Tumor seeding incidentally found two years after robotic—Assisted radical nephrectomy for papillary renal cell carcinoma. A case report and review of the literature

Abstract

INTRODUCTION

Port-site metastasis or peritoneal spread after laparoscopic surgery for urological malignancies is a rare phenomenon accounting for 0.09% and 0.03% of the cases respectively.

PRESENTATION OF CASE

We present a case of tumor seeding in the omentum found in a female patient after previous transperitoneal robotic-assisted radical nephrectomy (RARN) for papillary renal cell carcinoma (RCC). Two years after the robotic operation, the patient was diagnosed with cervical clear cell carcinoma and underwent radical hysterectomy with lymphadenectomy and omentectomy. A neoplastic omental nodule was incidentally identified intraoperatively. Pathological characteristics and immunohistochemistry revealed features of papillary RCC. Two years after the hysterectomy, the patient is clinically cancer free, without any adjuvant therapy for her cervical cancer.

DISCUSSION

To the best of our knowledge, we report the first case of tumor seeding in the omentum following RARN for organ confined low grade papillary (T2aN0M0) RCC. No risk factors that could explain the tumor seeding were identified. The neoplastic cells had a low proliferative index (Ki-67 < 5%) and a decreased capability to metastasize.

CONCLUSION

Tumor seeding as a result of robotic assisted laparoscopic nephrectomy, although rare, might represent a novel way of tumor inoculation deprived of or with low malignant potential.

1. Introduction

During open or laparoscopic resection of a malignant tumor, tumor cell spillage or even direct inoculation of neoplastic cells can occur. In a small percentage of cases, early recurrent tumors can develop within the scar tissue or the trocar sites, known as port-site metastases.¹ In urological malignancies, port-site metastasis or peritoneal spread after laparoscopic surgery is a rare phenomenon accounting for 0.09% and 0.03% of the cases respectively.² Although the etiology of this phenomenon is not clearly understood, factors such as the aggressiveness and the type of the tumor, laparoscopic related factors, host immune response and local processes in the wound have been implicated. The results of most published studies demonstrate that renal cell carcinoma (RCC) is the least of all urological malignancies in developing port-site metastasis or peritoneal spread, with only rare cases being reported in the literature.³

In the present case an asymptomatic tumor implant in the omentum following robotic assisted radical nephrectomy (RARN) for organ confined, Furhman grade 1 (T2aN0M0) RCC is reported, which was incidentally identified two years after the initial operation due to the surgical staging procedure for a gynecological malignancy.

2. Presentation of case

On January 2011, a 75-year-old woman was referred to our clinic with a diagnosis of clear cell cervical carcinoma. Two years earlier the patient had undergone a right transperitoneal RARN for papillary renal cell carcinoma. Since then, the patient has been compliant with her routine follow-up with no indications of metastasis.

A radical hysterectomy with lymphadenectomy and omentectomy was performed. The histology report confirmed the presence of a clear cell cervical carcinoma of the tubulo-cystic variety. All 24 excised lymph nodes were free of disease. Yet, a small omental nodule, measuring 0.5 cm in diameter was identified which had features consistent with a low-grade papillary renal cell carcinoma. Immunohistochemistry was performed and the tumor had a low proliferative index (Ki-67 < 5%) and, as opposed to the cervical neoplasm, it was CD10 positive (Fig. 1). The initial nephrectomy slides were reviewed and the morphological features of the omental nodule proved identical to those of the renal tumor. Moreover, the video from the robotic operation was retrieved, with the aim to find potential causes of tumor spillage, possible serosal lesions or breach in oncological principals.

Fig. 1.

(A) Histology of the papillary renal cell carcinoma (H&E, ×200), (B) histology of the clear cell cervical carcinoma (H&E, ×200), (C) histology of omental “implant” (H&E, x100), (D) histology of omental “implant” (H&E, ×200), (E) strong diffuse CD10 positivity of the omental “implant” (×400), (F) rare Ki-67 positive nuclei in the cells of the omental “implant” (×400).

The robotic assisted laparoscopic transperitoneal nephrectomy was conducted in a standard manner using three robotic ports and two assistant ports, one of which was used mainly to retract the liver and the other for clip applying, retraction and suction. The artery and vein was legated separately before any manipulation of the organ. Meticulous dissection was applied with no entering into the tumor, while no hemorrhage or loss of pneumoperitoneum took place. An endoscopic bag was used to retrieve the specimen from a small right inguinal incision. The postoperative period was uneventful. The surgical specimen weighed 549 g with the kidney and its perirenal fat being intact. The final pathologic examination revealed a stage pT2a, Furhman grade 1, type 1 papillary renal cell carcinoma (PRCC) with negative surgical margins.

3. Discussion

Tumor seeding usually as a result of dissemination and concomitant implantation of neoplastic cells on the peritoneal surface is a phenomenon observed after laparoscopic surgical manipulation for both benign and malignant disease.^4,5 In most reported cases the reason of tumor spillage was iatrogenic. Nevertheless, metastatic deposits mostly in port sites, even in cases where no risk factors could be identified have been reported.

In our present case, despite the “lege artis” robotic intervention, a neoplastic omental lesion with the features of a low-grade papillary renal cell carcinoma was incidentally identified two years after the initial surgery. As opposed to cases of peritoneal carcinomatosis or port site metastasis the tumor did not seem to invade the underlying tissue since there was no fibroblastic stromal reaction nor any inflammatory infiltrate around the neoplastic papillae. The omental tumor seemed on histological examination to have harmoniously cohabited the host tissue. No port site metastasis was identified.

The above findings let us comment on the heterogeneity of malignant tumors. As already known, tumors consist of different cell clones demonstrating a great variation in a number of cellular and functional properties such as immunogenicity, tumorigenicity, cell surface properties, drug sensitivity and the ability to invade and metastasize.⁶ As expected, cells with different metastatic potential have been isolated from primary tumors. Some cells are tumorigenic but not metastatic and have little or no probability of producing metastasis while others are tumorigenic and highly metastatic.⁷ Moreover, for a metastasis to occur, a neoplastic cell must overcome a series of steps comprising its detachment from the initial tumor, the invasion of the extracellular matrix, the migration through the vascular channels and the readherence to another organ. It should also avoid immune surveillance and grow to form a new colony by inducing a neovascularization.³

The present case let us speculate that although no macroscopic surgically induced tumor spillage was observed, probably some tumorigenic but non-metastasizing neoplastic cells that under normal conditions could not overcome the several steps that are involved in the metastatic process, might have been transferred and facilitated in producing a new neoplastic colony. In order to survive, these cells might have had the ability to secrete growth factors and induce the formation of new vessels. Yet, they might have had a low doubling cycle, which has prevented the early formation of a grossly identifiable tumor. This hypothesis is strengthened by the low proliferative index (Ki-67 < 5%) that was identified in the present case, as measured immunohistochemically with MIB1 antibody. In case these neoplastic cells have a decreased capability to metastasize, they might not represent a threat for the patient. Indeed, more than two years after the hysterectomy, the patient is clinically cancer free. She denied any adjuvant therapy for her cervical cancer.

In the urologic literature, few reports of tumor seeding and port site metastasis have been published, most of which account for transitional cell carcinomas.³ In a multinstitutional survey, tumor seeding was observed in 13 cases (0.1%) of 10,912 laparoscopic procedures for urologic malignancies. In the same study, no tumor seeding regarding RCC was observed in a total of 2604 laparoscopic radical nephrectomies.⁵ Castillo et al. reported 2 cases of their own series and conducted a Medline search where a total of 29 cases of port site metastasis or tumor seeding secondary to laparoscopic urologic procedures were found out of 17 studies published in the English literature.³ From these 31 cases mentioned, 6 cases concerned RCC. Since then 3 more cases of port site recurrence of RCC have been published.^8–10

There is no doubt that poor surgical technique with traumatic manipulation of the tumor may violate the primary tumor boundaries and consequently promote tumor seeding.¹¹ Although, port site metastases have occurred even in occasions where: an endoscopic bag was used, no morcellation of the specimen was done and no risk factors could be identified. Such cases have been reported by Dhobada et al. and Castillo et al.^3,12 In the first report, port site metastasis occurred 8 months following a laparoscopic radical nephrectomy for a stage T2N0M0 grade 3 RCC, while in the second report the port site metastasis followed a laparoscopic partial nephrectomy for stage T1N0M0 grade 3 RCC.

To the best of our knowledge we report the first case of tumor seeding in the omentum following robotic assisted laparoscopic radical nephrectomy for organ confined low grade papillary (T2aN0M0) RCC. In our case, we could not identify any risk factors that could explain the intraperitoneal seeding. In fact no morcellation was undertaken and in any case the tumor was not violated, while the specimen was retrieved intact by an endoscopic bag. There were no comorbidities that could compromise the host's immune response, nor any ascites was noted. Apart from povidone-iodine irrigation of laparoscopic instruments and intraperitoneal irrigation of any kind, all other preventive measures described by Tsivian and Sidi were applied.¹¹

4. Conclusion

Tumor seeding as a result of robotic assisted laparoscopic nephrectomy is rare. Adherence to surgical oncological principals is of paramount importance, while several measures described in the literature could prevent neoplastic deposits after laparoscopic procedures. In some cases, no evident etiology can be identified, while the neoplastic cells may have a reduced ability to metastasize thus posing minimal threat to the patient.

Conflict of interest

We would like to declare that we do not have any financial interest directly or indirectly related to the subject of the study as well as potential financial benefit resulting from the presentation of the described case report.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Author contributions

Achilles Ploumidis and Theodoros Panoskaltsis wrote the manuscript. Data collection done by Theophani Gavresea and Petros Yiannou. Study design and data analysis done by Niki Yiannakou and Kitty Pavlakis.