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Ann Thorac Surg 2001;72:203-207
© 2001 The Society of Thoracic Surgeons

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Original article: general thoracic

Thymoma: trends over time

Accepted for publication March 13, 2001.

Address reprint requests to Dr Moore, 127 Darling St, Balmain, NSW 2041, Australia
e-mail: moore127{at}bigpond.net.au

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. This is a review of a series of patients who presented with thymoma over the most recent 20-year period. Changes and trends in disease patterns were documented.

Methods. Data were collated retrospectively but all pathology slides were reviewed. Survival functions were estimated using the Kaplan-Meier method.

Results. Seventy-one patients had a partial or total thymectomy during this period for a thymoma. Average age was 55 years. Twenty-three patients (32%) had myaesthenia gravis. Eighteen patients (25%) were asymptomatic. Thirty-three patients (47%) had stage 1 disease. Complete resection was achieved in 60 patients (85%). Five-year survival was 88%. Fifty percent of patients with myesthenia gravis showed improvement in symptoms.

Conclusions. Five- and 10-year survival rates in this study are better than in other series. We attribute this to an increasing number of patients with stage 1 and stage 2 disease, particularly those with myasthenia gravis who now have screening computer tomography, and also to the surgical intent of aiming to achieve complete resection even if excision of adjacent tissue is required.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Tumors within the thymus gland can be both primary and metastatic. Thymomas are primary tumors that arise from the epithelial cells within the gland and account for 50% of anterior mediastinal masses and 15% of mediastinal tumors. These tumors are often associated with parathymic syndromes, most commonly myesthenia gravis (MG) [1].

Surgical resection is the preferred therapeutic option. Radiotherapy has had varying roles. It has been used as postoperative adjuvant therapy, as additional therapy after debulking procedures and less frequently as primary and neoadjuvant therapy [2].

There are only a few large series in the literature describing the characteristics of thymomas and treatment outcomes. These studies have spanned 3 or 4 decades, over which time, diagnostic modalities, terminology regarding classification, and therapeutic approaches have changed [3–5]. It has therefore been difficult to compare series and outcomes. This is a review of the experience at one cardiothoracic unit over the most recent 20 years, particularly noting changes and trends over time.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
A consecutive series of patients presenting to the cardiothoracic unit between January 1975 and September 1995 were reviewed. Data were collected retrospectively from hospital records and from a prospective database that had been established by the unit in 1984. Follow-up continued until September 2000.

All the pathology slides were reexamined and the cases classified by one pathologist, initially according to two different systems, Bernatz and colleagues [4] or Salyer and Eggleston [6] and according to the 1985 classification of Marino and Muller-Hermelink [7]. This allowed direct comparison with a similar study by Pescarmona [8]. The cases were also evaluated in the light of the later modification to this classification by Kirchner and associates [9, 10] to include well-differentiated thymic carcinoma as well as the simplified classification of Suster and Moran [11]. Cases of unequivocal thymic carcinoma and tumors not derived from thymic epithelium such as lymphoma were excluded.

Data collection included background demographic details such as, age, sex, and comorbidity (as measured by the American Society of Anesthesiology Score [13]); presenting symptoms, associated syndromes, investigations performed and details about the surgery which included the surgeon, technical approach, staging according to the Masaoka [13] system, length of stay and complications. Other treatment given was also recorded.

Outcomes included length of survival and tumor recurrence. Any improvement in symptoms of patients with MG was measured by a simple objective scale (Table 1). Survival functions were estimated using the Kaplan-Meier method [14] and comparisons made using ² tests and logistic regression [15, 16].

	Results

Top Abstract Introduction Patients and methods Results Comment References

The remaining 71 patients had a mean age of 55 (SD 12.3) and 38 patients (54%) were male. Twenty-three patients (32%) had MG and 5 (10%) had other malignancies. Most patients had ASA scores of 1 or 2.

Fifty-three patients (75%) were symptomatic. Common symptoms were those associated with MG (21 patients, 30%), chest pain (14 patients, 20%), or a persistent cough (13 patients, 18%). Every patient had a chest roentgenogram and computer tomography (CT) scan. Forty-seven patients (66%) had a mediastinal abnormality or mass on plain chest x-ray films. Twenty-four patients (34%) had fine needle aspirates and half of these were diagnostic. Other tests included those for MG (26 patients, 37%) and tumor markers (8 patients, 11%) to exclude germ cell tumors.

The preferred surgical approach was through median sternotomy (60 patients, 85%). Complete macroscopic resection was achieved in 60 patients (85%) and was more likely for those patients with stage 1 and stage 2 disease (p < 0.00001). In order to achieve macroscopic clearance adjacent tissue was occasionally resected en bloc (Table 2). There were 25 complications in 20 patients. The most common complication was respiratory (9 patients), followed by atrial fibrillation (4 patients). There was only 1 death, a patient who had MG and who died from respiratory failure.

Tumors ranged from 1.5 cm to 16 cm with a mean of 8.1 cm. The tumor size was significantly smaller (p = 0.03) in those patients with MG and also in those patients with stage 1 or 2 versus those with stage 3 or 4 disease (p = 0.002).

The largest group of tumors were classified as cortical according to the Marino and Muller-Hermelink [7] system as outlined in Table 3 and these tumors showed a predominance in those patients with MG (p = 0.005). There were 33 patients (46%) with stage 1 disease, 16 (23%) with stage 2, 13 (18%) with stage 3, and 9 (13%) with stage 4 disease. Patients with MG had earlier staged tumors than those without MG, but this difference was not significant (p = 0.08).

There was a trend to suggest that those patients with MG had a survival advantage; however, this was not statistically significant (p = 0.06) Histopathology had no bearing on survival no matter which classification was used. The stage of the disease in contrast was highly prognostic (p < 0.0001; Fig 1), as was the ability to achieve complete resection (p < 0.0001; Fig 2).

View larger version (21K): [in this window] [in a new window]   Fig 1. Survival by stage: stage 1, n = 33 (dotted black line); stage 2, n = 16 (solid gray line); stage 3, n = 13 (solid black line); stage 4, n = 9 (dotted gray line). p < 0.0001.

View larger version (16K): [in this window] [in a new window]   Fig 2. Survival by resection: complete resection, n = 60 (black line); partial resection, n = 11 (gray line). p < 0.0001.

A greater number of patients presented to the cardiothoracic unit in the latter part of this 20-year period. Although the proportion of patients with MG did not alter significantly over time there was a higher proportion of patients with stage 1 and 2 disease and a marked increase in the number of complete resections achieved over time (Fig 3).

View larger version (15K): [in this window] [in a new window]   Fig 3. Variation in type of operation: complete resection, n = 60 (black line); partial resection, n = 11 (gray line).

View larger version (29K): [in this window] [in a new window]   Fig 4. Variation in length of stay: no myasthenia gravia, n = 50 (black bar); myasthenia gravis, n = 21 (gray bar). (LOS = length of stay; MG = myasthenia gravis.)

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Survival after surgical resection of a thymoma is usually long term. The literature has concentrated on the identification of prognostic indicators whether it be clincopathologic stage, the presence of a paraneoplastic syndrome, or histopathologic classification. In this study, only the stage of the tumor and the ability to achieve a complete resection were significant predictors of survival.

Despite improvements in magnetic resonance imaging and CT scanning, staging is still dependent upon intraoperative assessment and pathologic review of the specimen. It is generally agreed, however, that the stage of the disease will clearly impact upon survival outcomes, as demonstrated in this study and in others [3–5]. Capsular invasion can be difficult to assess. It is possible that understaging of these tumors as a result of the inaccuracies of the subjective assessment by the surgeon or pathologic assessment may account for the few recurrences in patients with stage 1 and 2 disease reported in this series [3, 4].

Histopathologic classification of thymic tumors has been subject to long-running controversy. Although it has been generally agreed that tumors with an overtly malignant cytologic appearance can be delineated as a separate prognostic group of thymic carcinoma, classification of the more well differentiated thymic tumors has proved more difficult. Many attempts have been made to derive a histopathologic classification for these tumors that is both reproducible and has prognostic significance. The classification of Bernatz [5] and the similar classification used by Salyer and Eggleston [6] were based on both the morphology of the epithelial component of the tumor and the relative extent of lymphocytic infiltration. Although this classification was usually easy to apply, it was generally found to be a poor predictor of behavior. This was acknowledged in the paper by Salyer and Eggleston [6].

The classification of Marino and Muller-Hermelink [7], as originally published, attempted to classify thymomas histogenetically, based on the morphology of the epithelial cell component. A number of studies appear to show a relationship between the histologic type using this scheme and clinical behavior [8, 17] while other studies have not been able to demonstrate a relationship independent of stage [18, 19].

This classification has also been criticized for lack of reproducibility in everyday practice [20] and its histogenetic basis has been called into question. A revised classification included a category of well-differentiated thymic carcinoma which further added to the controversy [9, 10].

A simplified classification has been offered by Suster and Moran [11] that divides thymic tumors into thymoma, atypical thymoma and thymic carcinoma. This classification recognizes the futility of trying to subtype well-differentiated thymomas into prognostic categories by their histologic appearance. The category of atypical thymoma [21] consists of tumors with a predominance of epithelial cells showing mild to moderate cytologic atypia. This grouping is equivalent to the well-differentiated thymic carcinoma group of the modified Marino, Muller-Hermelink [7] classification. In our series, however, only four tumors had these features, with patient survival ranging from 27 months to more than 10 years.

Suster and Moran [11] also highlighted the importance of clear surgical margins and the lack of correlation between survival and histopathologic staging. Our study supports the views of Suster and Moran [11].

Thymomas are indolent tumors with a potential for local recurrence rather than metastasis and the best means of control or cure is surgical resection no matter what the histologic type. The primary aim in treating these patients was to achieve complete macroscopic resection and microscopic clearance, which at times required concomitant pulmonary resection. Involved tissue was removed en bloc if possible. If complete resection was not possible, there was an attempt to debulk disease. The results of this aggressive approach have been reflected in the increasing number of patients over time who had a complete macroscopic resection. Survival was significantly better in those patients in whom complete macroscopic resection was achieved.

Only stage 3 or 4 patients were offered radiotherapy as adjunctive or additional therapy but those having partial resection and radiotherapy tended to do better than if they had had no resection or no treatment.

The survival rates were higher than in other reported series [3–5]. We attribute this firstly to an increasing number of patients with stage 1 or 2 disease and secondly to the directed attempts at achieving complete resection at the time of surgery as evidenced by the number of concomitant procedures and an increasing number of complete macroscopic resections over time. This is possibly due to earlier detection, particularly in those patients with MG, who have significantly smaller tumors and marginally improved survival outcomes. Most of these patients were newly diagnosed with MG and had routine CT scans detecting stage 1 and 2 tumors. The early detection of these tumors enabled complete resection with better survival rates.

At the time of follow-up, only half of the patients with MG reported an improvement in symptoms after resection. Regardless of this it should be emphasized that resection of a thymoma for a patient with MG should not be performed with the aim of improving symptoms but rather with the intent of resecting a potentially malignant tumor.

The results indicate that some patients will show some improvement in symptoms; however, it is impossible to assess to what degree this improvement was attributable to medication or to surgery even if a detailed neurologic assessment of patients with MG was performed.

Length of stay did not change over time for patients with MG. Their underlying medical problems cause significant complications and they frequently require more extensive preoperative workup. However, for patients without MG there was a trend to a decreased length of stay. In the last 6 years most of these patients have been referred to one particular surgeon within the unit. In addition, the increasing numbers of patients being seen each year have resulted in a greater experience, which may contribute to this decrease in length of stay.

Thymomas are most appropriately treated by complete surgical resection, resulting in a 96% 10-year survival. Therefore any significant mediastinal abnormality noted on chest x-ray film or CT scan must be investigated further in order to detect potentially resectable thymomas. For high-risk patients such as those with MG, we advocate routine CT scans so that a potentially malignant tumor can be detected early and complete excision made possible. [12]

	References

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