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Schweiz Med Wochenschr 1999;129:148791 Peer reviewed article

Original article

F. Salajka Department of Respiratory Diseases and Tuberculosis, Masaryk University Hospital, Brno (CZ)

Occurrence of haemoptysis in patients with newly diagnosed lung malignancy

Summary
Aim: To evaluate the correlation of the histological type of tumour and the bronchoscopic finding with the occurrence of haemoptysis in patients with pulmonary malignancy. Methods: In a retrospective study the records of all patients with proven lung tumours were reviewed with emphasis on histological type, location of endobronchial tumour, TNM stage in relation to the presence of haemoptysis in the patients history. Results: Out of 536 patients with pulmonary malignancy, haemoptysis was present in 113, being more frequent in patients with NSCLC than SCLC and in patients with primary pulmonary tumour than those with pulmonary metastases (both p<0.05). According to the location of endobronchial tumours, haemoptysis occurred in 31% of patients with a central process, in 13% of patients with intermedial and 12% with peripheral locations, respectively. According to the TNM classification the portion of patients with haemoptysis increased with tumour size. Conclusion: Haemoptysis as the initial sign of pulmonary malignancy occurs mostly in patients with centrally located tumours. However, in individual patients the onset of bleeding is influenced by the histological type of tumour and the tumour size. Keywords: haemoptysis; malignant lung tumour; bronchoscopy

Zusammenfassung
Ziel: Untersuchungen zur Beziehung zwischen Tumortyp und bronchoskopischem Befund und Hmoptoe beim Lungenkarzinom. Methodik: Retrospektive Studie ber alle Patienten mit nachgewiesenem Lungentumor unter Einbezug folgender Parameter: histologischer Typ, Lokalisation des endobronchialen Tumors, TNM-Stadium, Vorhandensein einer Hmoptysis. Resultate: Unter 536 Patienten mit malignen Lungentumoren wiesen 113 eine Hmoptysis auf. Diese war hufiger bei nicht kleinzelligen Karzinomen und bei Patienten mit primren Lungentumoren (nicht kleinzellig versus kleinzellig und primres Lungenkarzinom versus Lungenmetastasen p <0,05). In bezug auf die Lokalisation im Bronchialbaum kam es bei 31% der Patienten mit zentralen Tumoren zu Blutungen, verglichen mit 13% bei intermediren und 12% bei peripheren Tumoren. Die Beziehung zwischen TNM-Klassifikation und Hmoptysis ergab eine Hufung mit zunehmendem T-Stadium. Schlussfolgerung: Eine Hmoptoe als Initialmanifestation eines malignen Lungentumors tritt vor allem bei Patienten mit grossen, zentral lokalisierten, nicht-kleinzelligen Karzinomen auf. Keywords: Hmoptysis; maligner Lungentumor; Bronchoskopie

Correspondence: Frantis ek Salajka, M.D. Department of Respiratory Diseases and Tuberculosis Masaryk University Hospital Jihlavska 20 CZ-639 00 Brno e-mail: fsalaj@med.muni.cz

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Original article Introduction


Haemoptysis represents a frequent symptom in pulmonary service. Haemoptysis is present in 517% of patients [14]. Haemoptysis is frequent in patients with malignant lung tumour [5, 6]. Although haemoptysis occurs as complication of a known disease in the majority of patients, some patients present with haemoptysis as initial manifestation of malignant disease. Predictive factors for haemoptysis in in-

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dividual patients remain unclear. The portion of patients with haemoptysis as initial manifestation of malignancy is also unknown. The aim of our study was to answer these questions by evaluating the relation between bronchoscopic findings, histological types and the occurrence of haemoptysis in patients with newly diagnosed lung malignancies.

Methods
In a retrospective study the records of all patients referred to the Department of Respiratory Diseases, Masaryk University Hospital, Brno (CZ), in whom primary or secondary malignant lung tumours were diagnosed in a 5-year period, were reviewed for the histological type of tumour, bronchoscopic findings and occurrence of haemoptysis. Histological and/or cytological evidence of tumour type was demonstrated in all patients with primary lung malignancy. In some patients with secondary pulmonary tumour the location of primary tumour and clinical criteria were admitted as sufficient evidence of the metastatic origin. Into evaluation were taken individual histological types as well as the entire group of non-small cell lung cancer (NSCLC) consisting of patients with epidermoid carcinoma, undifferentiated carcinoma, adenocarcinoma, and large-cell carcinoma. The occurrence of haemoptysis was followed in detail in patients history. In our clinic thorough questioning concerning the possible occurrence of haemoptysis is an integral part of personal history taken in all patients, with emphasis on the first-ever onset of blood in sputum, on the frequency of this symptom and the amount of expectorated blood. As mentioned already, only bronchoscopically examined patients were included into the study. Taking into account that the source of bleeding in patients with malignant lung tumour is the endobronchially growing tumours tissue, the proximal edge of tumours infiltration and/or exophyte was evaluated during bronchoscopic examination. The location in trachea or main bronchi was declared as central changes, that in lobar bronchi as intermedial changes. The patients with endobronchially growing tumour in a more peripheral location as well as those with only indirect bronchoscopic signs of tumour and with normal finding were included into the group with peripheral changes. The patients without haemoptysis were classified in the same way. The size of the tumour according to the TNM classification was also drawn from the records for a detailed evaluation. Statistical evaluation of obtained data was made at the Centre for Mathematical Modelling in Biology and Medicine, Masaryk University, Brno (CZ). Fisher-exact and Mann-Whitney tests were performed using the CSS Statistica Package, StatSoft Inc., USA.

Results
Primary bronchogenic carcinoma was demonstrated in 536 patients and secondary malignant lung tumour in 61 patients during the evaluated period. Apart from them suspicion of primary pulmonary malignancy only based on clinical and roentgenological criteria was postulated in 19 patients and bronchoscopy was not performed in further 28 patients with bronchogenic carcinoma. These patients were not included in the study. In 5 of them personal history was positive for haemoptysis. In our group of 597 patients haemoptysis as an initial sign of tumour was present in 113 of them (table 1). Haemoptysis was significantly more frequent in patients with non-small cell carcinoma in comparison with patients with small cell carcinoma and in primary lung tumours in comparison with pulmonary metastases (all p <0.05). The differences among individual types of non-small cell carcinoma did not reach statistical significance. 1488 At bronchoscopic examination endobronchially growing tumours pathological changes in central region were found in 217 patients and those in intermedial region in 137 patients. The remaining 243 patients were classified as peripheral changes group. Pulmonary metastases were significantly more often located in the peripheral region than primary lung tumours (p <0.05); other differences did not reach statistical significance. Assessing haemoptysis as one of initial signs of pulmonary malignancy, the relationship between its occurrence and location of endobronchial tumour changes was evaluated in individual histological types. In the table (table 1) the portion of patients with haemoptysis of all patients with a particular histological type is demonstrated for each of the evaluated tumour locations. In almost all types of carcinoma with the exception of undifferentiated carcinoma haemoptysis occurred most frequently in

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Original article
of haemoptysis in patients with centrally located tumours was confirmed when the TNM classification was used for the evaluation. The number of patients classified in individual grades of T classification is demonstrated in table 2 together with the portion of patients with haemoptysis. In total, haemoptysis was present in no patient in T1 grade, in 16% of patients in T2, in 23% of patients in T3, and in 38% of patients in T4 grade, respectively. The occurrence of haemoptysis in T4 patients was significantly higher than in T1 and T2 patients (both p <0.05).
peripheral all 44 101 16 31 7 155 44 248 haemoptysis 4 (9.1%) 14 (13.9%) 7 (43.8%) 3 (9.7%) 0 (0%) 24 (15.5%) 1 (2.3%) 29 (11.7%) total all 144 291 40 50 11 392 61 597 haemoptysis 19 (13.2%) 65 (22.3%) 12 (30.0%) 10 (20.0%) 2 (18.2%) 89 (22.7%) 5 (8.2%) 113 (18.9%)

patients with endobronchial tumour located in the central airways. The differences in the occurrence of haemoptysis between central and intermedial as well as between central and peripheral groups were significant in the whole group of patients, in the NSCLC group and in epidermoid carcinoma patients (all p <0.05). In metastatic patients, the incidence of haemoptysis with central process was significantly higher than in patients with peripheral changes (p <0.05). The remaining differences were not statistically significant. The trend towards more frequent occurrence
Table 1
Frequency of haemoptysis according to histological type and tumour location. * = number of all patients with endobronchial tumour in particular location; ** = number (and portion) of patients with haemoptysis out of all patients with endobronchial tumour in particular location histological type small cell squamous undifferentiated adenocarcinoma large-cell NSCLC (total) metastasis total central all* 62 127 12 6 2 147 8 219 haemoptysis** 13 (21.0%) 43 (33.9%) 2 (16.7%) 3 (50.0%) 2 (100%) 50 (34.0%) 3 (37.5%) 68 (31.1%) intermedial all 38 63 12 13 2 90 9 142

haemoptysis 2 (5.3%) 8 (12.7%) 3 (25.0%) 4 (30.8%) 0 (0%) 15 (16.7%) 1 (11.1%) 19 (13.4%)

Table 2
Frequency of haemoptysis according to histological type and tumour size. * = number of all patients with particular tumour size; ** = number (and portion) of patients with haemoptysis out of all patients with particular tumour size

T grade

I all* haemoptysis** 0 0 0 0 0 0 0 0

II all 100 203 29 38 9 279 44 423 haemoptysis 13 (13%) 35 (17%) 10 (34%) 9 (24%) 0 54 (19%) 2 (5%) 69 (16%)

III all 31 57 10 9 2 78 6 115 haemoptysis 2 (6%) 18 (32%) 2 (20%) 0 2 (100%) 22 (28%) 2 (33%) 26 (23%)

IV all 12 29 1 1 0 31 4 47 haemoptysis 4 (33%) 12 (41%) 0 1 (100%) 0 13 (42%) 1 (25%) 18 (38%)

small cell epidermoid undifferentiated adenocarcinoma mixed type NSCLC metastasis total

1 2 0 2 0 4 7 12

Discussion
The majority of studies focused on patients examined for haemoptysis discuss the problem of how many cases of the total number of patients with haemoptysis are caused by a particular disease. However, the information concerning the frequence of haemoptysis in the whole group of patients with a certain disease, and the factors influencing the onset of bleeding in these patients, still remains unsufficient. The data about patients with bronchogenic carcinoma are presented in some studies, in contrast with other diagnoses where this information is not available. Cahill [7] reports that haemoptysis is mentioned in the history of 710% of patients with newly diagnosed lung cancer. In the group of 279 patients, referred by Baric [8], in whom the diagnosis of bronchogenic carcinoma was proved, haemoptysis was present in 13%. According to Spiro [9], haemoptysis as the sole initial symptom is present in 5% of lung cancer patients, but as one of initial symptoms (coupled with cough, chest pain, fatigue etc.) in 50%. White [10] reports a 16% incidence of haemoptysis in the group of 1202 patients with bronchogenic carcinoma. Among 2000 bronchogenic carcinoma patients included in the Veterans Administration Lung Cancer Group (VALG) haemoptysis as an initial symptom was present in 29%, in the metaanalysis evaluating 8638 patients the incidence increased up to 41% [11]. The reported portion of patients with pulmonary metastases 1489

Original article
from extrapulmonary tumours presenting with haemoptysis also varies in the wide range between 12% and 28% [12, 13]. The incidence of haemoptysis in 19% of our patients with lung tumour lies in the lower part of the reported values. Bloedner [14] discussed the dependence of the occurrence of initial haemoptysis on the histological type of lung tumour. In the group of 767 patients haemoptysis as the sole or one of the initial symptoms was present in 26% of 373 patients with epidermoid carcinoma, in 21% of 244 patients with small cell carcinoma, in 16% of 64 patients with giant cell carcinoma, and in 14% of 86 patients with adenocarcinoma. According to Spiros summarised data [9], haemoptysis is present in 31% of patients with epidermoid carcinoma, in 29% of patients with small cell carcinoma, in 16% of patients with adenocarcinoma and in 6% of patients with undifferentiated giant cell carcinoma. In contrast with the results of the previously mentioned studies in our study the occurrence of haemoptysis in patients with small cell carcinoma was lower than in patients with all other types of tumour except those with pulmonary metastasis. This difference could not be explained by a more pronounced peripheral location of tumour in these patients. The portion of patients with SCLC classified in the group with peripheral changes was the lowest among all groups of patients and, on the other hand, haemoptysis was less frequent in all locations of endobronchial tumour in these patients. Also, when the size of tumour according the TNM classification as evaluated, no significant differences were found in comparison with other groups. The situation was different in patients with pulmonary metastasis of extrapulmonary tumour, where the absolutely lowest incidence of haemoptysis (8%) was found. In this group small peripheral lesions were diagnosed as demonstrated by the evaluation of the tumour size using the TNM classification as well as by the observed location of endobronchial changes. The low portion of patients with haemoptysis in this group could be considered as a sign of an early diagnosis of these processes, probably resulting from complaints connected either with growth of primary tumour in processes not yet diagnosed, or with regular controls in patients with already known diagnosis of primary malignancy.

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Haemoptysis in patients with primary adenocarcinoma was rather frequent in our group (20%) in comparison with other histological types as well as with the previously reported studies [9, 14]. The size of these tumours was rather small at the time of diagnosis; the T grade according to the TNM classification as well as portions of patients with central, intermedial and peripheral changes were very close to those observed in patients with pulmonary metastases. However, the incidence of haemoptysis was evidently higher in adenocarcinoma patients, being completely comparable with that in other non-small cell carcinomas.

Conclusion
The histological type of tumours can be assessed as one of possible factors strongly influencing the observed differences in the incidence of haemoptysis occurring as initial sign of malignant lung tumour. It should be emphasised, however, that our data do not correspond completely with the previously published studies. On the other hand, the data already published seem to vary in a too wide range to enable a conclusive description of the situation. In our opinion there is a shortage of information concerning the relationship between the histological type of malignant lung tumour and the onset of haemoptysis as a consequence of tumours biological properties. Further studies should bring the definite answer to this question. According to our results haemoptysis occurs mostly in patients with endobronchial tumour growing in the central airways. This was observed in almost all histological types of malignancies although due to the low number of patients statistical significance was attained only in the groups of patients with epidermoid carcinoma and pulmonary metastases. However, the possibility cannot be ruled out that the central location assessed bronchoscopically could be in some cases the manifestation of the primary site of the origin of the still small sized tumour rather than the evidence of an already advanced process. To answer this question a more complex assessment including results of roentgenological and CT examinations would be necessary.

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Original article

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