Original article
Zonal mapping of sentinel lymph nodes in penile cancer patients using fused SPECT/CT imaging and lymphoscintigraphy

https://doi.org/10.1016/j.urolonc.2018.09.002Get rights and content

Highlights

  • Using a combination of lymphoscintigraphy and fused SPECT-CT, we have demonstrated for the first time that the pattern of lymphatic drainage is such that the sentinel lymph nodes may be located in the inferior zones according to Daseler's classification.

  • The radiological boundary for Zone V has also been defined.

  • The location of lymph nodes in the inferior zones may account for disease recurrence.

Abstract

Purpose

To define the anatomical location of sentinel lymph nodes (SLN) in penile cancer patients based on Daseler's original zonal description using a combination of single photon emission computed tomography-computed tomography (SPECT-CT), cross sectional imaging and lymphoscintigraphy and characterise the limits of Zone V.

Materials and methods

Patients with primary penile cancer ≥T1G2 were included in the study. A total of 113 groins with impalpable inguinal lymph nodes (cN0) underwent planar lymphoscintigraphy and SPECT-CT. The sentinel lymph nodes were mapped on cross sectional imaging according to Daseler's anatomical description. Using measurements from fixed anatomical landmarks, a custom-made software program mapped the SLNs. SLNs were mapped to the previously undefined Zone V using 3 approaches to avoid observational bias: (a) as perceived by the uroradiologist, (b) limiting Zone V to a 5 mm radius from the sapheno-femoral junction or (c) using a 10 mm radius from the sapheno-femoral junction.

Results

Using SPECT-CT, drainage to the groins was seen in 109 of the 113 cN0 groins (96.5%). The majority of the SLNs were located in the central and superior quadrants with 38.2% lying within Zone I, 45% in Zone II and 13% in Zone V. More importantly, sentinel lymph nodes were still localised to the inferior zones with 3% located in Zone III and 0.8% in Zone IV.

Conclusions

Using a hybrid of SPECT-CT, cross sectional imaging and lymphoscintigraphy we have demonstrated that SLNs may be located in the inferior zones. We also define the limits of Zone V as an area of 5 mm radius from the sapheno-femoral junction.

Introduction

Squamous cell carcinoma of the penis is rare with an incidence of 0.3 to 1.6 new cases per 100,000 males per year in Western Europe and North America [1], [2]. Anatomical and observational studies have demonstrated that the lymphatic drainage from the penis initially travels to the superficial inguinal lymph nodes followed by the deep inguinal lymph nodes before spreading to the pelvic lymph nodes [3], [4]. Previous studies have also shown that the most important prognostic indicator in patients diagnosed with penile cancer is the presence of metastatic inguinal lymph node disease [5], [6]. This is demonstrated by the fact that patients presenting with palpable metastatic inguinal lymph nodes have a 5 year disease specific survival ranging from approximately 25% to 77% for those with more extensive inguinal node metastases and those with small volume lymph node involvement (typically <2 nodes), respectively [5]. In patients with no evidence of inguinal metastases, (pN0) surgical resection of the primary penile tumour is generally curative for the majority of patients [7]. Therefore an accurate assessment of the inguinal lymph node status should be performed for both prognostic and for therapeutic benefit.

Clinically impalpable inguinal lymph nodes (cN0 disease) still have a 15% to 24% chance of harbouring micrometastatic disease [8], [9], [10]. Therefore subjecting all newly diagnosed patients to a radical inguinal lymphadenectomy would mean that over 75% of patients would undergo unnecessary inguinal lymphadenectomy with the associated morbidity rate of over 50% [8], [9], [10].

Conventional imaging modalities (CT and MRI) have a low sensitivity and variable specificity in detecting micrometastatic disease in the inguinal and pelvic lymph nodes [11], [12], [13], [14]. Therefore dynamic sentinel lymph node biopsy (DSNB) has been developed to detect occult disease and ensure that only those cN0 patients with definite micrometastatic disease proceed to a radical inguinal lymphadenectomy [15], [16].

The inguinal region is commonly divided into five anatomical zones in order to define the location of the lymph nodes and is based on the extensive work by Daseler et al. [17]. This predefined pattern of lymphatic drainage forms the basis for the surgical boundaries for an inguinal lymphadenectomy whereas lymphangiographic studies have defined the location of the sentinel lymph node [18]. Previously there has only been one study which has assessed the lymphatic drainage pattern in penile cancer using a combination of SPECT-CT and lymphoscintigraphy [19].

The aim of this study was to define the zonal anatomical location of the sentinel lymph nodes in the inguinal region based on Daseler's classification using a combination of SPECT-CT, cross sectional imaging and lymphoscintigraphy. The distribution of the sentinel lymph node aids in defining the surgical boundaries for both a superficial modified inguinal lymphadenectomy and radical inguinal lymphadenectomy as well as providing a radiological definition for Zone V.

Section snippets

Materials and methods

A total of 60 consecutive penile cancer patients with impalpable inguinal nodes (cN0) were included in the study and underwent imaging using lymphoscintigraphy, SPECT-CT and dynamic sentinel lymph node biopsy using 99mTc nanocolloid as part of our institutions standard of care, which did not require additional ethical review. All patients had a prior diagnosis of primary SCC with a stage and grade ≥ pT1G2 and consented for the sentinel node procedure as part of their standard management. Those

Nuclear imaging acquisition protocol

Anterior dynamic lymphoscintigraphy was performed for 10 minutes immediately after injection with 0.4 ml of 99mTc- nanocolloid. Images were obtained using a dual-head gamma camera (Discovery NM/CT 670, General Electric, USA). In addition, anterior and lateral static images were obtained after 15 minutes, static films at 5-minutes and delayed static images at 2 hours post injection, with simultaneous transmission scanning using a cobalt-57 flood source to outline the body contour for orientation.

Image interpretation

The sentinel lymph node was defined as the first lymph node receiving lymphatic drainage from the penis. To accurately determine the anatomical location of the radioactive sentinel lymph nodes (SLNs) in the groin, fused MRI/CT and SPECT-CT images were analysed. Using the fused SPECT-CT images, the position of the SLN(s) was plotted into the corresponding Daseler's zones [17]. If more than one lymph node was noted on lymphoscintigraphy in the inguinal region then the node(s) with the higher

Zonal classification in penile carcinoma

Although Rouvière was the first to define a classification system for the superficial inguinal lymph nodes [21], Daseler's zones are still routinely used with division into four quadrants and a central zone overlying the sapheno-femoral junction (SFJ) (Fig. 1).

Zonal mapping of the SLN in this study

As the limit for Zone V is essentially arbitrary, in order to avoid observational bias three distinct approaches were used to classify the SLN into the respective zones in the groin, by our uroradiologist.

The coronal and trans-axial SPECT images were analysed and the SLN was plotted into one of the five zones in the groin using the following three distinct approaches based on Daseler's classification.

  • Approach 1: as perceived by the specialist uroradiologist.

  • Approach 2: limiting Zone V to a 5 mm

Tables, graphs and statistical analysis

The Excel Spreadsheet (Microsoft) was used for data analysis and SPSS (Chicago, IL, USA) was used to perform statistical analysis. Using the measurements by the uroradiologist, a custom-made program, YiSTAT© (Cambridge, UK), using a mathematical model allowed the mapping of the SLN to scale, pixel to mm ratio, onto a two dimensional image of the groin, based on the SLN distance from the SFJ in the X-axis and Y-axis.

Results

Of the 60 patients (120 groins), included in the study, 113 groins were cN0 as in the remaining 7 a contralateral radical lymphadenectomy had already been performed due to either palpable disease or suspicious lymph nodes on imaging. On the planar lymphoscintigraphic images, drainage was seen in 107 of the 113 cN0 groins, leading to a visualisation rate of 94.7%. Using SPECT, drainage was seen in 109 of the 113 cN0 groins leading to visualisation in 96.5% of cases. In one patient with bilateral

Zonal mapping of sentinel nodes

A total of 131 sentinel nodes were found using SPECT-CT imaging. All of the sentinel nodes were located in the inguinal region, with no localisation of the sentinel node to the pelvic lymph node chain. The number of SLNs detected per groin was 68 on the right and 63 on the left.

Using each of the approaches for node localisation, Tables 2 and 3 show the distribution of the nodes in each groin.

Mapping of sentinel lymph nodes in the groin

The YiSTAT© customised software was utilised. The SLNs were mapped per groin using Daseler's classification. A 5 mm radius from the SFJ was used to define Zone V. In Figs. 2 and 3 each green cross represents an individual SLN from the dataset.

Distribution of positive sentinel lymph nodes

A total of 8 of 60 patients (13.3%) with clinically node-negative lymph nodes had at least one positive sentinel lymph node with metastatic disease in the inguinal region. The sentinel lymph node was found to harbour micrometastatic disease in 9 groins of 8 patients (one patient had tumour in bilateral sentinel lymph nodes). The primary tumour in these cases showed the presence of lymphovascular invasion in only 2 cases.

A subanalysis of the distribution of the metastatic SLNs in the respective

Discussion

The identification of distinct lymph node groups within the inguinal region, by Rouvière, was an important landmark [21]. Subsequent investigators have attempted to highlight the regional anatomy of the inguinal region as part of the surgical management of genital cancers and melanoma. Indeed it was Daseler's laborious work and description of the lymphatics of the inguinal region based on anatomical dissections that defined the exact boundaries of the superficial inguinal lymph nodes [17] and

Conclusions

This study has demonstrated that using a combination of lymphoscintigraphy and fused SPECT-CT, we have demonstrated for the first time that the pattern of lymphatic drainage is such that the sentinel lymph nodes may be located in the inferior zones according to Daseler's classification as well as defining the radiological boundary for Zone V, which was previously defined as being at the sapheno-femoral junction but did not take into consideration the variability in the size of the individual

Conflict of interest

The authors confirm that there is no conflict of interest in relation to the work performed in this study and the interpretation of the results. In particular there has been no external funding for this study.

Acknowledgments

Mr. Asif Muneer is supported by the NIHR Biomedical Research Centre University College London Hospital.

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