Unusual cause of dysphagia: inflammatory pseudotumor of the lung.

Abstract: Inflammatory pseudotumor (IPT) is a rare disease that usually occurs in the lung. Patients with IPT are usually asymptomatic, with a solitary pulmonary nodule or mass detected on routine chest roentgenogram. IPT can behave as a malignant tumor both clinically and radiologically. Cough, fever, dyspnea, and hemoptysis are the usual presenting symptoms. This report describes the case of a 37-year-old man with a 4-month course of dysphagia secondary to lower esophageal invasion by the posterior mediastinal extension of a lung IPT.

Key Words: dysphagia, inflammatory pseudotumor, lung

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Inflammatory pseudotumor (IPT) is an uncommon, essentially nonneoplastic, tumor-like process that usually occurs in children and young people. (1) The lung is the most frequent site of involvement. The lesion is usually detected incidentally on routine chest radiography as a solitary pulmonary nodule. (2,3) Although regarded as a benign lesion, it may have aggressive features. Dysphagia is a rare symptom that occurs as the result of invasion of the posterior mediastinum and produces esophageal obstruction. (4,5) It may be severe and life-threatening. We report a case of pulmonary inflammatory pseudotumor of the lung that presented with severe and progressive dysphagia.

Case Report

A 37-year-old male presented with difficulty swallowing for 4 months. The clinical history was unremarkable except for dysphagia. An esophagogram demonstrated luminal narrowing at the distal segment of the esophagus, sparing the cardia. Neither esophagogram nor endoscopy revealed ulceration or mucosal abnormality. Posteroanterior and lateral chest radiographs showed a right pericardiac mass and ipsilateral pleural effusion, in addition to a smaller parenchymal nodule in the right middle lobe (Fig. 1). Contrast-enhanced computed tomography (CT) of the thorax depicted a lobulated mass, 6 X 8 cm in size with coarse calcification, which was located at the right lower lobe, extending to the posterior mediastinum. There was esophageal wall thickening at the distal segment, and the tissue planes between the mass and the esophagus were obscured (Fig. 2). On magnetic resonance imaging (MRI), the mass showed higher signal intensity than that of skeletal muscle on [T.sub.1] and was hyperintense on [T.sub.2]-weighted images. Also, MRI revealed that the wall of the esophagus was infiltrated by the mass (Fig. 3).

Percutaneous CT-guided lung biopsy was performed, which showed inflammatory and mesenchymal cells without any malignant component. Exploration with a right posterolateral thoracotomy revealed a hard, oval mass occupying the majority of the lower lobe with two satellite lesions. The pulmonary ligament was thick and hard, partially surrounding the esophagus in a 5- to 7-cm-long segment. The ligament was cut, and a standard lower lobectomy was performed. After the operation, the patient was discharged in good condition, except for a continuous dysphagia. A new esophagogram was obtained that revealed severe luminal narrowing at the same level of the previous examination. The passage of contrast material occurred with gravity. There was prestenotic dilation of the proximal esophagus (Fig. 4). The patient underwent repeat operation because of progressive and disabling dysphagia. Distal esophagectomy with tubal gastroesophagostomy was performed through a left thoracophrenolaparotomy 2 months after the first operation.

Microscopically, regions of organized pneumonia with prominent fibroblastic activity were observed, which were close to the surrounding lung parenchyma. Samples obtained from the central region of the mass revealed lymphoid aggregates forming germinal centers and plasma cells. Accompanying plasma cell infiltration and proliferation of spindle-shaped cells in the form of crossing bundles were seen (Fig. 5). With immunohistochemical stains, plasma cells revealed the same amount of positive reaction for [kappa]- and [lambda]-light chains (polyclonality). On the other hand, spindle-shaped cells revealed positive reaction with vimentin, whereas there was no reaction with desmin, actin, and S-100. These findings suggested inflammatory myofibroblastic tumor of the lung, and immunohistochemical analysis with ALK (anaplastic lymphoma kinase) was performed. Only spindle cells revealed moderate positive reaction with ALK. Mitotic activity was very low, and occasional mitotic figures were seen (0 to 1/high power field). MIB-1 score was 0.5. No reaction was obtained with p53. The final histopathologic diagnosis was IPT of the lung.

Histologic examination of the distal esophagectomy specimen revealed adventitial and deep muscular infiltration of the esophagus, whereas the mucosal layer was intact.

One month after the distal esophagectomy, the patient was admitted with severe dysphagia and dyspnea, which was progressive in nature. Palliative radiotherapy was administered. A total dose of 40 Gy was given in 20 fractions from the anteroposterior fields to the tumor volume. Despite the therapy, the patient continued to worsen and died 10 months after the initial diagnosis.

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Discussion

IPT, also known as plasma cell granuloma and inflammatory myofibroblastic tumor, is a rare, nonneoplastic lesion, consisting mainly of spindle-shaped mesenchymal and inflammatory cells. (1,5) It is most commonly seen in the lung, although it may also be seen in extrapulmonary sites such as the central nervous system, urinary tract, solid abdominal viscera, and lymphoid organs. (6) Such lesions account for less than 1% of all lung tumors with no sex preponderance. There is an increased predilection in children. (2,7) The underlying cause and pathogenesis remain uncertain and may be an unregulated reparative response of injured tissue. A history of lower respiratory tract infection is present in 18 to 30% of cases. (4,8)

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Macroscopically, IPTs are well-circumscribed, unencapsulated, white-yellow masses, firm in consistency. On microscopic examination, these lesions consist of a variable mixture of fibroblast and granulation tissue, fibrous tissue, and inflammatory cells, to include lymphocytes, histiocytes, giant cells, macrophages, neutrophils, eosinophils, and, typically, a large number of plasma cells. (1,4) In most instances, transbronchial and transthoracic needle biopsy are insufficient for diagnosis. Also, frozen sections at the time of operation are often indeterminate. (1,7)

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Although its pathogenesis is still accepted as uncertain, it was recently discovered that some of the IPTs show chromosomal rearrangement involving the ALK receptor tyrosine kinase locus (band 2p23) with expression of ALK in the myofibroblastic spindle cells but not in the inflammatory cells. That expression can be demonstrated by immunohistochemical or fluorescent in situ hybridization. Cytogenetic banding studies were the first assays indicative of a neoplastic pathogenesis of the IPT. (9,10) Cytoplasmic positivity in myofibroblastic cells for ALK using monoclonal antibodies is detectable in approximately 50% of IPT cases (11). On the other hand, according to the recent literature, most of the other cases also have clonal cytogenetic changes such as HMGIC rearrangement. (12,13)

Many patients are asymptomatic and are diagnosed incidentally on routine chest radiography. IPTs may have aggressive features, and they may encase bronchi or invade mediastinal structures, chest wall, and diaphragm. In such instances, cough, fever, dyspnea, pulmonary infection, and hemoptysis are the usual presenting manifestations. Multiple recurrences and metastatic spread can also be seen. (5,7,14)

Dysphagia is an extremely rare presenting symptom of IPT of the lung. It occurs when the mass causes lower esophageal obstruction by surrounding or infiltrating the esophagus. To our knowledge, there have only been four such cases reported in the English literature. (5,15-17)

Radiologic features of IPT are variable and nonspecific. CT most commonly reveals a well-marginated lobulated mass of heterogenous attenuation with variable patterns of contrast enhancement. MRI shows intermediate signal intensity on [T.sub.1]-weighted and high signal intensity on [T.sub.2]-weighted images. Dystrophic/calcification within the lesion is not rare and is seen more frequently in children than in adults. Multiple lung lesions, pneumonic consolidation, atelectasis, hilar masses, and cavitation are unusual findings. (4)

CT and MRI are helpful for demonstrating the extent of the potentially aggressive disease. Central airway, vascular, esophageal, diaphragmatic, and chest wall invasion can be delineated by these modalities. However, conventional barium studies are the gold standard radiologic modality for characterizing esophageal involvement. (15)

Conclusion

Although variable success in the treatment of these lesions with corticosteroids, radiation, and antibiotics has been reported, surgery remains the preferred treatment modality. (7,18,19) Early and complete surgical resection of the IPT provides cure and prevents local recurrence. (20) However, complete resection is usually extremely difficult. Persistence of the mass and symptoms may necessitate further operations, as in our patient.

Accepted January 31, 2005.

References

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16. Corneli G, Alifano M, Forti PS, et al. Invasive inflammatory pseudotumor involving the lung and the mediastinum. Thorac Cardiovasc Surg 2001;49:124-126.

17. Hutchins GM, Eggleston JC. Unusual presentation of pulmonary inflammatory pseudotumor (plasma cell granuloma) as esophageal obstruction. Am J Gastroenterol 1979;71:501-504.

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19. Shirakusa T, Kusano T, Motonaga R, et al. Plasma cell granuloma of the lung resection and steroid therapy. Thorac Cardiovasc Surg 1987;35:185-188.

20. Sakurai H, Hasegawa T, Watanabe S, et al. Inflammatory myofibroblastic tumor of the lung. Eur J Cardiothorac Surg 2004;25:155-159.

RELATED ARTICLE: Key Points

* Inflammatory pseudotumor of the lung is a rare, nonneoplastic lesion, consisting mainly of spindle-shaped mesenchymal and inflammatory cells.

* It is often incidentally detected during routine chest radiographs as a solitary pulmonary mass.

* Although benign, it may be locally very aggressive and may mimic a malignant lesion.

* Dysphagia is an unusual symptom. It develops secondary to esophageal infiltration by posterior mediastinal extension of the inflammatory pseudotumor. Dysphagia may be progressive and life threatening.

* In general, radiologic features of these tumors are variable and nonspecific. Computed tomography and magnetic resonance imaging are useful in determining the extent of this aggressive process.

Canan Akman, MD, Fazilet Oner Dincbas, MD, Buge Oz, MD, Bengi Gurses, MD, Fatih Kantarci, MD, Ahmet Demirkaya, MD, and Hasan Tuzun, MD

From the Department of Radiology, the Department of Radiation Oncology, the Department of Pathology, and the Department of Cardiovascular Surgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Reprint requests to Dr. Canan Akman, Istanbul University, Cerrahpasa Medical Faculty, Department of Radiology, 34300-Istanbul, Turkey. Email: [e-mail]