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Inflammatory Myofibroblastic Tumor Presenting With Esophageal Obstruction and an Inflammatory Syndrome

2008; Elsevier BV; Volume: 86; Issue: 4 Linguagem: Inglês

10.1016/j.athoracsur.2008.03.056

1552-6259

Alicia Privette, P G Fisk, Bruce J. Leavitt, Kumarasen Cooper, Laurence E. McCahill,

Soft tissue tumor case studies

Inflammatory myofibroblastic tumor is a rare neoplasm of intermediate malignant potential. Although inflammatory myofibroblastic tumor occurs at multiple anatomic locations, an esophageal lesion is extremely rare. We describe a 43-year-old man who presented with severe dysphagia and an inflammatory syndrome, secondary to esophageal inflammatory myofibroblastic tumor. The patient was treated successfully with esophagectomy and remains disease free at 1 year. This case illustrates the complexities involved in managing a large esophageal myofibroblastic tumor and highlights that esophagectomy, rather than enucleation, should be the treatment of choice. Inflammatory myofibroblastic tumor is a rare neoplasm of intermediate malignant potential. Although inflammatory myofibroblastic tumor occurs at multiple anatomic locations, an esophageal lesion is extremely rare. We describe a 43-year-old man who presented with severe dysphagia and an inflammatory syndrome, secondary to esophageal inflammatory myofibroblastic tumor. The patient was treated successfully with esophagectomy and remains disease free at 1 year. This case illustrates the complexities involved in managing a large esophageal myofibroblastic tumor and highlights that esophagectomy, rather than enucleation, should be the treatment of choice. Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential that may present as a submucosal mass. Although IMT has been described in many anatomic locations, esophageal IMT is extremely rare and difficult to diagnose preoperatively. The cause and clinical course of esophageal IMT is unclear; therefore, there is no standardized treatment. We describe the differential diagnosis of submucosal esophageal lesions, management options for esophageal IMT, and our treatment of the largest (9.6 × 5.5 cm) mass believed to be reported in the literature. A 43-year-old man presented with 1 year of worsening dysphagia and odynophagia and a 6-month weight loss and food avoidance. The patient denied smoking and alcohol intake. Initial esophagogastroduodenoscopy demonstrated a large, pedunculated mass of the distal esophagus with overlying mucosal erosion, but without evidence of Barrett's esophagus. Initial biopsies were nondiagnostic. The patient required hospitalization for intractable chest pain and poor nutrition. A nasojejunal feeding tube was placed using fluoroscopy. Barium esophagram demonstrated a pedunculated distal intraluminal mass causing significant dilatation and obstruction (Fig 1). A computed tomographic scan of the chest, abdomen, and pelvis showed no evidence of metastasis or lymphadenopathy. Positron emission tomography was negative, except for increased uptake in the esophageal mass. Endoscopic ultrasound (EUS) demonstrated an obstructing mass that seemed to be submucosal in origin, with overlying mucosal necrosis. There was no evidence of muscularis propria involvement or lymphadenopathy. Core biopsies were obtained. A preliminary diagnosis of esophageal IMT was made based on core biopsy results (ie, myofibroblastic spindle cells) and immunohistochemical stains (ie, alpha-smooth muscle actin and anaplastic lymphoma kinase protein). The patient had persistent fevers and moderate leukocytosis, which were attributed to a tumor-specific inflammatory response. The patient continued to have severe chest pain, requiring large doses of narcotics. Attempts to improve nutritional status preoperatively with enteral feedings were unsuccessful. It was believed that operative intervention was required. Based on preoperative imaging that demonstrated a lower esophageal submucosal mass, a left thoracotomy was performed for a planned enucleation. Myotomy revealed significant adherence to the muscularis propria making enucleation impossible. In addition, the large tumor size and proximity to the heart prohibited complete resection of the proximal margin through the left chest. The procedure was converted to an Ivor-Lewis esophagogastrectomy through an abdominal incision and a right thoracotomy, which proceeded without complications. Gross pathology demonstrated a tan-yellow to brown ovoid mass (9.6 × 5.5 × 4.8 cm). The luminal component extended distally into the proximal stomach and had overlying mucosal ulceration and underlying granulation tissue (Fig 2). Proximal esophageal and distal gastric margins were negative. Microscopically, the tumor extended through the muscularis propria into the adventitia and consisted of spindled cells admixed with scattered chronic inflammatory cells (ie, lymphocytes, plasma cells) (Fig 3). Areas of increased cellularity contained focal, mild cytologic atypia. A single focus of lymphatic vascular invasion was identified. Five paraesophageal lymph nodes were negative for metastases. Spindle cells were diffusely positive for anaplastic lymphoma kinase, and focally positive for alpha-smooth muscle actin. S-100 showed weak nonspecific staining. Tests for CD34, c-kit, and desmin were negative.Fig 3High-power view of myofibroblastic cells with characteristic cytologic atypia. (Hematoxylin & Eosin stain, 40× magnification.)View Large Image Figure ViewerDownload (PPT) The patient's postoperative course was unremarkable. Inflammatory symptoms resolved and preoperative chest pain also resolved rapidly. Postoperatively the patient tolerated a regular diet and was discharged home on postoperative day 14. At 1 year, the patient denied pain and had moderate weight gain and a return to baseline physical activity. A computed tomographic scan showed no evidence of recurrence. Inflammatory myofibroblastic tumor is a rare neoplasm that can occur in various anatomic locations, most commonly in the lungs and mesentery or omentum, and it is equally distributed across gender (ratio, 1 female to 1.4 males) [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar]. Esophageal IMT is extremely rare. Two large multicenter studies of 128 IMT cases failed to identify a single esophageal lesion and only 10 cases of esophageal IMT have been reported in the literature [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar, 4Kurihara K. Mizuseki K. Ichikawa M. et al.Esophageal inflammatory pseudotumor mimicking malignancy.Intern Med. 2001; 40: 18-22Crossref PubMed Scopus (17) Google Scholar, 5Marchi S. Costa F. Mumolo M.G. et al.Post-traumatic inflammatory pseudotumor of the esophagus.Gastrointest Endosc. 2001; 54: 397-399Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 6Saklani A.P. Pramesh C.S. Heroor A.A. et al.Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (11) Google Scholar]. Histologically, IMT consists of myofibroblastic mesenchymal spindle cells accompanied by inflammatory infiltrates [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar]. The three classifications are: (1) myxoid vascular with an inflammatory infiltrate resembling granulation tissue or nodular fasciitis, (2) compact spindle cell with inflammation, and (3) hypocellular fibrous [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar]. The pathogenesis of IMT remains unclear, but an exaggerated response to injury and inflammation has been proposed due to its reported association with Epstein-Barr virus, gastroesophageal reflux, and trauma [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 4Kurihara K. Mizuseki K. Ichikawa M. et al.Esophageal inflammatory pseudotumor mimicking malignancy.Intern Med. 2001; 40: 18-22Crossref PubMed Scopus (17) Google Scholar, 5Marchi S. Costa F. Mumolo M.G. et al.Post-traumatic inflammatory pseudotumor of the esophagus.Gastrointest Endosc. 2001; 54: 397-399Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 6Saklani A.P. Pramesh C.S. Heroor A.A. et al.Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (11) Google Scholar]. Esophageal IMT is difficult to distinguish from more common submucosal esophageal lesions. Esophageal leiomyoma, gastrointestinal stromal tumor, and esophageal IMT may present with similar symptoms, such as pain and dysphagia [5Marchi S. Costa F. Mumolo M.G. et al.Post-traumatic inflammatory pseudotumor of the esophagus.Gastrointest Endosc. 2001; 54: 397-399Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 6Saklani A.P. Pramesh C.S. Heroor A.A. et al.Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (11) Google Scholar, 7Zwischenberger J.B. Savage C. Bhutani M.S. Esophagus.in: Townsend Jr, C.M. Beauchamp R.D. Evers B.M. Mattox K.L. Sabiston textbook of surgery. 17th ed. Saunders, Philadelphia, PA2004: 1116-1117Google Scholar]. Although IMT can occur at any age, it presents most commonly in children and young adults, whereas leiomyoma and gastrointestinal stromal tumor are more common in older patients (ie, fourth to fifth decade of life) [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar, 7Zwischenberger J.B. Savage C. Bhutani M.S. Esophagus.in: Townsend Jr, C.M. Beauchamp R.D. Evers B.M. Mattox K.L. Sabiston textbook of surgery. 17th ed. Saunders, Philadelphia, PA2004: 1116-1117Google Scholar]. A distinguishing feature of IMT (15% to 30% of cases) is the presence of an inflammatory syndrome consisting of fever, weight loss, malaise, anemia, thrombocytosis, polyclonal hyperglobulinemia, and elevated erythrocyte sedimentation rate, which has been attributed to cytokine stimulation [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar]. After resection, symptoms and laboratory abnormalities resolve rapidly [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar]. Our patient demonstrated several aspects of this syndrome (ie, fever, weight loss, malaise, and thrombocytosis) that were completely resolved within weeks of resection. The diagnostic test of choice for submucosal lesions is EUS. Endoscopic ultrasound findings for leiomyoma and gastrointestinal stromal tumor are a hypoechoic lesion of the muscularis propria [8Gan S.I. Rajan E. Adler D.G. et al.Role of EUS.Gastrointest Endosc. 2007; 66: 425-434Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar]. However, EUS characterization and final pathology correlate in only 77% of cases and there were no IMT-specific EUS descriptions found in the available literature [8Gan S.I. Rajan E. Adler D.G. et al.Role of EUS.Gastrointest Endosc. 2007; 66: 425-434Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar]. Although not recommended for suspected leiomyoma, endoscopic biopsy can be used to distinguish gastrointestinal stromal tumor and IMT [7Zwischenberger J.B. Savage C. Bhutani M.S. Esophagus.in: Townsend Jr, C.M. Beauchamp R.D. Evers B.M. Mattox K.L. Sabiston textbook of surgery. 17th ed. Saunders, Philadelphia, PA2004: 1116-1117Google Scholar]. Inflammatory myofibroblastic tumor is characterized by a positive anaplastic lymphoma kinase immunohistochemical immunoreaction in approximately 50% of tumors [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar]. Gastrointestinal stromal tumor exhibits c-kit and CD34 immunopostivity, and leiomyoma is typically positive for desmin and actin [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 7Zwischenberger J.B. Savage C. Bhutani M.S. Esophagus.in: Townsend Jr, C.M. Beauchamp R.D. Evers B.M. Mattox K.L. Sabiston textbook of surgery. 17th ed. Saunders, Philadelphia, PA2004: 1116-1117Google Scholar, 8Gan S.I. Rajan E. Adler D.G. et al.Role of EUS.Gastrointest Endosc. 2007; 66: 425-434Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar]. The submucosal location can make biopsies difficult to obtain and IMT specimens are often inconclusive or misdiagnosed [4Kurihara K. Mizuseki K. Ichikawa M. et al.Esophageal inflammatory pseudotumor mimicking malignancy.Intern Med. 2001; 40: 18-22Crossref PubMed Scopus (17) Google Scholar, 5Marchi S. Costa F. Mumolo M.G. et al.Post-traumatic inflammatory pseudotumor of the esophagus.Gastrointest Endosc. 2001; 54: 397-399Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 6Saklani A.P. Pramesh C.S. Heroor A.A. et al.Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (11) Google Scholar]. The available esophageal IMT literature describes tumors of varying sizes and multiple treatment modalities ranging from observation and anti-reflux therapy to surgery [3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar, 4Kurihara K. Mizuseki K. Ichikawa M. et al.Esophageal inflammatory pseudotumor mimicking malignancy.Intern Med. 2001; 40: 18-22Crossref PubMed Scopus (17) Google Scholar, 5Marchi S. Costa F. Mumolo M.G. et al.Post-traumatic inflammatory pseudotumor of the esophagus.Gastrointest Endosc. 2001; 54: 397-399Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 6Saklani A.P. Pramesh C.S. Heroor A.A. et al.Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (11) Google Scholar]. The most commonly reported primary therapy is surgical resection (ie, enucleation and partial or total esophagectomy) [4Kurihara K. Mizuseki K. Ichikawa M. et al.Esophageal inflammatory pseudotumor mimicking malignancy.Intern Med. 2001; 40: 18-22Crossref PubMed Scopus (17) Google Scholar, 5Marchi S. Costa F. Mumolo M.G. et al.Post-traumatic inflammatory pseudotumor of the esophagus.Gastrointest Endosc. 2001; 54: 397-399Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 6Saklani A.P. Pramesh C.S. Heroor A.A. et al.Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (11) Google Scholar]. The use of enucleation versus esophagectomy must be balanced between the recurrence risk and operative morbidity. Once considered benign, IMT is currently classified as a true neoplasm with intermediate biologic potential due to its association with a chromosomal abnormality of the anaplastic lymphoma kinase-receptor tyrosine kinase gene (40% to 75% of IMTs) [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar]. Inflammatory myofibroblastic tumor can also exhibit locally aggressive behavior and rare instances of metastasis [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar]. Locally recurrent IMT has been associated with anaplastic lymphoma kinase mutation, extapulmonary lesions, and incomplete resection [1Coffin C.M. Hornick J.L. Fletcher C.D. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520Crossref PubMed Scopus (624) Google Scholar, 2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar]. Recurrence rates for complete resection are 8% to 10% but, as a whole, these rates can range as high as 25% to 40% [3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar]. Enucleation was initially considered for this patient due to his poor preoperative nutritional status and lack of muscularis involvement on EUS. Due to the size and intraoperative findings of muscularis involvement, we elected to proceed to esophagectomy. Complete surgical resection of a large or obstructing tumor is more difficult with enucleation, increasing the risk of recurrence, and has only been reported in a single case involving a relatively small tumor (2.5 cm) [4Kurihara K. Mizuseki K. Ichikawa M. et al.Esophageal inflammatory pseudotumor mimicking malignancy.Intern Med. 2001; 40: 18-22Crossref PubMed Scopus (17) Google Scholar]. We now believe that esophagectomy (whether partial or total) should be the procedure of choice for large (> 2.5 cm) or obstructing esophageal IMTs or any tumor with muscularis propria involvement. Enucleation should be reserved for small (< 2.5 cm) tumors without evidence of muscularis involvement on EUS. Due to the risk of recurrence, the patient should undergo radiologic surveillance yearly for several years. The use of chemotherapy and radiation is controversial and has been used primarily for nonoperable or incompletely resected tumors or palliation [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1254) Google Scholar, 3Kovach S.J. Fischer A.C. Katzman P.J. et al.Inflammatory myofibroblastic tumors.J Surg Onc. 2006; 94: 385-391Crossref PubMed Scopus (210) Google Scholar]. In conclusion, esophageal IMT is a rare diagnosis that should be included in the differential diagnosis of dysphagia associated with submucosal or pedunculated esophageal neoplasms. The primary treatment of esophageal IMT should be complete surgical resection. The selection of a surgical procedure should be based on preoperative evaluation of tumor size and involvement of the muscularis propria.