult but is facilitated by bolus contrast administration followed by prompt CT scanning at the level of abnormality. The lung is appreciably enhanced whilst tumour enhancement is minimal and delayed. The most marked difference between the two is seen from 40 s to 2 min after contrast injection.

Differentiating central lung tumours from mediastinal masses can also be problematic. Marginal spiculation, nodularity or irregularity between the mass and the surrounding lung almost always indicated the mass had arisen in the lung. A smooth interface suggested that the mass was mediastinal in location. A notable exception was Hodgkins lymphoma which may occasionally cross the pleura, invade the lung and result in a poorly marginated mass, mimicking a lung mass.

The following features can be viewed as suspicious for an obstructing neoplasm when associated with pneumonia:

1) the "S" sign of Golden, indicating a fissure deviated around a central tumour mass;

2) pneumonia confined to one lobe (or more if supplied by a common, obstructed bronchus) especially if > 35-yrs-old and accompanied by volume loss or mucus filled bronchi with no air bronchograms present;

3) localized pneumonia that persists for > 2 weeks or recurs in the same lobe. Hila enlargement is a common presenting feature in patients with lung cancer. The presence of a tumour mass or enlarged lymph nodes will give a dense hilum. Generally speaking the more lobular the shape the more likely that adenopathy is present.

Diagnostic staging of nonsmall cell lung cancer

The revised international system for staging lung cancer incorporates the tumour, node, metastasis (TNM) subset system and shows improved survival rates with more accurate staging and appropriate selection of patients for definitive surgical treatment by distinguishing the IIIa from the IIIb group.

Survival percentage at 5 yrs by clinical stage for the more advanced stages remains poor, emphasizing the importance of early detection. The overall 5-yr survival of only 5.3% serves to underline the preponderance of advanced-stage disease at presentation.

Precise tumour (T) and nodal (N) staging is imperative as it determines subsequent treatment, especially when considering neo-adjuvant therapy for IIIa and IIIb disease. Only approximately one-half of the TNM stages derived from CT agree with operative staging, with patients being both under and over staged.

However, quick access to investigation, high histological confirmation rates (at bronchoscopic/transthoracic biopsy or at thoracotomy), routine CT scanning and review of every patient by a thoracic surgeon is known to substantially increase successful surgical resection.

Tumour status

The distinction between T3 and T4 tumours is critical because it separates conventional surgical and nonsurgical management. T4 tumours may be readily identified by virtue of their invasion of a vertebral body, obvious invasion of the mediastinum or heart or the presence of lung parenchymal metastases. T3 tumours can however be more difficult to grade principally because of the difficulties of distinguishing simple extension of the tumour into the mediastinal pleura or pericardium (T3) from actual invasion (T4).

Mediastinal invasion. Minimal invasion of mediastinal fat is considered resectable by many surgeons. Contact with the mediastinum is not enough to diagnose mediastinal invasion.

The Radiologic Diagnostic Oncology Group compared CT and MRI in 170 patients with NSCLC, 90% of whom went on to thoracotomy. There was no significant difference between the sensitivity of the two modalities (63% and 56% respectively) or the specificity (84% and 80%) for distinguishing between T3-4 and T1-2 tumours, except when receiver operating characteristic analysis was performed on the statistics. These showed that MRI is better than CT at diagnosing mediastinal invasion. MRI is particularly useful in determining invasion of the myocardium or tumour extension into the left atrium via the pulmonary veins.

Chest wall invasion. CT assessment of tumour chest wall invasion is variable with quoted sensitivities ranging from 38–87% and specificities from 40–90%. Invasion of the chest wall by a mass results in a T3 score. This does not mean the mass is irresectable per se but en bloc resection of the mass and adjacent chest wall is necessary which carries an associated increase in mortality and morbidity. Ultrasound has been cited as an additional technique for chest wall assessment. MRI is a useful technique in establishing chest wall invasion. It relies on the demonstration of infiltration or disruption of the normal extra pleural fat plane on T1-weighted images or parietal pleural signal hyperintensity on T2 weighting. The diagnostic yield is further improved by intravenous gadolinium contrast medium. Sagittal and coronal MRI better display the anatomical relationships at the lung apex as opposed to axial CT.

In superior sulcus or Pancoast tumours detection of tumour invasion beyond the lung apex into the brachial plexus, subclavian artery or vertebral body by MRI has been found to be 94% accurate as opposed to 63% for CT, although multislice CT with nonaxial reconstruction may improve this figure. Surface coils and thin sections (5 mm) are advised for MRI of such tumours.

Pleural invasion. Effusions in patients with lung cancer can be benign, especially with a postobstructive pneumonia or malignant due to pleural metastases, often characterized by pleural nodularity. Such an effusion renders the tumour T4 and irresectable, though this should be confirmed by thoracocentesis or pleural biopsy.

Nodal status

The most important predictor of outcome in the majority of patients with lung cancer limited to the chest is the presence or absence of involved mediastinal lymph nodes. N3 nodal disease is not an option surgically whilst the management of N2 disease is debatable.

Mediastinoscopy and CT are recognized to be the most valuable techniques for evaluation of mediastinal lymph node metastases but the arrival of PET has begun to influence patient management in the limited number of centres where it is available.

The enthusiasm for the usefulness of CT in assessing nodal status grew throughout the 1980s. In 1984, LIBSHITZ and MCKENNA demonstrated CT sensitivity and specificity of 67% and 66% respectively using a nodal size of 1 cm to distinguish between benign nodes and those seeded with metastases. In 1988 STAPLES et al. demonstrated 79% sensitivity and 65% specificity for CT using a 1-cm long axis nodal cut-off measurement. More recently in a study of hila and mediastinal nodes at CT compared to pathological examination, sensitivities and specifi- cities for metastatic involvement were only 48% and 53% with an overall accuracy of 51%.

Despite these statistics, CT is still recommended as the standard strategy for the investigation of lung cancer, CT and mediastinoscopy in all patients proving too expensive. It is recommended that mediastinoscopy and biopsy be reserved for nodes with a short axis diameter of > 1 cm in size. Further refinements of indications for mediastinoscopy have been recommended with its omission in patients with T1 lesions and negative nodes at CT, unless the cell type is adeno- or large cell carcinoma.

CT may help to serve as a road map to guide fibreoptic bronchoscopy and biopsy and help identify enlarged nodes that are beyond the reach of the mediastinoscope. It also alerts the surgeon to the presence of anatomical anomalies.

No significant difference has been found between the ability of CT and MRI to detect N2 or N3 mediastinal metastases. The combination of respiratory movement artefact and poorer spatial resolution inherent with MRI can mean that small discrete nodes as seen on CT can appear as a larger, indistinct, single nodal mass on MRI, leading to the erroneous diagnosis of nodal enlargement. MRI is also poor at detecting nodal calcification and may thus misclassify enlarged benign nodes as malignant.

Metastatic status

A meta-analysis of 25 studies evaluating clinical examination and imaging findings (CT head, abdomen or bone scintigraphy), found the risk of metastases detected by imaging to be < 3% if clinical examination is normal.

If clinical examination is positive for metastatic disease then metastases will be found by imaging in approximately 50% of patients.

The metastases most commonly affected brain, bone, liver, and adrenal glands in that order. How best to identify these patients preoperatively and prevent a needless thoracotomy is not clear. The literature is divided, with some studies showing that screening all patients for extrathoracic metastases before thoracotomy is cost-effective and others finding that this was not the case. It is now standard to include the adrenals and liver as part of a staging CT of the chest and upper abdomen.

More recently, a multicenter, prospective randomized trial of 634 patients by the Canadian Oncology Group was designed to finally answer the question concerning whether to search for occult metastases in the asymptomatic patient with a resectable lung tumor and no clinical suggestion of extrathoracic spread. Although thoracotomy without recurrence occurred less often in patients who underwent full investigation (bone scintigraphy and CT of the head, thorax, and abdomen) as opposed to limited investigation (CT of the thorax with mediastinoscopy and other investigations as clinically indicated), the survival results were similar. In the meantime, we agree with the recommendations of Silvestri, that, before attempted resection, all patients should have a comprehensive clinical examination and even the subtless of abnormalities should be investigated. Asymptomatic patients with Stage I disease should not be investigated further, but a routine search for metastases is recommended in any patient with known or suspected N2 disease.

Diagnostic staging of small cell lung cancer

SCLC is distinguished from NSCLC by its rapid tumour doubling time, development of early widespread metastases and almost exclusive occurrence in smokers. It is divided into two stages: limited disease, which is confined to the ipsilateral hemithorax within a single, tolerable radiotherapy port and extensive disease which covers all other disease including distant metastases. Systemic therapy is required for all patients with SCLC, even those with limited disease. Mediastinal radiotherapy is not always indicated in patients with extensive disease making the distinction between the two stages important. To avoid an exhaustive search for extensive disease (e.g. chest, liver, adrenal and cranial CT, bone scans, marrow aspirates etc.) an alternative approach is to allow clinical symptoms to direct imaging, terminating on the discovery of extensive disease. Given the fact that cranial CT in SCLC is positive in 15% of patients at diagnosis, one-third of whom are asymptomatic and that early treatment of brain metastases yields a lower rate of chronic neurological morbidity, it seems reasonable to begin any extrathoracic staging with brain imaging.

DIFFERENTIAL DIAGNOSTICS OF THE

LUNG CANCER AND PNEUMONIAS

The anamnesis of disease is very important. Frequently patients with acute pneumonia point out the acute beginning with a fever. The important information is the patient is for the first time or repeatedly was ill. If he was repeatedly ill, radiological inspection before and after treatment was carried out.

In differential diagnostics of chronic nonspecific pneumonia and the central cancer crucial importance has X-ray examination. Performance of chest roentgenograms in two projections, direct and lateral, is necessary in the beginning and after treatment. It is necessary to note, that segmentary and lobular forms of a chronic nonspecific pneumonia differ from a LC, that they extremely seldom have strictly share or segmentary extent. As a rule, defeat of a part of one lobe is observed. Inflammatory process tends to be distributed through an interlobar rima to the next lobe. The both lower lobes, upper right lobe, and 2-nd and 6-th segments are affected more often. Borders of shadow, as a rule, are indistinct and rough.

The spherical form of focuses of a pneumonia are visible usually only in one projection, more often in a direct one. In another projection their form comes nearer to triangular or wrong oval. The peripherial LC is necessary to differentiate with a ball-shaped chronic nonspecific pneumonia. As against focuses of a chronic pneumonia the peripherial LC has more correct spherical form in two projections and more precise tuberous external contours.

At the central LC in most cases there are two groups of attributes: ones display tumoral process, others – its complications (a pneumonitis, enlarged lymph nodes of a lung hilar and a mediastinum, an exudate in a pleural cavity). To the most authentic and convincing attributes displaying tumoral process are concerned: the image of peribronchial or endobronchial tumoral node, narrowing or a stump of a main, lobular or segmental bronchi.

In differential diagnostics sputum cytologic examinations on presence of cancer cells helps. It is recommended to carry out not less than 5 examinations.

Big difficulties are connected with differential diagnostics of a cancer of a midlobar bronchus syndrome which obturation is accompanied by an atelectasis of a lobe. Among patients with the isolated defeat of an average lobe by various pathological processes, the cancer meets at 16-17 %. The isolated cancer defeats of a midlobar bronchus represent the greatest difficulties in differential diagnostics with chronic inflammatory defeats. At a LC in level-by-level pictures in a oblique or lateral projection the sign of "stump", or "ablation" of a lobar bronchus is taped. The shadow of tumoral node on a background of blackout is sometimes visible. The final decision of a question on character of a stenosis becomes possible only after a bronchoscopy with a biopsy.
DIFFERENTIAL DIAGNOSTICS OF THE

LUNG CANCER AND THE TUBERCULOSIS

Frequently LC has some similar clinical and radiological signs with pulmonary tuberculosis. Therefore an appreciable part of patients with a LC is wrongly long time under observation of phthisiatricians with the diagnosis of various clinical forms of tuberculosis and receives specific treatment. The cancer mainly amazes persons of elderly and senile age, while tuberculosis – persons of younger age.

In an anamnesis of patients with a LC are frequently repeated pneumonias. In patients with tuberculosis there are frequent indications on contact with a person with tuberculosis at home or at work. In case of LC tuberculine assays, as a rule, negative while at a tuberculosis they are positive or sharply positive. Presence of micobacteria of tuberculosis in a sputum also considerably facilitates differential diagnostics of a LC.

The central LC most frequently is necessary to differentiate with a tubercular infiltrate in a hilar zone, a tubercular lymphadenitis.

It is especially difficult to differentiate pathology when tubercular process grasps a lobe or a segment. In these cases cancer focus in lung will correspond to an atelectasis with all radiological attributes of the last one, and at tuberculosis it will correspond to a specific pneumonia. Radiologically the shadow of a tubercular infiltrate is less homogenic and intensive, indistinct on edges, less closely connected with a hilar zone and progresses from center to periphery. For tuberculosis is typically bilaterial defeat of lungs, fibrosis and inclusions of a lime. For infiltrative tuberculosis is more often than for a cancer the acute beginning, high temperature, tussis, chest pain.

Peripherial LC is difficult to differentiate from tuberculoma or caseoma. Incapsulated centers and focuses of a fiber-caseous nature make a basis of tuberculomas (the original chronic form of a tuberculosis). Tuberculomas make approximately 4-5 % among other forms of the tuberculosis revealed primarily. Tuberculomas as the same as cancer tumors, have precise borders. They are the centers of a caseous pneumonia and before break in a bronchus proceed completely asymptomatically. Caseomas are most frequently localized subpleurally and contain calcinates. Formation of a cavity is not specific only for these diseases, because this sign also happens in case of the cavitary form of a peripherial LC.

Around the tuberculomas and caseomas are frequently tuberculous focuses and calcified lymph nodes near lung hilar are observed. At tuberculosis around the tumor center usually is inflammatory infiltration. At a peripherial cancer the perifocal phenomena are absent. It is also known, that tuberculomas are extremely rare (2-3 %) localized in forward segments, and also in the lower lobes. However, last stage of differential diagnostics of these two diseases is the thoracotomy and sometimes only morphological examination of the removed material.
INTERNATIONAL CLASSIFICATION OF THE LUNG CANCER BY TNM (6TH EDITION, 2002) AND THE STAGE GROUPING