WHO histologic classification is a prognostic indicator in thymoma

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.     

Clinical usefulness of the WHO histological classification of thymoma.

PURPOSE: Rosai et al. published the World Health Organization (WHO) classification of thymic epithelial tumors in 1999, and its clinical usefulness seems to be established. It is our purpose to find the clinically relevant diagnostic points in the WHO Histological Classification of Thymoma. METHODS: Thymomas surgically removed from 100 consecutive patients at Juntendo University Hospital between October 1983 and February 2002 were classified according to the WHO histological classification. We assessed overall survival and recurrence-free rate calculated for each tumor type in the WHO classification compared with those of tumors classified by the Masaoka system. RESULTS: The thymic epithelial tumors in this series comprised 10 type A, 15 type AB, 18 type B1, 21 type B2, 33 type B3, and 3 type C tumors according to the WHO classification. Based on the Masaoka system, the disease was stage I in 53 patients, stage II in 30, stage III in 15, and stage IV in 2. The 15-year recurrence-free rate was 100% for type A, AB and B1, while the rates for types B2 and B3 were 66.7% and 54.5%, respectively. The 10-year recurrence-free rate was 66.7% for type C. The 15-year recurrence-free rate of the 64 patients with type A, AB, B1, and B2 thymomas was significantly higher from that of the 33 patients with type B3 thymoma (p=0.0026). CONCLUSION: When using the WHO classification, it is critical to distinguish type B3 thymoma from other tumor types.     

Recurrent myasthenia gravis due to a pleural implant 3 years after radical thymectomy

Although recurrence of a thymoma is rare, pleural dissemination or local relapses have been described. We present a patient who underwent complete thymectomy for a thymoma, type AB according to the World Health Organization classification and stage II according to Masaoka, followed by adjuvant radiotherapy. Three years later, a relapse of the myasthenic symptoms occurred. An isolated pleural implant above the left diaphragm was removed by video-assisted thoracoscopy. Pathology confirmed the recurrence of the thymoma. As this is a rare occurrence, no precise therapeutic guidelines exist. In our case, surgical resection of the recurrence with adjuvant immunomodulating therapy for myasthenia provided good results.     

Complete resection of the invasive thymoma combined with replacement of aortic arch and pneumonectomy

A 68-year-old male was found an abnormal shadow on chest X-ray and was diagnosed as thymoma by computed tomography (CT)-guided needle biopsy. As the tumor invaded the aortic arch, left main pulmonary artery and the lung, thymectomy combined resection of the surrounding tissues was performed for the complete resection. The aortic arch was replaced with cardiovascular graft under cardiopulmonary bypass, with the aid of selective cerebral perfusion. The left pneumonectomy was performed because the tumor invaded to the left main pulmonary artery and to the lung parenchyma. Masaoka stage III and histologic type B2 were diagnosed according to the World Health Organization classification. The patient has been well without recurrence or metastasis after the surgery for 2 years. A complete resection of the thymoma invaded to great vessels should be performed to expect for the good curability and prognosis.     

Results of surgical treatment of thymomas with special reference to the involved organs

OBJECTIVE: The purpose of this study is to clarify the significance of the particular involved organ as a prognostic factor and its relation to other previously reported factors. METHODS: The prognoses of 194 consecutive patients with thymoma who had undergone complete or subtotal resection were reviewed retrospectively. Survival was evaluated as actuarial freedom from tumor death. Analysis of prognostic factors was performed by the Kaplan-Meier method with the log rank test and Cox's proportional hazards model. RESULTS: The Masaoka staging system and involvement of the great vessels were the independent prognostic factors in the entire study group; age, sex, histologic subtype, completeness of resection, association of myasthenia gravis, or involvement of other organs were not factors. The 10-year and 20-year survivals were 99% and 90% in stage I, 94% and 90% in stage II, 88% and 56% in stage III, 30% and 15% in stage IVa, 0% and 0% in stage IVb, 93% and 83% in the absence of involvement of the great vessels, and 54% and 20% in the presence of it. Involvement of the great vessels was also the single independent prognostic factor in the patients with stage III disease although completeness of resection or involvement of other organs were not. The 10-year and 20-year survivals in patients with stage III disease were 97% and 75% in the absence of involvement of the great vessels, and 70% and 29% in the presence of it. CONCLUSION: Although the Masaoka staging system is a valuable prognostic factor, the category of stage III is heterogeneous and consists of 2 groups with distinct prognoses depending on involvement of the great vessels.     

胸腺瘤的诊断、治疗和预后

目的：探讨影响胸腺瘤的诊断,治疗及预后的相关因素。方法：回顾性分析116例胸腺瘤的临床资料,运用寿命表法计算其生存率,以生存,复发或转移率为指标,进行研究。结果：胸部X线等影像学检查是本病诊断的主要手段,重症肌无力是最常见的伴随疾病,发生率为25．0％（29／116）。扩大胸腺及胸腺瘤切除可降低Ⅰ、Ⅱ期肿瘤的复发率（x^2=4.941,P=0.0219),放疗和化疗等综合治疗可以提高疗效。组织学分型（M－H）法与临床分期有明显的相关性,能更有效地反映胸腺瘤的侵袭性(=0.385,P=0.007),本组患者3,5,10年生存率分别为81．2％,67．9％和40．5％,肿瘤分期与生存率明显呈负相关（r=-0.897,P=0.000)。结论：肿瘤的组织类型,病理分期及综合治疗方法是影响患者预后的重要因素,伴随疾病对患者的预后无明显影响。     

Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification

Background

The aim of this study was to document the prognosis of thymic epithelial tumors (TETs) according to new the World Health Organization (WHO) classification.

Methods

We retrospectively reviewed 150 patients with TETs that were confirmed pathologically during 11 years (from 1992 to 2002) in Severance Hospital, Seoul, Korea.

Results

TETs were classified as type A, AB, B1, B2, B3, or C, tumors and these represented 7 (4.7%), 26 (17.3%), 13 (8.7%), 45 (30.0%), 26 (17.3%), and 33 (22.0%) cases, and the 5-year survival rates were 100%, 93%, 89%, 82%, 71%, and 23%, respectively. Their Masaoka stages were I, II, III, IVa, and IVb, with 53 (35.3%), 39 (26.0%), 20 (13.3%), 22 (14.7%), and 16 (10.7%) cases. Tumor invasiveness, recurrence, completeness of resection, and tumor-related death were more frequent in types AB, B2, B3, and C than in types A and B1. Multivariate analysis showed that Masaoka stage (p < 0.001) and the WHO classification (p = 0.019) were significant independent prognostic factors.

Conclusions

The WHO classification is associated with tumor invasiveness, recurrence, completeness of resection, and tumor-related death, and has good correlation with Masaoka stage. The WHO histologic subtypes are an independently significant prognostic factor with respect to survival in our multivariate analysis. Types AB, B2, B3, and C showed invasive behaviors and R1 or R2 resections were frequently performed. Postoperative adjuvant radiotherapy was effective, but long-term follow-up is recommended because of decreased survival after 5 years following operation. The WHO classification may be helpful in clinical practice for the assessment and treatment of TET patients.     

Thymomas: clinical-pathological correlations

AIM: Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical features of the patients. We present the results of a retrospective analysis on patients, operated on for a thymoma, whose specimens were available, to compare the WHO thymoma histologic classification to the clinical behavior of the tumors. METHODS: The specimens of 69 patients, who underwent surgical treatment between 1983 and 1998, were analyzed, comparing the clinical features of the patients and the hystological typing of the neoplasm, according to the WHO classification. A survival analysis of clinical and pathological prognostic factors was carried out. RESULTS: The incidence of thymus-related syndrome was related to the histological subtype and increases progressively from A to B3, while in C subtype the incidence was nihl. With a mean follow-up of 108 months (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3 intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and 88.9%. Because of the absence of deaths related to thymomas in most samples it was not possible to perform a comparison among different histological types and different clinical stages. CONCLUSIONS: The WHO histologic classification seems to correlate with the incidence of thymus related syndromes and the clinical stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C thymoma the WHO classification did not prove to be a prognostic factor.     

Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients

A series of 141 patients with thymoma was studied with regard to the way in which complete resection followed by postoperative radiation therapy influenced prognosis according to the stage and histologic type of thymoma. Postoperative radiation therapy (30 Gy in 3 weeks to 50 Gy in 6 weeks) was performed in 73.1% of the patients. Thirty-five of 48 patients with thymoma invading the surrounding tissues (stage III) underwent complete resection, with survival rates of 100% at 5 years and 94.7% at 10 and 15 years. The prognosis in these patients was comparable with those in 45 patients with no invasion (stage I) and in 33 patients with capsular invasion (stage III), all of whom underwent complete resection. Complete resection was done in 18 of 26 patients with epithelial cell thymoma, and there were no deaths by tumor until 15 years after the operation. There were no statistically significant differences in the survival rates of patients undergoing complete resection according to cell type (33 of 36 patients with lymphocyte predominant type and 61 of 77 patients with mixed cell type). The survival rate in six patients with epithelial cell type who underwent subtotal resection was not significantly different from that of 12 patients who underwent biopsy alone. Our findings indicate that complete resection of thymoma followed by postoperative radiation therapy results in a "benign" postoperative course, regardless of the stage and histologic type. Therefore, an aggressive surgical approach, such as resection of the superior vena caval system followed by reconstruction with a ringed polytetrafluoroethylene graft and/or complete pleuropneumonectomy, is justified for advanced thymoma, although the long-term results of such extended operations are still unclear.     

Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma?

OBJECTIVE: To determine whether or not patients with completely resected Masaoka stage II thymoma benefit from postoperative radiotherapy (RT). METHODS: We retrospectively review the case records and compared the long-term outcomes of patients affected by Masaoka stage II thymoma treated by resection alone with same stage thymoma patients submitted to resection and RT. Surgical specimens were reviewed to confirm pathological stage, negative resection margins and histological subtype. RESULTS: Between 1988 and 2000, we performed 197 resections for thymoma; 58 patients resulted to be affected by completely resected tumours with microscopic transcapsular invasion (stage IIA, n=25) or macroscopic invasion into the surrounding fatty tissue with or without adhesion to the mediastinal pleura (stage IIB, n=33). Thirty-two patients underwent only complete surgical resection (14 stage IIA and 18 stage IIB); 26 patients underwent complete resection and subsequent mediastinal RT (11 stage IIA and 15 stage IIB). RT dosages were 45-54grays (Gy), in 25-30 fractions. Histological subtypes were similarly represented in both groups. Median follow-up was 91 months (range 9-170). Five intrathoracic recurrences occurred: three radiated patients (2 stage IIB - 1 AB and 1 B2 thymoma; 1 stage IIA B1 thymoma) and two not-radiated patients (1 stage IIA AB thymoma and 1 stage IIB B1 thymoma). Disease-free survival rate at 5- and 10-year were 94% and 87%, respectively. Log-rank test showed no difference in Kaplan-Meier survival curves (p=0.432) between radiated and not-radiated patients. CONCLUSIONS: These data support the concept that radical surgical resection alone should be considered a sufficient treatment for stage II thymoma.     

胸腺瘤患者预后因素分析

目的 探讨影响胸腺瘤患者术后远期生存率的相关因素。方法 回顾性分析我科1973—2000年间手术治疗的69例胸腺瘤，应用Kaplan—Meier法和Cox比例风险模型对可能影响胸腺瘤术后远期生存率的因素进行单因素和多因素分析。结果 全组患者5年、10年、15年生存率分别为83．3％、67．4％、41．9％。单因素分析显示年龄、Masaoka分期、WHO组织学分类、肿瘤切除范围、Rosai／Levine分类对胸腺瘤患者术后长期生存率有显著影响(P＜0．01)，但经多因素分析表明仅Masaoka分期(P＜0．01)、肿瘤切除范围(P＜0．05)、年龄(P＜0．05)是独立的预后因素。结论 对胸腺瘤应积极进行手术治疗，即使姑息性切除亦有助于提高远期生存。     

Oncological significance of WHO histological thymoma classification

OBJECTIVES: The clinical significance of thymoma histology remains controversial because of the numerous histological classifications of thymic epithelial tumors. Universal classification of such tumors was achieved by the World Health Organization (WHO) in 1999. We studied the prognostic significance of this classification. METHODS: We studied clinical features and postoperative survival in cases of thymoma, but not thymic carcinoma, based on WHO histological classification in 286 patients undergoing surgery between 1958 and 2001. RESULTS: Tumors were 19 type A, 79 type AB, 59 type B1, 102 type B2, and 27 type B3. The proportion of invasive tumors increased by type--from A to AB, B1, B2, and B3. The great vessels were involved more frequently in type B2 and B3 tumors than in type A, AB, and B1 tumors. The 20-year survival was 100% in type A, 87% in type AB, 91% in type B1, 65% in type B2, and 38% in type B3 tumors. Multivariate analysis showed Masaoka staging and WHO histological classification to be significant independent prognostic factors, while age, gender, myasthenia gravis association, resection completeness and great vessel involvement were not. In stage III patients, 13 of 45 patients with type B2 and B3 tumor died of their tumors, while no tumor deaths occurred in 11 patients with type A, AB, and B1 tumors. CONCLUSION: WHO histological classification realistically reflects the oncological behavior of thymoma.     

Thoracoscopic Resection of Middle Mediastinal Noninvasive Thymoma: Report of a Case

We performed thoracoscopic resection of a middle mediastinal noninvasive thymoma in a 69-year-old woman. Chest computed tomography on admission showed a tumor, 75 x 48 x 32 mm in size, and pathological examination revealed a spindle-cell, noninvasive thymoma, of type A according to the World Health Organization classification, and stage I according to the Masaoka staging system. Thymomas are prone to ectopic occurrence, and should be considered in the differential diagnosis of middle mediastinum tumors.     

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.     

Therapy for thymic epithelial tumors

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes. The rarity of this tumor has somewhat obscured the optimal treatment for this disease. The World Health Organization classification system, which published in 1999, appears to be an advance in our understanding of thymoma. The Masaoka classification is now the most widely accepted and is an excellent predictor of the prognosis of thymoma. Now the International Thymic Malignancy Interest Group is currently engaged in the development of a validated formal TNM classification system for thymic malignancies. The optimal treatment of thymoma is performed according to its clinical stage. Surgery remains the mainstay of treatment for thymic epithelial tumors. Minimally invasive surgery including thoracoscopic surgery and robotic surgery for stage I and II thymomas is increasing now. The value of postoperative radiotherapy in completely resected stage II or III tumors is questionable. As thymomas have a moderate response rate to chemotherapy or radiotherapy, multimodality therapy involving surgery, chemotherapy and radiotherapy appears to increase the rate of complete resection and survival in the advanced (stage III and IV) thymomas.     

Recurrent thymoma in patients with myasthenia gravis

One hundred sixty-six patients underwent operation for myasthenia gravis between 1977 and 1989. Thirty-eight patients had associated thymoma, registering stages I (n = 17), II (n = 9), III (n = 11), and IVa (n = 1) according to the classification of Masaoka and colleagues. Extended thymectomy was performed on 128 patients without thymoma; thymothymectomy, with resection of the anterior mediastinal fat and tissues adherent to the tumor, was performed in all patients with thymoma. There were no instances of early or late death. Neuromuscular function improved, and clinical myasthenic symptoms stabilized in almost all patients except 2 patients in stage III and 1 patient in stage IVa, who had an exacerbation of the myasthenic symptoms associated with recurrence of thymoma. All the recurrent tumors were on the pleura and could be resected. The suspected cause of recurrence is either dissemination of tumor cells as a result of operative manipulation or undetected disseminated foci that existed at the time of the first operation. The resections of the recurrent invasive thymomas localized on the pleura were easily performed and improved the myasthenic symptoms.     

Prognosis and therapeutic response according to the world health organization histological classification in advanced thymoma

Purpose

The clinical efficacy of the World Health Organization (WHO) classification of thymoma has been reported to be a prognostic factor for patients with thymomas. This study focuses on the relationship between the therapeutic response and the WHO histological classification in patients with advanced thymoma.

Methods

A retrospective review was performed on 22 patients with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1, 7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3, respectively.

Results

Surgery was performed on 10 patients. There were 2 complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of 18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy, chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The response rate in 9 patients with type A-B2 was significantly better than that in 9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P = 0.0001). Only the WHO classification was significantly associated with survival, with type B3 having a worse prognosis than A-B2 (P = 0.01).

Conclusions

Type B3 thymoma showed a lower response rate to treatments and thus shorter survival. The WHO classification is a good predictive factor for therapeutic response in advanced thymoma.     

31例胸腺瘤外科治疗分析

目的总结胸腺瘤外科治疗的临床特点。方法对2012-01—2014-06经31例行外科手术治疗的胸腺瘤患者的临床资料进行回顾性分析。结果胸腺瘤合并重症肌无力23例(74.2%)。全组完全切除率为87.1%。临床Ⅰ、Ⅱ期完全切除率100%,Ⅲ期完全切除率66.7%。全组无手术死亡。80.0%的A型和75.0%AB型分布在Ⅰ期,而100%的B3型分布在Ⅲ期。AB型胸腺瘤中合并重症肌无力占50%,其余各型中合并重症肌无力的比例均超过50%。结论胸腺瘤组织学分型与临床分期有密切关系,二者结合对判断预后更准确。AB型胸腺瘤患者中合并重症肌无力的比例最低,其余各型合并重症肌无力的比例则较大,诊治胸腺瘤患者时需警惕是否合并重症肌无力。     

Thymoma: a review of the clinical and pathological findings in 65 cases.

INTRODUCTION: Although rare, thymoma is the most common tumour of the anterior mediastinum. In an effort to assess the clinical and pathologic characteristics of this tumour and to determine whether clinicopathologic stage or histopathologic classification correlates with clinical outcome, in the Department of Pathology and the Department of Surgery at the University of Saskatchewan we reviewed all cases of thymoma registered in the province of Saskatchewan using the database of the Saskatchewan Cancer Centre. METHODS: In 65 patients with a diagnosis of thymoma or thymic carcinoma identified from the Saskatchewan Cancer Centre database between Jan. 1, 1960, and Dec. 31, 2000, we studied the presentation, diagnostic investigations, therapeutic interventions, tumour size, postoperative course, clinical stage, histopathologic classification, disease recurrence and mortality. RESULTS: Of the 65 patients, 17 (26%) were asymptomatic and 11 (17%) had symptoms consistent with myasthenia gravis. Surgical resection is most commonly performed through a median sternotomy and frequently requires en bloc resection of one or more adjacent structures. The overall survival of patients with thymomawas found to correlate with the clinical stage as described by Masaoka and colleagues and with complete tumour resection. A trend to clinicopathologic correlation was observed when applying the histologic classification systems of Suster and Moran and the World Health Organisation, but this trend was not statistically significant. CONCLUSIONS: Thymoma is a rare tumour with a variable clinical presentation. Clinical outcome correlates with clinical stage and the ability to achieve complete tumour resection.     

胸腺上皮肿瘤WHO分型与系统性免疫炎症指数的相关性

目的探讨胸腺上皮肿瘤的WHO组织学分型与系统性免疫炎症指数的相关性。 方法收集2017年1月至2019年12月经手术后病理学检查证实的胸腺上皮肿瘤患者的临床资料。根据WHO(2015版)胸腺上皮性肿瘤分型,将纳入研究的患者分为低危组、高危组和胸腺癌组;以同期接受手术治疗的胸腺良性肿物患者作为对照。所有患者于术前4 d内获取外周血内血小板、中性粒细胞、淋巴细胞计数,计算系统性免疫炎症指数。比较各组间系统性免疫炎症指数的差异,并分析其与肿瘤恶性程度的相关性。 结果共纳入胸腺上皮性肿瘤患者46例(低危组20例,高危组19例,胸腺癌组7例)和对照组患者34例。胸腺癌组系统性免疫炎症指数显著高于其余三组(P＝0.009)。系统性免疫炎症指数与胸腺上皮性肿瘤的恶性程度显著相关(r＝0.244,P＝0.032)。 结论系统性免疫炎症指数与基于WHO分型的胸腺上皮性肿瘤恶性程度具有显著相关性,可作为胸腺上皮肿瘤恶性程度的临床预测指标。