MALIGNANT AXILLARY LYMPHADENOPATHY -

Transcription

1 MALIGNANT AXILLARY LYMPHADENOPATHY - A PROBLEM FOR MANAGEMENT C T Lim, R Nambiar ABSTRACT Axillary lymph nod nlargmnt can b th first and only manifstation of malignancy. Although lymphoma and mtastasis from mlanoma, brast and lung cancrs ar known causs, th primary tumour may rmain undtctd in som cass dspit xhaustiv invstigations. Thrfor, onc th diagnosis of malignancy is confirmd by clinical xamination followd by histology, furthr invstigations should b limitd to a sarch for tratabl malignancis only. Extnsiv invstigations with a hop of discovring th primary is uslss and not cost ffctiv. Clos follow up may occasionally rval nw clinical signs whn furthr invstigations can b justifid. This papr rports th clinical approach to diagnosis and managmnt of such cass with xampls of illustrativ cass. Kywords : axillary lymph nod, mtastasis, mlanoma, brast carcinoma, lymphoma, lung carcinoma SINGAPORE MED J 1991; Vol 32: INTRODUCTION Enlargd lymph nods in th axilla, lik crvical lymphadnopathy, may b th first prsnting fatur of malignancy in patints though this is lss commonly ncountrd in clinical practic. Unlik crvical lymph nod mtastasis whr th primary tumour is prdominantly in th had and nck rgions, malignancy in th axillary lymph nods is usually du to lymphoma or mtastasis from primary tumour in th brast, lung or skin. Lss frquntly th primary sits includ thyroid gland, gastrointstinal tract and kidny. Th challng in th managmnt of a patint prsnting with nlargd axillary lymph nod lis in stablishing th diagnosis of malignancy and th sit and typ of th occult primary tumour, both of which influnc th tratmnt and prognosis of th patint. Th four cass blow rprsnt a varity of malignancis which prsntd initially as "a lump in th armpit. CASE 1 A 76 -yar -old Chins man, prsntd with a right axillary lump and backach for on month. H had no othr systmic symptoms whatsovr. On xamination, his gnral condition was satisfactory. A firm mobil lump of 4 cm in diamtr was palpatd in th right axilla. His livr was palpabl at 8 cm blow th costal margin. Chst radiograph was normal but lumbar spin radiographs showd rtrolisthsis of L3 vrtbra ovr L4. Th CT scan of abdomn confirmd hpatomgaly with multipl livr noduls, nlargd para -aortic lymph nods and tumour in th L3 vrtbral body. As th fin ndl aspiration cytology of th axillary lymph nod showd only lymphocyts, an xcision biopsy of th lymph nod was prformd. Histology rvald follicular larg cll non -Hodgkin lymphoma (Fig la & b). Th patint was tratd with chmothrapy and radiothrapy with satisfactory rspons. CASE 2 A 69 -yar -old Chins lady, had a 3 -cm diamtr lump in hr right axilla xcisd in a clinic on month prior to hr consultation. Th histology of th xcisd lump rvald adnocarcinoma. On xamination, no abnormality was dtctd in hr brasts. Howvr, a mammogram dmostratd a lsion suspicious of malignancy in hr right brast (Fig 2a & b). A total mastctomy with axillary claranc was don. Histology confirmd a 1 -cm diamtr infiltrativ duct carcinoma in th uppr mdial quadrant of th brast (Fig 2c). No furthr lymph nod mtastasis was dtctd in th xcisd axillary tissu. Following sugry, sh was givn Tamoxifn. Fig la - Follicular lymphoma involving an axillary lymph nod. (20X. H&E). Fig lb - Highr magnification showing an infiltrat of abnormal larg lymphoid clls (200X. H&E) Dpartmnt of Surgry Singapor Gnral Hospital Outram Road Singapor 0316 C T Lim, MBBS, FRCS (Edin & Glas) Rgistrar R Nambiar, FRCS (Eng & Edin), FRACS Snior Surgon & Had Corrspondnc to : Prof R Nambiar 409

2 CASE 3 A 24 -yar -old Chins lady, complaind of a lump in hr right axilla for on month. Th lump was gradually gtting biggr and painful. Two yars ago, sh had a 0.5 cm diamtr papillomatous lump on hr right latral chst wall xcisd by a gnral practitionr and th histology was rportd as Spitz Fig 2a & b - Mammograms of cas 2. Th clinically impalpabl brast cancr lsion is sn as an ara of fin microcaicification. cal valuation including histochmical tsts confirmd malignant mlanoma (Fig 3a & 3b). A right axillary claranc was don but did not show any mtastasis in th rmaining lymph nods. A rviw of th prviously xcisd lump from th chst wall rvald it to b a mlanoma. Four months aftr th axillary claranc, th patint was notd to b fr of furthr mtastasis. CASE 4 A 63 -yar -old Chins man, prsntd with a lump in his right armpit for two wks. H had a long history of tobacco consumption. On xamination, mild clubbing of his fingrs wr notd. A 2 -cm diamtr mobil lymph nod was prsnt in his right axilla. Clinical xamination of his chst licitd signs of consolidation on th uppr zon of his right lung and a chst radiograph showd this to b a larg soft tissu mass in th right uppr lob (Fig 4a & b). Fin ndl aspiration cytology yildd clumps of malignant clls with littl cytoplasm (Fig 4c). Flxibl bronchoscopy rvald tumour in th right uppr bronchus which on biopsy was rportd as oat cll carcinoma. H was givn palliativ radiothrapy. Fig 3a - Fin ndl aspirat cytology of a mtastasis malignant mlanoma. Tumour clls show abundant cytoplasm. H&6:) Fig 2c - Infiltrativ lobular carcinoma of th brast which was not palpabl and prsntd as a mtastasis to th axillary lymph nod. (100X. H&E) navus. On xamination, a 4 -cm diamtr firm mobil lymph nod was palpatd in hr right axilla. No lsion was dtctd in hr brasts, chst and on th skin. Hr livr was not palpabl. Chst radiograph and mammogram did not rval any lsion. Fin ndl aspiration cytology of th lump did not indicat any malignancy. Th lymph nod was xcisd. Frozn sction rvald carcinoma of undtrmind origin. Furthr pathologi- i da k $....ffi :,. ti Stlarsarr b? t.. 1 r., á 8,,2 {...V4 y 1r`...is.;! i :. s " Lpsl! y,l. }..:. `..ï ;., s æ.... :.a S._ %`ti. {A4,..ó _r a %., aa i a 8.,y 6 j 0.0,r + 8..":04~ s us i a{.l.{é ;i J g1:n ` -.Ix..f+t S. 4 R. p. *its.: ,- ì Y ^ L -,1 B-..-a. tiy r.-,..:.iii.. M rl x aa, ^.2. ``q.`+i`:--.r :..... y t Y V.M., lpr S ` : + 1 b],.y \I {`(T fli! i. tita l y^y4 a, Q :.r. v) t,/i\.sc.yk;i. I. P)1r,! )!f}i `i,to :. Fig 3b - Mtastatic malignant mlanoma invading th subcapsular sinus of an axillary lymph nod. (200X. H&E) \`t`.. -. ti : d4 á!y2ivf1{l.i ii Si1r.Ç ñr.!, {x;,ivl i9/.crt31ay1sï :t,i Y--..1,-.4.1;t1:.;!.4 g?gr Vlti -YR+..i ilwt`iptcffl a,. 1T91 ;.Y. i. )Ia it;1.t/,.: `ld..-1+-l Cf,7.,)w il^?_:n l.m.íñ!!,.t.bii...4.l YÁ!JR}1. a.iu`3,.-t. a DISCUSSION Patints prsnting with axillary lymphadnopathy ar ncountrd not infrquntly in clinical practic. Although th majority of th cass may b bnign, th probability of mtastatic lymphadnopathy bing th first prsnting symptom of malignancy is high. In a study of 72 patints prsnting with unilatral axillary lymphadnopathy, 76.4% was du to bnign lsions, lymphoma accountd for 13.9%, and mtastass wr found in th rmaining 9.7%tit. In womn, th most likly primary sit for mtastasis in th axillary lymph nods is th brast as sn in Cas 2("). Rarly such a prsntation can occur in mad. Primary m- 410

3 Fig 4a - Chst X-ray of cas 4 dmonstrating a tumour in th uppr zon of th right lung. It 4 Fig 4b - CT scan of cas 4 rvaling a larg solid lsion in th sam rgion. YIRITdOY.n dimm- ]MIPJ 09:S9 IR4 1- {7111. `v Fig 4c - Fin ndl aspirat cytology of a mtastic at cll carcinoma to th axillary lymph nod. Clustr of small clls with hyprchromatic nucli showing nuclar moulding ar sn. (200X. Papanicolau) ; k. y 04. r : - i, : :. its..ay.,.,. i spt,s -.1 ` t, ::, : y. S %..S oi y :, / n.* P inc, 4rZ v. t t+.>. si +.4 : i. -.. r mours in th lung and skin ar also common sourcs of mtastass to th axillary lymph nods as illustratd by thr cass prsntd hr. Lss frquntly, th axillary mtastasis may aris from primary tumours in th thyroid gland, gastrointstinal tract, ovary and kidnys"t. In an adult, an nlargd, discrt axillary lymph nod should b considrd malignant, ithr mtastatic or primary, till provn othrwis). This was th clinical approach in all th four.cass hr. Th managmnt should bgin with a dtaild history and a thorough clinical xamination of all possibl primary sits (Fig 1). Initial imaging invstigation should includ a chst radiography and mammogram in womn. If th patint had undrgon surgical rmoval of any skin lump, birth mark or othr lsion, vry attmpt must b mad to obtain th histological rport as wll as th histological slids of th xcisd spcimn. A scond histological opinion must b obtaind to valuat th diagnosis. Such ffort was fruitful in Cas 3, in whom a bnign Spitz nvus was th initial diagnosis but on histological rviw, th diagnosis was confirmd to b a malignant mlanoma. Unncssary invstigations for th occult primary tumour can b avoidd in this way. Ilistopathological Diagnosis Fin ndl aspiration cytology (FNAC) may provid a prliminary diagnosis of malignancy and aid th tratmnt plan. This procdur, prformd in th clinic, is quick, asy and saf. Howvr, an xprincd pathologist must b availabl to xamin th smars. Th ovrall snsitivity of FNAC for mtastass in suprficial lymph nods was found to b as high as 96.5%0. Howvr, FNAC for lymphoma is known to b lss accurat, bing snsitiv in only 67.5%. Thr wr no fals positiv instancs but th fals ngativ rat was 11.3%. Howvr, th diagnosis of bnignity should not b confirmd without an opn biopsy of th lymph nod. If th FNAC is positiv for malignancy and th primary lsion is still not idntifid at this stag, furthr invstigations basd on th cytology ar don to locat th primary sit. FNAC was don in thr cass but th histological diagnosis was obtaind in only on patint, Cas 4. In Cas 1, although lympohocyts wr sn in th FNAC, th diagnosis of lymphoma could only b mad on th xcisd lymph nod. In Cas 3, th typ of malignancy was difficult to diagnos histologically and th diagnosis of malignant mlanoma was concludd only aftr histochmical studis. Th most important stp in patint managmnt is to obtain an accurat histologic diagnosis, particularly in cass in which th FNAC rvals malignant clls and th primary lsion rmains obscur. An xcision biopsy of th lymph nod should b don at this stag whn th history, clinical xamination and invstigations ar still inconclusiv. Howvr, xcision biopsy of th lymph nod must b avoidd bfor th patint lias bn thoroughly valuatd for th occult primary tumour. This happnd in Cas 2 whr th lymph nod was xcisd bfor a mammogram was don. Th clinician has to liais closly with th pathologist whn opn biopsy of th lymph nod is don. Th whol lymph nod should b xcisd and snt frsh to th pathologist who will portion it for frozn sction, paraffin sction, immunohistological studis, and lctron microscopys4.9t. Th valu of an xprincd pathologist cannot b ovrmphasisd in this xrcis. Occult Primary Tumour Mtastatic cancr from an occult primary tumour is dfind as histologically provn mtastatic carcinoma in which no primary sit bn idntifid dspit a thorough history, carful physical xamination and scrning tsts. This is found in 3 to 411

4 Plan of Managmnt of Unilatral Axillary Lymph Nod Enlargmnt History Clinical Examination spcially brast, lung, skin, thyroid, abdomn Appropriat Invstigations, g full blood count, chst radiograph, mammogram Primary Lsion Suspctd No Primary Lsion Found Furthr Invstigations to Localis Tratmnt of th Bnign/Malignant Diss 1 v Fin Ndl Aspiration Cytology of Nod Ngativ/Suspicious For Malignancy Positiv for Malignancy Furthr Appropriat Invstigations 1 EXcision Biopsy of Axillary Lymph Nod J y Bnign Malignant (Unknown Primary Tumour) Appropriat Tratmnt y No Primary Tumour Found Lymphoma Primary Tumour Found -j Tratmnt of Malignant Disas 4 Mlanoma trat with axillary claranc Adnocarcinoma to look for brast, prostat, ovary, thyroid tumours Othrs palliativ tratmnt Small Cll Undiffrntiatd Tumour to look for lympoma, bronchognic carcinoma, Erwings sarcoma 4% of all thos prsnting with malignancyt0>. This group of patints poss a challnging and somwhat controvrsial problm in diagnosis and tratmnt. Th aim of idntifying th primary sit is to hav a bttr dirctd tratmnt for th patint. Numrous studis hav strssd th futility of ovr invstigations; th tim and xpnss involvd, th low dtction rat, th lack of ffctiv tratmnt whn th primary is found, and abov all, th strss and discomfort brought to an alrady symptomatic patintt<.m> In a study of 254 patints with mtastass from occult primary tumour, it was rportd that mdian survival priod was only nin months with a rang of on to 215 months. Th two yar survival rat was 15%, th thr yar and fiv yar rats wr 11% and 9% rspctivly. Ninty-thr prcnt did from th tumour whil th rmaindr did from othr causst" t. Larg Cll Undiffrntiatd Tumour to look for lymphoma, xtragonadal grm cll tumour In anothr rport on 46 patints with mtastatic adnocarcinoma or undiffrntiatd tumour from occult primary, th mdian survival priod was only 20 wks from th tim of histologic diagnosist" t. Although invstigations ar rquird to dtrmin th sit of th primary tumour as wll as th xtnt of th disas, th succss rat of idntifying th primary sit is low. In a rviw of 87 patints with unknown primary adnocarcinoma or undiffrntiatd carcinoma, th invstigators could dtct th primary tumour aftr xtnsiv non surgical invstigations in only 8 patintsm). Grnbrg and Lawrnct"t approachd this problm by sarching for th most tratabl malignancis, whn th pathologist is abl to classify th mtastasis into on of th thr groups; adnocarcinoma, small cll undiffrntiatd cancr and larg cll undiffrntiatd cancr. Tratabl adnocarcinomas ar brast, prostat, ovary and thyroid tumours. Tratabl small cll cancrs ar bronchognic carcinoma, lymphoma and 412

5 Ewings sarcoma- Tratabl larg cll undiffrntiatd cancrs includ lymphoma and xtragonadal grm cll tumour. This classification would dtrmin th nd for furthr invstigations to locat th occult primary tumour. If th primary tumour rmains unidntifid aftr xtnsiv work -up, th clinician should stop furthr invstigations and giv supportiv tratmnt to th patints with unknown primary adnocarcinoma and undiffrntiatd carcinoma as th mdian survival priod is only about 20 wks from th tim of diagnosis. In som cntrs, mpirical systmic chmothrapy, g 5 flurouracil, doxorubicin and mithomycin C, is adminstrd to ths patints. Advocators of this tratmnt rgim claimd a rspons rat of 30% and a mdian survival rat of 14 months for thos who rspondd to th tratmnt, although th drug - rlatd mortality rat was about 9%. Othr invstigators hav not substantiatd such optimistic rsultst4t. Occult brast carcinoma is dfind as histologically provn carcinoma of th brast with axillary nodal involvmnt in a patint who has manifstd no signs or symptoms of any abnormality of th brastm. Th ag distribution was similar to that of brast carcinoma in gnral. Th rasons givn for th failur to dtct th primary sit in th brast includ th small siz of th primary lsion, th dp location of th lsion within th brast, and surrounding inflammatory raction. Mammogram should b don and any suspicious lsion is biopsid with mammographic localisation bfor th axillary lump is xcisd. Howvr, a ngativ mammogram dos not rul out th prsnc of an occult brast tumour. Patl t alo rportd six out of ight patints with axillary mtastass and positiv or suspicious mammography wr found to hav brast cancr, as compard to only four out of nin with ngativ mammography. If thr is no abnormality in th brast or a brast biopsy is normal, thn an xcision of th axillary mass is don. During xcision, whthr th lump is in th lymph nod or in th tail of th brast should b dtrmind. Estrogn and progstron rcptor assays should b don on th xcisd spcimn as this may idntify th primary tumour. Also, this may b th only opportunity to dtrmin th stroid hormon rcptor status of th malignancy bcaus in som cass, aftr sctioning th xcisd brast tissu, th primary tumour is nvr found or th quantity of tumour tissu is inadquat for th hormon rcptor analysism. Th high frquncy with which th brast is ultimatly found to hav th primary tumour sit has ld many clinicians to rcommnd modifid radical mastctomy. A primary brast tumour will b found on carful sctioning of th brast in ovr 50% of th cass. Radiothrapy without mastctomy as th primary tratmnt is usually not rcommndd. Th survival rat of patints with occult brast cancr is similar or somwhat bttr than that of patints with clinically ovrt brast cancr/24.r). Th incidnc of unknown primary mlanoma is rportd to b in th rang of 4 to 9%. Typically, thr is no history to suggst th primary tumour, and th diagnosis is mad aftr biopsy of an nlargd lymph nod or rsction of a viscral mtastasis(). Mlanoma is postulatd to aris d novo in lymph nods, rsulting in apparnt lymph nod mtastasis with no obvious primary ]. Th most accptd xplanation of unknown primary mlanoma is th spontanous rgrssion of a primary cutanous lsion. Th clinician must always find out if th patint has undrgon any prvious xcision of "bnign" mol or skin lump as in Cas 3. If xcision has bn prformd, th histologic spcimn must b r-valuatd. In th physical xamination, th skin is sarchd carfully for possibl primary. Any suspicious lsion is biopsid. An ophthalmoscopy is don as wll. Th xtnt of mtastass is also assssd in th physical xamination and by chst radiography, livr function tst, livr scan and brain scan. If ths studis do not rval dissminatd disas, a radical lymphadnctomy of th axilla is pr- formd114"81 Th outcom of patints with unknown primary mlanoma is highly variabl, ranging from apparnt cur to rapid tumour dissmination and dath. CONCLUSION Th four clinical cass prsntd hr rprsnt th common varity of malignancis that may occur in axillary lymph nods. Th clinician must b alrt to th possibility of malignancy whn an adult patint prsnts with a singl larg discrt lymph nod in axilla. In th work -up to locat th primary tumour, th clinician must dvis a plan of managmnt that is cost-ffctiv. A dtaild history is takn, a thorough clinical xamination conductd, rlvant invstigations carrid out and FNAC don to dtrmin th prsnc of malignancy in th axillary lymph nod. If th FNAC is ngativ for malignancy or if th FNAC is positiv for malignancy and th primary tumour rmains unknown, an xcision biopsy of th lymph nod is carrid out aftr liaising with th pathologist. Th xcisd lymph nod is snt frsh to th pathologist who will thn prform th rlvant analyss on th spcimn to arriv at a diagnosis. Th tratmnt and prognosis will dpnd ntirly on th histological diagnosis. ACKNOWLEDGEMENT Th authors would lik to thank Dr Carol Kwan of Dpartmnt of Pathology, SGH for hr hlp with histological illustrations. REFERENCES I. Pirc El t, Gray HK, Dockry MB. Surgical significanc of th isolat axillary adnopathy. Ann Surg 1957; 145: Fignbrg Z, Zr M, Dintsman M. Axillary mtastasis from an unknown primary sourc. Isr 1 Md 1976; 12: Copland EM, McBrid CM. Axillary mtastass from unknown primary sits. Ann Surg 1973; 178: Grnbrg BR, Lawrnc IIJ. Mtastatic cancr with unknown primary. Md Clin North Am 1988; 72: Patl 1, Nmoto T Rosnr D t al. Axillary lymph nod mtastasis from an occult brast cancr. Cancr 1981; 47; Fttrman L, Atti JN, Rosnbrg B. Carcinoma in axillary lymph nods as an indicator of brast cancr. Surg Gyncol & Obstt 1962;114: Own 11W, Dockrty MB, Gray IIK. Occult carcinoma of th brast. Surg Gyncol Obstt 1954; 98: Martlli G, Piloni S Lpra Pt al. Fin ndl aspiration cytology in suprficial lymph nods: An analysis of 266 cass. Eur J Surg Oncol 1989; 15: Garbrn AO, Ric P t al. Mtastatic malignant disas of unknown origin. Am 1 Surg 1983; 145: Stckl RJ, Kagan AR. Diagnostic prsistnc in working up mtastatic cancr with an unknown primary sit. Radiology 1980; 134: Didolkar MS, Famous N, Elias EG, Moor RH. Mtastatic carcinomas from occult primary tumours. Ann Surg 1977; 186: McMillan JII, Lvin E, Stphns RH. Computd tomography in valuation of mtastatic adnocarcinoma from an unknown primary sit. Radiology 1982; 143: Stwart JF, Tattrsall, Woods RL, Fox RM. Unknown primary adnocarcinoma: Incidnc of ovrinvstigatin and natural history. Br Md ; 1: Klop CT. Mtastatic cancr of axillary lymph nod without a dmonstrabl primary lsion. Ann Surg 1950; 1311: Ostn RT, Kopf G, Wilson RE. In pursuit of th unknown primary. Am J Surg 1978; 135:

6 16. Giuliano Ali, Mosly 11S, Morton DL. Clinical aspcts of unknown primary mlanoma. Ann Surg 1980; 191: Gupta D, Bowdn L, Brg J. Malignant mlanoma of unknown origin. Surg Obsts Gyncol 1969; 128: Panagopoulos E. Mtastatic malignant mlanoma of unknown primary origin: A study of 30 cass. J Surg 1980; 191: