Preoperative Localization of Neck Recurrences from Thyroid Cancer: Charcoal Tattooing Under Ultrasound Guidance

Abstract

Background:

Reoperation for thyroid cancer recurrence is a surgical challenge in previously dissected necks, and there is a need for a reliable procedure for surgeon guidance. In this study, the usefulness of preoperative charcoal tattooing for surgical guidance was evaluated.

Methods:

From July 2007 to May 2010, 53 patients (40 females; M _age=44 years, range 19–76 years) were prospectively included for preoperative localization of neck recurrences from differentiated (n=46) or medullary thyroid cancer (n=7). Preoperative cytological assessment was performed for at least one lesion in each patient. Ultrasound (US) imaging was performed with high-frequency probes (8–14 Mhz). Micronized peat charcoal (0.5–3 mL) was injected under US guidance using a 25 gauge needle, 0–15 days preoperatively.

Results:

A total of 106 lesions were selected for charcoal tattooing. Of these, 101 had been tattooed, and 102 were removed (85 metastases, 17 benign on pathology). The tolerance of charcoal injection was good in all but three patients. A mean volume of 1 mL of charcoal was injected with a mean of two targets per patient. Charcoal labeling facilitated intraoperative detection in 56 “difficult” lesions (i.e., small size, dense fibrosis, anatomical pitfalls), and charcoal trace facilitated intraoperative guidance in 17 lesions. Feasibility and usefulness rates were 83% and 70.7% respectively.

Conclusion:

These findings suggest that charcoal tattooing under US guidance is an easy to implement, safe, and useful procedure for surgeon guidance in neck reoperation for thyroid cancer.

Introduction

Surgical reintervention for the recurrence of differentiated thyroid cancer is a technical challenge because of fibrous scar tissue and damaged anatomical landmarks in previously dissected necks. Today, surgical resection is the main curative treatment option for local recurrence of well differentiated thyroid cancer. Widespread use of ultrasound (US) and serum thyroglobulin (Tg) measurements in monitoring algorithms increase the rate of early detection of persistent or recurrent disease (1,2). A reliable preoperative procedure for localization should optimize complete excision of neoplastic foci. Tattooing targets with a charcoal suspension is a new technique in neck disease localization, and to date this procedure is supported by only three studies reporting encouraging results (3 –5). In this current prospective study, the authors' experience in preoperatively localizing thyroid cancer recurrences in the neck by fine-needle injection of charcoal pigment under US guidance is reported. Technical endpoints, feasibility, and usefulness are discussed.

Patients and Methods

From July 2007 to May 2010, patients who were candidates for neck reoperation for nonpalpable recurrent disease from differentiated or medullary thyroid cancer were prospectively included. All lesions were visualized with US. Recurrent disease was assessed by cytology in all but three patients who had a medullary carcinoma in whom recurrent disease was assessed based on a combination of elevated serum calcitonin levels, positron emission tomography–computed tomography (PET-CT) and US findings. The first 15 patients have been previously reported (4). This prior article dealt with the preliminary results in terms of success rate and described the complications observed initially.

Informed consent was obtained from each patient. Presurgical US imaging was performed using a machine with high-frequency probes (8–14 Mhz; Aplio; Toshiba, Otawara, Japan) for extensive testing of the characteristics of suspicious and/or malignant lesions: number, localization, size, and suspicious features for malignancy. Experienced radiologists in head and neck diseases performed all US examinations and US-guided fine-needle biopsies. On US imaging, suspicious lymph nodes were characterized based on criteria reported in the literature (i.e., size, microcalcifications, cystic changes, loss of hilum, and peripheral vascularization) (6 –9).

The aim of presurgical localization was to target the most difficult lesions to excise. The issue of which targets to select was discussed by the surgeon and the radiologist before each procedure. During surgery, a systematic re-exploration of the neck compartment was performed, and resection was based on the intraoperative findings. The resection was limited to the charcoal tattooed lesions when no other lesions were found, or further lymph nodes were resected if the compartment has not been completely dissected during the previous surgery. The criteria that were taken into account were: size, location of the potential targets, and the surgical status (number of previous operations of the neck, field of resection).

Between 0.5 and 3 mL of micronized peat charcoal (“Sterile Pigment Cender's”; Derm Tech, Pavillons sous Bois, France) was injected in each node under US guidance using a fine needle (25 gauge) and a 5 mL syringe, 0–15 days preoperatively. Needle insertion was performed after local cutaneous anesthesia (Emla^® patch). As a matter of precaution, when the tip of the needle was positioned in or just next to the suspicious lesion, the charcoal suspension was continuously injected inside and during the needle withdrawal to leave a trace of charcoal directed toward the lesion.

All operations were performed by one of two experienced endocrine surgeons (J.P.T. and D.H.). Surgery was planned according to preoperative imaging findings (US, ¹³¹I scintigraphy, PET-CT) and consisted of a careful dissection to excise any lymph node or mass found in the suspected area. In patients with radioiodine avid lesions, an intraoperative radioactivity probe was also used (10).

Intraoperative reports included surgeon observations about charcoal deposit: presence or absence and location of the pigment (inside, just next to, or distant from the lesions) and the influence of tattooing for facilitating detection. The surgeon considered that the procedure was facilitated when the dissection was guided by the trace of charcoal on the path of the needle toward the target and/or if the target itself became visible due to the deposition of pigment inside or around it. Fibrosis was noted if considered significant by the surgeon.

US preoperative findings were then compared to intraoperative findings and to the pathology report. The success rate and usefulness of the preoperative charcoal tattooing as well as failure and complications of this technique were then evaluated.

Results

Population and target lesions

Fifty-three patients (40 females; M _age=44 years, range 19–76 years) with recurrent disease in the neck from thyroid cancer were prospectively included, and a total of 106 lesions were identified for charcoal tattooing. The primary cancer was papillary carcinoma (n=45, 85%), followed by Hürthle cell carcinoma (n=1, 2%) or medullary carcinoma (n=7, 13%). The number of previous operations per patient ranged from one to five (M=1.8): one previous operation (n=26), two (n=16), three (n=7), four (n=3), five (n=1). Of the 106 targets, 100 were surgically removed and underwent histological analysis: 83 were metastases from thyroid cancer, and 17 were benign on pathology (reactive lymph nodes n=10, granuloma n=4, thyroid remnant n=1, parathyroid gland n=1, and neuroma n=1). Surgery failed to remove six targets: two were reoperated and were found to be metastases on final histological analysis; in the remaining four cases (small lesions, characterized as suspicious only by US), the postoperative follow-up was normal.

The mean size of the lesions was 9.7 mm (median 9 mm; range 3–26 mm). Lesions were ≤10 mm in 71 cases (67%), of which 27 were ≤6 mm (25%).

Targets were localized in the central compartment (levels VI, VII, and thyroidectomy bed) in 57 cases (54%) and in lateral compartments (levels II, III, IV, and V) in 49 cases (46%).

The mean number of tattooed lesions was two per patient (range 1–6): 1 lesion in 28 patients, 2 in 10, 3 in 9, 4 in 3, 5 in 2, and 6 in 1 patient. A mean charcoal volume of 1 mL (range 0.5–3) was injected.

US for determination of malignancy

In each patient, preoperative cytological assessment was performed for at least one lesion and additionally for lesions whose excision would have modified the extent of surgery. For each lesion, malignancy was supported by cytology in 42 cases (39.6%), preoperative ¹³¹I uptake in 20 (19%), and FDG uptake in 18 (17%).

An additional 26 (24.5%) lesions were detected by US alone in 10 patients with proven disease elsewhere. Among these 26 additional suspicious lesions, 13 (50%) revealed metastases on pathology, 9 (35%) were benign lymph nodes, and 4 nodes <5 mm in size could not be removed. In these cases, the postoperative Tg level after stimulation was undetectable.

Feasibility and limitations

Charcoal pigment was injected in 101 of the 106 initial lesions. In five cases, the operator considered that the lesions were not accessible for fine-needle targeting at the time of the procedure. The operator did not perform charcoal injection because the location was behind or just next to vessels in four cases and because of small size (3 mm) in one case. In 88 targets (83%), charcoal injection could be achieved safely, and charcoal deposit was confirmed intraoperatively. Thirteen lesions had been injected but were not found intraoperatively. Intraoperative reasons for missed lesions despite charcoal injection were limited visibility because of charcoal diffusion or, conversely, a lack of or insufficient charcoal deposit.

Usefulness of charcoal tattooing

Usefulness was based on the intraoperative findings. Charcoal tattooing was estimated to be useful in 75 of the 106 targets (70.7%) because the trace of charcoal pigment placed during withdrawal of the needle was visible and facilitated dissection toward the target in 17 cases. Additionally, in 58 cases, the lesions themselves were detected due to the pigment deposit inside or just next to the lesion. Conversely, 13 lesions, which were successfully marked and removed, were not taken into account in the estimation of the usefulness rate because the surgeon considered that they were easy to detect. These lesions were >1 cm in size and located in lateral compartments or were palpable.

The surgeons considered that intraoperative detection would have been difficult without charcoal guidance for the following lesions: small size ≤6 mm (n=20), when lesions were embedded in dense fibrosis (n=23), anatomical pitfalls (n=13), and for lesions where radioguided surgery failed (n=2). The anatomical pitfalls included lesions masked by large vessels (n=8), thymus (n=1), lesions embedded in a muscle (n=2), and atypical location in a small supraclavicular compartment just in front of the level IV aponeurosis (n=2).

Tolerance and complications

During injection, three patients suffered from marked pain without any local complications. In one of these cases, the pathology revealed a neuroma. Tolerance of the injection was considered good in all other patients (slight to moderate discomfort).

During charcoal injection, the fine needle injured the carotid artery in two patients with small lesions of 5 and 6 mm located in level VII and VI respectively. In these patients, the intraoperative findings revealed locally circumscribed hematomas without clinical symptoms.

In one case of a benign granuloma colored by charcoal, the histological analysis was difficult because of pigment saturation.

No permanent or transient laryngeal recurrent nerve palsy was observed after charcoal tattooing.

Discussion

The management of recurrent disease requires a multidisciplinary approach, and surgery remains the most common treatment in recurrent or persistent well differentiated thyroid cancer (11 –13). The lesions to be removed must be precisely localized preoperatively as much as possible.

US identification and accessibility of lesions is required for charcoal tattooing. Recurrent lesions are frequently multiple, and preoperative ultrasonography is decisive because it may reveal additional suspicious lesions that should be addressed in order to assure complete excision (2,14 –17). In our patients, 26 (24.5%) additional lesions were detected by US alone, and 50% of these lesions proved to be malignant on histological analysis.

The surgical management of recurrent or persistent disease in thyroid cancer is a challenge and needs experienced hands (18). Currently, there is a lack of a reliable procedure for surgeon guidance. To date, the most common procedure for intraoperative guidance is the use of a gamma probe to detect radioiodine-avid foci (10,19 –22). Nevertheless, false negative and false positive findings or background artifacts may occur and limit its efficacy. Moreover, the localization of lesions that are not radioiodine-avid remains problematic. Other radioguided methods as well as other radiotracers such as FDG were recently developed for the intraoperative guidance of nonradioiodine-avid cancer, but cost, availability, and signal-to-noise issues may limit their widespread use (23 –30). Other modalities such as intraoperative US exploration, hook needle insertion, or tattooing using blue dye have also been described, but to the authors' knowledge, their efficacy, safety, and feasibility have not yet been established, and they have been evaluated in only a few published studies in head and neck disease (31 –37).

Charcoal tattooing represents an interesting method, and its use has been proposed recently in neck reoperations for thyroid cancer with promising results (3 –5). This method has been previously used in skin tattoos for centuries and more recently, in the 1990s, in breast cancer (38 –42). The physical and pharmacological properties of charcoal pigment allow limited diffusion and improved stability that represents a key characteristic in soft-tissue tattooing (43 –45). Furthermore, this procedure is easy to implement, as tattooing may be performed even one month before surgery in the radiology unit and in the ambulatory setting, which means that surgery can be planned later.

Objective evaluation of the usefulness of a preoperative localization procedure in regards to intraoperative findings is difficult to assess and, ideally, should compare parameters such as operation time, rate of removed lesions, and rate of complications between surgeries with and without the procedure for the same lesions. Of course, this is unachievable in a clinical trial setting, due to the variability of presentations of neck recurrences of thyroid carcinomas.

In our study, the usefulness and failure rates were based on intraoperative findings and on the estimation of the facilitation of the operation by an experienced surgeon. Basically, the main challenges in the reoperation of the neck are the small size of the lesions and the presence of fibrous scar tissue. Small-sized lesions are potentially more difficult to detect intraoperatively. As such, small lesions were preferentially selected and widely represented in the current cohort (67% were ≤10 mm, including 25% of lesions ≤6 mm).

On the other hand, US is unfortunately unable to differentiate the normal soft tissues from fibrous scar tissue, which is known to be a potential surgical trap. Therefore, the complexity of intraoperative detection of some lesions embedded in fibrous tissue would be misestimated by preoperative US.

Considering that targets were selected that would potentially be the most difficult to excise for charcoal tattooing, the current results show a high rate of feasibility (83%), and the procedure was considered useful by the surgeon in 70.7% of cases. In a study by Kang et al., the success rate was higher (96%) and was obtained by evaluating the number of marked lesions removed. However, it is important to notice that the injected lesions were predominantly located in the lateral compartments (70%) (4). In the present study, the targets that were located in the central compartments were slightly more prevalent (54%) than those in the lateral compartments (46%).

However, the lateral compartments are known to be more accessible to fine-needle targeting under US guidance, as well as to surgical exploration. Moreover, the dissection of these levels does not represent a surgical challenge in terms of postoperative morbidity. Of note, Soprani et al. tattooed exclusively the lesions that were located in the central compartments (level VI), and the concomitant localizations in other levels were not marked because selective neck dissection was performed (5). In the present study, some lateral lesions were marked when it was felt that this would facilitate the surgery and optimize a complete excision. This included the lesions that modified the extent of surgery and that were associated with potential anatomical traps (some level IV targets masked by great vessels, targets embedded in muscle). In addition, the aim was to tattoo some lesions to ensure inclusion in the dissection for small or macroscopically non-suspicious lesions.

Charcoal tattooing is a technical challenge and needs experienced hands in fine-needle biopsy/targeting under US guidance. The majority of our targets were not easy to locate because they were predominantly localized in central compartments in the vicinity of the trachea and/or great vessels and, furthermore, were of small size. Nevertheless, except for some cases of hematoma and cough, the tolerance was considered good and similar to that of fine-needle aspiration biopsy with moderate discomfort. Of note, 56% of our patients underwent more than one targeting procedure safely. Ideally, the tip of the needle should be positioned into the lesion in order to color the target itself. In the study by Soprani et al., the authors preferred to avoid injection inside the lesions, and they marked only the needle withdrawal track in order to avoid compromising histological examination (5). In the current study, as well as in that by Kang et al. (4), the injection of pigment inside the target itself did not affect histological examination, and only one case of difficult histological analysis was observed due to pigment saturation in a benign granuloma. However, not all the lesions could be tattooed. For the lesions that were not accessible for fine-needle targeting, as well as for lesions that were embedded in dense fibrous scar tissue, a trace of charcoal as near as possible to the target and along the path of the needle was found to be useful for surgical guidance, as well for the detection of the lesions. Therefore, a systematic injection of pigment along the path of the needle can be recommended for optimizing the localization of a lesion.

The principle causes of failure of the procedure appeared to be a widespread diffusion of charcoal in the surgical field as well as a lack of pigment deposit. The reasons may not be uniform and are probably partially combined. It is estimated that the degree of fibrosis of the tissue surrounding the target, the size and the consistence of the lesion itself, as well as the blockage of the needle tip by charcoal particles play an important role at the time of injection and might partially explain the failure rate. A blockage of the needle tip by charcoal particles because of peat charcoal suspension characteristics (particulate form and insoluble in water) has been previously described as a serious problem in tattooing breast lesions, and it was also been observed by the authors (41). Because of an initially positive tissue pressure, as well as a blockage of the needle tip, the injection might not be performed at a constant pressure along the path of the needle, which would make the volume of the injected charcoal difficult to control. Thus, in the present study, surgical data proved to be important in order to retrospectively correlate the histological findings with the US findings to understand better the reasons for failure and to improve the learning curve in the preoperative labeling.

Conclusion

Charcoal tattooing under US guidance represents an interesting and reliable method for surgical guidance in the reoperation of neck recurrences of thyroid cancer. The procedure is not expensive, easy to implement, and well tolerated by the patients. Ideally, the targets to be addressed for preoperative tattooing should be evaluated and discussed by the US operator and the surgeon. The efficacy of this method depends on the experience of the US operator in charcoal labeling, and cooperation with the surgeon is strongly recommended for a better understanding of the surgical needs in order to optimize the procedure.

Footnotes

Acknowledgment

A special acknowledgment to Dr. Jean Paul Travagli who made this work possible and for his expert advice.

Author Disclosure Statement

No competing financial interests exist.

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