Rethinking Small Renal Masses: A Case Series of Metastatic Presentations
Sarbartha Kumar Pratihar 1, Jemesh Singh Maharjan 2, Nikhil Saurabh 3, Aadhar Khera 2,
Indra Prakash Mandal 3, Onkar Singh Sangha 2, Ashish Khanna 1, Sudhir Kumar Rawal 4, Amitabh Singh *5
*Correspondence to: Amitabh Singh, Rajiv Gandhi Cancer Institute and Research Centre, Sir Chotu Ram Marg, Sector 5, Rohini, New Delhi, PIN 110085.
© 2026 Amitabh Singh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 16 July 2026
Published: 01 August 2026
DOI: https://doi.org/10.5281/zenodo.21767347
Introduction
Small Renal Masses (SRMs) refer to clinically staged T1a solid, or cystic kidney lesions no larger than 4 cm that demonstrate contrast enhancement on imaging.[1] Traditionally, SRMs have been regarded as predominantly indolent entities due to slow tumor growth rate of 1-3 mm annually and a reported metastatic rate of only around 1-3%.[2] This seemingly favorable natural history has encouraged the conservative or minimally invasive management strategies. Approximately 25% of SRM cases turn out to be benign, further reinforcing the perception that aggressive workup or treatment may be unnecessary in many patients.
The growing use and availability of advanced imaging modalities has led to a rising rate of incidental SRM detection. Multiple treatment options are currently available - including active surveillance, recommended particularly for tumors <2 cm or in elderly/comorbid patients. Watchful waiting is reserved for patients with limited life expectancy.[3,4] Ablative therapies, including cryoablation and radiofrequency ablation, offer minimally invasive, image-guided tumor destruction with good local control and renal function preservation, and are particularly suited for patients unfit for surgery, though they carry a higher local recurrence risk compared to surgery.[5,6] Partial nephrectomy remains the standard of care for fit patients due to equivalent cancer outcomes and superior renal preservation, as compared to radical nephrectomy.[6,7]
Despite this conventional understanding, the assumption that small size equates to biological indolence deserves critical re-examination. Tumor size alone cannot reliably rule out aggressive or metastatic behavior, and studies highlight that SRMs may have the possibility of synchronous metastasis at the time of diagnosis.[8] We present three cases of SRMs with distant metastases at initial presentation, challenging the notion that small renal masses are uniformly low-risk. Each case provides a clinically distinct exception to the standard expected behavior of SRMs and underscores the need for vigilance even in lesions that would traditionally be considered candidates for conservative management.
Case 1
A 72-year-old male was evaluated for hematuria of one year's duration, during which he was diagnosed with a left renal mass 2.1 x 2.4 cm with a metastatic lytic lesion in the left femoral neck on FDG PET-CT performed on 16.07.2025.
He underwent left hip replacement for fracture of the neck of femur on 17.07.2025. Biopsy of the femoral head and neck specimen was suggestive of metastatic carcinoma with an IHC profile consistent with a renal primary - IHC positive for CAIX (BOX-TYPE), negative for AMACR, CK7, and CD117. He subsequently underwent cytoreductive robotic left nephron-sparing surgery on 08.08.2025. Histopathology confirmed clear cell renal cell carcinoma, WHO/ISUP grade 2, TNM stage pT1a.
The patient received adjuvant immunotherapy with Inj Pembrolizumab 200 mg for 6 cycles along with Tab Axitinib 5 mg. His 6-month FDG PET-CT evaluation showed no evidence of disease.
Case 2
A 68-year-old hypothyroid male presented with recent onset of back pain and lower abdominal pain. On evaluation, he was found to have a metabolically active exophytic lesion at the lower pole of the left kidney measuring 2.0 x 2.3 cm, with multiple pelvic and para-aortic lymph nodes and multiple skeletal sclerotic lesions suggestive of metastatic disease on FDG PET-CT. CT-guided biopsy from the left para-aortic lesion performed on 24.09.2025 revealed metastatic carcinoma with an IHC profile consistent with a renal primary - IHC positive for CK and PAX8, negative for CK7, CK20, CAIX, NKX3, P40, PSAP, 34BE12, AR, and TTF1.
He received 4 fractions of palliative SBRT to D12, left femur, and left 4th and 9th ribs. The patient was treated with Inj Pembrolizumab 200 mg for 8 cycles along with Tab Axitinib 5 mg. His 3-month FDG PET-CT evaluation demonstrated a good partial response to therapy.
Case 3
A 69-year-old male presented with back pain and was found to have multiple metabolically active lytic lesions in multiple vertebrae, pelvic bones, and bilateral femur on FDG PET-CT performed on 08.02.2024. Biopsy from the D9 vertebral lesion was suggestive of metastatic carcinoma favouring a renal primary - IHC positive for CK and PAX8, negative for P40. MRI of the whole abdomen performed on 20.02.2024 revealed a mass 1.6 x 2.4 cm over the upper pole of the left kidney. He underwent left robot-assisted nephron-sparing surgery on 27.02.2024, with an uneventful postoperative course. Histopathology confirmed clear cell renal cell carcinoma, pT1aNx.
He was started on Tab Sunitinib 50 mg after 2 weeks, along with palliative radiotherapy to D9, D12, L5, left acetabulum, right ischium, and bilateral femur - 30 Gy in 10 fractions, completed on 27.03.2024. He presented after 3 months with increasing back pain and lower limb weakness. FDG PET-CT performed on 07.06.2024 showed an increase in the lytic and soft tissue component with further extension into the spinal canal at D9 and D12. He underwent L4 left hemilaminectomy and decompression on 11.06.2024 for L4-L5 lumbar canal stenosis. He was subsequently switched to Tab Cabozantinib 20 mg for 7 days followed by 40 mg. The patient is currently doing well on this regimen.
|
SN |
Topics |
Case 1 |
Case 2 |
Case 3 |
|
1 |
Age/Sex |
72 years / Male |
68 years / Male |
69 years / Male |
|
2 |
Clinical Presentations |
Hematuria |
Back pain, low abdominal pain |
Back pain |
|
3 |
Initial Diagnostic Imaging(CECT / FDG PET-CT / MRI) |
FDG PET: Left renal mass (2.1 x 2.4 cm) with metastatic lesion in left femoral neck |
FDG PET: Left renal mass (2.0 x 2.3 cm) with multiple para-aortic and skeletal sclerotic lesions |
FDG PET: Multiple metabolically active lytic lesions in vertebrae, pelvic bones, bilateral femurMRI: Left renal mass (1.6 x 2.4 cm) upper pole |
|
4 |
Biopsy (IHC) |
Biopsy from left femoral neck: Metastatic carcinoma, primary of renal origin.IHC: Positive for CAIX (BOX-TYPE); negative for AMACR, CK7, CD117 |
CT-guided biopsy from left para-aortic region: Metastatic carcinoma consistent with renal primary.IHC: Positive for CK and PAX8; negative for CK7, CK20, CAIX, NKX3, P40, PSAP, 34BE12, AR, TTF1 |
Biopsy from D9 vertebral lesion: Metastatic carcinoma favoring renal cell carcinoma primary.IHC: Positive for CK and PAX8; negative for P40 |
|
5 |
Treatment (Surgery, Immunotherapy, CT, RT) |
Cytoreductive left nephron-sparing surgeryInj Pembrolizumab 200 mg x6 cycles + Tab Axitinib 5 mg |
Palliative SBRT x4 fractions to D12, left femur, left 4th and 9th ribsInj Pembrolizumab 200 mg x8 cycles + Tab Axitinib 5 mg |
Left nephron-sparing surgeryTab Sunitinib 50 mg + RT 30 Gy in 10 fractions to D9, D12, L5, left acetabulum, right ischium, bilateral femur |
|
6 |
Follow-up |
3 months - FDG PET: No evidence of disease |
3 months - FDG PET: Good partial response |
3 months - Increased back pain and weaknessFDG PET: Increase in lytic and soft tissue component, extension into spinal canal (D9, D12)L4 left hemilaminectomy and decompressionSwitched to Tab Cabozantinib 20 mg then 40 mg |
Discussion
These three cases collectively challenge the long-held perception that small renal masses (SRMs) are uniformly indolent lesions with negligible risk of systemic spread. For decades, SRMs have been regarded as biologically quiet, supported by reports of low annual growth rates, high rates of benign histology (approximately 20-30%), and metastatic rates cited as low as 1-2%.[2,10] This prevailing understanding has formed the scientific basis for conservative management pathways, including active surveillance in select patient populations, often without comprehensive metastatic staging.
The evidence in favour of active surveillance for SRMs is substantial and well-established. The landmark prospective DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) registry, enrolling 497 patients over five years, demonstrated equivalent cancer-specific survival between active surveillance and primary intervention cohorts, reporting no cancer-specific deaths in the surveillance arm and confirming that active surveillance was non-inferior to immediate surgery.[11] The same registry's 10-year update continued to support the oncological safety of this approach for carefully selected patients.[12]
A large systematic review by Mir et al. evaluating 457 patients across multiple AS cohorts reported a median linear growth rate of just 0.22 cm/year for SRMs, with consistently low rates of metastasis and cancer-specific mortality across all series.[13] A more recent systematic review and quantitative analysis encompassing 2,066 patients on active surveillance reported a pooled cancer-specific survival rate of 99% and a metastasis-free survival rate of 97.9% over a mean follow-up of 53 months.[14] Similarly, a large Danish cohort of 563 active surveillance patients across three institutions followed from 2012 to 2023 recorded metastatic progression in only one patient - further corroborating the predominantly indolent nature of most SRMs.[15]
These robust datasets have appropriately led major urological guidelines - including those of the American Urological Association (AUA) and the European Association of Urology (EAU) - to endorse active surveillance as a safe and reasonable strategy for elderly, comorbid, or surgically unfit patients.[5,6] Sebastia et al., in a review of active surveillance for SRMs, similarly concluded that the growth rate and the possibility of developing metastasis in SRMs are extremely low, and that active surveillance with routine imaging follow-up represents a legitimate and guideline-endorsed management option.[16]
However, the cases presented in this series demonstrate that this reassuring statistical picture does not apply uniformly to all patients, and the outcomes due to this are clinically real and consequential. In all three patients, metastatic disease was diagnosed either concurrently with or prior to the identification of the primary renal lesion - all of which measured less than 3 cm. Notably, in Case 3, the diagnosis of RCC was made only after the patient underwent workup for widespread skeletal metastases, with the renal primary identified retrospectively on MRI. This pattern of metastasis-first presentation, arising from a radiologically small renal lesion, directly contradicts the intuition that small tumors can be safely observed without systemic staging.
The first case illustrates an unusual scenario in which metastatic RCC was first identified in the femoral neck - causing a pathological fracture - before the renal primary was formally characterised. The second case highlights the importance of thorough evaluation in patients presenting with back or abdominal symptoms, where comprehensive imaging revealed an occult small renal primary with extensive nodal and skeletal metastatic burden. Both cases responded well to systemic immunotherapy with pembrolizumab and axitinib, reflecting contemporary first-line management for metastatic RCC.
The third case, by contrast, demonstrated disease progression on sunitinib with spinal cord compromise, requiring escalation to cabozantinib - a second-line TKI with proven efficacy in this setting - alongside urgent neurosurgical decompression.
The biological rationale for metastatic potential in SRMs is increasingly supported by the literature. Despite being classified as T1a, SRMs represent a heterogeneous group with variable molecular profiles. Thompson et al. demonstrated that the risk of synchronous metastasis increases significantly once tumor size exceeds 3 cm, but also documented that metastatic disease may still occur in lesions smaller than 2 cm, confirming that there is no truly safe size threshold below which metastasis can be entirely excluded.[9] Similarly, Klatte et al. reported that tumor diameter alone is not an adequate surrogate for biologic aggressiveness, and that a measurable subset of SRMs presents with metastatic disease at diagnosis.[10] Reported synchronous metastatic rates across the literature are approximately 0-1% for tumors less than 2 cm, 1-3% for tumors measuring 2-3 cm, and around 5-8% for tumors between 3-4 cm.[5,9,10] A recent single-center series by Luciani et al. further highlighted the metastatic potential of very small RCCs (less than or equal to 2 cm), reinforcing the concept that even lesions within the lowest size category cannot be assumed to be biologically inert.[8]
These observations reflect the fundamental biological heterogeneity of SRMs, rather than the widespread belief of no metastatic potential of these entities. Importantly, a systematic review by Smaldone et al. noted that among SRMs progressing to metastasis during active surveillance, 23% showed no measurable growth during the surveillance period - a finding that suggests growth rate alone cannot serve as a reliable surrogate for aggressive behavior.[17] This observation underscores a critical limitation of the surveillance model: the very parameters used to trigger intervention (growth > 0.5 cm/year or size > 4 cm) may fail to identify the biologically aggressive subset most at risk of systemic spread.
The present series aligns with these observations: all three patients had renal masses between 1.5 and 3 cm yet already demonstrated synchronous skeletal and/or nodal metastases at presentation. This underscores the inadequacy of tumor size alone as a stratification tool for metastatic risk. Biological factors - including histological subtype, nuclear grade, sarcomatoid differentiation, and molecular markers - may be far more relevant predictors of aggressive behavior than morphological size, yet these are often inaccessible without tissue sampling at initial presentation.
From a practical standpoint, these cases reinforce that clinicians should maintain a low threshold for cross-sectional metabolic staging - such as FDG PET-CT or CT of the chest, abdomen, and pelvis - even in patients with apparently small renal masses, particularly those presenting with symptoms such as back pain, bone pain, or unexplained constitutional features. Furthermore, the finding of skeletal or nodal lesions of uncertain origin - as in Cases 1 and 3 - should include renal cell carcinoma in the differential diagnosis, prompting targeted renal imaging even when no prior renal abnormality has been documented.
It is equally important to acknowledge that these cases do not argue against active surveillance as a valid management strategy for SRMs in appropriately selected patients. The evidence base supporting surveillance in elderly or comorbid individuals with small, slow-growing lesions remains robust.[3,4,11,13] Rather, these cases argue for a more individualised risk assessment framework - one that incorporates clinical symptoms, lesion morphology, growth kinetics, metabolic activity, and ideally tissue biopsy - rather than relying on size alone as the arbiter of metastatic risk. Patient selection criteria for active surveillance, as recommended by both AUA and EAU guidelines, should be rigorously applied, and any deviation from expected clinical behaviour should prompt reassessment of the surveillance plan.
Conclusion
Together, these cases underscore the biological heterogeneity of SRMs and demonstrate that metastatic potential cannot be reliably excluded based on tumor size alone. While the evidence from large prospective registries confirm that the vast majority of SRMs follow an indolent course amenable to active surveillance, a clinically meaningful minority can present with synchronous distant metastases - even from lesions well under 3 cm. The varied clinical presentations in this series, ranging from pathological fracture to back pain and incidental detection of widespread skeletal metastases, further emphasise the need for heightened clinical suspicion and careful patient selection when considering conservative management strategies.
The risk of synchronous metastasis in SRMs is low but real, with reported rates ranging from 1% to 13%, trending higher in tumors approaching 4 cm.[8] However, no size threshold completely excludes the possibility of metastatic disease. A small RCC should always be kept in mind as a potential primary when widespread metastases are identified without an evident source. These cases serve as an important reminder that size-based risk stratification, while useful as a starting point, must not replace individualised clinical judgment, comprehensive staging, and multidisciplinary evaluation in the management of renal masses.
References