Pulmonary Inflammatory Myofibroblastic Tumor Invading the Gastroesophageal Junction

Pulmonary inflammatory myofibroblastic tumors are rare neoplasms of intermediate malignant potential. Most patients are asymptomatic and present with incidental findings on imaging. Dysphagia due to direct invasion into the esophagus is an extremely rare presentation of this uncommon tumor. The diagnosis is difficult to make preoperatively. Complete surgical resection offers the best chance of cure. We describe a 27-year-old man who presented with progressive dysphagia and the diagnosis was only revealed after en bloc resection of the esophagus, cardia, and left lower lobe. Pulmonary inflammatory myofibroblastic tumors are rare neoplasms of intermediate malignant potential. Most patients are asymptomatic and present with incidental findings on imaging. Dysphagia due to direct invasion into the esophagus is an extremely rare presentation of this uncommon tumor. The diagnosis is difficult to make preoperatively. Complete surgical resection offers the best chance of cure. We describe a 27-year-old man who presented with progressive dysphagia and the diagnosis was only revealed after en bloc resection of the esophagus, cardia, and left lower lobe. Pulmonary inflammatory myofibroblastic tumors are rare mesenchymal tumors of uncertain origin. Hence, they are also referred to as inflammatory pseudotumors, plasma cell granulomas, xanthogranulomas, or fibrous histiocytomas. This reflects their debatable identity of neoplasm vs inflammation. We present a case involving a symptomatic 27-year-old man with extremely rare invasion into the esophagus and describe the management and outcome. These tumors are difficult to diagnose preoperatively; however, complete surgical resection offers definitive diagnosis and excellent treatment. The literature on the characteristics of these tumors will also be reviewed. A 27-year-old man presented with a 6-month history of vague retrosternal pain and progressive dysphagia to solids without weight loss. An upper endoscopy demonstrated a tight gastroesophageal junction. Upon retroflexion, a firm submucosal mass in the cardia was noted, with a small area of central mucosal ulceration. Multiple biopsy specimens of this area demonstrated only mild chronic inflammation, with focal areas of early goblet cell metaplasia. A chest computed tomography image showed a large 7- × 4-cm mass intricately involving the gastroesophageal junction and left lower lobe, without evidence of regional lymphadenopathy or metastases (Fig 1). This prompted several repeat upper endoscopies and an endoscopic ultrasound, biopsy specimens from which again revealed nonmalignant squamous or columnar epithelium with unremarkable smooth muscle bundles. Given the persistence of symptoms and the failure to derive a definitive diagnosis, the patient was referred for surgical resection. Because of the location and bulky nature of the tumor, a left thoracoabdominal approach was used. The mass was observed to be approximately 8 × 5 cm, intimately involving the wall of the distal esophagus, proximal cardia, and medial basal segment of the left lower lobe. An en bloc resection of the distal esophagus, gastric cardia, and a portion of the left lower lobe was performed with a 1-cm rim of diaphragm. The surgical specimen consisted of large, irregular, rubbery to firm tumor showing a white fibrous appearance on cut section. The tumor was partially encapsulated at the pleuropulmonary aspect, while appearing more infiltrative at the esophagogastric end (Fig 2). The tumor epicenter was localized at the periphery of the resected lung from which it most likely originated and extensively penetrated downward into the wall of the esophagus and stomach. It involved the pleura, the periesophageal space, the gastric serosa, muscularis propria, and submucosa of the esophagus, and stomach, with no obvious ulceration into the mucosal surface. Histologically, the pulmonary margin, proximal esophageal, and distal gastric mucosal margins were free of tumor. Focally, the tumor involved a surgical margin microscopically at the level of the diaphragm. Most of the mass was composed of dense collagenized fibrous stroma admixed with plasma cell-rich, inflammatory infiltrate. Only focally, a cellular component was seen forming fascicles of mildly atypical spindle-shaped myofibroblasts. This component did not display mitotic activity and was devoid of tumor necrosis (Figs 3A–D). The KI67 proliferation index did not exceed 1% and supported the low proliferative activity of this tumor. The specimen contained 40 regional lymph nodes, which were negative for malignant cells. The infiltrative characteristics and morphology of this neoplasm were highly consistent with inflammatory myofibroblastic tumor. Immunostains for anaplastic lymphoma kinase (ALK)-1, smooth muscle actin (SMA), S100, CD68, and desmin were negative. The patient's postoperative course was uncomplicated, and he was discharged on postoperative day 10. The patient is currently 18 months after resection and has undergone serial computed tomography scans every 6 months, without any evidence of recurrence. IMTs are rare neoplasms of intermediate malignant potential that can arise from various anatomic locations, including the lung (most common), omentum, mesentery, and rarely the genitourinary tract, heart and central nervous system [1Privette A. Fisk P. Leavitt B. Cooper K. McCahill L. Inflammatory myofibroblastic tumor presenting with esophageal obstruction and an inflammatory syndrome.Ann Thorac Surg. 2008; 86: 1364-1367Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. Direct invasion of the foregut by pulmonary IMTs, as described in the present case, is extremely rare. An incidence of 0.04% to 1.2% for pulmonary IMTs has been reported and is distributed evenly across genders, but they occur mostly in children and young adults [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor) A clinicopathologic and immunohistochemical study of 84 cases.Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1312) Google Scholar, 3Cerfolio R.J. Allen M.S. Nascimento A.G. et al.Inflammatory pseudotumors of the lung.Ann Thorac Surg. 1999; 67: 933-936Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 4Sakurai H. Hasegawa T. Watanabe S. Suzuki K. Asamura H. Tsuchiya R. Inflammatory myofibroblastic tumor of the lung.Eur J Cardiothorac Surg. 2004; 25: 155-159Crossref PubMed Scopus (92) Google Scholar, 5Takeda S. Onishi Y. Kawamura T. Maeda H. Clinical spectrum of pulmonary inflammatory myofibroblastic tumor.Interact Cardiovasc Thorac Surg. 2008; 7: 629-633Crossref PubMed Scopus (37) Google Scholar]. Histologically, these tumors are defined by spindle cells in a fascicular or storiform pattern amongst abundant inflammatory cells [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor) A clinicopathologic and immunohistochemical study of 84 cases.Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1312) Google Scholar] and have thus been in the past referred to as inflammatory pseudotumors, plasma cell granulomas, xanthogranulomas, or fibrous histiocytomas [3Cerfolio R.J. Allen M.S. Nascimento A.G. et al.Inflammatory pseudotumors of the lung.Ann Thorac Surg. 1999; 67: 933-936Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 6Melloni G. Carretta A. Ciriaco P. et al.Inflammatory pseudotumor of the lung in adults.Ann Thorac Surg. 2005; 79: 426-432Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar]. The term “pseudotumor” reflects the debate surrounding its identity: a true neoplasm vs an example of unregulated inflammation [5Takeda S. Onishi Y. Kawamura T. Maeda H. Clinical spectrum of pulmonary inflammatory myofibroblastic tumor.Interact Cardiovasc Thorac Surg. 2008; 7: 629-633Crossref PubMed Scopus (37) Google Scholar]. Arguments for the former center on the fact that they mimic malignancy clinically with local invasion and local recurrence. In very rare circumstances they have been found to metastasize [5Takeda S. Onishi Y. Kawamura T. Maeda H. Clinical spectrum of pulmonary inflammatory myofibroblastic tumor.Interact Cardiovasc Thorac Surg. 2008; 7: 629-633Crossref PubMed Scopus (37) Google Scholar, 6Melloni G. Carretta A. Ciriaco P. et al.Inflammatory pseudotumor of the lung in adults.Ann Thorac Surg. 2005; 79: 426-432Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar]. Furthermore, IMTs have been associated with genetic abnormalities such as rearrangements of the anaplastic lymphoma kinase (ALK) gene and DNA aneuploidy. However, they may be simply a product of uncontrolled inflammation considering that they are composed of a mosaic of inflammatory cells, are associated with Epstein-Barr virus, human herpesvirus-8, and gastroesophageal reflux disease, and have been noted to decrease in size with anti-inflammatory agents like corticosteroids [1Privette A. Fisk P. Leavitt B. Cooper K. McCahill L. Inflammatory myofibroblastic tumor presenting with esophageal obstruction and an inflammatory syndrome.Ann Thorac Surg. 2008; 86: 1364-1367Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. The presentation of IMTs varies depending on their site of origin. The symptoms of pulmonary IMTs may include dry cough, fever, hemoptysis, and dyspnea, but most are discovered incidentally on chest roentgenogram [4Sakurai H. Hasegawa T. Watanabe S. Suzuki K. Asamura H. Tsuchiya R. Inflammatory myofibroblastic tumor of the lung.Eur J Cardiothorac Surg. 2004; 25: 155-159Crossref PubMed Scopus (92) Google Scholar, 5Takeda S. Onishi Y. Kawamura T. Maeda H. Clinical spectrum of pulmonary inflammatory myofibroblastic tumor.Interact Cardiovasc Thorac Surg. 2008; 7: 629-633Crossref PubMed Scopus (37) Google Scholar, 6Melloni G. Carretta A. Ciriaco P. et al.Inflammatory pseudotumor of the lung in adults.Ann Thorac Surg. 2005; 79: 426-432Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar]. The symptoms of esophageal and gastric IMTs include pain and dysphagia [7Saklani A.P. Pramesh C.S. Heroor A.A. Saoji R. Sharma S. Deshpande R.K. Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (12) Google Scholar]. Furthermore, IMTs can cause constitutional symptoms, including fever, malaise, weight loss, anemia, and thrombocytosis, which resolve after resection of the tumor [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor) A clinicopathologic and immunohistochemical study of 84 cases.Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1312) Google Scholar]. The current patient presented with a 6-month history of increasing dysphagia, which is in keeping with the mass effect imposed on the esophagus. The diagnosis of IMTs is difficult to make preoperatively [8Fang F.C. Lee S.C. Hsu H.H. Peng Y.J. Chang H. Cheng Y.L. Inflammatory myofibroblastic tumor of the lung: unusual presentation.Lung. 2008; 186: 191-193Crossref PubMed Scopus (6) Google Scholar]. Pulmonary IMTs are well-circumscribed, solitary, peripheral, homogenous or heterogeneous nodules on chest roentgenograms and computed tomography [8Fang F.C. Lee S.C. Hsu H.H. Peng Y.J. Chang H. Cheng Y.L. Inflammatory myofibroblastic tumor of the lung: unusual presentation.Lung. 2008; 186: 191-193Crossref PubMed Scopus (6) Google Scholar]. Biopsy specimens from these lesions usually demonstrate inflammation and frequently result in an inconclusive diagnosis, and can even be misdiagnosed [5Takeda S. Onishi Y. Kawamura T. Maeda H. Clinical spectrum of pulmonary inflammatory myofibroblastic tumor.Interact Cardiovasc Thorac Surg. 2008; 7: 629-633Crossref PubMed Scopus (37) Google Scholar, 8Fang F.C. Lee S.C. Hsu H.H. Peng Y.J. Chang H. Cheng Y.L. Inflammatory myofibroblastic tumor of the lung: unusual presentation.Lung. 2008; 186: 191-193Crossref PubMed Scopus (6) Google Scholar]. This scenario was certainly true with the current patient, where multiple biopsy specimens did not yield a diagnosis. Immunohistochemical staining for ALK (positive in 50% of IMTs), cytokeratin, laminin, SMA, muscle-specific actin (MSA), calponin, fibronectin, and desmin is variably and inconsistently positive in IMT, and in our patient these stains were negative. As with all tumors, recommended treatment for IMTs is complete surgical resection [1Privette A. Fisk P. Leavitt B. Cooper K. McCahill L. Inflammatory myofibroblastic tumor presenting with esophageal obstruction and an inflammatory syndrome.Ann Thorac Surg. 2008; 86: 1364-1367Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 7Saklani A.P. Pramesh C.S. Heroor A.A. Saoji R. Sharma S. Deshpande R.K. Inflammatory pseudotumor of the esophagus.Dis Esophagus. 2001; 14: 274-277Crossref PubMed Scopus (12) Google Scholar, 8Fang F.C. Lee S.C. Hsu H.H. Peng Y.J. Chang H. Cheng Y.L. Inflammatory myofibroblastic tumor of the lung: unusual presentation.Lung. 2008; 186: 191-193Crossref PubMed Scopus (6) Google Scholar]. However, not all patients with microscopically positive margins recur. Indeed, the risk of recurrence for incomplete resection is only 60% [1Privette A. Fisk P. Leavitt B. Cooper K. McCahill L. Inflammatory myofibroblastic tumor presenting with esophageal obstruction and an inflammatory syndrome.Ann Thorac Surg. 2008; 86: 1364-1367Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 3Cerfolio R.J. Allen M.S. Nascimento A.G. et al.Inflammatory pseudotumors of the lung.Ann Thorac Surg. 1999; 67: 933-936Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar]. Survival after complete resection is 91% at 5 years and 77% at 10 years [5Takeda S. Onishi Y. Kawamura T. Maeda H. Clinical spectrum of pulmonary inflammatory myofibroblastic tumor.Interact Cardiovasc Thorac Surg. 2008; 7: 629-633Crossref PubMed Scopus (37) Google Scholar]. Results from nonsurgical treatment have been disappointing, and it is reserved for those patients who are inoperable, palliative, or who had incomplete resection [2Coffin C.M. Watterson J. Priest J.R. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor) A clinicopathologic and immunohistochemical study of 84 cases.Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1312) Google Scholar]. Radiologic surveillance is the recommended appropriate follow-up [1Privette A. Fisk P. Leavitt B. Cooper K. McCahill L. Inflammatory myofibroblastic tumor presenting with esophageal obstruction and an inflammatory syndrome.Ann Thorac Surg. 2008; 86: 1364-1367Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. At present, IMT is regarded as a neoplasm of intermediate biologic potential because of the tendency for local recurrence, which is 25% for abdominopelvic lesions and less when arising in the lung. The incident of metastasis is extremely rare, and no available morphologic indicators can be useful in predicting such behavior.