Case Presentation
A 63-year-old male with a past medical history notable for a remote, seven pack-year tobacco history and recently diagnosed Stage 4 renal cell carcinoma (PAX 8(+)/TTF-1(-)) complicated by metastasis to the right hilum status post radiation and recent initiation of Nivolumab and Ipilimumab presented to our facility in the context of a two-week history of shortness of breath and fatigue. Of note, four months prior to presentation the patient visited his primary care physician in the context of a three-week history of an unexplained cough. Chest radiograph demonstrated a right hilar mass, which was confirmed on computed tomography, measuring 6.9 cm x 3.3 cm x 4.3 cm, and resulted in severe narrowing of the Superior Vena Cava with associated deformity of the right upper lobe and pulmonary artery. CT also demonstrated the presence of a heterogenous left renal mass measuring 6.3 cm x 5.8 cm x 5.6 cm and the patient was referred for biopsy which demonstrated metastatic renal cell carcinoma. He was subsequently initiated on radiation therapy directed toward the hilar mass (4000cGY) with a planned two-week course, which he completed 3 weeks prior to our hospital presentation. Following induction of radiation therapy, he was initiated on immunotherapy with Nivolumab/ Ipilimumab. Three days following his second cycle of Nivolumab/ Ipilimumab, he presented to our facility.
On presentation the patient reported shortness of breath that began two days after his first immunotherapy treatment, characterized initially as dyspnea on exertion and fatigue that acutely worsened and progressed following his second cycle of immunotherapy to involve dyspnea at rest. He had no associated fevers, chills, chest pain, cough, leg swelling, recent travel, or sick contacts. On presentation the patient was afebrile, tachycardic (140 beats per minute), and normotensive (SBP ranging from 100-120 mmHg), with a preserved oxygen saturation (97%) on room air. Initial laboratory workup demonstrated a preserved VBG (pH 7.39/pCO2 42.9 mm Hg/pO2 31.5 mm Hg/HCO3 26.2 mEq/L) and NT-proBNP (37 pg/mL), with an elevated troponin of 2.1 ng/mL, and D-dimer (1.07 mcg/mL). Complete blood count and basic metabolic panel were unremarkable, however aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated to 166 units/L and 129 units/L, respectively. Alkaline phosphatase and bilirubin were within normal limits. Creatine Kinase was elevated to 1266 units/L. Chest computed tomography (CT) demonstrated a 6.7 cm x 4 cm right hilar mass consistent with prior imaging with no appreciable change in size compared to the chest CT completed four months prior, with continued narrowing of the SVC (Figure 1 ). There were multiple, small scattered irregular nodular densities throughout the right lung suspicious for metastatic disease, without associated pleural effusions. The heterogeneous left-sided renal cell mass measuring 4.6 cm x 5.3 cm (Figure 2 ) was once again appreciated, with noted interval decrease in size. Electrocardiogram demonstrated sinus tachycardia, left atrial enlargement, delayed R-wave progression, and subtle, diffuse ST elevations and PR depressions (Figure 3 ). Nuclear medicine scan was performed which demonstrated no evidence of pulmonary embolism.
Due to concern for SVC compression and an associated demand ischemia, he received three liters of crystalloid and was transferred to the medicine service for further evaluation. On presentation to the medicine ward, he remained persistently tachycardic and demonstrated no resolution of his elevated Troponin despite resuscitation, which peaked at 2.6 ng/mL. Echocardiography was performed that demonstrated a preserved ejection fraction, mildly enlarged right ventricle, and a moderately elevated pulmonary artery systolic pressure (47 mm Hg), with no evidence of cardiac deformation. Additional diagnostic workup revealed an undetectable TSH (< 0.005 µIU/mL) and an elevated free T4 (5.54 ng/dL), which were previously noted to be normal one month prior to initiation of Nivolumab/ Ipilimumab. Given his marked PR and ST segment changes, he was given a presumptive diagnosis of immunotherapy-mediated myopericarditis and initiated on 1mg/kg Prednisone. Cardiology and Oncology were consulted who noted a low probability of immunotherapy-mediated myopericarditis but agreed with presumptive steroid therapy. He demonstrated clinical improvement on prednisone and was discharged on a two-week taper with plans for outpatient follow up with Oncology.
On follow up two weeks post-discharge, that patient continued to note symptomatic improvement with near resolution of his underlying dyspnea. Repeat echocardiogram demonstrated no significant changes. Laboratory diagnostics demonstrated a down-trending CK (322 units/L) and in discussion with his outpatient Oncologist, steroid therapy was discontinued. Seven days following steroid cessation, the patient experienced recurrence of his shortness of breath and developed associated proximal muscle weakness. Laboratory diagnostics revealed an elevated CK (1,147 units/L) and as a result, he was re-started on steroids and immunotherapy was abandoned.