CASE REPORT

Invasive Inflammatory Myofibroblastic Tumor of the Lung

Daniel A. van den Heuvel, MD,* Ruth G. Keijsers, MD,† Hendrik W. van Es, MD, PhD,*Gerben P. Bootsma, MD, PhD,‡ Peter C. de Bruin, MD, PhD,§ Franz M. Schramel, MD, PhD,�

and Johannes P. van Heesewijk, MD, PhD*

Abstract: Inflammatory myofibroblastic tumor (IMT) of the lungis a rare tumor but it should be considered when dealing withprimary lung tumors in children, adolescents, and nonsmokingadults. It is, from a pathologic point of view, a benign tumorcomposed of a spindle cell proliferation and inflammatory cells.Its clinical behavior, however, is variable with a benign evolutionat one, and a malignant evolution with recurrent and metastaticdisease at the other end of the spectrum. Diagnosis is verydifficult and often only possible after resection of the tumor. Wepresent a case of pulmonary IMT in a 15-year-old male withmalignant features on radiographic and 18F-Fluoro-deoxyglucosepositron emission tomography imaging. Pathogenesis, pathologyfindings, clinical behavior, and imaging of pulmonary IMT arebriefly discussed.

Key Words: Inflammatory myofibroblastic tumor, Pseudotumor,Pulmonary.

(J Thorac Oncol. 2009;4: 923–926)

CASE REPORTA 15-year-old male patient without a relevant medical

history was referred to our institution for analysis of a largemass in the lower lobe of the left lung. He had been asymp-tomatic until a few weeks before admission when he experi-enced a short period of hemoptysis. Apart from an occasionalstabbing left-sided chest pain, not related to respiration, therewere no other pulmonary manifestations. His vital signs andphysical examination were unremarkable. Laboratory inves-tigation showed a mildly elevated C-reactive protein but wasotherwise normal.

A chest radiograph showed a mass-like consolidationin the left lower lobe with hilar enlargement and a largesmooth calcification posterior to the heart. Pleural effusion

could not be excluded on the basis of these radiographs(Figure 1).

Computed tomography of the chest demonstrated alarge heterogeneous mass in the left lower lobe with one largeand several smaller calcifications. There was no interfacewith the lateral wall of the left ventricle, part of the lefthemidiaphragm, pleura of the oblique fissure and dorsalpleura, and chest wall (Figure 2). There was no evidence ofmetastases or lymphadenopathy. The mass had a systemicblood supply through the left bronchial artery and two largevessels branching from the supradiaphragmatic aorta suggest-ing a sequestration. Angiography confirmed the systemicblood supply and supported the diagnosis of a pulmonarysequestration. 18F-Fluoro-deoxyglucose positron emission to-mography scan showed a large lobulated mass with a maxi-mum standardized uptake value of 12 and a cold retrocardialzone corresponding with the large calcification. At bronchos-copy there was no endobronchial component of the massvisible, but there was compression of the lingular bronchusand obstruction of the lower lobe bronchus caused bythe tumor.

At this stage in the work-up of the mass the differentialdiagnosis was either a malignancy (pleomorphic carcinoma,low-grade sarcoma, malignant fibrous histiocytoma) or anintrapulmonary sequestration although these rarely containlarge calcifications. Because no definite histopathologic di-agnosis could be obtained through either transthoracic fineneedle aspiration, lymphnode biopsies or a video assistedthorascopy guided biopsy, an explorative thoracotomy wasperformed. This showed a large vascularized, aggressivelooking tumor in the lower lobe which could not be separatedfrom the upper lobe, pericardium and diaphragm. Because ofthese findings a lobectomy was not possible and an intraperi-cardial pneumonectomy was performed with partial resectionof pericardium and diaphragm.

On gross pathology, a pale firm mass was noted inthe left lower lobe with a diameter of approximately 11cm. Transsection revealed a solid central calcified noduleof 5 cm (Figure 3). In the surrounding lung tissue, aninfiltrative process (organizing pneumonia type) and bron-chiectasis were found. There was invasion in mediastinumand pericardium with tumor positive margins at these sites.Histopathology revealed a monotonous spindle cell prolif-eration with an inflammatory component consisting ofplasma cells and small lymphoid cells (Figure 4). Therewas evidence of vascular invasion but no mitotic activity

Departments of *Radiology, †Nuclear Medicine, St. Antonius Hospital,Nieuwegein; ‡Department of Pulmonary Medicine, Atrium MedicalCenter, Heerlen; Departments of §Pathology, and �Radiology, St. Anto-nius Hospital, Nieuwegein, The Netherlands.

Disclosure: The authors declare no conflicts of interest.Address for correspondence: Daniel A. van den Heuvel, MD, Department of

Radiology, St. Antonius Hospital, Nieuwegein, The Netherlands. E-mail:d.van.den.heuvel@antonius.net

Copyright © 2009 by the International Association for the Study of LungCancerISSN: 1556-0864/09/0407-0923

Journal of Thoracic Oncology • Volume 4, Number 7, July 2009 923

or atypical cells were seen. Immunohistochemical investi-gations were positive for alfa SMA and vimentine andnegative for cytokeratine stains, CD 34, anaplastic lym-phoma kinase-1, desmine, and S100. Because of thesefindings a malignant tumor such as pleomorfic carcinomaor a sarcoma was unlikely and the process was diagnosedas an inflammatory myofibroblastic tumor (IMT) alsoknown as an inflammatory pseudotumor.

DISCUSSIONIMT is a spindle cell proliferation of which the exact

etiology is still not completely understood. Different namesare used in the literature depending on the predominant celltype encountered in the lesion; plasma cell granuloma ortumor, xanthogranuloma, plasmacell/histiocytoma com-plex or post inflammatory pseudotumor. Matsubara et al.1

used the term inflammatory pseudotumor and describedthree subgroups also depending on the cell type mostencountered in a mass: organizing pneumonia, fibroushistiocytoma, and lymphoplasmocytic type. In all threetypes, an intraalveolar organizing inflammation was ob-served and they hypothesized that an inflammatorypseudotumor probably originates as organizing pneumo-nia. In 1990, Pettinato et al.2 were among the first to usethe term IMT because the immunohistochemical featuresof the spindle cells in these lesions resemble those ofmyofibroblasts. Although most reports suggest an inflam-matory pathogenesis with an exaggerated response to tis-sue damage and subsequently pseudotumor formation,there are reports suggesting a true neoplastic nature with clonalchromosomal changes in chromosome 2.3,4 These changes arefound in region 2p23 with activation of the anaplastic lymphomakinase gene proving that at least a few IMT’s are indeed trueneoplasms rather than reactive processes.

IMT’s are relatively common primary lung tumors inchildren accounting for approximately 20% of all primarylung tumors.5 Patients are often asymptomatic but whensymptoms do occur they commonly consist of fever, cough,pain, hemoptysis, or weight loss.

Imaging findings are nonspecific and range from benignlooking solitary peripheral lung nodules to endobronchialnodules in the larger airways or large aggressive lookingtumors with invasion and metastases.6,7 When IMT’s presentas central masses there is often involvement of hilar struc-tures and the mediastinum. Calcifications are unusual but areencountered in about 15%. Lymphadenopathy is also anuncommon finding. 18F-Fluoro-deoxyglucose positron emis-sion tomography is not able to differentiate between an IMT

FIGURE 1. Posteroanterior chest radiograph showing amass-like consolidation in the left lower lobe with enlarge-ment of the left hilum and a large smooth calcificationposterior to the heart.

FIGURE 2. Axial contrast-enhancedcomputed tomography (CT) scanshows a large heterogeneous massin the left lower lobe with one largeand several smaller calcifications. (A)There is no interface with the wallof the left ventricle (black arrow)and pleura. (B) Coronal reconstruc-tion demonstrating hilar and upperlobe involvement and a large solidcentral calcification correspondingwith the calcification seen on thechest radiograph (asterisk). Thewhite arrow is pointing toward oneof the supplying arteries branchingfrom the descending aorta. S,spleen; L, liver.

van den Heuvel et al. Journal of Thoracic Oncology • Volume 4, Number 7, July 2009

Copyright © 2009 by the International Association for the Study of Lung Cancer924

and a malignancy because both can demonstrate increasedmetabolic activity.8

Imaging, fine needle aspiration, or true cut biopsiesare often not able to distinguish between a IMT, a sarcoma,or other low-grade malignancies. Diagnosis has proven tobe very difficult and almost only possible after resectionof the tumor. Resection and immunohistochemical inves-tigations are essential to differentiate IMT’s from malig-nancies such as low-grade myofibrosarcoma and othertumors.

Treatment of IMT’s should consist of radical resec-tion. Melloni et al. and Lee et al. demonstrated this in theirseries in which they described the clinical history, imagingcharacteristics, and clinical outcome in patients with IMT.

Complete resection and tumor size less than or equal to 3cm were associated with a better survival. Overall 3-yearand 5-year survival rates were 82% and 74%, respective-ly.9,10 The role of corticosteroids, chemo- or radiationtherapy is unclear.

CONCLUSIONAn IMT is a rare lesion of the lung, but needs to be

considered when dealing with primary pulmonary tumors inthe lung in children, adolescents, and nonsmoking adults. Thetrue nature of this lesion remains controversial. It can reflectan exaggerated inflammatory response to tissue damage withsubsequently pseudotumor formation but it may also be a trueneoplastic process. Diagnosis has proven to be very difficultand often only possible after resection of the tumor andimmunohistochemical investigation. Prognosis seems to berelated to tumor size and completeness of the resection.Incomplete resection can result in poor clinical outcomestressing its potential malignant behavior.

We presented a case of an IMT in a symptomaticpatient with hemoptysis and thoracic pain. At the time ofsurgery the differential diagnosis was either a lung seques-tration or a malignancy. An IMT was diagnosed after resec-tion which, unfortunately, was incomplete. At 4-year follow-up, however, the patient was doing well and imaging showedno metastatic or recurrent disease.

REFERENCES1. Matsubara O, Tan-Liu NS, Kenney RM, Mark EJ. Inflammatory pseudotumors

of the lung: progression from organizing pneumonia to fibrous histiocytoma orplasma cell granuloma in 32 cases. Hum Pathol 1988;19:807–814.

2. Pettinato G, Manivel JC, De Rosa N, Dehner LP. Inflammatory myofi-broblastic tumor (plasma cell granuloma). Clinicopathologic study of 20cases with immunohistochemical and ultrastructural observations. Am JClin Pathol 1990;94:538–546.

3. Su LD, Atayde-Perez A, Sheldon S, Fletcher JA, Weiss SW. Inflamma-tory myofibroblastic tumor: cytogenetic evidence supporting clonalorigin. Mod Pathol 1998;11:364–368.

FIGURE 3. Gross pathology left lung resection specimen.There is a white, firm-elastic tumor (diameter 11 cm) in thelower lobe with extension into the upper lobe (arrowheads).The mass contains a focal calcification that correlates withthe calcification seen on the imaging studies (asterisk). Dia-phragm and pericardial tissue can not be recognized prop-erly in this picture. The arrow is pointing toward the upperlobe bronchus. LUL, left upper lobe; LLL, left lower lobe.

FIGURE 4. Microscopy (hematoxylin-eosin stain, magnifica-tion: original �200) showing a spindle cell proliferation setin a collagenous stroma with an inflammatory component oflymphocytes and plasma cells.

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4. Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, PerlmanEJ. Recurrent involvement of 2p23 in inflammatory myofibroblastictumors. Cancer Res 1999;59:2776–2780.

5. Cohen MC, Kaschula RO. Primary pulmonary tumors in childhood: areview of 31 years experience and the literature. Pediatr Pulmonol1992;14:222–232.

6. Kim TS, Han J, Kim GY, Lee KS, Kim H, Kim J. pulmonary inflam-matory pseudotumor (inflammatory myofibroblastic tumor) CT featureswith pathologic correlation. J Comput Assist Tomogr 2005;29:633–639.

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manifestations of inflammatory pulmonary pseudotumor in children.Pediatr Radiol 1999;29:112–116.

8. Kuo PH, Spooner S, Deol P, Monchamp T. Metastatic inflammatorymyofibroblastic tumor imaged by PET/CT. Clin Nucl Med 2006;31:106–108.

9. Melloni G, Carretta A, Ciriaco P, et al. Inflammatory pseudotumor of thelung in adults. Ann Thorac Surg 2005;79:426–432.

10. Lee HJ, Kim JS, Choi YS, et al. Treatment of inflammatory myofibro-blastic tumor of the chest: the extent of resection. Ann Thorac Surg2007;84:221–224.

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