Mediastinal diseases: clinical and therapeutic aspects

ORIGINAL ARTICLE

Mediastinal diseases: clinical and therapeutic aspects^*

Roberto Saad Júnior^I (te sbct); Maria Elisa Ruffolo Magliari^II; Júlio Mott Ancona Lopez^III

^IHead Professor. Specialist title by the Brazilian Society for Thoracic Surgery

^IIDoctor in Medicine

^IIIResident Physician

^{Correspondence}

ABSTRACT

Background: Mediastinal affections are common and encompass a great number of different diagnoses.

Objective: To analyze the clinical aspects and the therapeutic response of 114 patients with mediastinal diseases treated at the Thoracic Surgery Department of Santa Casa de São Paulo Hospital, from 1979 and 1997.

Method: The patients were grouped according to the benign or malignant nature of the disease, and the two groups were compared regarding gender, age bracket, symptomatology, topography of the lesion, mortality, and response to treatment.

Results: Sixty-three patients had neoplasia: 31 benign and 32 malignant. Fifty-one cases were not neoplastic. No difference was found between the groups regarding gender or age bracket. Half of the patients were between 20 and 49 years of age. The anterior mediastinum was the most frequently affected compartment (66 patients), followed by the upper mediastinum (18 patients), the posterior mediastinum (16 patients), and the middle mediastinum (14 patients). The most frequent histological types were: benign thymus diseases (N = 40), mesenchymal tumors (N = 17), lymphomas (N = 15), neural tumors (N = 9), and germ cell tumors (N = 8). Malignant tumors were more frequently symptomatic (91%), and benign tumors were more frequent in asymptomatic patients (92%). The most frequent symptoms were related to myastenia gravis, followed by dyspnea and chest pain. Weight loss, anorexia and fever were significantly more frequent in patients with malignant neoplasias.

Conclusions: Regarding the clinical aspects we can state that benign lesions were predominant, that mediastinal diseases were more prevalent in young adults, and that benign lesions were more frequent in asymptomatic patients. Treatment (clinical/surgical) was effective in most patients, benefiting approximately 90% of the patients with benign affections and 45% of the patients with malignant tumors. In 73% of the benign affections, surgical treatment was capable of achieving the cure. Mortality resulting from complications was 1.75%.

Key words: Mediastinum. Mediastinal disease/epidemiology. Mediastinal neoplasms.

Introduction

The mediastinum, in addition to containing various organs and vital structures is the site of several uncommon lesions as well as manifestations of a number of systemic diseases.⁽¹⁾ Possibly, the large variety of tumors and cysts is due to the embryonic complexity of local structures resulting from different combinations of the three embryonic layers.⁽²⁾ Some lesions, such as esophageal tumors and vascular and diaphragmatic defects, although not considered mediastinal diseases may sometimes present themselves as such and must be taken into account at differential diagnosis.

When all indications for thoracic surgery are considered, mediastinal lesions are not frequent. Oldham and Sabiston⁽³⁾ observed a ratio of 1:3,400 corresponding to 0.029% admissions for such lesions in third line hospitals. Trench and Saad Jr⁽⁴⁾ up to 1968, reported 2,456 surgical cases at the Thoracic Surgery Department of the “Santa Casa de São Paulo”, of which 85 were mediastinal tumors. Records show that from 1979 to 1997, 1 in 2,569, 0.038% of admissions at the hospital was due to mediastinal tumors (SAME-SCSP – Medical Files and Statistics Service, Santa Casa de São Paulo).

This study intended to analyze the clinical aspects: gender, age bracket, symptoms, site of lesion, therapeutic response, and mortality rate of patients assisted at the Thoracic Surgery Department of the Santa Casa de São Paulo from November 1979 to June 1997.

Sample size and methods

One hundred and fourteen patients with mediastinal disease admitted at the Heart and Lung Unit, Surgery Department of Santa Casa de São Paulo between November, 1979 and June 1997 were studied.

In this study, the mediastinum was divided according to the classical patterns that is to say, into a superior and an inferior portion, separated by a plan that goes from the Louis angle to the fourth intervertebral disc. The lower compartment, with the heart as its point of reference is subdivided in three parts: anterior, middle, and posterior.

Patients were grouped according to the benign or malignant nature of the lesion. The two groups were then analyzed following these clinical aspects: gender, age bracket, symptoms, site, postoperative complications, histological diagnosis, and treatment.

Two tests, the chi-square and the Fisher’s exact test, were used for comparison of frequencies of each pathology. Student’s t test and variance analysis were used in the comparison of averages. Kruskal-Wallis’ non-parametrical test was used for quantitative variables that did not present a normal distribution or variance homogeneity. A 5% alpha was established for the significance analysis by means of the Epi-Info, version 6.04-B software, for database processing and calculation.

Results

The sample size was of 114 patients, of which 61 (53.5%) were female and 53 (46.4%) were male. For the case of benign tumors, ages ranged from 5 to 80 years, with a mean of 38.6 and a median of 37 years and for malignancies, ages ranged from 17 to 79 years, with a mean of 42.2 and a median of 40 years. In terms of nature of the mediastinal lesion, 82 patients (71.9%) had benign lesions (51 non-neoplastic lesions, 31 benign tumors), and 32 (28%) had malignant tumors.

With regard to gender, no difference in the distribution of frequency of mediastinal diseases was disclosed according to their benign or malignant nature or to analysis of the anatomic and pathological findings.

The mean age of patients, bearers of benign or malignant lesions was similar; however benign thyroid diseases tended to be more frequent in older patients.

The distribution of patients’ age bracket in terms of nature of the disease also did not show significant differences. Nevertheless, it was observed that both benign and malignant lesions were most frequent at ages ranging from 20 to 49 years (50.4%). It was also observed that in this age bracket, incidence of thymus diseases (22%) is significantly higher than that of other benign manifestations. Lymphoma is the most frequent (10%) malignant mediastinal disease of patients in this age bracket.

The topography of tumors disclosed a higher prevalence in the anterior mediastinal compartment for benign and for malignant lesions. However, considering the benign or malignant nature of the lesions there was no significant difference in terms of location. Tables 1, 2, 3, and ⁴ respectively show distribution of the lesions in the anterior, middle, posterior, and superior compartments.

Of those found in the anterior mediastinum, thymus benign lesions were more frequent than the others reported (60.6%).

Data regarding symptoms of 78 patients were assessed. Twenty four (30.8%) patients were non-symptomatic at the time of diagnosis. Of these two (8.3%) had malignant tumors and 22 (91.7%) patients had benign lesions. Similarly, symptoms were more prevalent among patients with malignant disease, that is to say of the 34 symptomatic patients, 29 (91.3%) presented with malignant neoplasms. In these patients loss of weight, fever, and anorexia were the most frequent symptoms.

The mean time span for duration of the symptoms was similar for patients with benign (11.4 months) or malignant (10.2 months) lesions.

Information about intra and postoperative complications was obtained for 98 patients: 81 (82.7%) had no complications at all while 17 (17.3%) patients presented 23 complications with arrhythmia, pneumonia and pleural effusion being most frequent. (Tables 5 and 6).

The mean follow-up period was of 28.1 months for patients with benign lesions, and of 36.6 months for patients who had malignant neoplasms further, recovery and symptom improvement were more frequent among patients with benign lesions (63.4%).

Discussion

In the group under study no difference was found for gender, as stated by Wychulis et al⁽⁵⁾. Meyer and Ochsner⁽⁶⁾ had reported a higher incidence for some diseases in special age groups, a fact that can be observed in neural tumors which in some cases may affect primarily children. This point could not be assessed in the present study because patients under 12 years are assisted by the Pediatric Surgery Department.

For benign and malignant lesions the age of more than half of the patients ranged from 20 to 49 years. Davis et al⁽⁷⁾ studied 400 patients with mediastinal lesions finding a higher incidence of mediastinal masses between 30 and 50 years of age, with a significantly higher incidence of malignancy around the forty year age group, comparable to our findings.

Benign mediastinal findings accounted for 71.9% of the cases; Ximenes Neto and Almeida⁽⁸⁾ observed 59% of benign lesions in 80 cases of mediastinal tumors, and for Strollo et al,⁽⁹⁾ this frequency was of 66%.

Regarding symptoms, literature concurs that benign tumors are more frequently asymptomatic⁽¹⁰⁾ than malignant ones; however there is a recent tendency to an increasing number of patients with asymptomatic malignant tumors along with lesser tumor size at diagnosis due to the development of better diagnostic procedures.⁽⁷⁾ Approximately 77% of our patients had no symptoms, while most reports in literature state a 50 to 65% rate of asymptomatic patients.⁽¹¹⁾

It was also observed that 92% of the patients with malignant tumor were symptomatic; Ximenes Neto and Almeida⁽⁸⁾ registered a higher incidence of malignant tumors in symptomatic patients.

Most mediastinal tumors follow a pattern related to age, site of origin and effects on adjacent structures.⁽¹²⁾ In some cases, roentgenograms and tumor site may supply data for a quite precise diagnosis.⁽¹³⁾

Just as with other authors,^{(8, 9)} in our cohort, the anterior mediastinum was the site most frequently (57.8%) affected. When only malignant lesions are analyzed, 71.9% (primary lymphomas) were located in the anterior-superior mediastinum, as reported by Davis et al.⁽⁷⁾

Thymus adenoma was the most frequent benign neoplasm, usually located in the anterior mediastinum and myastheniagravis was present in 45.5% of these patients. In most studies, frequency of thymus adenoma ranges from 12% to 19% of primary mediastinal masses, ^{(11, 14)} being the most common tumor in the anterior region .Treatment of thymus adenoma is always surgical. In case of a malignancy (carcinoma), surgery must be followed by radiotherapy and/or chemotherapy.

Presence of myasthenia gravis does not entail a worse prognosis for surgery, ^{(8, 15)} on the contrary, it substantiates its indication, since after surgery symptoms improve significantly. Saad Jr et al⁽¹⁶⁾ observed that over a follow-up period of 46 months, 75% of the patients with myasthenia gravis improved after surgery. In our study, 81% patients over a mean follow-up period of 38.5 months showed a change for the better.

Myasthenia gravis can be associated with several patterns of thymus alterations. Ximenes and Barbosa ⁽¹⁷⁾ found a thymus with normal histological aspect in 20% of the myasthenia gravis patients. Our statistics show that, 70% of such patients had a thymus with a normal histological aspect or had a thymus inflammation.

Mesenchymal tumors were the second most frequent lesion accounting for 14.9% of all mediastinal tumors. In the majority of studies they account for 6% of the total of mediastinal tumors,⁽⁵⁾ with a high incidence of malignancy.⁽¹⁸⁾ Lipomas are the most common mesenchymal tumors in the mediastinum.⁽¹⁹⁾ This type of tumor has no preference for gender or age and may progress to large volumes. On the other hand, should they be small and non-symptomatic and should roentgenograms strongly suggest their benign nature, ⁽⁴⁾ surgery may be postponed as took place in two of our cases.

In the current study, lymphoma was the most frequent malignancy with 15 cases (13.1%), whereas Wychulis et al, ⁽⁵⁾ spoke of 10% of the cases, and Davis et al, ⁽⁷⁾ mentioned 12.5%.

Among the 15 patients with lymphoma, 10 had Hodgkin’s disease and five had non-Hodgkin’s disease. All of the Hodgkin’s disease cases were of the nodular sclerosis histological type.

Five patients had non-Hodgkin’s lymphoma which is a more frequent tumor in adults. It has no preference for mediastinal location and 20% appear initially in the mediastinum, however they are mostly disseminated at diagnosis.

The germ cell tumors are a result of abnormal primary germ cell migration at embryogenesis with teratoma being the most common subtype.⁽⁴⁾ In this study eight patients had germ cell tumors, with 25% of malignant cases similar to what Moran and Suster described.⁽²⁰⁾ In one case, suspicion of malignant teratoma was confirmed at preoperative by roentgenograms. Chest x-ray may exhibit calcifications in 26% of the cases and structures such as teeth or bones can seldom be recognized. ⁽²¹⁾

Thyroid masses represent almost 50% of all superior mediastinum lesions and are mostly benign. In our study they corresponded to precisely 50% of all lesions in the superior mediastinum.

Mediastinal tuberculosis and sarcoidosis are characterized by hilar and para-tracheal lymph node enlargement which may be associated with a pulmonary infiltrate typical of these diseases. In the current study there were six patients with sarcoidosis and two patients with tuberculosis all of which exhibited good response to specific treatment.

Three patients had bronchogenic cysts, all had respiratory symptoms and were submitted to surgery.

Pleural-pericardial or celomic cysts stem from the persistence of the ventral recess of the primitive pericardial cavity or may be caused by an abnormal fusion of the embryonic pleura. On roentgenograms homogeneous and smooth masses at the right cardiophrenic angle are apparent. ⁽¹⁹⁾ Every cyst, even if benign, must be surgically excised due to eventual future complications, as well as because of their location in sites common for malignant diseases which may lead to confusion at diagnosis.⁽¹⁷⁾ We had two patients with pericardial cysts who showed good evolution after surgery. In both cases diagnosis was achieved only during thoracotomy. During surgery it was observed that these cysts had narrow pedicles in communication with the pericardial sac. Thus, it was decided to resect them and suture the pericardium.

Lesions that simulate mediastinal masses may appear in the heart and large vessels.²²⁾ We had a coronary artery aneurism which was submitted to exploratory thoracotomy.

Nine patients died during follow-up; two of them had benign lesions and seven had malignancies. At the immediate postoperative, one patient with rabdomyosarcoma that invaded the heart died from irreversible arrhythmia and another with myasthenia gravis developed necrotic-hemorrhagic pancreatitis and also died.

In the late postoperative, seven patients died: one with myasthenia gravis due to a complication of a superior vena cava lesion (30^th postoperative day), two with lymphoma, one due to infection, another caused by anoxic coma, (30^th postoperative day), and four because of malignancy recurrence. Overall hospital mortality was of 1.75%, with a 3.2% for malignant tumor patients and 1.2% for benign lesions. Late mortality (36.6 months mean period) for 18 patients with malignant neoplasms whom we were able to follow-up in the outpatient care service was of 33%.

Over the years, some changes in the behavior of mediastinal lesions have been noted. In our Service, Saad Jr. et al ⁽²³⁾ carried out an earlier work, from 1979 to 1986, in which they analyzed the same cases as in the first phase of this study. They observed a prevalence of neural tumors, therefore a higher frequency of lesions in the posterior mediastinum. No incidence of lymphoma was reported. An increase in the number of malignant tumors was also observed, from 22.3% in the Saad Jr et al study⁽²³⁾ to 26.5% in this study. This difference, although without a statistical significance discloses the same tendency as that described by Cohen et al. ⁽²⁴⁾

In this study of 114 patients with mediastinal lesions we considered data of clinical and therapeutic aspects which allowed us to reach the following conclusions: mediastinal lesions are not common in general hospitals; they are more frequent among young adults and they are more prevalent in the anterior mediastinum. Benign lesions are more frequently asymptomatic, they have a low mortality rate and improvement or even recovery may be expected after adequate treatment.

Received for publication on 22/01/03

Approved, after review, on 17/04/03

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*

Research performed at the Surgery Department of Faculdade de Ciências Médicas da Santa Casa de São Paulo, Thoracic Surgery Discipline.

Publication Dates

• Publication in this collection
  02 Dec 2003
• Date of issue
  Aug 2003

History

• Accepted
  17 Apr 2003
• Received
  22 Jan 2003