May 1, 2014 - Introduction. Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy which arises from Merkel cells located in the basal layer ...
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Cardiac Metastasis in Merkel Cell Carcinoma Introduction Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy which arises from Merkel cells located in the basal layer of the epidermis. Merkel cells have synaptic contacts with somatosensory afferents and are associated with the sense of light touch discrimination of shapes and textures. MCC has a propensity to widespread metastases and is found mainly in elderly, white patients. MCC occurs at a younger age in immunosuppressed patients, and is associated with UV radiation exposure and infection with Merkel cell polyomavirus. The incidence is rising, with a tripling of the overall incidence between 1986 and 2001 (SEER database1). Case Report An 80-year-old man presented with melena and fresh red blood per rectum, associated with lightheadedness, but no other symptoms. His past medical history included metastatic MCC. Eleven months earlier he had received concurrent chemoradiation treatment to a 7-cm left anterior axillary mass, a 1.5-cm subcutaneous nodule on the left arm, and a mass in the left supraclavicular fossa. 50 Gy was delivered in 25 doses to the left axilla and supraclavicular fossa, with a boost of 4 Gy in two doses to the subcutaneous masses and an additional boost of 2 Gy to the left axilla, with concurrent carboplatin area under the curve of 2. The primary lesion was never identified. Positron emission tomography/computed tomography (PET-CT) performed 2 months after treatment demonstrated an excellent response to treatment, with complete resolution of the left supraclavicular and left arm masses. The left axillary mass had reduced significantly in size to 1 cm from the previous 7 cm, and there was also a significant reduction in glucose avidity. During the current presentation, the patient remained hemodynamically stable. He was dyspnoeic on exertion, but otherwise denied any cardiorespiratory symptoms. On examination, a mobile, 2-cm lymph node was palpable in the left axilla. His jugular venous pressure was not elevated, pulsus paradoxus was not present, and there was no pedal edema. The chest was clear on auscultation and heart sounds were normal. Despite multiple investigations, including two CT mesenteric angiograms, a definitive cause for the bleeding was not identified. The patient reported experiencing a similar episode previously which had been associated with campylobacteriosis. Another speculated factor was the patient’s regular aspirin. It was postulated that the rectal bleeding may have been due to back pressure on the venous system from the cardiac lesion, exacerbated by the aspirin. The aspirin was ceased and the bleeding resolved spontaneously. CT mesenteric angiography did not identify active bleeding in the small or large bowel. However, it incidentally revealed a large, lobulated filling defect in the right atrium eccentrically located along the posterior aspect. e52
© 2014 by American Society of Clinical Oncology
Fig 1.
Transthoracic echocardiography demonstrated a 3.7 ⫻ 2.0 cm and 2.0 ⫻ 1.8 cm multilobulated, heterogeneous right atrial mass, extending into the inferior vena cava.1a There was no pericardial effusion, normal biventricular size and normal systolic function. The left atrium was mildly dilated the and left ventricular ejection systolic fraction was 60%. Subsequent transesophageal echocardiography confirmed a 3 ⫻ 1.7 cm atrial mass,withpossiblytwopedicles,andextensionintotheinferiorvenacava. Comparedwithaprevioustransesophagealechocardiographyperformed 4 months earlier, the mass was new. Cardiac magnetic resonance imaging (Fig 1) confirmed a lobulated right atrial mass (arrow). [18F]-fluorodeoxyglucose (FDG) –PET/CT scan (Fig 2) demonstrated an intensely FDG-avid, enlarged left axillary lymph node (standardized uptake value, 13.7), and moderate to intense uptake in the right atrial mass (standardized uptake value, 8.8), but no evidence of metastatic disease elsewhere. Biopsy of the right atrial mass confirmed metastatic MCC. The patient received palliative radiation treatment, delivering 36 Gy 12 times to the right atrium using PET fusion. The patient tolerated treatment well. CT of the chest, abdomen and pelvis performed at 4 months, and again at 7 months, post treatment demonstrated resolution of the right atrial mass. There was no evidence of metastatic disease elsewhere. Of note, there was a small (7 mm) anterior pericardial effusion likely due to the radiotherapy. At follow-up 10 months after treatment, the patient remained well and asymptomatic. Discussion MCC has a propensity to metastasize widely. However, cardiac metastasis is extremely rare, with few cases reported in the literature to date.2 While cardiac metastases uncommonly present clinically, autopsy series have reported cardiac metastases to be present in 11.8% of patients with malignancy.3 The most common malignancies, in decreasing frequency, are lung, lymphoma, breast, leukemia, stomach, melanoma, liver, and colon. Another autopsy study reported Journal of Clinical Oncology, Vol 32, No 13 (May 1), 2014: pp e52-e53
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Diagnosis in Oncology
size of the axillary mass from 7 cm to 1 cm, and associated reduction in FDG avidity on PET. There was complete, sustained response in the other sites of disease, including the 1.5-cm subcutaneous nodule, and the FDG-avid disease in the supraclavicular fossa. The resolution of the atrial mass was, again, consistent with this radiosensitivity. Cardiac metastases may be more common in MCC than currently though and clinically this has several implications. Firstly, it should alert the clinician to consider cardiac metastases in patients with a background of MCC, who present with cardiac or respiratory symptoms. With increasing use of systemic treatment and an increased life expectancy, in combination with improved diagnostics and greater accessibility, it would be anticipated that the frequency of diagnosis of cardiac metastases would increase. Furthermore, the evidence suggests that the presence of cardiac metastases coincides with widespread metastatic disease. Whether this is cause or effect is not understood. However, it does have prognostic significance, and therefore has a bearing on treatment options. While surgical intervention, or best supportive care have been the treatment approaches in the majority of cases reported previously, we suggest that a palliative course of radiation treatment is also a valid treatment choice. Given the relatively noninvasive nature of treatment, the poor prognosis of the patient, and the exquisite radiosensitivity of MCC, we propose that this could provide the greatest palliation of symptoms while avoiding the potential morbidity and possible mortality of cardiac surgery.
Clare F. Suttie Royal North Shore Hospital, St Leonards, New South Wales, Australia
George Hruby Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
Lisa Horvath Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
John Thompson Melanoma Institute Australia; Mater Hospital, North Sydney; Sydney Medical School, The University of Sydney, Sydney; Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
Fig 2.
melanoma and leukemia to be the most common malignancies to metastasize to the heart.4 Melanoma represents the tumor with the highest rate of cardiac metastasis.5 Fiala et al4 have postulated that routes of dissemination of tumor cells to the heart are through lymphatics as well as blood vessels. In the previously reported cases of MCC cardiac metastases, patients have presented with cardiorespiratory symptoms. These have ranged from dyspnea, chest pain and arrhythmias, to cardiac tamponade. In this case, the patient was diagnosed incidentally through a mesenteric angiogram. Moreover, in the case reports patients have been treated with best supportive care, and in one case surgically. Only one patient was treated with radiotherapy, as was the patient in this report. MCC is highly radiosensitive. Sundaresen et al6 reported 26 patients with biopsy-confirmed MCC treated definitively with either radiotherapy or chemoradiation treatment. At two years, 89% of all patients and 85% of those with macroscopic disease were free of infield recurrence. In this case, despite the infield recurrence in the left axilla, the exquisite radiosensitivity was evident in the dramatic reduction in
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. SEER Survival Monograph: Cancer Survival Among Adults: U. S. SEER Program, 1988-2001, Patient and Tumor Characteristics. Bethesda, MD, National Cancer Institute, 2007, pp 251-612 (NIH Pub No. 07-6215) 1a. Fong, LS, Mathur M, Bhindi R, et al. Right atrial Merkel cell tumour metastasis characterization using a multimodality approach. Eur Heart J 33:2205, 2012 2. Conley M, Hawkins K, Ririe D: Complete heart block and cardiac tamponade secondary to Merkel cell carcinoma cardiac metastases. South Med J 99:74-78, 2006 3. Abraham KP, Reddy V, Gattuso P: Neoplasms metastatic to the heart: Review of 3314 consecutive autopsies. Am J Cardiovascular Pathol 3:195-198, 1990 4. Fiala W, Schneider J: Heart metastasis of malignant tumors: An autopsy study. Schweiz Med Wochenschr 112:1497-1501, 1982 5. Glancy DL, Roberts WC: The heart in malignant melanoma: A study of 70 autopsy cases. Am J Cardiol 21:555-571, 1968 6. Sundaresan P, Hruby G, Hamilton A, et al: Definitive radiotherapy or chemoradiotherapy in the treatment of Merkel cell carcinoma. Clin Oncol (R Coll Radiol) 24:e131-e136, 2012
DOI: 10.1200/JCO.2012.48.3073; published online ahead of print at www.jco.org on January 27, 2014
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