Therapeutic Challenges of a Renal Collision Tumour Comprising Clear Cell Renal Cell Carcinoma and Metastatic Breast Carcinoma: A Case Report

Therapeutic Challenges of a Renal Collision Tumour Comprising Clear Cell Renal Cell Carcinoma and Metastatic Breast Carcinoma: A Case Report | Research Square Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Therapeutic Challenges of a Renal Collision Tumour Comprising Clear Cell Renal Cell Carcinoma and Metastatic Breast Carcinoma: A Case Report AJP Fulton, AY Warren, S Appukutty, A Matakidou, W Ince, B O’Carrigan, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8777574/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Collision tumours, defined by the coexistence of two histologically distinct neoplasms within a single organ, are rare and typically arise from a shared cell lineage. We report a unique case of a 64-year-old woman with a history of estrogen receptor (ER)–positive, HER2-negative breast carcinoma who developed a renal mass later identified as a collision tumour comprising clear cell renal cell carcinoma (ccRCC) and metastatic breast carcinoma. Initial imaging and biopsy suggested ccRCC alone; however, post-nephrectomy histopathology revealed metastatic breast carcinoma foci within the ccRCC and renal sinus fat, confirmed by ER, GATA3, and mammaglobin positivity. This case illustrates diagnostic challenges in distinguishing synchronous primaries from metastases, where limited sampling may obscure dual pathology. Management required balancing nephrectomy for ccRCC with CDK4/6 inhibitor–based therapy for metastatic breast cancer and consideration of adjuvant immunotherapy. Multidisciplinary evaluation and molecular characterisation are essential for optimal precision-guided care in such complex malignancies. Collision Tumour Renal Cell Carcinoma Breast Carcinoma Figures Figure 1 Figure 2 Figure 3 Introduction Collision tumours are rare entities defined by the coexistence of two histologically distinct neoplasms in the same organ. Within the kidney, collision tumours most often involve combinations of different subtypes of renal cell carcinoma 1 . The coexistence of a primary renal neoplasm with a metastasis from another primary site is exceptionally uncommon. Breast carcinoma metastasising to the kidney is uncommon, and its coexistence with a primary clear cell renal cell carcinoma (ccRCC) in the same renal lesion are exceptionally rare. Such presentations pose diagnostic and therapeutic challenges, particularly in distinguishing the metastasis from a synchronous primary tumour, as management strategies differ markedly between these two scenarios. We report a case of a patient with metastatic hormone receptor–positive breast carcinoma who developed a renal mass subsequently found to represent a collision tumour composed of ccRCC and metastatic breast carcinoma. Results Clinical Background A 64-year-old female with a background of sickle cell trait and a prior estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative right breast carcinoma was reviewed in the renal oncology clinic for a new renal mass. At the time of her initial breast cancer diagnosis in 2002, she received neoadjuvant doxorubicin and paclitaxel chemotherapy, followed by a right mastectomy and axillary node clearance. Adjuvant radiotherapy was completed in June 2002, and she remained disease-free for over two decades. Clinical Course In early 2025, she presented with progressive generalized pain initially attributed to fibromyalgia. Routine blood tests demonstrated a normocytic anaemia and an elevated alkaline phosphatase level. Further evaluation with cross-sectional imaging revealed multiple mixed lytic and sclerotic bone lesions and an incidental 65mm right renal mass (cT1b as per UICC TNM 8th edition) (Fig. 1 ). She was initially investigated on a myeloma pathway, but serum electrophoresis, immunofixation, and free light chain assays were unremarkable. The renal mass was subsequently evaluated by the urology team and a percutaneous biopsy confirmed grade 2 clear cell renal cell carcinoma (ccRCC). Bone metastases from RCC are typically lytic, whereas mixed lytic and sclerotic bone lesions are far more common in metastatic breast cancer.The case was therefore discussed at the regional multidisciplinary team (MDT) meeting given the above. It was considered that the bone lesions would most likely represent recurrence of her prior breast malignancy. Subsequent CA15-3 testing demonstrated an elevated result of 1215 kU/L, in keeping with likely breast carcinoma metastases. A targeted bone biopsy was therefore performed, which demonstrated metastatic adenocarcinoma consistent with recurrent breast carcinoma, ER positive and HER2 negative. A diagnosis of metastatic breast carcinoma and a synchronous right kidney renal cell carcinoma was therefore made. The patient commenced first-line systemic therapy with letrozole and ribociclib. Given the confirmed clear cell RCC was cT1b, she was referred for surgical resection. Histopathology findings On 21 August 2025, she underwent a robot assisted laparoscopy radical nephrectomy. Histopathological examination revealed a 60mm grade 3 clear cell renal cell carcinoma without sarcomatoid or rhabdoid morphology. Formal staging was reported as pT3a pNx(UICC TNM 8th Edition) with a Leibovich score of 6/11. Resection margins, including the renal vein margin, were clear. Within the ccRCC tumour and the renal sinus fat, there were incidental multiple small foci of metastatic breast adenocarcinoma. Morphologically, these foci were composed of nests of cells and tubules/glands. The tumour cells had round/oval vesicular nuclei with inconspicuous nucleoli and a moderate amount of pale eosinophilic cytoplasm. On immunohistochemical (IHC) staining, these tumour cells were positive for AE1/3, GATA-3, ER and Mammaglobin. They were negative for PR, S100, TTF1, CK7, CK5/6, Calretinin, Chromogranin-A, Synaptophysin, CDX2, P63, 34BE12, Pax-8 and WT1. The morphology and immunoprofile confirmed metastatic breast carcinoma (Figs. 2 and 3 ). Management plan The patient had been commenced on treatment for metastatic ER positive, HER2 negative breast cancer with a combination of letrozole and ribociclib prior to her renal surgery. Ribociclib was paused over the perioperative period and was recommenced once she had recovered post nephrectomy. Postoperatively, she was reviewed in the renal oncology clinic to discuss the potential role of adjuvant pembrolizumab for high-risk localised renal cancer treatment. This adjuvant renal cancer treatment was under consideration given her likely durable response to first line ER positive breast cancer treatment 2 . The anticipated benefits and possible toxicities of Pembrolizumab were carefully reviewed, alongside the need to continue systemic therapy for breast cancer. Following a shared decision-making discussion, the patient elected for active surveillance for any recurrence of her renal cell carcinoma and continuation of breast cancer management with ribociclib and letrozole. Denosumab was also initiated in view of bone metastases. She is currently tolerating treatment well, and follow-up CT imaging is awaited to assess response. Discussion Collision tumours represent the co-existence of two histologically distinct neoplasms within a single organ, without histologic mixture or transition. While they have been reported in various organs, their occurrence in the kidney most often involves dual primary renal cell carcinomas or combinations of renal and urothelial neoplasms 1 . The coexistence of a primary renal cell carcinoma and metastatic breast carcinoma within the same renal mass is exceedingly rare, with only isolated case reports describing breast metastases in renal tumours 3 . Whereas, two coexisting primary tumours is much commoner 4 . To our knowledge, this is the first reported case of a renal collision tumour comprising clear cell renal cell carcinoma (ccRCC) and metastatic estrogen receptor (ER)–positive, HER2–negative breast carcinoma late recurrence. The pathogenesis of collision tumours remains incompletely understood. Several mechanisms have been proposed. For synchronous tumours arising from a common histological background, several mechanisms have been proposed. This includes microenvironment alteration by one tumour facilitating the development of the other, differentiation from a common precursor or independent evolution in adjacent cells due to shared common oncogenic stimuli 5 , 6 . For collision tumours that consist of different primary tissues, microenvironment features are felt to provide a selective advantage for metastasis development 7 . In the present case, metastatic breast carcinoma foci were embedded within the ccRCC and renal sinus fat. A number of lipid metabolites are known to be selective estrogen receptor modulators that both in vivo and in vitro have demonstrated the ability to enhance the proliferation of ER positive breast carcinomas 8 . As such, the highly vascular nature and lipid-rich microenvironment of ccRCC may provide a fertile niche for metastatic seeding. From a diagnostic perspective, this case highlights the importance of maintaining a broad differential diagnosis when evaluating renal masses in patients with prior malignancies. Radiologically, distinguishing a metastatic lesion from a primary renal neoplasm can be challenging. Percutaneous biopsy provides valuable histological confirmation but may be limited by sampling error, as metastatic foci may represent only a minor component within the dominant tumour mass. Multidisciplinary discussion incorporating histopathology, radiology, and clinical context is therefore essential. Therapeutically, the presence of two distinct malignancies within one organ complicates management decisions. ccRCC is primarily treated surgically when localised, whereas metastatic breast carcinoma is managed systemically. In this case, nephrectomy was undertaken both for local control and to obtain definitive histopathological characterisation. Post-operatively, systemic therapy with a CDK4/6 inhibitor and aromatase inhibitor was continued for metastatic ER positive breast cancer. The potential role of adjuvant pembrolizumab for the high-risk ccRCC component was discussed in the context of emerging evidence 9 , though combining immune checkpoint inhibition with CDK4/6 inhibition raises concerns regarding additive hepatotoxicity and pneumonitis risk. Early-phase data in ER positive breast cancer combining CDK4/6 inhibition with pembrolizumab suggest mixed safety profiles and uncertain synergistic efficacy 10 , 11 . This underscores the need for caution and multidisciplinary evaluation and informed decision making before concurrent administration in such collision tumours. Conclusion This case underscores the necessity of individualised treatment planning when diagnosing and managing synchronous malignancies with divergent biological behaviours and therapeutic paradigms. It also illustrates the evolving landscape of cancer survivorship, wherein patients successfully treated for an initial malignancy may present years later with new or metastatic disease, occasionally in anatomically and biologically unexpected combinations. Further molecular characterisation of such collision tumours, including genomic or transcriptomic profiling, may provide insight into shared pathways of tumour progression, microenvironmental permissiveness, and potential therapeutic vulnerabilities. This may help to inform optimal management strategies in these rare cases and help to minimise potential toxicities from combination approaches. Methods This case was identified during multidisciplinary review at Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Clinical data, imaging, histopathological findings, and treatment details were obtained from electronic medical records and institutional databases. All information was anonymised prior to analysis and reporting. Formalin-fixed paraffin-embedded (FFPE) tissue from the nephrectomy specimen was examined using haematoxylin and eosin staining and a panel of immunohistochemical markers, including ER, GATA3, mammaglobin, CK7, Pax-8, and WT1, performed according to standard diagnostic laboratory protocols. Histopathological review was undertaken by consultant pathologists to confirm the coexistence of distinct tumour components. Cross-sectional imaging was reviewed by specialist radiologists, and representative images were included to illustrate key findings. The case was discussed at a regional oncology–urology multidisciplinary team (MDT) meeting to guide diagnosis and management. Written informed consent for publication of clinical details and images was obtained from the patient. Ethical approval was waived in accordance with institutional policy for single-patient case reports. This report was prepared in compliance with the CARE guidelines, and the corresponding checklist is included as supplementary material. Abbreviations ccRCC – Clear cell renal cell carcinoma CDK4/6 - Cyclin dependant kinases 4 and 6 CDX2 - Caudal-Type homeobox 2 CK5/6 - Cytokeratins 5 and 6 CK7 – Cytokeratin 7 ER – Estrogen receptor HER2 – Human epidermal growth factor receptor 2 MDT – Multidisciplinary team Pax-8 – Paired box gene 8 PR – Progesterone receptor TTF1 – Thyroid transcription factor 1 UICC TNM - Union for International Cancer Control Tumour–Node–Metastasis Classification WT1 – Wilms tumour Declarations Data Availability: All data supporting the findings of this report are included within the article. Additional anonymised clinical or histopathological information can be made available from the corresponding author upon reasonable request, in accordance with institutional and ethical guidelines. Acknowledgements: We would like to acknowledge the Departments of Oncology, Pathology, Radiology, and Surgery in Cambridge University Hospitals for their valuable contributions and collaborative input in the management and review of this case. We would also like to thank the individual who is the subject of this case report for their willingness to share their experience, which has made this report possible and contributes to ongoing learning and improvement in clinical practice. GDS is supported by The Mark Foundation for Cancer Research (RG95043) , the Cancer Research UK Cambridge Centre (C9685/A25177 and CTRQQR-2021\100012) and NIHR Cambridge Biomedical Research Centre (NIHR203312). The Human Tissue Research Bank is supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. AYW is supported by the Cancer Research UK Cambridge Centre (C9685/A25177) and NIHR Cambridge Biomedical Research Centre (NIHR203312). Author Contributions: AM obtained initial informal consent. AJPF obtained formal patient consent, collected clinical information, and drafted the manuscript. AYW and SA provided the histopathological images and contributed to manuscript review. AS provided the radiological images and contributed to manuscript review. JOJ provided project oversight and manuscript review. WI, BO, KF, TE, GDS, KM critically reviewed the manuscript and provided corrections and feedback. All authors approved the final version for submission. Competing Interests: GDS has received educational grants from AstraZeneca; consultancy fees from Evinova and Qurin; travel expenses from MSD; he is Clinical lead (urology) National Kidney Cancer Audit and Topic Advisor for the NICE kidney cancer guideline. WJH holds advisory and research roles at AstraZeneca, MSD, GSK, J+J, Merck Serono, Recordati, Ipsen, Regeneron and Bayer. TE is a Roche employee and has shares in both Roche and AstraZeneca. AM is a GSK employee and has shares in GSK and AstraZeneca KF has advisory, consultancy or speaker fees from ESAI, Ipsen, Merck, Eusa, MSD, Kyowa Kirin, Regeneron and Sanofi and conference support from Ipsen, MSD and EUSA and Institutional research funding from Merck, Exelixis. AW is a member of National Kidney Cancer Audit Clinical Reference Group. KM receives consultancy fees from Pfizer, AstraZeneca, FORTREA and NOVARTIS. They have received international meeting sponsorship from Novartis, Roche and Pfizer. References Lerma, L. A. et al. Actual encounters of the kidney kind: Exploring 48 cases of renal collision tumors through the lens of literature. Hum. Pathol. 145 , 26–33 (2024). Hortobagyi, G. N. et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N. Engl. J. Med. 386 , 942–950 (2022). Amin, M., Radkay, L., Pantanowitz, L., Fine, J. & Parwani, A. Tumor-to-tumor metastasis (TTM) of breast carcinoma within a solitary renal angiomyolipoma: a case report. Pathol. Res. Pract. 209 , 605–608 (2013). Vogt, A. et al. Multiple primary tumours: challenges and approaches, a review. ESMO Open 2 , e000172 (2017). Belle Mbou, V., Sanglier, F., Pestre-Munier, J., Descazeaud, A. & Labrousse, F. Renal collision tumours: three additional case reports. BMC Urol. 22 , 113 (2022). Michalinos, A., Constantinidou, A. & Kontos, M. Gastric collision tumors: an insight into their origin and clinical significance. Gastroenterol. Res. Pract. 2015 , 314158 (2015). Bulte, C. A., Hoegler, K. M. & Khachemoune, A. Collision tumors: A review of their types, pathogenesis, and diagnostic challenges. Dermatol. Ther. 33 , e14236 (2020). Zipinotti Dos Santos, D. et al. The impact of lipid metabolism on breast cancer: a review about its role in tumorigenesis and immune escape. Cell Commun. Signal. CCS 21 , 161 (2023). Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma | New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2312695. Rugo, H. S. et al. Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study. NPJ Breast Cancer 8 , 118 (2022). Yuan, Y. et al. Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Eur. J. Cancer Oxf. Engl. 1990 154 , 11–20 (2021). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 31 Mar, 2026 Reviews received at journal 27 Feb, 2026 Reviewers agreed at journal 27 Feb, 2026 Reviewers invited by journal 27 Feb, 2026 Editor assigned by journal 26 Feb, 2026 Submission checks completed at journal 26 Feb, 2026 First submitted to journal 03 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information

Related documents

• Therapeutic challenges of a renal collision tumour comprising clear cell renal cell carcinoma and metastatic breast carcinoma: a case report.#486261
• Therapeutic Challenges of a Renal Collision Tumour Comprising Clear Cell Renal Cell Carcinoma and Metastatic Breast Carcinoma: A Case Report#272045
• Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer#442090
• Kidney cancer.#666008
• A Research Study for Patients With Metastatic Renal Cell Carcinoma#628531