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A 51-year-old man presents to emergency after suddenly experiencing weakness on the right side of his body. At the same time, he notes, he began to slur his speech.

He has had no health issues recently or in the past, and takes no medications regularly. He has no chest pain, dyspnea, or palpitations; nor has he had any fevers, chills, cough, or neck pain.

At the time of the abrupt onset of weakness, he reports having had a brief headache, for which he has taken an Excedrin tablet (250 mg aspirin, 250 mg acetaminophen, 65 mg of caffeine).

He explains that although he quit smoking 11 years ago, he used to smoke; clinicians estimate that he has a 20 pack-year history.

Clinicians note a significant drooping on the right side of his face.

His motor strength is 0/5 in right upper extremity, 2/5 in right lower extremity, and 5/5 in left upper and lower extremities. The patient has intact sensation in all extremities.

Physical exam findings on arrival:

• Heart rate: 69
• Blood pressure: 127/74
• Respiratory rate: 16
• Oxygen saturation: 97% on 2 liters oxygen via nasal cannula
• NIH Stroke Score: 12

Diagnostic studies find all of the patient's electrolytes and lipids within reference ranges.

Other test findings include:

• Total cholesterol: 167 mg/dL
• Red blood cells: 7.08 m/mm³ (normal range: 4.00–5.70 m/mm³)
• Hemoglobin: 20.4 g/dL (normal range: 13.5–17.0 g/dL)
• Hematocrit: 62.0% (normal range: 37.0%–50.0%)

Findings of a CT scan of the head without contrast, and intracranial CT angiogram are both normal. Brain MRI without contrast reveals an acute infarct: the left corona radiata, the posterior limb of the internal capsule, and the posterior left putamen are involved.

Urinalysis is performed at the suggestion of the consulting hematologist, who notes the importance of assessing the patient for evidence of a renal mass, which can be associated with secondary polycythemia.

Hospital Day 1

Urinalysis report includes 1+ blood and 3-9 red blood cells. As a result, clinicians perform an abdominal ultrasound. Abdominal ultrasound reveals a 5.1-cm heterogeneous solid mass suspicious for neoplasm in the lower pole of the right kidney.

Hospital Day 4: Further investigation

Abdominal CT scan (Figure) identifies an enhancing mass measuring 5.7 × 4.3 × 5.5 cm – which clinicians believe suggests renal cell carcinoma (RCC).

Echocardiogram reveals hypertrophy of the left ventricle. Laboratory work is performed to assess the patient's polycythemia and hypercoagulability. Erythropoietin (EPO) level is 20.9 mIU/mL (normal range: 2.6–18.5 mIU/mL). Results of tests for JAK2 PCR, hemoglobin electrophoresis, prothrombin gene mutation, antiphospholipid antibody, factor V Leiden, BCR ABL mutation, antithrombin III, and ACL IgM/IgG are all negative, undetectable, or within normal limits.

Approach to treatment

The patient is admitted and receives tissue plasminogen activator (tPA) for his ischemic stroke, as recommended by the consulting neurologist. Additional therapeutic interventions include daily physical therapy and occupational therapy. He is permitted a regular diet following evaluation of his ability to speak and swallow.

About 24 hours after receiving tPA, daily treatment is initiated with 81 mg aspirin and atorvastatin 80 mg. A therapeutic phlebotomy is performed to manage his secondary polycythemia.

Hospital discharge: Follow-up and outcomes

The patient is discharged from hospital to an acute rehabilitation program. His NIH Stroke Score has decreased from 12 to 8. He is expected to remain in the program for about 2 weeks. Clinicians order both physical therapy and occupational therapy for 1 hour, 5 days/week, and speech therapy for half an hour, 5 days/week. Rehabilitation program includes balance, gait training, activities of daily living training, and oral motor and speech services.

The patient is advised by the urologist to have the renal mass reassessed within 1 month of discharge from the rehabilitation facility; he is expected to require a right partial or radical nephrectomy.

Discussion

Clinicians reporting this suggest it is the first report of an ischemic stroke due to secondary polycythemia from an EPO-secreting renal cell carcinoma – they urge a high level of suspicion for polycythemias when presented with acute embolic cerebral ischemia in a previously healthy, low-risk individual.

Focal cerebral ischemia may be caused by both polycythemia vera and by a potential paraneoplastic complication of RCC, secondary polycythemia, authors write. Usual causes of secondary polycythemia include adaptation to chronic obstructive pulmonary disease, high altitude, and erythropoiesis-stimulating agents such as androgens/anabolic steroids.

Case authors note that while only one to five percent of human RCCs have EPO-producing cells, such a presentation should prompt further hematologic workup. An EPO-secreting neoplasm can result in significantly increased blood viscosity, and thus increase the risk of vaso-occlusive events.

They write that outcomes may be better for patients whose tumors are found incidentally than for those who present with paraneoplastic syndromes (PNS) [such as anemia, polycythemia, hypercalcemia, and liver dysfunction], or PNS sequelae (such as stroke, in this case). This is based on a large retrospective of outcomes of patients with RCC and paraneoplastic syndromes, including polycythemia.

German suggests that paraneoplastic syndromes – particularly hypercalcemia - are important but often unrecognized biomarkers in RCC. Awareness is important because not only can a PNS develop in advanced stages of renal cell carcinoma, it can often be the first symptom of RCC.

While the contributing role of cancer in hypercoagulable states is well-established, they note that acute events are rarely directly correlated with elevated EPO.

Transient ischemic attacks due to paraneoplastic erythrocytosis have been documented, as has ischemic stroke due to secondary polycythemia of other etiologies. In addition, polycythemia vera, a slow-growing blood cancer which elevates absolute red blood cell mass in the absence of elevated EPO, can also present with acute embolic cerebral ischemia, the group notes.

Conclusions

Case authors express the hope that surgery to remove the carcinoma will resolve this patient's secondary polycythemia and alleviate the need to treat this condition, adding that this been observed in many of the paraneoplastic syndromes associated with renal cell carcinoma.

References

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