The Disappearance of Lymph Node Metastasis from Neuroendocrine Carcinoma after Endoscopic Ultrasound-guided Fine Needle Aspiration
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1 CASE REPORT The Dispperne of Lymph Node Metstsis from Neuroendorine Crinom fter Endosopi Ultrsound-guided Fine Needle Aspirtion Msyuki Shit 1, Hiroyuki Mtsuyshi 1, Akiko Todk 2, Hnko Kuri 3, Noyuki Tsutsumi 3, Keiko Sski 4 nd Hiroyuki Ono 1 Astrt A 75-yer-old Jpnese mn ws referred to our hospitl to undergo the exmintion of n enlrged peripnreti lymph node. Computed tomogrphy (CT) showed lymph node 47 mm in size tht ws loted ove the pnres hed nd eneth the liver. Endosopi ultrsound-guided fine needle spirtion (EUS- FNA) of the enlrged lymph node ws performed, nd n immunohistologil exmintion of the smple onfirmed histologil dignosis of neuroendorine rinom (NEC). The ptient refused tretment with hemotherpy nd insted hose to undergo oservtion. However, the lymph node the previously enlrged lymph node ws not visile on CT t 12 months fter the exmintion. Key words: spontneous regression, neuroendorine rinom, endosopi ultrsound-guided fine needle spirtion (Intern Med 55: , 2016) (DOI: /internlmediine ) Introdution The spontneous regression of mlignnt tumors is defined s the prtil or omplete dispperne of mlignnt tumor without therpy. This definition suggests tht spontneous regression pplies to ses in whih ner is not lwys ured permnently (1). Iwng estimted tht spontneous regression ourred in pproximtely 1 in 120,000 ner ses per yer in Jpn in 2011 (2). In ddition, his report showed tht the spontneous regression of gstri ner, whih ounts for 8% of ses of spontneous regression, is very rre nd tht regression of ggressive gstri ners suh s neuroendorine rinom (NEC) is espeilly unlikely. We herein report se in whih lymph node metstsis of NEC disppered fter endosopi ultrsound-guided fine needle spirtion (EUS-FNA). Cse Report A 75-yer-old Jpnese mn ws referred to our hospitl to undergo n exmintion of n enlrged peripnreti lymph node, whih hd een inidentlly deteted on dominl ultrsonogrphy tht ws performed to investigte pollkiuri. He hd een reltively helthy with pst medil history of olon polyps. His fmily history ws unremrkle. The ptient ws symptomti when he visited our hospitl. His physil exmintion nd lortory dt inluding tumor mrker levels (rinoemryoni ntigen, rohydrte ntigen 19-9) showed no normlities. Computed tomogrphy (CT) showed lymph node of 47 mm in size tht ws loted ove the pnres hed nd eneth the liver (Fig. 1, 2). This lymph node ws loted eneth the gstri ntrum nd not in ontt with the stomh. Upper gstrointestinl endosopy showed sumuosl tumor with ulertion t the gstri ntrum (Fig. 3). An immunohistologil exmintion of the gstri iopsy speimens re- Deprtment of Endosopy, Shizuok Cner Center, Jpn, Deprtment of Gstrointestinl Onology, Shizuok Cner Center, Jpn, Deprtment of Infetious Diseses, Shizuok Cner Center, Jpn nd Deprtment of Pthology, Shizuok Cner Center, Jpn Reeived for pulition Deemer 11, 2015; Aepted for pulition Ferury 8, 2016 Correspondene to Dr. Msyuki Shit, hemil.griulturl.dotor@gmil.om 2805
2 Intern Med 55: , 2016 DOI: /internlmediine Figure 1. Coronl dynmi omputed tomogrphy imges showing the sequentil hnges efore nd fter endosopi ultrsound-guided fine needle spirtion (EUS-FNA). An enlrged lymph node is seen eneth the udte loe of the liver efore EUS-FNA (). The lymph node developed entrl neroti re t 10 dys fter EUS-FNA (), nd ws not detetle t 12 months fter EUS-FNA (). Figure 3. The endosopy view of the sumuosl tumor t the gstri ntrum. Figure 2. Horizontl dynmi omputed tomogrphy imges showing the sequentil hnges efore nd fter endosopi ultrsound-guided fine needle spirtion (EUS-FNA). An enlrged lymph node is seen eneth the gstri ntrum efore EUS-FNA (). The lymph node developed entrl neroti re t 10 dys fter EUS-FNA (), nd ws not detetle t 12 months fter EUS-FNA (). Furthermore, the gstri tumor (white rrows) hd eome slightly lrger in size over the 12-months period (, ). veled dignosis of NEC tht ws positive for hromogrnin-a nd synptophysin, with Ki-67 index of more thn 80% (Fig. 4). EUS-FNA of the enlrged lymph node ws performed (Fig. 5). The exmintion of the smple otined from the lymph node onfirmed the immunohistologil dignosis of NEC (Fig. 6). Tretment with hemotherpy ws disussed with the ptient, ut he rejeted this opinion nd insted hose oservtion. A week fter the EUS-FNA proedure, the ptient experiened high fever (temperture of 40 ) nd ws redmitted. A lortory nlysis reveled tht his white lood ell ount nd C-retive protein level were normlly elevted. Two positive lood ultures reveled infetion with Streptoous onstelltus. CT demonstrted peripherlly en- 2806
3 DOI: /internlmediine d Figure 4. Histologil setions of the gstri iopsy speimen ( 100). A stined setion (Hemtoxylin nd Eosin stining) showing the histologil hrteristis of neuroendorine rinom, grde 3 (). The speimens were diffusely positive for hromogrnin-a (), synptophysin (), nd Ki-67 (d). hned low density mss t the lotion of the enlrged peripnreti lymph node (Fig. 1, 2). We suspeted tht he hd teremi nd n sess due to EUS-FNA, nd tretment with tzotm/piperillin (4.5 g q6h) ws strted nd ontinued for 16 dys. He reovered fter 3 weeks. At his request, no further tretment ws initited nd repet CT ws performed 6 months lter. Surprisingly, the lymph node tht hd een sujeted to EUS-FNA hd disppered. The lymph node remined undetetle t followup CT exmintion tht ws performed t 12 months fter EUS-FNA (Fig. 1, 2). However, 18 months fter EUS-FNA, the ptient presented with generl mlise. The lymph node remined undetetle, ut CT showed multiple liver tumors nd tht gstri tumor hd inresed (from 50 mm on the first CT to 60 mm) (Fig. 2 nd ). The ptient refused to undergo follow-up upper gstrointestinl endosopy; onsequently, we did not evlute the gstri tumor. We dignosed the hepti lesions s metstti tumors from the gstri NEC. The ptient ws mnged ording to the est supportive re poliy nd grdully worsened. He died of multiple orgn filure 19 months fter undergoing the EUS-FNA proedure. Disussion Figure 5. EUS-FNA of the enlrged lymph node ws performed. Bteremi is rre omplition fter dignosti endosopy. Severl erly studies showed n inidene rte of pproximtely 0-8% (3). EUS-FNA is reltively sfe method for dignosing nd evluting gstrointestinl nd nongstrointestinl mlignnies. Prophylti ntiiotis re therefore not reommended for the FNA of solid msses nd lymph nodes (4). Streptoous onstelltus, whih ws deteted in our se, is memer of the Streptoous milleri group. These orgnisms reside s prt of the norml flor in the humn orl vity nd the gstrointestinl trt nd hve the ility to use systemi infetion. β-ltm gents remin the tretment of hoie for Streptoous milleri infetions (5); thus, tretment with tzotm/piperillin ws effetive in our se. We ould not onfirm the dispperne of metstti lymph node fter EUS-FNA. The ptient died euse of the progression of the primry gstri ner; however, we on- 2807
4 DOI: /internlmediine d Figure 6. Histologil setions of the tissue otined y EUS-FNA ( 100). Stined setion (Hemtoxylin nd Eosin stining) showing the histologil hrteristis of neuroendorine rinom, grde 3 (). The speimens were diffusely positive for hromogrnin-a (), synptophysin (), nd Ki-67 (d). sidered tht the metstti lymph node might hve eome undetetle fter EUS-FNA due to spontneous regression. To dte, ording to key word survey of the Pu- Med dtse, severl studies hve reported dispperne of metstti lymph nodes in ner ptients fter FNA or iopsy proedures (6, 7). In ddition, the infiltrtion of inflmmtory ells ws found t the site of tumor regression. Some reports hve desried the umultion of T ells nd nturl killer (NK) ells in the histologil speimens of regressed tumors (7, 8). Tking into ount the ove points, we onsidered tht the immunologil responses might hve promoted the dispperne of the metstti lymph node in our se. We hypothesize tht the EUS guided-fine needle injetion of drugs promoting T ells nd NK ells tivities my e effetive in the tretment of mlignnt tumors. Chng et l. hve lredy reported the first ttempt of fine needle injetion under EUS guidne in ptients with dvned pnreti ner (9). Vrious ntitumor gents my e onsidered for immunologil therpy. Certin types of ner dvne y down-regulting T ell tivtion nd evde the immune system y expressing immunosuppressive progrmed deth 1 (PD-1) lignds (10). Severl studies hve shown tht the nti-pd-1 ntiody is key immune hekpoint drug. The nti-pd-1 ntiody plys key role in tumor therpy (11); hene, it my ply ritil role in EUS guided-fine needle injetion for tumor immunotherpy. In onlusion, lthough definite evidene is lking, immune modultion used y the EUS-FNA proedure might hve ontriuted to lol tumor regression. We onsidered tht EUS-FNA nd the ensuring teril infetion stimulted n immunologil phenomenon nd used the deth of the ner ells in the lymph node. Although further experiments re needed to onfirm this hypothesis, the fine needle injetion of immune-promoting drugs my e useful s tumor redution therpy in the future. The uthors stte tht they hve no Conflit of Interest (COI). Referenes 1. Kiser HE, Bodey B Jr, Siegel SE, Gröger AM, Bodey B. Spontneous neoplsti regression: the signifine of poptosis. In Vivo 14: , Iwng T. Studies on ses of spontneous regression of ner in Jpn in 2011, nd of hepti rinom, lung ner nd pulmonry metstses in the world etween 2006 nd Gn to Kgku Ryoho (Cner & Chemotherpy) 40: , 2013 (in Jpnese, Astrt in English). 3. Erly DS, Aost RD, Chndrsekhr V, Chthdi KV, Deker GA, et l; Committee ASoP. Adverse events ssoited with EUS nd EUS with FNA. Gstrointest Endos 77: , Hirot WK, Petersen K, Bron TH, et l. Guidelines for ntiioti prophylxis for GI endosopy. Gstrointest Endos 58: , Bert F, Briou-Lnelin M, Lmert-Zehovsky N. Clinil signifine of teremi involving the Streptoous milleri group: 51 ses nd review. Clin Infet Dis 27: , Bir AS, For AA, Leve C, Fkih MG. Spontneous regression of oloretl ner metstti to retroperitonel lymph nodes. Antiner Res 29: ,
5 DOI: /internlmediine Choi N, Cho JK, Bek CH, Ko YH, Jeong HS. Spontneous regression of metstti ner ells in the lymph node: se report. BMC Res Notes 7: 293, Triozzi PL, Fernndez AP. The role of the immune response in merkel ell rinom. Cners 5: , Chng KJ, Nguyen PT, Thompson JA, et l. Phse I linil tril of llogenei mixed lymphoyte ulture (ytoimplnt) delivered y endosopi ultrsound-guided fine-needle injetion in ptients with dvned pnreti rinom. Cner 88: , Ris A. Tumor immunotherpy direted t PD-1. N Engl J Med 366: , Toplin SL, Hodi FS, Brhmer JR, et l. Sfety, tivity, nd immune orreltes of nti-pd-1 ntiody in ner. N Engl J Med 366: , The Internl Mediine is n Open Aess rtile distriuted under the Cretive Commons Attriution-NonCommeril-NoDerivtives 4.0 Interntionl Liense. To view the detils of this liense, plese visit ( y-n-nd/4.0/) The Jpnese Soiety of Internl Mediine
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