The Current Staging

Systems of Thymoma

성균관대학교 흉부외과

최용수

2010 대한흉부외과학회 춘계학회

Thymoma

• the most common neoplasm of the anterior medi-

astinum

• “rather enigmatic tumor”

• controversy on histologic classification & staging

- low incidence

- wide range of histological appearance

- unique biologic behavior

Case : M/40, symptoms of myasthenia gravis

Bx. (mediastinotomy); Thymoma, WHO type A

Mass excision: Thymoma, WHO type B3

Definition & terms : confusion

• Thymoma

• Thymic epithelial tumor

• Thymic carcinoma

• Malignant thymoma

• Invasive thymoma

• Atypical thymoma

Thymoma : benign or malignant ?

• Thymic carcinoma : 흉선암 , malignant

• Thymoma : 흉선종 , benign?

– invasiveness of thymoma

– no clear histologic distinction

• Lymphoma, melanoma : malignant tumor

Histologic classification of thymic epithelial neoplasm (1)

Bernatz (1961)

Kirchner &Muller-Hermelink

(1989)WHO (1999)

Lymphocyte-predom-

inant

Mixed lymphoepithe-

lial

Epithelial- predomi-

nant

Medullary

Mixed

Predominantly cortical

Cortical

A (medullary)

AB (mixed)

B1 (organoid, predominantly cor-

tical)

B2 (cortical)

Epithelial-predomi-nant with cytologic atypia

Well-differentiated thymic carcinoma

B3 (epithelial)

High-grade carcinoma C*(thymic carcinoma)

•Now excluded in the new WHO classification

(2004) and

placed in a separate group of malignant epithelial

tumors.

Histologic classification of thymic epithelial neoplasm (2)

WHO (1999)

Suster &Mora

n(1999)

Suster & Moran(2006)

A (medullary)

AB (mixed)

B1 (organoid, predominantly

cortical)

B2 (cortical)

Thy-moma

Well-differentiated thymic ca.(thymoma, low-grade or grade I)

B3 (epithelial)Atypical thy-moma

Moderately differentiated thymic ca.(thymoma, intermediate grade or grade II)

C* (thymic carcinoma)Thymic carci-noma

Poorly differentiated thymic ca.(thymoma, high grade or grade III)

•Now excluded in the new WHO classification

(2004) and

placed in a separate group of malignant epithelial

tumors.

WHO classification & clinical stag-ing

TypeNum-ber of cases

Stage I II III IVa IVb

Invasive tumors

(%)

A 8 7 0 1 0 0 12.5

AB 44 27 15 1 0 1 38.6

B1 25 15 5 4 1 0 40.0

B2 36 11 10 12 2 1 69.4

B3 10 2 2 6 0 0 80.0

C 14 0 1 8 0 5 100.0

Unclassified 3 3 0 0 0 0 0.0

Totals 140 65 33 32 3 7 53.6

Okumura (2001)

Staging of thymoma

• Staging of thymoma continues to be a

controversial issue.

Thymoma has no official staging system!

Staging schemes of thymoma

Stage

Bergh(1978)Wilkins(197

9) Masaoka(1981) Stage

I Intact capsule or growth within the capsule

“Macroscopically completely encapsulated and

microscopically no capsular invasion

I

II Pericapsular growth into the mediasti-nal fat tissue

+ or adja-cent pleura or peri-cardium

Macroscopic invasion into surrounding fatty tis-

sue or mediastinal pleura

II-1 (IIa)

Microscopic invasion into capsule II-2 (IIb)

III Invasive growth into thesurrounding organs and/orintrathoracicmetastases

“

Macroscopic invasion into a neighboring organ (e.g., pericardium, great vessels, or lung)

III

Pleural or pericardial dissemination IVa

Hematogenous or lymphogenous metastases IVb

Overall survival rates of thymoma

Authors

Pa-

tients

num-

ber

Complete

resec-

tion rate

(%)

5-year, 10-year survival

Stage I Stage II Stage III Stage IVa

Kondo (2003) 924 92100%, 100%

98%, 98% 89%, 78% 71%, 47%

Nakahara(1988)

141 80100%, 100%

92%, 84% 88%, 77% 47%, 47%

Pan(1994) 112 80 94%, 87% 85%, 69% 63%, 58% 41%, 22%

Survival curve of thymoma : Korea

연세대 . Chest (2005) 성균관대 . Br J Ca (2007)

n=195n=108

Criticisms on Masaoka staging

1. not well suited for the staging of thymic carcinomas

2. not provide an appreciable prognostic separation

between stages I and II

3. Definition of stage II is unclear. Tumors invading the medi-

astinal pleura are at higher risk of recurrence than the other

stage II tumors.

4. no description of residual tumor

5. Stage III thymoma is highly heterogenous in terms of in-

volved organs.

6. The TNM system classification of thymic epithelial tumors

has not been established.

Bedini (2005), Kondo(2005)

Modification of Masaoka staging

• Koga et al. (1994)

– simplified into two groups

– non-invasive for stages I and II

– invasive for stages III and IV

Modification of Masaoka staging

Stage Trastek(1989) Kornstein(1995)

I Completely encapsulatedNo capsular invasion

Intact capsule

IIGrowth into capsule

Invasion into surrounding fat; adja-

cent mediastinal pleura

Growth within capsule

(a) Microscopic invasion through capsule into

adjacent mediastinal tissue

(b) Gross and microscopic invasion through

capsule

into surrounding fat or adjacent pleura or

pericardium

IIIInvasion into neighboring structures

(pericardium, lung, great

vessels)

Invasion into surrounding structures (great vessels, lung)

IV(a) Pleural or pericardial metastasis(b) Lymphatic or hematogenous metastasis

(a) Pleural or pericardial dissemination(b) Lymphogenous or hematogenous metas-tasis

Staging (French Classification)- Groupe d'Etudes des Tumeurs Thymique, GETT 1982

Stage Ia. Encapsulated, noninvasive. Total excision.

b. Localized invasion to mediastinal structures. Total excision.

Stage

II

a. Invasive growth into the surrounding organs. Total

excision.

Stage

III

a. Invasive growth into the surrounding organs. Incomplete

excision.

b. Invasive growth into the surrounding organs. Biopsy of

tumor.

Stage

IV

a. Largely invading tumor cells with (supra)clavicular nodes

or pleural or pulmonary grafts (metastases) .

b. Hematogenous metastasis (1 or more).

Verley and Hollmann classification (1985)

Stage Characteristics

I Encapsulated, noninvasive tumor; total excision

Ia without adhesion to the environment

Ib with fibrous adhesion to mediastinal structures

II Localized invasiveness, e.g., pericapsular growth into the mediastinal

fat tissue or adjacent pleura or pericardium

IIa complete excision

IIb incomplete excision, with local remnants of tumor

III Largely invading tumor

IIIa invasive growth into the surrounding organs and/or intrathoracic tu-

morous grafts (pleura, pericardium)

IIIb lymphogenous or hematogenous metastasis

Prognostic categories for thymoma

proposed by Suster and Moran (2003)

Favorable

Group IEncapsulated or minimally invasive thymoma

Completely excised

Equivalent to WHO histologic types A, AB, B1, B2

Group IIEncapsulated or minimally invasive thymoma

Completely excised

Equivalent to WHO histologic type B3

Group IIIWidely invasive thymoma or thymoma with implants

Completely excised

All histologic types

Unfavor-able

Group IVWidely invasive thymoma or thymoma with implants

Incompletely excised

All histologic types

Group V

Widely invasive thymoma with or without intrathoracic

metastases

Unresectable/biopsy only

All histologic types

Group VIWidely invasive thymoma with distant metastases

Unresectable/biopsy only

All histologic types

New staging systems for testing

Stage

Description

I Tumors without any invasion into other structures/structures/structures/organs regardless of capsular involvement

II Scheme 1: tumors smaller than 10 cm in diameter and involving only one neighboring structure/organ

Scheme 2: tumors of all combinations of diameter and number of involved strctures/organs other than those in stage III

III Scheme 1: tumors of all combinations of diameter and number of involved structures/or-gans other than those in stage II

Scheme 2: tumors 10 cm or more in diameter and involving two or more neighboring struc-tures/organs

IV Tumors with pleural or pericardial dissemination (IVa) or lymphatic/vascular metastasis (IVb)

Asamura (2004)

Masaoka stag-ing

Scheme 1 Scheme 2

Tumor size : thymoma prognosis

• Bloomberg(1995) : 11cm

• Wright(2005) : 8cm

• Nakagawa(2003) : 10cm

Survival of patients with stage III disease

Results Of Surgical Treatment Of Thymomas With Special

Reference To The Involved Organs

Okumura (1999)

Stage III Thymic Epithelial Neoplasms are Not Homogeneous

with Regard to Clinical, Pathological, and Prognostic Fea-

tures 성균관대 . J Thorac Oncol (2009)

LN metatasis : 2.4%hematogenous metastasis : 5.3%

Proposed TNM schemes for thymoma and thymic carcinoma

Yamakawa, Masaoka (1991)

T

T1Macroscopically completely encapsulated and without microscopic capsular invasion

T2Macroscopic adhesion or invasion into surround-ing fatty tissue or pleura or microscopic in-vasion of the capsule

T3Invasion into neighboring organs such as great vessels, pericardium, lung

T4 Pleural or pericardial dissemination

N

N0 No lymph node metastasis

N1 Metastasis to anterior mediastinal lymph nodes

N2Metastasis to intrathoracic lymph nodes (other than anterior mediastinal nodes)

N3 Metastasis to extrathoracic lymph nodes

MM0 No distant metastases

M1 Hematogenous metastases

Stage T N M

I T1 N0 M0

II T2 N0 M0

III T3 N0 M0

IVA T4 N0 M0

IVBAny N1-

3 M0

Any Any M1

Pattern of LN metastasisKondo (2003)

Thymoma Thymic carci-noma

The INT (Istituto Nazionale Tumori) TNM-Based Staging System

T1 No capsular invasion

T2 Microscopic invasion into the capsule, or extracapsular involvement limited to the surrounding fatty tissue or normal thymus

T3 Direct invasion into the mediastinal pleura and/or anterior pericardium

T4Direct invasion into neighboring organs, such as sternum, great vessels, and lungs; implants to the me-diastinal pleura or pericardium, only if anterior to phrenic nerve

N0 No lymph node metastasis

N1 Metastasis to anterior mediastinal lymph nodes

N2 Metastasis to intrathoracic lymph nodes other than anterior mediastinal nodes

N3 Metastasis to prescalene or supraclavicular nodes

M0 No hematogenous metastasis

M1a Implants to the pericardium or mediastinal pleura beyond the sites defined in the T4 category

M1b Hematogenous metastasis to other sites, or involvement of lymph nodal stations other than those de-scribed in the N categories

i Locally restricted dis-ease

T1-2 N0 M0

ii Locally advanced dis-ease

T3-4 N0 M0

anyT N1-2 M0

iii Systemic disease anyT N3 M0

anyT anyN M1

Stage grouping Classification of residual dis-easeR0 No residual tumor

R1 Microscopic residual tumor

R2a

Local macroscopic residual tumor after reductive resection (> 80% of the tumor)

R2b

Other features of residual tumor

Progression-free survival

Masaoka staging INT(Istituto Nazionale Tumori) staging

Thymoma vs. Thymic ca.

normal thymus

thy-moma

thymic carcinoma

Thymic carcinomas

Low-grade

malig-

nancy

Well-differentiated squamous cell carcinoma

Basaloid carcinoma

Mucoepidermoid carcinoma

Large-cell carcinoma with Castleman's disease

High-grade

malig-

nancy

Lymphoepithelioma-like carcinoma

Poorly differentiated squamous cell

Adenosquamous carcinoma

Clear cell carcinoma

Papillary adenocarcinoma

Mucinous adenocarcinoma

Sarcomatoid carcinoma

Poorly differentiated carcinoma

Hepatoid thymic carcinoma

Anaplastic/undifferentiated carcinoma

1. stage III thy-

moma

2. thymic carci-

noma

Key points of thymic tumor stag-ing

• By multivariate analysis, the most important prognos-

tic factors in patients with thymomas are stage and

completeness of resection.

• All stages and all histologic subtypes of thymoma

have the potential to spread to distant sites.

Frank C. Detterbeck, Alden M. Parsons

Pearson’s thoracic and esophageal surgery, 3rd Edition. chapter 131. Thymic tumors: A review of current diagnosis, classification and treatment

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