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Journal of Clinical Oncology, Vol 26, No 21 (July 20), 2008: pp. 3643-3644 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.7866
Merkel Cell Carcinoma Metastatic to the HeartNational Cancer Institute, Bethesda, MD A 76-year-old man was admitted with altered mental status for 3 days and worsening right cervical spine pain radiating to his clavicle over the last month. The patient's medical history was significant for multiple myeloma, diagnosed 5 years earlier. He was treated with melphalan and prednisone initially and later with thalidomide. He also had Merkel cell carcinoma 8 years earlier of his right upper extremity, treated with resection and radiation with two local recurrences. The first recurrence was treated with resection and radiation again; the second, 2 years later, was treated with resection and four cycles of etoposide and cisplatin with no evidence of disease thereafter. Further history includes diabetes mellitus type 2, hypertension, chronic kidney disease, obstructive sleep apnea, and two episodes of deep vein thrombosis. On admission, blood pressure was 96/59 mmHg, pulse rate 104 bpm, body temperature 37.4°C, and respiratory rate 16 breaths per minute. Orientation to person, place, and time was absent, but there were no other focal deficits. Neck veins were flat and mucous membranes dry. Chest was clear to auscultation, heart sounds were normal with a systolic ejection murmur grade 2/6 at left sternal border, and there were no bruits. Abdomen was benign, there was no bony tenderness, and lower extremities had trace pitting edema with venous stasis changes and good pulses. Laboratory tests revealed a decreased hemoglobin of 8.6 g/dL and an elevated international normalized ratio of 4.6. A lactate dehydrogenase of 454 U/L, β-2 microglobulin of 22 mg/L, and serum IgG of 5.1 g/dL were all elevated. Serum viscosity was normal. Blood urea nitrogen was 52 mg/dL, creatinine of 2.9 mg/dL, and corrected calcium was 11.4 mg/dL were all elevated. Imaging with computed tomography of the brain revealed no stroke; however, chest radiograph did show an increased cardiac dimension and a concern for pericardial effusion. The patient was hydrated with intravenous fluids with resolution of his altered mental status. The following day, a computed tomography of the chest without contrast revealed a 5.0 x 3.0 x 3.6 cm expansile mass of the left ninth rib extending to the costo-vertebral junction, a new pericardial effusion, and a questionable cardiac mass. A trans-thoracic echocardiogram was recommended and revealed a 7 x 4 cm cardiac mass without hemodynamic compromise and an ejection fraction of 55%. To better characterize this mass, a cardiac magnetic resonance imaging was performed, which revealed a homogeneous mass within the right atrium (Fig 1center arrow). The mass filled virtually the entire chamber and measured 8.5 cm anterior-posterior x 9.5 cm transverse x 9.8 cm cranio-caudal with extension laterally to the right, extending through the pericardial fat and pericardium into the lung parenchyma (Fig 1 left arrow). The lesion extended along the cardiac wall to the level of the right ventricle and left ventricular walls. A very small opening was present between the superior vena cava through the mass to the right ventricle. A small to moderate pericardial effusion was also noted. The patient remained fully alert and his altered mental status was attributed to hypercalcemia and azotemia secondary to progression of his multiple myeloma. Evaluation was also notable for increased immunoglobin G levels, lytic skeletal lesions, and probable extramedullary cardiac plasmacytoma, all in keeping with this diagnosis. However, given the history of two cancers, biopsy of the atrial tumor was indicated before initiating therapy since treatment for multiple myeloma may not have addressed and could have worsened this new cardiac mass. A biopsy of the right atrium was then performed via cardiac catheterization and touch preps revealed few epithelial cells, few small round blue cells, and few plasmacytoid cells. The permanent section revealed cardiac muscle with myocyte hypertrophy. After extensive discussion with the patient and his family, despite the nondiagnostic biopsy, it was reasoned that this mass most likely represented progression of his myeloma. A chemotherapy regimen of bortezomib and melphalan was recommended based on an overall response rate of 68% in patients with relapsed or refractory myeloma.1 He tolerated the first 3 days of treatment well but then developed hypoxia and nocturnal agitation. Electrocardiogram, laboratory, and radiographic evaluations were nondiagnostic and comfort care measures were initiated. Two days later the patient died. Postmortem histology confirmed plasmacytoma at the ninth thoracic rib lesion with sheets of small cells with abundant eosinophilic cytoplasm, eccentric nuclear locations, and clock-face nuclear pattern (Fig 2). Examination of the heart revealed a 12 x 10 cm mass involving the pericardium, invading both atria, encasing the great vessels and attached to a portion of the right lung (Fig 3). Histologic examination demonstrated small round blue-cell tumor with a high mitotic rate and areas of necrosis. Neuroendocrine features were present with a salt-and-pepper chromatin, and immunohistochemistry with CK20 revealed paranuclear dot positivity confirming a diagnosis of Merkel cell carcinoma (Fig 4).
Merkel cell carcinoma is a neuroendocrine skin cancer, associated with a newly discovered Merkel cell polyomavirus.2 It usually presents as a single, painless, flesh-colored to violaceous nodule on sun-exposed areas. It more commonly occurs in fair-skinned, elderly, or immunosuppressed patients. The incidence is increasing with more than 1,200 new cases diagnosed each year in the United States, and a disease-specific mortality rate of 25%.3,4 There is recurrence in up to one half of patients, which commonly involves skin, liver, bone, and brain.5 Cardiac metastases from all tumors are relatively common, and autopsy series show a range of 8% to 12%.6,7 Malignancies with a high prevalence of cardiac metastases include melanoma, lung, breast, soft tissue sarcomas, lymphoma, and leukemia.8 Extramedullary plasmacytoma of the heart is rare, and few cases have been reported in the literature. Chemotherapy alone has been shown to achieve a good response rate and prolong survival.9 Indeed, our patient had clinical, laboratory, and radiographic evidence of multiple myeloma progression including likely cardiac plasmacytoma. Merkel cell carcinoma metastatic to the heart is exceedingly rare and there have been few cases of intracardiac metastasis reported in the literature.10,11,12 There are no randomized controlled trials for the management of Merkel cell carcinoma. Therapy consists of wide local excision for node-negative disease and the addition of radiation for node-positive disease with 5-year survival of 81% and 52% respectively.13 Due to similarities in immunohistochemistry and morphology with small-cell lung cancer, metastatic disease is treated with various combination chemotherapy regimens of cisplatin and etoposide, or vincristine, cyclophosphamide, and doxorubicin. Platinum-based regimens have response rates of 60% to 75%, however median survival is measured in months.14,15 The recently described Merkel cell poliomavirus is an exciting discovery and will provide opportunity to explore new targeted therapies for this disease. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Berenson JR, Yang HH, Sadler K, et al: Phase I/II trial assessing bortezomib and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. J Clin Oncol 24:937-944, 2006 2. Feng H, Shuda M, Chang Y, et al: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science [Epub ahead of print on January 17, 2008] 3. Nghiem P, McKee PH, Haynes HA: Merkel cell (cutaneous neuroendocrine) carcinoma, in Sober AJ, Haluska FG (eds): Skin Cancer. Hamilton, Ontario, BC Decker Inc., 2001, pp 127-141 4. Hodgson NC: Merkel cell carcinoma: Changing incidence trends. J Surg Oncol 89:1-4, 2005[CrossRef][Medline] 5. Tai PT, Yu E, Tonita J, et al: Merkel cell carcinoma of the skin. J Cutan Med Surg 4:186-195, 2000[Medline] 6. Abraham KP, Reddy V, Gattuso P: Neoplasms metastatic to the heart: Review of 3314 consecutive autopsies. Am J Cardiovasc Pathol 3:195-198, 1990[Medline] 7. Silvestri F, Bussani R, Pavletic N, et al: Metastases of the heart and pericardium. G Ital Cardiol 27:1252-1255, 1997[Medline] 8. Burke A, Virmani R: Atlas of Tumor Pathology: Tumors of the Heart and Great Vessels (3rd series). Washington, DC, American Registry of Pathology, 1995 9. Chim CS, Loong F, Ma ES, et al: Plasma cell problems: Case 2—Extramedullary cardiac plasmacytoma presenting with cardiac tamponade. J Clin Oncol 23:3140-3143, 2005 10. Jongbloed MR, Kanen BL, Visser M, et al: Case 2: Intracardiac metastasis from a Merkel cell carcinoma. J Clin Oncol 22:1153-1156, 2004 Mar 11. Yamana N, Sueyama H, Hamada M: Cardiac metastasis from Merkel cell skin carcinoma. Int J Clin Oncol 9:210-212, 2004[Medline] 12. 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[CrossRef][Medline] 13. Allen PJ, Bowne WB, Jaques DP, et al: Merkel cell carcinoma: Prognosis and treatment of patients from a single institution. J Clin Oncol 23:2300-2309, 2005 14. Tai PT, Yu E, Winquist E, et al: Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: Case series and review of 204 cases. J Clin Oncol 18:2493-2499, 2000 15. Voog E, Biron P, Martin JP, et al: Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer 85:2589-2595, 1999[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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