Multimodality Treatment of Thymoma: A Prospective Study

Background. Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy.

Methods. Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients.

Results. The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049).

Conclusions. Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.     

Adjuvant radiotherapy after complete resection of thymoma.

Seventy patients were studied after undergoing complete resection of thymoma to determine the effect of postoperative adjuvant mediastinal radiotherapy on prognosis, with regard to clinical stage, histological type, and pleural factor. Pleural factor was defined as follows: p0, no adhesion to the mediastinal pleura; p1, fibrous adhesion to the mediastinal pleura without microscopic invasion; and p2, microscopic invasion of the mediastinal pleura. Recurrence of thymoma after complete resection was observed in 13 patients, 12 (92%) with pleural dissemination, 6 (46%) with local recurrence, and 2 (15%) with distant metastasis (types of recurrence are overlapping). In stage I and stage II p0 patients, no recurrence was observed, regardless of mediastinal radiotherapy. Whereas mediastinal irradiation completely prevented recurrence in stage II p1 patients, 4 (36.4%) nonirradiated stage II p1 patients experienced recurrence. In stage II p2 patients, 75% had pleural dissemination even after radiotherapy. A high incidence of recurrence was also observed in stage III, nonirradiated (25%) and irradiated (30%) patients. The results suggest that mediastinal irradiation for stage I and II p0 patients is not always necessary, and that therapy for stage II p1 is essential and also expected to decrease the recurrence rate. On the other hand, in stage II p2 and stage III thymomas, mediastinal irradiation is not sufficient to prevent pleural recurrence even after complete resection. Our classification based on pleural factor is useful for better selection of appropriate postoperative treatment for thymoma patients.     

Treatment of thymomas. A report of 67 cases.

From 1979 to 1989, 126 patients were treated for thymic tumors. Of these, 67 (53%) had thymomas occurring in 27 men and 40 women; the mean age was 46 years: 24 patients had no symptoms and myasthenia gravis was present in 21 cases. A complete resection was performed in 45 patients, associated in 22 with postoperative adjuvant treatment (radiotherapy, 2; radio- and chemotherapy, 20). Two patients had a partial resection followed by radiotherapy and chemotherapy. Twenty patients had initially only a biopsy and were treated by irradiation in 3 cases, radio- plus chemotherapy in 16, radio- plus chemotherapy and subsequent resection in 1 case. The staging was carried out according to the GETT Classification (stage I A:26; I B:6; II:12; III A:1; III B:18; IVA:4). Thymomas were found to be of predominant epithelial type in 12 cases, predominantly lymphocytic type in 9, and mixed in 46. No recurrence occurred after complete resection. The overall 10-year survival was 71.1%. A good correlation was found according to staging: 96% in stage I; 80% in stage II; 35% in stage III. Presence of myasthenia gravis did not affect the results. The best prognostic factor remains complete resection with postoperative radiotherapy to prevent recurrences. The role of adjuvant chemotherapy needs further evaluation.     

Short-course induction chemoradiotherapy with paclitaxel for stage III non-small-cell lung cancer

Background. This study assessed toxicity, tumor response, disease control, and survival after short-course induction chemoradiotherapy and surgical resection in patients with stage III non-small-cell lung carcinoma.

Methods. Forty-five patients with stage III non-small-cell lung carcinoma received 12-day induction therapy of a 96-hour continuous infusion of cisplatin (20 mg/m² per day), 24-hour infusion of paclitaxel (175 mg/m²), and concurrent accelerated fractionation radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was scheduled for 4 weeks later. Postoperatively, a second identical course of chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given.

Results. Induction toxicity resulted in hospitalization of 18 (40%) patients for neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who underwent thoracotomy, resection for cure was possible in 32 (71%) patients. Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19 months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were from recurrent disease, three were from treatment, and two were unrelated. Recurrent disease was distant in 21 patients, distant and locoregional in 2, and locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected 24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for pathologic responders, 22% for nonresponders (p < 0.001); 83% for downstaged patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63% for resectable patients, 14% for unresectable patients (p = 0.007).

Conclusions. We conclude that short-course neoadjuvant therapy with paclitaxel (1) has manageable toxicity and a low treatment mortality, (2) results in good tumor response and downstaging, (3) provides excellent locoregional control with most recurrences being distant, and (4) has improved the median survival compared with historical controls. Survival was better in stage IIIA patients, resectable patients, pathologic responders, and patients downstaged to mediastinal node negative disease (stage 0, I, or II).     

Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation

BACKGROUND: Adjuvant radiation after resection of Masaoka stage II thymoma is widely advocated, but the evidence supporting it is controversial. Studies addressing this issue generally report few patients and lump all patients beyond stage I together in the analysis. METHODS: We retrospectively compared outcomes of stage I and II thymomas treated by resection alone with thymomas treated by resection plus radiation. Histology was re-reviewed to confirm pathologic staging and resection margin status. RESULTS: Between February 1992 and 2002, we performed 167 resections for thymoma. Of these, 70 patients were believed to have tumors in stage IIb or less intraoperatively, and all of these patients underwent complete resection. We reviewed the histopathology of 62 of 70 patients. Thirty thymomas demonstrated less than complete transcapsular microscopic invasion (stage I) and 40 thymomas demonstrated microscopic transcapsular invasion or macroscopic invasion into surrounding fatty tissue (stage II). Forty-seven patients underwent surgery without postoperative mediastinal radiotherapy. Dosages in the 23 radiated patients (3 stage I and 20 stage II) consisted of 45 to 55 Gy. Median follow-up was 70.3 months. Stage II patients who were radiated (n = 20) and those who were not radiated (n = 20) consisted of identical proportions in stages IIa and IIb. Two patients recurred (1 unradiated stage I patient and 1 radiated stage IIb patient). Overall 5-year survival rate was 91%. All who died were free of recurrence at time of death. Log-rank test showed no difference in Kaplan Meier survival curves (p = 0.32) between the radiated and unradiated groups. CONCLUSIONS: These data support the contention that margin-negative surgical resection alone is sufficient treatment for both stages I and II thymoma.     

A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma

BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival. METHODS: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning. RESULTS: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors (P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30. CONCLUSION: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.     

Local recurrence in complete resection for non-small cell lung cancer

307 patients with complete resection for non-small cell lung cancer between 1989 and 1996 were examined to evaluate the clinical features of local recurrence. Postoperative recurrence was observed in 104 of the 307 patients. At the first recurrence, local recurrences occurred in 21 (20%) of the 104 patients, distant metastases in 72 (69%), and combined recurrences in 11 (11%). 32 patients had local recurrences in 47 localizations, bronchial stump recurrences occurred in 11 (34%) of 47 localizations, hilarmediastinal lymph node metastases in 18 (56%), supraclavicular lymph node metastases in 10 (31%), contralateral mediastinal lymph node metastases in 1 (0%), and malignant effusion in 7 (22%). Lymph node metastases in the hilusmediastinum were the most common mode of the local recurrences (22%), and each mode of solely subclavian lymph node metastases and malignant effusion was 16%. The incidence of local recurrences increased as invasion into the lymphatic and/or blood vessels was demonstrated (p < 0.05). The results of our study implies that despite of lymph node dissection, latent disease persisted in the small lymphatic and/or blood vessels from hilus to subclavian sites. Postoperative adjuvant therapy including radiation will be beneficial to improvement of local control for patients invaded to lymph and/or blood vessels.     

Tumors of the thymus and thymic region: I. Clinicopathological studies on thymomas

A series of 43 patients with thymoma was reviewed. The patients were classified with respect to some factors of prognostic significance. The tumors were reclassified histologically, and a staging system with three defined stage-groups was applied to the series on the basis of operative findings and histological examination of surgical specimens. Surgical-pathological staging is of high prognostic and therapeutic importance in thymomas. Complete removal of the tumor was possible in the 25 patients with stage I or II disease and in 14 of the 18 patients with stage III tumors. Pleural metastases were observed in half of the patients with stage III disease. Even patients with extensive local spread or pleural metastases were subject to tumor resection. The treatment of choice is radical resection along in stage I; radical extirpation and, if indicated, postoperative radiotherapy in stage II; and radical resection whenever possible, even in cases of pleural spread, in stage III, with postoperative radiotherapy and chemotherapy. Myasthenia gravis is an indication rather than a contraindication to radical treatment of thymoma, although some patients may deterioratte. The importance of total thymectomy is stressed.     

Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study

BACKGROUND: The aim of this study was to clarify the characteristics of recurrence and the effectiveness of surveillance tools after curative resection for colorectal cancer. METHODS: We enrolled 5230 consecutive patients (stage I, 1367; stage II, 1912; stage III, 1951) who underwent curative resection at 14 hospitals from 1991 to 1996. All patients were followed up intensively, and their outcomes were investigated retrospectively. RESULTS: Of the 5230 patients, 906 developed recurrence. The recurrence rates of stage I, II, and III cancers were 3.7%, 13.3%, and 30.8%, respectively (P < .0001). The curves of the cumulative appearance rate of recurrence in stage II and III patients showed a rapid increase for the first 3 years. Recurrence after 5 years was less than 1% in each stage. Clinical visits combined with measurements of tumor markers detected the majority of recurrences except in the case of lung metastasis. In contrast, 43.4% of hepatic recurrences were detected by liver imaging, and 48.4% of pulmonary recurrences were noted by chest x-ray. The 5-year survival rates after primary colorectal surgery in patients who underwent resection for recurrence were better than in those without resection: 55% vs 11% in hepatic recurrence, 68% vs 13% in pulmonary recurrence, and 48% vs 22% in local recurrence (all P < .001). CONCLUSION: It is useful to take these characteristics of recurrence into account in the management of patients after curative resection for colorectal cancer and in the setting of clinical trial for follow-up after curative resection for colorectal cancer.     

Thymoma--a retrospective study of 48 cases

Of the 48 thymomas operated on between 1968 and 1985 50% were associated with myasthenia gravis, in 25% diagnosis was made due to accidental X-ray findings. In the staging according to Masaoka et al. [10] the following distribution was noted: I:22, II:5, III:18, IV:3. The 5-year survival rate of the 37 curatively resected patients was 78.5% (stage I: 88.6%, stage III: 55.6%). No stage III patient with residual tumor survived more than 2 years. Predominantly epithelial tumors had a significantly worse prognosis as compared to those with lymphocytic predominance. None of the 4 patients with category II thymoma survived more than 15 months. Association with myasthenia proved to have a negative prognostic influence in stage I and II patients. Frequency of local recurrences and metastases is documented. The value of irradiation and chemotherapy is discussed.     

Surgical treatment of thymic carcinomas

Five cases of surgically treated thymic carcinoma are reported. The patients (4 men and a woman) ranged in age from 46 to 76 years old with a mean of 64.6. Four patients were asymptomatic and an abnormal shadow on X-ray films was noted. One remaining patient suffered from hoarseness. One patient had stage II disease and the others had stage III. Surgical tumor resection was performed in all cases. Only 1 patient among the 5 underwent a successful complete resection. Histological examinations of the resected specimens revealed squamous cell carcinoma of thymus. Four specimens were poorly differentiated and 1 is moderately differentiated carcinoma. All patients received radiation therapy post operatively. Three patients are alive without any recurrence 6, 8 and 109 months after the surgery. Thymic carcinomas are frequently invasive or metastatic at the time of diagnosis. But poorly differentiated group, in squamous cell carcinoma, mucoepidermoid carcinoma and besaloid carcinoma, are characterized by a low incidence of local recurrence and distant metastasis. They also have a good sensitivity for the radiation. Therefore complete surgical resection combined with postoperative radiation therapy should be a choice in treating thymic carcinomas. We considered that complete resection and postoperative radiation therapy is a curative therapy for thymic carcinomas.     

Adjuvant radiation therapy for stage II thymoma

BACKGROUND: Thymoma is difficult to study because of its indolent natural history. The criteria for administration of adjuvant radiation therapy remain controversial, and it is unclear whether patients with Masaoka stage II thymoma benefit from adjuvant radiation. The goal of this report was to determine whether or not this group benefits from radiation therapy in terms of disease-specific survival and tumor recurrence. METHODS: Case records of the Massachusetts General Hospital were retrospectively reviewed from 1972 to 1999. One hundred fifty-five patients underwent resection for thymoma, of which, 49 had stage II disease. The world literature was reviewed using a Medline search (1966 to 2001), and a secondary review of referenced works was performed. RESULTS: Fourteen stage II patients underwent radiation therapy. Thirty-five did not receive radiation therapy. Baseline prognostic factors between radiated and nonradiated groups were similar. All patients underwent complete resection. The addition of adjuvant radiotherapy did not significantly alter local or distant recurrence rates in stage II thymoma. Disease-specific survival at 10 years in stage II patients was 100% with radiotherapy and without radiotherapy (p = 0.87). There was one recurrence in the nonradiated group at 180 months, which was outside the usual radiation portal. CONCLUSIONS: Most stage II patients do not require adjuvant radiation therapy and can be observed after complete resection.     

Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection

BACKGROUND: Little is known about the metastatic pattern in patients with extrahepatic metastasis after the removal of primary hepatocellular carcinoma (HCC). The aim of the present study was to determine the clinicopathologic characteristics and prognosis of patients with extrahepatic metastasis from HCC according to the recurrence pattern. METHODS: Among the patients who underwent hepatic resection for HCC between 1981 and 2001, 80 patients had no recurrence; 221 patients had intrahepatic recurrence, and 47 patients experienced extrahepatic metastasis within a mean follow-up period of 4.8 +/- 3.7 years (+/-SD; range, 2-15 years). The pattern of extrahepatic metastasis after hepatic resection was divided into pattern I (first recurrence in the liver and then spread outside the liver after repetitive intrahepatic recurrences and repetitive locoregional treatments), pattern II (simultaneous recognition of intrahepatic and extrahepatic recurrences), and pattern III (extrahepatic, but no intrahepatic, lesions at first recurrence). RESULTS: There were significant differences in proportions of patients with invasion of the portal vein, hepatic vein, or inferior vena cava, intrahepatic metastases, and tumor stage between patients with intra- and extrahepatic metastases. The disease-free survival and extrahepatic metastasis-free survival in pattern I were better than pattern II. Survival after extrahepatic metastasis did not correlate with the 3 patterns. CONCLUSION: Although long-term overall survival was better in patients with pattern I of extrahepatic recurrences, prognosis was poor in all patterns once extrahepatic metastasis developed.     

Type AB thymoma with brain metastasis: Report of a case

Type AB thymomas are considered to be nonaggressive tumors, and the great majority are classified as Masaoka stage I or II. This report presents a case with Masaoka stage I and type AB thymoma, which metastasized to the brain 2 years 5 months after removal of the primary tumor. The original mediastinal lesion was adhesive but not invasive to the lung. The patient is now alive with multiple tiny pulmonary metastases 3 years after complete resection of the brain metastasis. Some reports of recurrent thymomas have suggested that the presence of peritumoral adherence to the adjacent structures might be a risk factor for recurrence in patients with such noninvasive thymomas. During the development of fibrosis which thus causes adhesion, the tumor may have an increased chance to metastasize because of the increased vessels and lymphatics.     

Significance of extramucosal residual tumor at the bronchial resection margin

Extramucosal microscopic residual disease (MRD) at the bronchial resection margin was identified in 45 (1.6%) of 2,890 patients who underwent resection of primary non-small cell lung cancer between 1975 and 1985. In 9 of these patients, residual tumor was confined to submucosal lymphatics, whereas in the other 36, MRD was found in peribronchial soft tissue. All patients underwent complete mediastinal lymphadenectomy. Three patients had stage I disease, 3 had stage II, 33 had stage IIIa, 4 had stage IIIb, and 2 had stage IV. Recurrent disease developed in 34 (81%) of the evaluable patients; the recurrence was local in 11 (32%). Median time from operation to diagnosis of local recurrence was 8 months. Sixty percent of the recurrences in the N0 group were local, and only 23% of those in the N2 group were local. Extramucosal MRD is most frequently associated with advanced-stage disease. Postoperative therapy had no effect on the development of recurrent disease. We found no difference in survival between patients whose initial site of recurrence was local as opposed to distant. Median survival after the identification of either local or distant recurrence was 5 months. The finding of extramucosal MRD identifies a subset of patients with a poorer prognosis compared with those with clear resection margins.     

Localized carcinoma of the external ear is an unrecognized aggressive disease with a high propensity for local regional recurrence.

Management problems in patients with recurrent squamous cell carcinoma (SCC) of the external ear (pinna) have prompted a review of the management and treatment outcomes of patients who present with localized disease. Forty patients were seen over a 15-year period (1972 to 1991). Thirty-six were men, and 4 were women, with an age range from 43 to 93 years (average age: 71 years). Presenting TNM status was stage 0 in 2 patients, stage I in 15 patients, stage II in 13 patients, stage III in 2 patients, stage IV in 4 patients, and unknown stage in 4 patients. Thirty-six patients had clinically negative nodes at presentation (N0), and 4 had palpable nodes (N+). The primary treatment was local excision in 13 patients, Mohs' micrographic surgery in 16 patients, local excision plus external beam radiotherapy in 4 patients, and radical resection (parotidectomy/neck dissection/mastoidectomy) with or without radiotherapy in 5 patients. Two patients with stage IV disease died after diagnosis and prior to treatment, and two other patients with stage IV disease received palliative chemotherapy. Twenty patients developed recurrence from 2 months to 8 years. It included nine local recurrences, eight regional recurrences (parotid/neck/mastoid), and three distant metastases (lung or brain). After treatment of the recurrences in 20 patients, 8 are alive 15 months to 16 years later, 2 patients died of other diseases, and 10 patients died of SCC. The recurrences were managed by reoperation, radiotherapy, or chemotherapy. From the results of this study, we conclude that localized carcinoma of the external ear has a high propensity for local and regional failure and merits more aggressive treatment of the primary lesion and elective treatment of the regional lymph nodes and parotid gland in high-risk patients.     

The management of locally recurrent soft-tissue sarcoma.

Thirty-eight patients with locally recurrent soft-tissue sarcomas of various histologic types and grades but with no evidence of distant metastases were studied. Twenty-five patients had more than one local recurrence. Most primary lesions had been initially treated by simple or "wide local" excision with removal of little or no surrounding normal tissue. The most common site for recurrence was the extremity. Sixteen patients received preoperative intra-arterial Adriamycin (30 mg/day X three days) and radiation therapy (3500 R over ten days) followed by wide resection of the recurrence and the previous operative field. Tumor-free margins were confirmed microscopically. There were no subsequent local recurrences in this group. In five patients, no preoperative therapy was used, and the resection was incomplete because of proximity to vital structures. In these patients, postoperative radiation therapy and chemotherapy could not prevent continued local tumor progression. Amputation for control of local recurrence was necessary in only three patients. the remaining patients underwent either resection alone or resection in combination with postoperative radiation and/or chemotherapy. Life-table analysis of these 38 patients shows an unexpectedly high predicted five-year survival of 76% (87% for patients whose local recurrence could be completely resected). This high salvage rate clearly justifies aggressive treatment of patients with local recurrences alone and warrants attempts to salvage functional extremities.     

Management of stage I and II thymoma

With a knowledgeable assessment of the clinical presentation and demographic and radiologic characteristics, most thymomas can be reliably identified preoperatively without the need for a biopsy. Surgery is the mainstay of treatment for stage I and II thymoma. The rate of complete resection is essentially 100% by open techniques, and recurrences are rare. A complete thymectomy via a sternotomy is the standard approach. Adjuvant radiotherapy after a complete resection does not appear to be of benefit. In the rare event of a recurrence, an aggressive approach should be taken with re-resection whenever possible.     

Treatment of recurrent thymic tumors

Surgery is the cornerstone of therapy for recurrent thymic tumors. The pattern of recurrence is, however, less defined. Between 1966 and 1988, we operated on 83 patients with thymoma, 11 of whom underwent surgery for recurrence (group I). In 1989, we initiated a prospective multimodality protocol and have enrolled 128 patients with 9 (7%) recurrences since (group II). In group I, 1 patient was originally at stage I, 2 were at stage II, 5 at stage III, and 3 at stage IV. The patients underwent 1 (#10) or 2 (#1) reoperations and 5 showed histological progression of malignancy. One patient died postoperatively, 6 died of disease, and 3 are alive and disease free 18 to 22 years after the first operation. In group 2, no patient was originally at stage I, 1 was at stage II, 4 were at stage III, and 4 at stage IV. Reoperation (5 patients) was followed by chemotherapy and 2 showed histological progression of disease. One patient died after 2 years, and 4 patients are alive after 6 to 11 years. All recurrent tumors were thymomas with cortical differentiation. Early onset of recurrence was a negative prognostic factor. Thymomas can recur also at early stages. A multimodality approach is indicated also for early stage lesions based on histology.     

Parosteal osteosarcoma

Forty-one cases of parosteal osteosarcoma were reviewed clinically, radiologically and pathologically. The fibrous and cartilaginous elements of each tumour were graded from I to IV for malignancy. Primary intramedullary involvement was found in one third of Grade I lesions, two-thirds of Grade II and nearly 90% of Grade III lesions. Thirty-five patients with adequate follow-up were also studied and evaluated as to the adequacy of surgical management in relation to the later development of local recurrence or metastasis or both. No metastases were seen from Grade I tumours despite a number of local recurrences. One third of patients with Grade II and half of those with Grade III tumours developed pulmonary metastases and died, all with involvement of the medullary cavity before distant spread. No patients with adequate surgical management developed local recurrence; in those with inadequate treatment there was an 88% local recurrence rate.