Non-osseous soft tissue metastasis in the foot from renal cell carcinoma
- Nusrat Jahan and
- Shabnam Rehman
- Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
- Correspondence to Dr Nusrat Jahan; n.jahan@ttuhsc.edu
Abstract
Metastatic tumours of the distal extremities, also known as acrometastases, are rare. The majority of the acrometastases involve bones—involvement of the soft tissues of the feet and hands is extremely rare. We report a case of clear cell renal cell carcinoma metastasised to the soft tissues of the foot. The patient presented with pain and swelling in his right foot. Diagnosis of acrometastases frequently gets delayed due to the rarity of this condition and resultant low clinical suspicion. Possibility of metastatic disease should be entertained as an important differential diagnosis when patients with a history of cancer present with musculoskeletal symptoms. A systematic evaluation incorporating thorough clinical assessment, advanced imaging techniques like MRI and pathological examination is critical to establish the diagnosis.
Background
Metastatic tumours in the extremities distal to the elbows and knees are conglomerated together under the umbrella term acrometastases. Acrometastases are relatively rare and account for approximately 0.1%–0.2% of all metastatic cancers.1–3 Lung, breast, genitourinary and gastrointestinal cancers are the most common primary tumours that metastasise to the distal extremities.1–5 The majority of the reported acrometastases are to bones, such as tibia, fibula, radius, ulna, tarsal, metatarsal, carpal, metacarpal or phalangeal bones.4 6 Soft tissue metastases of the distal extremities from a non-contiguous primary are extremely rare, and only a few cases have been reported in the literature.7 8 Here, we present a case of clear cell renal cell carcinoma (RCC) metastasised to the soft tissue of the foot. This case emphasises the importance of considering acrometastases as a potential differential diagnosis when patients, especially patients with a diagnosis of cancer, present with local symptoms in the distal extremities.
Case presentation
A 70-year-old Caucasian man with history of clear cell RCC of the right kidney and right open total nephrectomy was referred to medical oncology with the concern of disease progression. The patient initially presented to a gastroenterologist in May 2018 due to abdominal pain, weight loss and fatigue of several months. He had no significant past medical history. However, he was a former smoker and smoked more than 80 pack-years prior to quitting a year before the presentation. An abdominal CT scan was done for evaluation, and it revealed a large, heterogeneous, right renal mass, measuring 8.5 cm×5.6 cm×6.7 cm. His chest X-ray was negative for any metastasis. Subsequently, the patient underwent a right open radical nephrectomy in June 2018. The final pathology showed clear cell RCC with no sarcomatoid differentiation, Fuhrman nuclear grades 3–4 (figure 1). The tumour was limited to the kidney, and margins were not involved by the invasive carcinoma. Pathological staging was pT1bNxMx. Post-surgery his urologist had been following him with regular clinical examinations and scans.
Six months after his nephrectomy, in January 2019, a surveillance CT abdomen and pelvis with renal mass protocol showed an enhanced 1.9 cm nodule (19 Hounsfield units) at the inferior aspect of left kidney along with several nodules in the bases of both lungs. At that time no intervention was pursued, and the plan was to follow these lesions closely with repeat scans. Subsequent CT chest, abdomen and pelvis in 4 months showed enlarged pulmonary nodules, bilateral hilar lymphadenopathy, stable left renal mass and a new right adrenal mass. With the concern of metastatic disease, the patient was referred to medical oncology.
Investigations
A biopsy from one of the right lung nodules was consistent with metastatic clear cell RCC. An MRI of the brain showed a 6 mm enhanced lesion along the left motor cortex with surrounding vasogenic oedema suggestive of metastatic disease to the brain with no midline shift or mass-effect. While on treatment, as outlined below, the patient complained of right foot pain leading to X-ray of the right foot that was negative for any fracture or obvious lytic lesion. A subsequent contrast-enhanced MRI of the right foot showed a 2.4 cm intensely contrast-enhanced soft tissue mass along the plantar aspect of the midfoot adjacent to the plantar fascia (figure 2). A biopsy from the foot lesion showed metastatic clear cell RCC (figure 3).
Treatment
After confirmation of metastatic clear cell RCC, the patient was started on treatment with ipilimumab and nivolumab combination according to CheckMate 214 trial.9 10 He also underwent stereotactic radiosurgery to the brain lesion.
Outcome and follow-up
Patient’s immunotherapy was interrupted by a couple of interim hospitalizations—first-time due to a seizure from radiation necrosis and second-time due to diarrhoea and hypotension. At a follow-up visit prior to his cycle 2 of immunotherapy, the patient complained of worsening deep-seated pain in the right foot. The pain had been present for a few weeks and had been getting progressively worse causing difficulty in ambulation. As reported above, plain roentgenograms of the right foot were negative for any fracture and lytic lesion. A subsequent MRI of the right foot showed an enhanced soft tissue mass along the plantar aspect of the midfoot (figure 2). With the concern for metastatic disease, a biopsy was pursued, and pathology confirmed metastatic clear cell RCC (figure 3). Later, he was referred to radiation oncology for palliative radiation to the foot lesion. However, prior to radiation oncology visit, after cycle 2 of immunotherapy, he got admitted to the hospital with diarrhoea and hypotension. Infectious work-up was negative and the patient improved with conservative measures. Repeat CT chest, abdomen and pelvis done during hospital admission showed decreases in the size of pulmonary nodules, and stable left renal and right adrenal lesions. After discharge, the patient decided against any further therapy despite having partial response and opted to pursue palliative care only.
Discussion
RCC accounts for approximately 10%–20% of acrometastases.1–5 11 Like other primary tumours, RCC acrometastases commonly involve bones rather than soft tissues.12–16 In general, metastatic tumours to soft tissues are rare and comprise only 1.3%–1.6% of all soft tissue tumours.7 8 Often they tend to involve soft tissues of the proximal extremities and body wall rather than the distal extremities.7 8 17 18 In a case series of soft tissue metastases from non-contiguous primary tumours, Plaza et al reported one case of soft tissue metastasis to foot from a melanoma among 118 patients over a 30-year period from a tertiary care centre.7 Likewise, Abed et al described two cases of soft tissue metastases to foot in a series of 100 cases of soft tissue metastases from distant primaries.8 To the best of our knowledge, this would be the second case of soft tissue acrometastasis from RCC to foot in the published literature. Potter et al reported a case of RCC metastasised to the subcutaneous tissue of the left fifth toe.19 In addition, McConnell et al described a case of metastatic RCC in the knee joint and Bibi et al described a case of metastatic RCC in the soft tissues of the hand.20 21 There are some reports of cutaneous and subungual metastases as well.22 The pathophysiology behind this relatively low incidence of soft tissue metastases to the distal extremities is poorly understood. One explanation could be relatively low and variable blood supply in the distal extremities.
In general, the majority of the patients with acrometastases have a known history of cancer. However, in approximately 10% of cases, acrometastases could be the first clinical manifestation of underlying occult malignancies.2 12 13 23 The latter often present to orthopaedic physicians for evaluation of possible sarcomas.8 The most common presenting features for acrometastases are local pain, swelling, loss of functionality, pathological fracture and so on.5 8 12 13 18 One of the challenges with diagnosing acrometastases is lack of clinical suspicion. In large case series, Evans et al reported 16 weeks of median delay (range: 6—104 weeks) in diagnosis of skeletal acrometastases after the onset of symptoms.24 In another case series, Yang et al described a median delay of 24 weeks between the onset of foot symptoms and the diagnosis of skeletal acrometastases of the foot (IQR: 20—36 weeks).25 Advanced imaging techniques, such as MRI and CT scans, are helpful for early identification of the lesions and ruling out of other pathologies. In our case, the interval between the onset of acral symptoms and the diagnosis of acrometastasis was around 10 weeks.
The majority of the acrometastases are associated with disseminated malignancies—they usually carry a poor prognosis. Although average median survival varied between different case series, it is usually less than a year after the diagnosis of acrometastases.1 2 4 Rarely, acrometastases could be the only site of distant metastasis and these patients tend to have a relatively good prognosis.5
Given the rarity of acrometastases, there are no standard guidelines for their management—treatment is often individualised based on the clinical scenario. In cases of disseminated malignancies, local treatment like radiation or surgery for palliation of symptoms along with systemic therapy for malignancy is a reasonable approach. In oligometastatic cases, metastasectomy with treatment of the primary tumours is also a commonly adopted approach, and these patients tend to have a longer survival.1 15 23
Our patient developed soft tissue acrometastasis in his right foot from his disseminated clear cell RCC. After diagnosis of systemic recurrence, the patient was started on ipilimumab and nivolumab combination—one of the recommended first-line therapies for metastatic RCC.10 We also planned for palliative radiation therapy to the foot metastasis. However, the patient opted for comfort care due to poor quality of life and ultimately succumbed to the disease.
Learning points
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Acral soft tissue metastases from distant primary cancers are very rare, and often their diagnosis is delayed due to low clinical suspicion.
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The most common presenting features of acrometastases are local pain and swelling. When patients present with pain and swelling of the distal extremities, acrometastases need to be considered as a potential differential diagnosis, especially when there is a known history of cancer.
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Acrometastases are often associated with disseminated malignancies. However, rarely they could be the initial manifestation of an underlying occult malignancy. A systematic evaluation incorporating thorough clinical assessment, advanced imaging techniques like MRI and tissue sampling is important to establish the diagnosis.
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Primary care providers, oncologists and orthopaedic surgeons need to be aware of this clinical condition as patients often present to them with this relatively rare condition.
H&E staining of the nephrectomy specimen: clear cell RCC, nuclei are irregular and hyperchromatic (Fuhrman nuclear grades 3–4). RCC, renal cell carcinoma.
MRI with contrast of the right foot showing a soft tissue mass measuring 2.4 cm in diameter abuts the plantar fascia. The mass shows contrast enhancement. No other significant bony or soft tissue abnormality is noted.
H&E staining of core-needle biopsy of the right foot lesion: metastatic clear cell RCC. RCC, renal cell carcinoma.
Acknowledgments
The authors thank the patient and his family for giving the opportunity to take care of the patient.
Footnotes
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Contributors NJ conducted literature search, reviewed case, participated in paper’s conception, planning and writing the manuscript. SR took care of the patient, participated in paper’s conception, planning and writing the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Not required.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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