Introduction

Ureteral metastasis is an uncommon entity. Breast and stomach are the common primary malignancies, which spread to the ureter (1). Renal cell carcinoma (RCC), mainly of the clear cell variety, spreads via hematogenous and lymphatic pathways to the lung, liver and bones. Although, few case reports of renal adenocarcinoma metastasizing to the ureteric stump have been reported, all have been of clear cell carcinoma variety (2). We present the first-ever case of drop metastasis of a rare variant of RCC to the ipsilateral ureter.

Case Report

A sixty-five-year-old diabetic and hypertensive male presented with hematuria in May 2020. On imaging, he had an eight cm left renal mid pole tumor with renal vein thrombus without distant metastasis. He underwent left robotic radical nephrectomy with para-aortic and hilar lymph node dissection. On gross examination, the tumor was unencapsulated, multinodular, solid, soft and friable with a yellowish-brown cut surface and extended into the renal sinus fat. The renal vein branch also showed a tumor thrombus and the mass did not infiltrate into perinephric fat. On histology, the tumor was composed of large cells arranged in papillary and tubular arrangements (Figure 1). The tumor cells showed a pleomorphic grade 3 nuclei and abundant granular cytoplasm. Focal cytoplasmic clearing, rhabdoid morphology, areas of necrosis and a few tumor giant cells were seen, however, sarcomatoid morphology was not seen. On immunohistochemistry, the tumor cells expressed Alpha-methylacyl-CoA racemase (AMACR) strongly and diffusely. They were negative for Ca 9, CD10, cytokeratin-7 (CK-7), C-kit, TFE3 and Melan A (Figure 2). A diagnosis of oncocytic variant of papillary RCC (OPRCC), type 2 with focal rhabdoid features, International Society of Urological Pathology nuclear grade 3 and pathological stage pT3aN0 was given. Ureteric and vascular margins were free. At six months, follow-up ultrasonography showed a three cm hypoechoic lesion in the left iliac fossa. In view of a raised creatinine level of 2.41 mg/dL, fluorodeoxyglucose, positron emission tomography (PET) computerized tomography (CT) scan without contrast was performed. It showed an avid soft tissue lesion of size 2.8 cm in the proximal aspect of the left ureteric stump abutting the left psoas muscle (Figure 3). Urine cytology was negative for malignant cells. In view of increased avidity for PET scan, it was decided to excise the mass. The patient underwent robotic excision of the left ureteric stump with bladder cuff excision and left pelvic lymph node dissection. Pathological examination revealed a tumor in the left ureteric wall filling up the lumen similar in appearance to the previously excised left renal tumor (Figure 4). The immunohistochemistry profile was similar to the renal tumor and it was Pax 8 positive with negativity for the urothelial markers Gata 3, uroplakin and p63. A diagnosis of an OPRCC type 2 infiltrating muscularis propria of the ureter and periureteric adipose tissue was given, consistent with drop metastasis in a known case. The pelvic nodes were negative for metastasis. His post-operative recovery was uneventful. Currently, he is doing well on a one-year follow-up. Written valid informed consent has been obtained from the patient for the publication of this manuscript.

Discussion

The unpredictable nature of RCC with regard to its presentation, spread and metastasis is well known. Although the majority of the metastases are widespread, up to 10% can be solitary as well (3). RCC metastasizing to the ureter is an uncommon entity. There have been 57 cases of RCC metastasizing to ureter in the literature (4). Several mechanisms responsible for cancer spread are the hematogenous route, retrograde spread through veins and lymphatic channels and direct spread by seeding of urothelium (2). Any mechanism could be responsible for the solitary ureteral metastasis in the current case.

Our patient was incidentally found to have a ureteric mass on a routine follow-up after radical nephrectomy. Since PET CT showed uptake, the differential diagnoses were metastatic RCC or transitional cell carcinoma of the ureter. Generally, a surgical approach is preferred for solitary renal cancer metastasis due to high resistance to chemotherapy and radiotherapy and metastasectomy provides the best shot at cure (5). Thus, we performed robotic excision of the ureteric stump and bladder cuff along with left pelvic lymph node dissection much like Bhoopathy et al. (6) who performed a similar case robotically in a metastatic clear cell carcinoma. The histopathology reports of both, the radical nephrectomy specimen and ureteric stump were similar with regards to histological subtype (OPRCC), presence of necrosis and immunohistochemical features.

Although clear cell carcinoma is a common renal malignancy, papillary subtypes can be found in 10 to 15% cases (7). Papillary RCC (PRCC) has traditionally been divided into types 1 and 2 based on the nuclear features (8). The new 2016 edition of the World Health Organization Classification of Tumors of the Urinary and Male Genital Organs has mentioned an oncocytic variant (9). It was reported for the first time in 2005 in a series of 10 cases. The tumor is uncommon and there is a lack of understanding of its immunohistochemical features that makes the classification controversial (10). In 2016, Han et al. (11) characterized ORPCC as having a papillary structure with a single layer of cells with round or polygonal nuclei and eosinophilic granular cytoplasm. On immunohistochemistry, above 90% of the cells were positive for AMACR, whereas a few showed positivity for CD10 and vimentin (11). In this study, these pathological findings were mirrored, although CD10 was negative and vimentin immunostaining was not performed. The presence of rhabdoid features and areas of necrosis are associated with a poor prognosis. Until now, only 3 cases of metastatic OPRCC have been reported, none of them to the ureter (11). The current case, despite not having sarcomatoid features, metastasized to the ipsilateral ureter metachronously within six months of nephrectomy, highlighting the rarity of the case. The presence of renal vein thrombus, large areas of necrosis and partial rhabdoid morphology in the radical nephrectomy specimen were indicators of aggressive pathology and likely contributed to early metastasis. All of the previously reported cases of RCC metastasis to the ureteric stump have been of the clear cell type, which have occurred in a time interval ranging from four months to 12 years from nephrectomy (2).

Conclusion

The new oncocytic variant of PRCC is not well studied and can have serious metastatic implications. Clinicians must bear in mind that non-clear cell RCC can also metastasize to the ureter and ureteric masses are not always of transitional cell variety. This should be considered by pathologists while evaluating any kidney-related specimen showing oncocytic features. This is the first case report of non-clear cell variety of drop metastasis of a rare histological variant of RCC to the ipsilateral ureter. Further studies should help characterize and predict this uncommon variant.

Acknowledgements

Publication: The results of the study were not published in full or in part in form of abstracts.

Contribution: There is not any contributors who may not be listed as authors.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

Ethics

Informed Consent: Written valid informed consent has been obtained from the patient for the publication of this manuscript.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L., Concept: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L., Design: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L., Data Collection or Processing: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L., Analysis or Interpretation: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L., Literature Search: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L., Writing: V.A., T.B.Y, S.W., A.S., A.A., B.K., A.R., O.P., Y.L.