Breast Metastasis from Renal Cell Carcinoma: A Case Report and Systematic Review of the Literature

Abstract

Objective: This study aimed to investigate the clinicopathological characteristics and prognostic outcomes of breast metastasis from renal cell carcinoma (RCC) via a case report and systematic review.

Patient and methods: This study present a case of a 53-year-old female who developed metachronous right breast and axillary lymph node metastases 20 months after right radical nephrectomy for RCC. Furthermore, a systematic review of the literature was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We retrieved 69 previously reported cases from 1980 to 2026 and performed a pooled analysis of 70 total cases (including our own) to evaluate clinical features and survival outcomes.

Results: The median age at the diagnosis of breast metastasis was 64.5 years, with a striking female predominance (92.9%). Metachronous metastases accounted for 68.6% of cases, with a median disease-free interval (DFI) of 6 years (interquartile range [IQR]: 3–10 years) after nephrectomy. The upper outer quadrant was the most frequently affected site (nearly one-third of cases). Statistical analysis revealed no significant correlation between the laterality of the primary RCC and the side of breast metastasis (55.0% vs. 50.0%, P = 0.84). The median overall survival (OS) following the diagnosis of breast metastasis was 48.6 months.

Conclusion: Breast metastasis from RCC typically presents as a late recurrence with no lateral predilection, predominantly affects the upper outer quadrant, and is associated with a relatively favorable median survival. Therefore, clinicians must maintain a high index of suspicion for any breast mass in patients with a history of RCC, regardless of the DFI.

Graphical abstract

Keywords

carcinoma / renal cell / neoplasm metastasis / breast

Introduction

Renal cell carcinoma (RCC) is a predominant urologic malignancy characterized by hypervascular features, and clear cell RCC (ccRCC) accounts for approximately 80% of all histological subtypes. Prognosis is strongly stage-dependent, with 5-year survival rates declining from 95% in localized disease (stage Ⅰ) to approximately 10% in metastatic presentations^[1]. While pulmonary, hepatic, and skeletal metastases represent common patterns of distant dissemination, mammary involvement remains exceptionally rare; only sporadic cases have been reported.

Due to its extreme rarity, breast metastasis from RCC is frequently misdiagnosed as primary breast carcinoma at first presentation, often resulting in inappropriate surgical or systemic treatment. In current clinical guidelines, the optimal diagnostic algorithm, therapeutic strategy, and prognostic factors for this entity remain poorly defined. Although scattered case reports have documented this phenomenon, they remain fragmented and have never been systematically synthesized.

To address this critical knowledge gap, we report a rare case of a 53-year-old female who developed solitary axillary lymphadenopathy with concurrent breast metastasis 20 months after radical nephrectomy for clear cell RCC (ccRCC), with definitive diagnosis established through comprehensive immunohistochemical (IHC) profiling. Recognizing that an isolated case report is insufficient to derive clinical insights, we subsequently conducted a comprehensive literature review of all publicly reported cases. This combined case report and systematic review aimed to (1) highlight key IHC and radiological features that differentiate metastatic RCC from primary breast malignancies, (2) characterize clinical patterns, management approaches, and survival outcomes, and (3) provide the first evidence-based framework for the diagnosis and multidisciplinary management of this rare metastatic presentation.

Materials and methods

Case presentation

A 53-year-old Chinese female presented to our clinic on April 15, 2024, with a 2-week history of a palpable right axillary mass. Physical examination revealed a solitary, mobile lymph node measuring approximately 3 cm in her right axilla region, characterized by smooth surface, and absence of tenderness or cutaneous involvement. There were nonpalpable lumps in bilateral breast and contralateral axilla and no other abnormal findings in physical examination. The patient’s medical history was significant for ccRCC treated with right radical nephrectomy on August 5, 2022. Pathological analysis of the nephrectomy specimen demonstrated a pT1N1M0 lesion (American Joint Committee on Cancer [AJCC] 8th edition) with Fuhrman nuclear grade 1–2. Notably, the tumor exhibited intact pseudocapsule formation and was devoid of lymphovascular invasion (LVI) or perineural invasion (PNI). The patient did not receive adjuvant therapy and reported no family history of malignancy or other comorbid conditions.

Subsequent ultrasonographic examination identified well-circumscribed hypoechoic masses in the lower inner quadrant of the right breast (13 mm × 10 mm) and right axilla (30 mm × 28 mm), both demonstrating regular morphology. Doppler imaging revealed sparse peri-tumoral vascularity in the breast lesion versus abundant intralesional flow in the axillary mass (Figure 1A–D). Mammographic evaluation demonstrated round, high-density lesions with circumscribed margins and absence of microcalcifications (Figure 1E and F). The patient underwent right axillary lymphadenectomy with minimally invasive rotary excision of the right breast lesion. Following referral to our institution, comprehensive restaging with contrast-enhanced thoraco-abdomino-pelvic computed tomography (CT) was performed after multidisciplinary review of prior imaging and histopathological specimens. The contrast-enhanced CT demonstrated arterial phase hyperenhancing residual lesions in the right breast and axillary region (Figure 1G–J), consistent with the hypervascular profile characteristic of RCC.

Histopathological evaluation (Figure 2) revealed tumor cells arranged in nested and acinar patterns within a prominent vascular network of delicate thin-walled vessels. The neoplastic cells exhibited characteristic clear cytoplasm with uniform round nuclei containing finely dispersed chromatin and inconspicuous nucleoli. IHC profile demonstrated strong positivity for epithelial marker: cytokeratin (CK); renal lineage markers: paired box protein-8 (PAX-8) and carbonic anhydrase IX (CA-IX); mesenchymal markers: vimentin and cluster of differentiation (CD) 10; RCC-specific marker: renal cell carcinoma marker (RCC-ma); cell adhesion marker: p120 (membranous pattern). Negative reactivity was observed for breast lineage markers: cytokeratin 7 (CK7) and GATA-binding protein 3 (GATA-3); hormone receptor: estrogen receptor (ER). This distinct morphological pattern coupled with the immunophenotypic profile (renal nuclear PAX-8+/CA-IX+/RCC-ma+ with CK7–/GATA3–) confirms the diagnosis of metastatic ccRCC to breast parenchyma and axillary lymph nodes (ALN).

The patient initiated sunitinib therapy at 50 mg/day. Repeating CT scanning at 6 weeks demonstrated stable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Treatment-related adverse events included grade 1 stomatitis and grade 3 thrombocytopenia, prompting dose modification to an intermittent schedule: 50 mg daily for 3 weeks followed by one-week treatment holiday. Subsequent monitoring revealed only persistent grade 1 thrombocytopenia. At the most recent follow-up (25 months after the initial diagnosis of breast metastasis), the patient was alive and receiving maintenance targeted therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

Literature retrieval strategy

A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines^[2]. PubMed, Embase, Web of Science Core Collection, and China National Knowledge Infrastructure (CNKI) databases were searched from database inception to May 15, 2026. The search strategy combined Medical Subject Headings (MeSH) and free-text terms (or their Chinese translations) using Boolean operators: (“renal cell carcinoma” or “kidney cancer” or “hypernephroma”) and (“breast metastasis” or “mammary metastasis” or “axillary lymph node metastasis” or “chest wall metastasis”). No language or publication date restrictions were applied; non-English articles were translated by certified medical translators.

Eligibility criteria

Studies were included if they met all of the following: (1) histologically confirmed primary RCC (any subtype); (2) documented metastatic involvement of the breast parenchyma; (3) provided extractable clinical, pathological, or follow-up data. Case reports, case series, and retrospective cohort studies were eligible. Exclusion criteria comprised: (1) non-RCC primary renal malignancies; (2) primary breast carcinoma with secondary renal spread; (3) conference abstracts, editorials, or reviews lacking original patient-level data; (4) full-text unavailable online; (5) duplicate publications of the same patient.

Study selection and data extraction

Titles and abstracts were independently screened by two reviewers. Potentially eligible articles underwent full-text assessment. Discrepancies were resolved through consensus or adjudication by a third senior author. A standardized, pilot-tested extraction form was used to collect: demographic data, laterality (left, right or bilateral) of renal tumor, histopathological subtype, laterality and quadrant of breast tumor, ALN status, synchronous or metachronous metastasis, interval from nephrectomy to metastasis (metachronous only), and survival outcomes (if mentioned). For articles published in languages other than English and Chinese, a large language model (Qwen3.7-max, Alibaba Cloud, China) was utilized to assist in translating the full texts into English. All translated texts were manually verified by the authors to ensure semantic accuracy before data extraction. All extracted data were cross-verified independently.

Risk of bias and quality assessment

Given the observational nature of case-level evidence, methodological quality was appraised using the Joanna Briggs Institute (JBI) critical appraisal checklist for case reports. Eight domains (diagnostic certainty, temporal sequence, follow-up adequacy, reporting completeness, etc.) were scored as “Yes,” “No,” “Unclear,” or “Not Applicable.” Studies achieving ≥ 6/8 “Yes” responses were classified as high quality. Due to inherent design limitations of case reports, formal risk-of-bias mitigation was not feasible.

Statistical analysis

All available full text of relevant reports were reviewed, values of key related variables were extracted. Data were sorted in Excel and analyzed in GraphPad Prism software (version 9.5.0; GraphPad Software, USA). Continuous variables were described using mean ± standard deviation (SD) or median (interquartile range [IQR]), as appropriate. Categorical variables were described using numbers (percentages). χ²-square test was used to compare the proportion between the two groups. Kaplan–Meier was used to estimate the survival curve.

Results

Study selection

Our initial systematic search across multiple databases yielded a total of 3997 records. After removing duplicates and screening titles and abstracts, 77 articles were retrieved for detailed assessment. Between 1980 and 2026, a total of 80 cases of breast metastasis from RCC were reported in 77 publications. The publication years and geographical distribution of these cases are presented in Supplementary file 1. Of these, 11 articles were excluded for the following reasons: full text unavailable online (n = 10)—likely attributable to the advanced age of the publications, lack of digital archiving, or database access restrictions—and case series lacking detailed individual clinical information (n = 1). Ultimately, 66 articles comprising 69 patients met the inclusion criteria and were included in the systematic review^[3–68]. The PRISMA flow diagram of the study selection process is presented in Supplementary file 2.

Quality assessment and risk of bias

The methodological quality of the 66 included case reports was evaluated using the JBI critical appraisal checklist. Overall, the reporting quality was moderate. As illustrated in the summary plot (Figure 3), a high proportion of the included studies adequately reported patient demographics (Q1, 100%), clinical history (Q2, 97%), and diagnostic assessments, including histopathological (H&E) findings and/or IHC profiling (Q4, 85%). However, several domains exhibited a high risk of reporting bias. Notably, long-term follow-up outcomes (Q6) and the identification of adverse events or treatment-related complications (Q7) were poorly documented, with only 62% and 61% of the studies providing sufficient details, respectively. Detailed, study-level quality assessments are provided in the traffic light plot (Supplementary file 3). These reporting deficiencies highlight the inherent information bias in the current literature and should be considered when interpreting the pooled survival outcomes.

Summary stacked bar plot illustrating the proportion of the 66 included studies that met each criterion of the JBI critical appraisal checklist. The horizontal axis represents the eight specific JBI appraisal domains (Q1–Q8), and the vertical axis denotes the percentage of studies. The color-coded bars represent the appraisal judgments: green (“Yes”, indicating adequate reporting/low risk of bias), red (“No”, indicating inadequate reporting/high risk of bias), yellow (“Unclear”). The plot reveals that while baseline characteristics and diagnostic evaluations were generally well-documented, critical domains such as post-intervention outcomes (Q6) and adverse events (Q7) exhibited substantial reporting deficiencies.

Patients’ clinical characteristics and outcomes

Combined with our own newly reported case, a total of 70 patients were included in the final pooled analysis. The demographic and clinical characteristics were shown in Table 1. Female patients accounted for 92.9%; the median age was 64.5 years; more than two-thirds (68.6%) of patients were diagnosed with RCC several years or even more than 10 years ago; time interval between nephrectomy and onset of breast metastasis ranged from several months to 28 years; the median time to breast metastasis after nephrectomy was six years (P25–75, 3–10 years). Additionally, 15.7% of cases had history or family history of breast cancer.

As to the localized area of metastatic renal cell tumor in the breast, upper outer quadrant was the most common place of breast metastasis occurring, nearly one-third metastasis occurred in the upper outer quadrant. In addition, RCC seemed to metastasize more frequently to the upper hemisphere of breast than lower hemisphere (Table 1). Based on the available information, 34 cases were diagnosed as left RCC and 27 as right RCC. It was questionable whether the tumor was more prone to spread to the ipsilateral breast; however, ipsilateral breast metastasis rate for left and right RCC was 55.0% and 50.0% respectively, we failed to demonstrate a lateral proportional difference between left and right RCC (Figure 4A, χ² = 0.041, P = 0.84). Forty-five had sufficient follow-up data available for survival analysis, the estimated median overall survival was 48.6 months, survival curve was depicted in Figure 4B.

Discussion

Breast metastases originating from extramammary malignancies represent a rare clinical entity, constituting only 0.2% of all breast malignancies treated at Washington University during 1991–2006^[69]. Epidemiological studies consistently identify melanoma as the predominant primary malignancy, accounting for 30%–60% of reported cases^[69,70]. Notably, RCC metastases to the breast remain exceptionally uncommon.

The differential diagnosis between primary breast carcinoma and metastatic RCC is of paramount clinical importance, as misdiagnosis could lead to unnecessary radical mastectomy and inappropriate systemic therapies. More than 80% of cases were found with solitary lesions, however, the imaging findings were different from primary breast cancer. For example, under mammography, they generally do not have spiculated margins, skin or nipple retraction, due to the absence of desmoplastic reaction, calcifications are not frequently present in metastatic lesions^[71]. Pathologically, primary breast cancers typically express markers such as GATA3, ER, PR, and Mammaglobin, metastatic ccRCC is characteristically positive for PAX-8, CD10, and Vimentin. The diagnostic challenge of identifying rare metastatic lesions from RCC is not unique to the breast; it is similarly encountered in other atypical metastatic sites, such as the pancreas^[72].

One of the most striking findings of our pooled analysis is the temporal pattern of metastasis. RCC is notorious for its unpredictable and prolonged natural history, often recurring decades after the initial curative-intent nephrectomy. In our cohort, over two-thirds (68.6%) of the cases were metachronous, with a median disease-free interval (DFI) of 6 years, and some occurring up to 28 years postoperatively. This underscores the critical necessity for lifelong surveillance in RCC survivors. Clinicians should not dismiss a newly emerged breast mass as a primary breast cancer or a benign lesion merely because the patient had a nephrectomy many years prior.

Regarding the spatial distribution, our analysis revealed that the upper outer quadrant is the most common site for RCC breast metastasis, accounting for nearly one-third of the cases, with a general predilection for the upper hemisphere of the breast. This distribution closely mirrors the anatomical incidence of primary breast carcinoma, which is largely attributed to the greater volume of glandular tissue and richer vascular supply in the upper outer quadrant.

Furthermore, the inherent limitations of case reports significantly impact the robustness of our pooled data. Our quality assessment revealed that long-term follow-up outcomes and treatment-related adverse events were suboptimally documented, with only 62% and 61% of the studies providing sufficient details, respectively. This reporting deficiency introduces substantial information bias and underscores the urgent need for standardized reporting frameworks, such as the CARE (case report) guidelines, to ensure minimum follow-up standards and comprehensive toxicity documentation in future publications. Additionally, selection and publication bias inherently skew the pooled survival estimates. Because case reports disproportionately feature patients with exceptionally long survival, atypical presentations, or successful surgical outcomes, our calculated median overall survival of 48.6 months likely overestimates the true prognosis of the broader RCC patient population with breast metastasis. To mitigate these biases and capture unselected, real-world clinical data, future research must transcend isolated case reports and prioritize the establishment of multi-institutional, prospective registries or collaborative databases dedicated to rare extramammary metastases.

Conclusion

Breast metastasis from RCC is a rare but clinically distinct entity characterized by a propensity for late recurrence (median DFI of six years), a predilection for the upper outer quadrant, and a lack of lateral correlation with the primary renal tumor. Future prospective, multi-institutional registries are warranted to mitigate reporting biases and further elucidate the optimal multidisciplinary management strategies for this rare metastatic presentation.

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