Nuran ~enel Be~e,* Mustafa Ozgiiroglu,** Sergiilen Dervi~oglu,***. Kaya Kanberoglu,**** and Ahmet Ober*. Gastric cancer metastatic to skeletal muscle is an ...
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Radiation Medicine: Vol. 24 No. 2, 150-153 p.p., 2006
Skeletal Muscle: An Unusual Site of Distant Metastasis in Gastric Carcinoma Nuran ~enel Be~e,* Mustafa Ozgiiroglu,** Sergiilen Dervi~oglu,*** Kaya Kanberoglu,**** and Ahmet Ober* Gastric cancer metastatic to skeletal muscle is an unusual entity. Surgery, systemic chemotherapy, or radiotherapy to the metastatic mass can be treatment options for achiving palliation. Case Report: A patient with multiple skeletal muscle metastases that occurred during followup after gastrectomy and adjuvant chemo-radiotherapy is reported. Magnetic resonance imaging (MRI) demonstrated soft-tissue masses involving the posterior fight paralumbar and posterior left paradorsal muscles. Biopsy showed metastatic infiltrating adenocarcinoma. The patient did not respond to palliative chemotherapy. Palliative radiotherapy was administered to the painful mass. Based on this case, the diagnosis of muscle metastases and treatment options for palliation are discussed.
Key words: gastric cancer, skeletal muscle metastases, palliative radiotherapy, chemotherapy
INTRODUCTION
C
ANCER OF THE STOMACH REMAINS THE SECOND MOST
frequent malignancy in the world/Although local and lymphatic spread towards the regional lymph nodes has been extensively studied, the patterns of distant metastases are either relatively infrequent or probably poorly documented. According to autopsy series, gastric cancer remains rather locoregional and usually produces distant metastasis only in the first organ the circulation reaches, which is likely to be the liver or lung? Gastric cancer metastatic to skeletal muscle is extremely uncommon. Here, a gastric cancer patient with diagnoses of multiple muscle metastases during his follow-up and the treatment options for palliation are discussed. CASE R E P O R T A 60-year-old male patient was admitted to the surgical unit with a 6-month history of gastric pain and nausea. Gastroduedonal endoscopy disclosed a 5• cm exophytic mass on the antrum of the stomach with central Received May 30, 2005; revision accepted September 26, 2005. Departments of *Radiation Oncology, **Internal Medicine, Medical Oncology Section, ***Pathology and ****Radiology, Cerrahpasa Medical School, istanbul University Reprint requests to Nuran ~enel Be~e, M.D., Department of Radiation Oncology, Cerrahpa~a Medical School, istanbul University, Fatih 34098, istanbul, TURKEY.
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ulceration that was proved to be adenocarcinoma by biopsy. Physical examination and chest x-ray showed no abnormality. His blood analyses were normal other than an elevated level of serum carcinoembrionic antigen (CEA) which was 109 ng/ml. Computerized axial tomographic (CAT) examination of the abdomen showed enlargement of the gastric wall with an increased density of perigastric fatty tissues. He underwent surgery, and distal subtotal gastrectomy and gastrojejunostomi were performed with dissection of the perigastric nodal areas. Upon macroscopic examination of the specimen, a tumor was detected on the lesser curvature of the antrum that was 7 cm in length, 3 cm in width, and 1.5 cm in depth. The macroscopic appearance was that of an ulceration with invasion of the gastric wall beyond the serosa. There was a 4.cm margin of normal tissue proximally and 2 cm distally. Microscopic examination revealed a signet-ring-cell adenocarcinoma, and serosal invasion was confirmed. There was no tumor cell involvement on microscopic examination of the proximal, distal, and radial surgical margins. Only 9 lymph nodes were detected at pathological examination because of D 1 dissection, and no lymph node metastases were observed. He was placed in an adjuvant chemoradiotherapy program because of pathologic stage T3NOM0 gastric adenocarcinoma. The first course of chemotherapy (5FU 425 mg/m2/day intravenous (IV) bolus D1-5 and leucovorin 20 mg/mZ/day IV bolus D1-5) was given 6 weeks after surgery, and radiotherapy was started on the 28 th day following chemotherapy. Radiotherapy was RADIATION MEDICINE
CASE R E P O R T
Fig. 1. A fat-saturated T2 axial image reveals increased signal intensity on the right longissimus dorsi, illiocostalis lumborum, and quadratus lumborum muscles, without bone involvement.
Fig. 2. A fat-saturated T2 axial image reveals increased signal intensity involving the left erector spinae muscle.
delivered with a Co60 unit. The radiation fields included the tumor bed and major nodal chains: lesser and greater curvature; celiac axis including pancreoduodenal, splenic, suprapancreatic, and porta hepatis; and paraaortic to the level of mid-L 4. Fifty percent of the right kidney was in the field, so that three-fourths of the left kidney was spared to maintain renal function. The postoperative gastric remnant, splenic hilus, and porta hepatis were identified by preoperative CT scan, surgical clips, and barium swallow during simulation. Kidneys were identified on simulation films after IV contrast. A total dose of 45 Gy with a fraction size of 1.8 Gy was planned. He was treated in the supine position using parallel opposed anterior-posterior/posterior-anterior (AP/PA) fields, and the dose was calculated at mid-plane. Concomitant chemotherapy [5-FU 400 mg/ma/day intravenous (IV) bolus and leucovorin 20 mg/m2/day IV bolus] was administered during the first 4 days of radiotherapy. Radiotherapy was stopped at 37.8 Gy, and the third cycle of chemotherapy, which was planned to be given during the last 3 days of irradiation, was omitted because of persistent grade III thrombocytopenia. The patient received 2 additional cycles of maintenance chemotherapy (5-FU 425 mg/mZ/day IV bolus D1-5 and Leucovorin 20 mg/mZ/dayIV bolus D 1-5) with a 4-week interval after the correction of thrombocytopenia. He was followed-up without evidence of disease for 13 months following surgery, but he started to complain of swelling and tenderness along with his right lumbar region. Physical examination showed a 7x6 cm subcutaneous, tender mass on the right longissimus dorsi muscle. His serum CEA level was elevated to 268 ng/ml but was at normal levels during his follow-up analyses.
No abnormalities were described at gastroscopy, chest x-ray, abdominal ultrasonography, or bone scans. On abdomino-pelvic magnetic resonance imagining (MRI), fat-saturated T2 images revealed increased signal intensity in the right longissimus dorsi, illiocostalis lumborum, and quadratus lumborum muscles at lumbar levels 4 and 5 (Fig. 1). Another soft-tissue mass, which was not detected at his physical examination, was demonstrated with MRI scans involving the left erector spinae muscle at dorsal levels 11-12 (Fig. 2). Taking into account the patient' s history of primary tumor, the initial radiological diagnosis should have been skeletal metastasis; however, no skeletal involvement was seen on MRI. Also there was no typical contour or texture of a skeletal soft tissue mass extending into extra-skeletal space. Secondary radiological diagnosis included myosifts either purulent or non-purulent. There were no other signs of spondilitis on MRI; thus infectious myositis was dismissed but non-infectious myositis and muscle metastasis could not be excluded. Therefore, a needle biopsy of the right longissimus dorsi muscle was performed. Histolopathological examination of the biopsy specimen showed a poorly differentiated, partly signet-ring cell metastatic tumor infiltrating adenocarcinoma (Fig. 3). In the course of time, the mass at the fight lumbar region became painful. Thus, he was put on palliative chemotherapy for gastric carcinoma with multiple muscle metastases. He received 2 cycles of 5-FU 500 mg/m2/ day IV bolus Dl-3, leucovorin 20 mg/m2/day IV bolus D 1-3, cisplatin 50 mg/mZ/day IV bolus D3, at a 4-week interval. After the second course, his blood creatinine level increased to 1.9 mg/dl, and no reduction in pain and no objective response were achieved. The chemo-
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therapy regimen was changed, and UFT 400 rag/day orally was started. Tramadol (50 mg, 3 times daily per oral) was also given for pain relief. He used UFT for 8 weeks until the progression in pain and in the size of the metastatic soft-tissue masses. Chemotherapy was stopped and the patient referred for palliative radiotherapy. A total dose of 30 Gy irradiation was applied to the right paralumbar metastatic mass in 10 fractions with a Co-60 unit. His pain decreased and the dose of tramadol was reduced gradually. In the course of time, although objective progression was observed at the left paradorsal mass, he did not have any pain related to this metastasis. The patient is alive with disease and with mild lumbar pain at 24 months after surgery. DISCUSSION Despite its high blood supply, skeletal muscle is a rare site of hematogenous metastases from any malignancy. Autopsy studies suggest that the frequency of muscle metastases is between 0.8% to 16%. 3 A literature review in 1998 by Herring et al. 4 found 52 cases in addition to their own 15 cases. In 2004, Tuoheti et alr also reported 12 cases of muscle metastases originating from different primaries. In both of these studies the lung was found to be the most common primary source. Skeletal muscle metastasis arising from gastric carcinoma is a rare entity. When the literature was reviewed, few other reports of gastric cancer with skeletal muscle metastases were found. 6-11In all of these reported cases, muscle metastases were either the presenting symptom or were revealed synchronously with gastric cancer. In this current report, skeletal muscle metastasis was diagnosed during the follow-up. In the study by Tuoheti et al? in which 12 cases of muscle metastases originating from different primaries is reported, 2 patients with a gastric primary developed distant muscle metastases during their follow-ups. The paravertebral muscles are the most frequently involved site of muscle metastases from a gastric primary. When the first involved site is the iliopsoas muscle, retroperitoneal spread must be considered as the most probable pathway. However, in our case, because posterior paravertehral muscles were involved, ahematogenous metastases with an arterial route was considered. The clinical features of metastatic carcinoma to skeletal muscles closely resemble those of soft tissue sarcomas in many respects. 12 However, if there is a known primary cancer, a soft tissue metastasis can be considered. Radiographic evaluation of the mass often provides valuable information. Although MRI is not specific for skeletal muscle metastasis, plain radiogram and CT were of little value with regard to the character 152
Fig. 3. Top, Fibrous tissue next to skeletal muscle is infiltrated by metastatic tumor cells, arranging in cords and tubules, some of which reveal mucin containing clear cytoplasms that push aside the nuclei and resemble signetring cells (hematoxylin and eosin, x200). Bottom, the morphologic features are similar to the patient's primary tumor. (Hematoxylin and eosin, •
of the mass when compared with MRI. Imaging with intravenous gadolinium enhancement was especially helpful when planning the biopsy of these lesions, as it is useful for evaluating the vascularity of the tumor? An abscess formation or myositis should be considered for differential diagnosis as well as primary soft tissue sarcoma. For a certain diagnosis, biopsy is mandatory. Treatment should be specific to the clinical setting and the condition of the patient. Although many combination chemotherapy regimens have been studied, response rates range from 18% to 53%, and the median survival of patients with advanced gastric cancer continues to be dismal. ~A 5-FU, leucovorin and cisplatin combination was given to our patient after the diagnoses of distant metastases following 8 months of adjuvant chemotherapy. However, no response was obtained and, owing to the nefrotoxicity of cisplatin, oral UFT, an oral RADIATION MEDICINE
CASE REPORT
fluorinated pyrimidine, was started. Even though a response rate of up to 49% is reported with UFT, ~3the disease progressed under UFT, and palliative radiotherapy was administered. It was reported that radiotherapy effectively controlled the 'pain' and 'size' of metastatic lesions in patients with skeletal muscle metastases arising from different primaries? While skeletal metastasis is often manifested as part of disseminated disease, the radiotherapy dose should be specific. The location and depth of the metastatic lesion plays a role in determining the total dose and fractionation as well as the patient's performance status. A palliative dose of 30 Gy was given because of the patient's having multiple metastases, and the mass was neighboring the spinal cord and postoperative irradiation fields. The radiotherapy dose can be increased if the metastatic lesion is located in another area such as the gluteal muscles. Excision of the painful mass may be helpful in carefully selected patients, especially in patients with solitary metastasis after a long disease-free interval and if the primary tumor is under control. It was reported that wide excision effectively relieved the clinical symptoms of patients with effective control of the metastatic lesion. TM We did not plan to give our patient further treatment because the disease is accepted as chemo-resistant. Although this is an early report, palliation was obtained and pain is under control with palliative radiotherapy. If the patient complains further because of the soft tissue mass located at the paradorsal area, palliative radiotherapy can be a treatment option. REFERENCES
1) Kepreh MS, Kelsen DP, Tepper JE. Cancer of the stomach. In Cancer: Principles and Practice of Oncology (Devita VT, Hellman S, Rosenberg SA eds.; Lippincott-Williams & Wilkins, Philadelphia), pp. 1092-1126, 2001.
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2) Debois JM. Metastases from cancer of the stomach. In Tx Nx M1. The Anatomy and Clinics of Metastatic Cancer (Kluwer Academic Publishers, London), pp. 373-380, 2002. 3) Debois JM. Metastases to the muscles. In Tx Nx M1. The Anatomy and Clinics of Metastatic Cancer (Kluwer Academic Publishers, London), pp. 215-216, 2002. 4) 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. 5) Tuoheti Y, Okada K, Osanai T, et al. Skeletal muscle metastases of carcinoma: a clinicopathological study of 12 cases. Jpn J Clin Oncol, 34: 210-214, 2004. 6) Rosenbaum LH, Nicholoas JJ, Slasky BS, Obley DL, Ellis LD. Malignant myositis ossificans: occult gastric carcinoma presenting as an acute rheumatic disorder. Ann Rheum Dis, 43: 95-97, 1984. 7) Porile JL, Olopade OI, Hoffman PC. Gastric adenocarcinoma presenting with soft tissue masses. Am J Gastroenterol, 85: 76-77, 1990. 8) Allen A, Wetzel L, Borek D. Malignant myositis ossificans. A case report. Tumori, 78: 55-58, 1992. 9) Narvaez JA, Narvaez J, Clavaguera MT, Juanola X, Valls C, Fiter J. Bone and skeletal muscle metastases from gastric adenocarcinoma: unusual radiographic, CT and scintigraphic features. Eur Radiol, 8: 1366-1369, 1998. 10) Pestalozzi C, von Hochsetter AR. Muskel-Metastaze als Ersmanifestation eines Adenokarzinoms des Magnes. Schweiz Med Wonchenschr, 128: 1414-1417, 1998. (in German) 11) Kondo S, Onodera H, Kan S, Uchida S, Toguchida J, Imamura M. Intramuscular metastasis from gastric cancer. Gastric Cancer, 5:107-111, 2002. 12) Hatori M, Sasano H, Hoshikawa K, Sakuma T, Okaniwa G, Sakurai M. Skeletal muscle metastasis secondary to adenocarcinoma of the lung. Orthopedics, 4: 145-7, 1996. 13) Hanauske AR. UFT in gastric cancer: current status and future developments. Oncology (Williston Park), 11 (9 Suppl 10) : 113-118, 1997.
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