Clinical manifestation of RCC leptomeningealcarcinomatosis—A case study

Abstract

Whilst tumour spread to the meninges is not uncommon, occurring in up to 20% of various other tumours, leptomeningeal carcinoma from a primary renal cell carcinoma (RCC) is rare. To date, we are aware of only 3 other reported cases. We describe a 45-year-old man who underwent a radical nephrectomy for a large renal cell carcinoma of clear cell subtype. 1 month post nephrectomy, he was re-admitted with vague neurological symptoms and was subsequently found to have malignant cells in his CSF. He deteriorated rapidly and was deceased within 10 days post admission.

1. Introduction

Renal cell carcinoma (RCC) is the most common type of primary renal tumour. Although many patients present with localized resectable disease, up to 1/3 of patients have locally advanced or metastatic disease by the time of diagnosis.¹ The most common sites of metastases are lung, bone, liver and CNS in descending order. CNS metastasis occurs in approximately 5% of patients with RCC.² Brain metastases is a well-documented phenomenon, however, to date we are only aware of 3 other case of documented leptomeningeal carcinomatosis from a primary RCC.^2–4 Conversely, seeding of tumour cells onto the leptomeninges is relatively common for other types of carcinoma and occurs in up to 20% of patients diagnosed with breast, lung cancer or melanoma.⁵

2. Case report

A 45-year-old man with an initial ECOG score of zero was first seen with left flank pain and haematuria for investigation. A triple phase CT scan demonstrated a large left renal mass with features suspicious for a RCC and no evidence of metastatic dissemenination (Fig. 1). He then underwent an uncomplicated open left nephrectomy 2 months later under epidural anaesthesia and was discharged home 8 days post-operatively with follow up appointments arranged.

Fig. 1.

. Triple phase CT abdomen – a large multi-lobulated left renal mass, measuring approximately 11 cm × 15 cm × 20 cm is present. There is internal speckled calcification and contrast enhancement. The mass has prominent vessels around it, consistent with neovascularisation and appearance in keeping with a large renal cell carcinoma (sagittal and coronal views).

Histological analysis of the resected left kidney revealed Furhman nuclear grades II–III clear cell renal cell carcinoma (Fig. 2) with tumour confinement to the renal capsule (Fig. 3). However metastatic deposits were identified in 1 para-aortic nodule (Fig. 4) and 1 mesenteric nodule resected during surgery. Thus the renal cancer was a Stage III (T2N1M0) as per AJCC⁶ staging system.

Fig. 2.

Macroscopic sectioning of the left kidney revealing the tumour that has a heterogenous and multinodular appearance comprising of solid yellow and friable tan regions admixed with cystic areas and showing a solid central scar.

Fig. 3.

Photomicrograph demonstrating the clear cell renal cancer (H&E staining).

Fig. 4.

Micrographic section through the paraaortic lymph node showing numerous epithelioid like cells with moderately abundant eosinophilic cytoplasm and having nuclear pleomorphism (H&E staining).

He re-presented 3 weeks later with a 3-day history of fever and back pain in the mid-thoracic region extending up to the neck but also radiating down the legs bilaterally. He also complained of intermittent paraethesia of the toes but did not have difficulty mobilising.

On physical examination, he was afebrile and his neurological system was unremarkable. His cranial nerves were intact and power in his upper and lower limbs were 5/5 throughout. A CT head did not demonstrate any evidence of CNS pathology. A CT abdomen–pelvis also showed no intra-abdominal pathology. An MRI of his back was performed to rule out an epidural abscess and this too was negative (Fig. 5). He was discharged from the emergency department with simple and opioid analgesia.

Fig. 5.

MRI brainstem and spine – no evidence of compression or narrowing of the thecal sac. No epidural collection or mass within the spinal canal demonstrated. The cord is of normal signal and dimension. No evidence of bony metastasis.

One week later he again re-presented with worsening symptoms. In addition to his back pain, he now complained of a severe headache associated with photophobia and retro-orbital pain on downward gaze. He also had poor appetite over this period of time and noticed bilateral facial tingling. On examination, he was afebrile with normal vitals but looked dehydrated and malnourished. New neurological signs included a stocking distribution of temperature sensation loss up to the knees. Cranial nerve examination was otherwise unremarkable. Power and reflexes of the lower limbs were also normal. He was admitted for rehydration, nasogastric feeding and observation. ECOG score was 1 at time of admission.

His full blood count was normal and his electrolyte profile was only remarkable for mild hyponatremia that was present on previous tests. Lumbar puncture (LP) was performed; opening pressure of 6 cm H20 and macroscopically CSF was a pale yellow colour. CSF biochemistry revealed a very high protein level (8.5 g/L) and low glucose (0.2 mmol/L). CSF viral, bacterial and fungal cultures were negative.

Whilst waiting for the CSF cytology, his condition deteriorated rapidly over a few days. He became delirious and developed multiple cranial nerve palsies i.e. diplopia on downgaze emanating from right eye, dysarthria, dysphagia, bilateral severe LMN CN VII weakness and bilateral tongue fasciculations with mild weakness. By this time it also became increasing difficulty for him to get out of bed. In summary the clinical impression was that of progressive cranial neuropathies and lower limb radiculopathy with the concern of possible meningeal carcinomatosis given his recent renal cell cancer. CSF cytology ultimately demonstrated a few large atypical cells with irregular nuclei consistent with malignancy (Fig. 6). Unfortunately, the CSF sample was insufficient for immuno-histochemical testing and the patient's family were not keen for further repeat lumbar punctures. The CSF and renal cell cancer histology did however share similarities in that they both had nuclear pleomorphism and abundant cytoplasm and cytoplasmic vacuolation.

Fig. 6.

Cytological examination of cerebrospinal fluid demonstrating low numbers of large atypical cells with irregular nuclei, singly and some with cohesion, consistent with malignant cells.

The option of chemotherapy was discussed with the patient and his family. However due to the patient's poor functional status at this stage, his family opted for palliative care only. He passed away 10 days after admission.

3. Discussion

Tumour spread to the meninges occurs in 5–20%^5,7 of all solid tumours with breast, lung, melanoma, lymphomas and leukemias most commonly associated with this. Leptomeningeal carcinoma from a primary RCC is rare however. Headache, cranial nerve palsies, altered conscious state and back/ radicular pain or changes in sensation are common manifestations.⁵ Once clinically suspected, a lumbar puncture or FLAIR MRI should be performed to confirm the diagnosis. A lumbar puncture may reveal elevated proteins with reduced glucose in the CSF. The presence of atypical cells in CSF cytology is highly specific for meningeal carcinomatosis, however false negative rates of up to 40% have been reported in literature. In contrast, FLAIR MRI is highly sensitive for meningeal carcinomatosis. Abnormal hyperintensity within the sulci and periventricular regions on a contrast-enhanced FLAIR MRI has been shown to be specific and as sensitive, if not superior to contrast-enhanced T1, spin-echo T2 weighted and non-contrast FLAIR images for meningeal carcinomatosis.⁸ Hydrocephalus without an obvious obstructing lesion is another common finding on neuro-maging.²

The prognosis of RCC is based on the American Joint Committee on Cancer (AJCC) TMN staging system. Survival ranges from >90% five-year survival rate for stage 1 disease (T1N0M0) to <10% five-year survival rate for stage 4 disease (M1). Untreated, the median survival for patients with leptomeningeal carcinomatosis is 4–6 weeks.

4. Conclusion

Although leptomeningeal carcinomatosis from a primary RCC is rare, clinicians must be suspicious of its presence in a patient who presents with back pain and vague neurological symptoms post-nephrectomy even in an otherwise thought to be localized disease (T1 and T2). The suspicion should be promptly followed up with appropriate investigations. This is because untreated RCC leptomeningeal carcinoma confers such an unfavourable prognosis. The role of Sorafenib in improving progression-free survival has been demonstrated for advanced RCC in various trials. In particular its ability to limit disease progression in a patient with RCC leptomeningeal carcinomatosis has been reported in another case study.⁴

Conflict of interest

There are no conflicts of interest. For the purpose of confidentiality, all identifying materials have been removed from the radiological and pathological images.

Written informed consent was obtained from the patient's next of kin for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request

Funding

None

Ethical approval

As our patient in this case report passed away soon after diagnosis, written informed consent has been obtained from his wife to allow us to publish this report detailing his rare surgical condition. In addition, all radiological and pathological images have no identification labels on them to further protect his identity.