Asymptomatic Muscle Metastases From Esophageal Adenocarcinoma

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25

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24

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2007

JOURNAL OF CLINICAL ONCOLOGY

Asymptomatic Muscle Metastases From Esophageal Adenocarcinoma 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.

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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 Journal of Clinical Oncology, Vol 25, No 24 (August 20), 2007: pp 3780-3786

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Diagnosis in Oncology

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Kozyreva et al

Fig 4.

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. 3782

Olga N. Kozyreva Division of Hematology and Oncology, Sylvester Comprehensive Cancer Center, Miami, FL

Dmitry A. Mezentsev Department of Medicine, University of Miami, Miami, FL

David R. King Department of Surgery, University of Miami, Miami, FL

Carmen R. Gomez-Fernandez Department of Pathology, University of Miami, Miami, FL

Bach Ardalan Division of Hematology and Oncology, Sylvester Comprehensive Cancer Center, Miami, FL

Alan S. Livingstone Department of University of Miami Medical Group/University of Miami Surgery, University of Miami, Miami, FL

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 2. Araki K, Kobayashi M, Ogata T, et al: Colorectal carcinoma metastasis to skeletal muscle. Hepatogastroenterology 41:405-408, 1994 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 JOURNAL OF CLINICAL ONCOLOGY

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Diagnosis in Oncology

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 6. Sudo A, Ogihara Y, Shiokawa Y, et al: Intramuscular metastasis of carcinoma. Clin Orthop Relat Res 296:213-217, 1993 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

12. Eisenstein R, Kuettner KE, Neapolitan C, et al: The resistance of certain tissues to invasion. Am J Pathol 81:337-348, 1975 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 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

DOI: 10.1200/JCO.2007.12.1962

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Primary Renal Lymphoma Presenting With Paraneoplastic Limbic Encephalitis A 58-year-old nonhypertensive, nondiabetic presented with headache and short-term memory loss of 4 months. He had generalized clonic tonic seizures 1 day before his hospitalization. There was no history of fever, vomiting, trauma, drug intake, or anything suggestive of any other neurological deficit. He complained of decreased appetite and weight loss of 5 kg over the previous 4 months. His past medical history was unremarkable. His general and systemic examination was normal. The neurological examination was unremarkable except for recent memory loss. The complete blood picture and biochemistry were within normal limits. His HIV serology was negative. A contrast enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy of the brain revealed abnormalities involving the corpus callosum extending into bifrontotemporal white matter and both thalamocapsulo-ganglionic regions (Fig 1). The CSF analysis showed lymphocytic pleocytosis with mild elevation of proteins and normal sugar, and lactate dehydrogenase and was negative for malignant cells. The anti-Ro, Hu, Yo, and Ma2 antibodies were negative. Because the clinical and radiological features were suggestive of paraneoplastic limbic encephalitis (PLE), computed tomography scans of the chest and abdomen were done to rule out occult malignancy. The computed tomography scan of the abdomen showed a large lobulated hypodense mass arising from the mid and lower pole of the right kidney without enlarged lymph nodes or invasion of adjacent organs (Fig 2). A provisional diagnosis of PLE, possibly secondary to a renal cell carcinoma, was made. The patient underwent a laproscopic right radical nephrectomy. Histopathology showed a cellular tumor with increased mitotic activity (Fig 3) and large areas of necrosis suggestive of a poorly differentiated malignancy, possibly high-grade non-Hodgkin’s lymphoma (NHL). The diagnosis of diffuse large B-cell lymphoma was confirmed by immunohistochemistry, which was positive for CD20 (Fig 4), CD30 with high MIB-1 labeling index, and negative for CD3. A [18F]fluorodeoxyglucose (FDG) positron emission tomography scan done after surgery showed FDG uptake in the peri callosal white matter and both corona radiata, with hypometabolic area in the anterior corpus callosum. The rest of the body was negative for any abnor-

Fig 1.

mal foci of FDG uptake. The bone marrow biopsy was normal. A final diagnosis of primary renal lymphoma with PLE was made. His memory loss recovered during the following 3 weeks. He is now on chemotherapy with rituximab and cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone. At the time of publication, the patient continues to be well on chemotherapy. Primary renal lymphoma is extremely rare and constitutes 0.7% of extra nodal lymphomas1 and 0.1% of all malignant lymphomas.2 Because the kidney is devoid of lymphatics, the existence of this entity is often debated.3 However, the negative positron emission tomography scan after surgery in our patient confirms the diagnosis and adds evidence to its existence. Common symptoms at presentation include flank pain, renal insufficiency, hematuria, and systemic symptoms like 3783

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