chromatin remodeling factor ¥¯¥í¥Þ¥Á¥ó¥ê¥â¥Ç¥ê¥ó¥°°ø»Ò
SMARCB1(INI1)-deficient pleural sarcoma
ºîÀ®Ãæ
Case presentation µ¤¶»¤Çȯ¾É¤·¤¿SMARCA4-deficient thoracic sarcoma¤Î1Îã †
IWT case 49 year-old male
Xǯ9·î±¦¼«Á³µ¤¶»¤Ç¶»¹Ð¶À²¼¥Ö¥éÀÚ½ü½Ñ»þ, ¶»Ëì¤Î¼ðáî¤òƱ»þ¤ËÀÚ½ü¤¹¤ë. plasmacytoid ¤Þ¤¿¤Ï rabdoid cell¤Î¤Ó¤Þ¤óÀÁý¿£¤ò¼¨¤¹¼ðáç.
·Úº¿¤¬¤ï¤º¤«¤ËÍÛÀ¤È¤Ê¤ê, ºÇ½é plasmacytoma¤ÈDx¤µ¤ì¤¿¤¬Â¾¤Îmyeloma marker±¢À, light chain PCR¤Ïnon-clonal¥Ñ¥¿¡¼¥ó¤Ç¤¢¤Ã¤¿.ÄɲäÎÌÈÀ÷¤Ç, vimentin, CD99(MIC2)ÍÛÀ¡¢CD34, BCL2¤¬¤´¤¯°ìÉô¤ËÍÛÀ¤Ê¤Éʬ²½ÉÔÌÀ¤ÎÆù¼ð.
5¥õ·î¸å±¦¼çµ¤´É»Ù¤ò°µÇ÷¤·¤Û¤È¤ó¤ÉÊĺɤ¹¤ëµðÂç¤Ê¼ðáç¤òǧ¤á¤¿. ¾±¡¤Ç¶ÛµÞÊü¼ÍÀþÎÅË¡¤ª¤è¤Ó²½³ØÎÅË¡¤ò¹Ô¤¦¤¬¸ú²Ì¤Ê¤·. ¼ðáçÀÚ½ü+±¦ÇÙ¾åÍÕÀÚ½ü¤ò¤ª¤³¤Ê¤¤Æù´ãŪ¤Ë¤Ï¼ðáç¤Ï´°Á´ÀÚ½ü¤Ç¤¤¿. ÉÂÍý¿ÇÃǤÏÈóŵ·¿Åª¤Ç¤¢¤ë¤¬ malignant SFT. Åö±¡¤ËºÆÆþ±¡, radiation therapy¤ò¤ª¤³¤Ê¤¦. ¸ú²Ì˳¤·¤¯, ¼ðáç¤Ï¿Ê¹Ô¤·¸ÆµÛÉÔÁ´¤Ç±Ê̲¤µ¤ì¤ë.
 |  |  |  | CT pneumothorax | ½Ä³Ö¼ðáî¤Ê¤·. | ½ÑÃæ¶»¹Ð¶À¼Ì¿¿ | Ŧ½ÐɸËÜ |
Êɦ¶»Ëì¼ðáîÀÚ½üɸËÜ ÉÂÍýÁÈ¿¥½ê¸«
 |  |  |  | pleura tumor loupeÁü | pleura tumor x400:¡ | pleura tumor x200¡§¢ | pleura tumor x200¡§£ |
ÉôʬŪ¤ËºÙ˦ÀÜÃåÀ¤¬Ä㤯Á¤ÊÁÈ¿¥Áü¤òÄ褹¤ë.
¡ rhabdoid cells¤¬Ì©¤ËÁý¿£¤¹¤ëÁÈ¿¥Áü. ³Ë¤ÏÎà±ß·Ávesicular¤Ç, Ãæ¿´À¤ÎÂç·¿³Ë¾®ÂΤò1¸Ä¤â¤Ä.¡¡ºÙ˦¼Á¤Ï¹¥»ÀÀ.
µå¾õ¤ÎÉõÆþÂÎÍͤˤߤ¨¤ë¹½Â¤¤¬½Ð¸½¤·, ³ËÊкߤä³Ë¤ò°µÇÓ¤·, »°Æü·î/Ⱦ·î¾õ¤Î³Ë¤¬¤ß¤é¤ì¤Æ¤¤¤ë. mitosis¤¬»¶ºß. ·Á¼ÁºÙ˦¤¬¾¯¿ôº®ºß¤·¤ÆÇ§¤á¤é¤ì¤ë.
¢ ¾¯Î̤ÎÀþ°ÝÀÁÈ¿¥¤ò´Ö¼Á¤ËÎà±ß·Á/¿ÎÇ·Á¤Îvesicular¤Ê³Ë¤È¹¥»ÀÀ, øÌÀ¤ÊºÙ˦¼Á¤ò¤â¤ÄÎà¾åÈéÍͤÎÃæ¡ÁÂç·¿¤ÎºÙ˦¤¬½¸äÈ, Áý¿£¤·¤Æ¤¤¤ë.mitosis¤¬Â¿¤¤. ÊÕ±ï¤Ë¤Ïrhabdoid cells¤Îchohesive¤ÊÁý¿£¤¬Ç§¤á¤é¤ì¤ë.
£ ´Ö¼Á¤ÎÀþ°ÝÁÈ¿¥¤¬Â¿¤¯, ¾Ë»Ò²½¤ämyxomatous change¤¬Ç§¤á¤é¤ì¤ë. Æó³Ë¤ÎÂç·¿µðºÙ˦¤¬»¶ºß¤·¤Æ¤¤¤ë. ºÙ˦¤Î¿·¿¤Ï¹âÅ٤ǤϤʤ¤°õ¾Ý.
 |  |  |  | CD34 | CD34-spindle cells | CD99(MIC2) | Vimentin |
 |  | CK(AE1/3)¤Ï±¢À. MIB-1¤Ï>90% |
Vimentin, CD99(MIC2)¤Ï¤Ó¤Þ¤óÀ¤ËÍÛÀ¤ò¼¨¤¹. CD34¤Ïfocal¤ËÍÛÀ. °Û·¿ spindle cell¤Ë¤âÍÛÀ¤òÄ褹¤ë.
EMA¤Ï¾¯¿ô¤ÎÍÛÀºÙ˦¤¢¤ê. BCL2¤Ï¥ê¥ó¥Ñµå¤ËÍÛÀ. ¼ðáçºÙ˦¤Ï¤Û¤Ü±¢À. ø¤¯À÷¤Þ¤ëºÙ˦¤¬¤´¤¯¾¯¿ô¤¢¤ë. CK(AE1/3)¤Ï±¢À.
p53¤Ï¤Ó¤Þ¤óÀ, 80%¤ËÍÛÀ. (photo½àÈ÷Ãæ). MIB-1 LI¤Ï>90%.
 |  |  |  | BRG1(SMARCA4) | BRG1(SMARCA4) | INI1(SMARCAB1) | p53 |
BRG1¤Ï³ËÀ÷¿§À¤¬¾Ã¼º. internal control¤Î·ì´ÉÆâÈé¤ä±ê¾ÉºÙ˦¤Ï³Ë¤ËÍÛÀ¤È¤Ê¤ë. INI1(SNF5/SMARCAB1)¤Ï¤Ó¤Þ¤óÀ¤ËÍÛÀ. p53¤¬Â¿¤¯¤Î¼ðáçºÙ˦¤ËÍÛÀ¤È¤Ê¤ë.
¶»¹Ð¶À²¼¥Ö¥éÀÚ½ü½Ñ5¥õ·î¸å, ½Ä³Ö¼ðáî¤ÇºÆÈ¯. ¾±¡¤Ç¼ðáçÀÚ½ü¡Ü±¦ÇÙ¾åÍÕÀÚ½ü¤ò»Ü¹Ô. Æù´ãŪ¤Ë¤Ï¼ðáç¤Ï´°Á´¤ËÀÚ½ü¤Ç¤¤¿.
ÉÂÍý¿ÇÃǤÏ, Èóŵ·¿Åª½ê¸«¤Ê¤¬¤émalignant solitary fibrous tumor¤È¤µ¤ì¤¿.(˶¸¡»þÅÀ¤Ç¤ÏSMARCA4-DTS¤Î¼À´µ³µÇ°¤Ï¤Ê¤¯, Ã諤âÆÀ¤é¤ì¤Æ¤¤¤Ê¤«¤Ã¤¿.)
½é¿Ç¤«¤é11¥õ·î, ¶»Éô¤Ä¤«¤¨´¶½Ð¸½. CT¤Çµ¤´Éʬ´ôÉô¤«¤é²£³ÖËì¿©Æ»Îö¹¦¤òÄ̤ê, Ê¢¹ÐÆâ¤Ø¿ÊŸ, ¿©Æ»¤ª¤è¤ÓÂçÆ°Ì®¤ò°Ïå夹¤ëµðÂç¤Ê¼ðá礬ºÆÈ¯¤·¤¿. ¾±¡¤Ç¤Î¹³¤¬¤óºÞ´¶¼õÀ¥Æ¥¹¥È¤Î·ë²Ì¤è¤ê, CDDP+5FU¤Ë¤è¤ë²½³ØÎÅË¡¤¬¤ª¤³¤Ê¤ï¤ì¤¿¤¬¸ú²Ì˳¤·¤¯Á´¿È¾õÂÖ°²½. ¸ÆµÛÉÔÁ´¤¬¿Ê¹Ô¤·½é¿Ç¤è¤êÌó1ǯ¤Î·Ð²á¤Ç±Ê̲¤µ¤ì¤¿.

Autopsy findings: macro
SMARCA4(BRG-1)-deficient thoracic sarcoma †
2015ǯ Le Loarer F¤é¤Ë¤è¤êʬÎàÉÔǽÆù¼ð¤ÎRNA-seq¤«¤é ¿·¤·¤¤¼À´µ·², SMARCA4-deficient thoracic sarcoma¤È¤·¤Æ19Î㤬¤Þ¤È¤á¤é¤ì, Nature Genetics¤ËÎ×¾²ÉÂÍýÁü¤ä°äÅÁ»Ò¤ÎÊѰ۽긫¤¬Êó¹ð¤µ¤ì¤¿.*1
Î×¾²Áü
Le Loarer¤é¤ÎÊó¹ð¤·¤¿ºÇ½é¤Î¾ÉÎã*1
- Á´19Î㤬¶»¹Ð¤Ëȯ¾É.½Ä³Ö(n=13), ¶»Ëì(n=5), ÇÙ(n=1). Âç·¿°µÇÓÀ¤Î¼ðáî¤ÇÃæ±ûÃÍ13cm, (3.5-21cm). ½Ä³Ö, ¶»Ëì¼ðáî¤ÏÄ̾ï¶á˵¤ÎÇÙ, ÇÙÀí=5, ÇÙÌç=4, ¤ª¤è¤Ó¶»ÊÉ=10¤Ë¿»½á¤·¤Æ¤¤¤ë.
- ºÇ¤âØí´µ¿ô¤Î¿¤¤Ç¯Îð¤Ï 30-35ºÐ Ãæ±ûÃÍ41ºÐ(28-72ºÐ). ÃËÀÍ¥°Ì. n=16/19 ¤ÇµÊ±ì¼Ô n=17/19¤Ë¿¤«¤Ã¤¿.
¼ãǯ¼Ô¤Ë¤ª¤³¤ë¸²Ãø¤Ê¥ê¥ó¥ÑÀáÉÂÊÑ¤È ¿¯½±À¶»ÉôÉÂÊѤϰÀ¥ê¥ó¥Ñ¼ð, NUT midline carcinoma(carcinoma with BRD3-NUTM1/ BRD4-NUTM1 fusion)¤òÎ×¾²Åª¤Ëµ¿¤ï¤»¤ë.
- ²½³ØÎÅË¡¤Ë¤ÏÄñ¹³À¤Ç¶É½ê¤ÇÁáµÞ¤ËÁýÂ礹¤ë.³°²ÊŪÀÚ½ü¤ò2Îã¤Ë¤ª¤³¤Ê¤¤¥Þ¥¯¥í¤ÇÃÇü±¢À¤Ç¤¢¤Ã¤¿¤¬1¤«·î°ÊÆâ¤ËºÆÈ¯¤·¤¿.
Median OS¤Ï 7¥õ·î.( 1-20¥õ·î). 1Îã¤ò½ü¤¶É½ê¼ðáî¤Ç»àË´(n=17/18).
ÆüËܤÎ12¾ÉÎã(¹ñΩ¤¬¤ó¥»¥ó¥¿¡¼¾ÉÎã)*2
- 27 - 82ºÐ(Ãæ±ûÃÍ39ºÐ), ÃËÀ11/ ½÷À1.
- 11/12Î㤬ÇÙ¤Ëemphysema, bullae¤òͤ·¤Æ¤¤¤¿. primary site¤Ï, ¶»ÊÉ=1, ¶»Éô˵ÀÔÄÇ=2, ÇÙ=4Îã¤Ç, Ʊ»þ¤Ë¸åÊ¢Ëì(1), Ê¢¹ÐÆâ(1), ½Ä³Ö¤Ë¿ÊŸ(1), Ç٤Τß(1). ½Ä³Ö=4,Ʊ»þ¤Ë¹üÈ׹ФޤǿÊŸ(1). æþãÝ=1.
- ž°Ü¤¬, ¶»Ëì(1Îã), ¥ê¥ó¥ÑÀá(5), ´Î(4), ÇÙ(3), ¹ü(3), Éû¿Õ(2), °ß(2), Èé²¼(1), ÍñÁã(1)¤Ëǧ¤á¤é¤ì¤¿.
Sauter JL et al. (Mayo clinic¾¤Î12Îã)*3
- 44-76ºÐ¡ÊÃæ±ûÃÍ59ºÐ) ÃËÀ9: ½÷À3
- ¾É¾õ¤Ï¸ÆµÛº¤Æñ, ¶»ÄË, ¶»¿å, ÓÒÅÇ, ·ñÂÕ´¶, ÂνŸº¾¯. ¤³¤Î¾, ³Æ¡¹1Îã¤ËIJ¹üž°Ü¤Ë¤è¤ë²¼»èÄˤÈæÎÏ, Ǿž°Ü¤Ë¤è¤ë¤Æ¤ó¤«¤ó¾É¾õ¤¬¤ß¤é¤ì¤¿.
- ¼ðáç¤ÎÉô°Ì¤Ï, ½Ä³Ö=7(58%), ÇÙ=3(25%), ¶»Ëì=2(17%). ½éȯ»þ¤Ëž°Ü¡Ü; Éû¿Õ, Ǿ, ÇÙÌç¥ê¥ó¥ÑÀá.¡¡1Îã¤Ï·Ð²áÃæ(1¥õ·î)¤Ë¹ÈϤÊž°Ü(¥ê¥ó¥ÑÀá, Éû¿Õ, ¿´Ëì, ÇÙ, ¹ü, Ǿ)¤ò¤¤¿¤·¤¿.¡¡
Perret R, et al(2019 Am J Surg Pathol)*4¥Õ¥é¥ó¥¹¤Î30¾ÉÎã
- 28 - 90ºÐ(Ãæ±ûÃÍ48ºÐ). ÃËÀ27/½÷À3 (9:1)µÊ±ì¼Ô¤¬Â¿¤¤(87%).
- ½Ä³Ö=13Îã, ¶»Ëì=5Îã(¤¦¤Á2Îã¤Ï¿ȯ), ÇÙ=2Îã. Ê£¿ô¡´ï¤Ëȯ¾É=10Îã= ½Ä³Ö¤ÈÇÙ=2, ½Ä³Ö¤ÈÇÙÌç= 4, ½Ä³Ö¤È¶»Ëì¤ÈÇÙ=1, Ç٤ȶ»Ëì=3.
- Â礤ʿ»½áÀ¼ðáî¤ÇÎÙÀܤ¹¤ë¡´ï¤ò°µÇÓ¤·¤Æ¤¤¤ë. ²èÁü¤Ç¤Ï¥ê¥ó¥Ñ¼ð, NUT midline carcinoma, æõºÙ˦¼ðá礬µ¿¤ï¤ì¤¿.
- ž°Ü¤¬77%¤Î¾ÉÎã¤Ëǧ¤á¤é¤ì¤Æ¤¤¤ë. ¥ê¥ó¥ÑÀá>¹ü>Éû¿Õ>´Î>¾Ã²½´É>Ãæ¿õ¿À·Ð>¿Õ
- OS Ãæ±ûÃͤÏ7¥õ·î¤Èͽ¸åÉÔÎÉ.
SMARCA4 †
SMARCA4¡§SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4.
GeneID:6597 (NM 003072) ¶Éºß 19p13.2, 19 NC_000019.10 (10960997..11062277). 40¥¨¥¯¥½¥ó.
rhaboid feature¤ÏBAF complex¤ÎÉԳ貽¤òÈ¿±Ç¤¹¤ë·ÁÂÖ³ØÅªÆÃħ¤Ç¤¢¤ë¤È¤¹¤ëÊó¹ð¤òÁ°Äó¤È¤·. *5 *6.*7*8*918Îã¤Îrhabdoid cell¤«¤é¤Ê¤ëSMARCB1(SNF5/INI1)¤¬Êݤ¿¤ì¤Æ¤¤¤ëʬÎàÉÔǽÆù¼ð¤ÎmRNA¥·¡¼¥¯¥¨¥ó¥¹¤ò¥¹¥¯¥ê¡¼¥Ë¥°.
ºÇ½ªÅª¤ËSMARCA4ÊѰۤò¼¨¤¹19Îã¤ò²òÀϤ·nonsense mutation(n = 10), frame shift (n=6), missense (n=2)¤ò¸¡½Ð, ¤ª¤è¤Ósplice site¡Ên=1)¤¬Ç§¤á¤é¤ì¤¿. (±¦¿Þ)*1
SMARCA4°Ê³°¤Î°äÅÁ»Ò°Û¾ï¤Ç¤Ï, TP53ÊѰۤ¬È¿ÉüÀ¤Ëǧ¤á¤é¤ì¤ë¤Î¤ß¤Ç¤¢¤Ã¤¿.
ÆüËÜ(¹ñΩ¤¬¤ó¥»¥ó¥¿¡¼)¤Î12¾ÉÎã¤Î°äÅÁ»Ò²òÀϤǤÏ, 5Îã¤Î²òÀϤ¬²Äǽ¤Ç¤¢¤Ã¤¿. D543fs(1629delC), L553fs(1658del19), E700X(G2098T), H799fs(2396delA), Q1012X(C3034T),¤ò¸¡½Ð¤·¤¿. *2
SMARCA4ÊѰۤËHOT SPOT¤Ïǧ¤á¤é¤ì¤Ê¤¤¤è¤¦¤Ç¤¢¤ë.
phenotype: ÌȱÖÀ÷¿§¤Î½ê¸«. †
ʸ¸¥; Or(Le Loarer, et al*1), J(Japanese cases*2), F(French cases*4), A(American-Mayo,etc cases*3)
¿ÇÃǤËɬ¿Ü¤È¹Í¤¨¤é¤ì¤ëÌÈÀ÷·ë²Ì
- Èù¾®¤ÊÀ¸¸¡ÁÈ¿¥¤Ç¤Î¿ÇÃǤǤÏSMARCA4, SMARCA2ξ¼Ô¤Î¾Ã¼º¤ÈSOX2¤¬¤Ó¤Þ¤óÀ¤ËÀ÷¿§(³Ë¤ËÍÛÀ)¤µ¤ì¤ë¤³¤È¤¬ÍÍÑ. Or, J, F, A
- SMARCA4(BRG-1);¾Ã¼ºOr, J, F, A¤¢¤ë¤¤¤Ï¤Ó¤Þ¤óÀ¤Ëȯ¸½¤¬¸º¾¯¤·¤Æ¤¤¤ë.J
- SOX2: ³Ë¤Ë¤Ó¤Þ¤óÀ, ¶¯ÍÛÀ¤ò¼¨¤¹(96%). SMARCA4·ç¼ºÇÙ´â¾ÉÎã¤Ç¤Ï±¢ÀOr. SMARCA4-loss case¤Î4Îã¤Ë, ¤Ó¤Þ¤óÀ¤Ë¶¯ÍÛÀ.SMARCA4¤¬Êݤ¿¤ì¤Æ¤¤¤ësarcoma¤Ç¤ÏÁ´Îã±¢ÀA. ÍÛÀ¤¬85%, ¡Þ¤¬11%F.
¤½¤Î¾ÍÛÀ¤ò¼¨¤¹¹³ÂÎ
- CD34(67%):¼ðáçºÙ˦¤Î¿¤¯¤¬ÍÛÀ¤È¤Ê¤ë. CD34ÍÛÀ; 3/5Îã(60%)A. 52%¤¬¡Ü, 11%¤¬¡ÞF
- SALL4:°ìÉô¤Î¾ÉÎã(33%)¤Ë, focal¤ËÀ÷¤Þ¤ë.Or. 9%¤¬ÍÛÀ, 24%¤¬¡ÞF.
- MIC2(CD99)¡§3/6Îã¤ÇÍÛÀJ.40%(6/15)¤ËÍÛÀF.
- p53: 7/10¾ÉÎã¤Ë¶¯¤¯¤Ó¤Þ¤óÀ(>90%¤ÎºÙ˦)ÍÛÀ.J
- SMARCAB1(INI1); ÊÝ»ý¤µ¤ì¤Æ¤ª¤ê·ç»¤Ï¤Ê¤¯³ËÍÛÀ.Or, J, F, A
- CK(AE1/3, etc), EMA¤Ê¤É¤Î¾åÈé¥Þ¡¼¥«; ¤Û¤È¤ó¤É(97%)¤¬ CK(AE1/3), EMA, ¤Î¤¦¤Á¤É¤Á¤é¤«1¤Ä¤Î¾åÈé¥Þ¡¼¥«¤ò¤òȯ¸½¤¹¤ë. Ä̾ï°ìÉô¤ÎºÙ˦¤ËÍÛÀ¤È¤Ê¤ëOr. CK(AE1/3)¤Ï¾¯¿ô¤ÎºÙ˦¤ËÍÛÀ 10(83%). ¤Ó¤Þ¤óÀ¤Îȯ¸½¤Ï¤É¤Î¾ÉÎã¤Ë¤â¤ß¤é¤ì¤Ê¤«¤Ã¤¿.A. CAM5.2(1/1), CK7(1/3), EMA(8/10)¤ËÍÛÀJ.CK,EMA¤Ï22%¤¬¡Ü, ³Æ¡¹32%,59%¤¬¡Þ, CK7(1/7), F
- SMARCB1(INI1, SNF2): ȯ¸½¤ÏÊݤ¿¤ì¤Æ¤¤¤ë.
- TTF1, p63: 1Îã¤ËÀ÷¤Þ¤ë.¡¡TTF-1; 1Îã¤Î¤ß¼åÍÛÀJ. ¤³¤ÎÎã¤ÏCK¤Ï±¢ÀA TTF1¤Ï4%¤Ë¡Þ, p63¤Ï5%¤Ë¡ÞF.
- Synaptophysin (1/4). 18%(3/17)F
±¢À½ê¸«¤ÎÌȱÖÀ÷¿§
- p40, NUT¤ÏÁ´Îã±¢ÀF, A, J.¡¡Desmin, NUT, S-100¤Ï±¢À.
- DNA mismatch repair proten: PMS2, MSH6¤ÏÊÝ»ý¤µ¤ì¤Æ¤¤¤ë. ¾Ã¼º¤Ê¤·.
- CK20(0/3), 34¦ÂE12(0/1), p40 or p63(0/5), napsinA(0/3), HNF4¦Á(0/5), NUT(0/4), CD45(0/7), ALK/p80(0/3), CD20(0/4), CD79a(0/4), CD3(0/4), CD5(0/3), TdT(0/1), CD30(0/6), CD31(0/4), ERG(0/2), S100(0/10), HMB45(0/2), MelanA(0/1), NKX2.2(0/8), chromograninA(0/3), CD56(0/2), PLAP(0/3), C-KIT(0/6), hCG(0/2), alpha-fetoprotein(0/2), OCT3(0/7), MUC480/2), SMA(0/4), HHF35(0/2), desmin(0/7), myogenin(0/4).°Ê¾åJ
- CD5(0/16), CK5/6(0/17),CD45(0/18),chromograninA(0/17), PLAP(0/10), CD117(0/16), WT1(0/6), Desmin(0/23), Myogenin(0/23), CD56(0/16)F
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