A REFRACTORY NEUTROPENIC PNEUMONIA. S. Regenbogen 1 , A. Rosen 2 ; 1 University of California, San Francisco, CA LEARNING OBJECTIVE: 1) Diagnose and treat Bronchiolitis Obliterans Organizing Pneumonia (BOOP) in patients with hematologic malignancies who present with pneumonia. CASE INFORMATION: A 59-year-old man with cryptogenic pancytopenia was admitted with 3 weeks of cough, fatigue and fever. Bone marrow was markedly hypocellular, but nondiagnostic. He had no hematuria, rheumatic symptoms, or toxin or radiation exposure, except for 6 months on a Naval nuclear submarine. He attributed his condition to myelosuppression from chronic ibuprofen use. Admission vitals were temp 39C, BP 133/71, pulse 78, 02 sat 97% on room air. He had no bleeding or bruising, and no lymphadenopathy. Lung exam showed crackles and egophony at the right mid-chest. Spleen and liver were not palpable. CBC showed WBC 0.4, Hct 34, Plt 102, and ANC 0.2. CXR showed dense right-sided infiltrates. Blood and induced sputum cultures were repeatedly negative and broncho-alveolar lavage was nondiagnostic. Despite treatment with broad-spectrum antibiotics and antifungals, his lung exam and CXR continued to worsen. His neutropenia persisted despite 3 weeks of stem cell growth factors. On day 15, immunoperoxidase staining confirmed the diagnosis of hairy cell leukemia. He underwent open splenectomy, which increasd his WBC to 3.13, and ANC to 2.35. Open lung biopsy (OLB) on day 22 was consistent with BOOP. He was treated with high dose steroids and discharged on a prolonged prednisone taper. DISCUSSION: BOOP is an inflammatory response to lung injury, with edematous plugs of granulation tissue and interstitial fibrosis. It is associated with infection, autoimmunity, hematologic cancers, and other conditions. Patients present with a subacute, febrile illness with dry cough and dyspnea that is unresponsive to antibiotics. CXR shows patchy alveolar infiltrates with airspace consolidation, and PFTs reveal a mixed restrictive/obstructive pattern. Transbronchial biopsy is often nondiagnostic, therefore requiring OLB for definitive diagnosis. BOOP is usually responsive to steroids, but relapse is common. In one series (Am J Resp Crit Care Med 161:723, 2000), among patients with hematologic cancers undergoing OLB for an unknown pulmonary process, BOOP was the most common finding±20% of cases where a diagnosis was made. BOOP accounted for 30% of the diagnoses missed by bronchoscopy but found on OLB. Identification of a specific diagnosis on OLB significantly increased survival. In the setting of refractory pneumonia in a patient with a hematologic malignancy, the diagnosis of BOOP should be considered. OLB is advised if other procedures fail to identify a cause. LEARNING OBJECTIVES: 1. Participants will learn to recognize skeletal muscles as a rare metastatic site for the cancers. 2. Participants will learn diagnosis and treatment of esophageal cancer. 3. Participants will learn the incidence, pathophysiology, diagnostic strategy and treatment of skeletal muscle metastasis. CASE INFORMATION: Introduction: Although comprising 50% of body mass with a very rich blood supply, skeletal muscle is rarely the site of metastatic disease with only 242 cases having previously been reported (1) . Although primary cancers of the lung, colon, genitourinary tract and blood are most frequently involved (1, 35) , gastroesophageal adenocarcinoma has never been reported. We report a case of thigh muscle metastasis from primary adenocarcinoma of the gastroesophageal junction. CASE REPORT A 71-year-old African American male presented with severe right thigh pain, causing him to be unable to walk. His medical diagnoses included Stage IV Adenocarcinoma of the Gastroesophageal junction, hypertension, COPD (chronic obstructive pulmonary disease), and GERD (gastroesophageal reflux disease). He was an active smoker and Ex-alcoholic. Physical examination was remarkable only for his cachectic state and an extremely tender right upper thigh. Despite NSAID (non-steroidal anti-inflammatory drug) and full dose narcotic analgesia, the patient continued to complain of severe pain in his thigh. Thigh X-rays showed no lytic or blastic lesions. Bone scan did not show any metastasis. A MRI was done and showed a deep 2 x 4-cm soft tissue muscle mass in the right thigh without bony involvement, just anterior and medial to the femur. Diagnostic considerations included a soft tissue metastasis or a sarcoma. A CT guided needle biopsy of the right thigh mass was positive for metastatic adenocarcinoma consistent with the primary esophageal cancer. Radiation therapy was started to the patient's right thigh with a good response. At the time of discharge, the patient was walking without pain receiving narcotic analgesia. Upon returning to the clinic after 2 weeks for follow-up, he continued to walk without difficulty receiving outpatient radiation therapy. DISCUSSION: The incidence of adenocarcinoma of the esophagus and esophagogastric junction has been increasing over the past 25 years (2, 3, 4, 5) , with cancer of the esophagus (used to be predominantly squamous cell carcinoma) ranking among the ten most frequent cancers in the world. Although direct muscle invasion by carcinoma is well recognized, distant metastasis to skeletal muscle is uncommon (6). The present case is unique in that the localized thigh pain was produced by metastatic involvement to the thigh musculature without any osseous or perineural lymphatic extension. Even though autopsy series report a 0.8% to 20% (8,9,10,11,12) incidence of microscopic intramuscular metastasis, only a few cases of visible metastasis to the muscle have been described in the literature (7, 13, 14, 15, 16) . Accordingly, muscle metastasis often remains asymptomatic often undetected by both physical examination as well as diagnostic imaging procedures. The reported incidence, therefore, might be infrequent because of either a lack of recognition, underreporting, or infrequent autopsy evaluation for muscle metastasis. (7). Furthermore, it may be that only a fraction of patients with metastases to muscle survive long enough to allow clinical detection (17). Just why metastases to skeletal muscle is so rare is still unknown (17, 18) . Multiple factors, such as blood flow, intramuscular blood pressure, blood flow per unit of weight (millilitres/minute per gram); local changes in pH, as well as local temperature distribution may be involved. (6, 9, 11, 19, 20, 21, 22) . Organs with a high incidence of metastatic carcinoma such as lung, liver and bone have a constant blood flow. Although equally rich in its vasculature, it has been suggested that the blood flow in skeletal muscle is variable, is under the influence of Betaadrenergic receptor control, and is subject to varying tissue pressure that may affect tumor implantation (20,23). Although some have suggested that protease inhibitors in the muscle's extracellular matrix may resist tumor cell invasion (24), it may be the production of lactic acid and other metabolites by skeletal muscle that inhibits tumor cell growth. (20, 18) Whereas two thirds of all cancers metastatic to muscle are carcinomas, about one third are from leukemias and lymphomas with rare cases originating from melanoma. (25). Accordingly, although factors in the recipient site may be responsible for the relatively low rates of metastasis to muscle, properties of the primary tumor may also be involved. Furthermore, the differentiation between a primary soft tissue sarcoma and metastatic carcinoma to muscle is important as the treatment and prognosis is markedly different. Although the presence of a soft tissue mass caused by metastatic carcinoma may be misdiagnosed easily as a soft tissue sarcoma on physical examination and imaging studies (10), the current literature does not provide any clinical or radiographic characteristics that helps distinguish the two (17). Whereas 50% of carcinomas and sarcomas metastatic to muscle occur in the lower extremity, a greater percentage of upper extremity (26%) carcinomatous metastases occurs then has been reported for soft tissue sarcomas (10%). In addition, most of the cases reported are located in one muscle group or in one part of the body (26, 27, 28) . Although various imaging studies were used to identify metastases to muscle, none were specific for differentiating among carcinoma, sarcoma, or other muscle disorders. Plain radiographs, radionuclide scanning, and angiography have not been beneficial in differentiating carcinoma from sarcoma (17) although it has been thought that MRI imaging is superior to CT scanning (29, 30) . CT guided fine needle aspiration provide a rapid, minimally invasive means of diagnosis (17). Treatment options include radiation therapy, surgery or a combination of the two. Reports suggest surgical resection followed by adjuvant radiation or chemotherapy provides excellent palliative results (31,32,33). Although solitary metastases less then 4 cm in diameter can be treated by excisional biopsy (34), other reports suggest a less invasive approach may be better due to a low incidence of functional disability and because of the poor survival of these patients. Surgical resection is often reserved for those lesions that fail to be controlled locally with radiation or when the tumor growth results in neurologic deficit. SUMMARY: Although metastasis to skeletal muscle is extremely uncommon, physicians must remain aware of its occurrence, as its detection often requires specific evaluation. Differentiation between a primary soft tissue sarcoma and metastatic carcinoma to muscle is important, as their treatment and prognosis are so markedly different. The current literature does not provide any clinical or radiographic characteristic (plane x-ray or bone scans) that distinguishes metastatic carcinoma to muscle from soft tissue sarcoma (17). MRI, however, appears promising, and it should be considered earlier in the diagnostic work up. Treatment continues to remain palliative as metastatic carcinoma to muscle continues to remain a late event, with an overall poor prognosis.