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Original Article
Evaluation of lymph node re activity in
diffe re ntiate d thyroid carcinoma
Head and Neck Service of Heliópolis Hospital (Hosphel), São Paulo, Brazil
Ali Amar, Abrão Rapoport, Marilene Paladino RosasINTRODUCTION
The develo pment o f metastases is the mo st no table characteristic o f malignant neo plasias. The filter functio n o f lymph no des was suggested last century by Vircho w, which led to the idea o f inc lud ing lymp ha tic tre a tme nt in surg ic a l management o f metastases. Altho ugh such lo cal and regio nal disease co ntro l became a co mmo n o bjective in treatment o f head and neck cancer, it was frequently seen to be inefficient and insufficient. Fro m 1 9 5 3 with the wo rk o f Black et al,1 evidence emerged abo ut the active ro le o f lymph no des in the fig ht a g a inst meta sta ses. The sub seq uent characterization of lymphocyte subpopulations and their distributio n within lymph no des led to studies o f lymphatic reactivity in cancer patients.2 -6 The inco nsistency o f the results, to gether with the fact that the simple existence o f a metastasis co nstituted the main aggravating facto r in the diagno sis o f epidermo id carcino ma, resulted in these findings no t being applied clinically. In the light o f evidence that lymph no des do no t functio n as effective mechanical barriers and their resectio n do es no t significantly impro ve the o verall survival o f these patients, the evaluatio n o f their immuno lo g ical functio n has gained new interest.
The contrasting behavior seen in differentiated
ABSTRACT
Contex t: The develo pment o f metastases is the mo st no table characteristic o f malignant neo plasias. The filter functio n o f lymph no des, which led to the idea o f including lymphatic treatment in surgical management o f metastases.
O bjectives: To evaluate mo rpho lo g ical alteratio ns in neck no des in the presence o f differentiated thyro id carcino ma (DTC): hyperplasia, histio cyto sis, desmo plasia, capsular rupture, necro sis and their relatio n to the bio lo g ical behavio r o f these neo plasias.
Design: Retro spective study.
Setting: University referral unit.
Participants: 9 8 DTC patients, from 1 9 7 7 to 1 9 9 2 , 1 8 cases were selected for histological analyses, of which 1 4 were female and 4 males, with an average age of 5 0 .2 years. From these cases, 2 9 0 lymph nodes were analyzed (8 1 with metastasis), with an average of 1 6 lymph nodes/ patient.
M a in M ea surem ents: Mo rpho lo g ical evaluatio n o f paraffin cuts stained by HE was do ne using an o ptical micro sco pe, lo o king fo r presence o f the abo vementio ned neo plasias and their UICC-TN M (1 9 9 7 ) stag ing .
Results: Sinus histiocytosis was 2 .4 times more frequent in the absence of lymph node metastasis (pNo). Disease recurrence occurred in 5 patients, all of whom were more than 4 0 years old (p= 0 .2 4 ) and 4 of whom had necrosis (p= 0 .0 2 ). Six patients with predominance of paracortical hyperplasia (p= 0 .0 2 ) did not show as much relapse into disease as those with less than 6 metastasis lymph nodes (p= 0 .0 0 9 ).
Conclusions: The presenc e o f pa ra c o rtic a l hyperpla sia is a sso c ia ted with a b etter pro g no sis. The existenc e o f nec ro sis o r meta sta sis in mo re tha n 6 lymph no des in pa tients o ver 4 0 yea rs o f a g e is rela ted to hig her risk o f rela pse o f disea se in DTC.
Key W ords: Differentiated carcino ma. Thyro id. Lymph no de. Reactivity
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thyroid carcinoma (DTC) could contribute new ideas fo r the clarificatio n o f these questio ns, and the evaluatio n o f lymph no de reactivity is justified when the metastatic lymph no des are no t pro gno stic.
Ta ble 1 - Histiocytosis a nd lymph node meta sta ses
Histio cyto sis
Metastases Yes N o
Yes 1 9 6 2
N o 1 2 1 8 8
Ta ble 2 - Age, lymph nodes, necrosis a nd
hyperpla sia versus recurrence
Recurrence
Data Yes N o p-value
Ag e < 4 0 0 5
> 4 0 5 8 0 .2 4
Lymph no des < 6 0 9
> 6 5 3 0 .0 0 9
N ecro sis Yes 4 2
N o 1 1 1 0 .0 2
Paraco rtical Hyperplasia 0 6
Fo llicular Hyperplasia 5 2 0 .0 2
Ta ble 3 - Rela tionship betw een hyperpla sia , histiocytosis a nd meta sta sis
Paraco rtical O ther
Hyperplasia Hyperplasias
Metastasis Yes 2 3 1 8 6
N o 0 2 7 9
Histio cyto sis Yes 1 9 6 9
N o 0 4 1 7
Ta ble 4 - Rela tionship betw een ca psule rupture,
desmopla sia a nd necrosis
Capsule Rupture p-value
Desmo plasia (7 patients) 6 0 .5 9
N ecro sis (6 patients) 6 0 .1 1
Bo th 4 0 .1 4
METHODS
Via a retro spective study o f 9 8 cases o f DTC (mo dified o r recurrent) submitted to cervical neck surg ery at the Head and N eck Service o f Helió po lis Ho spital (Ho sphel), São Paulo , Brazil, fro m 1 9 7 7 to 1 9 9 2 , 1 8 cases were selected to evaluate the lymph no de reactivity in the presence o r absence o f metastasis. There were 1 4 female and 4 male cases, with an ag e rang e fro m 1 0 to 7 5 years o ld (median o f 5 1 ) and a fo llo w-up time fro m 2 to 1 5 5 mo nths (median o f 5 7 ).
The histo patho lo g ical evaluatio n o f lymph no de re a c tivity wa s do ne via mo rpho lo g ic a l analysis under an o ptical micro sco pe o f laminae sta ine d b y he mo to xylin e o sine , using the fo llo w ing c rite ria : hyp e rp la sia (fo llic ula r, pa ra c o rtic a l, mixe d a nd sinus), histio c yto sis, d e smo p la sia , c a p sule rup ture , ne c ro sis, calcificatio n and internal metastasis extensio n (g reater o r less than 5 0 % o f the sectio n surface). The frequency o f the different criteria was evaluated, co nsidering the to tal number o f lymph no d e s a nd the p re se nc e o f me ta sta se s. The c la ssific a tio n o f the p a tie nts fo llo w e d the p re d o mina nt re a c tiva tio n a nd the simp le p re se nc e o f c a p sule rup ture , ne c ro sis, desmo plasia and calcificatio n. The relatio nships b e tw e e n the d iffe re nt fa c to rs a nd w ith the recurrence were all analyz ed.
Statistical Metho ds. The statistical analysis was do ne using Fisher’s exact test with p values o f < 5 %, with the assistance o f G raphpad InstatTM (1 9 9 3 versio n) and EPI IN FO (versio n 6 .0 ).
RESULTS
After the examination of 290 lymph nodes, of which 81 had metastases, sinus histiocytosis was diagnosed in 140 lymph nodes (Table 1 and Fig. 1). Disease recurrence co rrelated with age was o bserved in 5 cases with ages greater than 4 0 years, during a follow-up period of 15 to 45 months. C o mp a ring the a ve ra g e numb e r o f metastatic lymph no des in the g ro up that was free o f disease with the number in the g ro up with re c urre nc e , w e me a sure d 4 . 4 a nd 8 . 4 ,
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re spe c tive ly. Six me ta sta se s w a s c o nside re d predictive o f DTC recurrence. N ecro sis o ccurred in 1 3 metastatic lymph no des in six patients and this reactio n was co nsidered sig nificant.
Table 2 sho ws the evaluatio n o f hyperplasia, fo r which the paraco rtical and fo llicular areas were cho sen fo r the study.
In lymph nodes with paracortical hyperplasia, the number of metastases and histiocytoses was not significant, with 23 lymph nodes being evaluated and metastases being absent in two of them. In other types o f hyperplasia, the relatio nship was 1 8 6 evaluated and 79 with absence. For histiocytosis with paraco rtical hyperplasia, 1 9 lymph no des were positive for metastases and 4 were negative, and with other forms of hyperplasia the relationship was 69 positive and 117 negative lymph nodes (Table 3). Table 4 presents the relatio nship between capsule rupture, desmo plasia and necro sis was measured in 1 3 patients, with o ccurrence in 4 3 metastatic lymph no des. There was mo re than o ne reactio n in 1 0 cases.
DISCUSSION
The inverse relatio n between histio cyto sis and metastasis o ccurs because o f the need fo r lymph no de structures to react against tumo r cells. Berg2 de mo nstra te d tha t histio c yto sis de c re a se d a s metastasis size increased, with predo minance o f this reactivity pattern in non-metastatic lymph nodes, which agrees with o ur experience (Table 1 ). Ho o n et al7 sho wed that when a paraco rtical hyperplasia pattern is present, the incidence o f metastasis and sinus hystio cyto sis is lo w, demo nstrating that there is an effective lympho cyte immune reactio n. This was present in o ur experience (Fig. 1 ).
The relatio nship between disease recurrence and ag e (Table 2 ) leads to the o bservatio n o f wo rse pro g no sis in patients who are mo re than 4 0 years o ld, because o f the incidence o f distant metastasis pro ducing regressive immune status.6 ,8 Reg arding the number o f metastatic lymph no des (Ta b le 2 ), the o c c urre nc e o f mo re tha n 6 me ta sta se s inc re a se s d ise a se re c urre nc e in
Fig. 1 - Sinus histiocytosis – Hematoxylin Eosine / 400x
Fig. 2 - Follicular hyperplasia – Hematoxylin Eosine / 125x
Fig. 3 - Paracortical hyperplasia – Hematoxylin Eosine / 250x
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patients who are mo re than 4 0 years o ld, as also repo rted by o thers.6 ,8 -1 0
The presence o f necro sis (Table 2 ) po ssibly demo nstrates a lo w immune reactio n status in less differentiated neo plasias. At the same time, the simultaneo us o ccurrence o r no n-o ccurrence o f necro sis, desmo plasia and capsule rupture in the same patient (Table 4 ) may sug g est a reg io nal event,1 1 ,1 2 in spite o f these fa c to rs no t b eing pro g no stic. Furthermo re, the inverse relatio nship between disease recurrence and paraco rtical hyp e rp la sia , a nd the d ire c t re la tio nship to fo llicular hyperplasia demo nstrate that the fo rmer is a pro tectio n reactio n to wards the pro liferatio n o f T cells and the latter is a pro liferative pattern that indicates a wo rse pro g no sis1 3 -1 5 (Table 3 ).
Finally, we co nclude that this reactivity pattern in lymph no des sho uld be used ro utinely, in asso ciatio n with new histo chemical reactio ns, so as to differentiate pro g no stic facto rs in the recurrence o f DTC.
REFERENCES
1. Black MM, Kerpe S, Speer FD. Lymph no de structure in patients with cancer o f the breast. Am J Path 1953;24:505-21.
2. Berg JW. Sinus histio cyto sis: a fallacio us measure o f ho st resistance to cancer. Cancer 1956;9:935-9.
3. Bennet SH, Futrell JW, Ro th JA, et al. Pro gno stic significance o f his-to lo gic ho st respo nse in cancer o f the larynx o r hypo pharynx. Can-cer 1971;28:1255-65.
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5. Tsakraklides V, Olso n P, Kersey JH, et al. Pro gno stic significance o f the regio nal lymph no de histo lo gy in cancer o f the breast. Cancer 1974;34:1259-67.
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8. Sugino K, Kure Y, Iwasaki H, et al. Metastases to regio nal lymph no des, lymph no de recurrence, and distant metastases in no n-ad-vanced papillary thyro id carcino ma. Jpn J Surg 1995;25:324-8. 9. Berlinger NT, Tsakraklides V, Po llak K, et al. Immuno lo gic
assess-ment o f regio nal lymph no de histo lo gy in relatio n to survival in head and neck carcino ma. Cancer 1976;37:697-705.
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11. Schantz SP. Bio lo gic staging o f head and neck cancer. Curr. Op. Oto laringo l. Head and Neck Surg 1993;1:107-13.
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RESUMO
O bjetivos: Verific a r a s a ltera ç õ es mo rfo ló g ic a s desenc a dea da s no s linfo no do s c ervic a is na presenç a de c a rc ino ma diferenc ia do da tireó ide (CDT), esta b elec endo a rela ç ã o entre o s a c ha do s: hiperpla sia (fo lic ula r, pa ra c o rtic a l, sinusa l e mista ), histio c ito se, desmo pla sia , ruptura c a psula r, nec ro se, c a lc ific a ç ã o e o c o mpo rta mento b io ló g ic o desta s neo pla sia s.
Loca l: Serviç o de c irurg ia de c a b eç a e pesc o ç o do Ho spita l Helió po lis. M étodo: 1 8 pa c ientes c o m CDT fo ra m sub metido s a esva z ia mento c ervic a l (rec urrenc ia l o u mo dific a do ) de 1 9 7 7 à 1 9 8 8 . Va riá veis estuda da s: Fo ra m a na lisa do s 2 9 0 linfo no do s, sendo 8 1 meta stá tic o s (2 4 ,4 %) – média de 1 6 linfo no do s po r pa c iente. Fo ra m a na lisa do s pela c o lo ra ç ã o HE e a va lia do s pa râ metro s c o mo hiperpla sia (fo lic ula r, pa ra c o rtic a l, sinusa l e mista ), desmo pla sia , histio c ito se, ruptura c a psula r, nec ro se e c a lc ific a ç ã o ) e esta dia do s pelo TN M do UICC de 1 9 9 7 . Resulta dos: a histio c ito se sinusa l fo i 2 ,4 vez es ma is freq üente no s linfo no do s sem metá sta ses (pN o ). A rec idiva da do enç a o c o rreu em 5 pa c ientes, to do s c o m ida de ma io r o u ig ua l a 4 0 a no s (p=0 ,2 4 ), do s q ua is 4 a presenta va m nec ro se linfo no da l (p=0 ,0 2 ). O s pa c ientes c o m hiperpla sia
pa ra c o rtic a l nã o desenvo lvera m rec idiva da do enç a (p=0 ,0 2 ), da mesma fo rma c o mo a q ueles c o m 6 linfo no do s meta stá tic o s (p=0 ,0 0 9 ). Conclusões: a presenç a de histio c ito se tem rela ç ã o inversa c o m a presenç a de metá sta se no linfo no do , e a hiperpla sia pa ra c o rtic a l a sso c ia -se a um melho r pro g nó stic o . A existênc ia de nec ro se o u metá sta se em 6 o u + linfo no do s, em pa c ientes c o m ida de a c ima de 4 0 a no s, a sso c ia -se à rec idiva da do enç a .
Ali Am a r - MD, Surg eo n a t Helió po lis Ho spita l (Ho sphel), Sã o Pa ulo
Abrã o Ra poport - MD, Surg eo n at Helió po lis Ho spital (Ho sphel), São Paulo
M a rilene Pa la dino Rosa s - MD, Patho lo g ist at Helió po lis Ho spital (Ho sphel), São Paulo
Sources of Funding: N o t declared
Conflict of interest: N o t declared
La st received: 2 december 1 9 9 8
Accepted: 2 1 january 1 9 9 9
Address for correspondence:
Abrão Rapo po rt
Praça Amadeu Amaral 4 7 cj 8 2 CEP 0 1 3 2 7 -0 1 0 - São Paulo / SP - Braz il
