Prognostic Relevance of WHO Classification and Masaoka Stage in Thymoma

Although thymomas are relatively common mediastinal tumors, to date not only has a universal system of pathologic classification not been established but neither has a clearly defined predictable relationship between treatment and prognosis been made. Recently, a new guideline for classification was reported by WHO, and efforts, based on this work, have been made to better define the relationship between treatment and pro­gnostic outcome. In the present study a comparative analysis between the WHO classification and Masaoka stage system with the clinical disease pattern was conducted. Material and Method: A total of 98 patients undergoing complete resection for mediastinal thymoma between Juanuary 1993 and June 2003 were included in the present study. The male female ratio was 48 : 50 and the mean age at operation was $49.6{\pm}13.9\;years.$ A retrospective analytic comparison studying the relationship between the WHO classification and the Masaoka stage system with the clinical disease pattern of thymoma was conducted. Pathologic slide specimens were carefully examined, details of postoperative treatment were documented, and a relationship with the prognostic outcome and recurrence was studied. Result: There were 7 patients in type A according to the WHO system of classification, 14 in AB, 28 in B 1, 23 in B2, 18 in B3, and 9 in type C. The study of the relationship between the Masaoka stage and WHO classification system showed 4 patients to be in WHO system type A, 7 in type AB, 22 in B 1, 17 in B2, and 3 in type B3 among 53 $(54{\%})$ patients shown to be in Masaoka stage I. Among 28 $(28.5{\%})$ patients in Masaoka stage II system, there were 2 patients in type A, 7 in AB, 4 in B 1, 2 in B2, 8 in B3, and 5 in type C. Among 15 $(15.3{\%})$ in Masaoka stage III, there were 1 patient in type B1, 3 in B2, 7 in B3, and 4 in type C. Finally, among 2 $(2{\%})$ patients found to be in Masaoka stage IV there was 1 patient in type B1, and 1 in type B2. The mean follow up duration was $28{\pm}6.8$ months. There were 3 deaths in the entire series of which 2 were in type B2 (Masaoka stages III and IV), and 1 was in type C (Masaoka stage II). Of the patients that experienced relapse, 6 patients remain alive of which 2 were in type B2 (Masaoka III), 2 in type B3 (Masaoka I and III) and 2 in type C (Masaoka stage II). The 5 year survival rate by the Kaplan-Meier method was $90{\%}$ for those in type B2 WHO classification system, $87.5{\%}$ for type C. The 5 year freedom from recurrence rate was $80.7{\%}$ for those in WHO type B2, $81.6{\%}$ for those in type B3, and $50{\%}$ for those in type C. By the Log-Rank method, a statistically significant correlation between survival and recurrence was found with the WHO system of classification (p<0.05). An analysis of the relationship between the WHO classification and Masaoka stage system using the Spearman correction method, showed a slope=0.401 (p=0.023), showing a close correlation. Conclusion: As type C of the WHO classification system is associated with a high postoperative mortality and recurrence rate, aggressive treatment postoperatively and meticulous follow up are warranted. The WHO classification and Masaoka stage system were found to have a close relationship with each other and either the WHO classification method or the Masaoka stage system may be used as a predict prognostic outcome of Thymoma.

흉선종양에서의 WHO 분류와 Masaoka 병기, 임상양상간의 상관관계연구

흥선종양은 비교적 흔한 종격종 종양이나 이제까지 병리학적 분류가 통일된 것이 없었으며 또한 치료 및 예후와의 연관성이 잘 확립되어 있지 않았다. 최근에서야 WHO 분류가 발표되었고 이에 따른 치료 계획과 치료에 따른 예후와의 상관관계가 보고되기 시작했다. 본 연구는 WHO 분류와 Masaoka병기 그리고 임상양상 간의 상관관계를 조사하였다. 대상 및 방법: 대상환자는 서울아산병원 흉부외과에서 1993년 1월부터 2003년 6월까지 완전절제술을 시행 받았던 흥선종양 환자 98명으로 하였다. WHO 분류의 조사를 위하여 병리조직 slide를 다시 검토하였으며 수술 후 Masaoka병기와의 관련성, 술 후 추가적인 치료와 예후에 대한 관계 및 재발여부에 관하여 의무기록 조사를 통하여 후향적으로 조사하였다. 결과: 98예의 대상 환자 중 남녀 비는 48 : 50이었으며 수술 연령은 평균 $49.6{\pm}13.9$세였다. WHO 분류에 따르면 type A 6명, AB 14명, B1 18명, B2 23명, B3 18명, C 9명이었다. Masaoka 병기와 WHO 분류와의 관계를 보면 Masaoka 병기 I 53명 $(54{\%})$ 중에서 WHO type A 4명, AB 7명, B1 22명, B2 17명, B3 3명이었으며 Masaoka 병기 II 28명$(28.5{\%})$ 중에서는 WHO type A 2명, AB 7명, B1 4명, B2 2명, B3 8명, C 5명이었고 Masaoka병기 III 15명$(15.3{\%})$ 중에서는 WHO type B1 L명, B2 3명, B3 7명, C 4명이었으며 Masaoka병기 IV 2명$(2{\%})$ 중에서는 WHO type B1 1명, B2 1명이었다. 평균 추적 기간은 $28{\pm}6.8$개월이었다. 사망 환자는 3명으로 type B2에서 2명(Masaoka 병기 III, IV), 그리고 type C에서 1명(Masaoka병기 II)이었다 재발 후 생존해 있는 환자는 총 6명이었으며 이 중 type B2에서 2명(Masaoka 병기 III), type B3에서 2명(Masaoka 병기 I, III) type C에서 2명(Masaoka 병기 II)이었다. Kaplan-Meier방법으로 통계 처리한 결과 WHO분류상 type B2에서 5년 생존율은 $90{\%}$ 였으며 type C에서 5년 생존율은 $87.5{\%}$였다. 재발률을 보면 class B2에서 5년 무병 생존율 $80.7{\%}$, B3에서 $81.6{\%}$, C에서 $50{\%}$였다. Log-Rank 방법에서 보면 WHO분류와 생존율, 재발률 사이에 통계학적으로 상관관계가 있는 것으로 나타났다(p<0.05). WHO 분류와 Masaoka분류의 상관 관계를 보면 Spearman correction method출 이용한 통계에서 상관관계 곡선이 slope=0.401 (p=0.023)으로 밀접한 관계가 있다고 하겠다. 결론: WHO분류의 type C의 경우 수술 후 재발률과 사망률이 높으므로 수술 후보다 적극적인 치료와 추적관찰이 필요할 것으로 생각된다. WHO분류와 Masaoka 병기간에는 상호 밀접한 관계가 있는 것으로 생각되며 WHO분류 및 Masaoka병기 모두 흥선종의 예후의 예측 인자가 될 수 있을 것으로 생각된다.