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.