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Annals of Surgical Oncology 8:209-214 (2001)
© 2001 Society of Surgical Oncology

ORIGINAL ARTICLES

The Value of Cloquet’s Node in Predicting Melanoma Nodal Metastases in the Pelvic Lymph Node Basin

Luc J. A. Strobbe, MD, Arjen Jonk, MD, Augustinus A. M. Hart, MS, Johannes L. Peterse, MD, Theo Wobbes, MD, PhD, Omgo E. Nieweg, MD, PhD and Bin B. R. Kroon, MD, PhD

From the Departments of Surgery (LJAS, OEN, BBRK), Radiotherapy (AAMH), and Pathology (JLP), The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; the Department of Surgery (LJAS), Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands; the Department of Surgery (AJ), Streekziekenhuis Kon. Beatrix, Winterswijk, The Netherlands; and the Department of Surgical Oncology (TW), University Hospital St Radboud, Nijmegen, The Netherlands.

Correspondence: Address correspondence and reprint requests to: B. B. R. Kroon, MD, PhD, Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Fax: 31-20-5122554.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: A selection of melanoma patients with groin metastases can benefit from a pelvic (iliac/obturator) lymph node dissection in addition to the infrainguinal dissection. However, there are no reliable criteria to determine which patients may benefit from such an inguinal-pelvic lymphadenectomy.

Methods: In 142 patients (group A) out of a review of 214 groin dissections performed between 1980 and 1994, the tumor status of Cloquet’s node was traced retrospectively. In 52 additional patients (group B), the status of Cloquet’s node was registered prospectively. The number of positive lymph nodes and the total numbers of retrieved nodes were recorded as well. All patients underwent a combined therapeutic inguinal-pelvic lymph node dissection between January 1995 and June 1999 in a tertiary referral center.

Results: Cloquet’s node was free of disease in 18 of 39 patients with involved pelvic nodes in the retrospective study (sensitivity, 54%; negative predictive value, 83%). In the prospective study, 9 of the 20 patients with involved pelvic nodes had a tumor-free Cloquet’s node (sensitivity, 55%; negative predictive value, 78%). Additional immunohistochemical staining of Cloquet’s node resulted in a sensitivity of 65%. In the combined group A&B, the number of positive nodes in the inguinal region (cutoff point more than three nodes) had a sensitivity of 41% and a negative predictive value of 78% to determine the pelvic nodal status. When we combined the number of positive inguinal nodes and Cloquet’s node in group A&B, the best sensitivity was 56% and the best negative predictive value was 82%.

Conclusions: Cloquet’s node has a low sensitivity to predict the pelvic nodal tumor status. This was barely improved when we accounted for the number of positive inguinal nodes. Groin lymph node dissections should encompass the iliac and obturator compartments in patients with palpable inguinal node metastases.

Key Words: Melanoma • Lymphadenectomy • Cloquet • Pelvic lymph nodes


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Melanoma metastases to the regional node basin can be managed surgically by performing a lymph node dissection, with curative or palliative intent. The extent of the dissection of metastases in the lymph nodes of the groin is controversial due to the specific anatomy of the region.

The lymph nodes in the groin are found in the inguinal region with the femoral and inguinal lymph nodes and in the pelvic region, which contains the iliac and obturator nodes. The inguinal nodes lie superficial from the abdominal wall and within the femoral triangle. The pelvic nodes are situated along the iliac vessels and in the obturator fossa. The inguinal ligament separates the inguinal (superficial) nodes from the pelvic (deep) nodes. Lymphatic ducts pass medial from the femoral vein through the femoral canal to connect the two nodal areas.

A melanoma on the lower half of the body that disseminates through the lymphatic system will progress in a stepwise fashion and initially will affect only the inguinal nodes. In the absence of distant disease, inguinal node dissection will cure a patient with involvement limited to these nodes. Combined therapeutic inguinal-pelvic lymph node dissection will cure the patient when subsequent spread has affected the pelvic nodes as well.1,2 It is difficult to determine which patients will benefit from the more extensive node dissection.3

Mann, Coit, and Brennan2,4,5 suggested that the tumor status of Cloquet’s lymph node has prognostic value in determining involvement of pelvic nodes. Cloquet’s node is the first lymph node underneath the inguinal ligament and lies in the narrow waist of the hourglass-shaped groin basin. Interest in the need for additional pelvic node dissection has increased with the advent of lymphatic mapping and sentinel lymph node biopsy. Pelvic nodes are unlikely to be involved when a superficial sentinel node contains only a microscopic amount of disease.6–8

This evolution increased our interest in the value of the transitional node of Cloquet as a possible predictor of deep node involvement. We decided to investigate this issue in two ways. First, we undertook a retrospective review of the status of Cloquet’s node in relation to the other lymph nodes of the completely dissected groin. The second step was a prospective registration of the same data in 52 consecutive patients who underwent a complete therapeutic lymph node dissection with curative intent.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Between January 1980 and January 1995, 214 melanoma patients underwent an inguino-pelvic node dissection with a curative intent at The Netherlands Cancer Institute. In 142 of these patients, the status of Cloquet’s node was documented. This group (group A) consisted of 52 males and 90 females with a median age of 51 years (range, 16–81). The primary melanoma was located on the leg in 110 of these patients and on the trunk in 20. The remaining 12 patients had metastases from an unknown primary melanoma. The median Breslow thickness was 2.6 mm (range, 0.3–11 mm) in the 105 patients in whom this could be determined.

Palpable superficial nodes were present in 131 patients. In the remaining 11 patients, nonpalpable superficial nodes were removed when metastatic pelvic nodes were found during isolated regional perfusion. No patient underwent elective lymph node dissection.

Group B consisted of 53 consecutive patients (which included one patient without detectable Cloquet’s node) who underwent a therapeutic iliac-obturator lymph node dissection with curative intent between January 1995 and June 1999. These patients were treated at The Netherlands Cancer Institute with the exception of four patients who were treated at the University Hospital Nijmegen. There were 25 male and 28 female patients, with a median age of 50 years (range, 19–89). The primary melanoma was located on the leg in 40 patients and on the trunk in eight. The primary melanoma site was unknown in the other five patients. The median Breslow thickness was 4.0 mm (range, 0.9–7.1 mm). In 46 patients, the node dissection was carried out for palpable metastases, whereas in seven a tumor positive sentinel node was the indication. In the group B patients, the surgeons meticulously searched for Cloquet’s node and submitted this node separately for pathological examination.

No evidence of deep nodal involvement was present in either group A or B patients on preoperative physical examination, ultrasonography, or computed tomography scans as far as these were performed. Various surgeons used various incisions. All surgeons removed the inguinal, femoral, external iliac, and obturator nodes. All lymph nodes were assigned to one of these nodal regions, and all were examined separately by the pathologist. The microscopic examination consisted of one or two sections per lymph node, stained with hematoxylin and eosin. From Cloquet’s nodes in group B, found to be tumor-free in the presence of positive pelvic nodes, serial sections were stained immunohistochemically in search for HMB 45 and S 100.

The ability to predict the pelvic lymph node tumor-status was determined based on the status of Cloquet’s node, on the number of involved inguinal nodes, and on both parameters combined. These data were calculated for group A and B separately and for the two groups combined.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Of the 142 patients in group A, 39 (27.5%) had tumor-positive pelvic nodes. Two patients in whom an inguinal lymph node dissection was performed after finding positive pelvic nodes in the course of an isolated limb perfusion had only iliac/obturator nodal disease. Cloquet’s node was tumor-positive in 21 of these patients with pelvic nodal disease, which resulted in a 54% sensitivity (Table 1). In 13 patients with a positive Cloquet’s node, the pelvic lymph nodes were not yet involved, which resulted in an overall false-positive rate of 38%.


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  		TABLE 1. Results, in Group A (142 Patients)
 
There is a relation between the number of positive inguinal nodes and the tumor status of the pelvic nodes. More tumor-positive than negative pelvic nodes are found when the inguinal region contains more than three positive nodes (Table 1). Cloquet’s node was never false-negative in the 25 patients with more than three tumor-positive inguinal lymph nodes. A false-positive Cloquet’s node, however, occurred in 9 of these 25 patients in whom no pelvic tumor was found, with a resulting positive predictive value of 41% and a 64% sensitivity.

Of the 53 prospectively studied patients (group B), 20 had tumor-affected pelvic nodes (38%). Cloquet’s node could not be retrieved in one patient. The node of Cloquet was tumor-positive in 11 of these 20 patients, which resulted in a 55% sensitivity and a negative predictive value of 78%. Cloquet’s node was false-negative in 45% (Table 2). A median number of 6.5 pelvic nodes (range, 3–13) was retrieved. Immunohistochemical staining for S 100 and HMB 45 on the nine false-negative Cloquet’s nodes revealed two of these nodes to be tumor-positive after all. This raised the sensitivity to 65% and the negative predictive value to 82%.


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  		TABLE 2. Results in Group B (52 Patients)
 
In 10 patients, more than three positive inguinal nodes were found (Table 2). The presence more than three metastatic inguinal nodes as a predictor of pelvic node involvement carries a sensitivity of 40% and a negative predictive value of 71% (Table 2).

Because the results of the two groups are comparable (P = .22), the results of group A and B are combined for the discussion and conclusions (Table 3).


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  		TABLE 3. Results in Group A & B (194 Patients)
 
As a next step, the combination of the two predictive factors (Cloquet’s node and number of positive inguinal nodes) was tested for its predictive value. In most patients, the two factors predicted the same status for the deep nodes. In 26 cases of the 194, however, conflicting predictions were found. We had to decide which factor the heaviest weight should be assigned: a higher sensitivity or a higher specificity. The results are presented in Table 4. Choosing for optimal sensitivity gives a still disappointing 56% sensitivity and an 82% negative predictive value. The opposite choice leaves us with a 39% sensitivity and a negative predictive value of 79%.


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  		TABLE 4. Probability of Positive Pelvic Nodes in Relation to the Combination of the Status of Cloquet’s Node and the Number of Positive Inguinal Nodes
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Of the 194 assessable patients who underwent a complete node dissection, 59 (30%) had involved pelvic nodes. This is not unlike data gathered from 849 patients described in the literature. Various investigators found that 13% to 52% of their patients had involved pelvic nodes.1,2,4,5,9–11 However, meaningful comparison of data from various investigators suffers from patient selection bias.

From our combined series of patients, we derive that either a tumor-positive Cloquet’s node or the presence of more than three involved inguinal nodes means a 69% risk (positive predictive value) of additional nodes that bear disease. The simultaneous presence of both factors increases that risk to 63% to 88%.

Several other investigators looked at Cloquet’s node as an indicator of deep node involvement (Table 5) and found the predictive value of a tumor-positive Cloquet’s node to be less than what the current study showed: 27% to 79%.4,11,12


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  		TABLE 5. Probability of Positive Pelvic Nodes in Relation to the Status of Cloquet’s Node, LiteratureReview
 
It seems that roughly four out of five patients with a tumor-involved Cloquet’s node have deep nodes that contain metastatic disease. This is in accordance with our current understanding that disseminated melanoma progresses through the lymphatic system in a sequential fashion.6,13 Apparently the disease had not yet gone beyond Cloquet’s node in the other one in five patients. This latter estimate is probably too high, given the technical constraints that limit pathologists in their evaluation of a lymph node dissection specimen. These findings lead us to conclude that pelvic node dissection is indicated when Cloquet’s node is involved. The same can be concluded for the presence of more than three metastatic inguinal nodes.

A tumor-negative Cloquet’s node means an 82% (negative predictive value) chance of absence of additional involved nodes in our patients. More than three involved inguinal nodes means a 78% chance of absence of involved deeper nodes. The simultaneous absence of both factors does not improve the negative predictive value beyond 82%.

Immunohistochemical evaluation of Cloquet’s node improved the negative predictive value to 82% in our group B and to 86% in Shen et al.’s series.11

Coit and Brennan4 found a 95% negative predictive value in a selected group of 84 patients. Although differences in patient populations may be responsible for at least some of the differences, it seems that lymphatic vessels bypass Cloquet’s node in a variable but substantial number of patients. The incidence and the pathways of these lymphatics are the subject of further study at our institution.

The conclusion from the present data is that too many patients will not be treated for their pelvic lymph node metastases when a tumor-free Cloquet’s node is used to justify omission of further dissection. The potential benefit from removal of metastatic pelvic nodes is substantial: some 25% to 35% of these patients will live for at least 5 years, and 20% will live for at least 10 years.1,2 The additional morbidity as a result from the more extensive operation is limited.1,10

Because both a tumor-positive and a tumor-negative Cloquet’s node should lead to a pelvic dissection, there is not much point in looking at this node. Combining the tumor status of Cloquet’s node with the number of involved superficial nodes does not improve the predictive value sufficiently. Immunohistochemical techniques provide only limited additional discriminating power over classic histological specimen staining.

Clinical examination, ultrasound, and computed tomography scan have limited value in the detection of pelvic node metastases, unless the nodes become significantly enlarged.9,14,15 Recently, several reports on the value of the positron emission tomography scan in metastatic melanoma reported high sensitivity figures for the detection of subclinical lymph node metastases.16–20 However, the value of positron emission tomography scanning in combination with the examination of Cloquet’s node remains to be determined.

The present study concerns patients with palpable inguinal metastases. These results should not be extrapolated to patients with a tumor-involved node found in an elective lymph node dissection and to patients in whom the sentinel lymph node contains metastatic disease. These patient categories have a much smaller risk of involvement of deeper nodes. In sentinel node patients, lymphoscintigraphy can be used to determine the need for pelvic node dissection. Scintigraphy usually indicates whether the lymph node next-in-line is situated beyond the inguinal ligament.

In conclusion, the tumor status of Cloquet’s node does not predict accurately the tumor status of the pelvic lymph nodes. Looking at this node separately does not improve patient management. Additional use of the number of involved superficial nodes does not improve the predictive value sufficiently. Groin lymph node dissections should encompass the iliac and obturator compartments in patients with palpable inguinal node metastases.

Received for publication March 21, 2000. Accepted for publication October 27, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Strobbe LJA, Jonk A, Hart AAM, Nieweg OE, Kroon BBR. Positive iliac and obturator nodes in melanoma: Survival and prognostic factors. Ann Surg Oncol 1999; 6: 255–62.[Abstract]
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  11. Shen P, Conforti A, Turner R, et al. Is the node of Cloquet the sentinel node for the iliac/obturator node group? Poster presentation at: the American Radium Society, Kona, Hawaii, April 17–21, 1999.
  12. Illig L, Aigner KR, Biess B, et al. Diagnostic excision of Rosenmüllers node. Cancer 1989; 61: 1200–6.[CrossRef]
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  16. Dietlein M, Krug B, Groth W, et al. Positron emission tomography using 18F-fluorodeoxyglucose in advanced stages of malignant melanoma: A comparison of ultrasonographic and radiological methods of diagnosis. Nucl Med Commun 1999; 20: 255–61.[Medline]
  17. Hsueh EC, Gupta RK, Glass EC, Yee R, Qi K, Morton DL. Positron emission tomography plus serum TA90 immune complex assay for detection of occult metastatic melanoma. J Am Coll Surg 1998; 187: 191–7.[CrossRef][Medline]
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  19. Macfarlane DJ, Sondak V, Johnson T, Wahl RL. Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. J Clin Oncol 1998; 16: 1770–6.[Abstract]
  20. Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography: Results of a prospective study of 100 patients. Cancer 1998; 82: 1664–71.[CrossRef][Medline]



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