Signet-ring Cell Carcinoma of the Gallbladder Complicated by Pulmonary Tumor Thrombotic Microangiopathy
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1 CASE REPORT Signet-ring Cell Crinom of the Glller Complite y Pulmonry Tumor Thromoti Mirongiopthy Yoshinori Ohno 1, Teru Kumgi 1,2, Tir Kuro 1, Mitsuhito Koizumi 1, Nouki Azemoto 1, Hirofumi Ymnishi 1,MyuO 3, Msshi Hirook 1, Msnori Ae 1, Yoshio Ike 1, Bunzo Mtsuur 1, Morikzu Onji 1, Yoshiko Sog 4, Yousuke Mizuno 4, Atsurou Sugit 4 n Yoihi His 1 Astrt Biliry ringe ws performe in 71-yer-ol mn with ostrutive junie of unknown origin; however, he ie ue to ute pulmonry filure. At utopsy, prolifertion of enorinom ells ws oserve in the glller muos trnsitioning from isolte signet-ring ell rinom (SRCC) to the suseros n ile uts without growth towr the glller lumen. Furthermore, firoellulr intiml prolifertion, tumor emoli n orgnize thromi were oserve in the smll pulmonry rteries. The finl ignosis ws glller rinom omplite y SRCC ssoite pulmonry tumor thromoti mirongiopthy (PTTM). PTTM my present s rpily progressive yspne, n high level of linil suspiion is require to mke the ifferentil ignosis. Key wors: signet-ring ell rinom, glller, pulmonry tumor thromoti mirongiopthy (Intern Me 53: , 2014) () Introution Glller rinom (GBC) is known to e n ggressive neoplsm, thus proviing erly etetion n ril surgery is mntory in orer to hieve etter prognosis (1). However, pproximtely 50% of ptients with GBC present with the isese t vne stge, with looregionl spre n lymph noe metstsis (2). Aenorinom is the most ppreite histologil type of GBC, while signetring ell rinom (SRCC) is extremely rre (2). In generl, the ggressive ehvior of SRCC is eviene y its infiltrtion of the surrouning strom, ro issemintion n high teneny to proue peritonel metstses in the gstrointestinl trt (3). In ition, in ptients with pulmonry tumor thromoti mirongiopthy (PTTM), histologil exmintions revel meil n intiml hypertrophy, intiml firosis n firinoi nerosis of the internl elsti lmin of smll rteries n rterioles (4, 5). Pulmonry hypertension n or pulmonle inue y tumor emoli using PTTM re rre n extremely iffiult to ignose prior to eth (6). We herein present se of SRCC of the glller omplite y PTTM. Cse Report A 71-yer-ol Jpnese mn ws mitte to our hospitl ue to right upper ominl pin n junie in My He h history of totl gstretomy for gstri mlignnt lymphom in On mission, he ws junie, n mss ws plple in the right upper omen with tenerness. Lortory tests showe normlities in the levels of heptoiliry enzymes n iliruin: AST=380 U/L, ALT=252 U/L, ALP=2,591 U/L, GGT=1,087 U/L n totl iliruin=8.6 mg/l. The levels of tumor mrkers were lso elevte: rinoemryoni ntigen=529 ng/ml n ro- Deprtment of Gstroenterology n Metology, Ehime University Grute Shool of Meiine, Jpn, Deprtment of Community Meiine, Ehime University Grute Shool of Meiine, Jpn, Resieny Progrm, Ehime University Hospitl, Jpn n Pthology Division, Ehime University Hospitl, Jpn Reeive for pulition Otoer 17, 2013; Aepte for pulition Deemer 17, 2013 Corresponene to Dr. Teru Kumgi, terukum@m.ehime-u..jp 1125
2 Intern Me 53: , 2014 Figure 1. (, ) Aominl ontrst-enhne ompute tomogrphy (CE-CT): () erly phse; () lte phse. CE-CT showe slight enhnement of soft tissue surrouning the ile ut n res jent to the eli rtery. () Aominl MRI with T2-weighte imging revele lesion of high signl intensity long the intrhepti ile ut with fous in the hepti portl region. () MRCP emonstrte slightly ilte intrhepti ile ut n iffuse nrrowing of the extrhepti ile ut. hyrte ntigen 19-9=82 U/mL. Imging stuies Aominl ultrsonogrphy revele iliry sluge n swelling of the glller, lthough no wll thikness or polypoi lesions were oserve. Aominl ontrstenhne ompute tomogrphy (CT) showe slight enhnement of soft tissue surrouning the ile ut n res jent to the eli rtery (Fig. 1, ), with lymphenopthy in the ominl vity. Chest CT i not show ny signifint finings. Aominl MRI with T2-weighte imging showe lesion of high signl intensity long the intrhepti ile ut with fous in the hepti portl region (Fig. 1). Mgneti resonne holngiopnretogrphy (MRCP) lso emonstrte slightly ilte intrhepti ile ut n iffuse nrrowing of the extrhepti ile ut (Fig. 1). Clinil ourse A ignosis of ile ut rinom ws suspete se on the ove-mentione finings, lthough the fetures oserve on the imging stuies were typil. The ilttion of the intrhepti ile ut ws reltively mil ompre to the egree of extrhepti ile ut stenosis. Therefore, hemtologil isorers, inluing mlignnt lymphom, were inlue in the ifferentil ignosis. Perutneous trnshe- pti glller ringe ws initilly performe to reue the ptient s symptoms, whih revele muus in the glller. Perutneous trnshepti iliry ringe ws lso performe, s the intrhepti ile ut exhiite suffiient ilttion for neele insertion; however, oth proeures file to improve the ptient s junie, n inste his onition progresse. Bile ytology of speimens otine using oth proeures were negtive. Dyspne n erese in the loo oxygen level were oserve, n the ptient s onition further eteriorte the y efore his eth. He ie on the 16th hospitl y ue to rpi progression of the isese. An utopsy ws performe fter otining onsent from his fmily. Autopsy At utopsy, the mrosopi finings were signifint for Glisson s psule expnsion in the hepti portl trt, n the ptient s glller ws fully pke with muus, lthough the muosl surfe of the glller ws smooth. There ws ongestion in oth lungs; however, no thromi were etete in the hilum of the pulmonry rtery. Mirosopilly, infiltrtion of SRCC ws oserve surrouning the intrhepti n extrhepti ile uts, lthough the tumor itself h not infiltrte the ile ut muos (Fig. 2, ). In ition, infiltrtion of signet ring ells ws note in the lymphti vessels. The prolifertion of well- 1126
3 Intern Me 53: , 2014 B Figure 2. Histopthologil finings. () Prolifertion of SRCC roun the ile ut (B), [Hemtoxylin n Eosin (H&E) stining, 40]. () SRCC (H&E stining, 200). (, ) The glller. () Prolifertion of well-ifferentite enorinom (H&E stining, 20), () estroying the musle lyer (rrow) n infiltrtion of SRCC into the suseros (H&E stining, 200) (rrowhes). Figure 3. Histopthologil finings of PTTM in the pulmonry rteries of the periphery of oth lungs (left pnels, Hemtoxylin n Eosin stining; right pnels, Elsti-Msson stining). (, ) Firoellulr intiml prolifertion: () 300 μm in imeter; () 500 μm in imeter. () Tumor emoli. () Orgnize thromi. ifferentite enorinom ws oserve in the glller muos, infiltrting into the suseros without growth towr the glller lumen (Fig. 2). Aitionlly, trnsi- tion from well-ifferentite enorinom to SRCC ws etete in the res of infiltrtion (Fig. 2). Lymph noe metstsis, s well s iret invsion to the pnres n 1127
4 Intern Me 53: , 2014 uoenum, ws lso seen. Furthermore, firoellulr intiml prolifertion with the presene of tumor emoli n orgnize thromi ws oserve in the periphery of the smll pulmonry rteries with imeter of μm (Fig. 3). The finl ignosis ws SRCC of the glller extening to the extr- n intrhepti ile uts n iretly inving jent orgns omplite y PTTM. Disussion We enountere se of SRCC of the glller omplite y PTTM tht ws ignose t utopsy. Aenorinom is the most ommon histologil type of glller rinom, while SRCC is extremely rre. Nevertheless, onventionl enorinom my osionlly e seen mixe with SRCC (7). SRCC n rise in virtully ny orgn, lthough most lesions originte from the stomh, rest or olon (8, 9). SRCC frequently metstsizes to peritonel surfes, s well s the regionl lymph noes, ovries n lungs (9). In Jpn, the iniene of SRCC hs een reporte to e pproximtely 1% of ses of primry glller rinom ignose t utopsy (10). Minmi et l. summrize 21 ses of SRCC of the glller in Jpn (11). Their results showe slightly higher prevlene mong women, with higher rtes of ses mixe with other types of orgnize muinous rinom, wellifferentite enorinom n/or squmous ell rinom. In ition, mny ses involving elevte lesions in the glller lumen were oserve. Mny of the ptients were ignose with SRCC of the glller fter unergoing holeystetomy. The verge survivl rte ws s short s 19 months. Mking the ignosis ws very iffiult in the present se for two resons. First, poor finings of glller rinom were oserve in the vrious imging stuies ue to n unusul pttern of expnsion; i.e., the tumor not growing into the glller lumen, ut rther infiltrting the suseros. Seon, the tumor exhiite poor expnsion into the intrhepti ile ut ompre to the egree of ommon ile ut stenosis, n infiltrtion of SRCC ws oserve surrouning the intrhepti n extrhepti ile uts. In the present se, there ws lso mrke intiml firoplsi n meil hypertrophy involving smll pulmonry rterioles onsistent with ignosis of PTTM, whih is hrterize y the presene of multiple mirothromi n intiml myofirolst prolifertion (5). Ptients with PTTM often present with rpily progressive yspne n ute pulmonry hypertension (12). PTTM hs een reporte to e oserve in % of vers with extrthori mlignnies. Gstri enorinom is the mlignny most frequently ssoite with PTTM (5). Only two ses of PTTM rising from metstti glller rinom hve een reporte, one of whih involve SRCC of the glller (6, 13). Urug et l. reporte tht, mong 2,215 onseutive utopsy ses of rinom, 30 ptients (1.4%) were ignose with efinitive PTTM (14). The mein survivl time following the initition of oxygen supplementtion ws nine ys. There re some reports of the ntemortem ignosis of PTTM using pulmonry wege spirtion ytology, lung iopsies, positron emission tomogrphy or lung perfusion sns (12, 15-18). However, PTTM is generlly iffiult to ignose prior to eth n is primrily etete se on pthologi finings, s oserve in the present se. In summry, we herein reporte se of SRCC of the glller ssoite with PTTM. It is importnt to reognize the origin of the primry tumor in orer to optimize tretment. The prolifertion of signet-ring ells in ptients with glller enorinom worsens the prognosis. A high level of linil suspiion is require to mke n ntemortem ignosis of PTTM. The uthors stte tht they hve no Conflit of Interest(COI). Referenes 1. Bzn F, Snhez J, Aguilr G, et l. Metstti glller enorinom with signet-ring ells. J Me Cse Rep 5: 458, Henson DE, Alores-Sver J, Corle D. Crinom of the glller. Histologi types, stge of isese, gre, n survivl rtes. Cner 70: , Lzno-Pone EC, Miquel JF, Muñoz N, et l. Epiemiology n moleulr pthology of glller ner. CA Cner J Clin 51: , Shiels DJ, Ewrs WD. Pulmonry hypertension ttriutle to neoplsti emoli: n utopsy stuy of 20 ses n review of the literture. Criovs Pthol 1: , Von Hery A, Illes A, Wlherr R, et l. Pulmonry tumor thromoti mirongiopthy with pulmonry hypertension. Cner 66: , Mlni AK, Gupt C, Kutty AV, Betlej T. Pulmonry tumor thromoti mirongiopthy from metstti glller rinom: n unusul use of severe pulmonry hypertension. Dig Dis Si 52: , Alores SJ, Eel HD, Dvi SK. Tumors of the glller, extrhepti ile uts, n mpull of vter. In: Atls of Tumor Pthology, Thir Series, Fsile 27. Arme Fores Institute of Pthology, Wshington DC, 2000: Chu PG, Weiss LM. Immunohistohemil hrteriztion of signet-ring ell rinoms of the stomh, rest, n olon. Am J Clin Pthol 121: , Pvi I, Mrusi Z, Miji A, et l. A se of signet-ring ell rinom of the glller: immunohistohemistry n ifferentil ignosis. At Clin Crot 49: , Annul of the Pthologil Autopsy Cses in Jpn The Jpnese Soiety of Pthology (in Jpnese). 11. Minmi Y, Ngno Y, Ue M, et l. A se of resete signet ring ell rinom rising from the glller. Nihon Gekkei Gkki Rengoukishi (Journl of Jpnese College of Surgeons) 34: , 2009 (in Jpnese, Astrt in English). 12. Shih HM, Lin CC, Shio YW. Pulmonry tumor thromoti mirongiopthy. Am J Emerg Me 29: 241.e3-241.e4, e Luis DA, Drri J, Sn Miguel P, et l. A se of seonry pulmonry hypertension ue to mirosopi pulmonry tumor ell emolism from glller rinom. Respirtion 64: , Urug H, Fujii T, Kuroski A, et l. Pulmonry tumor thromoti mirongiopthy: linil nlysis of 30 utopsy ses. Intern 1128
5 Intern Me 53: , 2014 Me 52: , Bhuvneswrn JS, Venkithlm CG, Snhymni S. Pulmonry wege spirtion ytology in the ignosis of reurrent tumour emolism using pulmonry rteril hypertension. Int J Criol 39: , Urug H, Morokw N, Enomoto T, et l. A se of pulmonry tumor thromoti mirongiopthy ssoite with lung enorinom ignose y CT-guie lung iopsy. Nihon Kokyuki Gkki Zsshi (Journl of the Jpnese Respirtory Soiety) 46: , 2008 (in Jpnese, Astrt in English). 17. Tshim Y, Ae K, Mtsuo Y, et l. Pulmonry tumor thromoti mirongiopthy: FDG-PET/CT finings. Clin Nul Me 34: , Keenn NG, Niholson AG, Olershw PJ. Ftl ute pulmonry hypertension use y pulmonry tumour thromoti mirongiopthy. Int J Criol 124: e11-e13, The Jpnese Soiety of Internl Meiine
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