Brnchscpic and Rentgengraphic Crrelates f a Psitive Transbrnchial Needle Aspiratin in the Staging f Lung Cancer*. Edward Harrw, M.D., F.C.C.R; Michael Halber, M.D.; Stephen Hardy, M.1:; and Wdliam Halteman, Ph.D. A study was cnducted t determine the brnchscpic and chest rentgengraphic 6ndings assciated with a psitive TBNA. One hundred 6fty-seven f 465 patients wh were diagnsed r the 8rst time as having carcinma fthe lung had a psitive aspirate. Brnchscpic Bdings assciated with a psitive TBNA f N2 ndes were carinai widening and endbrnchial disease, especially f the right upper lbe. Mediastinal adepathy nted n chest rentgengrams and subcaridal ndes n CAT scads were assciated with a psitive aspirate as well. In 34 f465 patients, TBNA was the nly means festablishing the diagnsis fpulm0 nary m a la useful, i ~ simple and safe prcedure, TBNA can be used t stage the mediastinum in patients with lung cancer and is mst likely t be psitive with endbrnchial and ndal disease. It can als racili. therapeutic decisin-making in patients whse surgical candidacy is marginal. (Ched 1991; 100:1592-96) CAT=cmputed axial tmgraphy; nna=tradsbrnchial ~ e aspiratiil T ransbrnchial needle aspiratin, first intrduced in 1958 by Schieppattil fr use with the rigid brnchscpe and mre recently adapted fr the fiberptic instrument by Wang and Terry in 1983, 2 has prved t be quite helpful in diagnsing and staging carcirima fthe lung. While this technique has been used t sample bth endbrnchial and peripheral lesins d i r e its c tefficacy l ~ in staging malignant lung disease by aspirating mediastinal lymph ndes is clearly ne f its mst imprtant applicatins. The indicatins fr its implementatin and the significance fa psitive result, hwever, remain unclear. Althugh the safety f the technique has been repeatedly verified,h there is, as yet, n cnsensus regarding the clinical circumstances in which the technique shuld be used t stage pulmnary malignancies. Fr this reasn, a retrspective study was cnducted t determine the brnchscpic and chest rentgengraphic findings likely t predict a psitive TBNA frm mediastinal ndes. METHODS Frm July f 1983 t June f 1989 the results f1'bna fcarinal and paratracheal ndes perfrmed in Bangr, ME were reviewed. Fur hundred sixty-6ve patients were diagnsed fr the 6rst time t have lung cancer and 157 (34 percent) f them had a psitive TBNA. These patients frm the basis f this s t ubrnchscpy d ~ with TBNA was perfrmed by fur practicing pulmnlgists; cytlgic analysis was accmplished accrding t standard tech- *Frm the Departments f Medicine, Radilgy and Pathlgy f Eastern Maine Medical Center and St. Jseph Hspital, Bangr, and the Department fmathematics, University fmaine, Orn. Manuscript received Nvember 5; revisin accepted March 26. Reprint requests: Dr. Harrw, 417 State Street, Bangr, ME 04401 1512 niques which previusly have been described. 4 Usually, tw carinal (ne anterir and ne psterir) and tw r three paratracbeal aspirates were btained and submitted as a single specimen. Samples were btained frm the carina and the right side f the distal trachea when brnchscpic r radilgic abnrmalities were nted in the right hemthrax. Similarly, carinal and left: paratracheal aspiratin was accmplished when left-sided disease was apparent. Tracheal cmpressin r carina! abnrmalities varied frm subtle t grss. Since it was nt clear t what degree deviatin frm the nrmal anatmy shuld be cnsidered signi&cant and because any abnrmality, albeit slight, might represent underlying pathlgy, any degree f cmpressin r carinal widening was cnsidered abnrmal. All patients with tracheal r carinal abnrmalities bad TBNA fthe carina r paratracheal wall, r bth, althugh patients with multiple areas ftracheal deviatin did nt always have each abnrmal lcatin sampled. The brncbscpic recrd feach fthese patients was reviewed and cded fr blunting r widening f the carina, the presence f tracheal deviatin r cmpressin and the character and lcatin f the brnchial pathlgy by ne f us (E.H.). Iftumr was nted in mre than ne fcal area, it was recrded as being situated in its mst prximal lcatin in the trachebrnchial tree. Because this was a retrspective s t umany d ~ patientshad films talcen at utlying hspitals which were nt readily available fr revievv. Fr that reasn the chest radigraphs f 195 and the CAT scans f 117 fthe mst recent subjects were interpreted and cded by ne Qf us (M.H.) accrding t the TNM system as described by Muntain. 8 Lymph ndes were cnsidered significant if they were at least 10 mm in their shrtest diameter. As all data are cunts, the results were analyzed using either chi-square analysis f cntingency tables r, in the case f small r zer cunts, Fisher's exact test fr 2 X 2 cntingency tables. RESULTS Transbrnchial needle aspiratin was perfrmed in all 465 patients wh were diagnsed fr the first time t have carcinma f the lung, and 157 frm a carinal and/r paratracheal lcatin (N2 ndes) were psitive. TNA In Staging f Lung Cancer (Harrw et8/)
Table I-Frequency fpaitie TBNA ita lmng Cancer Tumr Psitive TBNA % Psitive Small Adencarcinma Large Squamus Prly differentiated Sarcma Ttal Significant at p = 0.áá O O. Sixty-fur percent fpatients with small cell carcinma and 26 percent f patients with nn-small cell carcinma had a psitive mediastinal aspirate. Table 1 demnstrates the results fr each tumr type. Widening r blunting fthe carina (Table 2) was crrelated with a psitive TBNA (p=o.ooo) while tracheal cmpressin was nt. The presence fan abnrmal brnchscpic examinatin was assciated with a psitive TBNA (p<0.005) althugh the type flesin (intralumenal vs extrinsic cmpressin) was nt significant (Table 3). The lcatin fthe lesin within the trachebrnchial tree was t e w Tumr r t h invlving ~ the right upper lbe rifice was mre likely t yield a psitive N2 aspirate than carcinma invlving the left upper lbe (59 vs 32 percent). These findings were significant (p = 0.(01). Lesins in the trachea and main stem brnchi did nt, hwever, have a statistically higher likelihd fhaving psitive mediastinal ndes n TBNA than thse in the ther and mre distal areas fthe trachebrnchial tree (Table 4). In additin t brnchscpic findings, standard Table I-Crrelatin fpaitive TBNA with TrachetJl Appearance n Brnchacpy Brnchscpic Exatninatin Carina Nrmal Abnrmal Trachea Nrmal Cmpressin Right side Left side Anterir Psterir Multiple sites Significant at p=o.ooo. Table 3-Brnchacpic Finding. in lbtienta with a Psitive TBNA Brnchscpy Nrmal Intrinsic lesin Extrinsic cmpressin Significant at p<o.oo5. 620 97 350 104 36 0 113 230 142 10 4 Ofl 157 f465 Psitive TBNA 105 f366 52 f99 1150 373 42 0 92 14 f23 70 23 30f5 110 28 70f13 N. 26 f157 630 157 68 f157... z ~. 34 32 16 25 34 % Psitive 29 53 31 46 61 30 60 39 54 % Psitive 17 40 43 Table 4-Crrelatin fbrnchial Tumr l.dctjtin with G paititje TBNA Trachea 7 f13 (54 percent), Right brnchus Prximal 13 20 (65%) Distal 40 9 (44%) Right upper lbe Lbar* 43 f73 (59%) Segment.8 f21 (38%) Brnchus intermedius 6 f25 (24%) Right middle lbe 8 f 19 (42%) Right lwer lbe Apical 2 f7 (29%) Lbar 6 f21 (29%) Basal 2 f4 (50%) Signi6cant at p = 0.001. Table 5-Chat Rentgengraphic Findings with a POIitit1e TBNA-Lymphatknpatlay % Psitive Ndal size N. TBNA NO (all <10 mm) 160 77 21 Nl (hilar >10 mm) 18 f60 30 N2 (Paratracheal and 26 f55 47 subcarinal > 10 mm) >10& <15mm 110 24 46 >15 &'<20 mm 10fl 100 >20mm 140f21 66 Indeterminate 20 9 22 N3 (cntralateral) 20f3 66 Significant at p = 0.0055. Left brnchus Prximal 6 f8 (75%) Distal 5 f24 (21%) Left upper lbe Lbar 26 f82 (32%) Segment 30 19 (16%) Lingula 1 r8 (12%) Left lwer lbe Apical 20r8 (25%) Lbar 6 21 (29%) Basal 0 f3 (0%) chest rentgengrams and CAT scans were examined t determine which radigraphic findings were assciated with a psitive TBNA fthe mediastinum. Nt surprisingly, increasingsize and central lcatinfthe lymph ndes were assciated with a psitive TBNA (Table 5). The difference between N-Nl and N2-N3 ndes was significant at p<o.oo55. Examinatin f parenchymal shadws 00 chest rentgengrams revealed that psitive aspirates were nted even with small lesins since 8 f21 Tl lesins had a malignant cytlgic aspirate. Further review suggested that as the lesin extended t the midline, the likelihd fa psitive N2 aspirate increased (Table 6); hwever, these bservatins were nt statistically significant. Finally, parenchymal and ndal findings n chest rentgengrams were matched with mediastinal TBNA results t determine the likelihd fbtaining a psitive mediastinal aspirate when peripheral lesins withut demnstrable mediastinal adenpathy were nted (Table 1). Small peripheral lesins alne (stage TlNO) had a lw yield (1 f 11 psitive); hwever, the presence f enlarged hilar ndes in patients with peripheral parenchymal disease appeared t crrelate with a malignant N2 cytlgy (5 f 11 psitive). CHEST I 100 I 8 I DECEMBER, 1991 1583
Table 6-Chat Rentgengraphic Findinga with a P8itie TBNA-PanmchymtJllaina Table 8-Cheat CAT Scan Firadinga with a Pdtice TBNA-PanmchymtJllaina % Psitive CJ, Psitive Stage N. TBNA Lesin N. TBNA TO (n parenchymal lf3 33 TO (n parenchymal 00 2 0 shadw) shadw) TI «3 em surrunded 80f21 38 TI «3 em surrunded 40 11 36 T2 36 f106 34 T2 13 f29 45 A (>3 em surrunded 70 28 25 A (>3 em surrunded 10 7 14 8 (extends t visceral 10 9 II 8 (extends t pleura 30f5 60 pleura) r diaphragm) C (atelectasis/pneumnia 28 0 69 41 C (extends t hilum) 90 17 53 extends t hilus) T3 13 f53 24 T3 120 50 24 A (extends t chest 7 f20 35 A (extends t chest 30f18 17 wall) wall rdiaphragm) B (extends t 6 f33 18 B (extends t mediastinum) 9 f32 28 mediastinum) T4 90f15 60 T4 90 23 39 A (malignant effusin) 90 14 64 A (malignant effusin) 40 9 44 B (invades vertebrae) 00 0 0 B (invades vertebrae) 10fl 100 C (invades mediastinum) 00 1 0 C (invades mediastinum) 40 13 31 Findings n CAT scans als shwed that the extent fparenchymal disease did nt crrelate well with the frequency f a psitive TBNA (Table 8). Aspirates f mediastinal ndes were psitive 35 t 40 percent f the time when CAT scans shwed either hilar r mediastinal a d e n The p a absence t h ~ f adenpathy predicted a lw yield, while the presence fsubcarinal lymph ndes greater than 20 mm in size increased the likelihd f a psitive mediastinal aspirate significantly (p<0.01) when cmpared with lymph ndes f lesser size r thse in the paratracheal psitin (Table 9). In 34 f 465 cases (7 percent), TBNA f the mediastinum was the nly way lung cancer was diagnsed. Small cell carcinmawas the mst cmmn type in this subset f patients-13 cases. Other than minr bleeding which never caused airway cmprmise, hypxemia r bld lss requiring transfusin, Table 7-Frequency fa PaiOOe TBNA in PeriplaertJllaina witla and withut Hiltw AtI.erapGtIay n Chat Rentgengramthere were n significant cmplicatins in the 465 cases. There was ne false-psitive result, ie, n clinical r surgical evidence fneplastic disease in a patient with TBNA cytlgy reprted as being unequivcally malignant. This patient, admitted with pneumnia, had a left upper lbe infiltrate with hilar a d e n p a t h ~ A brnchscpic examinatin revealed nly inflammatry changes, but the left paratracheal TBNA shwed malignant cells. Mediastinscpy and mediastintmy; hwever, bth f ~ te demnstrate d malignant disease as did a repeat brnchscpy with TBNA. Fllw-up fr 1V2 years has failed t reveal either a recurrent infiltrate r tumr. Other than minr bleeding which never caused airway cmprmise, hypxemia r bld lss requiring transfusin, there were n significant cmplicatins in the 465 cases. Table 9-Chat CAT Scan Findinga willa Paitive T B N A - U J m p ~ Stage N. Percent TINO 10fll 9 T2NO 2 f26 8 A 2 f20 10 8 00f6 0 TINI 30 5 60 TiNI 20 6 33 A 20f5 40 B 00 1 0 Ttal 80 48 17 *Tl-lesiD <3 em surrunded by lung; T2A-Iesin >3 em surrunded by lung; T28-lesin >3 em extending t pleura r diaphragm; NO-hilar and mediastinal ndes <10 mm; Nl-hilar ndes >10 mm, mediastinal ndes <10 mm. Lymph Nde NO (all < 10 mm) Nl (hiiar > 10 mm) N2 (mediastinal>10 mm) Paratracheal >10 <15 mm Subcarinal > 10 <15 mm Paratracheal > 15 <20 mm Subcarinal > 15 <20 mm Paratracheal >20 mm Subcarinal >20 mm Indeterminate N3 (cntralateral>10 mm) Significant at p=o.oi. N. 00 21 60 18 300 70 30 11 10 6 lf5 00 1 50f16 200 30 00 1 30 9 'II Psitive TBNA 33 43 27 17 20 31 66 33 1514 TNA In StagIng f Lung cancer (HarfOW.t8/)
DISCUSSION Althugh a number fauthrsn have described the diagnstic efficacy f TBNA and demnstrated its capability in detecting the presence' f,mediastinal disease, the circumstances in which this technique shuld be emplyed t stage lung cancer and hw a psitive result shuld be interpreted remain uncertain. 7 8 Shure and Fedull0 3 and Shure 8 suggested that TBNA be perfrmed either in the presence f radilgically abnrmal ndes r endbrnchial tumr while Gay and Brutinel 9 used it fr staging nly when mediastinal disease was dcumented n chest tmgrams r CAT scans. S i m OSchenk O I ~ et al" suggested that it be used in patients with mediastinal adenpathy nted n either chest rentgengrams r CAT scans since they fund that TBNA was psitive in ne half f the patients ultimately determined t be unresectable due t mediastinal invasin. Our results were examined in the hpe fassessing thse circumstances in which TBNA fr staging purpses wuld be fvalue. The findings suggest that an abnrmal brnchscpic examinatin r the presence f radilgically demnstrable mediastinal disease is frequently assciated with a psitive TBNA f N2 ndes. Nt s u r p r i scarinal i n g l disease ~ nted n brnchscpy resulted in a substantial number f psitive aspirates. While ur results with carinal abnrmalities gave higher yields than thse reprted by thers, 3 this may be due t the fact that paratracheal and carinal specimens were bth btained and cmbined fr cytlgic examinatin rather than carinal aspirates alne. Ntewrthy was the determinatin that right upper lbe malignant disease f the majr lbar rifice was clearly assciated with a psitive TBNA. While disease f the distal trachea and prximal main stem brnchi appeared t result in high yields (65 t 67 percent), these findings were nt statistically higher than ther areas nted t be abnrmal n the brnchscpicexaminatin. Als finterest was the fact thattbna psitivity remained cnsiderable (25 t 30 percent) with middle and lwer lbe endbrnchial tumrs and did nt appear t decline as lesins became mre distally lcated within the trachebrnchial tree. Why right-sided tumrs mre frequently were assciated with a psitive TBNA cmpared with leftsided lesins is unclear. Ruviere 10 and Warren and Drinker,l1 in their studies fthe lymphatic drainage fthe lungs, reprted that the inferir and mid prtin fthe left lbe drain t the right side fthe mediastinal lymphaticchain. Baird,12 inhis reviewftheliterature, hwever, stated that the evidence t supprt this was weak. His study f surgical specimens shwed that upper lbe neplasms have ipsilateral spread althugh lwer lbe neplasms spread mre cmmnly t the infracarinal ndes frm the right lung than frm the left. Nhl,13 in his study flymphatic invlvement in lung cancer, suggests anther explanatin fincreased right-sided psitive aspiratins since he describes the left paratracheal area as having a relative paucity f lymph ndes when cmpared with the right. Of interest t the clinician is the extent t which chest rentgengraphic findings, and, in particular, a peripherally lcated lesin is likely t yield a psitive mediastinal cytlgy ntbna. Fr that reasn, chest radigraphs and CAT scans were crrelated with the findings n aspiratin f N2 ndes. The presence f mediastinal adenpathy n standard chest rentgengrams r enlarged subcarinal ndes n CAT scans strngly crrelated with a psitive aspirate. On the ther hand, the absence f significant adenpathy (hilar r mediastinal ndes <10 mm) was assciated with a negative aspirate-afinding previusly reprted by Schenk et al." Since histlgic study has shwn that up t 40 percent fmediastinal ndes less than 1 cm in size have metastatic disease,i" it is clear that a negative TBNA by n means precludes the mediastinal spread ftumr. The lcatin and extent f parenchymal disease n chest rentgengrams and CAT scans did nt crrelate with the frequency f a psitive mediastinal TBNA. Hwever, peripheral lesins withut assciated hoo r mediastinal disease rarely were assciated with a psitive TBNA. These bservatins appear t cnfirm the recmmendatins fthers3.. 9 that endbrnchial lesins are mst likely t yield a psitive aspirate, as are patients with radilgically demnstrable adenpath): Right upper lbe lesins, in particular, were assciated with a high yield, but N2 aspirates with endscpically visible tumrs in mre distal areas fthe trachebrnchial tree still were als psitive in 25 percent f the cases. Standard chest radigraphic findings in this study did nt identify a particular parenchymal pattern r tumr lcatin that was clearly assciated with a psitive N2 aspirate. The CAT scans were particularly helpful in predicting a negative result since there were n psitive aspirates in patients withut either hilar r mediastinal lymph nde enlargement. Where, then, des TBNA fit in the diagnstic armamentarium fr the staging f lung cancer? Endbrnchial and especially right upper lbe disease appears t give the highest yield and it wuld seem that TBNA shuld be perfrmed rutinely in circumstances where there is endbrnchially visible tumr r hilar r mediastinal lymphadenpathy is apparent n chest rentgengrams r CAT scans in patients wh are nt clearly inperable n clinical grunds alne. This study as well as several thersl-s have repeatedly cnfirmed the safety f this technique. In 7 percent fur cases, TBNA alne was the sle means f establishing the diagnsis f lung cancer and in CHEST I 100 I 6 I DECEMBER. 1991 1595
these patients it precluded the necessity f mre invasive diagnstic prcedures. Because f this, we feel that while desirable, the infrmatin prvided by cmputerized chest tmgraphy is nt essential. H, hwever, a CAT scan perfrmedprirt brnchscpy fails t demnstrate the presence f either enlarged hilar r mediastinal lymph ndes, then TBNA is nt warranted. F i n athere l 1 ~ are a number f patients with lung cancer wh have Significant cexistent pulmnary r cardivascular disease where resectinal surgery, while nt precluded n bjective grunds alne, is apprached with cnsiderable trepidatin. A psitive TBNA which, in this setting, dcuments the presence f mediastinal invlvement (even if nt evident n standard rentgengraphic examinatin f the chest) is ften quite helpful in permitting the clinician t preclude further cnsideratin fresectinal surgery. In these patients the prffmediastinal invlvement with tumr by a safe and simple prcedure like TBNA may be justified even in thse circumstances where a high diagnstic yield is nt anticipated. ACKNOWLEDGMENTS: The authrs wish t acknwledge the helpful cmments f Dr. Cliffrd Rsen, the data cllectin perfrmed by Frieda Davis and Karen Jhnsn, and the secret8rial assistance f Patrice Pler. REFERENCES 1 Schieppati E. Mediastinal lymph nde puncture thrugh the tracheal carina. Surg Gynecl Obstet 1958; 110:243-46 2 Wang n Terry PB. Transbrnchial needle aspiratin in the diagnsis and stagingfbrnchgenic carcinma. Am Rev Respir Dis 1983; 127:344-47 3 Shure D, Fedull E The rle ftranscarinal needle aspiratin in the staging f brnchgenic carcinma. Chest 1984; 86:693 96 4 Schenk DA, Bwer JH, Bryan CL, Currie RB, Spence TH, Duncan CA, et ale Transbrnchial needle aspiratin staging f brnchgenic carcinma. Am Rev Respir Dis 1986; 134:146-48 5 Harrw EM, Oldenburg FA, Lingenfelter MS, Smith AM. Transbrnchial needle aspiratin in clinical practice-afive-year experience. Chest 1989; 96:1268-72 6 Muntain CF. A new internatinal staging system fr lung cancer. Chest 1986; 89(suppl):225-335 7 Kvale PA. Transbrnchial needle aspiratin-is it cming fage? Chest 1985; 88:161-62 8 Shure D. Transbrnchial needle aspiratin-current status. May C Prc 1989; 64:251-54 9 Gay PC, Brutinel WM. Transbrnchial needle aspiratin in the practice f b r n cmay h C s cprc ~ 1989; 64:158-62 10 Ruviere H. Anatmie des lymphatiques de l'hmme. Paris: Massn, 1932 11 Warren MF, Drinker CK. Flw flymph frm lungs fthe dg. Am JPhysill942; 136:207-21 12 Baird JA. The pathways flymphatic spread fcarcinma fthe lung. BrJ Surg 1965; 52:868-75 13 Nhl HC. The spread f carcinma f the brnchus. Lndn: Uyd-Luke Ltd, 1962 14 McKenna RJ, Libshitz HI, Muntain CE, McMurtrey MJ. Bentgengraphic evaluatin f mediastinal ndes fr preperative assessment in lung cancer. Chest 1985; 88:206-10 1_ TNA In Staging f Lung cancer (Hanw etai)