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Journal of Clinical Oncology, Vol 25, No 24 (August 20), 2007: pp. 3780-3783 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.1962
Asymptomatic Muscle Metastases From Esophageal AdenocarcinomaDivision of Hematology and Oncology, Sylvester Comprehensive Cancer Center, Miami, FL
Department of Medicine, University of Miami, Miami, FL
Department of Surgery, University of Miami, Miami, FL
Department of Pathology, University of Miami, Miami, FL
Division of Hematology and Oncology, Sylvester Comprehensive Cancer Center, Miami, FL
Department of University of Miami Medical Group/University of Miami Surgery, University of Miami, Miami, FL A 72-year-old man initially presented with a 2-month history of severe dysphagia and a 25-pound weight loss. Endoscopy demonstrated an infiltrating mass in the distal esophagus. A biopsy revealed high-grade infiltrating adenocarcinoma with signet ring cells (Fig 1). The initial abdominal computed tomography (CT) showed a 6-cm length circumferential thickening of the distal esophagus with extension to the gastroesphageal junction and adjacent adenopathy. The chest, abdomen, and pelvis CT scans showed no evidence of metastatic disease in the liver, pancreas, or adrenal glands. At this point, the patient was referred to University of Miami Sylvester Comprehensive Cancer Center (Miami, FL) for further evaluation and treatment. An endoscopic ultrasound was performed, and the tumor was staged as T3N1Mx. Whole-body [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) was obtained for further staging and demonstrated avid pathologic uptake (max, 15.8 standardized uptake value [SUV]) in the distal esophagus corresponding with the known esophageal tumor. Avid nodular uptake within left deltoid muscle posteromedial to acromioclavicular joint, peak SUV measured 6.0. Avid nodular uptake in three locations within the right gluteus maximus muscle with peak SUV was 11.8. More superiorly there was an additional nodule of uptake in the right gluteus muscle measuring 4.8, and more inferomedially there was a third nodule of uptake in the right gluteus muscle, SUV measuring 10.3. There was a focal nodular uptake in the left gluteus maximus muscle, SUV 5.5 and additional focus of abnormal uptake in the left gluteus muscle was identified just dorsal to the left ischial tuberosity, peak SUV measuring 4.3. Focal intense nodular uptake within paraspinous musculature at the level of mid-dorsal spine, SUV measured 5.2 (Fig 2).
A CT-guided percutaneous biopsy of the biggest (2 cm) right gluteal lesion was performed and revealed a moderately differentiated adenocarcinoma consistent with primary esophageal cancer. The tumor cells are positive for CK7 and negative for CK20 and CDX-2 by immunohistochemistry (Fig 3). Due to the presence of multiple muscle metastases, surgery was not indicated, and the patient underwent systemic chemotherapy with oxaliplatin, docetaxel, floxuridine, and leucovorin. FDG-PET/CT was repeated after two cycles of chemotherapy and demonstrated an average of 50% decrease of SUVs in the distal esophagus as well in musculature. However, there was a new identified region within left sartorius muscle, just lateral to the femoral vessels with a maximum SUV of 4.6 (Fig 4). The patient's muscles metastasis remains asymptomatic, and the patient is receiving systemic chemotherapy.
Metastasis to the skeletal muscles is very rare and represents less than 1% of all hematogenous metastases from solid tumors.1,2,3,4 Some researchers reported only 15 cases of muscle metastasis during a 16-year period in which more than 54,000 newly diagnosed cancers were diagnosed.5 Muscle metastases account for less than 2.8% in primary soft tissue sarcomas.6 The most common primary tumors sites are lung (35%), gastrointestinal (23%), and kidney (19%).5 Other primary sites reported included melanoma, head and neck cancer, thyroid, breast, uterus, cervix, prostate, bladder, ovary, pancreas, and liver.5,7,8 The most frequent metastatic locations in skeletal muscles are the diaphragm: rectus muscle of the abdomen, deltoid, psoas and thigh muscles, intercostals, gluteus, and spinal muscles.5,8 Skeletal muscles account approximately for 43% to 50% of the body mass.9 Vascular embolization is a common modality for tumor metastasis, and skeletal muscles are well vascularized, receiving a large portion of total cardiac output. Therefore, it is unclear why muscles metastases are extremely rare. Muscular contraction and blood turbulence may create a hostile environment for the circulating tumor cell.10,11 High concentration of lactic acid may also suppress growth of tumor cells. Some studies suggest that muscles possess proteases and other inhibitors, which can block tumor invasion and development.12,13,14 The differential diagnosis of skeletal muscle metastases is either benign tumors, such as lipomas, angiomas, chondromas, osteomas, and myositis ossificans, or primary soft tissue sarcomas, such as synovialsarcomas, liposarcomas, extraosseous osteosarcomas, and chondrosarcomas. Other possible diagnoses are non-Hodgkin's lymphoma, intramuscular abscesses, hematomas, parasites, and foreign body. Biopsy is essential because treatment and prognosis are markedly different. The prognosis associated with skeletal muscle metastases is poor, consistent with the fact that it represents systemic disease. Only a few patients survive long enough for clinical detection of muscle metastases. Treatment options, depending on the clinical setting, include observation, radiotherapy, chemotherapy, and excision. Unfortunately, these approaches rarely alter the patient's outcome. Previously, a case of skeletal muscle metastases from esophageal adenocarcinoma was reported.15 However, multiple asymptomatic metastases to a distant skeletal muscle without evidence of other distant metastatic disease have not been reported. In conclusion, this case supports the previous reports that PET is superior to CT in detecting distant metastases for initial staging of esophageal carcinoma.16,17 PET scan is increasingly used for cancer staging; therefore, more cases of skeletal muscles metastasis are likely to be reported. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Menard O, Parache RM: Muscle metastasis of cancers [French]. Ann Med Interne (Paris) 142:423-428, 1991[Medline] 2. Araki K, Kobayashi M, Ogata T, et al: Colorectal carcinoma metastasis to skeletal muscle. Hepatogastroenterology 41:405-408, 1994[Medline] 3. Bennington JL, Kradjian RM: Site of metastases at autopsy in 523 cases of renal cell carcinoma, in Renal Carcinoma. Philadelphia, PA, Saunders, 1967, pp 143-145 4. Willis RA: Secondary tumors in sundry unusual situations, in The Spread of Tumors in the Human Body. London, Butterworths, 1973, pp 281-282 5. Herring CL Jr, Harrelson JM, Scully SP: Metastatic carcinoma to skeletal muscle: A report of 15 patients. Clin Orthop Relat Res 355:272-281, 1998[CrossRef][Medline] 6. Sudo A, Ogihara Y, Shiokawa Y, et al: Intramuscular metastasis of carcinoma. Clin Orthop Relat Res 296:213-217, 1993[Medline] 7. Garcia OA, Fernandez EG, Buelta SL, et al: Metastasis of malignant neoplasms to skeletal muscle Rev Esp Oncol 31:57-67, 1984 8. Alexiou J, Engelholm JL, De Beuckeleer L: Soft tissue metastases, in De Schepper AM (ed): Imaging of Soft Tissue Tumors. Berlin, Germany Springer Verlag, 1997, pp 361-371 9. Sinclair DC: Muscles and fasciae, in Romanes CF (ed): Cunningham's Textbook of Anatomy. New York, NY, Oxford University Press, 1981, pp 265-409 10. Mulsow FW: Metastatic carcinoma of skeletal muscles. Arch Pathol 35:112-114, 1943 11. Seely S: Possible reasons for the high resistance of muscle to cancer. Med Hypotheses 6:133-137, 1980[CrossRef][Medline] 12. Eisenstein R, Kuettner KE, Neapolitan C, et al: The resistance of certain tissues to invasion. Am J Pathol 81:337-348, 1975[Abstract] 13. Sorgente N, Kuettner KE, Soble LW, et al: The resistance of certain tissues to invasion: II. Evidence for extractable factors in cartilage which inhibit invasion by vascularized mesenchyme Lab Invest 32:217-222, 1975 14. Brem H, Folkman J: Inhibition of tumor angiogenesis mediated by cartilage. J Exp Med 141:427-439, 1975 15. Wu G, Bybel B, Brunken R, et al: PET detection of solitary distant skeletal muscle metastasis of esophageal adenocarcinoma. Clin Nucl Med 30:335-337, 2005[CrossRef][Medline] 16. Flamen P, Lerut A, Van Cutsem E, et al: Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 18:3202-3210, 2000 17. Meltzer CC, Luketich JD, Friedman D, et al: Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography. Clin Nucl Med 25:882-887, 2000[CrossRef][Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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