lymph node surgery in papillary thyroid carcinoma

Lymph Node Surgery in Papillary Thyroid CarcinomaErnst Gemsenjager, MD, Aurel Perren, MD, Burkhardt Seifert, PhD, Georges Schuler, MD,Ingrid Schweizer, MD, Philipp U Heitz, MD

BACKGROUND: The impact of nodal disease remains controversial in papillary thyroid carcinoma (PTC).STUDY DESIGN: One surgeon treated 159 unselected patients, who were followed up for 1 to 27 years. We

present a retrospective analysis with respect to nodal disease. Occult nodal disease was investi-gated, including metachronous nodal disease (mpN1) in primarily node negative patients (pN0,clinical [c]N0).

RESULTS: Therapeutic lymphadenectomies, prophylactic lymphadenectomies, or no lymphadenectomywere carried out in 42 (cN1), 29 (cN0), and 88 (cN0) patients, respectively, with stage pN1 in 41(98%), in 5 (17%), and in 2 (2.3%) patients, respectively (17% versus 2.3% p � 0.005).Sensitivity and specificity of clinical staging were 85% and 99%, respectively. More frequentprophylactic lymphadenectomy during the study period (p � 0.002) led to a nonsignificantincrease in stage pN1 (26% versus 30%). Immunohistochemistry led to upstaging of only 3%of histologically negative nodes and one (4%) pN0 patient. Nodal recurrence occurred in 8 of156 patients (5%) treated for cure, in 12% of pN1 versus 3% of pN0 cN0 tumors (p � 0.009),in 15% of TNM high-versus 3% of low-risk patients (p � 0.006), and in 5% each of patients,younger than 45 and 45 years or more. In TNM high-risk patients, tumor-related survival was50% for stage pN1 versus 86% for stage pN0, cN0 (p � 0.03) (100% and 100% in low-riskpatients).

CONCLUSIONS: The rate of occult nodal disease might be relatively low, and it does not frequently progress toclinical recurrent disease. Clinical nodal status might be valid for deciding the extent andradicality of node dissection. Prophylactic (central) lymphadenectomy should be carried outwithout radicality-associated morbidity. Macroscopic nodal disease warrants more rigorous,compartment-oriented lymphadenectomy. There is no rationale for detection of occult diseaseand micrometastasis by frozen section or immunohistochemistry. ( J Am Coll Surg 2003;197:182–190. © 2003 by the American College of Surgeons)

Optimal treatment for differentiated thyroid carcinoma(DTC) is controversial with respect to extent of thyroidresection, extent and technique of nodal dissection, anduse of prophylactic radioiodine treatment.1,2 In the ab-sence of controlled prospective studies, retrospective re-sults from manifold institutions are of interest. We con-ducted a 27-year retrospective study of a prospectivelydocumented personal series of DTC.3 The treatmentstrategy was selective use of less extensive therapy inselected low-risk patients, ie, with a low risk of recur-rence (curable).3,4 We present the results with respect to

lymph node status and dissection in papillary thyroidcarcinoma (PTC). During the study period, prophylac-tic lymphadenectomy was introduced. We examined theaccuracy of clinical nodal staging. The occurrence ofoccult nodal disease was investigated by histologic exam-ination of clinically negative nodes in patients with pro-phylactic lymphadenectomy, by immunohistochemicalanalysis (IHC) of histologically negative nodes, and byfollowup with respect to metachronous nodal disease(nodal recurrence) in node-negative patients. In this se-ries, occult nodal involvement was not a major clinicalproblem.

METHODSA total of 159 unselected consecutive patients sufferingfrom PTC were treated and followed from 1974 to2000; 156 patients were treated with curative intent.Clinical, operative, and pathologic data were assessed

No competing interests declared.

Received July 11, 2002; Revised February 27, 2003; Accepted February 27,2003.From the Surgical Clinic, Spital Zollikerberg (Gemsenjager, Schweizer), andthe Departments of Pathology (Perren, Schuler, Heitz) and Biostatistics (Se-ifert), University of Zurich, Zurich, Switzerland.Correspondence address: Professor Ernst Gemsenjager, Surgical Clinic, SpitalZollikerberg, CH. 8125 Zollikerberg/Zurich, Switzerland.

182© 2003 by the American College of Surgeons ISSN 1072-7515/03/$21.00Published by Elsevier Inc. doi:10.1016/S1072-7515(03)00421-6

prospectively. The records of 149 patients described pre-viously3 were updated. The patients were operated on byone surgeon (EG) or under his assistance. The treatmentstrategy consisted of a restricted interventional approachin selected low-risk patients.3,4 Followup in survivingpatients (n � 153) was 1 to 27 years (mean 8.1 years,median 6.0 years).

The histopathologic assessment was conducted byone pathologist (PhUH) and his staff, according to theWorld Health Organization classification.5 Patients withPTC were classified according to the age-related prog-nostic TNM classification system.6

ImmunohistochemistryParaffin blocks from 38 patients were available for im-munohistochemical examination. A total of 245 lymphnodes negative by conventional hematoxylin and eosinhistology were examined. Immunohistochemistry wasperformed on 4�m thin paraffin sections using an auto-mated Ventana BenchMark (Ventana, Tucson, AZ)stainer according to the manufacturer’s instructions. Inbrief, immunohistochemistry for cytokeratin was per-formed after 4 minutes of Protease 1 (Ventana) pretreat-ment using an antipancytokeratin antibody (Lu-5,1:250, Biomedicals AG, Augst, Switzerland). Thyreo-globulin staining was performed after 15 minutes of heatpretreatment in CC1 (Ventana) using a polyclonal anti-thyroglobulin antibody (1:30, rabbit polyclonal anti-bodies; Dako, Glostrup, Denmark). The biotinylatedsecondary antibodies were then visualized using diami-nobenzadine as chromogen according to the manufac-turer’s instruction (Ventana).7

LymphadenectomyNodal status was evaluated by clinical, ultrasound (since1986, with fine-needle aspiration biopsy in some pa-tients), and intraoperative macroscopic exploration,with a careful search for tracheoesophageal, Delphian,and upper mediastinal nodes of suspicious, glassy ap-pearance. In patients with macroscopic nodal involve-

ment (ie, with clinical stage N1 [cN1]6), therapeutic cen-tral or lateral lymphadenectomy (or both) wasperformed. This usually consisted of a systematic en blocnodal dissection of the central compartment (level VI),and in an ipsilateral selective neck dissection comprisingthe levels III and IV and including levels II and V whenthey were involved.

Since 1993, prophylactic (elective) central lymphad-enectomy has been performed in several patients withpre- and intraoperatively proved PTC, in the absence ofsuspicion of nodal involvement (cN0). No prophylacticnode dissection was performed with completion thy-roidectomy because of postoperative tissular changesthat render dissection more hazardous. As opposed tosystematic (en bloc) node dissection for therapy, prophy-lactic lymphadenectomy consisted of a less radical pro-cedure, ie, sampling, uni- or bilateral excision of peritra-cheoesophageal adipose tissue in fragments, some ofwhich contained macroscopically discernible, nonsuspi-cious small nodes.

Nodal positivity was determined as pN1 status at pri-mary treatment or with inclusion of metachronousnodal disease (mpN1) in patients who initially had apN0 status or who had no lymphadenectomy, in theabsence of clinical nodal disease (cN0). Nodal recurrencewas defined as reappearing nodal involvement in ini-tially pN1 patients 1 year or more after primary treat-ment, with nodal reoperation, or as mpN1 in initiallycN0 and pN0 patients.

The numbers of true-positive (TP), true-negative(TN), false-positive (FP), and false-negative (FN) clini-cal intraoperative diagnoses of nodal disease were noted.Sensitivity was calculated as TP/(TP � FN), and speci-ficity was calculated as TN/(TN � FP).

Statistical analysisNominal variables were compared between groups ofpatients using Fisher’s exact test. Numbers of nodes werecompared using the Mann-Whitney test. Pairwise com-parisons within patients were performed using Wilcox-on’s signed rank test. Survival and nodal recurrenceswere analyzed using Kaplan-Meier curves. Groups ofpatients were compared using the log-rank test. P valuesless than or equal to 0.05 were considered statisticallysignificant. Because of the low number of events, nomultivariate analysis was carried out.

Abbreviations and Acronyms

DTC � differentiated thyroid carcinomaPTC � papillary thyroid carcinomaIHC � immunohistochemical analysiscN � clinical nodal stagempN1 � metachronous pathological nodal involvement

183Vol. 197, No. 2, August 2003 Gemsenjager et al Lymphadenectomy in Thyroid Carcinoma

RESULTSSix of 159 patients died from carcinoma and 1 patient isalive with disease, all in the high-risk category (TNMstages III and IV) and including 6 with initial nodaldisease (pN1) and 3 with nodal recurrence. Stage distri-bution, treatment, and deaths from tumor are summa-rized in Table 1.

Clinical macroscopic (cN) and pathologic (pN)nodal stage.Forty-two of 159 patients (26%) had macroscopic evi-dence or suspicion of node positivity (cN1), and a pri-mary therapeutic lymphadenectomy was performed(Table 2). Pathologic stage was pN1 (true positive) in 41of 42 (98%) and pN0 (false positive) in 1 patient.

In 29 of 159 patients (18%) without clinical nodaldisease (cN0), a prophylactic (elective) lymphadenec-tomy was carried out, with pathologic stage pN1 (falsenegative) in 4 of 29 (14%) and stage pN0 (true negative)in 25 patients (86%). In 1 pN0 patient, a nodal recur-rence (metachronous disease, mpN1) occurred (false-negative rate 5 in 29 patients [17%]). Eighty-eight of159 patients (55%) without clinical, macroscopic intra-operative nodal involvement (cN0) had no primarylymphadenectomy (and no microscopic nodal examina-tion); in 2 patients, a nodal recurrence (mpN1) devel-oped, and a metachronous therapeutic lymphadenec-tomy was performed (false-negative rate 2.3%).

pT stagespT stages6 in primary N0 patients (n � 114) were pT1

(� 1 cm) in 36 (32%), pT2 (� 1 cm–4 cm) in 47 (41%),pT3 (� 4 cm) in 10 (9%), and pT4 (tumor extendsbeyond the thyroid capsule) in 21 patients (18%), re-spectively. For stage pN1 (n�45), the values were 5(11%), 18 (40%), 5 (11%), and 17 (38%), respectively.

Adjuvant treatment131I was administered at primary treatment to 6 of 41patients with pT1 tumor (15%), 35 of 65 patients withpT2 tumor (54%), 6 of 15 with pT3 tumor (40%), and24 of 38 with pT4 tumor (63%), respectively. Forty-three of 45 patients (96%) with stage pN1 received 131Iat primary treatment versus 28 of 114 patients (25%)with stage pN0, cN0 (p�0.0001).

Nodal statusIn sum, 48 of 159 patients (30%) had primary (n�45)or metachronous (n�3) nodal involvement (pN1),whereas 111 patients (70%) had no primary or meta-chronous nodal disease (pN0 n�25, cN0 without recur-rence n�86). These values are based on elective (pro-phylactic) lymphadenectomy in 25% of clinically N0

patients (29 of 117).Assuming elective lymphadenectomy and a false-

negative rate of 14% in all clinically N0 patients, anincidence of 36% (41 � 16 of 159) of truly N1 statuscan be deduced. When the 3 patients with metachro-

Table 1. Primary Treatment, Nodal Recurrence, and Death by Risk Groups (n � 159)

Treatment

TNM stage, n (%)

Total (%)I II III IV

Hemithyroidectomy 31 8 4 (1)* 0 27Total thyroidectomy 31 (2)† 13 1 (1)* 0 28Total thyroidectomy, 131I 29 (2)† 17 23 (3)*(4)† 2 (2)* 45Total (n) 91 38 28 2Total (%) 81 19 100

*Death (n � 6), alive with disease (n � 1).†Nodal recurrence (n).

Table 2. Pathologic and Clinical Nodal Stage in 159 Patients with Papillary Thyroid Carcinoma

Clinical nodal status Lymphadenectomy pN statusWith metachronouspN1 (initial N0) (n)

With nodal recurrence(initial pN1) (n)

cN1 (n � 42) 42 therapeutic* pN1 (n � 41) 5pN0 (n � 1) 0

cN0 (n � 117) 29 prophylactic† pN1 (n � 4) 0pN0 (n � 25) 1

88 none 2

*Systematic.†Sampling.

184 Gemsenjager et al Lymphadenectomy in Thyroid Carcinoma J Am Coll Surg

nous nodal involvement are included, the true rate of N1

status would be 38% ([57 � 3] of 159).In patients with primary node dissection (n�71), the

positive predictive value was 98% (41 of 42 patients),and the false-negative rate was 14% (4 of 29 patients),resulting in a sensitivity of 91% (41 of 45 patients) anda specificity of 96% (25 of 26 patients). When meta-chronous results in 88 cN0 and 26 pN0 patients aretaken into account (ie, 3 patients with mpN1), the false-negative rate was 6% ([4�3]/117 patients), the sensitiv-ity was 85% (41 of 48 patients), and the specificity was99% ([24�86]/110�1] patients). The overall accuracywas 95% ([159�8]/159 patients).

Variation during the study periodThe frequency of clinical nodal disease and of therapeu-tic lymphadenectomy did not change between the peri-ods 1974 to 1992 and 1993 to 2000 (18 of 69 [26%]versus 24 of 90 [27%]). In contrast, the frequency ofprophylactic lymphadenectomy increased (from 5 of 69[7%] to 24 of 90 [27%] patients; p�0.002), resulting inan increase of tumors with a primary histopathologicnodal examination (pN), from 23 in 69 (33%) to 48 in90 (53%) (p�0.016). pN1 status was found in 18 of 69patients (26%) in the first period, and in 27 of 90 pa-tients (30%) in the second period (NS); stage pN0 in-creased from 5 of 69 (7%) to 21 of 90 (23%) (p�0.009).Nodal recurrence was observed in 4 of 66 (6%) and in 4of 90 (4%) patients, during the first and the later period,respectively (NS).

Extent of lymphadenectomy (n�71): site of nodaldisease (n�45)Lymphadenectomy was performed at primary treatmentin the central compartment in 45 patients, with pN1

status in 19 patients; in the central and ipsilateral lateralcompartments in 23 patients, with nodal disease in bothcompartments in 15 patients, and in the central or lat-eral compartment alone in 3 and 5 patients, respectively;and in the lateral compartment alone in 3 patients withinvolved nodes.

So the central compartment was involved in 37 of 68dissections (therapeutic and prophylactic), and the lat-eral compartment was involved in 23 of 26 dissections(mostly therapeutic). More nodes were dissected andexamined in patients with pN1 versus pN0 status, insystematic versus selective (sampling) lymphadenec-tomy, in therapeutic versus prophylactic lymphadenec-

tomy, and in lateral versus central lymphadenectomy,respectively (Table 3).

Survival dataIn TNM I and II (low-risk) patients, the 20-year tumor-related survival and disease-free survival rates were100% and 96%, respectively, versus 55% and 62%, re-spectively, in TNM III and IV (high-risk) patients(p�0.0001).

Survival by nodal status (univariate analysis)The 20-year tumor-related survival in the whole groupwas 77% for (primary and metachronous) pN1 status(n�48), and 98% for pN0 � cN0 status (n�111)(p�0.002) (Fig. 1). In the subgroup of TNM low-riskpatients, the values were 100% and 100%, respectively,versus 50% (pN1 status) and 86% (N0 status) (10-yearsurvival), respectively, in high-risk patients (p�0.03).

Nodal recurrence (patients treated for cure[n�156])As shown in Table 4, nodal disease recurred in 5 of 42patients (12%) treated for cure with initial nodal disease(pN1), all 5 with macroscopic involvement, in 1 of 26(4%) pN0 tumors (NS, log-rank test), and in 2 of 88patients (2%) with cN0 status, without primary lymph-adenectomy. Metachronous disease (n�3) occurred 1.5,2, and 5 years, respectively, after primary total thyroid-ectomy for a pT2a tumor in two patients, and after totalthyroidectomy with 131I for a pT4a tumor, respectively.

In all patients, the nodal recurrence was ipsilateral. InN0 tumors, the site was central (level VI) in one, andlateral (levels III, IV) in two patients, respectively. InpN1 tumors, nodal recurrence occurred in the central

Table 3. Number of Nodes Examined*

Variable

Nodesexamined,

range (mean) p Value

StagepN1 1–51 (18) 0.0001pN0 1–14 (4)

LymphadenectomySystematic 1–51 (15) 0.0001Selective 1–8 (3)Therapeutic 1–51 (17) 0.0001Prophylactic 1–12 (4)Lateral 1–33 (13) 0.01Central 1–25 (7)

*Available in 61/71 patients with nodal dissection.


compartment, ie, the site of initial involvement in twopatients, and laterally in two patients (with initial in-volvement of levels II to IV); one patient with a central

and lateral recurrence initially had level VI involvement.A central nodal recurrence was observed in only 1 of 117cN0 patients, in 1 of 25 pN0 and in none of 4 pN1

Figure 1. Tumor-related survival by node status.

Table 4. Nodal Recurrence in Subgroups of Patients with Primary Treatment for Cure (n � 156)

Subgroup

Patients withnodal recurrence,

n (%)p

Value*Duration of followup

(y) (median)

Age (y)�45 4/73 (5) 6.5�45 4/83 (5) NS 6.0

pN1 5/42 (12) 4.5pN0 1/26 (4)

{3/114 (3) 0.009 6.5cN0 2/88 (2)TNM I 4/91 (4) 6.5

{4/129 (3) low riskII 0/38 (0)III 4/27 (15) high risk 0.006 5.0IV -4/27 (15)

LymphadenectomyTherapeutic (cN1) 5/39 (13) 4.5Prophylactic (cN0) 1/29 (4)

{3/117 (3) 0.006 6.5No lymphadenectomy (cN0) 2/88 (2)Use of 131I 6/69 (9) 6.0No use of 131I 2/87 (2) 0.054 7.0

*Log-rank test.


tumors, ie, in 1 of 29 patients having a prophylacticcentral dissection, and in none of 88 patients withoutlymphadenectomy (2 of whom had a lateral recurrence).

Treatment of nodal recurrence was surgical and radio-iodine, with external beam radiation in one patient. Twoin eight patients with nodal recurrence died, one from lo-coregional disease, the other one with pulmonary metasta-ses, 9 and 12 years, respectively after diagnosis. One patientis living with regional disease. Nodal recurrence occurredmore frequently in pN1 tumors as compared with pN0 �cN0 tumors (p�0.009) (Fig. 2), in patients with clinicalnodal involvement (with therapeutic lymphadenectomy)than in cN0 patients (p�0.006), and more frequently inTNM high-risk than low-risk patients (p�0.006) (Fig. 3).

ImmunohistochemistrySeven of 245 lymph nodes turned out to harbor occultmetastases (3%). But most of these nodes did not affectpN stage because they were detected in pN1 patients. In15 pN1 patients, a mean of 16 nodes (range 5 to 45) wasexamined. In four of these patients, immunohistochem-istry revealed six additional positive nodes. One micro-metastasis 0.5 mm in diameter was detected in 1 of 22pN0 patients (4%). In this group, a mean of 4 lymphnodes (1 to 17) were examined. Followup on this patientwith retrospective upstaging (pN1 [mi]) (micrometasta-sis only) revealed no recurrence in 9 years of followup.

Surgical morbidityIn 4 of 74 patients (5%) with central lymphadenectomy,ie, 2.5% of all patients, permanent recurrent laryngealnerve palsy occurred. In these patients, an extendednerve dissection (resection in one patient) was necessaryfor excision of extensive nodal metastases. In one patient(0.6%) with therapeutic lymphadenectomy, permanenthypoparathyroidism developed.

DISCUSSIONThe clinical and macroscopic intraoperative finding ofnodal metastatic involvement was histologically con-firmed in near 100% of our patients, and therapeuticlymphadenectomy was rarely performed in pN0 pa-tients. This high positive predictive value is based essen-tially on the clinical, sonographic, and intraoperativefinding of nodal enlargement (with fine-needle aspira-tion biopsy in some patients) and of suspicious, glassyappearance (even of small nodes). Enlarged nodes can befound in the absence of (primary or recurrent) meta-static involvement; Noguchi8 reported pN0 status in 6%of patients with enlarged nodes. In contrast, macro-scopic absence of nodal disease was correct in only 83%of our patients with node dissection, and in 17% of thesepatients occult disease would have been missed, under-staged, and undertreated by a strategy of therapeuticlymphadenectomy only.

Figure 2. Freedom from nodal recurrence by nodal status.


Also in the literature, inaccuracy of clinical macro-scopic staging refers essentially to frequent occult nodaldisease, found in 23% to 69% of patients with appar-ently negative nodes,9-11 with a proportion of exclusiveoccult nodal disease of 25% to 80% among pN1

tumors,12-14 determining a high rate (51% to 90%) ofpN1 status in patients undergoing systematic (en bloc)prophylactic (elective) node dissection,2,8,13,15-17 as com-pared with clinical nodal disease (21% to 35%).13,17

With routine node sampling,10,14 or sentinel lymph nodebiopsy18-21 and frozen section search for occult nodaldisease, more sensitive variants of selective, therapeuticlymphadenectomy were proposed, avoiding the morbid-ity of routine and unnecessary node dissection. Sam-pling and frozen sections of jugular nodes were used byRosen and Maltland10 to select patients with occult dis-ease in lateral nodes, for therapeutic instead of routineprophylactic functional lateral neck dissection. Theyconfirmed a high incidence (36%) of occult disease alsoin lateral nodes, which are reported to harbor metastaticdisease nearly as frequently as nodes of the central com-partment (47% to 62%).10,13,22,23

Selective procedures have the problem of a relevant orunknown false-negative rate, which might contribute toa relatively lower incidence of pN1 status (38% to54%)10,14,20,21 than that based on elective systematic node

dissections. But differences in the prevalence of pN1

status and of occult disease can also occur because ofvariation in different populations. So, using an electivecentral microdissection lymphadenectomy, Gimm andcolleagues16 found an 83% incidence of pN1 status;Tisell and associates12 reported only 51% nodal positiv-ity with the same technique, with only micrometastasisin 25% of the pN1 patients, with a mean yield of 16nodes in pN1 tumors and of 6 nodes in pN0 tumors.Based on a false-negative rate of 14%, we deduced a rateof only 36% primary nodal involvement in our patients(which is not significantly different from clinical disease[26%] in this relatively small series). Understaging byconventional histology was rare; few patients with neg-ative nodes (3%) and only one (4%) pN0 patient wereupstaged on the basis of immunohistochemistry (IHC)using anticytokeratin and antithyroglobulin antibodies.The clinical significance of micrometastasis detected byIHC has not been examined in PTC. Our patient withmicrometastasis remained recurrence free during 9 yearsof followup, and the additional positive nodes in pN1

tumors were of no clinical significance. On the basis ofthese results, we do not recommend routine use of IHCin the evaluation of lymph nodes in PTC, also in view ofthe rarity of nodal recurrence in our N0 patients. Weconcluded that in our population with PTC the inci-

Figure 3. Freedom from nodal recurrence by TNM risk group.


dences of clinical and of occult nodal disease were rela-tively low as compared with those in other reports,9-16

and accordingly, more frequent lymphadenectomy dur-ing the study period led to a significant increase of stagepN0 but not of pN1. Metachronous nodal disease was arare event in our pN0 and those clinically node-negativepatients without primary lymphadenectomy. The dis-crepancy between primary occult and metachronousclinical nodal involvement (14% versus 2.6%;p � 0.025), or between occult disease in patients withprophylactic versus those without lymphadenectomy(17% versus 2.3%; p � 0.005), strengthens the evi-dence that untreated occult disease does not frequentlylead to clinical nodal recurrence,2,23 as demonstrated byNoguchi8,9 for small PTC.

Low rates of nodal recurrence were attributed to moreradical modes of lymphadenectomy. Nilsson and col-leagues24 noted a 4% incidence, without primary radio-iodine, and McHenry and coworkers14 found a 7% re-currence rate, 2% in their pN0, and 19% in pN1

patients, respectively. Our results with less radical, orwithout lymphadenectomy in clinically node-negativepatients, without radioiodine in 75%, compare favor-ably, with nodal recurrence in 5% (12% in patients withpN1 status, 2.6% in node-negative patients;p � 0.009), with 92% 20-year recurrence-free survivalin clinically node-negative patients. In a few of thesepatients, about 3%, metachronous nodal disease wouldpossibly have been avoided by systematic prophylacticnode dissection. This strategy led to improvement inrates of nodal recurrence and of survival in other reportsand populations.8,15 But in thyroid cancer it has not yetbeen considered that stage migration by more accuratenodal dissection and staging might, per se, improve re-sults in pN0 and in pN1 tumors, invalidating compari-sons of treatment results (pN0 tumors are purified fromoccult nodal disease, and the pN1 population is “dilut-ed” by less aggressive, occult disease) (Will Rogersphenomenon).25

In our patients, a significant deterioration of thetumor-related survival by stage pN1 versus pN0, cN0 wasstrongly related to the TNM high-risk category, ie, topatients aged 45 years or more, confirming the validityof the age-related prognostic classification with respectto survival. It is of interest to note that staging olderpatients into the TNM low-risk categories I and II (ver-sus III) is widely based (in 46 of 57 [81%] of our pa-tients) on clinical not on histologic node negativity, be-

cause many surgeons do not routinely perform (elective)node dissections.26 This confirms the prognostic validityof clinical nodal staging.

Morbidity (n � 5, 3%) was limited to patients withsystematic therapeutic lymphadenectomy for extensivecentral nodal disease. Only one patient (1.4%) sufferedfrom permanent hypoparathyroidism after node dissec-tion. Henry and colleagues27 noted a 4% rate of defini-tive hypoparathyroidism after prophylactic central nodedissection, and they advised against its routine use. Inour patients, no morbidity was noted with less radicalprophylactic dissections. After systematic central nodedissection, hypoparathyroidism might be an importantissue.28

In summary, this study from one surgeon and onepathologist, with prospective documentation, indicatesthat the rates of clinical and of occult (including meta-chronous) nodal disease might be relatively low in apopulation with unselected PTC; and that occult nodaldisease might not frequently evolve in clinical recurrentdisease, irrespective of the pT stage. The benefit fromprophylactic central lymphadenectomy might be small,and its utility must further be followed. We observed acentral nodal recurrence in only 1 of 117 clinically node-negative patients, 29 of whom had a prophylactic nodedissection. Nevertheless, we continue to use elective cen-tral dissections, because: in some rare patients, it mightprevent the morbidity of a central nodal recurrence; pa-tients with (occult) nodal disease might have selectiveuse of prophylactic radioiodine; and the goal can beachieved without surgical morbidity, when a less radicalprocedure (sampling) is practiced. According to the newTNM classification29 an eventually low yield of nodes isaccepted for classifying as pN0. By contrast, a more rad-ical, systematic, compartment-oriented microdissectionlymphadenectomy is warranted in patients with obviousnodal disease, which, contrary to occult disease, is amarker for (curable or serious) nodal recurrence (despiteuse of radioiodine treatment). Regarding lateral nodes,no prophylactic dissection is recommended 30 in view ofthe discrepancy between occult and clinical recurrentdisease, and because lateral recurrence is amenable tometachronous therapeutic lymphadenectomy withoutmorbidity. In our patients, evaluation of the clinical,intraoperative nodal status was reasonably valid for de-ciding the extent and technique of node dissection. Wefound a rationale neither for search of occult disease by


frozen section of clinically negative (including sentinel)nodes, nor for using IHC detection of micrometastasis.

Author contributionsStudy conception and design: GemsenjagerAcquisition of data: Gemsenjager, Perren, SchweizerAnalysis and interpretation of data: Gemsenjager, Per-

ren, Seifert, Schuler, Schweizer, HeitzDrafting of manuscript: Gemsenjager, Perren, Seifert,

Schuler, Schweizer, HeitzCritical revision: Heitz, Schuler, Schweizer

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