It is , however , of interest to note that as regards the after-history of cases of serous pleural effusion , the Registrar at the Brompton Hospital , Dr. W. E. Lloyd , who has recently been following up a series , found that in all the patients over 45 , of which he had a fairly large proportion , subsequent examination showed definite radiological evidence of tuberculous infiltration of the lung parenchyma .sx 3 .sx The cases in which the disease is manifested by symptoms and signs which suggest the presence of localized intrathoracic infection are often the most difficult , and the diagnosis may be still further obscured by the fact that such infection does actually occur as a complication of lung carcinoma , the resulting abscess being dealt with as a primary condition , the true underlying cause being discovered only at autopsy .sx One of the best examples of this difficulty in differential diagnosis is afforded by Case 3 , p. 65 , which is remarkable for the length of time which elapsed between the first manifestation of disease and the occurrence of death .sx One is reminded of the aphorism of Sir William Gull , who in his comments upon the case already described ( loc .sx cit .sx ) , in which he notes the impossibility of making a diagnosis by physical examination only , observes finally " It is one of the evils of a too exclusively humoral pathology that it leads us to overlook the minute anatomical relations of disease which are in themselves often a key to the sequence of morbid changes .sx " It cannot be said that there is anything , either in the history or the physical signs , in these cases of malignant disease of the lung presenting features suggestive of intrathoracic suppuration , which can be regarded as characteristic of primary new growth , the existence of which , as the fons et origo of the trouble , is frequently a question only of suspicion .sx It must be realized that physical signs are merely the outward evidence of certain gross structural changes in the underlying organs , and that recognition of the pathological causes of these changes is the result of inference and is not directly dependent upon the signs alone .sx Hence it is inevitable that in some cases , where infection and suppurative processes have occurred in a lung which is the seat of a malignant growth , the only direct information which can be afforded by physical examination , aided by the usual methods of clinical pathology , is that localized infection does exist within the chest .sx The differential diagnosis between abscess and breaking-down growth is one which is often difficult , and the failure in some instances to be sure of the presence of growth during life is occasionally inevitable .sx The difficulty of locating an inter-lobar empyema by means of physical examination and the exploring needle is well known .sx Failure to find pus in a case where , in addition to fever , leucocytosis , and general appearance of toxaemia , the patient has signs suggesting consolidation of a lung , may give rise to a suspicion of new growth .sx The radiological evidence may sometimes decide the question , but here again the appearances are not infrequently indefinite .sx Apart from the cases which come under one of the foregoing heads , there is a considerable number in which the onset is slow and insidious , and in which in the early stages diagnosis by ordinary clinical methods may be impossible .sx Many of these are for some considerable time regarded merely as cases of chronic bronchitis , the only physical signs present being characteristic of the latter , and the general condition of the patient being so good that no suspicion of malignant disease is entertained .sx The persistence of bronchitic symptoms in any patient should always demand an explanation of the cause , especially in a person still in the prime of life , and whereas a quarter of a century ago cancer as a cause of bronchitis would hardly have been thought of , to-day it is a possibility which must always cross one's mind in the case of any bronchitic patient of middle age where no definite cause can be assigned , especially if the symptoms appear to be incommensurate with the physical signs present .sx As regards those cases in which , by reason of the extension of the growth , the diagnosis is more or less obvious owing to symptoms and signs indicative of pressure on other structures , it may appear unnecessary to classify them in a separate group .sx That I have done so is due to the fact that one does occasionally come across patients in this advanced stage who have not consulted a doctor until their condition has become one of real .sx distress , and who even then are pathetically unconscious of the gravity of the situation .sx It must also , however , be observed that pressure effects , though they characterize the later stages of the disease and herald the nearer approach of death , do vary both in degree and in kind , and that the absence of pain will often deceive a patient .sx It is for this reason that one must expect occasionally to see a case of primary malignant disease of the lung in which cyanosis , oedema , dyspnoea , and even a certain amount of stridor , though they render sufficiently obvious to a physician both the nature of the disease and the extent of its progress , are nevertheless the first indications which have induced the patient to seek medical opinion .sx In reference to the absence of conscious illness in some of these advanced cases , mention must also be made of the sudden onset of cerebral symptoms which occasionally represents the first and apparently the only manifestation of disease .sx Prof .sx Hall has recently given me an interesting account of more than one patient who was brought to the hospital in a state of coma and was thought to be suffering from cerebral thrombosis or haemorrhage .sx Death was proved by autopsy to be due to the deposit in the brain of metastatic tumours originating from a primary malignant growth in the lung .sx An extremely interesting series of cases of metastases in the central nervous system from unsuspected pulmonary carcinoma has recently been published by Ferguson and Rees , who report nine cases of primary intrathoracic growths with secondary deposits .sx in the brain or cord .sx In many of these the nervous symptoms were the first evidence of manifest illness in the patient .sx SYMPTOMS AND SIGNS .sx Cough .sx Practically all these patients suffer from cough from the earliest stages of the disease , although this is extremely variable both in its severity and in its character .sx Where the cough is of the barking variety , simulating to some extent the brassy cough of aneurysm , it is probable that X rays will reveal a mass sufficiently large to give rise to at least the suspicion of an intrathoracic tumour , and examination of the larynx may show some degree of unilateral paresis from involvement of the recurrent laryngeal nerve .sx One of the most distressing varieties of cough is that which occurs when the pleura is affected by growth , and the constant irritation results in the occurrence of this particular reflex .sx This is , of course , not peculiar to growth , and may occur in any condition giving rise to pleural irritation , but in cough of this description the possibility of growth must be borne in mind , especially if it be associated with dullness and deficient movement at the base of one lung .sx Sputum is usually scanty in the early stages , but later may be much more copious .sx There is little or nothing about the ordinary appearances of the sputum which is characteristic .sx The occurrence of streaks of blood in the phlegm , if repeated , may be suspicious , but does not really give one much information ; the occurrence of definite small haemoptyses at frequent intervals is much more suggestive in cases where phthisis and cardiovascular disease have definitely been excluded .sx The occurrence of purulent foul sputum in large amounts is not uncommon in cases of pulmonary growths , but is due to the presence of secondary complications such as bronchiectasis or abscess formation , with gangrene following necrosis and breaking down of the tumour .sx Very little systematic work has been done on the examination of sputum , but occasionally the presence of cancer cells has been demonstrated , usually in association with portions of tumour actually coughed up .sx Hampeln has described certain cells in the sputum which he regards as characteristic of cancer cells , but recognition of these is a matter of some uncertainty .sx Pain is a variable symptom , and usually occurs in the later stages of the disease either through extension to the pleura or from the pressure of metastatic deposits of growth on nerve trunks of a limb .sx The pain in the earlier stages is nearly always slight and may be absent altogether .sx In carcinoma involving the upper lobe it is not uncommon to find slight pain associated with some tenderness on pressure below the clavicle .sx This is in all probability due to pleural involvement , and may be accompanied by slight friction , audible on auscultation , though sometimes it is associated with the presence of enlarged glands .sx In some cases of mediastinal growths severe pain may occur , due to actual erosion of bone , similar to that met with in aneurysm .sx Not infrequently , where there is massive growth involving the whole of the lung , the patient will complain of very severe .sx paroxysmal attacks of pain which come on at intervals for no apparent reason .sx This is by no means a constant phenomenon , but when it does occur in the late stages it is rather characteristic .sx For the most part it may be said that cancer of the lung , like cancer in many other situations , tends to be a relatively painless disease .sx Dyspnoea is a much more frequent and characteristic symptom .sx Like cough , it is practically always present in some stage of the illness , and even in the earlier periods , when the patient first comes for examination , it generally seems to be one of the most prominent complaints , and is by no means always associated with extra exertion .sx I am inclined to regard it with particular suspicion in any bronchitic type of case where there is no evidence of marked emphysema , and where physical signs are absent for the moment or disproportionate to the severity of the symptoms .sx Apart from the presence of a large pleural effusion , the dyspnoea which accompanies pulmonary new growths tends to be constant , out of proportion to the physical signs , and , like the pain , often paroxysmal in type , especially in the late stages of the disease .sx It will often be observed in advanced cases that severe dyspnoea occurs as the result of movement or change of posture on the part of the patient ; the exact explanation of this is difficult to determine ; it is possible that it may be associated with pressure on the cardiac branches of the vagus due to altered mechanical conditions within the thorax .sx Stridor is occasionally present , and if persistent is probably due to pressure of a mass of enlarged glands in the immediate neighbourhood of the bifurcation of the trachea .sx It is , as a rule , not observed in cases of marked obstruction of one bronchus , where the other bronchus is free .sx The severe dyspnoea which sometimes occurs in cases where there has been no stenosis of a main bronchus has been attributed by Assmann to cancerous infiltration of the peribronchial and perivascular lymphatics ( lymphangitis carcinomatosa ) which produces a certain degree of spasm and also hinders ventilation , sometimes by the infiltration of a large number of alveoli .sx He observes that primary bronchial carcinoma does not usually produce such a high grade of respiratory disturbance , because the lymphangitis carcinomatosa in the neighbourhood of the primary tumour , though frequent , is usually not so extensive and spares large portions of the lung , at any rate on one side .sx The most striking examples of disturbance in breathing and cyanosis , without stenosis of a large bronchus , are , according to him , to be found in the so-called miliary carcinomatosis which is usually secondary to carcinoma of other organs , especially the stomach .sx Cyanosis as may readily be understood is to be expected rather in the condition just mentioned , or in the very late stages of primary growths which have increased to such an extent as to cause general pressure effects ; occasionally , however , a certain degree of cyanosis of the face and lips is seen early and unaccompanied by symptoms of distress , and as a point in differential diagnosis may have a certain significance .sx