ultrasonographic evaluation of small cervical lymph nodes in head and neck cancer

PII S0301-5629(98)00025-8

● Original Contribution

ULTRASONOGRAPHIC EVALUATION OF SMALL CERVICAL LYMPHNODES IN HEAD AND NECK CANCER

HIROSHI YOSHIDA,† HIROSHI YUSA,† EI UENO,‡ ERIKO TOHNO,* andHIROKO TSUNODA-SHIMIZU

§

†Department of Oral and Maxillofacial Surgery and‡Department of Metabolic and Endocrine Surgery, Institute ofClinical Medicine, University of Tsukuba; Tsukuba, Japan; *Department of Radiology, Tsukuba Memorial Hospital,

Tsukuba, Japan; and§Diagnostic Radiology, Kinu Medical Association Hospital, Mitsukaido, Japan.

(Received10 November1997; in final form 9 February1998)

Abstract—To establish sonographic criteria for differentiating metastasis and nonmetastasis in small cervicallymph nodes, correlations between sonographic parameters and histological diagnosis were statistically examinedin 117 lymph nodes with maximal diameter of up to 10 mm in the sonographic findings, consisting of 26metastatic and 91 nonmetastatic nodes. The equations obtained with logistic regression analysis showedlpredictive values of21.5 and 0.5 as effective cutoff-point criteria, and were considered to be a reliable indicatorfor differentiating small nodes with predictive values outside of21.5 < l < 0.5. The sensitivity, specificity andaccuracy with predictive values outside of21.5 < l < 0.5 were 83%, 97% and 95%, respectively. © 1998World Federation for Ultrasound in Medicine & Biology.

Key Words:Ultrasonography, Cervical lymph node, Metastasis, Head and neck cancer, Oral cancer, Logisticregression analysis, Squamous cell carcinoma.

INTRODUCTION AND LITERATURE

Staging of cervical lymph nodes in patients with primarysquamous cell carcinoma of the head and neck, andespecially of the oral cavity, is a major concern of oraland maxillofacial surgeons because evidence of meta-static lymph nodes is an important factor in determiningthe prognosis of patients and selecting the type of treat-ment (Grandi et al. 1985; Leemans et al. 1993; Martis etal. 1979; Mustard and Rosen 1963; Snow et al. 1982).Because clinical palpation of the neck is unreliable (Aliet al. 1985; Byers et al. 1988; Okamoto et al. 1988; Spiroand Strong 1971; van den Brekel et al. 1991b, c), com-puted tomography (CT), magnetic resonance imaging(MRI) and ultrasonography (US) have been commonlyused to evaluate the status of cervical lymph nodes, andhave permitted detection of metastatic lymph nodes thatwere clinically nonpalpable (Close et al. 1989; Friedmanet al. 1984; Mancuso et al. 1983; Stevens et al. 1985; vanden Brekel et al. 1991b, c). The size of the lymph nodesdepicted with these imaging modalities has been com-

monly accepted as a significant criterion for differentiat-ing malignant from benign nodes because the frequencyof metastatic involvement is certainly higher in enlargednodes (Shozushima et al. 1990; Steinkamp et al. 1994,1995; van den Brekel et al. 1990). A nodal diameter of 10or 15 mm in CT and MRI has been commonly employedas a size criterion for differentiating lymph nodes. How-ever, histological examinations have revealed that theincidence of metastatic involvement in small nodes witha diameter of less than 10 mm is not negligible (Don etal. 1995; Eichhorn and Schroeder 1993; Hajek et al.1986; Shozushima et al. 1990; Steinkamp et al. 1995;van den Brekel et al. 1990). To discriminate malignancyand benignity in small lymph nodes, central low attenu-ation and rim enhancement due to central necrosis, re-gardless of size, has been used as a criterion for malig-nancy in enhanced CT (Close et al. 1989; Feinmesser etal. 1987; Friedman et al. 1984; Lenz et al. 1993; Man-cuso et al 1981; Som 1987; Stern et al. 1990; Stevens etal. 1985; Watkinson et al. 1991). Although these char-acteristics constitute an important criterion for lymphnode metastases, particularly in small nodes (Lenz et al.1993; Som 1987), they are found in only 32 to 65% ofmetastatic lymph nodes (Lenz et al. 1993; Steinkamp etal. 1994). Additionally, fatty nodal replacement may

†Address correspondence to: Dr. Hiroshi Yoshida, Department ofOral and Maxillofacial Surgery, Institute of Clinical Medicine, Univer-sity of Tsukuba. 1-1-1 Tennoudai, Tsukuba-shi, Ibaraki-ken 305 Japan.E-mail: [email protected]

Ultrasound in Med. & Biol., Vol. 24, No. 5, pp. 621–629, 1998Copyright © 1998 World Federation for Ultrasound in Medicine & Biology

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resemble central necrosis and can occur in postinflam-matory and postirradiation nodes (Mancuso et al. 1983;Som 1987; Stern et al. 1990). Although MRI may be-come a slightly more sensitive technique for evaluatingcentral necrosis (Som 1987), it is currently less accuratethan CT in this regard because small nodes can bemasked by fat planes (Lenz et al. 1993; van den Brekelet al. 1991a; Yousem et al. 1992).

US has the ability to detect lymph nodes withdiameters greater than 4 or 5 mm (Eichhorn and Schr-oeder 1993; Gosepath et al. 1994; Ishii et al. 1991;Shozushima et al. 1990; Yusa et al. 1997), and todepict their internal structures (Vassallo et al. 1992,1993; Yusa et al. 1997). Although various sonographicfeatures have been proposed as criteria, those that maybe most valuable for differentiating malignant frombenign nodes are under dispute. Lymph node size of 7or 8 mm in minimal diameter has commonly beenindicated to be the most significant criterion for dis-crimination (Nakano et al. 1996; Sakai et al. 1988; vanden Brekel et al. 1991b, c) and accuracy rates of morethan 80% have been reported in differentiation ofcervical lymph nodes when including many enlargednodes with diameters greater than 10 mm (Baatenburgde Jong et al. 1989; Hayashi et al. 1994; van denBrekel et al. 1991b). However, accuracy has beenpresumed to be lower when only small nodes areevaluated. Some studies have reported that the accu-racy of US never exceeded 70% for clinically negativelymph nodes that were considered to be small (van denBrekel et al. 1991b, c).

Establishing a means of correct assessment of smallcervical lymph nodes is important in treatment of pa-tients with head and neck cancer, because there appearsto be an advantage in terms of survival and regionaldisease control if nodal metastases are treated while stilloccult (Spiro and Strong 1973; Spiro et al. 1986), andbecause unnecessary neck dissections would be dimin-ished. However, to our knowledge, there have not beenany studies to establish diagnostic criteria for evaluatingsmall lymph nodes, and diagnosis concerning the pres-ence or absence of metastasis has remained insufficient.US is effective for detecting small lymph nodes (Baaten-burg de Jong et al. 1989; Bruneton et al. 1984; Eichhornand Schroeder 1993; Furukawa et al. 1991; Hajek et al.1986; Ishii et al. 1991) and for accurately measuring theirsize (Gosepath et al. 1994). This study was conducted toestablish sonographic criteria for differentiating meta-static and nonmetastatic disease in small cervical lymphnodes of up to 10 mm in maximal diameter, with aretrospective correlation of ultrasonographic with histo-logical findings.

MATERIALS AND METHODS

Fifty patients with squamous cell carcinoma of thehead and neck region who underwent comprehensive orelective neck dissections at the Division of Oral andMaxillofacial Surgery, Tsukuba University Hospital,served as subjects. The patients consisted of 32 men and18 women ranging in age from 33 to 81 y with a meanage of 63 y. Primary tumor sites, in decreasing order offrequency, were 19 of the tongue, 17 of the gingiva, 5 ofthe maxillary sinus, 3 of the oropharynx, 2 each of themouth floor and the palate, and 1 each of the lower lipand the buccal mucosa. All patients underwent neckdissections within 2 weeks after US examination becauseof the presence of enlarged lymph nodes suspected ofmetastases from the primary lesion in the neck, andbecause of the site and stage of the primary tumor.

Commercially available Toshiba SSA-250A USsystem (Tokyo, Japan) with 7.5-MHz mechanical sectorannular array transducer (Toshiba SMA-736A, Tokyo,Japan) or Aloka SSD-2000 US system (Tokyo, Japan)with 10-MHz mechanical sector scanner (Aloka ASU-32WL, Tokyo, Japan) was employed. The patient’s neckwas scanned multidirectionally with ultrasound transmis-sion gel between the skin surface and the transducer. Amap of detected nodes was made for each patient, ac-cording to the anatomical location. The maximal diam-eter, minimal diameter, shape index, edge-definitioncharacteristic, pattern of margin, pattern and intensity ofinternal echoes, and existence of echogenic hilus forindividual detected lymph nodes were evaluated as diag-nostic parameters by consensus basis of two experts withabundant experience in ultrasonographic diagnosis. Themaximal diameter was defined as the largest diameter ofeach node, and minimal diameter was measured as thelargest diameter perpendicular to the maximal diameterin the axial plane. The shape index was calculated as theratio of the minimal to maximal diameters, so that alymph node with an index close to 1 was regarded asspherical. The edge-definition characteristic was quali-fied as the clarity of the border between a node and itsadjacent structures, and the pattern of margin signifiedthe regularity of the border between nodes and surround-ing structures. The intensity of internal echoes was clas-sified into four types relative to echo levels of the sur-rounding muscles: an-, hypo-, iso- and hyper-echoic, andthe pattern of internal echoes was categorized as homo-geneous or heterogeneous according to uniformity (Figs.1 and 2).

All visible and palpable cervical lymph nodes werecarefully examined in neck dissection specimens to de-termine if they were sonographically detected nodes,with reference to the size, location and relationship toadjacent structures on the nodal maps, such as the ster-

622 Ultrasound in Medicine and Biology Volume 24, Number 5, 1998

nocleidomastoid muscle, internal jugular vein and sub-mandibular gland. In groups of nodes, the node that mostnearly corresponded to the detected one was selected.Although all nodes were removed from specimens and

subjected to histological examination, only nodes thatcorrelated with ultrasonic observations and showed max-imal diameters of 10 mm or smaller in the sonographicfinding served as materials for this study.

Fig. 1. Lymph node showing maximal and minimal diameters of 9.3 mm and 3.7 mm, shape index of 0.40, clear edgedefinition, smooth margin, homogeneous internal echo pattern, hypoechoic internal echo intensity and presence of

echogenic hilus.

Fig. 2. Lymph node showing maximal and minimal diameters of 35.9 mm and 20.2 mm, shape index of 0.56, ill-definededge definition, irregular margin, heterogeneous internal echo pattern, isoechoic internal echo intensity and absence of

echogenic hilus.

US for small neck nodes● H. YOSHIDA et al. 623

The correlation between all sonographic parametersand histological diagnosis was statistically analyzed foreach lymph node. An unpairedt-test was employed forcomparison of the maximal diameter, minimal diameterand shape index between metastatic and nonmetastaticnodes. Fisher’s exact probability test was used for com-parison of the edge-definition characteristic, pattern ofmargin, pattern of internal echoes and existence of echo-genic hilus. Mann–Whitney’s U-test was applied to theintensity of internal echoes. Additionally, to assess thevalue of combining sonographic parameters used to dif-ferentiate nodes, logistic regression analysis was em-ployed, in which a criterion variable and explanatoryvariables consisted of the presence of metastatic disease

and the parameters with significant differences betweenmetastatic and nonmetastatic nodes, respectively. Allstatistical procedures were carried out using a statisticalanalysis software application program (SPSS 6.1 J, SPSSJapan Inc., Tokyo, Japan).

RESULTS

One hundred and seventeen resected lymph nodeswere correlated with the sonographic imaging. Thesecervical lymph nodes were incorporated in the drainageregions of the primary tumors, and all except a fewsubmental and submandibular nodes were clinically non-palpable. The anatomical locations of these nodes wereas follows: 38 submandibular, 28 mid internal jugular, 25superior internal jugular, 20 submental, 5 spinal acces-sory and 1 parotid. Of the 117 nodes, 26 were histolog-ically diagnosed as metastatic, and 91 as nonmetastatic.The maximal diameter of the smallest sonographicallydetected lymph node was 4 mm.

Comparing the size and shape of metastatic andnonmetastatic nodes, there were significant differences inthe maximal diameter, minimal diameter and shape index(Table 1). Metastatic lymph nodes showed larger maxi-mal and minimal diameters and more spherical shapethan nonmetastatic nodes. However, definitive cutoffpoints of size and shape criteria for differentiation werenot found because of a large range of overlap betweenmetastatic and nonmetastatic nodes, and because a de-crease in sensitivity accompanied the increase in speci-

Table 1. Relationship between size and shape of lymphnodes and histologic examination.

Size and shapeof lymph node

Histologic examination

Statisticalanalysis†

Metastatic(n 5 26)

Nonmetastatic(n 5 91)

SizeMaximal diameter (mm) 8.06 1.5 7.2 6 1.8 p 5 0.0408‡

Minimal diameter (mm) 6.06 1.4 4.3 6 1.6 p , 0.001*Shape

Shape index 0.766 0.13 0.626 0.19 p , 0.001*

† Unpairedt-test.‡ significant difference withp , 0.05.* significant difference withp , 0.01.

Table 2. Evaluation of size and shape criteria for diagnosis.

Criteria Range

No. ofmetastatic nodes

(n 5 26)

No. ofnonmetastatic nodes

(n 5 91)Cutoffpoint

Sensitivity(%)

Specificity(%)

Accuracy(%)

SizeMaximal diameter x# 5 0 16

5 , x # 6 3 10 5, x 100.0 17.6 35.96 , x # 7 6 14 6, x 88.5 28.6 41.97 , x # 8 5 21 7, x 65.4 44.0 48.78 , x # 9 4 14 8, x 46.2 67.0 62.49 , x # 10 8 16 9, x 30.8 82.4 70.9

Minimal diameter x# 4 2 524 , x # 5 6 16 4, x 92.3 57.1 65.05 , x # 6 7 8 5, x 69.2 74.7 73.56 , x # 7 5 10 6, x 42.3 83.5 74.47 , x # 8 3 2 7, x 23.1 94.5 78.68 , x # 9 3 2 8, x 11.5 96.7 77.89 , x # 10 0 1 9, x 0 98.6 76.9

Shape x# 0.5 2 310.5, x # 0.6 0 16 0.5, x 92.3 34.1 47.00.6, x # 0.7 5 15 0.6, x 92.3 51.6 60.70.7, x # 0.8 10 13 0.7, x 73.1 68.1 69.20.8, x # 0.9 7 4 0.8, x 34.6 82.4 71.80.9, x # 1.0 2 12 0.9, x 7.7 86.8 69.2

x for size criteria signifies actual measured value (mm); x for shape criteria signifies shape index (ratio of the minimal to maximaldiameters).


ficity with increasing threshold value (Table 2). Therewere also significant differences between metastatic andnonmetastatic nodes in the edge-definition characteristic,pattern of margin, pattern and intensity of internal ech-oes, and echogenic hilus, but no single parameter showeda clear cutoff criterion in differentiating malignant frombenign nodes, because of overlap in the sonographicfindings (Table 3).

In logistic regression analysis, all parameters eval-uated in the present study were initially employed asexplanatory variables. The actual measured values ofmaximal diameter, minimal diameter and shape indexwere employed. The edge-definition characteristic, pat-tern of margin, pattern and intensity of internal echoes,the existence of echogenic hilus, and presence of metas-tasis were replaced with ordinal variables: 0 for clearedge definition, 1 for ill-defined edge definition; 0 forsmooth margin, 1 for irregular margin; 0 for homoge-neous internal echo pattern, 1 for heterogeneous internalecho pattern; 0 for hypo- and isoechoic internal echoes,1 for an- and hyperechoic internal echoes; 0 for presenceof echogenic hilus, 1 for absence of echogenic hilus; and0 for nonmetastasis, 1 for metastasis. Of these variables,the echogenic hilus, internal echo pattern and the mini-mal diameter, in contributing order to predicting metas-tasis, were selected as explanatory variables by correla-tion matrix and stepwise regression analysis. Finally, thefollowing equation was derived by logistic regression

analysis to correlate histologic diagnosis and ultrasono-graphic features:

Y 51

1 1 e2l ~l 5 27.16651 3.3411X1

1 2.3447X2 1 0.5754X3) (1)

Y, representing the predictive value, is defined as lessthan 0.5 for nonmetastatic, and greater than 0.5 formetastatic nodes;l, also representing the predictivevalue, is defined as negative for nonmetastatic, and pos-itive for metastatic nodes;X1, signifying the existence ofechogenic hilus, is defined as 0 for presence and 1 forabsence;X2, signifying the internal echo pattern, is de-fined as 0 for homogeneous and 1 for heterogeneouspattern;X3, signifying the minimal diameter, is the ac-tual measured value (mm).

Fourteen (54%) of the 26 metastatic nodes showedpositive valuations, and 86 (95%) of the nonmetastaticnodes gave negative valuations. With a cutoff point ofl5 0, sensitivity, specificity and accuracy for all lymphnodes were 54%, 95% and 86%, respectively. Seventeen(15%) of the 117 lymph nodes, consisting of 12 meta-static and 5 nonmetastatic nodes, were erroneously diag-nosed by the equation. There was some overlap betweenmetastatic and nonmetastatic nodes within the range of21.5 , l , 0.5, and 10 of the 12 misdiagnosed meta-static nodes had predictive values within this range. Ofall metastatic nodes, 2 (8%), 14 (54%) and 10 (38%)nodes showed predictive values ofl , 21.5,21.5 , l, 0.5 andl . 0.5, whereas 73 (80%), 16 (18%) and 2(2%) of the 91 nonmetastatic nodes had predictive valuesof l , 21.5,21.5, l , 0.5 andl . 0.5, respectively.Sensitivity, specificity and accuracy for the nodes withpredictive values ofl , 21.5 andl . 0.5 were 92%,80%, 83%, and 38%, 98%, 85%, respectively (Table 4).When limited to nodes with predictive values outside therange of21.5 , l , 0.5, sensitivity, specificity andaccuracy rose to 83%, 97% and 95%, respectively.

DISCUSSION

Since Bruneton et al. (1984) reported the value ofUS in the detection of metastasis to the cervical lymphnodes, US examination has been widely accepted fordifferentiating metastatic from nonmetastatic nodes inpatients with primary head and neck cancer (Ahuja et al.1995; Ariji et al. 1991; Baatenburg de Jong et al. 1989;Eichhorn and Schroeder 1993; Evans et al. 1993; Fu-rukawa et al. 1991; Gosepath et al. 1994; Hajek et al.1986; Hayashi et al. 1994; Ishii et al. 1991; John et al.1993; Lenz et al. 1993; Naito 1990; Sakai et al. 1988;Shozushima et al. 1990; Steinkamp et al. 1995; Takes et

Table 3. Relationship between us parameters and histologicalexamination.

US parameters

Histological examination

Statisticalanalysis

Metastatic(n 5 26)

Nonmetastatic(n 5 91)

Edge definitionClear 22 89

p 5 0.0215†*Ill-defined 4 2

MarginSmooth 23 90

p 5 0.0339†*Irregular 3 1

Pattern of internal echoesHomogeneous 17 89

p , 0.001‡*Heterogeneous 9 2

Intensity of internal echoesAnechoic 0 0

p 5 0.0014‡§Hypoechoic 17 82Isoechoic 5 8Hyperechoic 4 1

Echogenic hilusPresence 1 47

p , 0.001‡*Absence 25 44

† significant difference withp , 0.05.‡ significant difference withp , 0.01.* Fisher’s exact probability test.§ Mann–Whitney’s U-test.

}

}}

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al. 1996; Tohnosu et al. 1989; van den Brekel 1991b, c;Vassallo et al. 1992, 1993; Westhofen 1987; Yusa et al.1997). Most studies evaluated accuracy rates of US foreach side of the neck and not for each node, because it isdifficult or impossible to establish correspondence be-tween sonographically detected nodes and those in aneck-dissection specimen, and because detection of asingle node metastasis results in the treatment of thewhole neck side. However, if a node that has beensonographically assessed as metastatic is histologicallyrevealed to be nonmetastatic, and another lymph nodethat has been sonographically evaluated as nonmetastaticin the same neck side is histologically revealed to bemetastatic, the net test result is correct for that neck sidebut erroneous for the individual nodes. Because the pur-pose of this study was to establish diagnostic criteria fordifferentiating metastasis in individual small lymphnodes, US and histologic findings were compared onnode-by-node basis, rather than on the basis of neck side.Although all visible and palpable nodes in the neck-dissection specimen were submitted to histological ex-amination, only the resected lymph nodes that could becorrelated with US served as materials. Sonographicallyundetected nodes were excluded from this study.

Among various sonographic criteria, size is gener-ally accepted as the most important diagnostic parameter(Nakano et al. 1996; Sakai et al. 1988; van den Brekel etal. 1991b, c). Cutoff points ranging from 5 to 10 mm inmaximal diameter or from 5 to 8 mm in minimal diam-eter have been proposed by various authors to distinguishmalignant from benign nodes, and nodes exceeding thespecific cutoff points were suspected of metastases di-ameter (Bruneton et al. 1984; Hajek et al. 1986; Hayashiet al. 1994; Nakano et al. 1996; Steinkamp et al. 1995;van den Brekel et al. 1991b, c). However, even small

lymph nodes may harbor metastases, and node enlarge-ment may be due to inflammation or benign hyperplasia(Ahuja et al. 1995; Bruneton et al. 1984; Eichhorn andSchroeder 1993; John et al. 1993; Johnson 1990; Lenz etal. 1993; Nakano et al. 1996; Sakai et al. 1988;Steinkamp et al. 1995; Sutton et al. 1988; van den Brekelet al. 1990; Vassallo et al. 1992). The present studyshowed significant difference in both the maximal andminimal diameters, but specific cutoff points for differ-entiation could not be found because of the large range ofoverlap between metastasis and nonmetastasis. Conse-quently, the size of lymph nodes is not considered to bepractical as a reliable indicator of metastatic disease insmall lymph nodes.

Lymph node shape has been proposed as a criterionfor differentiating nodal metastasis (Sakai et al. 1988;Steinkamp et al. 1995; Tohnosu et al. 1989; Vassallo etal. 1992, 1993), based on the observation that metastaticnodes lose their normally oval shape and appear morespherical than nonmetastatic nodes. The shape was de-termined by the ratio of the maximal and minimal diam-eters of individual nodes, so that ratios closer to1 indi-cate more spherical. Some authors (Sakai et al. 1988;Shozushima et al. 1990; Steinkamp et al. 1995; Vassalloet al. 1992) reported validity of a threshold value of2 formaximal:minimal diameter ratio, which is identical tothat of 0.5 for minimal:maximal diameter ratio in thisstudy for differentiating benign from malignant nodes,but our results showed that there was, again, an overlapbetween metastatic and nonmetastatic nodes for all shapecutoff points. Steinkamp et al (1995) described the pit-falls of the long-to-short-axis ratio approach, wherebytwo thirds of false-positive nodes presented with a long-axis diameter less than 9 mm. Accordingly, the shapeindices is not also considered to provide reliable criteria

Table 4. Evaluation ofl predictive value criteria for diagnosis.

Range ofl predictive value

No. ofmetastatic nodes

(n 5 26)

No. ofnonmetastatic nodes

(n 5 91)Cutoffpoint

Sensitivity(%)

Specificity(%)

Accuracy(%)

l # 26 0 126,l # 25 1 16 26 , l 100.0 1.1 23.125 , l # 24 0 21 25 , l 96.2 18.7 35.924 , l # 23 0 6 24 , l 96.2 41.8 53.823 , l # 22 0 13 23 , l 96.2 48.4 59.022 , l # 21.5 1 16 22 , l 96.2 62.6 70.1

21.5, l # 21 3 4 21.5, l 92.3 80.2 82.921 , l # 20.5 4 5 21 , l 80.8 84.6 83.8

20.5, l # 0 3 4 20.5, l 65.4 90.1 84.60 , l # 0.5 4 3 0, l 53.8 94.5 85.5

0.5, l # 1 1 0 0.5, l 38.4 97.8 84.61 , l # 1.5 2 1 1, l 34.6 97.8 83.8

1.5, l # 2 3 1 1.5, l 26.9 98.9 82.92 , l # 3 0 0 2, l 15.3 100.0 81.23 , l 4 0 3, l 15.3 100.0 81.2


for differentiation of nodes with maximal diameter of 10mm or smaller.

The internal echo pattern has been used as one ofthe criteria for differentiation in enlarged nodes (Ariji etal. 1991; Hayashi et al. 1994; Nakano et al. 1996; Sho-zushima et al. 1990; Vassallo et al. 1992), because aheterogeneous pattern indicative of a cystic, necrotic orsolid tumor has been more frequently observed in met-astatic nodes. Our results showed that there was a sig-nificant difference in the pattern and intensity of internalechoes between metastatic and nonmetastatic nodes, butmany lymph nodes in both groups were homogeneousand hypoechoic. Although one report (Shozushima et al.1990) has suggested that a well-delineated boundaryecho was highly likely to be consistent with metastasis,the results of the present study showed a majority ofnodes in both groups as clear edge definition and smoothmargin. Thus, edge-definition characteristic, pattern ofmargin, and pattern and intensity of internal echoes werenot considered useful as sole parameters for differentia-tion in small lymph nodes.

The echogenic hilus, which was originally thoughtto represent fat deposited within the medulla of the node(Marchal et al. 1985; Sakai et al. 1988; Sutton et al.1988), has been shown by Rubaltelli et al. (1990) to bedue to the converging sinuses within the medulla of thelymph node, providing numerous parallel interfaces.Some authors have concluded that the presence of echo-genic hilus could be regarded as a valid sign of benignity(Rubaltelli et al. 1990; Sutton et al. 1988), whereasothers have proposed that it was not specific for benig-nity or malignancy (Evans et al. 1993; Vassallo et al.1992). Our results revealed that the echogenic hilus wasabsent in 25 (96%) of metastatic and in 44 (48%) ofnonmetastatic nodes. Consequently, the presence ofechogenic hilus strongly suggested benignity, but itsabsence did not always prove malignancy.

In addition to the above-mentioned criteria, group-ing of lymph nodes (Ahuja et al. 1995; van den Brekel etal. 1991b, c), cystic change (Ahuja et al. 1995), sur-rounding soft tissue edema (Ahuja et al. 1995) and cor-tical width (Vassallo et al. 1992, 1993) have been used asparameters for differentiating malignant from benignnodes. The assessment of these parameters can be valu-able for discrimination of metastasis in enlarged nodes,but is difficult in small nodes.

Because each ultrasonic parameter has some limi-tation as a sole criterion, diagnostic criteria combiningseveral parameters have been proposed to syntheticallyand correctly differentiate malignant from benign lymphnodes (Hayashi et al. 1994; Naito 1990; Sakai et al.1988; Vassallo et al. 1993). The combined criteria wereused to evaluate lymph nodes by a scoring scale ofsonographic features, and concluded that such a scoring

scale was more advantageous than individual features fordifferentiating between benign and malignant nodes, andthat the statistical correlation with pathologic results washigher for total scores than for individual scores. How-ever, determining the appropriate weighting for eachsonographic feature is difficult, and was not completelyresolved (Vassallo et al. 1993). To resolve the problem,we employed logistic regression analysis, in which ex-planatory variates consisted of all parameters with sig-nificant differences between metastatic and nonmeta-static nodes, and quantitatively assessed whether sono-graphically detected nodes were metastatic (Yusa et al.1997). The equation obtained from this analysis is con-venient for clinical use, because thel value predictingmetastasis can be readily calculated by the substitution of0 or 1 for X1 andX2, and an actual measured value forX3.

With a cutoff point ofl 5 0, the equation showeda higher accuracy rate in differentiation of small lymphnodes than any one parameter used as a sole criterion inthis study. Because an overlap was less frequently ob-served in nodes with predictive values outside the rangeof 21.5 , l , 0.5,l predictive values of21.5 and 0.5could be effective as cutoff-point criteria. Sensitivity,specificity and accuracy of the equation for nodes withpredictive value outside of21.5 , l , 0.5 were 83%,97% and 95%, respectively. However, the results fornodes having predictive values within the range of21.5 , l , 0.5 were unsatisfactory. The lymph nodespresenting such values consisted of 14 metastatic and 16nonmetastatic nodes, which could not be significantlydifferentiated by comparison using any of the parametersevaluated. Consequently, we concluded thatl predictivevalues of21.5 and 0.5 were effective diagnostic criteriafor differentiating metastasis from nonmetastasis insmall nodes, and that the equation is a reliable indicatorin differentiation of small cervical lymph nodes withpredictive values outside of21.5 , l , 0.5, but islimited in the ability to discriminate nodes producingvalues within the range of21.5 , l , 0.5. New differ-entiating criteria are required to diagnose nodes of thelatter type. Because the sample size was small in thisstudy, further study on a larger group of small lymphnodes would be helpful to determine the reliability of theequation established by logistic regression analysis.

Based on the results obtained with the equation, wehave established the following criteria for differentiatingsmall cervical lymph nodes with maximal diameter lessthan 10 mm in US findings. Lymph nodes withl pre-dictive values greater than 0.5 in the drainage region ofa primary cancer of the oral and maxillofacial region canbe highly suspected of metastasis. Nodes with predictivevalues within the range of21.5 , l , 0.5 probablyconsist of both metastasis and nonmetastasis. To distin-


guish these nodes, US-guided fine-needle aspiration cy-tology or biopsy may be effective (Baatenburg de Jong etal. 1988, 1988, 1991, 1993; Bearcroft et al. 1995; Kruytet al. 1996; Takes et al. 1996; van den Brekel et al.1991b, c, 1993), although these methods have draw-backs, such as the possibility of puncturing the wrongnodes, obtaining insufficient material, puncturing thewrong part of a node and causing patient discomfort(Kruyt et al. 1996; Takes et al. 1996; van den Brekel etal. 1991b, c). Nodes withl predictive values smallerthan21.5 can be presumed to be nonmetastatic.

US can detect cervical lymph nodes, except retro-pharyngeal ones, with diameters greater than 4 or 5 mmin diameter (Baatenburg de Jong et al. 1989; Eichhornand Schroeder 1993; Gosepath et al. 1994; Ishii et al.1991; Shozushima et al. 1990; van den Brekel et al.1991b, c). However, there are many sonographicallyundetectable smaller nodes in a neck dissection speci-men, and histologic examination has revealed metastaticinvolvement even in nodes smaller than 5 mm (Don et al.1995; van den Brekel et al. 1990). Current imagingmodalities, such as CT, MRI and US, are limited in theirability to detect very small metastatic nodes, and newmethods for addressing this issue are strongly needed.

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ultrasonographic evaluation of small cervical lymph nodes in head and neck cancer

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