O r i g i n l A r t i c l e Singpore Med J 2006; 47(10) : 851 Brest crcinoms: why re they missed? Muttrk M, Pojchmrnwiputh S, Chiwun B ABSTRACT Introduction: Mmmogrphy hs proven to e n effective modlity for the detection of erly rest crcinom. However, 4-34 percent of rest cncers my e missed t mmmogrphy. Delyed dignosis of rest crcinom results in n unfvourle prognosis. The ojective of this study ws to determine the cuses nd chrcteristics of rest crcinoms missed y mmmogrphy t our institution, with the im of reducing the rte of missed crcinom. Methods: We reviewed the reports of 13,191 mmmogrms performed over five-yer period. Brest Imging Reporting nd Dt Systems (BI-RADS) were used for the mmmogrphicl ssessment, nd reports were cross-referenced with the histologicl dignosis of rest crcinom. Cuses of missed crcinoms were clssified. Results: Of 344 ptients who hd rest crcinom nd hd mmmogrms done prior to surgery, 18 (5.2 percent) filed to e dignosed y mmmogrphy. Of these, five were cused y dense rest prenchym oscuring the lesions, 11 were due to perception nd interprettion errors, nd one ech from unusul lesion chrcteristics nd poor positioning. Conclusion: Severl fctors, including dense rest prenchym oscuring lesion, perception error, interprettion error, unusul lesion chrcteristics, nd poor technique or positioning, re possile cuses of missed rest cncers. Keywords: rest cncer, mmmogrphy, missed dignosis Singpore Med J 2006; 47(10):851-857 INTRODUCTION Mmmogrphy is currently the most sensitive method for the detection of erly rest crcinom (1). Screening mmmogrphy is used to detect cliniclly-occult rest crcinom, while dignostic mmmogrphy is performed for ssessing symptomtic ptients or to further evlute n normlity detected on screening mmmogrphy. Nevertheless, most studies hve reported sensitivity of cncer detection in the rnge of 68-92% (2). Some occult cncers, even when plple, my not e evident t mmmogrphy. Delyed dignosis of rest crcinom results in n unfvourle prognosis. The ojective of this study ws to determine the cuses nd chrcteristics of rest crcinoms missed y mmmogrphy t our institution, with the im of reducing the rte of missed crcinom. METHODS We retrospectively reviewed 13,191 reports of mmmogrms performed over five-yer period from Jnury 1999 to Decemer 2003. Two stndrd mmmogrphy views were performed using dedicted film-screen unit (LoRd MIII, Dmurg, CT, USA). Mmmogrms of ech ptient were interpreted immeditely fter imging ws completed y one of two rest rdiologists. Additionl mmmogrphicl views or ultrsonogrphy (US) were performed on the sme dy. We used the Brest Imging Reporting nd Dt Systems (BI-RADS) (3) for the mmmogrphicl ssessment. Reports were cross-referenced with the histologicl dignosis of rest crcinom otined from the records of the Deprtment of Pthology. A flse-negtive mmmogrm ws defined s one in which ptient hd pthologicl dignosis of rest crcinom within one yer fter negtive or enign mmmogrphicl result. A flse-negtive mmmogrm ws lso scried to cses when the Deprtment of Rdiology Ching Mi University 110 Intvroros Rod Ching Mi 50200 Thilnd Muttrk M, MD Professor Pojchmrnwiputh S, MD Assistnt Professor Deprtment of Pthology Chiwun B, MD Associte Professor Correspondence to: Prof Mli Muttrk Tel: (66) 53 945 450 Fx: (66) 53 217 144 Emil: mmuttr@ mil.med.cmu.c.th
Singpore Med J 2006; 47(10) : 852 lesion could e seen retrospectively more thn yer lter. We defined true-positive mmmogrm s one in which the mmmogrphy ws reported s BI-RADS 5 (highly suggestive of mlignncy), nd BI-RADS 4 (suspicious normlity) nd the ptients were susequently pthologiclly dignosed to hve rest cncer. The sensitivity (percentge of rest cncers tht were identified with mmmogrphy) ws clculted y [truepositive/(true-positive+flse-negtive)] 100. The mmmogrms of those with missed cncers were nlysed y two rest rdiologists who were wre tht ech ptient hd rest crcinom ut were linded with respect to the loction of the tumours. Cuses of missed crcinoms were ctegorised into five types, nmely: (1) Dense rest prenchym oscuring lesion; (2) Perception error; (3) Interprettion error; (4) Unusul lesion chrcteristics; nd (5) Poor technique or positioning. The rest prenchyml density, fetures of the tumour, nd loction of the tumour were lso recorded. We nlysed the dt with descriptive sttistics. This study ws pproved y the Ching Mi University Institutionl Review Bord. RESULTS 805 ptients with rest crcinom were dignosed from pthologicl reports. Of these, 362 hd mmmogrphicl exmintions efore surgery ut mmmogrms were ville for review in only 344 ptients. Of the 344 ptients studied, 18 (5.2%) were considered to e missed dignosis, ccording to the criteri listed in the preceding section. The men ge of the ptients ws 50.8 yers (rnge 45-66 yers). The overll sensitivity of mmmogrphy in identifying crcinom ws 94.7%. Five of 18 ptients hd dignostic mmmogrphy nd 13 hd screening mmmogrphy. All five dignostic ptients presented with rest msses. Three of these five ptients hd multiple cysts with sutle re of rchitecturl distortion in one, fint pleomorphic microclcifictions in one, nd dense rest without mmmogrphicl normlity in the other one. In the other two ptients, one hd circumscried mss nd ws misinterpreted s complex cyst, one hd synchronous rest crcinoms with lesion on one side which ws missed due to poor positioning on the first exmintion. The clssifiction of rest prenchyml density in missed crcinoms ws heterogeneously dense in 17 ptients nd homogeneously dense in one. Types of missed crcinoms re shown in Tle I. Fetures of missed crcinoms re shown in Tle II. Loction of the tumours is shown in Tle III. Of these 18 ptients, one ws invsive loulr crcinom (ILC), four were ductl crcinom in situ, nd 13 were invsive ductl crcinom. According to TNM tumour stging, four were stge 0, seven were stge I, nd seven were stge II. Illustrtive cses re shown in Figs. 1-6. Tle I. Resons for missed crcinom. Reson for missed crcinom Numer of cses Dense rest prenchym 5 Perception error 7 Interprettion error 4 Unusul lesion chrcteristics 1 Poor positioning 1 Totl 18 Tle II. Mmmogrphicl fetures of missed rest crcinom. Mmmogrphicl feture Numer of cses Mss 4 Microclcifictions 2 Architecturl distortion 5 Asymmetricl density 2 No lesion seen 5 Totl 18 Tle III. Loctions of missed rest crcinom. Loction Numer of cses Lterl 6 Medil 1 Centrl 5 Retroglndulr 2 Sureolr 4 Totl 18 DISCUSSION The proportion of cncers missed y mmmogrphy vries widely in the literture, rnging from 4% to 34% (4,6-9). This wide rnge is due to the mny different nd vrile wys it hs een clculted nd reported in the literture. Comprison mong studies re difficult ecuse the popultions tht re considered my vry, from screening of
Singpore Med J 2006; 47(10) : 853 symptomtic ptients to symptomtic ptients referred for mmmogrphy. The qulity of mmmogrphy nd the experience of reders my lso not e uniform. The filure to detect cncer on mmmogrm my e cused y mny fctors, including dense rest prenchym oscuring lesion, sutle fetures of mlignncy, perception error, interprettion error, unusul lesion chrcteristics such s slow-growing tumours, nd poor technique or positioning (6-9). Five of our missed rest crcinoms occurred in ptients with dense rests (Fig. 1). The normlity ws not visile, even in retrospect. In fct, missed crcinoms hve een shown in multiple studies to occur more frequently in dense rests (4-6). Missed cncers were lso reported to e less dense, reltive to the immedite surrounding tissue (7). Clinicl rest exmintion nd US re commonly used to complement mmmogrphy nd more cncers re detected with these comintions (9-11). Techniques of digitl mmmogrphy, mgnetic resonnce imging nd nucler medicine studies for rest cncer screening re eing developed, nd my hve future role in improving the detection of rest cncer in ptients with dense firoglndulr tissue (9). Although we usully perform dditionl US in ptients with dense rests, we still missed the dignosis in the five ptients. This my e explined y the size nd type of the tumours. The smller the tumour size, the more likely they re to e missed. Tumours were smll in four screening ptients tht could e esily missed from oth mmmogrphy nd US. The other ptient presented with plple rest msses with negtive mmmogrphy ut US reveled multiple cysts. She ws susequently found to hve ILC. ILC is known to e difficult to dignose either y clinicl exmintion or imging due to the lck of desmoplstic rection (8). The overll sensitivity of US in the detection of ILC ws 68% (12). Perception nd interprettion errors re the most common cuses of our missed crcinoms (11/18), similr to the studies y Bird et l (6) nd Mrtin et l (13). Perception nd interprettion errors re cused y severl fctors, including deficient trining, lck of experience, sutle fetures of mlignncy, presence of n ovious finding, ftigue, inttention, hste, poor viewing conditions, nd distrctions. Sutle fetures of mlignncy re difficult to perceive. These sutle fetures re smll fint densities tht re visile on only one of the two views (Fig. 2), Fig. 1 Dense rest. () Screening ilterl mediolterl olique mmmogrms of 47-yer-old womn show dense rest without mss or microclcifictions. Two months lter, she returned nd complined of plple mss in the right upper outer qudrnt (RUOQ); () US imge of the RUOQ shows 1.5 cm irregulr hypoechoic mss. Excisionl iopsy reveled intrductl crcinom, cririform type with microinvsion. fint microclcifictions, or miniml rchitecturl distortion (Fig. 3). The presence of n ovious finding (Fig. 4) leding to overlooking of nother more sutle lesion is one of the common cuses of oservtion error (8,9). Two of our ptients who presented with rest msses were found to hve multiple circumscried msses on mmmogrms, leding to overlooking of the smll re of
Singpore Med J 2006; 47(10) : 854 c d Fig. 2 Perception error: lesion seen on one view. Screening mmmogrms of 45-yer-old womn. () Bilterl crniocudl (CC) views, nd () ilterl mediolterl olique (MLO) views, show dense rest nd fint focl incresed density (rrow) in the left retrommmry region seen on the CC view. Seven months lter, she returned nd complined of plple mss in the left rest. (c) Bilterl CC views, nd (d) ilterl MLO views, show 3-cm, ill-defined mss in the left retrommmry region. Fig. 3 Perception error: sutle rchitecturl distortion. Screening mmmogrms of 54-yer-old womn who hd history of left mstectomy for rest crcinom three yers go. () Right CC view tken two yers fter left mstectomy shows sutle rchitecturl distortion (rrow); () Right CC view otined one yer fter () clerly shows the lesion. rchitecturl distortion in one cse nd fint pleomorphic clcifictions in nother cse. Misinterprettion occurs when n normlity is oserved ut is interpreted s eing enign or proly enign lesion. We hd four misinterprettions. Of these, two hd enignppernce mss (Fig. 5), one hd fint pleomorphic microclcifictions, nd the other one hd n re of distortion seen on one view. They were interpreted s proly enign lesions nd were suggested to hve follow-up study. Trining nd experience re essentil for rdiologists responsile for mmmogrphicl interprettion. To void perception nd interprettion errors, rdiologists who interpret mmmogrms should hve specil trining in mmmogrphy. Right nd left rest mmmogrms of ech stndrd projection should e mounted ck-to-ck on view oxes. Creful ttention to mirror imge normlities or focl normlities is importnt, in order to identify
Singpore Med J 2006; 47(10) : 855 Fig. 5 Interprettion error, enign ppering mss. Bilterl MLO screening mmmogrms of 44-yer-old womn show 1 cm well-circumscried mss in the left sureol region. The lesion ws interpreted s cyst. Four months lter, she returned nd complined of plple lump in the left sureol. Excisionl iopsy reveled intrductl crcinom. Fig. 4 Perception error, presence of ovious lesions. Bilterl CC views of the sme rest in 51-yer-old womn who presented with left rest msses in () 1999 nd () 2000, show enign-ppering msses in the left rest (M) tht were found to e cysts on US. An re of rchitecturl distortion in the right reol (rrows in,) ws overlooked in 1999. Histology reveled invsive ductl crcinom. the sutle fetures of mlignncy. Additionl views my e needed to etter verify the lesion. The mrgins of msses nd chrcteristics of microclcifictions re est evluted with spot-compression nd mgnifiction views. A circumscried crcinom should lwys e considered in peri- or postmenopusl women who present with circumscried solid mss, since firodenom is not common in this ge group. Whenever fesile, the current mmmogrphicl exmintion should e compred with previous mmmogrms to look for new or progressive increse in density. Optiml viewing conditions needed for reding mmmogrms include view oxes with dequte luminnce, reduced extrneous light, nd low mient room light. Distrctions, such s the telephone nd checking of other non-mmmogrphicl exmintions, should e minimised. Doule reding hs een shown to llow detection of n dditionl 5%- 15% of cncers (14,15). Nevertheless, there is lck of mnpower in mny plces nd the cost of incresed mnpower is lso prolem. Computerided detection nd dignosis (CAD) represent reltively new technology tht my emerge in some mmmogrphy fcilities for doule reding. The CAD systems increse the sensitivity of rest cncer detection y rdiologists y up to 20% (16,17). Unusul lesion chrcteristics, such s lesion tht is locted in the deep retroglndulr region, enign ppernce, lck of desmoplstic rection,
Singpore Med J 2006; 47(10) : 856 d e c Fig. 6 Slow-growing crcinom. Bilterl screening CC views of the sme rest in 60-yer-old women otined in () 1994, () 1995, (c) 1997, (d) 1998, nd (e) 1999, show smll ill-defined mss in the inner qudrnt of the right rest tht ppered unchnged over four-yer period ut ws incresed in size in the 1999 films nd ws reported s suspicious. Histology reveled invsive ductl crcinom. nd slow or no growth, my e overlooked or missed during interprettion. In our study, one ptient hd lesion tht ws unchnged over four-yer period (Fig. 6). Poor mmmogrphicl positioning nd technique is nother common cuse of missed crcinom. One ptient with synchronous rest crcinoms in our study presented with left rest mss tht ws found to hve rest crcinom. However, eight months lter, she cme ck with plple mss in the right rest. The lesion ws locted deep in the retroglndulr region which ws not included in the first exmintion. High-qulity mmmogrphicl imges enhnce the rdiologist s ility to interpret mmmogrms with high sensitivity nd specificity. Imging should e free from rtifcts, nd performed with dequte exposure, high contrst, high resolution, proper compression, nd inclusion of the mximum mount of rest tissue (8,9,18).
Singpore Med J 2006; 47(10) : 857 A well-positioned mediolterl olique view is indicted y visulistion of the pectorlis muscle to the level of the nipple, convex ppernce of the pectorlis muscle, visulistion of the retroglndulr ft, rest tissue tht is well-compressed nd positioned in n up-ndout orienttion, nd n open infrmmmry fold. Findings on the crniocudl view tht indicte proper positioning include visulistion of the retroglndulr ft, nipple tht is profiled, inclusion of ll the medil firoglndulr tissues, nd the lterl firoglndulr tissue of the rest extends eyond the edge of the film. The difference etween the posterior nipple line mesurement on the mediolterl olique nd crniocudl views should not exceed 1 cm (19). In conclusion, recognition of these vrious fctors is instructive nd will help to decrese missed crcinoms in the future. ACKNOWLEDGEMENT We re grteful to the Ching Mi University Endowment Fund for supporting this reserch. REFERENCES 1. Tr L, Vitk B, Chen HH, et l. The Swedish two-county tril twenty yers lter. Updted mortlity results nd new insights from long-term follow-up. Rdiol Clin North Am 2000; 38:625-51. 2. Ynksks BC, Schell MJ, Bird RE, Desrochers DA. Ressessment of rest ccncers missed during routine screening mmmogrphy: community-sed study. AJR Am J Roentgenol 2001; 177:535-41. 3. Americn College of Rdiology. Brest Imging Reporting nd Dt System (BI-RADS), 2nd ed. Reston, VA: Americn College of Rdiology, 1995. 4. Wllis MG, Wlsh MT, Lee JR. A review of flse negtive mmmogrphy in symptomtic popultion. Clin Rdiol 1991; 44:13-5. 5. Mnn BD, Giulino AE, Bssett LW, et l. Delyed dignosis of rest cncer s result of norml mmmogrms. Arch Surg 1983; 118:23-4. 6. Bird RE, Wllce TW, Ynksks BC. Anlysis of cncers missed t screening mmmogrphy. Rdiology 1992; 184:613-7. 7. Goergen SK, Evns J, Cohen GPB, McMilln JH. Chrcteristics of rest crcinoms missed y screening rdiologists. Rdiology 1997; 204:131-5. 8. Huynh PT, Jrolimek AM, Dye S. The flse-negtive mmmogrm. RdioGrphics 1998; 18:1137-54. 9. Mjid AS, de Predes ES, Doherty RD, Shrm NR, Slvdor X. Missed rest crcinom: pitflls nd perls. RdioGrphics 2003; 23:881-95. 10. Moss HA, Britton PD, Flower CD, et l. How relile is modern rest imging in differentiting enign from mlignnt rest lesions in the symptomtic popultion? Clin Rdiol 1999; 54:676-82. 11. Crystl P, Strno SD, Shchrynski S, Koretz MJ. Using sonogrphy to screen women with mmmogrphiclly dense rests. AJR Am J Roentgenol 2003; 181:177-82. Comment in: AJR Am J Roentgenol 2004; 182:259-60. 12. Prmgul CP, Helvie MA, Adler DD. Invsive loulr crcinom: sonogrphic ppernce nd role of sonogrphy in improving dignostic sensitivity. Rdiology 1995; 195:231-4. 13. Mrtin JE, Moskowitz M, Milrth JR. Brest cncer missed y mmmogrphy. AJR Am J Roentgenol 1979; 132:737-9. 14. Thurfjell EL, Lernevll KA, Tue AA. Benefit of independent doule reding in popultion-sed mmmogrphy screening progrm. Rdiology 1994; 191:241-4. Comment in: Rdiology 1994; 193:582. 15. Hulk CA, Slnetz PJ, Hlpern EF, et l. Ptients opinion of mmmogrphy screening services: immedite results versus delyed results due to interprettion y two oservers. AJR Am J Roentgenol 1997; 168:1085-9. 16. Wrren Burhenne LJ, Wood SA, D Orsi CJ, et l. Potentil contriution of computer-ided detection to the sensitivity of screening mmmogrphy. Rdiology 2000; 215:554-62. Errtum in: Rdiology 2000; 216:306. Comment in: Rdiology 2003; 226:597-9. 17. Brem RF, Schoonjns JM. Rdiologist detection of microclcifictions with nd without computer-ided detection: comprtive study. Clin Rdiol 2001; 56:150-4. 18. Eklund GW, Crdenos G, Prsons W. Assessing dequcy of mmmogrphic imge qulity. Rdiology 1994; 190:297-307. 19. Bssett LW, Hirwi IA, DeBruhl N, Hyes MK. Mmmogrphic positioning: evlution from the view ox. Rdiology 1993; 188:803-6.