Biphasic SS

S2469 外陰部皮下腫瘤
1. 浜田医療センター 病理診断科 2.同皮膚科
3. 島根大学医学部器官病理学
長﨑真琴[1]、進藤真久[2]、石川典由[3]
2013.6.22
骨盤単純造影MRI
左外陰の外側の皮下脂肪織内に
境界明瞭な27.5mmの不整型腫瘤。
深部の筋肉など周辺の構造との境
界は明瞭に脂肪で境されている。
膀胱、膣、尿道には異常影認めず。
摘出検体
3.5×3.5×2cm
左会陰部（大陰唇部）皮下
の、周囲との境界明瞭な充
実性～嚢胞形成性腫瘍
C
B
A
Ki-67
C
B
A
A
Gitter
sharp abutment of gland with stroma
p53
A
B
Gitter
C
Gitter
C
p53
鑑別診断
Carcinoma with sarcomatoid elements
Carcinosarcoma
MPNST (glandular MPNST)
Synovial sarcoma
Sex cord tumor
Mesothelioma
Endometriosis
Monophasicな部分は、各種肉腫(fibrosarcoma, leiomyosarcoma,
MPNST, hemangiopericytoma)や癌（転移性癌、皮膚付属器の癌）、
低分化な部分はEwing’s sarcomaやPNETが鑑別にあがる。
CK7
CK7+
Vimentin +
CK7
vimentin
Bcl-2
Bcl-2+
CD99+
CD56+
CD56
CD99
免疫染色結果
２相型部分
充実部（small round
cell, epithelioid cell）
上皮成分（管状構造） 紡錘形細胞
CK (AE1/AE3, CAM5.2,
CK (AE1/AE3, CK7),
vimentin,
CD99,
CK7, CK19, 34βE12),
vimentin, Bcl-2, CD99,
陽性
EMA, vimentin,
CD56
NSE, CD56
Bcl-2 (focal), NSE
CK, Bcl-2, S100, CK (CAM5.2, CK20,
CK20, S100, αSMA,
αSMA, desmin, CK19, 34βE12, EMA,
desmin, CD10, CD34,
CD10, CD34, α- S100, αSMA, desmin,
α-inhibin, TTF-1,
inhibin, TTF-1,
CD10, CD34, α陰性
ER/PgR, CD56,
ER/PgR, NSE,
inhibin, TTF-1,
calretinin, WT-1,
calretinin, WT-1, ER/PgR, calretinin,
calponin
WT-1, calponin
calponin
免疫染色結果
２相型部分
充実部（small round
cell, epithelioid cell）
上皮成分（管状構造） 紡錘形細胞
CK (AE1/AE3, CAM5.2,
CK (AE1/AE3, CK7),
vimentin,
CD99,
CK7, CK19, 34βE12),
vimentin, Bcl-2, CD99,
陽性
EMA, vimentin,
CD56, TLE1
NSE, CD56, TLE1
Bcl-2(focal), NSE, TLE1
CK, Bcl-2, S100, CK (CAM5.2, CK20,
CK20, S100, αSMA,
αSMA, desmin, CK19, 34βE12, EMA,
desmin, CD10, CD34,
CD10, CD34, α- S100, αSMA, desmin,
α-inhibin, TTF-1,
inhibin, TTF-1,
CD10, CD34, α陰性
ER/PgR, CD56,
ER/PgR, NSE,
inhibin, TTF-1,
calretinin, WT-1,
calretinin, WT-1, ER/PgR, calretinin,
calponin
WT-1, calponin
calponin
TLE1: transducin-like enhancer of split 1
TLE1
Strong, diffuse nucleasr reactivity
TLE1
Carcinosarcoma, Carcinoma with sarcomatoid elements; 腺成分、紡
錘形細胞ともに核異型が強い。異所性成分。女性生殖器であ
れば、uterus由来のもの（malignant Mullerian tumor）が多い。
Glandular MPNST; NF1患者から発生。腺成分は時に杯細胞を伴う。
TLE1の染色性は弱い (Foo WC et.al. Am J Clin Pathol. 2011;
135: 839-844)。
Sex cord tumor; α-inhibinやcalretinin、PgRが陽性。
Maligant mesothelioma; 上皮成分と紡錘形細胞は移行像を示す。
Calretinin, WT-1陽性。
Endometriosis; 内膜腺。ER/PgR(+)。
Mixed tumor (spindle cell epithelioma); よく分化した上皮成分と紡
錘形細胞。異型性や核分裂活性はない。
→ Synovial sarcoma であれば、mast cellやcalcification、myxoid
changeがない点を除いて形態的、免疫形質的に矛盾しない。しか
し発生部位が希であり、年齢も高いことから断定には躊躇される。
Break-apart FISH: SS18 split-signal probe
50%以上の腫瘍細胞にsplit signalあり→ SS18/SSX遺伝子再構成あり
（札幌医大 長谷川匡教授）
診断
Synovial sarcoma, mixed type:
biphasic
epithelioid (monophasic)
poorly differentiated
(molecular: SS18/SSX (SS18 break-appart FISH))
Synovial sarcoma
Epidemiology
・58% of cases, between age 10 and 40years, and 77% occur before the age of
50years.
Sites of involvement
・deep soft tissue of the lower and upper extremities, often in a juxta-articular
location.
・15% arise in the trunk, 7% in the head and neck region.
・unusual sites of involvement; male and female external and internal sex organs,
kidney, adrenal gland, retroperitoneum, bone, CNS, peripheral nerve
(WHO classification of tumors of soft tissue and bone (2013))
Macroscopy
・3-10cm, usually circumscribed, colour and consistency variable, multinodular,
multicystic, calcification, metaplastic ossification, necrosis
Histopathology
・Biphasic (epithelial and spindle-cell) (30%)
・Ｍonophasic (fibrous, epithelial) (70%)
・Poorly differentiated (PD) (<5%)
Synovial sarcoma
Immunophenotype
・Biphasic: EMA, CK (7, 8, 14, 18, 19, 20)
・Monophasic: EMA , CK (7, 8, 18, 19)
・PD: EMA(nearly all), CK (50%)
・S100 (focal), CD34 (very rare), CD99
・TLE1: moderate to strong nuclear staining (80%)(not specific for SS)
Kosemehmetoglu K et al. TLE1 exoression is not specific for synovial sarcoma: a whole
section study of 163 soft tissue and bone neoplasms. Mod Pathol. 2009, 22: 872-878
Foo WC et al. Immunohistochemical staining for TLE1 distinguishes synovial sarcoma
from histologic mimics. Am J Clin Pathol, 2011, 135: 839-844
Genetics
・ t (X; 18)(p11; q11): SS18 gene (SYT or SSXT) on chromosome 18, SSX gene (SSX1,
SSX2 or SSX4) on the X chromosome are fused.
・2/3, SS18-SSX1; 1/3, SS18-SSX2; only a few, SS18-SSX4
・most biphasic SS, SS18-SSX1
・SS18-SSX fusion type, single most significant prognostic factor; survival, SS18SSX2 type > SS18-SSX1 type
Prognostic factors
・tumors with >20% PD histology , more aggressive behaviour
Female genital tractに発生したsynovial sarcomaの最近の論文
Kawauchi S et al. Synovial sarcoma arising in the vulva cytogenetically confirmed by SYT
break-apart reatrrangement fluorscence in situ hybridization: A case report and discussion
of diagnsitic methods. Oncol Lett. 2012, 4:955-959:
21-year-old Japanese female, Monophasic fibrous, poorly differentiated (PD), SS18/SSX (FISH)
Sumathi VP et al. Synovial sarcoma of the vulva and vagina: A clinicopathologic and
molecular genetic study of 4 cases. Int J Gynecol Pathol. 2011, 30: 84-91:
Okazaki et al (1976)
Nielsen et al (1996)
Nielsen et al (1996)
Smith et al (2005)
Ambani et al (2006)
Mitsuhashi et al (2006)
Pelosi et al (2007)
Holloway et al (2007)
White et al (2008)
Case 1 (2011)
Case 2 (2011)
Case 3 (2011)
Case 4 (2011)
age
24
30
37
90
33
23
40
50
33
24
43
29
27
site
diagnosis
vagina
Biphasic SS
vulva
Biphasic SS
vulva
Biphasic SS
ovary
Biphasic SS
vulva
Monophasic SS
fallopian tube Biphasic SS
vagina
PD SS
vulva
Monophasic SS
vulva
Monophasic SS
vulva
PD, Biphasic SS
vagina
PD, monophasic SS
vulva
PD, Biphasic SS
vulva
Monophasic SS
molecular
NA
NA
NA
NA
SS18/SSX (RT-PCR)
SS18/SSX1 (RT-PCR, SEQ)
SS18/SSX1 (FISH, RT-PCR)
NA
SS18-SSX2
SS18/SSX1 (RT-PCR, SEQ)
SS18/SSX1 (RT-PCR, SEQ)
SS18/SSX1 (RT-PCR, SEQ)
SS18/SSX2 (RT-PCR, SEQ)
Asher V et al. Synovial sarcoma of the vulva: a case report. J Medica Case Report. 2011,
5:95: 28-year-old Caucasian woman, Biphasic, SS18-SSX (RT-PCR)