Too Big to Miss

A 54-year-old woman with a past medical history of metastatic melanoma who started on immunotherapy 2 months prior presented with 3 weeks of shortness of breath.

At baseline, she had an excellent exercise tolerance. She initially presented to an outside hospital in August of 2017 with several months of non-productive cough, hoarseness, and drenching nightsweats. Computed tomography (CT) scan at that time revealed a 9.6 x 11.8 x 10.7 cm mass in the upper left chest, as well as hilar adenopathy, precarinal lymphadenopathy, multiple bilateral pulmonary nodules, and a small left-sided pleural effusion. A biopsy was consistent with BRAF wild-type melanoma. The pathology revealed nests of tumor cells elongated bundles, positive for S100, SOX10, TLE1, and PDL1. While awaiting the histology results, she began to experience dyspnea on exertion, limiting her exercise tolerance to less than 1 flight of stairs. Repeat scans showed the upper chest mass had increased to 10 x 14 x 12 cm, and her left pleural effusion had worsened. She received large volume thoracentesis with complete relief of her dyspnea of exertion. A catheter was placed. In early September 2017, she was started on ipilimumab 3 mg/kg and nivolumab 1 mg/kg with plans for infusions every 3 weeks. Radiation oncology was consulted and thought that the mass could not be safely irradiated.

Over the next 2 months, she again experienced worsening dyspnea on exertion. A transthoracic echocardiogram (TTE) in October 2017 revealed a moderate-sized circumferential pericardial effusion without evidence of increased pericardial pressures, an ejection fraction of 70%, normal diastolic function, and a right ventricle that was normal in size and function. In November 2017, she presented to the cardio-oncology clinic at The Hospital of University of Pennsylvania. By that time, she was unable to ambulate across the room without severe shortness of breath. She had associated lower leg swelling up to her mid-thigh, orthopnea causing her to sleep upright in a chair, and paroxysmal nocturnal dyspnea. She denied palpitations or chest pain. On further review of systems, she noted ongoing nighttime fevers and sweats, decreased appetite, and fatigue. She denied diarrhea, new rashes, pruritis, or hair or nail changes. In addition to her immunotherapies, she was on oxycodone, acetaminophen, and ondansetron as needed. She had no other pertinent cardiac, surgical, or psychological past medical history. She had no allergies.

In cardiology clinic, her vitals were

  • blood pressure of 102/70;
  • pulse of 114;
  • height of 5 ft and 6.5 in (1.689 m);
  • weight of 140 lb (63.5 kg);
  • blood oxygen saturation of 94%; and
  • body mass index of 22.26 kg/m2.

She was thin and uncomfortable but non-toxic appearing. She had a jugular venous pressure of 12 cm without Kussmaul sign and rightward deviation of her trachea. Her cardiac exam revealed a distinct point of maximal impulse in the midclavicular space, an S1 and an S2 but no S3, S4, murmur, or rub. The pulsus was 12 mmHg. Her lungs revealed slightly decreased respiratory sounds at the left base but no rales, rhonchi, or wheezing. She had 3+ pitting edema to the mid-thigh. Labs at that time were notable for normal liver function tests, a normal basic metabolic panel with a creatinine of 0.68, a normal thyroid stimulating hormone and thyroxine level, a normal complete blood count, and a troponin T <0.010. An electrocardiogram (ECG) (Figure 1) revealed sinus tachycardia and low voltages that were new compared to prior ECG in August 2017 (Figure 2). A chest CT with intravenous contrast had been ordered by her oncologist 2 days prior to the office visit (Figure 3), which was reviewed. The CT revealed increase in the left upper chest mass to 13 x 17 x 15 cm, with a new area of central necrosis. The pulmonary nodules, lymphadenopathy, and pleural effusion had all improved from prior visits.

Figure 1: ECG at Cardiology Clinic in November 2017

Figure 1

Figure 2: ECG at Office Visit in August 2017

Figure 2

Figure 3: CT Scan With Contrast of the Chest From November 2017

Figure 3

What is the appropriate next step in management?

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