Dentomaxillofacial Radiology (2006) 35, 18-23
© 2006 British Institute of Radiology
doi: 10.1259/dmfr/24536918
Correlation between the incidence of central nodal necrosis in cervical lymph node metastasis and the extent of differentiation in oral squamous cell carcinoma
Y Morimoto*,1,
H Kurokawa2,
T Tanaka1,
Y Yamashita2,
S Kito1,
S Okabe1,
T Takahashi2 and
T Ohba1
1 Department of Oral Diagnostic Science, Kyushu Dental College, Kokurakita-ku, Kitakyushu 803-8580, Japan;
2 Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kokurakita-ku, Kitakyushu 803-8580, Japan
*Correspondence to: Yasuhiro Morimoto, Division of Diagnostic Radiology, Department of Oral Diagnostic Science, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan; E-mail: rad-mori{at}kyu-dent.ac.jp
Received 27 January 2005;
revised 17 May 2005;
accepted 20 June 2005
 |
Abstract
|
|---|
Objectives: To investigate the incidence of central nodal necrosis (CNN) in the cervical lymph nodes of patients with oral squamous cell carcinoma (SCC) and the factors that influence the formation of CNN.
Methods: Lymph nodes shown as CNN on computed tomography (CT) films in 107 lymph nodes from 27 patients with oral SCC were selected. Lymph nodes with CNN on CT films were compared with the pathological findings of lymph nodes on specimens. We compared many kinds of factors influencing the formation of CNN, including the differentiated type, with the incidence of CNN.
Results: Significant relationships were found between the incidence of CNN in metastatic lymph nodes and the presence of well-differentiated SCC and the presence of keratinization in tumour cells.
Conclusions: The results indicated that if a patient had SCC with low-grade differentiation, CNN in small lymph nodes would be difficult to detect on CT scan. Therefore, noting changes in lymph node density in the absence of CNN on CT scans is necessary in case the primary tumour is low-grade SCC.
Keywords: central nodal necrosis;; lymphatic metastasis;; lymph node;; CT;; pathology
|
Introduction
|
|---|
Correctly diagnosing relatively smaller metastatic lymph nodes is important for determining the prognosis of patients with oral squamous cell carcinoma (SCC).1–7 The use of computed tomography (CT) scanning continues to be the best diagnostic method for pre-operative detection of metastatic neck disease.6–16 Currently accepted criteria for the CT diagnosis of relatively small nodal disease are not uniform, but the presence of central nodal necrosis (CNN) correlates strongly with malignancy.1,6–16 However, few studies to date have reported on the use of CT scanning for identifying the components of CNN in metastatic lymph nodes in patients with oral SCC and no studies have identified the factors that influence changes in metastatic lymph node density on CT scans.
Therefore, the objective of the present study was to identify the factors that influence the formation of CNN in patients with oral SCC and relatively small metastatic lymph nodes. At the same time, we wanted to demonstrate which components affect the appearance of CNN on CT.
|
Patients and methods
|
|---|
The subjects were 27 patients with SCC of the oral cavity who underwent radical neck dissection at Kyushu Dental College hospital between 1987 and 2000 (Table 1
). Nineteen patients underwent unilateral neck dissection and 8 underwent bilateral neck dissections. Overall, 27 comprehensive and 8 supraomohyoid neck dissection specimens were examined. None of the patients had previously undergone a neck dissection on the affected side or received pre-operative radiation therapy or chemotherapy.
All necks were examined with a contrast-enhanced CT scan no more than 1 month before surgery. Computed tomography was performed with a Toshiba X Vision RETM machine (Toshiba Co. Ltd, Tokyo, Japan) after the patient received an intravenous dose of 50 ml iohexol (300 mgI ml–1, Omunipaque 300TM; Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan) at the start of scanning and an additional 50 ml intravenous infusion during the scanning to allow better visualization of the vascular structures. Scanning was performed in the axial plane without angulation, in 5 mm thick contiguous sections from the cavernous sinuses to the thoracic inlet. Images were photographed with standard algorithms and soft-tissue windows.
All neck dissection specimens were photographed (PolaroidTM film and slides) post-operatively. Next, each specimen was prepared for pathological examination by fixation in 4% formaldehyde for 24 h.17
One hundred and seven lymph nodes, each less than 25 mm in maximum diameter, were collected as pathological specimens. We examined these specimens to determine the presence of dilated blood vessels in the lymph node capsule and tumour infiltration. The specimens were examined under an Olympus BX-50TM microscope (Olympus Optical Co., Ltd, Tokyo, Japan) equipped for photomicroscopy (Olympus PM-30TM lens). Photomicrographs were taken on Fuji Neopan SSTM film (Fuji Photo Film Co., Ltd, Tokyo, Japan) using the automatic exposure.
Next, the 107 lymph nodes were classified into three groups from the CT findings of density: homogeneous (Figure 1A), heterogeneous (Figure 1B), and central nodal necrosis (Figure 1C). The CT images were assessed according to a set of reference standards by two expert dental radiologists (YM and TT). We examined the maximum and minimum diameters of each lymph node, the width of rim enhancement, and the maximum and minimum diameters of the central low attenuation area to identify which factors influence the formation of CNN.
View larger version (109K):
[in this window]
[in a new window]
|
Figure 1 All lymph nodes were divided into three groups based on CT findings according to characteristics of density within lymph nodes. (A) Lymph node (arrowhead) has a homogeneous density on the axial CT scan. (B) Lymph node (arrowhead) has a heterogeneous density on the axial CT scan. (C) Lymph node (arrowhead) has a central nodal necrosis on the axial CT scan
|
|
To investigate which factors influence the formation of CNN, we analysed the relationships between patient sex, patient age, the size of the lymph nodes, the primary sites of SCC, the metastasis sites, the differentiated types of primary and metastatic SCC, the presence of keratinization in the tumour cells, the presence of a tumour necrosis nest in the tumour and the formation of CNN in metastatic lymph nodes. The relationships between the formation of CNN and these factors (other than the mode of invasion and the extent of invasion to the lymph nodes) were assessed using Fisher's Exact Test. The relationships between the formation of CNN and the mode or the extent of invasion to the lymph nodes were assessed using chi-squared analysis. The acceptable level was P<0.05 as significant correlation. Each variable was analysed separately. All analyses were carried out using Microsoft Excel 5.0TM software (Microsoft Corp., Redmond, WA).
The degree of differentiation was classified as well differentiated, moderately differentiated or poorly differentiated, according to the World Health Organization (WHO) pathological grading system. The mode of invasion to the lymph nodes was also classified as grade 1, grade 2, grade 3, grade 4-C, or grade 4-D as described by Yamamoto et al, according to the pattern of tumour cell invasion at the tumour-host interface.18 The extent of invasion into the lymph nodes (spread) was also classified as stage I, stage II, stage III or stage IV, as described by Honma.19 Briefly, in stage I, the metastatic tumour is found within only the afferent lymphatic duct and peripheral sinus. In stage II, the metastatic tumour infiltrates the lymphatic central sinus and lymphatic cortex. In stage III, the metastatic tumour infiltrates and replaces normal lymphatic tissues. In stage IV, the metastatic tumour spreads beyond the lymph nodes.
|
Results
|
|---|
The incidence of central nodal necrosis found on contrast CT scans of patients with oral SCC and relatively small cervical metastatic lymph nodes.
The distribution of patients is shown in Table 1
. Of the 27 patients with oral squamous cell carcinoma, 107 lymph nodes, each less than 25 mm in maximum diameter, were collected as pathological specimens and were matched with films of CT scans. Pathological examination determined that 22 of the 107 nodes from 11 of 27 patients were positive for metastasis (Table 1). Of the 22 metastatic lymph nodes, 10 revealed a low density in their centre and a thin ring-like enhancement rim, indicative of central nodal necrosis (CNN) (Table 2). Of the remaining 12 metastatic lymph nodes, 7 showed heterogeneous density and 5 showed homogeneous density on CT scan. Of the 85 negative lymph nodes, 81 (95.3%) showed homogeneous density and 4 (4.7%) showed heterogeneous density on CT scan (Table 2).
In the typical lymph node of the ten lymph nodes with CNN, the width of rim enhancement around CNN ranged about 1
2 mm on CT scan and was nearly uniform (Figure 2A). In these nodes, little hypertrophy of the lymph node capsule was seen, but the dilation of the capsular blood vessels was prominent (Figure 2B,C). In addition, the lymph nodes with the low attenuation area on CT scan had an area of well-differentiated carcinoma infiltration without exception (Figure 2B,C).
View larger version (117K):
[in this window]
[in a new window]
|
Figure 2 (A) Lymph node (arrowhead) corresponding to specimen of Figure 2B has a central nodal necrosis on the axial CT scan. (B) The whole pathological finding of the lymph node in Figure 2A. The lymph node is filled with well-differentiated squamous cell carcinoma. (C) Magnification of Figure 2B. The lymph node in Figure 2A,B shows a dilatation of the vessels of the capsule (arrowheads)
|
|
Identification of factors related to the change of density within lymph nodes seen on CT scans.
The relationships between the change of density in metastatic lymph nodes on CT scans and the many kinds of tumour-related parameters are shown in Tables 3–5. The results of Fisher's exact test showed a significant relationship between the degree of SCC differentiation and the incidence of CNN in metastatic lymph nodes (P<0.001) (Table 6). However, no significant relationship was found between the degree of SCC differentiation and the change of density between heterogeneity and homogeneity in metastatic lymph nodes (P=0.318) (Table 7). Using Fisher's Exact Test, a significant relationship was found between the presence of keratinization in tumour cells and the incidence of CNN in metastatic lymph nodes (P<0.001) (Table 8). However, no relationship was proven between the presence of a tumour necrosis nest as another parameter and the incidence of CNN (P=0.229) (Table 9). No relationship was found between the presence of keratinization in tumour cells and the change of density between heterogeneity and homogeneity in metastatic lymph nodes (P=0.145) (Tables 4 and 5).
View this table:
[in this window]
[in a new window]
|
Table 4 Relationship between CT findings and other parameters on pathological specimens in metastatic lymph nodes (LNs)
|
|
No relationship was found between the mode or the extent of invasion to the lymph nodes and the incidence of CNN in metastatic lymph nodes (P=0.155, P=0.484) (Tables 10 and 11).
No correlations were found between patient sex, patient age, primary site of SCC, metastatic node location, and the maximum area of lymph nodes and the incidence of CNN in metastatic lymph nodes (Table 3).
|
Discussion
|
|---|
Some studies have already identified components of CNN on the basis of comparisons between CT findings and pathological findings in metastatic lymph node.4,6,7,13,20–23 The results varied among the studies. Particularly, the components of the rim enhancement in CNN remained obscure on the CT scan.6,7,13,22–24 So far, one possible explanation of these components is hypertrophy of the lymph nodes.7,24 However, our present results indicate that the rim enhancement in CNN reflects the dilation of blood vessels in the lymph node capsule, but not hypertrophy of the lymph nodes, based on detailed pathological findings. Our identification of the components of CNN rim enhancement on the CT scan has pathological significance for the elucidation of CNN formation. In addition, the central area of low attenuation in CNN might reflect tumour infiltration, including a tumour necrosis nest and keratinization of the tumour cells. Our results on the central area of low attenuation seem to confirm Som's proposal that central areas of low attenuation on the CT scan might be areas of tumour infiltration, with a tumour necrosis nest and keratinization in the tumour cells, but not necessarily tumour necrosis.7 Therefore, CNN should be a conglomeritic complex of tumour infiltration and dilated capsular blood vessels based on our present study and previous reports.
We empirically recognized that there would be some patients with moderately differentiated or undifferentiated oral SCC in whom metastatic lymph nodes could not be diagnosed from the results of CT scans. However, the correlation between the extent of SCC differentiation in lymph nodes and the incidence of CNN in metastatic lymph nodes had not been clarified.7,24 Therefore, the most important result in our study is the significant relationship between the extent of SCC differentiation in lymph nodes and the incidence of CNN in metastatic lymph nodes. In most patients, the degree of SCC differentiation in metastatic lymph nodes was the same as that in the primary site. Our result suggests that diagnosing metastatic lymph nodes by CNN findings on the CT scan may depend on the degree of SCC differentiation. If patients with moderately differentiated or undifferentiated oral SCC in primary sites had metastatic lymph nodes, CNN would not be able to form in lymph nodes with a maximum diameter of less than 25 mm.
Furthermore, we propose a method for coping with such problems based on our present study. Lymph nodes of heterogeneous density on CT scans should be diagnosed as metastasis in patients with moderately differentiated or undifferentiated SCC in the primary sites, based on our results and those in other reports.7,24 Of course, the decision to perform neck dissection should depend on the obvious presence of metastatic lymph nodes.25 Therefore, we propose that clinicians should watch for density changes in lymph nodes on CT scans to determine whether to perform a biopsy for the presence of metastatic lymph nodes in patients with moderately differentiated or undifferentiated SCC in the primary sites.
Some explanative causes of differences between the extent of differentiated SCC and the incidence of CNN are mentioned below. The process of CNN formation might advance through changes in density, with heterogeneity preceding CNN.7 Perhaps a time lag exists between the tumour filling the lymph nodes and the detection of CNN on a CT scan, with good differentiation resulting in a shorter time lag than moderate or poor differentiation as reported by Som et al.14 Therefore, we compared the spread of SCC according to Honma's report with the incidence of CNN in metastatic lymph nodes.19 We found no significant difference between the two, perhaps because there was no case with stage I in the present study. To our surprise, metastatic lymph nodes without density changes on CT scans were present in cases with stages II and III in the moderate differentiated type of SCC. Perhaps the use of CT scans should be limited in diagnosing metastatic lymph nodes in patients with oral SCC. We physicians must still recognize the limitations of using CT scanning to diagnose metastatic lymph nodes in patients with oral SCC.
We could not find any other significant factors in relation to the incidence of CNN on CT scans in the present study. However, we need to study larger sample sizes to discover the incidence of CNN related-factors. In addition, we should obtain data from the CT scans and pathological examinations of patients with various types of oral SCC.
|
Acknowledgements
|
|---|
This study was supported in part by grants from the Grant in Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and a grant-in-aid for scientific research from President of Kyushu Dental College, to YM.
|
References
|
|---|
- Cummings BJ. Radiation therapy and treatment of the cervical lymph nodes. In: Cummings CW, Fredrickson JM, Harker LA (eds). Otolarynbology head and neck surgery, 2nd Edition, Vol 2, St. Louis, MO: Mosby-Year Book, 1993: pp. 1626–1648.
- Johnson JT. A surgeon looks at cervical lymph nodes. Radiology 1990; 175: 607–610.[Abstract/Free Full Text]
- Spiro RH. The management of neck nodes in head and neck cancer: a surgeon's view. Bull NY Acad Med 1985; 61: 629–637.[Medline]
- Batsakis JG. Tumor of the head and neck. clinical and pathological considerations, 2nd Edition. Baltimore, MD: Willimams & Wilkins, 1979.
- Kuisk H. Development, structure, and function of the lymphatic system. In: Kusik H (ed). Technique of lymphography and principles of interpretation. St Louis, MO: Green, 1971: pp. 5–14.
- Som PM. Update on imaging metastatic cervical lymph node: criteria and differential diagnosis. AJR Am J Roentgenol 1992; 158: 961–969.[Abstract/Free Full Text]
- Som PM. Lymph nodes. In: Som PM, Curtin HD (eds). Head and neck imaging, 3rd Edition. St Louis, MO: Mosby, 1996: pp. 772–793.
- Dooms GC, Hricak H, Crooks LE, Higgins CB. Magnetic resonance imaging of the lymph nodes: comparison with CT. Radiology 1984; 153: 719–728.[Abstract/Free Full Text]
- Friedman M, Shelton VK, Mafee M, Bellity P, Grybauskas V, Skolnik E. Metastatic neck disease: evaluation by computed tomography. Arch Otolaryngol 1984; 110: 443–447.[Abstract]
- Stevens MH, Harnsberger HR, Mancuso AA, Davis RK, Johnson LP, Parkin JL. Computed tomography of cervical lymph nodes: staging and management of head and neck cancer. Arch Otolaryngol 1985; 111: 735–739.[Abstract]
- Close LG, Merkel M, Vuitch MF, Reisch J, Schaefer SD. Computed tomographic evaluation of regional lymph node involvement in cancer of the oral cavity and oropharynx. Head and Neck 1989; 11: 309–317.
- Mancuso AA, Maceri D, Rice D, Hanafee W. CT of cervical lymph node cancer. AJR Am J Roentgenol 1981; 136: 381–385.[Abstract/Free Full Text]
- Feinmesser R, Freeman JL, Nojek AM. Metastaic neck disease: a clinical/radiographic/pathologic correlative study. Arch Otolaryngol 1987; 113: 1307–1310.[Abstract]
- Som PM. Lymph nodes of the neck. Radiology 1987; 165: 593–600.[Free Full Text]
- Yousem DM, Som PM, Hackney DB, Schwaibold F, Hendrix RA. Central nodal necrosis and extra capsular neoplastic spread in cervical lymph nodes: MR imaging versus CT. Radiology 1992; 182: 753–759.[Abstract/Free Full Text]
- Snow GB, Annyas AA, van Slooten EA, Bartelink H, Hart AA. Prognostic factors of neck node metastasis. Clin Otolaryngol 1982; 7: 185–192.[Medline]
- van den Brekel MW, Stel HV, Castelijns JA, Nauta JJ, van der Waal I, Valk J, et al. Cervical lymph node metastasis: assessment of radiologic criteria. Radiology 1990; 177: 379–384.[Abstract/Free Full Text]
- Yamamoto E, Kohama G, Sunakawa H, Iwai M, Hiratsuka H. Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity. Cancer 1983; 51: 2175–2180.[CrossRef][Medline]
- Honma Y. A study on metastasis to the cervical lymph node of oral cancer. Jpn J Oral Maxillofac Surg 1982; 28: 1667–1684. (In Japanese).
- Mancuso AA, Harnsberger HR, Muraki AS, Stevens MH. Computed tomography of cervical and retropharyngeal lymph nodes: normal anatomy, variants of normal, and applications on staging head and neck cance. Part I: Normal anatomy. Radiology 1983; 148: 709–714.[Abstract/Free Full Text]
- Mancuso AA, Harnsberger HR, Muraki AS, Stevens MH. Computed tomography of cervical and retropharyngeal lymph nodes: normal anatomy, variants of normal, and applications on staging head and neck cancer. Part II: Pathology. Radiology 1983; 148: 715–723.[Abstract/Free Full Text]
- Lee AS, Weissleder R, Brady TJ, Wittenberg J. Lymph nodes: microstructural anatomy at MR imaging. Radiology 1991; 178: 519–522.[Abstract/Free Full Text]
- Steinkamp HJ, Hosten N, Richter C, Schedel H, Felix R. Enlarged cervical lymph nodes at helical CT. Radiology 1994; 191: 795–798.[Abstract/Free Full Text]
- Harnsberger HR, et al. Lymph node disease. In: Harnsberger HR, et al. (eds). Diagnostic imaging head and neck, 1st Edition. Salt Lake City, UT, Amirsys, 2004: pp. III-2–2-33.
- William WC, Harold CP, (editors). The neck: diagnosis and surgery, 1st Edition. St Louis, MO: Mosby, 1994.
Top
Abstract
Introduction
