# Ultra-late triple metastasis to the breast, lung, and brain 25 years after nephrectomy for clear cell renal cell carcinoma: a case report and literature review

**Authors:** Sujian Xiao, Xinyu Wang, Xiaoling Deng, Xin Huang, Chuance Du, Huozhong Yuan, Yanyan Li, Qiliang Zhai

PMC · DOI: 10.3389/fonc.2026.1733997 · Frontiers in Oncology · 2026-01-21

## TL;DR

A woman developed cancer in her breast, lungs, and brain 25 years after kidney cancer surgery, highlighting the need for long-term monitoring and new treatment approaches.

## Contribution

Reports the first case of ultra-late triple metastasis from kidney cancer with a 25-year latency period.

## Key findings

- Triple metastasis to breast, lung, and brain occurred 25 years after initial kidney cancer treatment.
- Immunohistochemical analysis confirmed the metastatic origin as clear cell renal cell carcinoma.
- The case challenges current surveillance practices and suggests new treatment strategies for ultra-late recurrences.

## Abstract

Clear cell renal cell carcinoma (ccRCC) most commonly metastasizes to the lungs, lymph nodes, bones, and liver. Metastasis to the breast is exceptionally rare, representing less than 0.5% of cases. Herein, we report an unprecedented case of triple metastasis with the longest recorded latency period.

An 86-year-old female presented with a painless left breast mass 25 years after undergoing radical nephrectomy for ccRCC. Multi-modality imaging (mammography, ultrasound, MRI) revealed a suspicious breast lesion. Subsequent chest CT and PET-CT identified synchronous metastatic nodules in the lungs and brain. Histopathological examination of the resected breast mass confirmed metastatic carcinoma. The diagnosis of ccRCC metastasis was substantiated by an immunohistochemical profile positive for PAX8, CAIX, and CD10, while negative for estrogen receptor, progesterone receptor, and HER2.

This case highlights breast metastasis as a rare but critical differential diagnosis in patients with a history of ccRCC, even decades after initial treatment. It underscores the necessity of lifelong follow-up for ccRCC survivors and demonstrates the integral role of imaging and pathological confirmation in guiding clinical diagnosis. Furthermore, the remarkable 25-year latency period challenges existing surveillance paradigms and provides a compelling rationale for the use of combined immunotherapy and targeted agents in managing ultra-late, multi-metastatic recurrences.

## Linked entities

- **Proteins:** PAX8 (paired box 8), CA9 (carbonic anhydrase 9), MME (membrane metalloendopeptidase), ERBB2 (erb-b2 receptor tyrosine kinase 2)
- **Diseases:** clear cell renal cell carcinoma (MONDO:0005005)

## Full-text entities

- **Genes:** ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, CA9 (carbonic anhydrase 9) [NCBI Gene 768] {aka CAIX, MN}, MME (membrane metalloendopeptidase) [NCBI Gene 4311] {aka CALLA, CD10, CMT2T, NEP, SCA43, SFE}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}
- **Diseases:** Clear cell renal cell carcinoma (MESH:D002292), breast lesion (MESH:D061325), Metastasis (MESH:D009362), carcinoma (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12867817/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12867817/full.md

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Source: https://tomesphere.com/paper/PMC12867817